trying...<BR><?xml version="1.0" encoding="UTF-8" ?>
<!DOCTYPE eSearchResult PUBLIC "-//NLM//DTD esearch 20060628//EN" "https://eutils.ncbi.nlm.nih.gov/eutils/dtd/20060628/esearch.dtd">
<eSearchResult><Count>31</Count><RetMax>1</RetMax><RetStart>0</RetStart><QueryKey>1</QueryKey><WebEnv>MCID_676f086c5968e7a52d006d17</WebEnv><IdList>
<Id>39538854</Id>
</IdList><TranslationSet/><QueryTranslation>"Zhao-Nan"[All Fields] AND Cai[Author]</QueryTranslation></eSearchResult>
trying2...<BR>trying...<BR><?xml version="1.0" ?>
<!DOCTYPE PubmedArticleSet PUBLIC "-//NLM//DTD PubMedArticle, 1st January 2024//EN" "https://dtd.nlm.nih.gov/ncbi/pubmed/out/pubmed_240101.dtd">
<PubmedArticleSet>
<PubmedArticle><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">39538854</PMID><DateRevised><Year>2024</Year><Month>11</Month><Day>14</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1094-4087</ISSN><JournalIssue CitedMedium="Internet"><Volume>32</Volume><Issue>14</Issue><PubDate><Year>2024</Year><Month>Jul</Month><Day>01</Day></PubDate></JournalIssue><Title>Optics express</Title><ISOAbbreviation>Opt Express</ISOAbbreviation></Journal><ArticleTitle>Accurate two-dimensional simulation model and experimental demonstration in ultraviolet picosecond laser scribing ablation.</ArticleTitle><Pagination><StartPage>24041</StartPage><EndPage>24057</EndPage><MedlinePgn>24041-24057</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1364/OE.524351</ELocationID><Abstract><AbstractText>Laser patterning of copper thin films is essential for the electronics manufacturing industry. In this work, to efficiently and accurately describe the physics process of UV-ps laser ablating copper thin film, a two-temperature model (TTM) consisting of the electron-lattice system and phase explosion mechanism was proposed. The process of electron heating and electron-lattice heat transfer in single pulse ablation were revealed. The average relative errors (ARE) of simulated ablation depth and width were 6.24% and 4.82%, respectively. The process of laser scribing ablation presents the characteristics of repeated ablation in the overlapping ablation region and new ablation in the non-overlapping region. The physics essence of laser scribing is the multiple laser ablations with different energies on the cross-section. The laser scribing cross-section ablation was simulated on 2D TTM. Compared with 3D simulation, though the ARE of ablation depth and width of 2D simulation slightly increased from 15.81% and 5.69% to 18.96% and 8.76%, respectively, the average solving time decreased significantly, from 81960 s to 2140 s. This comprehensive study aims to offer some insights into the characteristics of UV-ps laser ablation of copper thin film.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Zhiying</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Caijie</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shixian</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Kai</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Kedong</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jiaming</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Qingmao</ForeName><Initials>Q</Initials></Author><Author ValidYN="Y"><LastName>Yan</LastName><ForeName>Xueqing</ForeName><Initials>X</Initials></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Kun</ForeName><Initials>K</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Opt Express</MedlineTA><NlmUniqueID>101137103</NlmUniqueID><ISSNLinking>1094-4087</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="medline"><Year>2024</Year><Month>11</Month><Day>14</Day><Hour>17</Hour><Minute>31</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2024</Year><Month>11</Month><Day>14</Day><Hour>17</Hour><Minute>30</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2024</Year><Month>11</Month><Day>14</Day><Hour>1</Hour><Minute>3</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">39538854</ArticleId><ArticleId IdType="doi">10.1364/OE.524351</ArticleId><ArticleId IdType="pii">552256</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">39504356</PMID><DateCompleted><Year>2024</Year><Month>11</Month><Day>06</Day></DateCompleted><DateRevised><Year>2024</Year><Month>11</Month><Day>06</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1946-6242</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>772</Issue><PubDate><Year>2024</Year><Month>Nov</Month><Day>06</Day></PubDate></JournalIssue><Title>Science translational medicine</Title><ISOAbbreviation>Sci Transl Med</ISOAbbreviation></Journal><ArticleTitle>Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population.</ArticleTitle><Pagination><StartPage>eadh9940</StartPage><MedlinePgn>eadh9940</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1126/scitranslmed.adh9940</ELocationID><Abstract><AbstractText>Nonalcoholic fatty liver disease (NAFLD) has become a common health care burden worldwide. The high heterogeneity of NAFLD remains elusive and impairs outcomes of clinical diagnosis and pharmacotherapy. Several NAFLD classifications have been proposed on the basis of clinical, genetic, alcoholic, or serum metabolic analyses. Yet, accurately predicting the progression of NAFLD to cirrhosis or hepatocellular carcinoma (HCC) in patients remains a challenge. Here, on the basis of a Chinese cohort of patients, we classified NAFLD into three distinct molecular subtypes (NAFLD-mSI, NAFLD-mSII, and NAFLD-mSIII) using integrative multiomics including whole-genome sequencing (WGS), proteomics, phosphoproteomics, lipidomics, and metabolomics across a broad range of liver, blood, and urine specimens. We found that NAFLD-mSI had higher expression of CYP1A2 and CYP3A4, which alleviate hepatic steatosis through mediating free fatty acid/bile acid-mTOR-FXR/PPAR&#x3b1; signaling. NAFLD-mSII displayed an elevated risk of liver cirrhosis along with increased hepatic infiltration of M1 and M2 macrophages because of lipid-triggered hepatic CCL2 and CRP production. NAFLD-mSIII exhibited a potential risk for HCC development by increased transcription of CEBPB- and ERCC3-regulated oncogenes because of activation of the EGF-EGFR/CHKA/PI3K-PDK1-AKT cascade. Next, we validated the existence of these three NAFLD molecular subtypes in an external cohort comprising 92 patients with NAFLD across three different Chinese hospitals. These findings may aid in understanding the molecular features underlying NAFLD heterogeneity, thereby facilitating clinical diagnosis and treatment strategies with the aim of preventing the development of liver cirrhosis and HCC.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Jingjing</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0003-1508-7084</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Huaizheng</ForeName><Initials>H</Initials><Identifier Source="ORCID">0009-0003-0131-9515</Identifier><AffiliationInfo><Affiliation>Department of Emergency, the Third Xiangya Hospital, Central South University, Changsha 410013, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaoxun</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0002-3892-7464</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0002-4597-6547</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><Identifier Source="ORCID">0000-0003-4737-3712</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shi</LastName><ForeName>Junping</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0001-9434-897X</Identifier><AffiliationInfo><Affiliation>Department of Infectious Diseases and Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, Zhejiang, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Jinjun</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0003-4275-9149</Identifier><AffiliationInfo><Affiliation>Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chi</LastName><ForeName>Xiaoling</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0003-3193-1943</Identifier><AffiliationInfo><Affiliation>Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ling</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-9027-7307</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Mengni</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Wen-Yue</ForeName><Initials>WY</Initials><Identifier Source="ORCID">0000-0003-4570-6835</Identifier><AffiliationInfo><Affiliation>Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Liangjun</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ouyang</LastName><ForeName>Jiafeng</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yuan</LastName><ForeName>Qian</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmacy, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liao</LastName><ForeName>Min</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Ya</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Mingqiao</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Ziqian</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Wan</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Chuanming</ForeName><Initials>C</Initials><Identifier Source="ORCID">0000-0003-4362-6612</Identifier><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yi</ForeName><Initials>Y</Initials><Identifier Source="ORCID">0009-0002-9313-1861</Identifier><AffiliationInfo><Affiliation>Department of Clinical Laboratory, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Qiong</ForeName><Initials>Q</Initials><Identifier Source="ORCID">0000-0003-1033-3098</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><Identifier Source="ORCID">0000-0001-9570-8666</Identifier><AffiliationInfo><Affiliation>School of Clinical Medicine and the First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shi-Ying</ForeName><Initials>SY</Initials><Identifier Source="ORCID">0000-0001-6601-4040</Identifier><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Byrne</LastName><ForeName>Christopher D</ForeName><Initials>CD</Initials><Identifier Source="ORCID">0000-0001-6322-7753</Identifier><AffiliationInfo><Affiliation>Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton and University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Targher</LastName><ForeName>Giovanni</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Verona, Verona, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella 37024, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ouyang</LastName><ForeName>Xinshou</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0003-3423-0042</Identifier><AffiliationInfo><Affiliation>Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Liqun</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0001-5643-4965</Identifier><AffiliationInfo><Affiliation>Department of Clinical Laboratory, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Zhongyong</ForeName><Initials>Z</Initials><Identifier Source="ORCID">0009-0003-8807-3094</Identifier><AffiliationInfo><Affiliation>Department of Medical Laboratory, Cheng du Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu 610213, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Ming-Hua</ForeName><Initials>MH</Initials><Identifier Source="ORCID">0000-0003-4984-2631</Identifier><AffiliationInfo><Affiliation>MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou 325000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Fengjun</ForeName><Initials>F</Initials><Identifier Source="ORCID">0000-0003-2679-8797</Identifier><AffiliationInfo><Affiliation>Department of Pharmacy, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Jin</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-8543-4566</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) Medical Research Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2024</Year><Month>11</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Sci Transl Med</MedlineTA><NlmUniqueID>101505086</NlmUniqueID><ISSNLinking>1946-6234</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006528" MajorTopicYN="Y">Carcinoma, Hepatocellular</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002681" MajorTopicYN="N" Type="Geographic">China</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008099" MajorTopicYN="N">Liver</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008103" MajorTopicYN="N">Liver Cirrhosis</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008113" MajorTopicYN="N">Liver Neoplasms</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055432" MajorTopicYN="N">Metabolomics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065626" MajorTopicYN="Y">Non-alcoholic Fatty Liver Disease</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D040901" MajorTopicYN="N">Proteomics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000095225" MajorTopicYN="N">East Asian People</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="medline"><Year>2024</Year><Month>11</Month><Day>6</Day><Hour>22</Hour><Minute>20</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2024</Year><Month>11</Month><Day>6</Day><Hour>22</Hour><Minute>19</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2024</Year><Month>11</Month><Day>6</Day><Hour>14</Hour><Minute>3</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">39504356</ArticleId><ArticleId IdType="doi">10.1126/scitranslmed.adh9940</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">38985995</PMID><DateRevised><Year>2024</Year><Month>07</Month><Day>29</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1527-3350</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2024</Year><Month>Jul</Month><Day>10</Day></PubDate></JournalIssue><Title>Hepatology (Baltimore, Md.)</Title><ISOAbbreviation>Hepatology</ISOAbbreviation></Journal><ArticleTitle>Hepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1097/HEP.0000000000001003</ELocationID><Abstract><AbstractText Label="BACKGROUND AND AIMS" NlmCategory="OBJECTIVE">Inflammatory response is crucial for bile acid (BA)-induced cholestatic liver injury, but molecular mechanisms remain to be elucidated. Solute Carrier Family 35 Member C1 (SLC35C1) can transport Guanosine diphosphate-fucose into the Golgi to facilitate protein glycosylation. Its mutation leads to the deficiency of leukocyte adhesion and enhances inflammation in humans. However, little is known about its role in liver diseases.</AbstractText><AbstractText Label="APPROACH AND RESULTS" NlmCategory="RESULTS">Hepatic SLC35C1 mRNA transcripts and protein expression were significantly increased in patients with obstructive cholestasis and mouse models of cholestasis. Immunofluorescence revealed that the upregulated SLC35C1 expression mainly occurred in hepatocytes. Liver-specific ablation of Slc35c1 ( Slc35c1 cKO ) significantly aggravated liver injury in mouse models of cholestasis induced by bile duct ligation and 1% cholic acid-feeding, evidenced by increased liver necrosis, inflammation, fibrosis, and bile ductular proliferation. The Slc35c1 cKO increased hepatic chemokine Ccl2 and Cxcl2 expression and T cell, neutrophil, and F4/80 macrophage infiltration but did not affect the levels of serum and liver BA in mouse models of cholestasis. Liquid chromatography with tandem mass spectrometry analysis revealed that hepatic Slc35c1 deficiency substantially reduced the fucosylation of cell-cell adhesion protein CEACAM1 at N153. Mechanistically, cholestatic levels of conjugated BAs stimulated SLC35C1 expression by activating the STAT3 signaling to facilitate CEACAM1 fucosylation at N153, and deficiency in the fucosylation of CEACAM1 at N135 enhanced the BA-stimulated CCL2 and CXCL2 mRNA expression in primary mouse hepatocytes and Primary Liver Carcinoma/Poliomyelitis Research Foundation/5- ASBT cells.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Elevated hepatic SLC35C1 expression attenuates cholestatic liver injury by enhancing CEACAM1 fucosylation to suppress CCL2 and CXCL2 expression and liver inflammation.</AbstractText><CopyrightInformation>Copyright &#xa9; 2024 The Author(s). Published by Wolters Kluwer Health, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Liangjun</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-7053-8661</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Pingfan</ForeName><Initials>P</Initials><Identifier Source="ORCID">0009-0008-9443-8340</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Mingqiao</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0003-3692-2552</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaoxun</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0002-1342-2507</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fei</LastName><ForeName>Shuke</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0002-3354-2274</Identifier><AffiliationInfo><Affiliation>The Second Affiliated Hospital, Department of Hepatobiliary, Pancreatic and Splenic Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0002-4597-6547</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ling</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-9027-7307</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Qiaoling</ForeName><Initials>Q</Initials><Identifier Source="ORCID">0000-0002-1342-2507</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Ziqian</ForeName><Initials>Z</Initials><Identifier Source="ORCID">0009-0005-2809-5130</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Wan</ForeName><Initials>W</Initials><Identifier Source="ORCID">0000-0001-5693-3342</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Guanyu</ForeName><Initials>G</Initials><Identifier Source="ORCID">0009-0003-1601-5928</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Zhixian</ForeName><Initials>Z</Initials><Identifier Source="ORCID">0009-0002-9654-6421</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Zuzhi</ForeName><Initials>Z</Initials><Identifier Source="ORCID">0009-0006-0852-0432</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Second Affiliated Hospital, Hengyang Medical School, University of South China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jianwei</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0001-9629-7475</Identifier><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Chengcheng</ForeName><Initials>C</Initials><Identifier Source="ORCID">0000-0002-0550-107</Identifier><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyer</LastName><ForeName>James L</ForeName><Initials>JL</Initials><Identifier Source="ORCID">0000-0002-8959-6036</Identifier><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Wensheng</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shi-Ying</ForeName><Initials>SY</Initials><Identifier Source="ORCID">0000-0001-6601-4040</Identifier><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Qiong</ForeName><Initials>Q</Initials><Identifier Source="ORCID">0000-0003-1033-3098</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Jin</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-8543-4566</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Second Affiliated Hospital, Hengyang Medical School, University of South China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2024</Year><Month>07</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Hepatology</MedlineTA><NlmUniqueID>8302946</NlmUniqueID><ISSNLinking>0270-9139</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2024</Year><Month>1</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2024</Year><Month>6</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2024</Year><Month>7</Month><Day>10</Day><Hour>18</Hour><Minute>42</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2024</Year><Month>7</Month><Day>10</Day><Hour>18</Hour><Minute>42</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2024</Year><Month>7</Month><Day>10</Day><Hour>15</Hour><Minute>13</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">38985995</ArticleId><ArticleId IdType="doi">10.1097/HEP.0000000000001003</ArticleId><ArticleId IdType="pii">01515467-990000000-00953</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Poupon R, Chazouill&#xe8;res O, Poupon RE. Chronic cholestatic diseases. J Hepatol. 2000;32:129&#x2013;40.</Citation></Reference><Reference><Citation>Wagner M, Fickert P. Drug therapies for chronic cholestatic liver diseases. Annu Rev Pharmacol Toxicol. 2020;60:503&#x2013;27.</Citation></Reference><Reference><Citation>Zhang Y, Hong JY, Rockwell CE, Copple BL, Jaeschke H, Klaassen CD. Effect of bile duct ligation on bile acid composition in mouse serum and liver. Liver Int. 2012;32:58&#x2013;69.</Citation></Reference><Reference><Citation>Sasaki M, Miyakoshi M, Sato Y, Nakanuma Y. Chemokine-chemokine receptor CCL2-CCR2 and CX3CL1-CX3CR1 axis may play a role in the aggravated inflammation in primary biliary cirrhosis. Dig Dis Sci. 2014;59:358&#x2013;64.</Citation></Reference><Reference><Citation>Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, et al. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight. 2017;2:e90780.</Citation></Reference><Reference><Citation>Zhang X, Li L, Zhao N, Pan Q, Zhang L, Xie Q, et al. A novel role for interleukin 32 in cholestasis. Clin Transl Med. 2021;11:e594.</Citation></Reference><Reference><Citation>Zhang L, Pan Q, Zhang L, Xia H, Liao J, Zhang X, et al. Runt-related transcription factor-1 ameliorates bile acid-induced hepatic inflammation in cholestasis through JAK/STAT3 signaling. Hepatology. 2023;77:1866&#x2013;81.</Citation></Reference><Reference><Citation>Lu L, Hou X, Shi S, K&#xf6;rner C, Stanley P. Slc35c2 promotes Notch1 fucosylation and is required for optimal Notch signaling in mammalian cells. J Biol Chem. 2010;285:36245&#x2013;54.</Citation></Reference><Reference><Citation>Zhang P, Haryadi R, Chan KF, Teo G, Goh J, Pereira NA, et al. Identification of functional elements of the GDP-fucose transporter SLC35C1 using a novel Chinese hamster ovary mutant. Glycobiology. 2012;22:897&#x2013;911.</Citation></Reference><Reference><Citation>Song Z. Roles of the nucleotide sugar transporters (SLC35 family) in health and disease. Mol Aspects Med. 2013;34:590&#x2013;600.</Citation></Reference><Reference><Citation>Sturla L, Rampal R, Haltiwanger RS, Fruscione F, Etzioni A, Tonetti M. Differential terminal fucosylation of N-linked glycans versus protein O-fucosylation in leukocyte adhesion deficiency type II (CDG IIc). J Biol Chem. 2003;278:26727&#x2013;33.</Citation></Reference><Reference><Citation>Etzioni A, Frydman M, Pollack S, Avidor I, Phillips ML, Paulson JC, et al. Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med. 1992;327:1789&#x2013;92.</Citation></Reference><Reference><Citation>L&#xfc;bke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, K&#xf6;rner C. Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nat Genet. 2001;28:73&#x2013;6.</Citation></Reference><Reference><Citation>L&#xfc;hn K, Wild MK, Eckhardt M, Gerardy-Schahn R, Vestweber D. The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. Nat Genet. 2001;28:69&#x2013;72.</Citation></Reference><Reference><Citation>Moriwaki K, Noda K, Nakagawa T, Asahi M, Yoshihara H, Taniguchi N, et al. A high expression of GDP-fucose transporter in hepatocellular carcinoma is a key factor for increases in fucosylation. Glycobiology. 2007;17:1311&#x2013;20.</Citation></Reference><Reference><Citation>Ament CE, Steinmann S, Evert K, Pes GM, Ribback S, Gigante I, et al. Aberrant fucosylation sustains the NOTCH and EGFR/NF-kappaB pathways and has a prognostic value in human intrahepatic cholangiocarcinoma. Hepatology. 2023;78:1742&#x2013;54.</Citation></Reference><Reference><Citation>Kammerer R, Zimmermann W. Coevolution of activating and inhibitory receptors within mammalian carcinoembryonic antigen families. BMC Biol. 2010;8:12.</Citation></Reference><Reference><Citation>Prall F, Nollau P, Neumaier M, Haubeck HD, Drzeniek Z, Helmchen U, et al. CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, endothelium, and myeloid cells in a wide range of normal human tissues. J Histochem Cytochem. 1996;44:35&#x2013;41.</Citation></Reference><Reference><Citation>Cruz PV, Wakai T, Shirai Y, Yokoyama N, Hatakeyama K. Loss of carcinoembryonic antigen-related cell adhesion molecule 1 expression is an adverse prognostic factor in hepatocellular carcinoma. Cancer. 2005;104:354&#x2013;60.</Citation></Reference><Reference><Citation>Horst AK, Wegscheid C, Schaefers C, Schiller B, Neumann K, Lunemann S, et al. Carcinoembryonic antigen-related cell adhesion molecule 1 controls IL-2-dependent regulatory T-cell induction in immune-mediated hepatitis in mice. Hepatology. 2018;68:200&#x2013;14.</Citation></Reference><Reference><Citation>Kelleher M, Singh R, O&#x2019;Driscoll CM, Melgar S. Carcinoembryonic antigen (CEACAM) family members and inflammatory bowel disease. Cytokine Growth Factor Rev. 2019;47:21&#x2013;31.</Citation></Reference><Reference><Citation>Schirbel A, Rebert N, Sadler T, West G, Rieder F, Wagener C, et al. Mutual regulation of TLR/NLR and CEACAM1 in the intestinal microvasculature: Implications for IBD pathogenesis and therapy. Inflamm Bowel Dis. 2019;25:294&#x2013;305.</Citation></Reference><Reference><Citation>Muturi HT, Ghadieh HE, Abdolahipour R, Stankus HL, Belew GD, Liu JK, et al. Loss of CEACAM1 in endothelial cells causes hepatic fibrosis. Metabolism. 2023;144:155562.</Citation></Reference><Reference><Citation>Al-Share QY, DeAngelis AM, Lester SG, Bowman TA, Ramakrishnan SK, Abdallah SL, et al. Forced hepatic overexpression of CEACAM1 curtails diet-induced insulin resistance. Diabetes. 2015;64:2780&#x2013;90.</Citation></Reference><Reference><Citation>Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, et al. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature. 2015;517:386&#x2013;90.</Citation></Reference><Reference><Citation>Nakamura K, Kageyama S, Kaldas FM, Hirao H, Ito T, Kadono K, et al. Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury. J Clin Invest. 2020;130:2689&#x2013;704.</Citation></Reference><Reference><Citation>Lucka L, Sel S, Danker K, Horstkorte R, Reutter W. Carcinoembryonic antigen-related cell-cell adhesion molecule C-CAM is greatly increased in serum and urine of rats with liver diseases. FEBS Lett. 1998;438:37&#x2013;40.</Citation></Reference><Reference><Citation>Dr&#xe1;berov&#xe1; L, &#x10c;ern&#xe1; H, Brodsk&#xe1; H, Boubel&#xed;k M, Watt SM, Stanners CP, et al. Soluble isoforms of CEACAM1 containing the A2 domain: Increased serum levels in patients with obstructive jaundice and differences in 3-fucosyl-N-acetyl-lactosamine moiety. Immunology. 2000;101:279&#x2013;87.</Citation></Reference><Reference><Citation>Li X, Li Y, Xiao J, Wang H, Guo Y, Mao X, et al. Unique DUOX2(+)ACE2(+) small cholangiocytes are pathogenic targets for primary biliary cholangitis. Nat Commun. 2023;14:29.</Citation></Reference><Reference><Citation>Chen R, Huang B, Lian M, Wei Y, Miao Q, Liang J, et al. A+T rich interaction domain protein 3a (Arid3a) impairs Mertk-mediated efferocytosis in cholestasis. J Hepatol. 2023;79:1478&#x2013;1490.</Citation></Reference><Reference><Citation>Pan Q, Zhang X, Zhang L, Cheng Y, Zhao N, Li F, et al. Solute carrier organic anion transporter family member 3A1 is a bile acid efflux transporter in cholestasis. Gastroenterology. 2018;155:1578&#x2013;92 e1516.</Citation></Reference><Reference><Citation>Pan Q, Zhu G, Xu Z, Zhu J, Ouyang J, Tong Y, et al. Organic anion transporting polypeptide (OATP) 1B3 is a significant transporter for hepatic uptake of conjugated bile acids in humans. Cell Mol Gastroenterol Hepatol. 2023;16:223&#x2013;42.</Citation></Reference><Reference><Citation>Huang Y, Zhang HL, Li ZL, Du T, Chen YH, Wang Y, et al. FUT8-mediated aberrant N-glycosylation of B7H3 suppresses the immune response in triple-negative breast cancer. Nat Commun. 2021;12:2672.</Citation></Reference><Reference><Citation>Pan Q, Xie Y, Zhang Y, Guo X, Wang J, Liu M, et al. EGFR core fucosylation, induced by hepatitis C virus, promotes TRIM40-mediated-RIG-I ubiquitination and suppresses interferon-I antiviral defenses. Nat Commun. 2024;15:652.</Citation></Reference><Reference><Citation>Kim ND, Moon JO, Slitt AL, Copple BL. Early growth response factor-1 is critical for cholestatic liver injury. Toxicol Sci. 2006;90:586&#x2013;95.</Citation></Reference><Reference><Citation>Li J, Zhu X, Zhang M, Zhang Y, Ye S, Leng Y, et al. Limb expression 1-like (LIX1L) protein promotes cholestatic liver injury by regulating bile acid metabolism. J Hepatol. 2021;75:400&#x2013;13.</Citation></Reference><Reference><Citation>Di Conza G, Tsai CH, Gallart-Ayala H, Yu YR, Franco F, Zaffalon L, et al. Tumor-induced reshuffling of lipid composition on the endoplasmic reticulum membrane sustains macrophage survival and pro-tumorigenic activity. Nat Immunol. 2021;22:1403&#x2013;15.</Citation></Reference><Reference><Citation>Zheng Y, Dai H, Chen R, Zhong Y, Zhou C, Wang Y, et al. Endoplasmic reticulum stress promotes sepsis-induced muscle atrophy via activation of STAT3 and Smad3. J Cell Physiol. 2023;238:582&#x2013;96.</Citation></Reference><Reference><Citation>Park DJ, Sung PS, Kim JH, Lee GW, Jang JW, Jung ES, et al. EpCAM-high liver cancer stem cells resist natural killer cell-mediated cytotoxicity by upregulating CEACAM1. J Immunother Cancer. 2020;8:e000301.</Citation></Reference><Reference><Citation>Hirao H, Kojima H, Dery KJ, Nakamura K, Kadono K, Zhai Y, et al. Neutrophil CEACAM1 determines susceptibility to NETosis by regulating the S1PR2/S1PR3 axis in liver transplantation. J Clin Invest. 2023;133:e162940.</Citation></Reference><Reference><Citation>Nagaishi T, Chen Z, Chen L, Iijima H, Nakajima A, Blumberg RS. CEACAM1 and the regulation of mucosal inflammation. Mucosal Immunol. 2008;1(Suppl 1):S39&#x2013;42.</Citation></Reference><Reference><Citation>Khairnar V, Duhan V, Patil AM, Zhou F, Bhat H, Thoens C, et al. CEACAM1 promotes CD8(+) T cell responses and improves control of a chronic viral infection. Nat Commun. 2018;9:2561.</Citation></Reference><Reference><Citation>Schwerd T, Pandey S, Yang HT, Bagola K, Jameson E, Jung J, et al. Impaired antibacterial autophagy links granulomatous intestinal inflammation in Niemann-Pick disease type C1 and XIAP deficiency with NOD2 variants in Crohn&#x2019;s disease. Gut. 2017;66:1060&#x2013;73.</Citation></Reference><Reference><Citation>Tan CY, Chan PS, Tan H, Tan SW, Lee CJM, Wang JW, et al. Systematic in vivo candidate evaluation uncovers therapeutic targets for LMNA dilated cardiomyopathy and risk of Lamin A toxicity. J Transl Med. 2023;21:690.</Citation></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">37851699</PMID><DateCompleted><Year>2023</Year><Month>10</Month><Day>23</Day></DateCompleted><DateRevised><Year>2023</Year><Month>10</Month><Day>25</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>18</Volume><Issue>10</Issue><PubDate><Year>2023</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS One</ISOAbbreviation></Journal><ArticleTitle>Speech errors in consecutive interpreting: Effects of language proficiency, working memory, and anxiety.</ArticleTitle><Pagination><StartPage>e0292718</StartPage><MedlinePgn>e0292718</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">e0292718</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0292718</ELocationID><Abstract><AbstractText>Interpreting can be seen as a form of language production, where interpreters extract conceptual information from the source language and express it in the target language. Hence, like language production, interpreting contains speech errors at various (e.g., conceptual, syntactic, lexical and phonological) levels. The current study delved into the impact of language proficiency, working memory, and anxiety on the occurrence of speech errors across these linguistic strata during consecutive interpreting from English (a second language) into Chinese (a first language) by student interpreters. We showed that speech errors in general decreased as a function of the interpreter's proficiency in the source (second) language and increased as a function of the interpreter's anxiety. Conceptual errors, which result from mistaken comprehension of the source language, decreased as a function of language proficiency and working memory. Lexical errors increased as a function of the interpreter's tendency of anxiety. Syntactic errors also decreased as a function of language proficiency and increased as a function of anxiety. Phonological errors were not sensitive to any of the three cognitive traits. We discussed implications for the cognitive processes underlying interpreting and for interpreting training.</AbstractText><CopyrightInformation>Copyright: &#xa9; 2023 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0002-2053-8970</Identifier><AffiliationInfo><Affiliation>Department of Translation, Interpreting and Intercultural Studies, Hong Kong Baptist University, Hong Kong, Hong Kong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Zhenguang G</ForeName><Initials>ZG</Initials><AffiliationInfo><Affiliation>Department of Linguistics and Modern Languages/Brain and Mind Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dong</LastName><ForeName>Yanping</ForeName><Initials>Y</Initials><Identifier Source="ORCID">0000-0002-9306-0461</Identifier><AffiliationInfo><Affiliation>School of International Studies, Zhejiang University, Hangzhou, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2023</Year><Month>10</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013060" MajorTopicYN="Y">Speech</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008570" MajorTopicYN="Y">Memory, Short-Term</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007802" MajorTopicYN="N">Language</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008037" MajorTopicYN="N">Linguistics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001007" MajorTopicYN="N">Anxiety</DescriptorName></MeshHeading></MeshHeadingList><CoiStatement>The authors have declared that no competing interests exist.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>6</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2023</Year><Month>9</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>10</Month><Day>23</Day><Hour>1</Hour><Minute>18</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2023</Year><Month>10</Month><Day>18</Day><Hour>18</Hour><Minute>43</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2023</Year><Month>10</Month><Day>18</Day><Hour>13</Hour><Minute>45</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2023</Year><Month>10</Month><Day>18</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">37851699</ArticleId><ArticleId IdType="pmc">PMC10584118</ArticleId><ArticleId IdType="doi">10.1371/journal.pone.0292718</ArticleId><ArticleId IdType="pii">PONE-D-21-19586</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>DeBot K. A bilingual production model: Levelt&#x2019;s &#x201c;speaking&#x201d; model adapted. The bilingualism Reader. 2000;420: 442.</Citation></Reference><Reference><Citation>Levelt WJ. Speaking: From intention to articulation. MIT press; 1993.</Citation></Reference><Reference><Citation>Levelt WJM, Roelofs A, Meyer AS. A theory of lexical access in speech production. Behavioral &amp; Brain Sciences. 1999;22(1): 1&#x2013;75. doi: 10.1017/s0140525x99001776</Citation><ArticleIdList><ArticleId IdType="doi">10.1017/s0140525x99001776</ArticleId><ArticleId IdType="pubmed">11301520</ArticleId></ArticleIdList></Reference><Reference><Citation>Bock K, Levelt WJ. Language production: Grammatical encoding. In: Gernsbacher MA, editor. Handbook of psycholinguistics. San Diego: Academic Press; 1994. pp. 945&#x2013;984.</Citation></Reference><Reference><Citation>Meyer AS, Belke E. Word form retrieval in language production. In: Gaskell G, editor. The Oxford handbook of psycholinguistics. Oxford, UK; 2007.</Citation></Reference><Reference><Citation>Fromkin VA. Errors in linguistic performance. New York: Academic Press; 1980.</Citation></Reference><Reference><Citation>Poulisse N. Slips of the Tongue. Philadephia: John Benjamins Publishing Company; 1999.</Citation></Reference><Reference><Citation>Oppenheim GM, Dell GS, Schwartz MF. The dark side of incremental learning: A model of cumulative semantic interference during lexical access in speech production. Cognition. 2010;114(2): 227&#x2013;252. doi: 10.1016/j.cognition.2009.09.007</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.cognition.2009.09.007</ArticleId><ArticleId IdType="pmc">PMC2924492</ArticleId><ArticleId IdType="pubmed">19854436</ArticleId></ArticleIdList></Reference><Reference><Citation>Vitkovitch M, Humphreys GW, Lloyd-Jones TJ. On naming a giraffe a zebra: Picture naming errors across different object categories. Journal of Experimental Psychology: Learning, Memory, and Cognition. 1993;19(2): 243.</Citation></Reference><Reference><Citation>Engelhardt PE, Bailey KG, Ferreira F. Do speakers and listeners observe the Gricean Maxim of Quantity?. Journal of memory and language. 2006;54(4): 554&#x2013;573.</Citation></Reference><Reference><Citation>VanGompel RP, VanDeemter K, Gatt A, Snoeren R, Krahmer EJ. Conceptualization in reference production: Probabilistic modeling and experimental testing. Psychological Review. 2019;126(3): 345&#x2013;373. doi: 10.1037/rev0000138</Citation><ArticleIdList><ArticleId IdType="doi">10.1037/rev0000138</ArticleId><ArticleId IdType="pubmed">30907620</ArticleId></ArticleIdList></Reference><Reference><Citation>MacLeod CM. Half a century of research on the Stroop effect: an integrative review. Psychological Bulletin. 1991;109(2): 163&#x2013;203. doi: 10.1037/0033-2909.109.2.163</Citation><ArticleIdList><ArticleId IdType="doi">10.1037/0033-2909.109.2.163</ArticleId><ArticleId IdType="pubmed">2034749</ArticleId></ArticleIdList></Reference><Reference><Citation>Hanley JR, Cortis C, Budd MJ, Nozari N. Did I say dog or cat? A study of semantic error detection and correction in children. Journal of experimental child psychology. 2016;142: 36&#x2013;47. doi: 10.1016/j.jecp.2015.09.008</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jecp.2015.09.008</ArticleId><ArticleId IdType="pubmed">26476973</ArticleId></ArticleIdList></Reference><Reference><Citation>Garrett MF. Levels of processing in sentence production. In: Butterworth B, editor. Language production. Vol. 1. London: Academic Press; 1980. pp. 177&#x2013;220.</Citation></Reference><Reference><Citation>Bock JK, Miller CA. Broken agreement. Cognitive Psychology. 1991;23(1): 45&#x2013;93. doi: 10.1016/0010-0285(91)90003-7</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/0010-0285(91)90003-7</ArticleId><ArticleId IdType="pubmed">2001615</ArticleId></ArticleIdList></Reference><Reference><Citation>Ivanova I, Pickering MJ, McLean JF, Costa A, Branigan HP. How do people produce ungrammatical utterances? Journal of Memory and Language. 2012;67(3): 355&#x2013;370.</Citation></Reference><Reference><Citation>Fromkin VA. The non-anomalous nature of anomalous utterances. Language. 1971;47: 27&#x2013;52.</Citation></Reference><Reference><Citation>Corley M, Brocklehurst PH, Moat HS. Error biases in inner and overt speech: Evidence from tongue twisters. Journal of experimental psychology: Learning. 2011;37(1): 162. doi: 10.1037/a0021321</Citation><ArticleIdList><ArticleId IdType="doi">10.1037/a0021321</ArticleId><ArticleId IdType="pubmed">21244112</ArticleId></ArticleIdList></Reference><Reference><Citation>Thierry G, Wu YJ. Brain potentials reveal unconscious translation during foreign-language comprehension. Proceedings of the National Academy of Sciences. 2007;104(30): 12530&#x2013;12535. doi: 10.1073/pnas.0609927104</Citation><ArticleIdList><ArticleId IdType="doi">10.1073/pnas.0609927104</ArticleId><ArticleId IdType="pmc">PMC1941503</ArticleId><ArticleId IdType="pubmed">17630288</ArticleId></ArticleIdList></Reference><Reference><Citation>Dong Y, Lin J. Parallel processing of the target language during source language comprehension in interpreting. Bilingualism: Language and Cognition. 2013;16(03): 682&#x2013;692.</Citation></Reference><Reference><Citation>Macizo P, Bajo MT. Reading for repetition and reading for translation: do they involve the same processes? Cognition. 2006;99(1): 1&#x2013;34. doi: 10.1016/j.cognition.2004.09.012</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.cognition.2004.09.012</ArticleId><ArticleId IdType="pubmed">16443446</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhao N, Chen X, Cai ZG. Planning ahead: Interpreters predict source language in consecutive interpreting. Bilingualism: Language and Cognition. 2022;25(4): 588&#x2013;602.</Citation></Reference><Reference><Citation>Ru&#xed;z JO, Macizo P. Lexical and syntactic target language interactions in translation. Acta psychologica. 2019;199: 102924. doi: 10.1016/j.actpsy.2019.102924</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.actpsy.2019.102924</ArticleId><ArticleId IdType="pubmed">31465976</ArticleId></ArticleIdList></Reference><Reference><Citation>Chmiel A, Janikowski P, Lijewska A. Multimodal processing in simultaneous interpreting with text: Interpreters focus more on the visual than the auditory modality. Target. 2020;32(1): 37&#x2013;58.</Citation></Reference><Reference><Citation>Cai ZG, Pickering MJ, Yan H, Branigan HP. Lexical and syntactic representations in closely related languages: Evidence from Cantonese&#x2013;Mandarin bilinguals. Journal of Memory and Language. 2011;65(4): 431&#x2013;445.</Citation></Reference><Reference><Citation>Hartsuiker RJ, Pickering MJ, Veltkamp E. Is syntax separate or shared between languages? Cross-linguistic syntactic priming in Spanish-English bilinguals. Psychological Science. 2004;15(6): 409&#x2013;414. doi: 10.1111/j.0956-7976.2004.00693.x</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.0956-7976.2004.00693.x</ArticleId><ArticleId IdType="pubmed">15147495</ArticleId></ArticleIdList></Reference><Reference><Citation>Maier RM, Pickering MJ, Hartsuiker RJ. Does translation involve structural priming? Quarterly Journal of Experimental Psychology. 2017;70(8): 1575&#x2013;1589. doi: 10.1080/17470218.2016.1194439</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/17470218.2016.1194439</ArticleId><ArticleId IdType="pubmed">27244646</ArticleId></ArticleIdList></Reference><Reference><Citation>Ru&#xed;z C, Paredes N, Macizo P, Bajo MT. Activation of lexical and syntactic target language properties in translation. Acta Psychologica. 2008;128(3): 490&#x2013;500. doi: 10.1016/j.actpsy.2007.08.004</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.actpsy.2007.08.004</ArticleId><ArticleId IdType="pubmed">17884001</ArticleId></ArticleIdList></Reference><Reference><Citation>Chmiel A, Lijewska A. Syntactic processing in sight translation by professional and trainee interpreters: Professionals are more time-efficient while trainees view the source text less. Target. 2019;31(3): 378&#x2013;397.</Citation></Reference><Reference><Citation>Jouravlev O, Lupker SJ, Jared D. Cross-language phonological activation: Evidence from masked onset priming and ERPs. Brain and Language. 2014;134: 11&#x2013;22. doi: 10.1016/j.bandl.2014.04.003</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.bandl.2014.04.003</ArticleId><ArticleId IdType="pubmed">24814580</ArticleId></ArticleIdList></Reference><Reference><Citation>Kim J, Davis C. Task effects in masked cross-script translation and phonological priming. Journal of Memory and Language. 2003;49(4): 484&#x2013;499.</Citation></Reference><Reference><Citation>Gerver D. The effects of noise on the performance of simultaneous interpreters: Accuracy of performance. Acta Psychologica. 1974;38(3): 159&#x2013;167. doi: 10.1016/0001-6918(74)90031-6</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/0001-6918(74)90031-6</ArticleId><ArticleId IdType="pubmed">4416240</ArticleId></ArticleIdList></Reference><Reference><Citation>Gile D. Basic concepts and models for interpreter and translator training. John Benjamins Publishing; 2009.</Citation></Reference><Reference><Citation>Zhao N. Speech Disfluencies in Consecutive Interpreting by Student Interpreters: The Role of Language Proficiency, Working Memory, and Anxiety. Frontiers in Psychology. 2022;13. Available from: 10.3389/fpsyg.2022.881778.</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fpsyg.2022.881778</ArticleId><ArticleId IdType="pmc">PMC9197251</ArticleId><ArticleId IdType="pubmed">35712188</ArticleId></ArticleIdList></Reference><Reference><Citation>Christoffels IK, DeGroot A, Waldorp LJ. Basic skills in a complex task: A graphical model relating memory and lexical retrieval to simultaneous interpreting. Bilingualism: Language and Cognition. 2003;6(3): 201&#x2013;211.</Citation></Reference><Reference><Citation>Dong Y, Cai R, Zhao N, Lin J. An empirical study on interpreting competence structures in student interpreters. Foreign Languages. 2013;36(4): 76&#x2013;86.</Citation></Reference><Reference><Citation>Jin Y, Fan J. Test for English majors (TEM) in China. Language Testing. 2011;28(4): 589&#x2013;596.</Citation></Reference><Reference><Citation>Tzou YZ, Eslami ZR, Chen HC, Vaid J. Effect of language proficiency and degree of formal training in simultaneous interpreting on working memory and interpreting performance: Evidence from Mandarin-English speakers. International Journal of Bilingualism. 2011;16(2). Available from: 10.1177/1367006911403197</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/1367006911403197</ArticleId></ArticleIdList></Reference><Reference><Citation>Carrell PL. Second language reading: Reading ability or language proficiency? Applied Linguistics. 1991;12(2): 159&#x2013;179.</Citation></Reference><Reference><Citation>Vandergrift L. Second language listening: Listening ability or language proficiency?. The Modern Language Journal. 2006;90(1): 6&#x2013;18.</Citation></Reference><Reference><Citation>DeJong NH, Groenhout R, Schoonen R, Hulstijn JH. Second language fluency: Speaking style or proficiency? Correcting measures of second language fluency for first language behavior. Applied Psycholinguistics. 2015;36(2): 223&#x2013;243.</Citation></Reference><Reference><Citation>VanHell JG, Tanner D. Second language proficiency and cross-language lexical activation. Language Learning. 2012;62: 148&#x2013;171.</Citation></Reference><Reference><Citation>Baddeley A. Working memory. Science. 1992;255(5044): 556&#x2013;559. doi: 10.1126/science.1736359</Citation><ArticleIdList><ArticleId IdType="doi">10.1126/science.1736359</ArticleId><ArticleId IdType="pubmed">1736359</ArticleId></ArticleIdList></Reference><Reference><Citation>Daneman M, Carpenter PA. Individual differences in working memory and reading. Journal of Verbal Learning and Verbal Behavior. 1980;19(4): 450&#x2013;466.</Citation></Reference><Reference><Citation>Mellinger CD, Hanson TA. Meta-analyses of simultaneous interpreting and working memory. Interpreting. 2019;21(2): 165&#x2013;195.</Citation></Reference><Reference><Citation>Christoffels IK, DeGroot AM, Kroll JF. Memory and language skills in simultaneous interpreters: The role of expertise and language proficiency. Journal of Memory and Language. 2006;54(3): 324&#x2013;345.</Citation></Reference><Reference><Citation>Kroll JF, Michael E, Tokowicz N, Dufour R. The development of lexical fluency in a second language. Second language research. 2002;18(2):137&#x2013;171.</Citation></Reference><Reference><Citation>Spielberger CD, Gorsuch RL, Lushene R, Vagg PR, Jacobs GA. Manual for the State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press; 1983.</Citation></Reference><Reference><Citation>Cooper CL, Davies R, Tung RL. Interpreting stress: Sources of job stress among conference interpreters. Multilingua-Journal of Cross-Cultural and Interlanguage Communication. 1982;1(2): 97&#x2013;108.</Citation></Reference><Reference><Citation>Gile D. Fidelity assessment in consecutive interpretation: An experiment. Target. 1995;7(1):151&#x2013;164.</Citation></Reference><Reference><Citation>Klonowicz T. Putting one&#x2019;s heart into simultaneous interpretation. In: Lambert S, Moser-Mercer B, editors. Bridging the Gap: Empirical Research in Simultaneous Interpretation. 1994. pp. 213&#x2013;224.</Citation></Reference><Reference><Citation>Longley P. The use of aptitude testing in the selection of students for conference interpretation training. Paper presented at the The Theoretical and Practical Aspects of Teaching Conference Interpretation; 1989.</Citation></Reference><Reference><Citation>Moser-Mercer B. Screening potential interpreters. Meta. 1985;30(1): 97&#x2013;100.</Citation></Reference><Reference><Citation>Moser-Mercer B, K&#xfc;nzli A, Korac M. Prolonged turns in interpreting: Effects on quality, physiological and psychological stress (Pilot study). Interpreting. 1998;3(1): 47&#x2013;64.</Citation></Reference><Reference><Citation>Alexieva B. A typology of interpreter-mediated events. The Translator. 1997;3(2): 153&#x2013;174.</Citation></Reference><Reference><Citation>Brisau A, Godijns R, Meuleman C. Towards a psycholinguistic profile of the interpreter. Meta. 1994;39(1): 87&#x2013;94.</Citation></Reference><Reference><Citation>Shen M, Liang J. Self-repair in consecutive interpreting: similarities and differences between professional interpreters and student interpreters. Perspectives. 2020. doi: 10.1080/0907676X.2019.1701052</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/0907676X.2019.1701052</ArticleId></ArticleIdList></Reference><Reference><Citation>Daneman M. Working memory as a predictor of verbal fluency. Journal of Psycholinguistic Research. 1991;20(6): 445&#x2013;464.</Citation></Reference><Reference><Citation>Saito S, Baddeley AD. Irrelevant sound disrupts speech production: Exploring the relationship between short-term memory and experimentally induced slips of the tongue. The Quarterly Journal of Experimental Psychology Section A. 2004;57(7): 1309&#x2013;1340. doi: 10.1080/02724980343000783</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/02724980343000783</ArticleId><ArticleId IdType="pubmed">15513248</ArticleId></ArticleIdList></Reference><Reference><Citation>Lin Y, Lv Q, Liang J. Predicting fluency with language proficiency, working memory, and directionality in simultaneous interpreting. Frontiers in Psychology. 2018;9: 1543. doi: 10.3389/fpsyg.2018.01543</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fpsyg.2018.01543</ArticleId><ArticleId IdType="pmc">PMC6110880</ArticleId><ArticleId IdType="pubmed">30186213</ArticleId></ArticleIdList></Reference><Reference><Citation>Craig A, Tran Y. Trait and social anxiety in adults with chronic stuttering: Conclusions following meta-analysis. Journal of fluency disorders. 2014;40: 35&#x2013;43. doi: 10.1016/j.jfludis.2014.01.001</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jfludis.2014.01.001</ArticleId><ArticleId IdType="pubmed">24929465</ArticleId></ArticleIdList></Reference><Reference><Citation>Yeh S, Liu M. A more objective approach to interpretation evaluation: Exploring the use of scoring rubrics. Journal of the National Institute for Compilation and Translation. 2006;34(4): 57&#x2013;78.</Citation></Reference><Reference><Citation>Cai R, Dong Y, Zhao N, Lin J. Factors contributing to individual differences in the development of consecutive interpreting competence for beginning student interpreters. Interpreter and Translator Trainer. 2015;9(1): 04&#x2013;120. doi: 10.1080/1750399X.2015.1016279</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/1750399X.2015.1016279</ArticleId></ArticleIdList></Reference><Reference><Citation>Mizera GJ. Working memory and L2 oral fluency. University of Pittsburgh; 2006.</Citation></Reference><Reference><Citation>Dong Y, Chen H, Yu Z. Developing an Interpreting Anxiety Scale. Foreign Language World. 2013;6: 57&#x2013;64.</Citation></Reference><Reference><Citation>Zhang JX, Schwarzer R. Measuring optimistic self-beliefs: A Chinese adaptation of the General Self-Efficacy Scale. Psychologia: An International Journal of Psychology in the Orient. 1995;38(3): 174&#x2013;181.</Citation></Reference><Reference><Citation>Gr&#xf6;mping U. Relative importance for linear regression in R: The package relaimpo. Journal of Statistical Software. 2006;17: 1&#x2013;27.</Citation></Reference><Reference><Citation>Johnson JW, Lebreton JM. History and use of relative importance indices in organizational research. Organizational Research Methods. 2004;7: 238&#x2013;257.</Citation></Reference><Reference><Citation>Jackson CN, VanHell JG. The effects of L2 proficiency level on the processing of wh-questions among Dutch second language speakers of English. International Review of Applied Linguistics in Language Teaching. 2011;49: 195&#x2013;219. doi: 10.1515/iral.2011.012</Citation><ArticleIdList><ArticleId IdType="doi">10.1515/iral.2011.012</ArticleId><ArticleId IdType="pmc">PMC3413290</ArticleId><ArticleId IdType="pubmed">22888175</ArticleId></ArticleIdList></Reference><Reference><Citation>Caplan D, Waters GS. Verbal working memory and sentence comprehension. Behavioral and Brain Sciences. 1999;22(1): 77&#x2013;94. doi: 10.1017/s0140525x99001788</Citation><ArticleIdList><ArticleId IdType="doi">10.1017/s0140525x99001788</ArticleId><ArticleId IdType="pubmed">11301522</ArticleId></ArticleIdList></Reference><Reference><Citation>Just MA, Carpenter PA. A capacity theory of comprehension: individual differences in working memory. Psychological Review. 1992;99(1):122. doi: 10.1037/0033-295x.99.1.122</Citation><ArticleIdList><ArticleId IdType="doi">10.1037/0033-295x.99.1.122</ArticleId><ArticleId IdType="pubmed">1546114</ArticleId></ArticleIdList></Reference><Reference><Citation>Martin RC, Freedman ML. Short-term retention of lexical-semantic representations: Implications for speech production. Memory. 2001;9(4&#x2013;6): 261&#x2013;280. doi: 10.1080/09658210143000173</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/09658210143000173</ArticleId><ArticleId IdType="pubmed">11594351</ArticleId></ArticleIdList></Reference><Reference><Citation>Martin RC, Yan H, Schnur TT. Working memory and planning during sentence production. Acta Psychologica. 2014;152: 120&#x2013;132. doi: 10.1016/j.actpsy.2014.08.006</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.actpsy.2014.08.006</ArticleId><ArticleId IdType="pubmed">25216074</ArticleId></ArticleIdList></Reference><Reference><Citation>Linck JA, Osthus P, Koeth JT, Bunting MF. Working memory and second language comprehension and production: A meta-analysis. Psychonomic Bulletin &amp; Review. 2014;21(4): 861&#x2013;883. doi: 10.3758/s13423-013-0565-2</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/s13423-013-0565-2</ArticleId><ArticleId IdType="pubmed">24366687</ArticleId></ArticleIdList></Reference><Reference><Citation>Dong Y, Cai R. Working memory in interpreting: A commentary on theoretical models. In: Wen Z, Mota M, McNeill A, editors. Working Memory in Second Language Acquisition and Processing: Theory, Research and Commentary. Vol. 87. Bristol: Multilingual Matters; 2015. pp. 63&#x2013;81.</Citation></Reference><Reference><Citation>Dam HV. What makes interpreters&#x2019; notes efficient? Features of (non)efficiency in interpreters&#x2019; notes for consecutive. In: Gambier Y, Shlesinger M, Stolze R, editors. Doubts and Directions in Translation Studies: Contributions from the EST Congress, Lisbon 2004. Amsterdam and Philadelphia: John Benjamins; 2007. pp. 183&#x2013;198.</Citation></Reference><Reference><Citation>Eysenck MW, Derakshan N, Santos R, Calvo MG. Anxiety and cognitive performance: attentional control theory. Emotion. 2007;7(2): 336. doi: 10.1037/1528-3542.7.2.336</Citation><ArticleIdList><ArticleId IdType="doi">10.1037/1528-3542.7.2.336</ArticleId><ArticleId IdType="pubmed">17516812</ArticleId></ArticleIdList></Reference><Reference><Citation>Hu Z, Zheng B, Wang X. The impact of a metacognitive self-regulation inventory in translator self-training: a pre-post study with English-Chinese translation students. The Interpreter and Translator Trainer. 2020. doi: 10.1080/1750399X.2020.184443</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/1750399X.2020.184443</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">37146714</PMID><DateCompleted><Year>2023</Year><Month>07</Month><Day>21</Day></DateCompleted><DateRevised><Year>2023</Year><Month>08</Month><Day>04</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2352-345X</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>2</Issue><PubDate><Year>2023</Year></PubDate></JournalIssue><Title>Cellular and molecular gastroenterology and hepatology</Title><ISOAbbreviation>Cell Mol Gastroenterol Hepatol</ISOAbbreviation></Journal><ArticleTitle>Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans.</ArticleTitle><Pagination><StartPage>223</StartPage><EndPage>242</EndPage><MedlinePgn>223-242</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jcmgh.2023.04.007</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S2352-345X(23)00061-9</ELocationID><Abstract><AbstractText Label="BACKGROUND &amp; AIMS">OATP1B3/SLCO1B3 is a human liver-specific transporter for the clearance of endogenous compounds (eg, bile acid [BA]) and xenobiotics. The functional role of OATP1B3 in humans has not been characterized, as SLCO1B3 is poorly conserved among species without mouse orthologs.</AbstractText><AbstractText Label="METHODS">Slc10a1-knockout (Slc10a1<sup>-/-</sup>), Slc10a1<sup>hSLCO1B3</sup> (endogenous mouse Slc10a1 promoter-driven human-SLCO1B3 expression in Slc10a1<sup>-/-</sup> mice), and human SLCO1B3 liver-specific transgenic (hSLCO1B3-LTG) mice were generated and challenged with 0.1% ursodeoxycholic-acid (UDCA), 1% cholic-acid (CA) diet, or bile duct ligation (BDL) for functional studies. Primary hepatocytes and hepatoma-PLC/RPF/5 cells were used for mechanistic studies.</AbstractText><AbstractText Label="RESULTS">Serum BA levels in Slc10a1<sup>-/-</sup> mice were substantially increased with or without 0.1% UDCA feeding compared with wild-type (WT) mice. This increase was attenuated in Slc10a1<sup>hSLCO1B3</sup>-mice, indicating that OATP1B3 functions as a significant hepatic BA uptake transporter. In&#xa0;vitro assay using primary hepatocytes from WT, Slc10a1<sup>-/-</sup>, and Slc10a1<sup>hSLCO1B3</sup>-mice indicated that OATP1B3 has a similar capacity in taking up taurocholate/TCA as Ntcp. Furthermore, TCA-induced bile flow was significantly impaired in Slc10a1<sup>-/-</sup> mice but partially recovered in Slc10a1<sup>hSLC01B3</sup>-mice, indicating that OATP1B3 can partially compensate the NTCP function in&#xa0;vivo. Liver-specific overexpression of OATP1B3 markedly increased the level of hepatic conjugated BA and cholestatic liver injury in 1% CA-fed and BDL mice. Mechanistic studies revealed that conjugated BAs stimulated Ccl2 and Cxcl2 in hepatocytes to increase hepatic neutrophil infiltration and proinflammatory cytokine production (eg, IL-6), which activated STAT3 to repress OATP1B3 expression by binding to its promoter.</AbstractText><AbstractText Label="CONCLUSIONS">Human OATP1B3 is a significant BA uptake transporter and can partially compensate Ntcp for conjugated BA uptake in mice. Its downregulation in cholestasis is an adaptive protective response.</AbstractText><CopyrightInformation>Copyright &#xa9; 2023 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Qiong</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Guanyu</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Ziqian</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Jinfei</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Queen Mary School, Nanchang University, Nanchang, Jiangxi, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ouyang</LastName><ForeName>Jiafeng</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tong</LastName><ForeName>Yao</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaoxun</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Liangjun</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Ya</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jianwei</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Chengcheng</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Wensheng</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shi-Ying</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, Connecticut.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyer</LastName><ForeName>James L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, Connecticut.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Jin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Insitute of Digestive Diseases of PLA, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China; Center for Cholestatic Liver Diseases and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China. Electronic address: jin.chai@cldcsw.org.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2023</Year><Month>05</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cell Mol Gastroenterol Hepatol</MedlineTA><NlmUniqueID>101648302</NlmUniqueID><ISSNLinking>2352-345X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D027361">Organic Anion Transporters</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001647">Bile Acids and Salts</NameOfSubstance></Chemical><Chemical><RegistryNumber>724L30Y2QR</RegistryNumber><NameOfSubstance UI="D014580">Ursodeoxycholic Acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Cell Mol Gastroenterol Hepatol. 2023;16(2):319-320. doi: 10.1016/j.jcmgh.2023.05.005</RefSource><PMID Version="1">37244292</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008099" MajorTopicYN="N">Liver</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D027361" MajorTopicYN="Y">Organic Anion Transporters</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001647" MajorTopicYN="N">Bile Acids and Salts</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014580" MajorTopicYN="N">Ursodeoxycholic Acid</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002779" MajorTopicYN="Y">Cholestasis</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Bile Acid Transporter</Keyword><Keyword MajorTopicYN="N">Cholestasis</Keyword><Keyword MajorTopicYN="N">OATP1B3</Keyword><Keyword MajorTopicYN="N">Proinflammatory Cytokine</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>10</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2023</Year><Month>4</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2023</Year><Month>4</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>7</Month><Day>21</Day><Hour>6</Hour><Minute>43</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2023</Year><Month>5</Month><Day>6</Day><Hour>9</Hour><Minute>42</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2023</Year><Month>5</Month><Day>5</Day><Hour>19</Hour><Minute>25</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2023</Year><Month>5</Month><Day>3</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">37146714</ArticleId><ArticleId IdType="pmc">PMC10394288</ArticleId><ArticleId IdType="doi">10.1016/j.jcmgh.2023.04.007</ArticleId><ArticleId IdType="pii">S2352-345X(23)00061-9</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Wagner M., Zollner G., Trauner M. New molecular insights into the mechanisms of cholestasis. J&#xa0;Hepatol. 2009;51:565&#x2013;580.</Citation><ArticleIdList><ArticleId IdType="pubmed">19595470</ArticleId></ArticleIdList></Reference><Reference><Citation>Arias I.M., Alter H.J., Boyer J.L., et al. Adaptive Regulation of Hepatocyte Transporters in Cholestasis. Fifth Edition. Wiley; 2009. The liver: biology and pathobiology; pp. 681&#x2013;703.</Citation></Reference><Reference><Citation>Klaassen C.D., Aleksunes L.M. Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Pharmacol Rev. 2010;62:1&#x2013;96.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2835398</ArticleId><ArticleId IdType="pubmed">20103563</ArticleId></ArticleIdList></Reference><Reference><Citation>Jung D., Podvinec M., Meyer U.A., et al. Human organic anion transporting polypeptide 8 promoter is transactivated by the farnesoid X receptor/bile acid receptor. Gastroenterology. 2002;122:1954&#x2013;1966.</Citation><ArticleIdList><ArticleId IdType="pubmed">12055601</ArticleId></ArticleIdList></Reference><Reference><Citation>Durmus S., van Hoppe S., Schinkel A. The impact of organic anion-transporting polypeptides (OATPs) on disposition and toxicity of antitumor drugs: insights from knockout and humanized mice. Drug Resist Updat. 2016;27:72&#x2013;88.</Citation><ArticleIdList><ArticleId IdType="pubmed">27449599</ArticleId></ArticleIdList></Reference><Reference><Citation>Suga T., Yamaguchi H., Sato T., et al. Preference of conjugated bile acids over unconjugated bile acids as substrates for OATP1B1 and OATP1B3. PLoS One. 2017;12</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5218478</ArticleId><ArticleId IdType="pubmed">28060902</ArticleId></ArticleIdList></Reference><Reference><Citation>Ismair M.G., Stieger B., Cattori V., et al. Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver. Gastroenterology. 2001;121:1185&#x2013;1190.</Citation><ArticleIdList><ArticleId IdType="pubmed">11677211</ArticleId></ArticleIdList></Reference><Reference><Citation>Briz O., Romero M.R., Martinez-Becerra P., et al. OATP8/1B3-mediated cotransport of bile acids and glutathione: an export pathway for organic anions from hepatocytes? J&#xa0;Biol Chem. 2006;281:30326&#x2013;30335.</Citation><ArticleIdList><ArticleId IdType="pubmed">16877380</ArticleId></ArticleIdList></Reference><Reference><Citation>van de Steeg E., Stranecky V., Hartmannova H., et al. Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J&#xa0;Clin Invest. 2012;122:519&#x2013;528.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3266790</ArticleId><ArticleId IdType="pubmed">22232210</ArticleId></ArticleIdList></Reference><Reference><Citation>Slijepcevic D., Kaufman C., Wichers C.G.K., et al. Impaired uptake of conjugated bile acids and hepatitis b virus pres1-binding in na+-taurocholate cotransporting polypeptide knockout mice. Hepatology. 2015;62:207&#x2013;219.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4657468</ArticleId><ArticleId IdType="pubmed">25641256</ArticleId></ArticleIdList></Reference><Reference><Citation>Vaz F.M., Paulusma C.C., Huidekoper H., et al. Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: conjugated hypercholanemia without a clear clinical phenotype. Hepatology. 2015;61:260&#x2013;267.</Citation><ArticleIdList><ArticleId IdType="pubmed">24867799</ArticleId></ArticleIdList></Reference><Reference><Citation>Erlinger S. NTCP deficiency: a new inherited disease of bile acid transport. Clin Res Hepatol Gastroenterol. 2015;39:7&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">25193235</ArticleId></ArticleIdList></Reference><Reference><Citation>Keitel V., Burdelski M., Warskulat U., et al. Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis. Hepatology. 2005;41:1160&#x2013;1172.</Citation><ArticleIdList><ArticleId IdType="pubmed">15841457</ArticleId></ArticleIdList></Reference><Reference><Citation>Yan Z., Li E., He L., et al. Role of OATP1B3 in the transport of bile acids assessed using first-trimester trophoblasts. J&#xa0;Obstet Gynaecol Res. 2015;41:392&#x2013;401.</Citation><ArticleIdList><ArticleId IdType="pubmed">25345542</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai S.Y., Ouyang X., Chen Y., et al. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight. 2017;2</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5333973</ArticleId><ArticleId IdType="pubmed">28289714</ArticleId></ArticleIdList></Reference><Reference><Citation>Roh Y.S., Cho A., Cha Y.S., et al. Lactobacillus aggravate bile duct ligation-induced liver inflammation and fibrosis in mice. Toxicol Res. 2018;34:241&#x2013;247.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6057294</ArticleId><ArticleId IdType="pubmed">30057698</ArticleId></ArticleIdList></Reference><Reference><Citation>Chai J., He Y., Cai S.Y., et al. Elevated hepatic multidrug resistance-associated protein 3/ATP-binding cassette subfamily C 3 expression in human obstructive cholestasis is mediated through tumor necrosis factor alpha and c-Jun NH2-terminal kinase/stress-activated protein kinase-signaling pathway. Hepatology. 2012;55:1485&#x2013;1494.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3297707</ArticleId><ArticleId IdType="pubmed">22105759</ArticleId></ArticleIdList></Reference><Reference><Citation>Le Vee M., Lecureur V., Stieger B., Fardel O. Regulation of drug transporter expression in human hepatocytes exposed to the proinflammatory cytokines tumor necrosis factor-alpha or interleukin-6. Drug Metab Dispos. 2009;37:685&#x2013;693.</Citation><ArticleIdList><ArticleId IdType="pubmed">19074973</ArticleId></ArticleIdList></Reference><Reference><Citation>Johnson D.E., O&#x2019;Keefe R.A., Grandis J.R. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018;15:234&#x2013;248.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5858971</ArticleId><ArticleId IdType="pubmed">29405201</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu E.H., Zheng Z.N., Xiao C.X., et al. IL-22 relieves sepsis-induced liver injury via activating JAK/STAT3 signaling pathway. J&#xa0;Biol Regul Homeost Agents. 2020;34:1719&#x2013;1727.</Citation><ArticleIdList><ArticleId IdType="pubmed">33179463</ArticleId></ArticleIdList></Reference><Reference><Citation>Xu G., Dai M., Zheng X., Lin H., Liu A., Yang J. Cholestatic models induced by lithocholic acid and alphanaphthylisothiocyanate: different etiological mechanisms for liver injury but shared JNK/STAT3 signaling. Mol Med Rep. 2020;22:1583&#x2013;1593.</Citation><ArticleIdList><ArticleId IdType="pubmed">32626965</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang L.J., Pan Q., Zhang L., et al. Runt-related transcription factor-1 ameliorates bile acid-induced hepatic inflammation in cholestasis via JAK/STAT3 signaling. Hepatology. 2023;77:1866&#x2013;1881.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC10921919</ArticleId><ArticleId IdType="pubmed">36647589</ArticleId></ArticleIdList></Reference><Reference><Citation>Pan Q., Zhang X., Zhang L., et al. Solute carrier organic anion transporter family member 3A1 is a bile acid efflux transporter in cholestasis. Gastroenterology. 2018;155:1578&#x2013;1592.e16.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6221191</ArticleId><ArticleId IdType="pubmed">30063921</ArticleId></ArticleIdList></Reference><Reference><Citation>Kim N.D., Moon J.O., Slitt A.L., Copple B.L. Early growth response factor-1 is critical for cholestatic liver injury. Toxicol Sci. 2006;90:586&#x2013;595.</Citation><ArticleIdList><ArticleId IdType="pubmed">16423862</ArticleId></ArticleIdList></Reference><Reference><Citation>Li J., Zhu X., Zhang M., et al. Limb expression 1-like (LIX1L) protein promotes cholestatic liver injury by regulating bile acid metabolism. J&#xa0;Hepatol. 2021;75:400&#x2013;413.</Citation><ArticleIdList><ArticleId IdType="pubmed">33746084</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang H., Zhang J., Zhang X., et al. Fluorofenidone ameliorates cholestasis and fibrosis by inhibiting hepatic Erk/-Egr-1 signaling and Tgf&#x3b2;1/Smad pathway in mice. Biochim Biophys Acta Mol Basis Dis. 2022</Citation><ArticleIdList><ArticleId IdType="pubmed">36154893</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu R.H., Chen C.M., Xia X.F., et al. Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine. Sci Rep. 2017;7:9214.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5569087</ArticleId><ArticleId IdType="pubmed">28835676</ArticleId></ArticleIdList></Reference><Reference><Citation>Pan Q., Luo G., Qu J., et al. A&#xa0;homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis. EMBO Mol Med. 2021</Citation><ArticleIdList><ArticleId IdType="pmc">PMC8573601</ArticleId><ArticleId IdType="pubmed">34585848</ArticleId></ArticleIdList></Reference><Reference><Citation>Nagy A., Gertsenstein M., Vintersten K., Behringer R. Third Edition. Cold Spring Harbor; 2003. Manipulating the mouse embryo: a laboratory manual; p. 24.</Citation></Reference><Reference><Citation>Oude Elferink R.P., Ottenhoff R., van Wijland M., et al. Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse. J&#xa0;Clin Invest. 1995;95:31&#x2013;38.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC295363</ArticleId><ArticleId IdType="pubmed">7814632</ArticleId></ArticleIdList></Reference><Reference><Citation>Ubags N.D.J., Suratt B.T. Isolation and characterization of mouse neutrophils. Methods Mol Biol. 2018;1809:45&#x2013;57.</Citation><ArticleIdList><ArticleId IdType="pubmed">29987781</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">37120214</PMID><DateCompleted><Year>2023</Year><Month>05</Month><Day>04</Day></DateCompleted><DateRevised><Year>2023</Year><Month>05</Month><Day>04</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-7145</ISSN><JournalIssue CitedMedium="Internet"><Volume>168</Volume><PubDate><Year>2023</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Food research international (Ottawa, Ont.)</Title><ISOAbbreviation>Food Res Int</ISOAbbreviation></Journal><ArticleTitle>Effects of endogenous capsaicin stress and fermentation time on the microbial succession and flavor compounds of chili paste (a Chinese fermented chili pepper).</ArticleTitle><Pagination><StartPage>112763</StartPage><MedlinePgn>112763</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.foodres.2023.112763</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0963-9969(23)00308-3</ELocationID><Abstract><AbstractText>Chili paste, is a popular traditional product derived from chili pepper, and its fermentation system is affected by the variable concentration of capsaicin, which originates from the peppers. In the present study, the effects of capsaicin and fermentation time on the microbial community and flavor compounds of chili paste were investigated. After capsaicin supplementation, the total acid was significantly decreased (p&#xa0;&lt;&#xa0;0.05) along with lower total bacteria, especially lactic acid bacteria. Lactiplantibacillus, Lactobacillus, Weissella, Issatchenkia, Trichoderma, and Pichia were the shared and predominant genera; whereas, the Bacteroides and Kazachstania abundance was significantly increased due to the selection effect of capsaicin over time. Additionally, alterations of the microbial interaction networks and their metabolic preferences led to less lactic acid content with greater accumulation of ethyl nonanoate, methyl nonanoate, etc. This study will provide a perspective for selecting chili pepper varieties and improving the quality of fermented chili paste.</AbstractText><CopyrightInformation>Copyright &#xa9; 2023 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Shi</LastName><ForeName>Qiao</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Institute of Agro-Products Processing, Yunnan Academy of Agricultural Sciences, Kunming, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Huihua</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Institute of Agro-Products Processing, Yunnan Academy of Agricultural Sciences, Kunming, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mei</LastName><ForeName>Yuan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Institute of Agro-products Processing Science and Technology, Sichuan Academy of Agricultural Sciences, Chengdu, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Junfei</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Agro-Products Processing, Yunnan Academy of Agricultural Sciences, Kunming, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Xinrui</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Institute of Agro-Products Processing, Yunnan Academy of Agricultural Sciences, Kunming, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Biqin</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Institute of Agro-Products Processing, Yunnan Academy of Agricultural Sciences, Kunming, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Yingli</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Institute of Agro-Products Processing, Yunnan Academy of Agricultural Sciences, Kunming, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Institute of Agro-products Processing Science and Technology, Sichuan Academy of Agricultural Sciences, Chengdu, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Menglu</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Agro-products Processing Science and Technology, Sichuan Academy of Agricultural Sciences, Chengdu, China. Electronic address: MengluYY@126.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Hong</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Institute of Agro-Products Processing, Yunnan Academy of Agricultural Sciences, Kunming, China. Electronic address: ynveg@163.com.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2023</Year><Month>03</Month><Day>27</Day></ArticleDate></Article><MedlineJournalInfo><Country>Canada</Country><MedlineTA>Food Res Int</MedlineTA><NlmUniqueID>9210143</NlmUniqueID><ISSNLinking>0963-9969</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>76-22-2</RegistryNumber><NameOfSubstance UI="D002164">Camphor</NameOfSubstance></Chemical><Chemical><RegistryNumber>S07O44R1ZM</RegistryNumber><NameOfSubstance UI="D002211">Capsaicin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000723071">ethyl nonanoate</NameOfSubstance></Chemical><Chemical><RegistryNumber>1490-04-6</RegistryNumber><NameOfSubstance UI="D008610">Menthol</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002164" MajorTopicYN="N">Camphor</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002211" MajorTopicYN="N">Capsaicin</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002212" MajorTopicYN="Y">Capsicum</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005285" MajorTopicYN="N">Fermentation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008610" MajorTopicYN="N">Menthol</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Capsaicin supplementation</Keyword><Keyword MajorTopicYN="N">Ethyl nonanoate</Keyword><Keyword MajorTopicYN="N">Kazachstania</Keyword><Keyword MajorTopicYN="N">Microbial diversity</Keyword><Keyword MajorTopicYN="N">Volatile characteristics</Keyword></KeywordList><CoiStatement>Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>10</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2023</Year><Month>3</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2023</Year><Month>3</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>5</Month><Day>1</Day><Hour>6</Hour><Minute>41</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2023</Year><Month>4</Month><Day>30</Day><Hour>0</Hour><Minute>42</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2023</Year><Month>4</Month><Day>29</Day><Hour>20</Hour><Minute>57</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">37120214</ArticleId><ArticleId IdType="doi">10.1016/j.foodres.2023.112763</ArticleId><ArticleId IdType="pii">S0963-9969(23)00308-3</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">36834588</PMID><DateCompleted><Year>2023</Year><Month>02</Month><Day>28</Day></DateCompleted><DateRevised><Year>2023</Year><Month>02</Month><Day>28</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1422-0067</ISSN><JournalIssue CitedMedium="Internet"><Volume>24</Volume><Issue>4</Issue><PubDate><Year>2023</Year><Month>Feb</Month><Day>06</Day></PubDate></JournalIssue><Title>International journal of molecular sciences</Title><ISOAbbreviation>Int J Mol Sci</ISOAbbreviation></Journal><ArticleTitle>Gut Microbiota Deficiency Exacerbates Liver Injury in Bile Duct Ligated Mice via Inflammation and Lipid Metabolism.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">3180</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/ijms24043180</ELocationID><Abstract><AbstractText>Bile components play a critical role in maintaining gut microbiota homeostasis. In cholestasis, bile secretion is impaired, leading to liver injury. However, it remains to be elucidated whether gut microbiota plays a role in cholestatic liver injury. Here, we performed a sham operation and bile duct ligation (BDL) in antibiotic-induced microbiome depleted (AIMD) mice and assessed liver injury and fecal microbiota composition in these mice. Significant reductions in gut microbiota richness and diversity were found in AIMD-sham mice when compared to sham controls. Three-day BDL leads to great elevation of plasma ALT, ALP, total bile acids, and bilirubin where reduced diversity of the gut microbiota was also found. AIMD further aggravated cholestatic liver injury evidenced by significantly higher levels of plasma ALT and ALP, associated with further reduced diversity and increased Gram-negative bacteria in gut microbiota. Further analyses revealed increased levels of LPS in the plasma of AIMD-BDL mice where elevated expression of inflammatory genes and decreased expression of hepatic detoxification enzymes were also found in liver when compared to the BDL group. These findings indicate that gut microbiota plays a critical role in cholestatic liver injury. Maintaining its homeostasis may alleviate liver injury in patients with cholestasis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Xueqian</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaoxun</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0002-3892-7464</Identifier><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Liangjun</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qiu</LastName><ForeName>Wen</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Chunwei</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Jin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shiying</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>The Liver Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Wensheng</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>82070599</GrantID><Agency>National Natural Science Foundation of China</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2023</Year><Month>02</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Int J Mol Sci</MedlineTA><NlmUniqueID>101092791</NlmUniqueID><ISSNLinking>1422-0067</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001647">Bile Acids and Salts</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000069196" MajorTopicYN="Y">Gastrointestinal Microbiome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D050356" MajorTopicYN="N">Lipid Metabolism</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008099" MajorTopicYN="N">Liver</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001652" MajorTopicYN="N">Bile Ducts</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002779" MajorTopicYN="Y">Cholestasis</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007249" MajorTopicYN="N">Inflammation</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001647" MajorTopicYN="N">Bile Acids and Salts</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008026" MajorTopicYN="N">Ligation</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">biliary ligation</Keyword><Keyword MajorTopicYN="N">cholestasis</Keyword><Keyword MajorTopicYN="N">gut microbiota</Keyword><Keyword MajorTopicYN="N">liver injury</Keyword><Keyword MajorTopicYN="N">transcriptome</Keyword></KeywordList><CoiStatement>The authors declare that they have no competing interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>12</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2023</Year><Month>1</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2023</Year><Month>1</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2023</Year><Month>2</Month><Day>25</Day><Hour>2</Hour><Minute>38</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2023</Year><Month>2</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>3</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2023</Year><Month>2</Month><Day>6</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">36834588</ArticleId><ArticleId IdType="pmc">PMC9960910</ArticleId><ArticleId IdType="doi">10.3390/ijms24043180</ArticleId><ArticleId IdType="pii">ijms24043180</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Liu H.X., Keane R., Sheng L., Wan Y.J. Implications of microbiota and bile acid in liver injury and regeneration. J. Hepatol. 2015;63:1502&#x2013;1510. doi: 10.1016/j.jhep.2015.08.001.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2015.08.001</ArticleId><ArticleId IdType="pmc">PMC4654653</ArticleId><ArticleId IdType="pubmed">26256437</ArticleId></ArticleIdList></Reference><Reference><Citation>Kostic A.D., Gevers D., Siljander H., Vatanen T., Hyotylainen T., Hamalainen A.M., Peet A., Tillmann V., Poho P., Mattila I., et al. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe. 2015;17:260&#x2013;273. doi: 10.1016/j.chom.2015.01.001.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.chom.2015.01.001</ArticleId><ArticleId IdType="pmc">PMC4689191</ArticleId><ArticleId IdType="pubmed">25662751</ArticleId></ArticleIdList></Reference><Reference><Citation>Zheng P., Zeng B., Zhou C., Liu M., Fang Z., Xu X., Zeng L., Chen J., Fan S., Du X., et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host&#x2019;s metabolism. Mol. Psychiatry. 2016;21:786&#x2013;796. doi: 10.1038/mp.2016.44.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/mp.2016.44</ArticleId><ArticleId IdType="pubmed">27067014</ArticleId></ArticleIdList></Reference><Reference><Citation>Le Chatelier E., Nielsen T., Qin J., Prifti E., Hildebrand F., Falony G., Almeida M., Arumugam M., Batto J.M., Kennedy S., et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541&#x2013;546. doi: 10.1038/nature12506.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nature12506</ArticleId><ArticleId IdType="pubmed">23985870</ArticleId></ArticleIdList></Reference><Reference><Citation>Lindheim L., Bashir M., Munzker J., Trummer C., Zachhuber V., Leber B., Horvath A., Pieber T.R., Gorkiewicz G., Stadlbauer V., et al. Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study. PLoS ONE. 2017;12:e0168390. doi: 10.1371/journal.pone.0168390.</Citation><ArticleIdList><ArticleId IdType="doi">10.1371/journal.pone.0168390</ArticleId><ArticleId IdType="pmc">PMC5207627</ArticleId><ArticleId IdType="pubmed">28045919</ArticleId></ArticleIdList></Reference><Reference><Citation>Kwong E.K., Puri P. Gut microbiome changes in Nonalcoholic fatty liver disease &amp; alcoholic liver disease. Transl. Gastroenterol. Hepatol. 2021;6:3. doi: 10.21037/tgh.2020.02.18.</Citation><ArticleIdList><ArticleId IdType="doi">10.21037/tgh.2020.02.18</ArticleId><ArticleId IdType="pmc">PMC7724179</ArticleId><ArticleId IdType="pubmed">33409398</ArticleId></ArticleIdList></Reference><Reference><Citation>Gawlik-Kotelnicka O., Strzelecki D. Adiposity in Depression or Depression in Adiposity? The Role of Immune-Inflammatory-Microbial Overlap. Life. 2021;11:117. doi: 10.3390/life11020117.</Citation><ArticleIdList><ArticleId IdType="doi">10.3390/life11020117</ArticleId><ArticleId IdType="pmc">PMC7913759</ArticleId><ArticleId IdType="pubmed">33557031</ArticleId></ArticleIdList></Reference><Reference><Citation>Lau H.C.H., Sung J.J., Yu J. Gut microbiota: Impacts on gastrointestinal cancer immunotherapy. Gut Microbes. 2021;13:1&#x2013;21. doi: 10.1080/19490976.2020.1869504.</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/19490976.2020.1869504</ArticleId><ArticleId IdType="pmc">PMC7808428</ArticleId><ArticleId IdType="pubmed">33435800</ArticleId></ArticleIdList></Reference><Reference><Citation>Garcia-Gutierrez E., Narbad A., Rodriguez J.M. Autism Spectrum Disorder Associated With Gut Microbiota at Immune, Metabolomic, and Neuroactive Level. Front. Neurosci. 2020;14:578666. doi: 10.3389/fnins.2020.578666.</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fnins.2020.578666</ArticleId><ArticleId IdType="pmc">PMC7578228</ArticleId><ArticleId IdType="pubmed">33117122</ArticleId></ArticleIdList></Reference><Reference><Citation>Lozupone C.A., Stombaugh J.I., Gordon J.I., Jansson J.K., Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220&#x2013;230. doi: 10.1038/nature11550.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nature11550</ArticleId><ArticleId IdType="pmc">PMC3577372</ArticleId><ArticleId IdType="pubmed">22972295</ArticleId></ArticleIdList></Reference><Reference><Citation>Turnbaugh P.J., Backhed F., Fulton L., Gordon J.I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3:213&#x2013;223. doi: 10.1016/j.chom.2008.02.015.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.chom.2008.02.015</ArticleId><ArticleId IdType="pmc">PMC3687783</ArticleId><ArticleId IdType="pubmed">18407065</ArticleId></ArticleIdList></Reference><Reference><Citation>Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrini V., Mardis E.R., Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027&#x2013;1031. doi: 10.1038/nature05414.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nature05414</ArticleId><ArticleId IdType="pubmed">17183312</ArticleId></ArticleIdList></Reference><Reference><Citation>Wong S.H., Zhao L., Zhang X., Nakatsu G., Han J., Xu W., Xiao X., Kwong T.N.Y., Tsoi H., Wu W.K.K., et al. Gavage of Fecal Samples From Patients With Colorectal Cancer Promotes Intestinal Carcinogenesis in Germ-Free and Conventional Mice. Gastroenterology. 2017;153:1621&#x2013;1633.e1626. doi: 10.1053/j.gastro.2017.08.022.</Citation><ArticleIdList><ArticleId IdType="doi">10.1053/j.gastro.2017.08.022</ArticleId><ArticleId IdType="pubmed">28823860</ArticleId></ArticleIdList></Reference><Reference><Citation>Zarrinpar A., Chaix A., Xu Z.Z., Chang M.W., Marotz C.A., Saghatelian A., Knight R., Panda S. Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism. Nat. Commun. 2018;9:2872. doi: 10.1038/s41467-018-05336-9.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41467-018-05336-9</ArticleId><ArticleId IdType="pmc">PMC6054678</ArticleId><ArticleId IdType="pubmed">30030441</ArticleId></ArticleIdList></Reference><Reference><Citation>Wichmann A., Allahyar A., Greiner T.U., Plovier H., Lunden G.O., Larsson T., Drucker D.J., Delzenne N.M., Cani P.D., Backhed F. Microbial modulation of energy availability in the colon regulates intestinal transit. Cell Host Microbe. 2013;14:582&#x2013;590. doi: 10.1016/j.chom.2013.09.012.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.chom.2013.09.012</ArticleId><ArticleId IdType="pubmed">24237703</ArticleId></ArticleIdList></Reference><Reference><Citation>Kusaczuk M. Tauroursodeoxycholate-Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives. Cells. 2019;8:1471. doi: 10.3390/cells8121471.</Citation><ArticleIdList><ArticleId IdType="doi">10.3390/cells8121471</ArticleId><ArticleId IdType="pmc">PMC6952947</ArticleId><ArticleId IdType="pubmed">31757001</ArticleId></ArticleIdList></Reference><Reference><Citation>Benakis C., Martin-Gallausiaux C., Trezzi J.P., Melton P., Liesz A., Wilmes P. The microbiome-gut-brain axis in acute and chronic brain diseases. Curr. Opin. Neurobiol. 2020;61:1&#x2013;9. doi: 10.1016/j.conb.2019.11.009.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.conb.2019.11.009</ArticleId><ArticleId IdType="pubmed">31812830</ArticleId></ArticleIdList></Reference><Reference><Citation>Cabrera-Rubio R., Patterson A.M., Cotter P.D., Beraza N. Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice. Sci. Rep. 2019;9:12324. doi: 10.1038/s41598-019-48784-z.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41598-019-48784-z</ArticleId><ArticleId IdType="pmc">PMC6707139</ArticleId><ArticleId IdType="pubmed">31444478</ArticleId></ArticleIdList></Reference><Reference><Citation>Qin N., Yang F., Li A., Prifti E., Chen Y., Shao L., Guo J., Le Chatelier E., Yao J., Wu L., et al. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014;513:59&#x2013;64. doi: 10.1038/nature13568.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nature13568</ArticleId><ArticleId IdType="pubmed">25079328</ArticleId></ArticleIdList></Reference><Reference><Citation>Loomba R., Seguritan V., Li W., Long T., Klitgord N., Bhatt A., Dulai P.S., Caussy C., Bettencourt R., Highlander S.K., et al. Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell Metab. 2017;25:1054&#x2013;1062.e1055. doi: 10.1016/j.cmet.2017.04.001.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.cmet.2017.04.001</ArticleId><ArticleId IdType="pmc">PMC5502730</ArticleId><ArticleId IdType="pubmed">28467925</ArticleId></ArticleIdList></Reference><Reference><Citation>Bajaj J.S., Heuman D.M., Hylemon P.B., Sanyal A.J., White M.B., Monteith P., Noble N.A., Unser A.B., Daita K., Fisher A.R., et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J. Hepatol. 2014;60:940&#x2013;947. doi: 10.1016/j.jhep.2013.12.019.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2013.12.019</ArticleId><ArticleId IdType="pmc">PMC3995845</ArticleId><ArticleId IdType="pubmed">24374295</ArticleId></ArticleIdList></Reference><Reference><Citation>Lee G., You H.J., Bajaj J.S., Joo S.K., Yu J., Park S., Kang H., Park J.H., Kim J.H., Lee D.H., et al. Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD. Nat. Commun. 2020;11:4982. doi: 10.1038/s41467-020-18754-5.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41467-020-18754-5</ArticleId><ArticleId IdType="pmc">PMC7536225</ArticleId><ArticleId IdType="pubmed">33020474</ArticleId></ArticleIdList></Reference><Reference><Citation>Munukka E., Rintala A., Toivonen R., Nylund M., Yang B., Takanen A., Hanninen A., Vuopio J., Huovinen P., Jalkanen S., et al. Faecalibacterium prausnitzii treatment improves hepatic health and reduces adipose tissue inflammation in high-fat fed mice. ISME J. 2017;11:1667&#x2013;1679. doi: 10.1038/ismej.2017.24.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/ismej.2017.24</ArticleId><ArticleId IdType="pmc">PMC5520144</ArticleId><ArticleId IdType="pubmed">28375212</ArticleId></ArticleIdList></Reference><Reference><Citation>Sinha S.R., Haileselassie Y., Nguyen L.P., Tropini C., Wang M., Becker L.S., Sim D., Jarr K., Spear E.T., Singh G., et al. Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation. Cell Host Microbe. 2020;27:659&#x2013;670.e655. doi: 10.1016/j.chom.2020.01.021.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.chom.2020.01.021</ArticleId><ArticleId IdType="pmc">PMC8172352</ArticleId><ArticleId IdType="pubmed">32101703</ArticleId></ArticleIdList></Reference><Reference><Citation>Kakiyama G., Pandak W.M., Gillevet P.M., Hylemon P.B., Heuman D.M., Daita K., Takei H., Muto A., Nittono H., Ridlon J.M., et al. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. J. Hepatol. 2013;58:949&#x2013;955. doi: 10.1016/j.jhep.2013.01.003.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2013.01.003</ArticleId><ArticleId IdType="pmc">PMC3936319</ArticleId><ArticleId IdType="pubmed">23333527</ArticleId></ArticleIdList></Reference><Reference><Citation>Maharshak N., Packey C.D., Ellermann M., Manick S., Siddle J.P., Huh E.Y., Plevy S., Sartor R.B., Carroll I.M. Altered enteric microbiota ecology in interleukin 10-deficient mice during development and progression of intestinal inflammation. Gut Microbes. 2013;4:316&#x2013;324. doi: 10.4161/gmic.25486.</Citation><ArticleIdList><ArticleId IdType="doi">10.4161/gmic.25486</ArticleId><ArticleId IdType="pmc">PMC3744516</ArticleId><ArticleId IdType="pubmed">23822920</ArticleId></ArticleIdList></Reference><Reference><Citation>Selvanantham T., Lin Q., Guo C.X., Surendra A., Fieve S., Escalante N.K., Guttman D.S., Streutker C.J., Robertson S.J., Philpott D.J., et al. NKT Cell-Deficient Mice Harbor an Altered Microbiota That Fuels Intestinal Inflammation during Chemically Induced Colitis. J. Immunol. 2016;197:4464&#x2013;4472. doi: 10.4049/jimmunol.1601410.</Citation><ArticleIdList><ArticleId IdType="doi">10.4049/jimmunol.1601410</ArticleId><ArticleId IdType="pubmed">27799307</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu T., Yu H., Zhang Z., Xie Y., Yang L., You F. Intestinal ELF4 Deletion Exacerbates Alcoholic Liver Disease by Disrupting Gut Homeostasis. Int. J. Mol. Sci. 2022;23:4825. doi: 10.3390/ijms23094825.</Citation><ArticleIdList><ArticleId IdType="doi">10.3390/ijms23094825</ArticleId><ArticleId IdType="pmc">PMC9102452</ArticleId><ArticleId IdType="pubmed">35563234</ArticleId></ArticleIdList></Reference><Reference><Citation>Mao J., Zhan H., Meng F., Wang G., Huang D., Liao Z., Chen M. Costunolide protects against alcohol-induced liver injury by regulating gut microbiota, oxidative stress and attenuating inflammation in vivo and in vitro. Phytotherapy Res. 2022;36:1268&#x2013;1283. doi: 10.1002/ptr.7383.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/ptr.7383</ArticleId><ArticleId IdType="pubmed">35084790</ArticleId></ArticleIdList></Reference><Reference><Citation>Gupta H., Suk K.T., Kim D.J. Gut Microbiota at the Intersection of Alcohol, Brain, and the Liver. J. Clin. Med. 2021;10:541. doi: 10.3390/jcm10030541.</Citation><ArticleIdList><ArticleId IdType="doi">10.3390/jcm10030541</ArticleId><ArticleId IdType="pmc">PMC7867253</ArticleId><ArticleId IdType="pubmed">33540624</ArticleId></ArticleIdList></Reference><Reference><Citation>Akira S., Uematsu S., Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783&#x2013;801. doi: 10.1016/j.cell.2006.02.015.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.cell.2006.02.015</ArticleId><ArticleId IdType="pubmed">16497588</ArticleId></ArticleIdList></Reference><Reference><Citation>Hakoupian M., Ferino E., Jickling G.C., Amini H., Stamova B., Ander B.P., Alomar N., Sharp F.R., Zhan X. Bacterial lipopolysaccharide is associated with stroke. Sci. Rep. 2021;11:6570. doi: 10.1038/s41598-021-86083-8.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41598-021-86083-8</ArticleId><ArticleId IdType="pmc">PMC7985504</ArticleId><ArticleId IdType="pubmed">33753837</ArticleId></ArticleIdList></Reference><Reference><Citation>Choi S.H., Kim S.G. Lipopolysaccharide inhibition of rat hepatic microsomal epoxide hydrolase and glutathione S-transferase gene expression irrespective of nuclear factor-kappaB activation. Biochem. Pharmacol. 1998;56:1427&#x2013;1436. doi: 10.1016/S0006-2952(98)00204-4.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0006-2952(98)00204-4</ArticleId><ArticleId IdType="pubmed">9827574</ArticleId></ArticleIdList></Reference><Reference><Citation>Nyagode B.A., Williams I.R., Morgan E.T. Altered inflammatory responses to Citrobacter rodentium infection, but not bacterial lipopolysaccharide, in mice lacking the Cyp4a10 or Cyp4a14 genes. Inflammation. 2014;37:893&#x2013;907. doi: 10.1007/s10753-013-9809-6.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s10753-013-9809-6</ArticleId><ArticleId IdType="pmc">PMC4035451</ArticleId><ArticleId IdType="pubmed">24413902</ArticleId></ArticleIdList></Reference><Reference><Citation>Robertson G., Leclercq I., Farrell G.C. Nonalcoholic steatosis and steatohepatitis. II. Cytochrome P-450 enzymes and oxidative stress. Am. J. Physiol. Liver Physiol. 2001;281:G1135&#x2013;G1139. doi: 10.1152/ajpgi.2001.281.5.G1135.</Citation><ArticleIdList><ArticleId IdType="doi">10.1152/ajpgi.2001.281.5.G1135</ArticleId><ArticleId IdType="pubmed">11668021</ArticleId></ArticleIdList></Reference><Reference><Citation>Kennedy E.A., King K.Y., Baldridge M.T. Mouse Microbiota Models: Comparing Germ-Free Mice and Antibiotics Treatment as Tools for Modifying Gut Bacteria. Front. Physiol. 2018;9:1534. doi: 10.3389/fphys.2018.01534.</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fphys.2018.01534</ArticleId><ArticleId IdType="pmc">PMC6220354</ArticleId><ArticleId IdType="pubmed">30429801</ArticleId></ArticleIdList></Reference><Reference><Citation>Chen S., Zhou Y., Chen Y., Gu J. fastp: An ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018;34:i884&#x2013;i890. doi: 10.1093/bioinformatics/bty560.</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/bioinformatics/bty560</ArticleId><ArticleId IdType="pmc">PMC6129281</ArticleId><ArticleId IdType="pubmed">30423086</ArticleId></ArticleIdList></Reference><Reference><Citation>Magoc T., Salzberg S.L. FLASH: Fast length adjustment of short reads to improve genome assemblies. Bioinformatics. 2011;27:2957&#x2013;2963. doi: 10.1093/bioinformatics/btr507.</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/bioinformatics/btr507</ArticleId><ArticleId IdType="pmc">PMC3198573</ArticleId><ArticleId IdType="pubmed">21903629</ArticleId></ArticleIdList></Reference><Reference><Citation>Edgar R.C. UPARSE: Highly accurate OTU sequences from microbial amplicon reads. Nat. Methods. 2013;10:996&#x2013;998. doi: 10.1038/nmeth.2604.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nmeth.2604</ArticleId><ArticleId IdType="pubmed">23955772</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang Q., Garrity G.M., Tiedje J.M., Cole J.R. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 2007;73:5261&#x2013;5267. doi: 10.1128/AEM.00062-07.</Citation><ArticleIdList><ArticleId IdType="doi">10.1128/AEM.00062-07</ArticleId><ArticleId IdType="pmc">PMC1950982</ArticleId><ArticleId IdType="pubmed">17586664</ArticleId></ArticleIdList></Reference><Reference><Citation>Kim D., Langmead B., Salzberg S.L. HISAT: A fast spliced aligner with low memory requirements. Nat. Methods. 2015;12:357&#x2013;360. doi: 10.1038/nmeth.3317.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nmeth.3317</ArticleId><ArticleId IdType="pmc">PMC4655817</ArticleId><ArticleId IdType="pubmed">25751142</ArticleId></ArticleIdList></Reference><Reference><Citation>Li B., Dewey C.N. RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform. 2011;12:323. doi: 10.1186/1471-2105-12-323.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/1471-2105-12-323</ArticleId><ArticleId IdType="pmc">PMC3163565</ArticleId><ArticleId IdType="pubmed">21816040</ArticleId></ArticleIdList></Reference><Reference><Citation>Love M.I., Huber W., Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550. doi: 10.1186/s13059-014-0550-8.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/s13059-014-0550-8</ArticleId><ArticleId IdType="pmc">PMC4302049</ArticleId><ArticleId IdType="pubmed">25516281</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">36759512</PMID><DateCompleted><Year>2023</Year><Month>02</Month><Day>13</Day></DateCompleted><DateRevised><Year>2023</Year><Month>12</Month><Day>20</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN><JournalIssue CitedMedium="Internet"><Volume>14</Volume><Issue>1</Issue><PubDate><Year>2023</Year><Month>Feb</Month><Day>09</Day></PubDate></JournalIssue><Title>Nature communications</Title><ISOAbbreviation>Nat Commun</ISOAbbreviation></Journal><ArticleTitle>Unique DUOX2<sup>+</sup>ACE2<sup>+</sup> small cholangiocytes are pathogenic targets for primary biliary cholangitis.</ArticleTitle><Pagination><StartPage>29</StartPage><MedlinePgn>29</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">29</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41467-022-34606-w</ELocationID><Abstract><AbstractText>Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease. Using single-cell RNA sequencing (scRNA-seq), fluorescence-activated-cell-sorting, multiplex immunofluorescence (IF) and RNAscope analyses, we identified unique DUOX2<sup>+</sup>ACE2<sup>+</sup> small cholangiocytes in human and mouse livers. Their selective decrease in PBC patients was associated with the severity of disease. Moreover, proteomics, scRNA-seq, and qPCR analyses indicated that polymeric immunoglobulin receptor (pIgR) was highly expressed in DUOX2<sup>+</sup>ACE2<sup>+</sup> cholangiocytes. Serum anti-pIgR autoantibody levels were significantly increased in PBC patients, regardless of positive and negative AMA-M2. Spatial transcriptomics and multiplex IF revealed that CD27<sup>+</sup> memory B and plasma cells accumulated in the hepatic portal tracts of PBC patients. Collectively, DUOX2<sup>+</sup>ACE2<sup>+</sup> small cholangiocytes are pathogenic targets in PBC, and preservation of DUOX2<sup>+</sup>ACE2<sup>+</sup> cholangiocytes and targeting anti-pIgR autoantibodies may be valuable strategies for therapeutic interventions in PBC.</AbstractText><CopyrightInformation>&#xa9; 2023. The Author(s).</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Li</LastName><ForeName>Xi</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Hematology, the Third Affiliated Hospital (Daping Hospital), Third Military Medical University (Army Medical University), Chongqing, 400042, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Li</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Xiao</LastName><ForeName>Jintao</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Wang</LastName><ForeName>Huiwen</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Hepatology and Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Guo</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, 410008, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Mao</LastName><ForeName>Xiuru</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Hepatology and Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Shi</LastName><ForeName>Pan</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hou</LastName><ForeName>Yanliang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaoxun</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Minghua</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0003-4984-2631</Identifier><AffiliationInfo><Affiliation>MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>He</LastName><ForeName>Yonghong</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Jingjing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Ya</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liao</LastName><ForeName>Min</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ling</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Xuan</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Qiong</ForeName><Initials>Q</Initials><Identifier Source="ORCID">0000-0003-1033-3098</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Qiaoling</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Qiao</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jianwei</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, the Second Affiliated Hospital (Xinqiao Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Zhe</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Hematology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Yongxiu</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Hematology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Assis</LastName><ForeName>David N</ForeName><Initials>DN</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shi-Ying</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyer</LastName><ForeName>James L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Xuequan</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0002-0807-5563</Identifier><AffiliationInfo><Affiliation>Center of Minimally Invasive Intervention, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China. hxuequan@163.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Can-E</ForeName><Initials>CE</Initials><Identifier Source="ORCID">0000-0003-2582-7613</Identifier><AffiliationInfo><Affiliation>Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, 410008, PR China. tangcane@csu.edu.cn.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, PR China. tangcane@csu.edu.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Xiaowei</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0002-1193-4277</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, PR China. liuxw@csu.edu.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Shifang</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0003-4229-0299</Identifier><AffiliationInfo><Affiliation>Department of Hepatology and Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, PR China. sfp1988@csu.edu.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Jin</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-8543-4566</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China. jin.chai@cldcsw.org.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P30 DK034989</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2023</Year><Month>02</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nat Commun</MedlineTA><NlmUniqueID>101528555</NlmUniqueID><ISSNLinking>2041-1723</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>EC 3.4.17.23</RegistryNumber><NameOfSubstance UI="D000085962">Angiotensin-Converting Enzyme 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.11.1.-</RegistryNumber><NameOfSubstance UI="D000074623">Dual Oxidases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.6.3.1</RegistryNumber><NameOfSubstance UI="C431515">DUOX2 protein, human</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008105" MajorTopicYN="Y">Liver Cirrhosis, Biliary</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000085962" MajorTopicYN="N">Angiotensin-Converting Enzyme 2</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000074623" MajorTopicYN="N">Dual Oxidases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004847" MajorTopicYN="N">Epithelial Cells</DescriptorName></MeshHeading></MeshHeadingList><CoiStatement>The authors declare no competing interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>6</Month><Day>4</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2022</Year><Month>10</Month><Day>31</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2023</Year><Month>2</Month><Day>9</Day><Hour>23</Hour><Minute>25</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2023</Year><Month>2</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>2</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2023</Year><Month>2</Month><Day>9</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">36759512</ArticleId><ArticleId IdType="pmc">PMC9911648</ArticleId><ArticleId IdType="doi">10.1038/s41467-022-34606-w</ArticleId><ArticleId IdType="pii">10.1038/s41467-022-34606-w</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Gulamhusein AF, Hirschfield GM. Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat. Rev. Gastroenterol. Hepatol. 2020;17:93&#x2013;110. doi: 10.1038/s41575-019-0226-7.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41575-019-0226-7</ArticleId><ArticleId IdType="pubmed">31819247</ArticleId></ArticleIdList></Reference><Reference><Citation>Lleo A, Leung PSC, Hirschfield GM, Gershwin EM. The pathogenesis of primary biliary cholangitis: a comprehensive review. Semin. Liver Dis. 2020;40:34&#x2013;48. doi: 10.1055/s-0039-1697617.</Citation><ArticleIdList><ArticleId IdType="doi">10.1055/s-0039-1697617</ArticleId><ArticleId IdType="pubmed">31537031</ArticleId></ArticleIdList></Reference><Reference><Citation>Lleo A, Maroni L, Glaser S, Alpini G, Marzioni M. Role of cholangiocytes in primary biliary cirrhosis. Semin. Liver Dis. 2014;34:273&#x2013;284. doi: 10.1055/s-0034-1383727.</Citation><ArticleIdList><ArticleId IdType="doi">10.1055/s-0034-1383727</ArticleId><ArticleId IdType="pmc">PMC4182310</ArticleId><ArticleId IdType="pubmed">25057951</ArticleId></ArticleIdList></Reference><Reference><Citation>Invernizzi P, et al. Future directions in genetic for autoimmune diseases. J. Autoimmun. 2009;33:1&#x2013;2. doi: 10.1016/j.jaut.2009.03.001.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jaut.2009.03.001</ArticleId><ArticleId IdType="pubmed">19410428</ArticleId></ArticleIdList></Reference><Reference><Citation>Chung BK, et al. Phenotyping and autoantibody production by liver-infiltrating B cells in primary sclerosing cholangitis and primary biliary cholangitis. J. Autoimmun. 2017;77:45&#x2013;54. doi: 10.1016/j.jaut.2016.10.003.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jaut.2016.10.003</ArticleId><ArticleId IdType="pubmed">27784538</ArticleId></ArticleIdList></Reference><Reference><Citation>Gershwin ME, Mackay IR. The causes of primary biliary cirrhosis:convenient and inconvenient truths. Hepatology. 2008;47:737&#x2013;745. doi: 10.1002/hep.22042.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/hep.22042</ArticleId><ArticleId IdType="pubmed">18098322</ArticleId></ArticleIdList></Reference><Reference><Citation>Wagner M, Trauner M. Recent advances in understanding and managing cholestasis. F1000Res. 2016;5:1&#x2013;10. doi: 10.12688/f1000research.8012.1.</Citation><ArticleIdList><ArticleId IdType="doi">10.12688/f1000research.8012.1</ArticleId><ArticleId IdType="pmc">PMC4841200</ArticleId><ArticleId IdType="pubmed">27134744</ArticleId></ArticleIdList></Reference><Reference><Citation>Wagner M, Zollner G, Trauner M. New molecular insights into the mechanisms of cholestasis. J. Hepatol. 2009;51:565&#x2013;580. doi: 10.1016/j.jhep.2009.05.012.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2009.05.012</ArticleId><ArticleId IdType="pubmed">19595470</ArticleId></ArticleIdList></Reference><Reference><Citation>Tomana M, Kulhavy R, Mestecky J. Receptor-mediated binding and uptake of immunoglobulin A by human liver. Gastroenterology. 1988;94:762&#x2013;777. doi: 10.1016/0016-5085(88)90252-1.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/0016-5085(88)90252-1</ArticleId><ArticleId IdType="pubmed">3338646</ArticleId></ArticleIdList></Reference><Reference><Citation>Matsumura S, et al. Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis. Hepatology. 2004;39:1415&#x2013;1422. doi: 10.1002/hep.20175.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/hep.20175</ArticleId><ArticleId IdType="pubmed">15122771</ArticleId></ArticleIdList></Reference><Reference><Citation>Alpini G, et al. Morphological, molecular, and functional heterogeneity of cholangiocytes from normal rat liver. Gastroenterology. 1996;110:1636&#x2013;1643. doi: 10.1053/gast.1996.v110.pm8613073.</Citation><ArticleIdList><ArticleId IdType="doi">10.1053/gast.1996.v110.pm8613073</ArticleId><ArticleId IdType="pubmed">8613073</ArticleId></ArticleIdList></Reference><Reference><Citation>Glaser S, et al. Differential transcriptional characteristics of small and large biliary epithelial cells derived from small and large bile ducts. Am. J. Physiol. Gastrointest. Liver Physiol. 2010;299:G769&#x2013;G777. doi: 10.1152/ajpgi.00237.2010.</Citation><ArticleIdList><ArticleId IdType="doi">10.1152/ajpgi.00237.2010</ArticleId><ArticleId IdType="pmc">PMC2950684</ArticleId><ArticleId IdType="pubmed">20576918</ArticleId></ArticleIdList></Reference><Reference><Citation>Boyer JL, Soroka CJ. Bile formation and secretion: An update. J. Hepatol. 2021;75:190&#x2013;201. doi: 10.1016/j.jhep.2021.02.011.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2021.02.011</ArticleId><ArticleId IdType="pubmed">33617926</ArticleId></ArticleIdList></Reference><Reference><Citation>Ueno Y, et al. Evaluation of differential gene expression by microarray analysis in small and large cholangiocytes isolated from normal mice. Liver Int. 2003;23:449&#x2013;459. doi: 10.1111/j.1478-3231.2003.00876.x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1478-3231.2003.00876.x</ArticleId><ArticleId IdType="pubmed">14986819</ArticleId></ArticleIdList></Reference><Reference><Citation>Efremova M, Vento-Tormo M, Teichmann SA, Vento-Tormo R. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat. Protoc. 2020;15:1484&#x2013;1506. doi: 10.1038/s41596-020-0292-x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41596-020-0292-x</ArticleId><ArticleId IdType="pubmed">32103204</ArticleId></ArticleIdList></Reference><Reference><Citation>Tang QJ, et al. Expression of polymeric immunoglobulin receptor mRNA and protein in human paneth cells: paneth cells participate in acquired immunity. Am. J. Gastroenterol. 2006;101:1625&#x2013;1632. doi: 10.1111/j.1572-0241.2006.00605.x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1572-0241.2006.00605.x</ArticleId><ArticleId IdType="pubmed">16863570</ArticleId></ArticleIdList></Reference><Reference><Citation>Liberal R, Gaspar R, Lopes S, Macedo G. Primary biliary cholangitis in patients with inflammatory bowel disease. Clin. Res. Hepatol. Gastroenterol. 2020;44:e5&#x2013;e9. doi: 10.1016/j.clinre.2019.05.002.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.clinre.2019.05.002</ArticleId><ArticleId IdType="pubmed">31171469</ArticleId></ArticleIdList></Reference><Reference><Citation>Chai, X. Q. et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV Infection. Preprint at https://www.biorxiv.org/content/10.1101/2020.02.03.931766v1 (2020).</Citation><ArticleIdList><ArticleId IdType="doi">10.1101/2020.02.03.931766v1</ArticleId></ArticleIdList></Reference><Reference><Citation>Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect. Dis. Poverty. 2020;9:45. doi: 10.1186/s40249-020-00662-x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/s40249-020-00662-x</ArticleId><ArticleId IdType="pmc">PMC7186534</ArticleId><ArticleId IdType="pubmed">32345362</ArticleId></ArticleIdList></Reference><Reference><Citation>Nayagam JS, et al. Patterns and prediction of liver injury with persistent cholestasis in survivors of severe SARS-CoV-2 infection. J. Infect. 2021;82:e11&#x2013;e13. doi: 10.1016/j.jinf.2021.03.029.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jinf.2021.03.029</ArticleId><ArticleId IdType="pmc">PMC8019401</ArticleId><ArticleId IdType="pubmed">33826926</ArticleId></ArticleIdList></Reference><Reference><Citation>Roth NC, et al. Post-COVID-19 cholangiopathy: a novel entity. Am. J. Gastroenterol. 2021;116:1077&#x2013;1082. doi: 10.14309/ajg.0000000000001154.</Citation><ArticleIdList><ArticleId IdType="doi">10.14309/ajg.0000000000001154</ArticleId><ArticleId IdType="pubmed">33464757</ArticleId></ArticleIdList></Reference><Reference><Citation>Bartoli A, Gitto S, Sighinolfi P, Cursaro C, Andreone P. Primary biliary cholangitis associated with SARS-CoV-2 infection. J. Hepatol. 2021;74:1245&#x2013;1246. doi: 10.1016/j.jhep.2021.02.006.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2021.02.006</ArticleId><ArticleId IdType="pmc">PMC7892314</ArticleId><ArticleId IdType="pubmed">33610679</ArticleId></ArticleIdList></Reference><Reference><Citation>European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J. Hepatol. 2017;67:145&#x2013;172. doi: 10.1016/j.jhep.2017.03.022.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2017.03.022</ArticleId><ArticleId IdType="pubmed">28427765</ArticleId></ArticleIdList></Reference><Reference><Citation>Ludwig J, Dickson ER, McDonald GS. Staging of chronic nonsup-purative destructive cholangitis (syndrome of primary biliary cirrhosis) Virchows Arch. A Pathol. Anat. Histol. 1978;379:103&#x2013;112. doi: 10.1007/BF00432479.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/BF00432479</ArticleId><ArticleId IdType="pubmed">150690</ArticleId></ArticleIdList></Reference><Reference><Citation>Nakanuma Y, et al. Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement. Pathol. Int. 2011;60:167&#x2013;174. doi: 10.1111/j.1440-1827.2009.02500.x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1440-1827.2009.02500.x</ArticleId><ArticleId IdType="pubmed">20403042</ArticleId></ArticleIdList></Reference><Reference><Citation>Andrews S, FastQC A. Quality control tool for high throughput sequence data. F1000Res. 2019;8:1874. doi: 10.12688/f1000research.21142.1.</Citation><ArticleIdList><ArticleId IdType="doi">10.12688/f1000research.21142.1</ArticleId><ArticleId IdType="pubmed">0</ArticleId></ArticleIdList></Reference><Reference><Citation>Chen S, Zhou Y, Chen Y, Gu J. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018;34:i884&#x2013;i890. doi: 10.1093/bioinformatics/bty560.</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/bioinformatics/bty560</ArticleId><ArticleId IdType="pmc">PMC6129281</ArticleId><ArticleId IdType="pubmed">30423086</ArticleId></ArticleIdList></Reference><Reference><Citation>Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet. 2011;17:12.</Citation></Reference><Reference><Citation>Dobin A, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15&#x2013;21. doi: 10.1093/bioinformatics/bts635.</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/bioinformatics/bts635</ArticleId><ArticleId IdType="pmc">PMC3530905</ArticleId><ArticleId IdType="pubmed">23104886</ArticleId></ArticleIdList></Reference><Reference><Citation>Liao Y, Smyth GK, Shi W. FeatureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014;30:923&#x2013;930. doi: 10.1093/bioinformatics/btt656.</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/bioinformatics/btt656</ArticleId><ArticleId IdType="pubmed">24227677</ArticleId></ArticleIdList></Reference><Reference><Citation>Satija R, Farrell JA, Gennert D, Schier AF, Regev A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 2015;33:495&#x2013;502. doi: 10.1038/nbt.3192.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nbt.3192</ArticleId><ArticleId IdType="pmc">PMC4430369</ArticleId><ArticleId IdType="pubmed">25867923</ArticleId></ArticleIdList></Reference><Reference><Citation>Korsunsky I, et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods. 2019;16:1289&#x2013;1296. doi: 10.1038/s41592-019-0619-0.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41592-019-0619-0</ArticleId><ArticleId IdType="pmc">PMC6884693</ArticleId><ArticleId IdType="pubmed">31740819</ArticleId></ArticleIdList></Reference><Reference><Citation>Yu G, Wang LG, Han Y, He QY. ClusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16:284&#x2013;287. doi: 10.1089/omi.2011.0118.</Citation><ArticleIdList><ArticleId IdType="doi">10.1089/omi.2011.0118</ArticleId><ArticleId IdType="pmc">PMC3339379</ArticleId><ArticleId IdType="pubmed">22455463</ArticleId></ArticleIdList></Reference><Reference><Citation>Mantri M, et al. Spatiotemporal single-cell RNA sequencing of developing chicken hearts identifies interplay between cellular differentiation and morphogenesis. Nat. Commun. 2021;12:1771. doi: 10.1038/s41467-021-21892-z.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41467-021-21892-z</ArticleId><ArticleId IdType="pmc">PMC7979764</ArticleId><ArticleId IdType="pubmed">33741943</ArticleId></ArticleIdList></Reference><Reference><Citation>Zheng Y, et al. GPER-deficient rats exhibit lower serum corticosterone level and increased anxiety-like behavior. Neural Plast. 2020;2020:8866187. doi: 10.1155/2020/8866187.</Citation><ArticleIdList><ArticleId IdType="doi">10.1155/2020/8866187</ArticleId><ArticleId IdType="pmc">PMC7474769</ArticleId><ArticleId IdType="pubmed">32908490</ArticleId></ArticleIdList></Reference><Reference><Citation>Cubero FJ, et al. Inactivation of caspase 8 in liver parenchymal cells confers protection against murine obstructive cholestasis. J. Hepatol. 2018;69:1326&#x2013;1334. doi: 10.1016/j.jhep.2018.08.015.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2018.08.015</ArticleId><ArticleId IdType="pubmed">30144553</ArticleId></ArticleIdList></Reference><Reference><Citation>Wi&#x15b;niewski JR, Zougman A, Nagaraj N, Mann M. Universal sample preparation method for proteome analysis. Nat. Methods. 2009;6:359&#x2013;362. doi: 10.1038/nmeth.1322.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nmeth.1322</ArticleId><ArticleId IdType="pubmed">19377485</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">36690641</PMID><DateRevised><Year>2023</Year><Month>02</Month><Day>02</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Print">2058-7716</ISSN><JournalIssue CitedMedium="Print"><Volume>9</Volume><Issue>1</Issue><PubDate><Year>2023</Year><Month>Jan</Month><Day>23</Day></PubDate></JournalIssue><Title>Cell death discovery</Title><ISOAbbreviation>Cell Death Discov</ISOAbbreviation></Journal><ArticleTitle>Hepatic TNFRSF12A promotes bile acid-induced hepatocyte pyroptosis through NF&#x3ba;B/Caspase-1/GSDMD signaling in cholestasis.</ArticleTitle><Pagination><StartPage>26</StartPage><MedlinePgn>26</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">26</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41420-023-01326-z</ELocationID><Abstract><AbstractText>Tumor necrosis factor receptor superfamily member-12A (TNFRSF12A) plays a critical role in inflammation and cell death. It is expressed in multiple tissues yet extremely low in normal liver. To date, little is known about its role in cholestasis. Therefore, we sought to delineate the role of TNFRSF12A in cholestasis and its underlying mechanisms. Human liver tissues were collected from patients with obstructive cholestasis (OC) or primary biliary cholangitis (PBC). Tnfrsf12a knockout (KO) mice were generated. Cholestasis was induced by bile-duct ligation (BDL) or 0.1% 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-feeding. Human hepatoma PLC/PRF/5-ASBT and THP1 cell lines or primary mouse hepatocytes were used for mechanistic studies. Hepatic TNFRSF12A expression was markedly increased in OC or PBC patients. Genetic ablation of Tnfrsf12a in BDL- and 0.1%DDC-induced cholestatic mice significantly attenuated cholestatic liver injury with remarkable reduction of hepatocyte pyroptosis but without changing scores of necroptosis and apoptosis. Morphological features of hepatocyte pyroptosis and increased levels of pyroptosis-related proteins, NLRP3, cleaved-Caspase-1, and cleaved-GSDMD in OC patients and BDL-mice confirmed this observation. Further mechanistic studies revealed that bile acids (BAs) induced TNFRSF12A expression by enhancing the transcription factor c-JUN binding to the TNFRSF12A promoter and subsequently initiated hepatocyte pyroptosis by the NF&#x3ba;B/Caspase-1/GSDMD signaling. Interestingly, TWEAK, a typical ligand of TNFRSF12A, secreted by infiltrated macrophages in cholestatic livers, enhanced TNFRSF12A-induced hepatocyte pyroptosis. Taken together, we report, for the first time, that hepatic TNFRSF12A is dramatically increased in human cholestasis. Deletion of TNFRSF12A inhibits BAs-induced hepatocyte pyroptosis through the NF&#x3ba;B/Caspase-1/GSDMD signaling and thereby ameliorates cholestatic liver injury. As such, targeting TNFRSF12A could be a promising approach to treating cholestasis.</AbstractText><CopyrightInformation>&#xa9; 2023. The Author(s).</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Liao</LastName><ForeName>Min</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Liao</LastName><ForeName>Junwei</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Central South University School of Sciences, Changsha, Hunan, 410083, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Qu</LastName><ForeName>Jiaquan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medical Imaging Technology, Medical College of Jishou University, Jishou, Hunan, 416000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Shi</LastName><ForeName>Pan</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Qiong</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaoxun</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Liangjun</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Ya</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Qiao</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Jin-Fei</ForeName><Initials>JF</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Queen Mary School, Nanchang University, Nanchang, Jiangxi, 330031, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jianwei</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Chengcheng</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shi-Ying</ForeName><Initials>SY</Initials><Identifier Source="ORCID">0000-0001-6601-4040</Identifier><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, CT, 06520, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Jin</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-8543-4566</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China. jin.chai@cldcsw.org.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China. jin.chai@cldcsw.org.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic-Associated Fatty Liver Diseases, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China. jin.chai@cldcsw.org.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2023</Year><Month>01</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cell Death Discov</MedlineTA><NlmUniqueID>101665035</NlmUniqueID><ISSNLinking>2058-7716</ISSNLinking></MedlineJournalInfo><CoiStatement>The authors declare no competing interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>8</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2023</Year><Month>1</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2023</Year><Month>1</Month><Day>7</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2023</Year><Month>1</Month><Day>23</Day><Hour>23</Hour><Minute>14</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2023</Year><Month>1</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>1</Month><Day>24</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2023</Year><Month>1</Month><Day>23</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">36690641</ArticleId><ArticleId IdType="pmc">PMC9871041</ArticleId><ArticleId IdType="doi">10.1038/s41420-023-01326-z</ArticleId><ArticleId IdType="pii">10.1038/s41420-023-01326-z</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Poupon R, Chazouilleres O, Poupon RE. Chronic cholestatic diseases. J Hepatol. 2000;32:129&#x2013;40. doi: 10.1016/S0168-8278(00)80421-3.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0168-8278(00)80421-3</ArticleId><ArticleId IdType="pubmed">10728800</ArticleId></ArticleIdList></Reference><Reference><Citation>Chiang JY. Bile acid metabolism and signaling. Compr Physiol. 2013;3:1191&#x2013;212. doi: 10.1002/cphy.c120023.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/cphy.c120023</ArticleId><ArticleId IdType="pmc">PMC4422175</ArticleId><ArticleId IdType="pubmed">23897684</ArticleId></ArticleIdList></Reference><Reference><Citation>Allen K, Jaeschke H, Copple BL. Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. Am J Pathol. 2011;178:175&#x2013;86. doi: 10.1016/j.ajpath.2010.11.026.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ajpath.2010.11.026</ArticleId><ArticleId IdType="pmc">PMC3070591</ArticleId><ArticleId IdType="pubmed">21224055</ArticleId></ArticleIdList></Reference><Reference><Citation>Ghanbarinejad V, Ommati MM, Jia Z, Farshad O, Jamshidzadeh A, Heidari R. Disturbed mitochondrial redox state and tissue energy charge in cholestasis. J Biochem Mol Toxicol. 2021;35:e22846. doi: 10.1002/jbt.22846.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/jbt.22846</ArticleId><ArticleId IdType="pubmed">34250697</ArticleId></ArticleIdList></Reference><Reference><Citation>Frissen M, Liao L, Schneider KM, Djudjaj S, Haybaeck J, Wree A, et al. Bidirectional Role of NLRP3 During Acute and Chronic Cholestatic Liver Injury. Hepatology. 2021;73:1836&#x2013;54. doi: 10.1002/hep.31494.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/hep.31494</ArticleId><ArticleId IdType="pubmed">32748971</ArticleId></ArticleIdList></Reference><Reference><Citation>Shi J, Gao W, Shao F. Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends Biochem Sci. 2017;42:245&#x2013;54. doi: 10.1016/j.tibs.2016.10.004.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.tibs.2016.10.004</ArticleId><ArticleId IdType="pubmed">27932073</ArticleId></ArticleIdList></Reference><Reference><Citation>Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526:660&#x2013;5. doi: 10.1038/nature15514.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nature15514</ArticleId><ArticleId IdType="pubmed">26375003</ArticleId></ArticleIdList></Reference><Reference><Citation>Szabo G, Petrasek J. Inflammasome activation and function in liver disease. Nat Rev Gastroenterol Hepatol. 2015;12:387&#x2013;400. doi: 10.1038/nrgastro.2015.94.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrgastro.2015.94</ArticleId><ArticleId IdType="pubmed">26055245</ArticleId></ArticleIdList></Reference><Reference><Citation>Luan J, Ju D. Inflammasome: a double-edged sword in liver diseases. Front Immunol. 2018;9:2201. doi: 10.3389/fimmu.2018.02201.</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fimmu.2018.02201</ArticleId><ArticleId IdType="pmc">PMC6167446</ArticleId><ArticleId IdType="pubmed">30319645</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai SY, Ge M, Mennone A, Hoque R, Ouyang X, Boyer JL. Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct-Ligated Mouse. Cell Mol Gastroenterol Hepatol. 2020;9:679&#x2013;88. doi: 10.1016/j.jcmgh.2019.12.008.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jcmgh.2019.12.008</ArticleId><ArticleId IdType="pmc">PMC7160576</ArticleId><ArticleId IdType="pubmed">31887435</ArticleId></ArticleIdList></Reference><Reference><Citation>Han D, Kim H, Kim S, Le QA, Han SY, Bae J, et al. Sestrin2 protects against cholestatic liver injury by inhibiting endoplasmic reticulum stress and NLRP3 inflammasome-mediated pyroptosis. Exp Mol Med. 2022;54:239&#x2013;51. doi: 10.1038/s12276-022-00737-9.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s12276-022-00737-9</ArticleId><ArticleId IdType="pmc">PMC8980001</ArticleId><ArticleId IdType="pubmed">35260799</ArticleId></ArticleIdList></Reference><Reference><Citation>Chicheportiche Y, Bourdon PR, Xu H, Hsu YM, Scott H, Hession C, et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem. 1997;272:32401&#x2013;10. doi: 10.1074/jbc.272.51.32401.</Citation><ArticleIdList><ArticleId IdType="doi">10.1074/jbc.272.51.32401</ArticleId><ArticleId IdType="pubmed">9405449</ArticleId></ArticleIdList></Reference><Reference><Citation>Poveda J, V&#xe1;zquez-S&#xe1;nchez S, Sanz AB, Ortiz A, Ruilope LM, Ruiz-Hurtado G. TWEAK-Fn14 as a common pathway in the heart and the kidneys in cardiorenal syndrome. J Pathol. 2021;254:5&#x2013;19.</Citation><ArticleIdList><ArticleId IdType="pubmed">33512736</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang M, Xie Z, Xu J, Feng Z. TWEAK/Fn14 axis in respiratory diseases. Clin Chim Acta. 2020;509:139&#x2013;48. doi: 10.1016/j.cca.2020.06.007.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.cca.2020.06.007</ArticleId><ArticleId IdType="pubmed">32526219</ArticleId></ArticleIdList></Reference><Reference><Citation>Pascoe AL, Johnston AJ, Murphy RM. Controversies in TWEAK-Fn14 signaling in skeletal muscle atrophy and regeneration. Cell Mol Life Sci. 2020;77:3369&#x2013;81. doi: 10.1007/s00018-020-03495-x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00018-020-03495-x</ArticleId><ArticleId IdType="pmc">PMC11104974</ArticleId><ArticleId IdType="pubmed">32200423</ArticleId></ArticleIdList></Reference><Reference><Citation>Burkly LC, Dohi T. The TWEAK/Fn14 pathway in tissue remodeling: for better or for worse. Adv Exp Med Biol. 2011;691:305&#x2013;22. doi: 10.1007/978-1-4419-6612-4_32.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/978-1-4419-6612-4_32</ArticleId><ArticleId IdType="pubmed">21153335</ArticleId></ArticleIdList></Reference><Reference><Citation>Burkly LC, Michaelson JS, Hahm K, Jakubowski A, Zheng TS. TWEAKing tissue remodeling by a multifunctional cytokine: role of TWEAK/Fn14 pathway in health and disease. Cytokine. 2007;40:1&#x2013;16. doi: 10.1016/j.cyto.2007.09.007.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.cyto.2007.09.007</ArticleId><ArticleId IdType="pubmed">17981048</ArticleId></ArticleIdList></Reference><Reference><Citation>Wiley SR, Winkles JA. TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor. Cytokine Growth Factor Rev. 2003;14:241&#x2013;9. doi: 10.1016/S1359-6101(03)00019-4.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S1359-6101(03)00019-4</ArticleId><ArticleId IdType="pubmed">12787562</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang Y, Zeng W, Xia Y. TWEAK/Fn14 axis is an important player in fibrosis. J Cell Physiol. 2021;236:3304&#x2013;16. doi: 10.1002/jcp.30089.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/jcp.30089</ArticleId><ArticleId IdType="pubmed">33000480</ArticleId></ArticleIdList></Reference><Reference><Citation>Dwyer BJ, Olynyk JK, Ramm GA, Tirnitz-Parker JE. TWEAK and LT&#x3b2; Signaling during Chronic Liver Disease. Front Immunol. 2014;5:39. doi: 10.3389/fimmu.2014.00039.</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fimmu.2014.00039</ArticleId><ArticleId IdType="pmc">PMC3923149</ArticleId><ArticleId IdType="pubmed">24592262</ArticleId></ArticleIdList></Reference><Reference><Citation>Aff&#xf2; S, Dominguez M, Lozano JJ, Sancho-Bru P, Rodrigo-Torres D, Morales-Ibanez O, et al. Transcriptome analysis identifies TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis. Gut. 2013;62:452&#x2013;60. doi: 10.1136/gutjnl-2011-301146.</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/gutjnl-2011-301146</ArticleId><ArticleId IdType="pmc">PMC4064940</ArticleId><ArticleId IdType="pubmed">22637703</ArticleId></ArticleIdList></Reference><Reference><Citation>Jakubowski A, Ambrose C, Parr M, Lincecum JM, Wang MZ, Zheng TS, et al. TWEAK induces liver progenitor cell proliferation. J Clin Invest. 2005;115:2330&#x2013;40. doi: 10.1172/JCI23486.</Citation><ArticleIdList><ArticleId IdType="doi">10.1172/JCI23486</ArticleId><ArticleId IdType="pmc">PMC1187931</ArticleId><ArticleId IdType="pubmed">16110324</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang GY, Garcia V, Lee J, Yanum J, Lin J, Jiang H. Nrf2 deficiency causes hepatocyte dedifferentiation and reduced albumin production in an experimental extrahepatic cholestasis model. PLoS One. 2022;17:e0269383. doi: 10.1371/journal.pone.0269383.</Citation><ArticleIdList><ArticleId IdType="doi">10.1371/journal.pone.0269383</ArticleId><ArticleId IdType="pmc">PMC9191739</ArticleId><ArticleId IdType="pubmed">35696363</ArticleId></ArticleIdList></Reference><Reference><Citation>Gaul S, Leszczynska A, Alegre F, Kaufmann B, Johnson CD, Adams LA, et al. Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis. J Hepatol. 2021;74:156&#x2013;67. doi: 10.1016/j.jhep.2020.07.041.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2020.07.041</ArticleId><ArticleId IdType="pmc">PMC7749849</ArticleId><ArticleId IdType="pubmed">32763266</ArticleId></ArticleIdList></Reference><Reference><Citation>Ahmadi A, Niknahad H, Li H, Mobasheri A, Manthari RK, Azarpira N, et al. The inhibition of NF&#x43a;B signaling and inflammatory response as a strategy for blunting bile acid-induced hepatic and renal toxicity. Toxicol Lett. 2021;349:12&#x2013;29. doi: 10.1016/j.toxlet.2021.05.012.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.toxlet.2021.05.012</ArticleId><ArticleId IdType="pubmed">34089816</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang X, Li L, Zhao N, Pan Q, Zhang L, Xie Q, et al. Chai JA novel role for interleukin 32 in cholestasis. Clin Transl Med. 2021;11:e594. doi: 10.1002/ctm2.594.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/ctm2.594</ArticleId><ArticleId IdType="pmc">PMC8611182</ArticleId><ArticleId IdType="pubmed">34841712</ArticleId></ArticleIdList></Reference><Reference><Citation>Chai J, He Y, Cai SY, Jiang Z, Wang H, Li Q, et al. Elevated hepatic multidrug resistance-associated protein 3/ATP-binding cassette subfamily C 3 expression in human obstructive cholestasis is mediated through tumor necrosis factor alpha and c-Jun NH2-terminal kinase/stress-activated protein kinase-signaling pathway. Hepatology. 2012;55:1485&#x2013;94. doi: 10.1002/hep.24801.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/hep.24801</ArticleId><ArticleId IdType="pmc">PMC3297707</ArticleId><ArticleId IdType="pubmed">22105759</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai SY, Yu D, Soroka CJ, Wang J, Boyer JL. Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis. J Hepatol. 2021;74:550&#x2013;9. doi: 10.1016/j.jhep.2020.09.035.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2020.09.035</ArticleId><ArticleId IdType="pmc">PMC7897288</ArticleId><ArticleId IdType="pubmed">33039404</ArticleId></ArticleIdList></Reference><Reference><Citation>Pan Q, Zhang X, Zhang L, Cheng Y, Zhao N, Li F, et al. Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis. Gastroenterology. 2018;155:1578&#x2013;1592.e16. doi: 10.1053/j.gastro.2018.07.031.</Citation><ArticleIdList><ArticleId IdType="doi">10.1053/j.gastro.2018.07.031</ArticleId><ArticleId IdType="pmc">PMC6221191</ArticleId><ArticleId IdType="pubmed">30063921</ArticleId></ArticleIdList></Reference><Reference><Citation>Genin M, Clement F, Fattaccioli A, Raes M, Michiels C. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer. 2015;15:577. doi: 10.1186/s12885-015-1546-9.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/s12885-015-1546-9</ArticleId><ArticleId IdType="pmc">PMC4545815</ArticleId><ArticleId IdType="pubmed">26253167</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, et al. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017:e90780.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5333973</ArticleId><ArticleId IdType="pubmed">28289714</ArticleId></ArticleIdList></Reference><Reference><Citation>Chai J, Cai SY, Liu X, Lian W, Chen S, Zhang L, et al. Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. J Hepatol. 2015;63:1440&#x2013;8. doi: 10.1016/j.jhep.2015.07.016.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2015.07.016</ArticleId><ArticleId IdType="pmc">PMC4686151</ArticleId><ArticleId IdType="pubmed">26212029</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">36647589</PMID><DateCompleted><Year>2023</Year><Month>10</Month><Day>25</Day></DateCompleted><DateRevised><Year>2024</Year><Month>03</Month><Day>09</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1527-3350</ISSN><JournalIssue CitedMedium="Internet"><Volume>77</Volume><Issue>6</Issue><PubDate><Year>2023</Year><Month>Jun</Month><Day>01</Day></PubDate></JournalIssue><Title>Hepatology (Baltimore, Md.)</Title><ISOAbbreviation>Hepatology</ISOAbbreviation></Journal><ArticleTitle>Runt-related transcription factor-1 ameliorates bile acid-induced hepatic inflammation in cholestasis through JAK/STAT3 signaling.</ArticleTitle><Pagination><StartPage>1866</StartPage><EndPage>1881</EndPage><MedlinePgn>1866-1881</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1097/HEP.0000000000000041</ELocationID><Abstract><AbstractText Label="BACKGROUND AND AIMS">Bile acids trigger a hepatic inflammatory response, causing cholestatic liver injury. Runt-related transcription factor-1 (RUNX1), primarily known as a master modulator in hematopoiesis, plays a pivotal role in mediating inflammatory responses. However, RUNX1 in hepatocytes is poorly characterized, and its role in cholestasis is unclear. Herein, we aimed to investigate the role of hepatic RUNX1 and its underlying mechanisms in cholestasis.</AbstractText><AbstractText Label="APPROACH AND RESULTS">Hepatic expression of RUNX1 was examined in cholestatic patients and mouse models. Mice with liver-specific ablation of Runx1 were generated. Bile duct ligation and 1% cholic acid diet were used to induce cholestasis in mice. Primary mouse hepatocytes and the human hepatoma PLC/RPF/5- ASBT cell line were used for mechanistic studies. Hepatic RUNX1 mRNA and protein levels were markedly increased in cholestatic patients and mice. Liver-specific deletion of Runx1 aggravated inflammation and liver injury in cholestatic mice induced by bile duct ligation or 1% cholic acid feeding. Mechanistic studies indicated that elevated bile acids stimulated RUNX1 expression by activating the RUNX1 -P2 promoter through JAK/STAT3 signaling. Increased RUNX1 is directly bound to the promotor region of inflammatory chemokines, including CCL2 and CXCL2 , and transcriptionally repressed their expression in hepatocytes, leading to attenuation of liver inflammatory response. Blocking the JAK signaling or STAT3 phosphorylation completely abolished RUNX1 repression of bile acid-induced CCL2 and CXCL2 in hepatocytes.</AbstractText><AbstractText Label="CONCLUSIONS">This study has gained initial evidence establishing the functional role of hepatocyte RUNX1 in alleviating liver inflammation during cholestasis through JAK/STAT3 signaling. Modulating hepatic RUNX1 activity could be a new therapeutic target for cholestasis.</AbstractText><CopyrightInformation>Copyright &#xa9; 2023 American Association for the Study of Liver Diseases.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Liangjun</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-7053-8661</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Qiong</ForeName><Initials>Q</Initials><Identifier Source="ORCID">0000-0003-1033-3098</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Lu</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0001-9631-4001</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xia</LastName><ForeName>Haihan</ForeName><Initials>H</Initials><Identifier Source="ORCID">0000-0003-2754-5281</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liao</LastName><ForeName>Junwei</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-4859-6427</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Central South University School of Life Sciences, Changsha, Hunan Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaoxun</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0002-1342-2507</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0002-4597-6547</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Qiaoling</ForeName><Initials>Q</Initials><Identifier Source="ORCID">0000-0002-1342-2507</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liao</LastName><ForeName>Min</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0002-6769-0080</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Ya</ForeName><Initials>Y</Initials><Identifier Source="ORCID">0000-0001-6831-854</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Qiao</ForeName><Initials>Q</Initials><Identifier Source="ORCID">0000-0003-4577-2971</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Jinfei</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0003-4741-131</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Queen Mary School, Nanchang University, Nanchang, Jiangxi Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ling</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-9027-7307</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Shijun</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0002-7593-9771</Identifier><AffiliationInfo><Affiliation>Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jianwei</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0001-9629-7475</Identifier><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Chengcheng</ForeName><Initials>C</Initials><Identifier Source="ORCID">0000-0002-0550-107</Identifier><AffiliationInfo><Affiliation>Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shi-Ying</ForeName><Initials>SY</Initials><Identifier Source="ORCID">0000-0001-6601-4040</Identifier><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyer</LastName><ForeName>James L</ForeName><Initials>JL</Initials><Identifier Source="ORCID">0000-0002-8959-6036</Identifier><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Jin</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-8543-4566</Identifier><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Disease of PLA, Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Digestive Diseases of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P30 DK034989</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2023</Year><Month>01</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Hepatology</MedlineTA><NlmUniqueID>8302946</NlmUniqueID><ISSNLinking>0270-9139</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001647">Bile Acids and Salts</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002793">Cholic Acids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050676">Core Binding Factor Alpha 2 Subunit</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C494086">STAT3 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050796">STAT3 Transcription Factor</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001647" MajorTopicYN="Y">Bile Acids and Salts</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002779" MajorTopicYN="Y">Cholestasis</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002793" MajorTopicYN="N">Cholic Acids</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050676" MajorTopicYN="N">Core Binding Factor Alpha 2 Subunit</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D022781" MajorTopicYN="N">Hepatocytes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007249" MajorTopicYN="Y">Inflammation</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008099" MajorTopicYN="N">Liver</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050796" MajorTopicYN="N">STAT3 Transcription Factor</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><CoiStatement>CONFLICTS OF INTEREST. The authors declare no conflicts of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>7</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2022</Year><Month>11</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>5</Month><Day>18</Day><Hour>6</Hour><Minute>42</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2023</Year><Month>1</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2023</Year><Month>1</Month><Day>17</Day><Hour>2</Hour><Minute>32</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2024</Year><Month>3</Month><Day>8</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">36647589</ArticleId><ArticleId IdType="mid">NIHMS1967319</ArticleId><ArticleId IdType="pmc">PMC10921919</ArticleId><ArticleId IdType="doi">10.1097/HEP.0000000000000041</ArticleId><ArticleId IdType="pii">01515467-202306000-00006</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Poupon R, Chazouilleres O, Poupon RE. Chronic cholestatic diseases. J Hepatol. 2000;32:129&#x2013;40.</Citation><ArticleIdList><ArticleId IdType="pubmed">10728800</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, et al. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight. 2017;2:e90780.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5333973</ArticleId><ArticleId IdType="pubmed">28289714</ArticleId></ArticleIdList></Reference><Reference><Citation>Allen K, Jaeschke H, Copple BL. Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. Am J Pathol. 2011;178:175&#x2013;86.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3070591</ArticleId><ArticleId IdType="pubmed">21224055</ArticleId></ArticleIdList></Reference><Reference><Citation>O&#x2019;Brien KM, Allen KM, Rockwell CE, Towery K, Luyendyk JP, Copple BL. IL-17A synergistically enhances bile acid-induced inflammation during obstructive cholestasis. Am J Pathol. 2013;183:1498&#x2013;507.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3814525</ArticleId><ArticleId IdType="pubmed">24012680</ArticleId></ArticleIdList></Reference><Reference><Citation>Gujral JS, Farhood A, Bajt ML, Jaeschke H. Neutrophils aggravate acute liver injury during obstructive cholestasis in bile duct-ligated mice. Hepatology. 2003;38:355&#x2013;63.</Citation><ArticleIdList><ArticleId IdType="pubmed">12883479</ArticleId></ArticleIdList></Reference><Reference><Citation>Bharadwaj U, Kasembeli MM, Robinson P, Tweardy DJ. Targeting janus kinases and signal transducer and activator of transcription 3 to treat inflammation, fibrosis, and cancer: rationale, progress, and caution. Pharmacol Rev. 2020;72:486&#x2013;526.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC7300325</ArticleId><ArticleId IdType="pubmed">32198236</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang T, Fahrmann JF, Lee H, Li YJ, Tripathi SC, Yue C, et al. JAK/STAT3-regulated fatty acid beta-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance. Cell Metab. 2018;27:1357.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6116734</ArticleId><ArticleId IdType="pubmed">29874570</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu EH, Zheng ZN, Xiao CX, Liu X, Lin XQ. IL-22 relieves sepsis-induced liver injury via activating JAK/STAT3 signaling pathway. J Biol Regul Homeost Agents. 2020;34:1719&#x2013;27.</Citation><ArticleIdList><ArticleId IdType="pubmed">33179463</ArticleId></ArticleIdList></Reference><Reference><Citation>Xu G, Dai M, Zheng X, Lin H, Liu A, Yang J. Cholestatic models induced by lithocholic acid and alphanaphthylisothiocyanate: different etiological mechanisms for liver injury but shared JNK/STAT3 signaling. Mol Med Rep. 2020;22:1583&#x2013;93.</Citation><ArticleIdList><ArticleId IdType="pubmed">32626965</ArticleId></ArticleIdList></Reference><Reference><Citation>Appleford PJ, Woollard A. RUNX genes find a niche in stem cell biology. J Cell Biochem. 2009;108:14&#x2013;21.</Citation><ArticleIdList><ArticleId IdType="pubmed">19562739</ArticleId></ArticleIdList></Reference><Reference><Citation>Sroczynska P, Lancrin C, Kouskoff V, Lacaud G. The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis. Blood. 2009;114:5279&#x2013;89.</Citation><ArticleIdList><ArticleId IdType="pubmed">19858498</ArticleId></ArticleIdList></Reference><Reference><Citation>Telfer JC, Rothenberg EV. Expression and function of a stem cell promoter for the murine CBFalpha2 gene: distinct roles and regulation in natural killer and T cell development. Dev Biol. 2001;229:363&#x2013;82.</Citation><ArticleIdList><ArticleId IdType="pubmed">11203699</ArticleId></ArticleIdList></Reference><Reference><Citation>Miyoshi H, Ohira M, Shimizu K, Mitani K, Hirai H, Imai T, et al. Alternative splicing and genomic structure of the AML1 gene involved in acute myeloid leukemia. Nucleic Acids Res. 1995;23:2762&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC307102</ArticleId><ArticleId IdType="pubmed">7651838</ArticleId></ArticleIdList></Reference><Reference><Citation>Tang X, Sun L, Wang G, Chen B, Luo F. RUNX1: a regulator of NF-&#x3ba;B signaling in pulmonary diseases. Curr Protein Pept Sci. 2018;19:172&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5876917</ArticleId><ArticleId IdType="pubmed">28990531</ArticleId></ArticleIdList></Reference><Reference><Citation>Bullinger L, Dohner K, Dohner H. Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol. 2017;35:934&#x2013;46.</Citation><ArticleIdList><ArticleId IdType="pubmed">28297624</ArticleId></ArticleIdList></Reference><Reference><Citation>Li Q, Lai Q, He C, Fang Y, Yan Q, Zhang Y, et al. RUNX1 promotes tumour metastasis by activating the Wnt/beta-catenin signalling pathway and EMT in colorectal cancer. J Exp Clin Cancer Res. 2019;38:334.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6670220</ArticleId><ArticleId IdType="pubmed">31370857</ArticleId></ArticleIdList></Reference><Reference><Citation>Tang X, Sun L, Jin X, Chen Y, Zhu H, Liang Y, et al. Runt-related transcription factor 1 regulates LPS-induced acute lung injury via NF-kappaB signaling. Am J Respir Cell Mol Biol. 2017;57:174&#x2013;83.</Citation><ArticleIdList><ArticleId IdType="pubmed">28314106</ArticleId></ArticleIdList></Reference><Reference><Citation>Tripathi DM, Rohilla S, Kaur I, Siddiqui H, Rawal P, Juneja P, et al. Immunonano-lipocarrier-mediated liver sinusoidal endothelial cell-specific RUNX1 inhibition impedes immune cell infiltration and hepatic inflammation in murine model of NASH. Int J Mol Sci. 2021;22:8489.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC8395158</ArticleId><ArticleId IdType="pubmed">34445195</ArticleId></ArticleIdList></Reference><Reference><Citation>Kaur S, Rawal P, Siddiqui H, Rohilla S, Sharma S, Tripathi DM, et al. Increased expression of RUNX1 in liver correlates with NASH Activity Score in patients with non-alcoholic steatohepatitis (NASH). Cells. 2019;8:1277.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6830073</ArticleId><ArticleId IdType="pubmed">31635436</ArticleId></ArticleIdList></Reference><Reference><Citation>Li X, Li Y, Xiao JT, Wang HW, Guo Y, Mao XR, et al. Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets of primary biliary cholangitis. Nat Commun. 2022. doi:10.1038/s41467-022-34606-w</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41467-022-34606-w</ArticleId><ArticleId IdType="pmc">PMC9911648</ArticleId><ArticleId IdType="pubmed">36759512</ArticleId></ArticleIdList></Reference><Reference><Citation>Huang J, Li Y, Xu D, Zhang X, Zhou X. RUNX1 regulates SMAD1 by transcriptionally activating the expression of USP9X, regulating the activation of hepatic stellate cells and liver fibrosis. Eur J Pharmacol. 2021;903:174137.</Citation><ArticleIdList><ArticleId IdType="pubmed">33933467</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang Y, Wang Q, Wang B, Gu Y, Yu H, Yang W, et al. Inhibition of EZH2 ameliorates bacteria-induced liver injury by repressing RUNX1 in dendritic cells. Cell Death Dis. 2020;11:1024.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC7708645</ArticleId><ArticleId IdType="pubmed">33262329</ArticleId></ArticleIdList></Reference><Reference><Citation>Pan Q, Zhang X, Zhang L, Cheng Y, Zhao N, Li F, et al. Solute carrier organic anion transporter family member 3A1 is a bile acid efflux transporter in cholestasis. Gastroenterology. 2018;155:1578&#x2013;92.e16.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6221191</ArticleId><ArticleId IdType="pubmed">30063921</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai SY, Yu D, Soroka CJ, Wang J, Boyer JL. Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis. J Hepatol. 2021;74:550&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC7897288</ArticleId><ArticleId IdType="pubmed">33039404</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang X, Li L, Zhao N, Pan Q, Zhang L, Xie Q, et al. A novel role for interleukin 32 in cholestasis. Clin Transl Med. 2021;11:e594.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC8611182</ArticleId><ArticleId IdType="pubmed">34841712</ArticleId></ArticleIdList></Reference><Reference><Citation>Chai J, Cai SY, Liu X, Lian W, Chen S, Zhang L, et al. Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. J Hepatol. 2015;63:1440&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4686151</ArticleId><ArticleId IdType="pubmed">26212029</ArticleId></ArticleIdList></Reference><Reference><Citation>Pozner A, Goldenberg D, Negreanu V, Le SY, Elroy-Stein O, Levanon D, et al. Transcription-coupled translation control of AML1/RUNX1 is mediated by cap- and internal ribosome entry site-dependent mechanisms. Mol Cell Biol. 2000;20:2297&#x2013;307.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC85390</ArticleId><ArticleId IdType="pubmed">10713153</ArticleId></ArticleIdList></Reference><Reference><Citation>Chai J, He Y, Cai SY, Jiang Z, Wang H, Li Q, et al. Elevated hepatic multidrug resistance-associated protein 3/ATP-binding cassette subfamily C 3 expression in human obstructive cholestasis is mediated through tumor necrosis factor alpha and c-Jun NH2-terminal kinase/stress-activated protein kinase-signaling pathway. Hepatology. 2012;55:1485&#x2013;94.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3297707</ArticleId><ArticleId IdType="pubmed">22105759</ArticleId></ArticleIdList></Reference><Reference><Citation>Pan Q, Luo G, Qu J, Chen S, Zhang X, Zhao N, et al. A homozygous R148W mutation in semaphorin 7A causes progressive familial intrahepatic cholestasis. EMBO Mol Med. 2021;13:e14563.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC8573601</ArticleId><ArticleId IdType="pubmed">34585848</ArticleId></ArticleIdList></Reference><Reference><Citation>Yang T, Poenisch M, Khanal R, Hu Q, Dai Z, Li R, et al. Therapeutic HNF4A mRNA attenuates liver fibrosis in a preclinical model. J Hepatol. 2021;75:1420&#x2013;33.</Citation><ArticleIdList><ArticleId IdType="pubmed">34453962</ArticleId></ArticleIdList></Reference><Reference><Citation>Hargrove L, Kennedy L, Demieville J, Jones H, Meng F, DeMorrow S, et al. Bile duct ligation-induced biliary hyperplasia, hepatic injury, and fibrosis are reduced in mast cell-deficient Kit (W-sh) mice. Hepatology. 2017;65:1991&#x2013;2004.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5444972</ArticleId><ArticleId IdType="pubmed">28120369</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">36521151</PMID><DateCompleted><Year>2023</Year><Month>05</Month><Day>24</Day></DateCompleted><DateRevised><Year>2023</Year><Month>05</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1939-1285</ISSN><JournalIssue CitedMedium="Internet"><Volume>49</Volume><Issue>6</Issue><PubDate><Year>2023</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Journal of experimental psychology. Learning, memory, and cognition</Title><ISOAbbreviation>J Exp Psychol Learn Mem Cogn</ISOAbbreviation></Journal><ArticleTitle>Syntactic encoding in written language production by deaf writers: A structural priming study and a comparison with hearing writers.</ArticleTitle><Pagination><StartPage>974</StartPage><EndPage>989</EndPage><MedlinePgn>974-989</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1037/xlm0001204</ELocationID><Abstract><AbstractText>In three structural priming experiments, we investigated whether deaf and hearing writers differ in the processes and representations underlying written language production. Experiment 1 showed that deaf writers of Mandarin Chinese exhibited comparable extents of structural priming and comparable lexical boosts, suggesting that syntactic encoding in written language production is similarly sensitive to prior lexical-syntactic experience in deaf and hearing writers. Experiment 2 showed that, while hearing writers showed a boost in structural priming when the prime and the target had homographic or heterographic homophone dative verbs compared to unrelated ones, deaf writers showed a homophone boost only with homographic homophone verbs but not with heterographic homophone verbs. This finding suggests that while hearing people develop associated lemmas for homophones due to phonological identity, deaf people do so due to orthographic identity. Finally, Experiment 3 showed no boost in structural priming in deaf writers or hearing writers when the prime and the target had the same verb of the same orthography (i.e., in the same script) than of different orthographies (i.e., between Simplified and Traditional Chinese), suggesting that neither hearing nor deaf people use orthographic identity to reactivate the prime structure. In all, the findings suggest that syntactic encoding in writing employs the same syntactic and lexical representations in deaf and hearing writers, though lexical representations are shaped more by orthography than phonology in deaf writers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Zhenguang G</ForeName><Initials>ZG</Initials><Identifier Source="ORCID">0000-0002-4097-6038</Identifier><AffiliationInfo><Affiliation>Department of Linguistics and Modern Languages, Chinese University of Hong Kong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Translation, Interpreting and Intercultural Studies, Hong Kong Baptist University.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Hao</ForeName><Initials>H</Initials><Identifier Source="ORCID">0000-0003-3596-0899</Identifier><AffiliationInfo><Affiliation>Institute of Linguistics, Shanghai International Studies University.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Zebo</ForeName><Initials>Z</Initials><Identifier Source="ORCID">0000-0002-3807-2398</Identifier><AffiliationInfo><Affiliation>Department of Linguistics and Modern Languages, Chinese University of Hong Kong.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thierfelder</LastName><ForeName>Philip</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Linguistics and Modern Languages, Chinese University of Hong Kong.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Agency>Chinese University of Hong Kong; Faculty of Arts</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2022</Year><Month>12</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Exp Psychol Learn Mem Cogn</MedlineTA><NlmUniqueID>8207540</NlmUniqueID><ISSNLinking>0278-7393</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007802" MajorTopicYN="Y">Language</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008037" MajorTopicYN="Y">Linguistics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006309" MajorTopicYN="N">Hearing</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014956" MajorTopicYN="N">Writing</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>5</Month><Day>24</Day><Hour>6</Hour><Minute>42</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2022</Year><Month>12</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>12</Month><Day>15</Day><Hour>16</Hour><Minute>34</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">36521151</ArticleId><ArticleId IdType="doi">10.1037/xlm0001204</ArticleId><ArticleId IdType="pii">2023-28020-001</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">36354145</PMID><DateCompleted><Year>2023</Year><Month>01</Month><Day>02</Day></DateCompleted><DateRevised><Year>2023</Year><Month>01</Month><Day>03</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1744-7909</ISSN><JournalIssue CitedMedium="Internet"><Volume>64</Volume><Issue>12</Issue><PubDate><Year>2022</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Journal of integrative plant biology</Title><ISOAbbreviation>J Integr Plant Biol</ISOAbbreviation></Journal><ArticleTitle>Arabidopsis Trithorax histone methyltransferases are redundant in regulating development and DNA methylation.</ArticleTitle><Pagination><StartPage>2438</StartPage><EndPage>2454</EndPage><MedlinePgn>2438-2454</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/jipb.13406</ELocationID><Abstract><AbstractText>Although the Trithorax histone methyltransferases ATX1-5 are known to regulate development and stress responses by catalyzing histone H3K4 methylation in Arabidopsis thaliana, it is unknown whether and how these histone methyltransferases affect DNA methylation. Here, we found that the redundant ATX1-5 proteins are not only required for plant development and viability but also for the regulation of DNA methylation. The expression and H3K4me3 levels of both RNA-directed DNA methylation (RdDM) genes (NRPE1, DCL3, IDN2, and IDP2) and active DNA demethylation genes (ROS1, DML2, and DML3) were downregulated in the atx1/2/4/5 mutant. Consistent with the facts that the active DNA demethylation pathway mediates DNA demethylation&#xa0;mainly at CG and CHG sites, and that the RdDM pathway mediates DNA methylation mainly at CHH sites, whole-genome DNA methylation analyses showed that hyper-CG and CHG DMRs in atx1/2/4/5 significantly overlapped with those in the DNA demethylation pathway mutant ros1 dml2 dml3 (rdd), and that hypo-CHH DMRs in atx1/2/4/5 significantly overlapped with those in the RdDM mutant nrpe1, suggesting that the ATX paralogues function redundantly to regulate DNA methylation by promoting H3K4me3 levels and expression levels of both RdDM genes and active DNA demethylation genes. Given that the ATX proteins function as catalytic subunits of COMPASS histone methyltransferase complexes, we also demonstrated that the COMPASS complex components function as a whole to regulate DNA methylation. This study reveals a previously uncharacterized mechanism underlying the regulation of DNA methylation.</AbstractText><CopyrightInformation>&#xa9; 2022 Institute of Botany, Chinese Academy of Sciences.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Shang</LastName><ForeName>Ji-Yun</ForeName><Initials>JY</Initials><Identifier Source="ORCID">0000-0003-1004-0818</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Xue-Wei</ForeName><Initials>XW</Initials><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Su</LastName><ForeName>Yin-Na</ForeName><Initials>YN</Initials><Identifier Source="ORCID">0000-0002-7319-5086</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Zhao-Chen</ForeName><Initials>ZC</Initials><Identifier Source="ORCID">0000-0002-0769-0388</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Xin</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0001-7147-9002</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>He</LastName><ForeName>Xin-Jian</ForeName><Initials>XJ</Initials><Identifier Source="ORCID">0000-0002-2878-7461</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 100084, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2022</Year><Month>12</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>China (Republic : 1949- )</Country><MedlineTA>J Integr Plant Biol</MedlineTA><NlmUniqueID>101250502</NlmUniqueID><ISSNLinking>1672-9072</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D029681">Arabidopsis Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D011505">Protein-Tyrosine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.1.1.-</RegistryNumber><NameOfSubstance UI="D000076983">Histone Methyltransferases</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011518">Proto-Oncogene Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.1.1.-</RegistryNumber><NameOfSubstance UI="D008780">Methyltransferases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.26.3</RegistryNumber><NameOfSubstance UI="C519654">DCL3 protein, Arabidopsis</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.26.3</RegistryNumber><NameOfSubstance UI="D043244">Ribonuclease III</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.2.2.-</RegistryNumber><NameOfSubstance UI="C519857">DML3 protein, Arabidopsis</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.2.2.-</RegistryNumber><NameOfSubstance UI="D045647">DNA Glycosylases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D017360" MajorTopicYN="Y">Arabidopsis</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019175" MajorTopicYN="N">DNA Methylation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D029681" MajorTopicYN="Y">Arabidopsis Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011505" MajorTopicYN="N">Protein-Tyrosine Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000076983" MajorTopicYN="N">Histone Methyltransferases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011518" MajorTopicYN="N">Proto-Oncogene Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018506" MajorTopicYN="N">Gene Expression Regulation, Plant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008780" MajorTopicYN="N">Methyltransferases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D043244" MajorTopicYN="N">Ribonuclease III</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045647" MajorTopicYN="Y">DNA Glycosylases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">DNA demethylation</Keyword><Keyword MajorTopicYN="N">DNA methylation</Keyword><Keyword MajorTopicYN="N">NRPE1</Keyword><Keyword MajorTopicYN="N">ROS1</Keyword><Keyword MajorTopicYN="N">development</Keyword><Keyword MajorTopicYN="N">histone methylation</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>8</Month><Day>8</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2022</Year><Month>11</Month><Day>9</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2022</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>1</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>11</Month><Day>10</Day><Hour>6</Hour><Minute>52</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">36354145</ArticleId><ArticleId IdType="doi">10.1111/jipb.13406</ArticleId></ArticleIdList><ReferenceList><Title>REFERENCES</Title><Reference><Citation>Agius, F., Kapoor, A., and Zhu, J.-K. (2006). Role of the Arabidopsis DNA glycosylase/lyase ROS1 in active DNA demethylation. Proc. Natl. Acad. Sci. U.S.A. 103: 11796-11801.</Citation></Reference><Reference><Citation>Alvarez-Venegas, R., and Avramova, Z. (2005). Methylation patterns of histone H3 Lys 4, Lys 9 and Lys 27 in transcriptionally active and inactive Arabidopsis genes and in atx1 mutants. Nucleic Acids Res. 33: 5199-5207.</Citation></Reference><Reference><Citation>Alvarez-Venegas, R., Pien, S., Sadder, M., Witmer, X., Grossniklaus, U., and Avramova, Z. (2003). ATX-1, an Arabidopsis homolog of trithorax, activates flower homeotic genes. Curr. Biol. 13: 627-637.</Citation></Reference><Reference><Citation>Aquea, F., Johnston, A.J., Ca&#xf1;on, P., Grossniklaus, U., and Arce-Johnson, P. (2010). TRAUCO, a Trithorax-group gene homologue, is required for early embryogenesis in Arabidopsis thaliana. J. Exp. Bot. 61: 1215-1224.</Citation></Reference><Reference><Citation>Ausin, I., Greenberg, M.V., Simanshu, D.K., Hale, C.J., Vashisht, A.A., Simon, S.A., Lee, T.-F., Feng, S., Espa&#xf1;ola, S.D., and Meyers, B.C. (2012). INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis. Proc. Natl. Acad. Sci. U.S.A. 109: 8374-8381.</Citation></Reference><Reference><Citation>Ausin, I., Mockler, T.C., Chory, J., and Jacobsen, S.E. (2009). IDN1 and IDN2 are required for de novo DNA methylation in Arabidopsis thaliana. Nat. Struct. Mol. Biol. 16: 1325-1327.</Citation></Reference><Reference><Citation>Bannister, A.J., and Kouzarides, T. (2005). Reversing histone methylation. Nature 436: 1103-1106.</Citation></Reference><Reference><Citation>Baumbusch, L.O., Thorstensen, T., Krauss, V., Fischer, A., Naumann, K., Assalkhou, R., Schulz, I., Reuter, G., and Aalen, R.B. (2001). The Arabidopsis thaliana genome contains at least 29 active genes encoding SET domain proteins that can be assigned to four evolutionarily conserved classes. Nucleic Acids Res. 29: 4319-4333.</Citation></Reference><Reference><Citation>Berr, A., McCallum, E.J., M&#xe9;nard, R., Meyer, D., Fuchs, J., Dong, A., and Shen, W.-H. (2010). Arabidopsis SET DOMAIN GROUP2 is required for H3K4 trimethylation and is crucial for both sporophyte and gametophyte development. Plant Cell 22: 3232-3248.</Citation></Reference><Reference><Citation>Berr, A., Xu, L., Gao, J., Cognat, V., Steinmetz, A., Dong, A., and Shen, W.-H. (2009). SET DOMAIN GROUP25 encodes a histone methyltransferase and is involved in FLOWERING LOCUS C activation and repression of flowering. Plant Physiol. 151: 1476-1485.</Citation></Reference><Reference><Citation>Cao, X., and Jacobsen, S.E. (2002). Locus-specific control of asymmetric and CpNpG methylation by the DRM and CMT3 methyltransferase genes. Proc. Natl. Acad. Sci. U.S.A. 99: 16491-16498.</Citation></Reference><Reference><Citation>Chen, L.Q., Luo, J.H., Cui, Z.H., Xue, M., Wang, L., Zhang, X.Y., Pawlowski, W.P., and He, Y. (2017). ATX3, ATX4, and ATX5 encode putative H3K4 methyltransferases and are critical for plant development. Plant Physiol. 174: 1795-1806.</Citation></Reference><Reference><Citation>Cheng, J., Niu, Q., Zhang, B., Chen, K., Yang, R., Zhu, J.K., Zhang, Y., and Lang, Z. (2018). Downregulation of RdDM during strawberry fruit ripening. Genome Biol. 19: 212.</Citation></Reference><Reference><Citation>Choi, Y., Gehring, M., Johnson, L., Hannon, M., Harada, J.J., Goldberg, R.B., Jacobsen, S.E., and Fischer, R.L. (2002). DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in Arabidopsis. Cell 110: 33-42.</Citation></Reference><Reference><Citation>Deng, S., Jang, I.C., Su, L., Xu, J., and Chua, N.H. (2016). JMJ24 targets CHROMOMETHYLASE3 for proteasomal degradation in Arabidopsis. Genes Dev. 30: 251-256.</Citation></Reference><Reference><Citation>Deng, S., Xu, J., Liu, J., Kim, S.H., Shi, S., and Chua, N.H. (2015). JMJ24 binds to RDR2 and is required for the basal level transcription of silenced loci in Arabidopsis. Plant J. 83: 770-782.</Citation></Reference><Reference><Citation>Ding, Y., Avramova, Z., and Fromm, M. (2011). The Arabidopsis trithorax-like factor ATX1 functions in dehydration stress responses via ABA-dependent and ABA-independent pathways. Plant J. 66: 735-744.</Citation></Reference><Reference><Citation>Duan, C.G., Wang, X., Xie, S., Pan, L., Miki, D., Tang, K., Hsu, C.-C., Lei, M., Zhong, Y., and Hou, Y.J. (2017). A pair of transposon-derived proteins function in a histone acetyltransferase complex for active DNA demethylation. Cell Res. 27: 226-240.</Citation></Reference><Reference><Citation>Finke, A., Kuhlmann, M., and Florian Mette, M. (2012). IDN2 has a role downstream of siRNA formation in RNA-directed DNA methylation. Epigenetics 7: 950-960.</Citation></Reference><Reference><Citation>Gehring, M., Huh, J.H., Hsieh, T.-F., Penterman, J., Choi, Y., Harada, J.J., Goldberg, R.B., and Fischer, R.L. (2006). DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation. Cell 124: 495-506.</Citation></Reference><Reference><Citation>Guo, L., Yu, Y., Law, J.A., and Zhang, X. (2010). SET DOMAIN GROUP2 is the major histone H3 lysine 4 trimethyltransferase in Arabidopsis. Proc. Natl. Acad. Sci. U.S.A. 107: 18557-18562.</Citation></Reference><Reference><Citation>He, X.J., Chen, T., and Zhu, J.K. (2011). Regulation and function of DNA methylation in plants and animals. Cell Res. 21: 442-465.</Citation></Reference><Reference><Citation>He, X.J., Hsu, Y.F., Zhu, S., Wierzbicki, A.T., Pontes, O., Pikaard, C.S., Liu, H.L., Wang, C.S., Jin, H., and Zhu, J.K. (2009). An effector of RNA-directed DNA methylation in arabidopsis is an ARGONAUTE 4- and RNA-binding protein. Cell 137: 498-508.</Citation></Reference><Reference><Citation>Hohenstatt, M.L., Mikulski, P., Komarynets, O., Klose, C., Kycia, I., Jeltsch, A., Farrona, S., and Schubert, D. (2018). PWWP-DOMAIN INTERACTOR OF POLYCOMBS1 interacts with polycomb-group proteins and histones and regulates Arabidopsis flowering and development. Plant Cell 30: 117-133.</Citation></Reference><Reference><Citation>Huang, H., Liu, R., Niu, Q., Tang, K., Zhang, B., Zhang, H., Chen, K., Zhu, J.K., and Lang, Z. (2019). Global increase in DNA methylation during orange fruit development and ripening. Proc. Natl. Acad. Sci. U.S.A. 116: 1430-1436.</Citation></Reference><Reference><Citation>Hung, F.Y., Lai, Y.C., Wang, J., Feng, Y.R., Shih, Y.H., Chen, J.H., Sun, H.C., Yang, S., Li, C., and Wu, K. (2021). The Arabidopsis histone demethylase JMJ28 regulates CONSTANS by interacting with FBH transcription factors. Plant Cell 33: 1196-1211.</Citation></Reference><Reference><Citation>Jiang, D., Gu, X., and He, Y. (2009). Establishment of the winter-annual growth habit via FRIGIDA-mediated histone methylation at FLOWERING LOCUS C in Arabidopsis. Plant Cell 21: 1733-1746.</Citation></Reference><Reference><Citation>Jiang, D., Kong, N.C., Gu, X., Li, Z., and He, Y. (2011). Arabidopsis COMPASS-like complexes mediate histone H3 lysine-4 trimethylation to control floral transition and plant development. PLoS Genet. 7: e1001330.</Citation></Reference><Reference><Citation>Kabelitz, T., Brzezinka, K., Friedrich, T., G&#xf3;rka, M., Graf, A., Kappel, C., and B&#xe4;urle, I. (2016). A jumonji protein with E3 ligase and histone H3 binding activities affects transposon silencing in Arabidopsis. Plant Physiol. 171: 344-358.</Citation></Reference><Reference><Citation>Kim, D., Paggi, J.M., Park, C., Bennett, C., and Salzberg, S.L. (2019). Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37: 907-915.</Citation></Reference><Reference><Citation>Krueger, F., and Andrews, S.R. (2011). Bismark: A flexible aligner and methylation caller for Bisulfite-Seq applications. Bioinformatics 27: 1571-1572.</Citation></Reference><Reference><Citation>Lang, Z., Lei, M., Wang, X., Tang, K., Miki, D., Zhang, H., Mangrauthia, S.K., Liu, W., Nie, W., and Ma, G. (2015). The methyl-CpG-binding protein MBD7 facilitates active DNA demethylation to limit DNA hyper-methylation and transcriptional gene silencing. Mol. Cell 57: 971-983.</Citation></Reference><Reference><Citation>Lang, Z., Wang, Y., Tang, K., Tang, D., Datsenka, T., Cheng, J., Zhang, Y., Handa, A.K., and Zhu, J.K. (2017). Critical roles of DNA demethylation in the activation of ripening-induced genes and inhibition of ripening-repressed genes in tomato fruit. Proc. Natl. Acad. Sci. U.S.A. 114: E4511-e4519.</Citation></Reference><Reference><Citation>Langmead, B., and Salzberg, S.L. (2012). Fast gapped-read alignment with Bowtie 2. Nat. Methods 9: 357-359.</Citation></Reference><Reference><Citation>Lei, M., Zhang, H., Julian, R., Tang, K., Xie, S., and Zhu, J.K. (2015). Regulatory link between DNA methylation and active demethylation in Arabidopsi. Proc. Natl. Acad. Sci. U.S.A. 112: 3553-3557.</Citation></Reference><Reference><Citation>Li, B., Carey, M., and Workman, J.L. (2007). The role of chromatin during transcription. Cell 128: 707-719.</Citation></Reference><Reference><Citation>Li, Q., Wang, X., Sun, H., Zeng, J., Cao, Z., Li, Y., and Qian, W. (2015). Regulation of active DNA demethylation by a methyl-CpG-binding domain protein in Arabidopsis thaliana. PLoS Genet. 11: e1005210.</Citation></Reference><Reference><Citation>Li, X., Wang, X., He, K., Ma, Y., Su, N., He, H., Stolc, V., Tongprasit, W., Jin, W., Jiang, J., Terzaghi, W., Li, S., and Deng, X.W. (2008). High-resolution mapping of epigenetic modifications of the rice genome uncovers interplay between DNA methylation, histone methylation, and gene expression. Plant Cell 20: 259-276.</Citation></Reference><Reference><Citation>Li, Y., Kumar, S., and Qian, W. (2018). Active DNA demethylation: Mechanism and role in plant development. Plant Cell Rep. 37: 77-85.</Citation></Reference><Reference><Citation>Liao, Y., Smyth, G.K., and Shi, W. (2014). featureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30: 923-930.</Citation></Reference><Reference><Citation>Liu, R., How-Kit, A., Stammitti, L., Teyssier, E., Rolin, D., Mortain-Bertrand, A., Halle, S., Liu, M., Kong, J., Wu, C., Degraeve-Guibault, C., Chapman, N.H., Maucourt, M., Hodgman, T.C., Tost, J., Bouzayen, M., Hong, Y., Seymour, G.B., Giovannoni, J.J., and Gallusci, P. (2013). A DEMETER-like DNA demethylase governs tomato fruit ripening. Proc. Natl. Acad. Sci. U.S.A. 112: 10804-10809.</Citation></Reference><Reference><Citation>Liu, R., and Lang, Z. (2020). The mechanism and function of active DNA demethylation in plants. J. Integr. Plant Biol. 62: 148-159.</Citation></Reference><Reference><Citation>Liu, Y., Liu, K., Yin, L., Yu, Y., Qi, J., Shen, W.-H., Zhu, J., Zhang, Y., and Dong, A. (2019). H3K4me2 functions as a repressive epigenetic mark in plants. Epigenet. Chromatin 12: 40.</Citation></Reference><Reference><Citation>Liu, Y., Zhang, A., Yin, H., Meng, Q., Yu, X., Huang, S., Wang, J., Ahmad, R., Liu, B., and Xu, Z.Y. (2018). Trithorax-group proteins ARABIDOPSIS TRITHORAX4 (ATX4) and ATX 5 function in abscisic acid and dehydration stress responses. New Phytol. 217: 1582-1597.</Citation></Reference><Reference><Citation>Matzke, M.A., and Mosher, R.A. (2014). RNA-directed DNA methylation: An epigenetic pathway of increasing complexity. Nat. Rev. Genet. 15: 394-408.</Citation></Reference><Reference><Citation>Morales-Ruiz, T., Ortega-Galisteo, A.P., Ponferrada-Mar&#xed;n, M.I., Mart&#xed;nez-Mac&#xed;as, M.I., Ariza, R.R., and Rold&#xe1;n-Arjona, T. (2006). Demeter and repressor of silencing 1 encode 5-methylcytosine DNA glycosylases. Proc. Natl. Acad. Sci. U.S.A. 103: 6853-6858.</Citation></Reference><Reference><Citation>Ning, Y.Q., Liu, N., Lan, K.K., Su, Y.N., Li, L., Chen, S., and He, X.J. (2020). DREAM complex suppresses DNA methylation maintenance genes and precludes DNA hypermethylation. Nat. Plants 6: 942-956.</Citation></Reference><Reference><Citation>Ortega-Galisteo, A.P., Morales-Ruiz, T., Ariza, R.R., and Rold&#xe1;n-Arjona, T. (2008). Arabidopsis DEMETER-LIKE proteins DML2 and DML3 are required for appropriate distribution of DNA methylation marks. Plant Mol. Biol. 67: 671-681.</Citation></Reference><Reference><Citation>Oya, S., Takahashi, M., Takashima, K., Kakutani, T., and Inagaki, S. (2022). Transcription-coupled and epigenome-encoded mechanisms direct H3K4 methylation. Nat. Commun. 13: 4521.</Citation></Reference><Reference><Citation>Penterman, J., Zilberman, D., Huh, J.H., Ballinger, T., Henikoff, S., and Fischer, R.L. (2007). DNA demethylation in the Arabidopsis genome. Proc. Natl. Acad. Sci. U.S.A. 104: 6752-6757.</Citation></Reference><Reference><Citation>Pien, S., Fleury, D., Mylne, J.S., Crevillen, P., Inze, D., Avramova, Z., Dean, C., and Grossniklaus, U. (2008). ARABIDOPSIS TRITHORAX1 dynamically regulates FLOWERING LOCUS C activation via histone 3 lysine 4 trimethylation. Plant Cell 20: 580-588.</Citation></Reference><Reference><Citation>Qi, P.L., Zhou, H.R., Zhao, Q.Q., Feng, C., Ning, Y.Q., Su, Y.N., Cai, X.W., Yuan, D.Y., Zhang, Z.C., Su, X.M., Chen, S.S., Li, L., Chen, S., and He, X.J. (2022). Characterization of an autonomous pathway complex that promotes flowering in Arabidopsis. Nucleic Acids Res. 50: 7380-7395.</Citation></Reference><Reference><Citation>Qian, W., Miki, D., Lei, M., Zhu, X., Zhang, H., Liu, Y., Li, Y., Lang, Z., Wang, J., and Tang, K. (2014). Regulation of active DNA demethylation by an &#x3b1;-crystallin domain protein in Arabidopsis. Mol. Cell 55: 361-371.</Citation></Reference><Reference><Citation>Qian, W., Miki, D., Zhang, H., Liu, Y., Zhang, X., Tang, K., Kan, Y., La, H., Li, X., and Li, S. (2012). A histone acetyltransferase regulates active DNA demethylation in Arabidopsis. Science 336: 1445-1448.</Citation></Reference><Reference><Citation>Robinson, M.D., McCarthy, D.J., and Smyth, G.K. (2010). edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26: 139-140.</Citation></Reference><Reference><Citation>Roudier, F., Ahmed, I., B&#xe9;rard, C., Sarazin, A., Mary-Huard, T., Cortijo, S., Bouyer, D., Caillieux, E., Duvernois-Berthet, E., Al-Shikhley, L., Giraut, L., Despr&#xe9;s, B., Drevensek, S., Barneche, F., D&#xe8;rozier, S., Brunaud, V., Aubourg, S., Schnittger, A., Bowler, C., Martin-Magniette, M.L., Robin, S., Caboche, M., and Colot, V. (2011). Integrative epigenomic mapping defines four main chromatin states in Arabidopsis. EMBO J. 30: 1928-1938.</Citation></Reference><Reference><Citation>Saleh, A., Alvarez-Venegas, R., Yilmaz, M., Le, O., Hou, G., Sadder, M., Al-Abdallat, A., Xia, Y., Lu, G., and Ladunga, I. (2008). The highly similar Arabidopsis homologs of trithorax ATX1 and ATX2 encode proteins with divergent biochemical functions. Plant Cell 20: 568-579.</Citation></Reference><Reference><Citation>Shang, J.Y., Lu, Y.J., Cai, X.W., Su, Y.N., Feng, C., Li, L., Chen, S., and He, X.J. (2021). COMPASS functions as a module of the INO80 chromatin remodeling complex to mediate histone H3K4 methylation in Arabidopsis. Plant Cell 33: 3250-3271.</Citation></Reference><Reference><Citation>Shang, J.Y., and He, X.J. (2022). Chromatin-remodeling complexes: Conserved and plant-specific subunits in Arabidopsis. J. Integr. Plant Biol. 64: 499-515.</Citation></Reference><Reference><Citation>Shilatifard, A. (2012). The COMPASS family of histone H3K4 methylases: Mechanisms of regulation in development and disease pathogenesis. Annu. Rev. Biochem. 81: 65-95.</Citation></Reference><Reference><Citation>Stroud, H., Greenberg, M.V., Feng, S., Bernatavichute, Y.V., and Jacobsen, S.E. (2013). Comprehensive analysis of silencing mutants reveals complex regulation of the Arabidopsis methylome. Cell 152: 352-364.</Citation></Reference><Reference><Citation>Tamada, Y., Yun, J.-Y., chul Woo, S., and Amasino, R.M. (2009). ARABIDOPSIS TRITHORAX-RELATED7 is required for methylation of lysine 4 of histone H3 and for transcriptional activation of FLOWERING LOCUS C. Plant Cell 21: 3257-3269.</Citation></Reference><Reference><Citation>Tang, K., Lang, Z., Zhang, H., and Zhu, J.K. (2016). The DNA demethylase ROS1 targets genomic regions with distinct chromatin modifications. Nat. Plants 2: 1-10.</Citation></Reference><Reference><Citation>Wickham, H. (2016). ggplot2: Elegant graphics for data analysis. Springer.</Citation></Reference><Reference><Citation>Wierzbicki, A.T., Haag, J.R., and Pikaard, C.S. (2008). Noncoding transcription by RNA polymerase Pol IVb/Pol V mediates transcriptional silencing of overlapping and adjacent genes. Cell 135: 635-648.</Citation></Reference><Reference><Citation>Williams, B.P., Pignatta, D., Henikoff, S., and Gehring, M. (2015). Methylation-sensitive expression of a DNA demethylase gene serves as an epigenetic rheostat. PLoS Genet. 11: e1005142.</Citation></Reference><Reference><Citation>Xue, M., Zhang, H., Zhao, F., Zhao, T., Li, H., and Jiang, D. (2021). The INO80 chromatin remodeling complex promotes thermomorphogenesis by connecting H2A.Z eviction and active transcription in Arabidopsis. Mol. Plant 14: 1799-1813.</Citation></Reference><Reference><Citation>Yang, R., Zheng, Z., Chen, Q., Yang, L., Huang, H., Miki, D., Wu, W., Zeng, L., Liu, J., Zhou, J.X., Ogas, J., Zhu, J.K., He, X.J., and Zhang, H. (2017). The developmental regulator PKL is required to maintain correct DNA methylation patterns at RNA-directed DNA methylation loci. Genome Biol. 18: 103.</Citation></Reference><Reference><Citation>Zang, C., Schones, D.E., Zeng, C., Cui, K., Zhao, K., and Peng, W. (2009). A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics 25: 1952-1958.</Citation></Reference><Reference><Citation>Zhang, C., Du, X., Tang, K., Yang, Z., Pan, L., Zhu, P., Luo, J., Jiang, Y., Zhang, H., and Wan, H. (2018a). Arabidopsis AGDP1 links H3K9me2 to DNA methylation in heterochromatin. Nat. Commun. 9: 1-14.</Citation></Reference><Reference><Citation>Zhang, C.J., Ning, Y.Q., Zhang, S.W., Chen, Q., Shao, C.R., Guo, Y.W., Zhou, J.X., Li, L., Chen, S., and He, X.J. (2012). IDN2 and its paralogs form a complex required for RNA-directed DNA methylation. PLoS Genet. 8: e1002693.</Citation></Reference><Reference><Citation>Zhang, H., Lang, Z., and Zhu, J.-K. (2018b). Dynamics and function of DNA methylation in plants. Nat. Rev. Mol. Cell Biol. 19: 489-506.</Citation></Reference><Reference><Citation>Zhang, H., and Zhu, J.K. (2012). Active DNA demethylation in plants and animals. Cold Spring Harb. Symp. Quant. Biol. 77: 161-173.</Citation></Reference><Reference><Citation>Zhang, X., Clarenz, O., Cokus, S., Bernatavichute, Y.V., Pellegrini, M., Goodrich, J., and Jacobsen, S.E. (2007). Whole-genome analysis of histone H3 lysine 27 trimethylation in Arabidopsis. PLoS Biol. 5: e129.</Citation></Reference><Reference><Citation>Zhang, X., Bernatavichute, Y.V., Cokus, S., Pellegrini, M., and Jacobsen, S.E. (2009). Genome-wide analysis of mono-, di-and trimethylation of histone H3 lysine 4 in Arabidopsis thaliana. Genome Biol. 10: R62.</Citation></Reference><Reference><Citation>Zhang, X., Yazaki, J., Sundaresan, A., Cokus, S., Chan, S.W.-L., Chen, H., Henderson, I.R., Shinn, P., Pellegrini, M., and Jacobsen, S.E. (2006). Genome-wide high-resolution mapping and functional analysis of DNA methylation in Arabidopsis. Cell 126: 1189-1201.</Citation></Reference><Reference><Citation>Zhao, Y., Xie, S., Li, X., Wang, C., Chen, Z., Lai, J., and Gong, Z. (2014). REPRESSOR OF SILENCING5 encodes a member of the small heat shock protein family and is required for DNA demethylation in Arabidopsis. Plant Cell 26: 2660-2675.</Citation></Reference><Reference><Citation>Zhou, J.X., Liu, Z.W., Li, Y.Q., Li, L., Wang, B., Chen, S., and He, X.J. (2018). Arabidopsis PWWP domain proteins mediate H3K27 trimethylation on FLC and regulate flowering time. J. Integr. Plant Biol. 60: 362-368.</Citation></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">35938531</PMID><DateCompleted><Year>2022</Year><Month>08</Month><Day>09</Day></DateCompleted><DateRevised><Year>2023</Year><Month>03</Month><Day>24</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2379-3708</ISSN><JournalIssue CitedMedium="Internet"><Volume>7</Volume><Issue>15</Issue><PubDate><Year>2022</Year><Month>Aug</Month><Day>08</Day></PubDate></JournalIssue><Title>JCI insight</Title><ISOAbbreviation>JCI Insight</ISOAbbreviation></Journal><ArticleTitle>SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e154113</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1172/jci.insight.154113</ELocationID><Abstract><AbstractText>Genetic polymorphisms are associated with the development of nonalcoholic fatty liver disease (NAFLD). Semaphorin7a (Sema7a) deficiency in mouse peritoneal macrophages reduces fatty acid (FA) oxidation. Here, we identified 17 individuals with SEMA7A heterozygous mutations in 470 patients with biopsy-proven NAFLD. SEMA7A heterozygous mutations increased susceptibility to NAFLD, steatosis severity, and NAFLD activity scores in humans and mice. The Sema7aR145W mutation (equivalent to human SEMA7AR148W) significantly induced small lipid droplet accumulation in mouse livers compared with WT mouse livers. Mechanistically, the Sema7aR145W mutation increased N-glycosylated Sema7a and its receptor integrin &#x3b2;1 proteins in the cell membranes of hepatocytes. Furthermore, Sema7aR145W mutation enhanced its protein interaction with integrin &#x3b2;1 and PKC-&#x3b1; and increased PKC-&#x3b1; phosphorylation, which were both abrogated by integrin &#x3b2;1 silencing. Induction of PKC&#x3b1;_WT, but not PKC&#x3b1;_dominant negative, overexpression induced transcriptional factors Srebp1, Chrebp, and Lxr expression and their downstream Acc1, Fasn, and Cd36 expression in primary mouse hepatocytes. Collectively, our findings demonstrate that the SEMA7AR148W mutation is a potentially new strong genetic determinant of NAFLD and promotes intrahepatic lipid accumulation and NAFLD in mice by enhancing PKC-&#x3b1;-stimulated FA and triglyceride synthesis and FA uptake. The inhibition of hepatic PKC-&#x3b1; signaling may lead to novel NAFLD therapies.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaoxun</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Jingjing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Qiong</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Ming-Hua</ForeName><Initials>MH</Initials><AffiliationInfo><Affiliation>NAFLD Research Center, Department of Hepatology, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Wen-Yue</ForeName><Initials>WY</Initials><AffiliationInfo><Affiliation>Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>Gang</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qu</LastName><ForeName>Jiaquan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Mingqiao</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ling</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Qiaoling</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wei</LastName><ForeName>Qinglin</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Qiao</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zou</LastName><ForeName>Lingyun</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Bioinformatics Center, Department of Microbiology of Third Military Medical University, Chongqing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bao'an Maternal and Child Health Hospital of Jinan University, Shenzhen, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ouyang</LastName><ForeName>Xinshou</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Section of Digestive Diseases, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shi-Ying</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyer</LastName><ForeName>James L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Jin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Center, and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>UL1 TR001863</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2022</Year><Month>08</Month><Day>08</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>JCI Insight</MedlineTA><NlmUniqueID>101676073</NlmUniqueID><ISSNLinking>2379-3708</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015703">Antigens, CD</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019012">Integrin beta1</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008055">Lipids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C485571">Sema7a protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D039961">Semaphorins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015703" MajorTopicYN="N">Antigens, CD</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D022781" MajorTopicYN="N">Hepatocytes</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019012" MajorTopicYN="N">Integrin beta1</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008055" MajorTopicYN="N">Lipids</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="Y">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065626" MajorTopicYN="Y">Non-alcoholic Fatty Liver Disease</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D039961" MajorTopicYN="N">Semaphorins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Genetic variation</Keyword><Keyword MajorTopicYN="N">Hepatology</Keyword><Keyword MajorTopicYN="N">Metabolism</Keyword><Keyword MajorTopicYN="N">Molecular biology</Keyword><Keyword MajorTopicYN="N">Mouse models</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>8</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2022</Year><Month>6</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>8</Month><Day>8</Day><Hour>6</Hour><Minute>2</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2022</Year><Month>8</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>8</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2022</Year><Month>8</Month><Day>8</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">35938531</ArticleId><ArticleId IdType="pmc">PMC9462498</ArticleId><ArticleId IdType="doi">10.1172/jci.insight.154113</ArticleId><ArticleId IdType="pii">154113</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Hodson L, Gunn PJ. The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state. Nat Rev Endocrinol. 2019;15(12):689&#x2013;700. doi: 10.1038/s41574-019-0256-9.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41574-019-0256-9</ArticleId><ArticleId IdType="pubmed">31554932</ArticleId></ArticleIdList></Reference><Reference><Citation>Friedman SL, et al. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24(7):908&#x2013;922. doi: 10.1038/s41591-018-0104-9.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41591-018-0104-9</ArticleId><ArticleId IdType="pmc">PMC6553468</ArticleId><ArticleId IdType="pubmed">29967350</ArticleId></ArticleIdList></Reference><Reference><Citation>Younossi ZM. Non-alcoholic fatty liver disease &#x2014; a global public health perspective. J Hepatol. 2019;70(3):531&#x2013;544. doi: 10.1016/j.jhep.2018.10.033.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2018.10.033</ArticleId><ArticleId IdType="pubmed">30414863</ArticleId></ArticleIdList></Reference><Reference><Citation>Alto LT, Terman JR. Semaphorins and their signaling mechanisms. Methods Mol Biol. 2017;1493:1&#x2013;25.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5538787</ArticleId><ArticleId IdType="pubmed">27787839</ArticleId></ArticleIdList></Reference><Reference><Citation>Yamada A, et al. Molecular cloning of a glycosylphosphatidylinositol-anchored molecule CDw108. J Immunol. 1999;162(7):4094&#x2013;4100.</Citation><ArticleIdList><ArticleId IdType="pubmed">10201933</ArticleId></ArticleIdList></Reference><Reference><Citation>Song Y, et al. The involvement of semaphorin 7A in tumorigenic and immunoinflammatory regulation. J Cell Physiol. 2021;236(9):6235&#x2013;6248. doi: 10.1002/jcp.30340.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/jcp.30340</ArticleId><ArticleId IdType="pubmed">33611799</ArticleId></ArticleIdList></Reference><Reference><Citation>De Minicis S, et al. Semaphorin 7A contributes to TGF-&#x3b2;-mediated liver fibrogenesis. Am J Pathol. 2013;183(3):820&#x2013;830. doi: 10.1016/j.ajpath.2013.05.030.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ajpath.2013.05.030</ArticleId><ArticleId IdType="pmc">PMC5819760</ArticleId><ArticleId IdType="pubmed">23850082</ArticleId></ArticleIdList></Reference><Reference><Citation>Czopik AK, et al. Semaphorin 7A is a negative regulator of T cell responses. Immunity. 2006;24(5):591&#x2013;600. doi: 10.1016/j.immuni.2006.03.013.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.immuni.2006.03.013</ArticleId><ArticleId IdType="pubmed">16713976</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu H, et al. Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1. Cell. 2010;142(5):749&#x2013;761. doi: 10.1016/j.cell.2010.07.040.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.cell.2010.07.040</ArticleId><ArticleId IdType="pmc">PMC2936782</ArticleId><ArticleId IdType="pubmed">20727575</ArticleId></ArticleIdList></Reference><Reference><Citation>Koh JM, et al. Association study of semaphorin 7a (sema7a) polymorphisms with bone mineral density and fracture risk in postmenopausal Korean women. J Hum Genet. 2006;51(2):112&#x2013;117. doi: 10.1007/s10038-005-0331-z.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s10038-005-0331-z</ArticleId><ArticleId IdType="pubmed">16372136</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhao Y, et al. A novel heterozygous intron mutation in SEMA7A causing kallmann syndrome in a female. Gynecol Endocrinol. 2020;36(3):218&#x2013;221. doi: 10.1080/09513590.2019.1680624.</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/09513590.2019.1680624</ArticleId><ArticleId IdType="pubmed">31650878</ArticleId></ArticleIdList></Reference><Reference><Citation>K&#xf6;rner A, et al. Sema7A is crucial for resolution of severe inflammation. Proc Natl Acad Sci U S A. 2021;118(9):e2017527118. doi: 10.1073/pnas.2017527118.</Citation><ArticleIdList><ArticleId IdType="doi">10.1073/pnas.2017527118</ArticleId><ArticleId IdType="pmc">PMC7936270</ArticleId><ArticleId IdType="pubmed">33637648</ArticleId></ArticleIdList></Reference><Reference><Citation>Zheng KI, et al. Clinical utility of the MAFLD definition. J Hepatol. 2021;74(4):989&#x2013;991. doi: 10.1016/j.jhep.2020.12.016.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2020.12.016</ArticleId><ArticleId IdType="pubmed">33347953</ArticleId></ArticleIdList></Reference><Reference><Citation>Li X, et al. Regulation of lipid metabolism in diabetic rats by Arctium lappa L. polysaccharide through the PKC/NF-&#x3ba;B pathway. Int J Biol Macromol. 2019;136:115&#x2013;122. doi: 10.1016/j.ijbiomac.2019.06.057.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ijbiomac.2019.06.057</ArticleId><ArticleId IdType="pubmed">31195041</ArticleId></ArticleIdList></Reference><Reference><Citation>Bodnar J, et al. Enzymatic removal of N-glycans by PNGase F coated magnetic microparticles. Electrophoresis. 2016;37(10):1264&#x2013;1269. doi: 10.1002/elps.201500575.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/elps.201500575</ArticleId><ArticleId IdType="pubmed">26872155</ArticleId></ArticleIdList></Reference><Reference><Citation>Siskov&#xe1; Z, et al. Fibronectin impedes &#x201c;myelin&#x201d; sheet-directed flow in oligodendrocytes: a role for a beta 1 integrin-mediated PKC signaling pathway in vesicular trafficking. Mol Cell Neurosci. 2006;33(2):150&#x2013;159. doi: 10.1016/j.mcn.2006.07.001.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.mcn.2006.07.001</ArticleId><ArticleId IdType="pubmed">16935002</ArticleId></ArticleIdList></Reference><Reference><Citation>Lee K, et al. Hepatic mitochondrial defects in a nonalcoholic fatty liver disease mouse model are associated with increased degradation of oxidative phosphorylation subunits. Mol Cell Proteomics. 2018;17(12):2371&#x2013;2386. doi: 10.1074/mcp.RA118.000961.</Citation><ArticleIdList><ArticleId IdType="doi">10.1074/mcp.RA118.000961</ArticleId><ArticleId IdType="pmc">PMC6283295</ArticleId><ArticleId IdType="pubmed">30171159</ArticleId></ArticleIdList></Reference><Reference><Citation>Costa C, et al. Expression of semaphorin 3A, semaphorin 7A and their receptors in multiple sclerosis lesions. Mult Scler. 2015;21(13):1632&#x2013;1643. doi: 10.1177/1352458515599848.</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/1352458515599848</ArticleId><ArticleId IdType="pubmed">26432853</ArticleId></ArticleIdList></Reference><Reference><Citation>Varga J, Pasche B. Transforming growth factor beta as a therapeutic target in systemic sclerosis. Nat Rev Rheumatol. 2009;5(4):200&#x2013;206. doi: 10.1038/nrrheum.2009.26.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrrheum.2009.26</ArticleId><ArticleId IdType="pmc">PMC3959159</ArticleId><ArticleId IdType="pubmed">19337284</ArticleId></ArticleIdList></Reference><Reference><Citation>Xie J, Wang H. Semaphorin 7A as a potential immune regulator and promising therapeutic target in rheumatoid arthritis. Arthritis Res Ther. 2017;19(1):10. doi: 10.1186/s13075-016-1217-5.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/s13075-016-1217-5</ArticleId><ArticleId IdType="pmc">PMC5251212</ArticleId><ArticleId IdType="pubmed">28109308</ArticleId></ArticleIdList></Reference><Reference><Citation>Esnault S, et al. Semaphorin 7A is expressed on airway eosinophils and upregulated by IL-5 family cytokines. Clin Immunol. 2014;150(1):90&#x2013;100. doi: 10.1016/j.clim.2013.11.009.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.clim.2013.11.009</ArticleId><ArticleId IdType="pmc">PMC3947215</ArticleId><ArticleId IdType="pubmed">24333536</ArticleId></ArticleIdList></Reference><Reference><Citation>Kang S, et al. Intestinal epithelial cell-derived semaphorin 7A negatively regulates development of colitis via &#x3b1;v&#x3b2;1 integrin. J Immunol. 2012;188(3):1108&#x2013;1116. doi: 10.4049/jimmunol.1102084.</Citation><ArticleIdList><ArticleId IdType="doi">10.4049/jimmunol.1102084</ArticleId><ArticleId IdType="pubmed">22198947</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang P, et al. Decreased expression of semaphorin 3A and semaphorin 7A levels and its association with systemic lupus erythematosus. Immunol Invest. 2020;49(1&#x2013;2):69&#x2013;80.</Citation><ArticleIdList><ArticleId IdType="pubmed">31412748</ArticleId></ArticleIdList></Reference><Reference><Citation>Lazova R, et al. The semaphorin 7A receptor plexin C1 is lost during melanoma metastasis. Am J Dermatopathol. 2009;31(2):177&#x2013;181. doi: 10.1097/DAD.0b013e318196672d.</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/DAD.0b013e318196672d</ArticleId><ArticleId IdType="pubmed">19318806</ArticleId></ArticleIdList></Reference><Reference><Citation>Linton MF, et al. The Role of Lipids and Lipoproteins in Atherosclerosis. In: Feingold KR, et al., eds. Endotext. MDText.com: 2019.</Citation><ArticleIdList><ArticleId IdType="pubmed">26844337</ArticleId></ArticleIdList></Reference><Reference><Citation>Pan Q, et al. Solute carrier organic anion transporter family member 3A1 is a bile acid efflux transporter in cholestasis. Gastroenterology. 2018;155(5):1578&#x2013;1592. doi: 10.1053/j.gastro.2018.07.031.</Citation><ArticleIdList><ArticleId IdType="doi">10.1053/j.gastro.2018.07.031</ArticleId><ArticleId IdType="pmc">PMC6221191</ArticleId><ArticleId IdType="pubmed">30063921</ArticleId></ArticleIdList></Reference><Reference><Citation>Lan W, et al. Glycochenodeoxycholic acid impairs transcription factor E3 -dependent autophagy-lysosome machinery by disrupting reactive oxygen species homeostasis in L02 cells. Toxicol Lett. 2020;331:11&#x2013;21.</Citation><ArticleIdList><ArticleId IdType="pubmed">32439580</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu M, et al. KIF5A-dependent axonal transport deficiency disrupts autophagic flux in trimethyltin chloride-induced neurotoxicity. Autophagy. 2021;17(4):903&#x2013;924. doi: 10.1080/15548627.2020.1739444.</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/15548627.2020.1739444</ArticleId><ArticleId IdType="pmc">PMC8078766</ArticleId><ArticleId IdType="pubmed">32160081</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu Y, et al. Acyl-CoA thioesterase 1 prevents cardiomyocytes from Doxorubicin-induced ferroptosis via shaping the lipid composition. Cell Death Dis. 2020;11(9):756. doi: 10.1038/s41419-020-02948-2.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/s41419-020-02948-2</ArticleId><ArticleId IdType="pmc">PMC7492260</ArticleId><ArticleId IdType="pubmed">32934217</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai SY, et al. Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis. J Hepatol. 2021;74(3):550&#x2013;559. doi: 10.1016/j.jhep.2020.09.035.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jhep.2020.09.035</ArticleId><ArticleId IdType="pmc">PMC7897288</ArticleId><ArticleId IdType="pubmed">33039404</ArticleId></ArticleIdList></Reference><Reference><Citation>Park H, et al. IRE1&#x3b1; kinase-mediated unconventional protein secretion rescues misfolded CFTR and pendrin. Sci Adv. 2020;6(8): eaax9914. doi: 10.1126/sciadv.aax9914.</Citation><ArticleIdList><ArticleId IdType="doi">10.1126/sciadv.aax9914</ArticleId><ArticleId IdType="pmc">PMC7030921</ArticleId><ArticleId IdType="pubmed">32128399</ArticleId></ArticleIdList></Reference><Reference><Citation>Hui KK, et al. GABARAPs dysfunction by autophagy deficiency in adolescent brain impairs GABAA receptor trafficking and social behavior. Sci Adv. 2019;5(4):eaau8237. doi: 10.1126/sciadv.aau8237.</Citation><ArticleIdList><ArticleId IdType="doi">10.1126/sciadv.aau8237</ArticleId><ArticleId IdType="pmc">PMC6457945</ArticleId><ArticleId IdType="pubmed">30989111</ArticleId></ArticleIdList></Reference><Reference><Citation>Ozaki I, et al. Regulation of TGF-&#x3b2;1-induced pro-apoptotic signaling by growth factor receptors and extracellular matrix receptor integrins in the liver. Front Physiol. 2011;2:78.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3199809</ArticleId><ArticleId IdType="pubmed">22028694</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">35851754</PMID><DateCompleted><Year>2022</Year><Month>09</Month><Day>08</Day></DateCompleted><DateRevised><Year>2022</Year><Month>10</Month><Day>31</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1755-5949</ISSN><JournalIssue CitedMedium="Internet"><Volume>28</Volume><Issue>10</Issue><PubDate><Year>2022</Year><Month>Oct</Month></PubDate></JournalIssue><Title>CNS neuroscience &amp; therapeutics</Title><ISOAbbreviation>CNS Neurosci Ther</ISOAbbreviation></Journal><ArticleTitle>Telitacicept following plasma exchange in the treatment of subjects with recurrent neuromyelitis optica spectrum disorders: A single-center, single-arm, open-label study.</ArticleTitle><Pagination><StartPage>1613</StartPage><EndPage>1623</EndPage><MedlinePgn>1613-1623</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/cns.13904</ELocationID><Abstract><AbstractText Label="INTRODUCTION">Neuromyelitis optica spectrum disorders (NMOSD), mainly mediated by B cells and AQP4 antibody, has a high rate of recurrence. Telitacicept is a novel drug specifically targeting the upstream signaling for the activation of B cell with its following production of autoimmune antibodies. Thus, it may be a promising approach. Our study preliminarily explored the potential safety and effectiveness of Telitacicept following plasma exchange in the treatment of recurrent NMOSD.</AbstractText><AbstractText Label="METHODS">This was a single-center, single-arm, open-label study enrolling eight patients with recurrent NMOSD in China. All patients received plasma exchange three times, followed by Telitacicept 240&#x2009;mg every week for 46 times. The primary endpoint was the time of first recurrence after enrollment. Secondary end points included: changes in Expanded Disability Status Scale score, Optic Spinal Impairment Scale score, Hauser Ambulation Index, number of lesions on MRI, retinal nerve fiber layer thickness measured by optical coherence tomography, latency and amplitude of visual evoked potential, titer of AQP4 antibody, and immune parameters of blood. Safety was also assessed. The study was registered with Chictr.org.cn (ChiCTR1800019427).</AbstractText><AbstractText Label="RESULTS">Eight eligible patients were enrolled. Relapse occurred in two patients (25%) and five patients (63%) remained relapse free after 48&#x2009;weeks of treatment. The time to first recurrence was prolonged and the number of recurrences was reduced (p&#x2009;&lt;&#x2009;0.001, power of test&#xa0;=&#xa0;1). One patient withdrew from the study due to low neutrophil count. No serious adverse events occurred.</AbstractText><AbstractText Label="CONCLUSIONS">In this small, uncontrolled study, Telitacicept following plasma exchange has the potential to be a safe treatment for patients with recurrent NMOSD. It may prolong the recurrence interval and reduces the annual count of recurrences. A multicenter randomized controlled study with a larger sample is thus feasible and needed to further assess its safety and efficacy.</AbstractText><CopyrightInformation>&#xa9; 2022 The Authors. CNS Neuroscience &amp; Therapeutics published by John Wiley &amp; Sons Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Jie</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-0016-1141</Identifier><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Xianguo</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Yu</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Shuting</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Clinical Research Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deng</LastName><ForeName>Ye</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Meichun</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0002-9921-9760</Identifier><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Ze</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Haojun</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qiu</LastName><ForeName>Huiying</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jin</LastName><ForeName>Yuyan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xue</LastName><ForeName>Jiahui</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guo</LastName><ForeName>Quan</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ni</LastName><ForeName>Liping</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hao</LastName><ForeName>Yong</ForeName><Initials>Y</Initials><Identifier Source="ORCID">0000-0003-3652-0449</Identifier><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guan</LastName><ForeName>Yangtai</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ChiCTR</DataBankName><AccessionNumberList><AccessionNumber>ChiCTR1800019427</AccessionNumber></AccessionNumberList></DataBank></DataBankList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2022</Year><Month>07</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>CNS Neurosci Ther</MedlineTA><NlmUniqueID>101473265</NlmUniqueID><ISSNLinking>1755-5930</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C496030">AQP4 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051401">Aquaporin 4</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001323">Autoantibodies</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007166">Immunosuppressive Agents</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D051401" MajorTopicYN="N">Aquaporin 4</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001323" MajorTopicYN="N">Autoantibodies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005074" MajorTopicYN="N">Evoked Potentials, Visual</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007166" MajorTopicYN="N">Immunosuppressive Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009471" MajorTopicYN="Y">Neuromyelitis Optica</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010951" MajorTopicYN="N">Plasma Exchange</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012008" MajorTopicYN="N">Recurrence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012160" MajorTopicYN="N">Retina</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Telitacicept</Keyword><Keyword MajorTopicYN="N">clinical study</Keyword><Keyword MajorTopicYN="N">effectiveness</Keyword><Keyword MajorTopicYN="N">neuromyelitis optica spectrum disorders</Keyword><Keyword MajorTopicYN="N">plasma exchange</Keyword><Keyword MajorTopicYN="N">safety</Keyword></KeywordList><CoiStatement>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="revised"><Year>2022</Year><Month>3</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>1</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2022</Year><Month>6</Month><Day>19</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2022</Year><Month>7</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>9</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>7</Month><Day>19</Day><Hour>8</Hour><Minute>46</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2022</Year><Month>7</Month><Day>18</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">35851754</ArticleId><ArticleId IdType="pmc">PMC9437241</ArticleId><ArticleId IdType="doi">10.1111/cns.13904</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177&#x2010;189.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4515040</ArticleId><ArticleId IdType="pubmed">26092914</ArticleId></ArticleIdList></Reference><Reference><Citation>Hor JY, Asgari N, Nakashima I, et al. Epidemiology of neuromyelitis Optica Spectrum disorder and its prevalence and incidence worldwide. Front Neurol. 2020;11:501.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC7332882</ArticleId><ArticleId IdType="pubmed">32670177</ArticleId></ArticleIdList></Reference><Reference><Citation>Kitley J, Leite MI, Nakashima I, et al. Prognostic factors and disease course in aquaporin&#x2010;4 antibody&#x2010;positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. 2012;135(Pt 6):1834&#x2010;1849.</Citation><ArticleIdList><ArticleId IdType="pubmed">22577216</ArticleId></ArticleIdList></Reference><Reference><Citation>Palace J, Lin DY, Zeng D, et al. Outcome prediction models in AQP4&#x2010;IgG positive neuromyelitis optica spectrum disorders. Brain. 2019;142(5):1310&#x2010;1323.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6487334</ArticleId><ArticleId IdType="pubmed">30938427</ArticleId></ArticleIdList></Reference><Reference><Citation>Kitley J, Waters P, Woodhall M, et al. Neuromyelitis optica spectrum disorders with aquaporin&#x2010;4 and myelin&#x2010;oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol. 2014;71(3):276&#x2010;283.</Citation><ArticleIdList><ArticleId IdType="pubmed">24425068</ArticleId></ArticleIdList></Reference><Reference><Citation>Sato DK, Callegaro D, Lana&#x2010;Peixoto MA, et al. Distinction between MOG antibody&#x2010;positive and AQP4 antibody&#x2010;positive NMO spectrum disorders. Neurology. 2014;82(6):474&#x2010;481.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3937859</ArticleId><ArticleId IdType="pubmed">24415568</ArticleId></ArticleIdList></Reference><Reference><Citation>Li X, Tian DC, Fan M, et al. Intravenous immunoglobulin for acute attacks in neuromyelitis optica spectrum disorders (NMOSD). Mult Scler Relat Disord. 2020;44:102325.</Citation><ArticleIdList><ArticleId IdType="pubmed">32653803</ArticleId></ArticleIdList></Reference><Reference><Citation>Kleiter I, Gahlen A, Borisow N, et al. Apheresis therapies for NMOSD attacks: a retrospective study of 207 therapeutic interventions. Neurol Neuroimmunol Neuroinflamm. 2018;5(6):e504.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6192689</ArticleId><ArticleId IdType="pubmed">30345331</ArticleId></ArticleIdList></Reference><Reference><Citation>Kleiter I, Gahlen A, Borisow N, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016;79(2):206&#x2010;216.</Citation><ArticleIdList><ArticleId IdType="pubmed">26537743</ArticleId></ArticleIdList></Reference><Reference><Citation>Schwartz J, Padmanabhan A, Aqui N, et al. Guidelines on the use of therapeutic apheresis in clinical practice&#x2010;evidence&#x2010;based approach from the writing Committee of the American Society for apheresis: the seventh special issue. J Clin Apher. 2016;31(3):149&#x2010;162.</Citation><ArticleIdList><ArticleId IdType="pubmed">27322218</ArticleId></ArticleIdList></Reference><Reference><Citation>Bonnan M, Valentino R, Debeugny S, et al. Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurol Neurosurg Psychiatry. 2018;89(4):346&#x2010;351.</Citation><ArticleIdList><ArticleId IdType="pubmed">29030418</ArticleId></ArticleIdList></Reference><Reference><Citation>Yamamura T, Kleiter I, Fujihara K, et al. Trial of Satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114&#x2010;2124.</Citation><ArticleIdList><ArticleId IdType="pubmed">31774956</ArticleId></ArticleIdList></Reference><Reference><Citation>Trebst C, Jarius S, Berthele A, et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the neuromyelitis Optica study group (NEMOS). J Neurol. 2014;261(1):1&#x2010;16.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3895189</ArticleId><ArticleId IdType="pubmed">24272588</ArticleId></ArticleIdList></Reference><Reference><Citation>Espiritu AI, Pasco PMD. Efficacy and tolerability of azathioprine for neuromyelitis optica spectrum disorder: a systematic review and meta&#x2010;analysis. Mult Scler Relat Disord. 2019;33:22&#x2010;32.</Citation><ArticleIdList><ArticleId IdType="pubmed">31136907</ArticleId></ArticleIdList></Reference><Reference><Citation>Duchow A, Chien C, Paul F, Bellmann&#x2010;Strobl J. Emerging drugs for the treatment of neuromyelitis optica. Expert Opin Emerg Drugs. 2020;25(3):285&#x2010;297.</Citation><ArticleIdList><ArticleId IdType="pubmed">32731771</ArticleId></ArticleIdList></Reference><Reference><Citation>La Cava A. Targeting the BLyS&#x2010;APRIL signaling pathway in SLE. Clin Immunol. 2013;148(3):322&#x2010;327.</Citation><ArticleIdList><ArticleId IdType="pubmed">23269199</ArticleId></ArticleIdList></Reference><Reference><Citation>Merrill JT, Wallace DJ, Wax S, et al. Efficacy and safety of atacicept in patients with systemic lupus erythematosus: results of a twenty&#x2010;four&#x2010;week, multicenter, randomized, double&#x2010;blind, placebo&#x2010;controlled, parallel&#x2010;arm, phase IIb study. Arthritis Rheumatol. 2018;70(2):266&#x2010;276.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6099253</ArticleId><ArticleId IdType="pubmed">29073347</ArticleId></ArticleIdList></Reference><Reference><Citation>van Vollenhoven RF, Kinnman N, Vincent E, Wax S, Bathon J. Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase II, randomized, placebo&#x2010;controlled trial. Arthritis Rheum. 2011;63(7):1782&#x2010;1792.</Citation><ArticleIdList><ArticleId IdType="pubmed">21452294</ArticleId></ArticleIdList></Reference><Reference><Citation>Dhillon S. Telitacicept: first Approval. Drugs. 2021;81(14):1671&#x2010;1675.</Citation><ArticleIdList><ArticleId IdType="pubmed">34463932</ArticleId></ArticleIdList></Reference><Reference><Citation>Huntington ND, Tomioka R, Clavarino C, et al. A BAFF antagonist suppresses experimental autoimmune encephalomyelitis by targeting cell&#x2010;mediated and humoral immune responses. Int Immunol. 2006;18(10):1473&#x2010;1485.</Citation><ArticleIdList><ArticleId IdType="pubmed">16914508</ArticleId></ArticleIdList></Reference><Reference><Citation>Moore PA, Belvedere O, Orr A, et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999;285(5425):260&#x2010;263.</Citation><ArticleIdList><ArticleId IdType="pubmed">10398604</ArticleId></ArticleIdList></Reference><Reference><Citation>Okada K, Matsushita T, Kira J, Tsuji S. B&#x2010;cell activating factor of the TNF family is upregulated in neuromyelitis optica. Neurology. 2010;74(2):177&#x2010;178.</Citation><ArticleIdList><ArticleId IdType="pubmed">20065253</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang H, Wang K, Zhong X, et al. Cerebrospinal fluid BAFF and APRIL levels in neuromyelitis optica and multiple sclerosis patients during relapse. J Clin Immunol. 2012;32(5):1007&#x2010;1011.</Citation><ArticleIdList><ArticleId IdType="pubmed">22644841</ArticleId></ArticleIdList></Reference><Reference><Citation>Hegazy M, Darwish H, Darweesh H, El&#x2010;Shehaby A, Emad Y. Raised serum level of APRIL in patients with systemic lupus erythematosus: correlations with disease activity indices. Clin Immunol. 2010;135(1):118&#x2010;124.</Citation><ArticleIdList><ArticleId IdType="pubmed">20116334</ArticleId></ArticleIdList></Reference><Reference><Citation>Shabgah AG, Shariati&#x2010;Sarabi Z, Tavakkol&#x2010;Afshari J, Mohammadi M. The role of BAFF and APRIL in rheumatoid arthritis. J Cell Physiol. 2019;234(10):17050&#x2010;17063.</Citation><ArticleIdList><ArticleId IdType="pubmed">30941763</ArticleId></ArticleIdList></Reference><Reference><Citation>Ding J, Cai Y, Deng Y, et al. Telitacicept following plasma exchange in the treatment of subjects with recurrent NMOSD: study protocol for a single&#x2010;center, single&#x2010;arm, Open&#x2010;Label Study. Front Neurol. 2021;12:596791.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC8044936</ArticleId><ArticleId IdType="pubmed">33868140</ArticleId></ArticleIdList></Reference><Reference><Citation>Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta&#x2010;1a treatment regimens in MS: the EVIDENCE trial. Neurology. 2002;59(10):1496&#x2010;1506.</Citation><ArticleIdList><ArticleId IdType="pubmed">12451188</ArticleId></ArticleIdList></Reference><Reference><Citation>Chen X, Hou Y, Jiang J, et al. Pharmacokinetics, pharmacodynamics, and tolerability of single ascending doses of RCT&#x2010;18 in Chinese patients with rheumatoid arthritis. Clin Pharmacokinet. 2014;53(11):1033&#x2010;1044.</Citation><ArticleIdList><ArticleId IdType="pubmed">25179916</ArticleId></ArticleIdList></Reference><Reference><Citation>Dall'Era M, Chakravarty E, Wallace D, et al. Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results of a multicenter, phase Ib, double&#x2010;blind, placebo&#x2010;controlled, dose&#x2010;escalating trial. Arthritis Rheum. 2007;56(12):4142&#x2010;4150.</Citation><ArticleIdList><ArticleId IdType="pubmed">18050206</ArticleId></ArticleIdList></Reference><Reference><Citation>Tak PP, Thurlings RM, Rossier C, et al. Atacicept in patients with rheumatoid arthritis: results of a multicenter, phase Ib, double&#x2010;blind, placebo&#x2010;controlled, dose&#x2010;escalating, single&#x2010; and repeated&#x2010;dose study. Arthritis Rheum. 2008;58(1):61&#x2010;72.</Citation><ArticleIdList><ArticleId IdType="pubmed">18163485</ArticleId></ArticleIdList></Reference><Reference><Citation>Velo&#x2010;Garcia A, Castro SG, Isenberg DA. The diagnosis and management of the haematologic manifestations of lupus. J Autoimmun. 2016, 2;74:139&#x2010;160.</Citation><ArticleIdList><ArticleId IdType="pubmed">27461045</ArticleId></ArticleIdList></Reference><Reference><Citation>Kessler RA, Mealy MA, Jimenez&#x2010;Arango JA, et al. Anti&#x2010;aquaporin&#x2010;4 titer is not predictive of disease course in neuromyelitis optica spectrum disorder: a multicenter cohort study. Mult Scler Relat Disord. 2017;17:198&#x2010;201.</Citation><ArticleIdList><ArticleId IdType="pubmed">29055457</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">35547390</PMID><DateRevised><Year>2022</Year><Month>05</Month><Day>16</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1664-2295</ISSN><JournalIssue CitedMedium="Print"><Volume>13</Volume><PubDate><Year>2022</Year></PubDate></JournalIssue><Title>Frontiers in neurology</Title><ISOAbbreviation>Front Neurol</ISOAbbreviation></Journal><ArticleTitle>Human Umbilical Cord Mesenchymal Stem Cells to Treat Neuromyelitis Optica Spectrum Disorder (hUC-MSC-NMOSD): A Study Protocol for a Prospective, Multicenter, Randomized, Placebo-Controlled Clinical Trial.</ArticleTitle><Pagination><StartPage>860083</StartPage><MedlinePgn>860083</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">860083</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3389/fneur.2022.860083</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="UNASSIGNED">Neuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating NMOSD.</AbstractText><AbstractText Label="METHODS" NlmCategory="UNASSIGNED">The trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC-MSCs. Patients will be treated with three different doses of hUC-MSCs: 1, 2, or 5 &#xd7; 10<sup>6</sup> MSC/kg&#xb7;weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years.</AbstractText><AbstractText Label="DISCUSSION" NlmCategory="UNASSIGNED">Although hUC-MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC-MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC-MSC in treating NMOSD and might be able to determine the optimal dose of hUC-MSC for NMOSD patients.</AbstractText><AbstractText Label="TRIAL REGISTRATION" NlmCategory="UNASSIGNED">The study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.</AbstractText><CopyrightInformation>Copyright &#xa9; 2022 Yao, Xie, Cai, Zhang, Deng, Gao, Wang, Xu, Ding, Wu, Zhao, Wang, Song, Wang, Xie, Li, Wan, Lin, Jin, Wang, Qiu, Zhuang, Zhou, Jin, Ni, Yan, Guo, Xue, Qian and Guan.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yao</LastName><ForeName>Xiao-Ying</ForeName><Initials>XY</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Clinical Research Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Yu</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deng</LastName><ForeName>Ye</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Mei-Chun</ForeName><Initials>MC</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Yi-Shu</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Hui-Ming</ForeName><Initials>HM</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Jie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Yi-Fan</ForeName><Initials>YF</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Ze</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Ya-Ying</ForeName><Initials>YY</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Li-Ping</ForeName><Initials>LP</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Chong</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ze-Zhi</ForeName><Initials>ZZ</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wan</LastName><ForeName>Wen-Bin</ForeName><Initials>WB</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jin</LastName><ForeName>Hai-Feng</ForeName><Initials>HF</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Kan</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qiu</LastName><ForeName>Hui-Ying</ForeName><Initials>HY</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhuang</LastName><ForeName>Lei</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jin</LastName><ForeName>Yu-Yan</ForeName><Initials>YY</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ni</LastName><ForeName>Li-Ping</ForeName><Initials>LP</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yan</LastName><ForeName>Jia-Li</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guo</LastName><ForeName>Quan</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xue</LastName><ForeName>Jia-Hui</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qian</LastName><ForeName>Bi-Yun</ForeName><Initials>BY</Initials><AffiliationInfo><Affiliation>Clinical Research Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Shanghai Clinical Research Promotion and Development Center, Shanghai Hospital Development Center, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guan</LastName><ForeName>Yang-Tai</ForeName><Initials>YT</Initials><AffiliationInfo><Affiliation>Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2022</Year><Month>04</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Neurol</MedlineTA><NlmUniqueID>101546899</NlmUniqueID><ISSNLinking>1664-2295</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">human umbilical cord mesenchymal stem cell (hUC-MSC)</Keyword><Keyword MajorTopicYN="N">multicenter trial</Keyword><Keyword MajorTopicYN="N">neuromyelitis optica spectrum disorder (NMOSD)</Keyword><Keyword MajorTopicYN="N">randomized controlled trial</Keyword><Keyword MajorTopicYN="N">study protocol</Keyword></KeywordList><CoiStatement>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>1</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2022</Year><Month>3</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>5</Month><Day>13</Day><Hour>11</Hour><Minute>12</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2022</Year><Month>5</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>5</Month><Day>14</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2022</Year><Month>4</Month><Day>25</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">35547390</ArticleId><ArticleId IdType="pmc">PMC9082633</ArticleId><ArticleId IdType="doi">10.3389/fneur.2022.860083</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology. (2006) 66:1485&#x2013;9. 10.1212/01.wnl.0000216139.44259.74</Citation><ArticleIdList><ArticleId IdType="doi">10.1212/01.wnl.0000216139.44259.74</ArticleId><ArticleId IdType="pubmed">16717206</ArticleId></ArticleIdList></Reference><Reference><Citation>Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. . A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. (2004) 364:2106&#x2013;12. 10.1016/S0140-6736(04)17551-X</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0140-6736(04)17551-X</ArticleId><ArticleId IdType="pubmed">15589308</ArticleId></ArticleIdList></Reference><Reference><Citation>Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. (2007) 6:805&#x2013;15. 10.1016/S1474-4422(07)70216-8</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S1474-4422(07)70216-8</ArticleId><ArticleId IdType="pubmed">17706564</ArticleId></ArticleIdList></Reference><Reference><Citation>Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol. (2014) 10:493&#x2013;506. 10.1038/nrneurol.2014.141</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrneurol.2014.141</ArticleId><ArticleId IdType="pmc">PMC4229040</ArticleId><ArticleId IdType="pubmed">25112508</ArticleId></ArticleIdList></Reference><Reference><Citation>Sellner J, Boggild M, Clanet M, Hintzen RQ, Illes Z, Montalban X, et al. . EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol. (2010) 17:1019&#x2013;32. 10.1111/j.1468-1331.2010.03066.x</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1468-1331.2010.03066.x</ArticleId><ArticleId IdType="pubmed">20528913</ArticleId></ArticleIdList></Reference><Reference><Citation>Mealy MA, Wingerchuk DM, Palace J, Greenberg BM, Levy M. Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy. JAMA Neurol. (2014) 71:324&#x2013;30. 10.1001/jamaneurol.2013.5699</Citation><ArticleIdList><ArticleId IdType="doi">10.1001/jamaneurol.2013.5699</ArticleId><ArticleId IdType="pubmed">24445513</ArticleId></ArticleIdList></Reference><Reference><Citation>Tahara M, Oeda T, Okada K, Kiriyama T, Ochi K, Maruyama H, et al. . Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. (2020) 19:298&#x2013;306. 10.1016/S1474-4422(20)30066-1</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S1474-4422(20)30066-1</ArticleId><ArticleId IdType="pubmed">32199095</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang C, Zhang M, Qiu W, Ma H, Zhang X, Zhu Z, et al. . TANGO study investigators. Safety and efficacy of tocilizumab vs. azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. (2020) 19:391&#x2013;401. 10.1016/S1474-4422(20)30070-3</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S1474-4422(20)30070-3</ArticleId><ArticleId IdType="pmc">PMC7935423</ArticleId><ArticleId IdType="pubmed">32333897</ArticleId></ArticleIdList></Reference><Reference><Citation>Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, et al. . Eculizumab in Aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. (2019) 381:614&#x2013;25. 10.1056/NEJMoa1900866</Citation><ArticleIdList><ArticleId IdType="doi">10.1056/NEJMoa1900866</ArticleId><ArticleId IdType="pubmed">31050279</ArticleId></ArticleIdList></Reference><Reference><Citation>Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, et al. . N-MOmentum study investigators. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. (2019) 394:1352&#x2013;63. 10.1016/S0140-6736(19)31817-3</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0140-6736(19)31817-3</ArticleId><ArticleId IdType="pubmed">31495497</ArticleId></ArticleIdList></Reference><Reference><Citation>Traboulsee A, Greenberg BM, Bennett JL, Szczechowski L, Fox E, Shkrobot S, et al. . Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. (2020) 19:402&#x2013;12. 10.1016/S1474-4422(20)30078-8</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S1474-4422(20)30078-8</ArticleId><ArticleId IdType="pmc">PMC7935419</ArticleId><ArticleId IdType="pubmed">32333898</ArticleId></ArticleIdList></Reference><Reference><Citation>Burt RK, Balabanov R, Han X, Burns C, Gastala J, Jovanovic B, et al. . Autologous non-myeloablative hematopoietic stem cell transplantation for neuromyelitis optica. Neurology. (2019) 93:e1732&#x2013;41. 10.1212/WNL.0000000000008394</Citation><ArticleIdList><ArticleId IdType="doi">10.1212/WNL.0000000000008394</ArticleId><ArticleId IdType="pmc">PMC6946475</ArticleId><ArticleId IdType="pubmed">31578302</ArticleId></ArticleIdList></Reference><Reference><Citation>Greco R, Bondanza A, Oliveira MC, Badoglio M, Burman J, Piehl F, et al. . Autologous hematopoietic stem cell transplantation in neuromyelitis optica: a registry study of the EBMT autoimmune diseases working party. Mult Scler. (2015) 21:189&#x2013;97. 10.1177/1352458514541978</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/1352458514541978</ArticleId><ArticleId IdType="pubmed">25078274</ArticleId></ArticleIdList></Reference><Reference><Citation>Hoay KY, Ratnagopal P. Autologous hematopoietic stem cell transplantation for the treatment of neuromyelitis optica in Singapore. Acta Neurol Taiwan. (2018) 27:26&#x2013;32.</Citation><ArticleIdList><ArticleId IdType="pubmed">30315559</ArticleId></ArticleIdList></Reference><Reference><Citation>Zannettino AC, Paton S, Arthur A, Khor F, Itescu S, Gimble JM, et al. . Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. J Cell Physiol. (2008) 214:413&#x2013;21. 10.1002/jcp.21210</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/jcp.21210</ArticleId><ArticleId IdType="pubmed">17654479</ArticleId></ArticleIdList></Reference><Reference><Citation>Hoogduijn MJ, Crop MJ, Peeters AM, Van Osch GJ, Balk AH, Ijzermans JN, et al. . Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev. (2007) 16:597&#x2013;604. 10.1089/scd.2006.0110</Citation><ArticleIdList><ArticleId IdType="doi">10.1089/scd.2006.0110</ArticleId><ArticleId IdType="pubmed">17784833</ArticleId></ArticleIdList></Reference><Reference><Citation>He Q, Wan C, Li G. Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells. (2007) 25:69&#x2013;77. 10.1634/stemcells.2006-0335</Citation><ArticleIdList><ArticleId IdType="doi">10.1634/stemcells.2006-0335</ArticleId><ArticleId IdType="pubmed">16973831</ArticleId></ArticleIdList></Reference><Reference><Citation>Carrion FA, Figueroa FE. Mesenchymal stem cells for the treatment of systemic lupus erythematosus: is the cure for connective tissue diseases within connective tissue? Stem Cell Res Ther. (2011) 2:23. 10.1186/scrt64</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/scrt64</ArticleId><ArticleId IdType="pmc">PMC3152993</ArticleId><ArticleId IdType="pubmed">21586107</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang LT, Ting CH, Yen ML, Liu KJ, Sytwu HK, Wu KK, et al. . Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials. J Biomed Sci. (2016) 23:76. 10.1186/s12929-016-0289-5</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/s12929-016-0289-5</ArticleId><ArticleId IdType="pmc">PMC5095977</ArticleId><ArticleId IdType="pubmed">27809910</ArticleId></ArticleIdList></Reference><Reference><Citation>Li JF, Yin HL, Shuboy A, Duan HF, Lou JY Li J, et al. . Differentiation of hUC-MSC into dopaminergic-like cells after transduction with hepatocyte growth factor. Mol Cell Biochem. (2013) 381:183&#x2013;90. 10.1007/s11010-013-1701-z</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s11010-013-1701-z</ArticleId><ArticleId IdType="pubmed">23737134</ArticleId></ArticleIdList></Reference><Reference><Citation>Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, et al. . Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. (2005) 106:1755&#x2013;61. 10.1182/blood-2005-04-1496</Citation><ArticleIdList><ArticleId IdType="doi">10.1182/blood-2005-04-1496</ArticleId><ArticleId IdType="pubmed">15905186</ArticleId></ArticleIdList></Reference><Reference><Citation>Gerdoni E, Gallo B, Casazza S, Musio S, Bonanni I, Pedemonte E, et al. . Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann Neurol. (2007) 61:219&#x2013;27. 10.1002/ana.21076</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/ana.21076</ArticleId><ArticleId IdType="pubmed">17387730</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu R, Zhang Z, Lu Z, Borlongan C, Pan J, Chen J, et al. . Human umbilical cord stem cells ameliorate experimental autoimmune encephalomyelitis by regulating immunoinflammation and remyelination. Stem Cells Dev. (2013) 22:1053&#x2013;62. 10.1089/scd.2012.0463</Citation><ArticleIdList><ArticleId IdType="doi">10.1089/scd.2012.0463</ArticleId><ArticleId IdType="pubmed">23140594</ArticleId></ArticleIdList></Reference><Reference><Citation>Fu Y, Yan Y, Qi Y, Yang L, Li T, Zhang N, et al. . Impact of autologous mesenchymal stem cell infusion on neuromyelitis optica spectrum disorder: a pilot, 2-year observational study. CNS Neurosci Ther. (2016) 22:677&#x2013;85. 10.1111/cns.12559</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/cns.12559</ArticleId><ArticleId IdType="pmc">PMC6492909</ArticleId><ArticleId IdType="pubmed">27219819</ArticleId></ArticleIdList></Reference><Reference><Citation>Abbaspanah B, Reyhani S, Mousavi SH. Applications of umbilical cord derived mesenchymal stem cells in autoimmune and immunological disorders: from literature to clinical practice. Curr Stem Cell Res Ther. (2021) 16:454&#x2013;64. 10.2174/1574888X16999201124153000</Citation><ArticleIdList><ArticleId IdType="doi">10.2174/1574888X16999201124153000</ArticleId><ArticleId IdType="pubmed">33238859</ArticleId></ArticleIdList></Reference><Reference><Citation>Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. . International panel for NMO diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. (2015) 85:177&#x2013;89. 10.1212/WNL.0000000000001729</Citation><ArticleIdList><ArticleId IdType="doi">10.1212/WNL.0000000000001729</ArticleId><ArticleId IdType="pmc">PMC4515040</ArticleId><ArticleId IdType="pubmed">26092914</ArticleId></ArticleIdList></Reference><Reference><Citation>Kitley J, Leite MI, Nakashima I, Waters P, McNeillis B, Brown R, et al. . Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. (2012) 135:1834&#x2013;49. 10.1093/brain/aws109</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/brain/aws109</ArticleId><ArticleId IdType="pubmed">22577216</ArticleId></ArticleIdList></Reference><Reference><Citation>Lam CL, Tse EY, Gandek B, Fong DY. The SF-36 summary scales were valid, reliable, and equivalent in a Chinese population. J Clin Epidemiol. (2005) 58:815&#x2013;22. 10.1016/j.jclinepi.2004.12.008</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jclinepi.2004.12.008</ArticleId><ArticleId IdType="pubmed">16018917</ArticleId></ArticleIdList></Reference><Reference><Citation>Koda M, Hanaoka H, Sato T, Fujii Y, Hanawa M, Takahashi S, et al. . Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury. BMJ Open. (2018) 8:e019083. 10.1136/bmjopen-2017-019083</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/bmjopen-2017-019083</ArticleId><ArticleId IdType="pmc">PMC5942478</ArticleId><ArticleId IdType="pubmed">29730616</ArticleId></ArticleIdList></Reference><Reference><Citation>Chen L, Xi H, Huang H, Zhang F, Liu Y, Chen D, et al. . Multiple cell transplantation based on an intraparenchymal approach for patients with chronic phase stroke. Cell Transplant. (2013) 22(Suppl 1):S83&#x2013;91. 10.3727/096368913X672154</Citation><ArticleIdList><ArticleId IdType="doi">10.3727/096368913X672154</ArticleId><ArticleId IdType="pubmed">23992950</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu J, Han D, Wang Z, Xue M, Zhu L, Yan H, et al. . Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells. Cytotherapy. (2013) 15:185&#x2013;91. 10.1016/j.jcyt.2012.09.005</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jcyt.2012.09.005</ArticleId><ArticleId IdType="pubmed">23321330</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhao Y, Tang F, Xiao Z, Han G, Wang N, Yin N, et al. . Clinical study of neuroregen scaffold combined with human mesenchymal stem cells for the repair of chronic complete spinal cord injury. Cell Transplant. (2017) 26:891&#x2013;900. 10.3727/096368917X695038</Citation><ArticleIdList><ArticleId IdType="doi">10.3727/096368917X695038</ArticleId><ArticleId IdType="pmc">PMC5657723</ArticleId><ArticleId IdType="pubmed">28185615</ArticleId></ArticleIdList></Reference><Reference><Citation>Jin JL, Liu Z, Lu ZJ, Guan DN, Wang C, Chen ZB, et al. . Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia. Curr Neurovasc Res. (2013) 10:11&#x2013;20. 10.2174/156720213804805936</Citation><ArticleIdList><ArticleId IdType="doi">10.2174/156720213804805936</ArticleId><ArticleId IdType="pubmed">23151076</ArticleId></ArticleIdList></Reference><Reference><Citation>Dongmei H, Jing L, Mei X, Ling Z, Hongmin Y, Zhidong W, et al. . Clinical analysis of the treatment of spinocerebellar ataxia and multiple system atrophy-cerebellar type with umbilical cord mesenchymal stromal cells. Cytotherapy. (2011) 13:913&#x2013;7. 10.3109/14653249.2011.579958</Citation><ArticleIdList><ArticleId IdType="doi">10.3109/14653249.2011.579958</ArticleId><ArticleId IdType="pubmed">21545234</ArticleId></ArticleIdList></Reference><Reference><Citation>Li JF, Zhang DJ, Geng T, Chen L, Huang H, Yin HL, et al. . The potential of human umbilical cord-derived mesenchymal stem cells as a novel cellular therapy for multiple sclerosis. Cell Transplant. (2014) 23(Suppl 1):S113&#x2013;22. 10.3727/096368914X685005</Citation><ArticleIdList><ArticleId IdType="doi">10.3727/096368914X685005</ArticleId><ArticleId IdType="pubmed">25385295</ArticleId></ArticleIdList></Reference><Reference><Citation>Can A, Celikkan FT, Cinar O. Umbilical cord mesenchymal stromal cell transplantations: a systemic analysis of clinical trials. Cytotherapy. (2017) 19:1351&#x2013;82. 10.1016/j.jcyt.2017.08.004</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jcyt.2017.08.004</ArticleId><ArticleId IdType="pubmed">28964742</ArticleId></ArticleIdList></Reference><Reference><Citation>Lu Z, Ye D, Qian L, Zhu L, Wang C, Guan D, et al. . Human umbilical cord mesenchymal stem cell therapy on neuromyelitis optica. Curr Neurovasc Res. (2012) 9:250&#x2013;5. 10.2174/156720212803530708</Citation><ArticleIdList><ArticleId IdType="doi">10.2174/156720212803530708</ArticleId><ArticleId IdType="pubmed">22873728</ArticleId></ArticleIdList></Reference><Reference><Citation>Mohyeddin Bonab M, Mohajeri M, Sahraian MA, Yazdanifar M, Aghsaie A, Farazmand A, et al. . Evaluation of cytokines in multiple sclerosis patients treated with mesenchymal stem cells. Arch Med Res. (2013) 44:266&#x2013;72. 10.1016/j.arcmed.2013.03.007</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.arcmed.2013.03.007</ArticleId><ArticleId IdType="pubmed">23684533</ArticleId></ArticleIdList></Reference><Reference><Citation>Meamar R, Nematollahi S, Dehghani L, Mirmosayyeb O, Shayegannejad V, Basiri K, et al. . The role of stem cell therapy in multiple sclerosis: an overview of the current status of the clinical studies. Adv Biomed Res. (2016) 5:46. 10.4103/2277-9175.178791</Citation><ArticleIdList><ArticleId IdType="doi">10.4103/2277-9175.178791</ArticleId><ArticleId IdType="pmc">PMC4817403</ArticleId><ArticleId IdType="pubmed">27110543</ArticleId></ArticleIdList></Reference><Reference><Citation>Barati S, Tahmasebi F, Faghihi F. Effects of mesenchymal stem cells transplantation on multiple sclerosis patients. Neuropeptides. (2020) 84:102095. 10.1016/j.npep.2020.102095</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.npep.2020.102095</ArticleId><ArticleId IdType="pubmed">33059244</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">35460276</PMID><DateCompleted><Year>2023</Year><Month>01</Month><Day>12</Day></DateCompleted><DateRevised><Year>2024</Year><Month>01</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1527-3350</ISSN><JournalIssue CitedMedium="Internet"><Volume>77</Volume><Issue>1</Issue><PubDate><Year>2023</Year><Month>Jan</Month><Day>01</Day></PubDate></JournalIssue><Title>Hepatology (Baltimore, Md.)</Title><ISOAbbreviation>Hepatology</ISOAbbreviation></Journal><ArticleTitle>Intestinal peroxisome proliferator-activated receptor &#x3b1;-fatty acid-binding protein 1 axis modulates nonalcoholic steatohepatitis.</ArticleTitle><Pagination><StartPage>239</StartPage><EndPage>255</EndPage><MedlinePgn>239-255</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/hep.32538</ELocationID><Abstract><AbstractText Label="BACKGROUND AND AIMS">Peroxisome proliferator-activated receptor &#x3b1; (PPAR&#x3b1;) regulates fatty acid transport and catabolism in liver. However, the role of intestinal PPAR&#x3b1; in lipid homeostasis is largely unknown. Here, intestinal PPAR&#x3b1; was examined for its modulation of obesity and NASH.</AbstractText><AbstractText Label="APPROACH AND RESULTS">Intestinal PPAR&#x3b1; was activated and fatty acid-binding protein 1 (FABP1) up-regulated in humans with obesity and high-fat diet (HFD)-fed mice as revealed by using human intestine specimens or HFD/high-fat, high-cholesterol, and high-fructose diet (HFCFD)-fed C57BL/6N mice and PPARA -humanized, peroxisome proliferator response element-luciferase mice. Intestine-specific Ppara or Fabp1 disruption in mice fed a HFD or HFCFD decreased obesity-associated metabolic disorders and NASH. Molecular analyses by luciferase reporter assays and chromatin immunoprecipitation assays in combination with fatty acid uptake assays in primary intestinal organoids revealed that intestinal PPAR&#x3b1; induced the expression of FABP1 that in turn mediated the effects of intestinal PPAR&#x3b1; in modulating fatty acid uptake. The PPAR&#x3b1; antagonist GW6471 improved obesity and NASH, dependent on intestinal PPAR&#x3b1; or FABP1. Double-knockout ( Ppara/Fabp1&#x394;IE ) mice demonstrated that intestinal Ppara disruption failed to further decrease obesity and NASH in the absence of intestinal FABP1. Translationally, GW6471 reduced human PPARA-driven intestinal fatty acid uptake and improved obesity-related metabolic dysfunctions in PPARA -humanized, but not Ppara -null, mice.</AbstractText><AbstractText Label="CONCLUSIONS">Intestinal PPAR&#x3b1; signaling promotes NASH progression through regulating dietary fatty acid uptake through modulation of FABP1, which provides a compelling therapeutic target for NASH treatment.</AbstractText><CopyrightInformation>Copyright &#xa9; 2022 The Author(s). Published by Wolters Kluwer Health, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yan</LastName><ForeName>Tingting</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>Yuhong</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yan</LastName><ForeName>Nana</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>State Key Laboratory of Natural Medicines , Key Laboratory of Drug Metabolism and Pharmacokinetics , China Pharmaceutical University , Nanjing , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hamada</LastName><ForeName>Keisuke</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Physiology and Pathophysiology , School of Basic Medical Sciences , Capital Medical University , Beijing , P.R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Remodeling-Related Cardiovascular Diseases , Ministry of Education , Beijing , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xia</LastName><ForeName>Yangliu</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Ping</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Changdong</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology , Second People's Hospital of Lianyungang City , Lianyungang , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qi</LastName><ForeName>Dan</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Pathology , National Cancer Center , Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Shoumei</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Lulu</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Jie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Qiong</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Changtao</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Physiology and Pathophysiology , School of Basic Medical Sciences , Peking University , Beijing , P.R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Molecular Cardiovascular Science , Ministry of Education , Beijing , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gavrilova</LastName><ForeName>Oksana</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Mouse Metabolism Core Laboratory , National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Krausz</LastName><ForeName>Kristopher W</ForeName><Initials>KW</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Patel</LastName><ForeName>Daxesh P</ForeName><Initials>DP</Initials><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Xiaoting</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Physiology and Pathophysiology , School of Basic Medical Sciences , Capital Medical University , Beijing , P.R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Remodeling-Related Cardiovascular Diseases , Ministry of Education , Beijing , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Xuan</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>12476Central Laboratory and Department of Laboratory Medicine , Shanghai Tenth People's Hospital , Tongji University , Shanghai , P.R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Laboratory Medicine , Shanghai Skin Disease Hospital , Tongji University , Shanghai , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hao</LastName><ForeName>Haiping</ForeName><Initials>H</Initials><Identifier Source="ORCID">0000-0003-2522-7546</Identifier><AffiliationInfo><Affiliation>State Key Laboratory of Natural Medicines , Key Laboratory of Drug Metabolism and Pharmacokinetics , China Pharmaceutical University , Nanjing , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Weiwei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>12476Central Laboratory and Department of Laboratory Medicine , Shanghai Tenth People's Hospital , Tongji University , Shanghai , P.R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Laboratory Medicine , Shanghai Skin Disease Hospital , Tongji University , Shanghai , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qu</LastName><ForeName>Aijuan</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Physiology and Pathophysiology , School of Basic Medical Sciences , Capital Medical University , Beijing , P.R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Remodeling-Related Cardiovascular Diseases , Ministry of Education , Beijing , P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gonzalez</LastName><ForeName>Frank J</ForeName><Initials>FJ</Initials><Identifier Source="ORCID">0000-0002-7990-2140</Identifier><AffiliationInfo><Affiliation>Laboratory of Metabolism , Center for Cancer Research , National Cancer Institute , National Institutes of Health , Bethesda , Maryland , USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2022</Year><Month>05</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Hepatology</MedlineTA><NlmUniqueID>8302946</NlmUniqueID><ISSNLinking>0270-9139</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D047493">PPAR alpha</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050556">Fatty Acid-Binding Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005227">Fatty Acids</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Hepatology. 2023 Jan 1;77(1):15-17. doi: 10.1002/hep.32592</RefSource><PMID Version="1">35633082</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065626" MajorTopicYN="Y">Non-alcoholic Fatty Liver Disease</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D047493" MajorTopicYN="N">PPAR alpha</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008099" MajorTopicYN="N">Liver</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059305" MajorTopicYN="N">Diet, High-Fat</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009765" MajorTopicYN="N">Obesity</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007422" MajorTopicYN="N">Intestines</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D050556" MajorTopicYN="N">Fatty Acid-Binding Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005227" MajorTopicYN="N">Fatty Acids</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><CoiStatement>Nothing to report.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>2</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2022</Year><Month>4</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2022</Year><Month>4</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>1</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>4</Month><Day>23</Day><Hour>8</Hour><Minute>34</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2023</Year><Month>2</Month><Day>27</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">35460276</ArticleId><ArticleId IdType="pmc">PMC9970020</ArticleId><ArticleId IdType="doi">10.1002/hep.32538</ArticleId><ArticleId IdType="pii">01515467-202301010-00023</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Younossi ZM. Non&#x2010;alcoholic fatty liver disease &#x2212; a global public health perspective. J Hepatol. 2019;70(3):531&#x2013;44.</Citation><ArticleIdList><ArticleId IdType="pubmed">30414863</ArticleId></ArticleIdList></Reference><Reference><Citation>Huang DQ, El&#x2010;Serag HB, Loomba R. Global epidemiology of NAFLD&#x2010;related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18(4):223&#x2013;38.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC8016738</ArticleId><ArticleId IdType="pubmed">33349658</ArticleId></ArticleIdList></Reference><Reference><Citation>Rotman Y, Sanyal AJ. Current and upcoming pharmacotherapy for non&#x2010;alcoholic fatty liver disease. Gut. 2017;66(1):180&#x2013;90.</Citation><ArticleIdList><ArticleId IdType="pubmed">27646933</ArticleId></ArticleIdList></Reference><Reference><Citation>Lassailly G, Caiazzo R, Ntandja&#x2010;Wandji LC, Gnemmi V, Baud G, Verkindt H, et al. . Bariatric surgery provides long&#x2010;term resolution of nonalcoholic steatohepatitis and regression of fibrosis. Gastroenterology. 2020;159(4):1290&#x2013;301.e5.</Citation><ArticleIdList><ArticleId IdType="pubmed">32553765</ArticleId></ArticleIdList></Reference><Reference><Citation>Arterburn DE, Telem DA, Kushner RF, Courcoulas AP. Benefits and risks of bariatric surgery in adults: a review. JAMA. 2020;324(9):879&#x2013;887.</Citation><ArticleIdList><ArticleId IdType="pubmed">32870301</ArticleId></ArticleIdList></Reference><Reference><Citation>Gross B, Pawlak M, Lefebvre P, Staels B. PPARs in obesity&#x2010;induced T2DM, dyslipidaemia and NAFLD. Nat Rev Endocrinol. 2017;13(1):36&#x2013;49.</Citation><ArticleIdList><ArticleId IdType="pubmed">27636730</ArticleId></ArticleIdList></Reference><Reference><Citation>Goldfine AB, Kaul S, Hiatt WR. Fibrates in the treatment of dyslipidemias &#x2010; time for a reassessment. N Engl J Med. 2011;365(6):481&#x2013;44.</Citation><ArticleIdList><ArticleId IdType="pubmed">21830963</ArticleId></ArticleIdList></Reference><Reference><Citation>Ip E, Farrell GC, Robertson G, Hall P, Kirsch R, Leclercq I. Central role of PPAR&#x3b1;&#x2010;dependent hepatic lipid turnover in dietary steatohepatitis in mice. Hepatology. 2003;38(1):123&#x2013;32.</Citation><ArticleIdList><ArticleId IdType="pubmed">12829994</ArticleId></ArticleIdList></Reference><Reference><Citation>Guerre&#x2010;Millo M, Rouault C, Poulain P, Andr&#xe9; J, Poitout V, Peters JM, et al. . PPAR&#x2010;alpha&#x2010;null mice are protected from high&#x2010;fat diet&#x2010;induced insulin resistance. Diabetes. 2001;50(12):2809&#x2013;14.</Citation><ArticleIdList><ArticleId IdType="pubmed">11723064</ArticleId></ArticleIdList></Reference><Reference><Citation>Montagner A, Polizzi A, Fouch&#xe9; E, Ducheix S, Lippi Y, Lasserre F, et al. . Liver PPAR&#x3b1; is crucial for whole&#x2010;body fatty acid homeostasis and is protective against NAFLD. Gut. 2016;65(7):1202&#x2013;14.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4941147</ArticleId><ArticleId IdType="pubmed">26838599</ArticleId></ArticleIdList></Reference><Reference><Citation>Brocker CN, Patel DP, Velenosi TJ, Kim D, Yan T, Yue J, et al. . Extrahepatic PPAR&#x3b1; modulates fatty acid oxidation and attenuates fasting&#x2010;induced hepatosteatosis in mice. J Lipid Res. 2018;59(11):2140&#x2013;52.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6210912</ArticleId><ArticleId IdType="pubmed">30158201</ArticleId></ArticleIdList></Reference><Reference><Citation>Ko CW, Qu J, Black DD, Tso P. Regulation of intestinal lipid metabolism: current concepts and relevance to disease. Nat Rev Gastroenterol Hepatol. 2020;17(3):169&#x2013;83.</Citation><ArticleIdList><ArticleId IdType="pubmed">32015520</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang GQ, Bonkovsky HL, de Lemos A, Burczynski FJ. Recent insights into the biological functions of liver fatty acid binding protein 1. J Lipid Res. 2015;56(12):2238&#x2013;47.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4655993</ArticleId><ArticleId IdType="pubmed">26443794</ArticleId></ArticleIdList></Reference><Reference><Citation>Madison BB, Dunbar L, Qiao XT, Braunstein K, Braunstein E, Gumucio DL. Cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine. J Biol Chem. 2002;277(36):33275&#x2013;83.</Citation><ArticleIdList><ArticleId IdType="pubmed">12065599</ArticleId></ArticleIdList></Reference><Reference><Citation>El Marjou F, Janssen KP, Hung&#x2010;Junn Chang B, Li M, Hindie V, Chan L, et al. . Tissue&#x2010;specific and inducible Cre&#x2010;mediated recombination in the gut epithelium. Genesis. 2004;39(3):186&#x2013;93.</Citation><ArticleIdList><ArticleId IdType="pubmed">15282745</ArticleId></ArticleIdList></Reference><Reference><Citation>Luo Y, Xie C, Brocker CN, Fan J, Wu X, Feng L, et al. . Intestinal PPAR&#x3b1; protects against colon carcinogenesis via regulation of methyltransferases DNMT1 and PRMT6. Gastroenterology. 2019;157(3):744&#x2013;59.e4.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC7388731</ArticleId><ArticleId IdType="pubmed">31154022</ArticleId></ArticleIdList></Reference><Reference><Citation>Brocker CN, Yue J, Kim D, Qu A, Bonzo JA, Gonzalez FJ. Hepatocyte&#x2010;specific PPARA expression exclusively promotes agonist&#x2010;induced cell proliferation without influence from nonparenchymal cells. Am J Physiol Gastrointest Liver Physiol. 2017;312(3):G283&#x2013;G299.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5401987</ArticleId><ArticleId IdType="pubmed">28082284</ArticleId></ArticleIdList></Reference><Reference><Citation>Newberry EP, Xie Y, Lodeiro C, Solis R, Moritz W, Kennedy S, et al. . Hepatocyte and stellate cell deletion of liver fatty acid binding protein reveals distinct roles in fibrogenic injury. FASEB J. 2019;33(3):4610&#x2013;25.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6404585</ArticleId><ArticleId IdType="pubmed">30576225</ArticleId></ArticleIdList></Reference><Reference><Citation>El&#x2010;Jamal N, Dubuquoy L, Auwerx J, Bertin B, Desreumaux P. In vivo imaging reveals selective PPAR activity in the skin of peroxisome proliferator&#x2010;activated receptor responsive element&#x2010;luciferase reporter mice. Exp Dermatol. 2013;22(2):137&#x2013;40.</Citation><ArticleIdList><ArticleId IdType="pubmed">23362873</ArticleId></ArticleIdList></Reference><Reference><Citation>Xie G, Yin S, Zhang Z, Qi D, Wang X, Kim D, et al. . Hepatocyte peroxisome proliferator&#x2010;activated receptor &#x3b1; enhances liver regeneration after partial hepatectomy in mice. Am J Pathol. 2019;189(2):272&#x2013;82.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6593252</ArticleId><ArticleId IdType="pubmed">30448405</ArticleId></ArticleIdList></Reference><Reference><Citation>Yang Q, Nagano T, Shah Y, Cheung C, Ito S, Gonzalez FJ. The PPAR&#x3b1;&#x2010;humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR&#x3b1;. Toxicol Sci. 2008;101(1):132&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2197159</ArticleId><ArticleId IdType="pubmed">17690133</ArticleId></ArticleIdList></Reference><Reference><Citation>Roberts RA. Peroxisome proliferators: mechanisms of adverse effects in rodents and molecular basis for species differences. Arch Toxicol. 1999;73(8&#x2013;9):413&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">10650911</ArticleId></ArticleIdList></Reference><Reference><Citation>Forman BM, Chen J, Evans RM. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator&#x2010;activated receptors &#x3b1; and &#x3b4;. Proc Natl Acad Sci U S A. 1997;94(9):4312&#x2013;17.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC20719</ArticleId><ArticleId IdType="pubmed">9113986</ArticleId></ArticleIdList></Reference><Reference><Citation>Kim JB, Wright HM, Wright M, Spiegelman BM. ADD1/SREBP1 activates PPAR&#x3b3; through the production of endogenous ligand. Proc Natl Acad Sci USA. 1998;95(8):4333&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC22489</ArticleId><ArticleId IdType="pubmed">9539737</ArticleId></ArticleIdList></Reference><Reference><Citation>Costet P, Legendre C, More J, Edgar A, Galtier P, Pineau T. Peroxisome proliferator&#x2010;activated receptor &#x3b1;&#x2010;isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis. J Biol Chem. 1998;273(45):29577&#x2013;85.</Citation><ArticleIdList><ArticleId IdType="pubmed">9792666</ArticleId></ArticleIdList></Reference><Reference><Citation>Hashimoto T, Cook WS, Qi C, Yeldandi AV, Reddy JK, Rao MS. Defect in peroxisome proliferator&#x2010;activated receptor &#x3b1;&#x2010;inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. J Biol Chem. 2000;275(37):28918&#x2013;228.</Citation><ArticleIdList><ArticleId IdType="pubmed">10844002</ArticleId></ArticleIdList></Reference><Reference><Citation>Ferri N, Corsini A, Sirtori C, Ruscica M. PPAR&#x3b1; agonists are still on the rise: an update on clinical and experimental findings. Expert Opin Investig Drugs. 2017;26(5):593&#x2013;602.</Citation><ArticleIdList><ArticleId IdType="pubmed">28343425</ArticleId></ArticleIdList></Reference><Reference><Citation>Pawlak M, Lefebvre P, Staels B. Molecular mechanism of PPAR&#x3b1; action and its impact on lipid metabolism, inflammation and fibrosis in non&#x2010;alcoholic fatty liver disease. J Hepatol. 2015;62(3):720&#x2013;33.</Citation><ArticleIdList><ArticleId IdType="pubmed">25450203</ArticleId></ArticleIdList></Reference><Reference><Citation>Newberry EP, Xie Y, Kennedy S, Han X, Buhman KK, Luo J, et al. . Decreased hepatic triglyceride accumulation and altered fatty acid uptake in mice with deletion of the liver fatty acid&#x2010;binding protein gene. J Biol Chem. 2003;278(51):51664&#x2013;72.</Citation><ArticleIdList><ArticleId IdType="pubmed">14534295</ArticleId></ArticleIdList></Reference><Reference><Citation>Newberry EP, Kennedy SM, Xie Y, Luo J, Crooke RM, Graham MJ, et al. . Decreased body weight and hepatic steatosis with altered fatty acid ethanolamide metabolism in aged L&#x2010;Fabp&#x2212;/&#x2212; mice. J Lipid Res. 2012;53(4):744&#x2013;54.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3307651</ArticleId><ArticleId IdType="pubmed">22327204</ArticleId></ArticleIdList></Reference><Reference><Citation>Newberry EP, Kennedy SM, Xie Y, Sternard BT, Luo J, Davidson NO. Diet&#x2010;induced obesity and hepatic steatosis in L&#x2010;Fabp&#x2212;/&#x2212; mice is abrogated with SF, but not PUFA, feeding and attenuated after cholesterol supplementation. Am J Physiol Gastrointest Liver Physiol. 2008;294(1):G307&#x2013;G314.</Citation><ArticleIdList><ArticleId IdType="pubmed">18032478</ArticleId></ArticleIdList></Reference><Reference><Citation>Newberry EP, Xie Y, Kennedy SM, Luo J, Davidson NO. Protection against Western diet&#x2010;induced obesity and hepatic steatosis in liver fatty acid&#x2010;binding protein knockout mice. Hepatology. 2006;44(5):1191&#x2013;205.</Citation><ArticleIdList><ArticleId IdType="pubmed">17058218</ArticleId></ArticleIdList></Reference><Reference><Citation>Chen A, Tang Y, Davis V, Hsu FF, Kennedy SM, Song H, et al. . Liver fatty acid binding protein (L&#x2010;Fabp) modulates murine stellate cell activation and diet&#x2010;induced nonalcoholic fatty liver disease. Hepatology. 2013;57(6):2202&#x2013;12.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3665693</ArticleId><ArticleId IdType="pubmed">23401290</ArticleId></ArticleIdList></Reference><Reference><Citation>Gajda AM, Zhou YX, Agellon LB, Fried SK, Kodukula S, Fortson W, et al. . Direct comparison of mice null for liver or intestinal fatty acid&#x2010;binding proteins reveals highly divergent phenotypic responses to high fat feeding. J Biol Chem. 2013;288(42):30330&#x2013;44.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3798498</ArticleId><ArticleId IdType="pubmed">23990461</ArticleId></ArticleIdList></Reference><Reference><Citation>Rodriguez Sawicki L, Bottasso Arias NM, Scaglia N, Falomir Lockhart LJ, Franchini GR, Storch J, et al. . FABP1 knockdown in human enterocytes impairs proliferation and alters lipid metabolism. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862(12):1587&#x2013;94.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5663247</ArticleId><ArticleId IdType="pubmed">28919479</ArticleId></ArticleIdList></Reference><Reference><Citation>Stojanovi&#x107; O, Altirriba J, Rigo D, Spiljar M, Evrard E, Roska B, et al. . Dietary excess regulates absorption and surface of gut epithelium through intestinal PPAR&#x3b1;. Nat Commun. 2021;12(1):7031.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC8639731</ArticleId><ArticleId IdType="pubmed">34857752</ArticleId></ArticleIdList></Reference><Reference><Citation>Hsu KT, Storch J. Fatty acid transfer from liver and intestinal fatty acid&#x2010;binding proteins to membranes occurs by different mechanisms. J Biol Chem. 1996;271(23):13317&#x2013;23.</Citation><ArticleIdList><ArticleId IdType="pubmed">8662836</ArticleId></ArticleIdList></Reference><Reference><Citation>Xie C, Takahashi S, Brocker CN, He S, Chen L, Xie G, et al. . Hepatocyte peroxisome proliferator&#x2010;activated receptor &#x3b1; regulates bile acid synthesis and transport. Biochim Biophys Acta Mol Cell Biol Lipids. 2019;1864(10):1396&#x2013;411.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC7423166</ArticleId><ArticleId IdType="pubmed">31195146</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">35339795</PMID><DateCompleted><Year>2022</Year><Month>06</Month><Day>08</Day></DateCompleted><DateRevised><Year>2022</Year><Month>07</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-7838</ISSN><JournalIssue CitedMedium="Internet"><Volume>225</Volume><PubDate><Year>2022</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Cognition</Title><ISOAbbreviation>Cognition</ISOAbbreviation></Journal><ArticleTitle>How do people interpret implausible sentences?</ArticleTitle><Pagination><StartPage>105101</StartPage><MedlinePgn>105101</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.cognition.2022.105101</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0010-0277(22)00089-0</ELocationID><Abstract><AbstractText>People sometimes interpret implausible sentences nonliterally, for example treating The mother gave the candle the daughter as meaning the daughter receiving the candle. But how do they do so? We contrasted a nonliteral syntactic analysis account, according to which people compute a syntactic analysis appropriate for this nonliteral meaning, with a nonliteral semantic interpretation account, according to which they arrive at this meaning via purely semantic processing. The former but not the latter account postulates that people consider not only a literal-but-implausible double-object (DO) analysis in comprehending The mother gave the candle the daughter, but also a nonliteral-but-plausible prepositional-object (PO) analysis (i.e., including to before the daughter). In three structural priming experiments, participants heard a plausible or implausible DO or PO prime sentence. They then answered a comprehension question first or described a picture of a dative event first. In accord with the nonliteral syntactic analysis account, priming was reduced following implausible sentences than following plausible sentences and following nonliterally interpreted implausible sentences than literally interpreted implausible sentences. The results suggest that comprehenders constructed a nonliteral syntactic analysis, which we argue was predicted early in the sentence.</AbstractText><CopyrightInformation>Copyright &#xa9; 2022. Published by Elsevier B.V.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Zhenguang G</ForeName><Initials>ZG</Initials><AffiliationInfo><Affiliation>Department of Linguistics and Modern Languages / Brain and Mind Institute, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: zhenugangcai@cuhk.edu.hk.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Translation interpreting and intercultural studies, Hong Kong Baptist University, Hong Kong Special Administrative Region.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pickering</LastName><ForeName>Martin J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Psychology, University of Edinburgh, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2022</Year><Month>03</Month><Day>24</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Cognition</MedlineTA><NlmUniqueID>0367541</NlmUniqueID><ISSNLinking>0010-0277</ISSNLinking></MedlineJournalInfo><SupplMeshList><SupplMeshName Type="Disease" UI="C538334">Nakajo syndrome</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D032882" MajorTopicYN="Y">Comprehension</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004893" MajorTopicYN="N">Erythema Nodosum</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005385" MajorTopicYN="N">Fingers</DescriptorName><QualifierName UI="Q000002" MajorTopicYN="N">abnormalities</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006309" MajorTopicYN="N">Hearing</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007802" MajorTopicYN="Y">Language</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009035" MajorTopicYN="N">Mothers</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012660" MajorTopicYN="N">Semantics</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Implausible sentences</Keyword><Keyword MajorTopicYN="N">Semantic interpretation</Keyword><Keyword MajorTopicYN="N">Structural priming</Keyword><Keyword MajorTopicYN="N">Syntactic analysis</Keyword><Keyword MajorTopicYN="N">Syntactic prediction</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>8</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2022</Year><Month>3</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2022</Year><Month>3</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2022</Year><Month>3</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>6</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>3</Month><Day>27</Day><Hour>20</Hour><Minute>22</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">35339795</ArticleId><ArticleId IdType="doi">10.1016/j.cognition.2022.105101</ArticleId><ArticleId IdType="pii">S0010-0277(22)00089-0</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">34724229</PMID><DateCompleted><Year>2022</Year><Month>03</Month><Day>24</Day></DateCompleted><DateRevised><Year>2022</Year><Month>03</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1469-8137</ISSN><JournalIssue CitedMedium="Internet"><Volume>233</Volume><Issue>2</Issue><PubDate><Year>2022</Year><Month>Jan</Month></PubDate></JournalIssue><Title>The New phytologist</Title><ISOAbbreviation>New Phytol</ISOAbbreviation></Journal><ArticleTitle>The RNA recognition motif-containing protein UBA2c prevents early flowering by promoting transcription of the flowering repressor FLM in Arabidopsis.</ArticleTitle><Pagination><StartPage>751</StartPage><EndPage>765</EndPage><MedlinePgn>751-765</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/nph.17836</ELocationID><Abstract><AbstractText>FLOWERING LOCUS M (FLM) is a well-known MADS-box transcription factor that is required for preventing early flowering under low temperatures in Arabidopsis thaliana. Alternative splicing of FLM is involved in the regulation of temperature-responsive flowering. However, how the basic transcript level of FLM is regulated is largely unknown. Here, we conducted forward genetic screening and identified a previously uncharacterized flowering repressor gene, UBA2c. Genetic analyses indicated that UBA2c represses flowering at least by promoting FLM transcription. We further demonstrated that UBA2c directly binds to FLM chromatin and facilitates FLM transcription by inhibiting histone H3K27 trimethylation, a histone marker related to transcriptional repression. UBA2c encodes a protein containing two putative RNA recognition motifs (RRMs) and one prion-like domain (PrLD). We found that UBA2c forms speckles in the nucleus and that both the RRMs and PrLD are required not only for forming the nuclear speckles but also for the biological function of UBA2c. These results identify a previously unknown flowering repressor and provide insights into the regulation of flowering time.</AbstractText><CopyrightInformation>&#xa9; 2021 The Authors. New Phytologist &#xa9; 2021 New Phytologist Foundation.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0001-7147-9002</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Graduate School of Peking Union Medical College, Beijing, 100730, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Su</LastName><ForeName>Xiao-Min</ForeName><Initials>XM</Initials><Identifier Source="ORCID">0000-0003-2657-3010</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Zhang-Wei</ForeName><Initials>ZW</Initials><Identifier Source="ORCID">0000-0003-2196-5058</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Jin-Xing</ForeName><Initials>JX</Initials><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Su</LastName><ForeName>Yin-Na</ForeName><Initials>YN</Initials><Identifier Source="ORCID">0000-0002-7319-5086</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Xue-Wei</ForeName><Initials>XW</Initials><Identifier Source="ORCID">0000-0001-8796-6374</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Ling</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0001-8711-047X</Identifier><AffiliationInfo><Affiliation>Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes, Institute of Plant and Food Science, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Zhe</ForeName><Initials>Z</Initials><Identifier Source="ORCID">0000-0001-9436-3299</Identifier><AffiliationInfo><Affiliation>Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes, Institute of Plant and Food Science, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>He</LastName><ForeName>Xin-Jian</ForeName><Initials>XJ</Initials><Identifier Source="ORCID">0000-0002-2878-7461</Identifier><AffiliationInfo><Affiliation>National Institute of Biological Sciences, Beijing, 102206, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Graduate School of Peking Union Medical College, Beijing, 100730, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 100084, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>11</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>New Phytol</MedlineTA><NlmUniqueID>9882884</NlmUniqueID><ISSNLinking>0028-646X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D029681">Arabidopsis Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D026161">MADS Domain Proteins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D017360" MajorTopicYN="Y">Arabidopsis</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D029681" MajorTopicYN="Y">Arabidopsis Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D035264" MajorTopicYN="N">Flowers</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018506" MajorTopicYN="N">Gene Expression Regulation, Plant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D026161" MajorTopicYN="N">MADS Domain Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000071377" MajorTopicYN="N">RNA Recognition Motif</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Arabidopsis</Keyword><Keyword MajorTopicYN="N">FLM</Keyword><Keyword MajorTopicYN="N">UBA2c</Keyword><Keyword MajorTopicYN="N">flowering time</Keyword><Keyword MajorTopicYN="N">histone</Keyword><Keyword MajorTopicYN="N">transcription</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>10</Month><Day>4</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>10</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>11</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>3</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>11</Month><Day>1</Day><Hour>17</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34724229</ArticleId><ArticleId IdType="doi">10.1111/nph.17836</ArticleId></ArticleIdList><ReferenceList><Title>References</Title><Reference><Citation>Amasino RM. 2005. Vernalization and flowering time. Current Opinion in Biotechnology 16: 154-158.</Citation></Reference><Reference><Citation>Amasino R. 2010. Seasonal and developmental timing of flowering. The Plant Journal 61: 1001-1013.</Citation></Reference><Reference><Citation>Balasubramanian S, Sureshkumar S, Lempe J, Weigel D. 2006. Potent induction of Arabidopsis thaliana flowering by elevated growth temperature. PLoS Genetics 2: e106.</Citation></Reference><Reference><Citation>Bao S, Hua C, Shen L, Yu H. 2020. New insights into gibberellin signaling in regulating flowering in Arabidopsis. Journal of Integrative Plant Biology 62: 118-131.</Citation></Reference><Reference><Citation>Boss PK, Bastow RM, Mylne JS, Dean C. 2004. Multiple pathways in the decision to flower: enabling, promoting, and resetting. Plant Cell 16: S18-31.</Citation></Reference><Reference><Citation>Bouch&#xe9; F, Lobet G, Tocquin P, Perilleux C. 2016. FLOR-ID: an interactive database of flowering-time gene networks in Arabidopsis thaliana. Nucleic Acids Research 44: D1167-1171.</Citation></Reference><Reference><Citation>Bouch&#xe9; F, Woods DP, Amasino RM. 2017. Winter memory throughout the plant kingdom: different paths to flowering. Plant Physiology 173: 27-35.</Citation></Reference><Reference><Citation>Bove J, Kim C, Gibson C, Assmann S. 2008. Characterization of wound-responsive RNA-binding proteins and their splice variants in Arabidopsis. Plant Molecular Biology 67: 71-88.</Citation></Reference><Reference><Citation>Buels R, Yao E, Diesh CM, Hayes RD, Munoz-Torres M, Helt G, Goodstein DM, Elsik CG, Lewis SE, Stein L et&#x2009;al. 2016. JBrowse: a dynamic web platform for genome visualization and analysis. Genome Biology 17: 66.</Citation></Reference><Reference><Citation>Burke KA, Janke AM, Rhine CL, Fawzi NL. 2015. Residue-by-residue view of in&#xa0;vitro FUS granules that bind the C-terminal domain of RNA polymerase II. Molecular Cell 60: 231-241.</Citation></Reference><Reference><Citation>Campos-Rivero G, Osorio-Montalvo P, S&#xe1;nchez-Borges R, Us-Camas R, Duarte-Ak&#xe9; F, De-la-Pe&#xf1;a C. 2017. Plant hormone signaling in flowering: an epigenetic point of view. Journal of Plant Physiology 214: 16-27.</Citation></Reference><Reference><Citation>Capovilla G, Symeonidi E, Wu R, Schmid M. 2017. Contribution of major FLM isoforms to temperature-dependent flowering in Arabidopsis thaliana. Journal of Experimental Botany 68: 5117-5127.</Citation></Reference><Reference><Citation>Chakrabortee S, Kayatekin C, Newby GA, Mendillo ML, Lancaster A, Lindquist S. 2016. Luminidependens (LD) is an Arabidopsis protein with prion behavior. Proceedings of the National Academy of Sciences, USA 113: 6065-6070.</Citation></Reference><Reference><Citation>Cho LH, Yoon J, An G. 2017. The control of flowering time by environmental factors. The Plant Journal 90: 708-719.</Citation></Reference><Reference><Citation>Corbesier L, Vincent C, Jang S, Fornara F, Fan Q, Searle I, Giakountis A, Farrona S, Gissot L, Turnbull C et&#x2009;al. 2007. FT protein movement contributes to long-distance signaling in floral induction of Arabidopsis. Science 316: 1030-1033.</Citation></Reference><Reference><Citation>Crevillen P, Dean C. 2011. Regulation of the floral repressor gene FLC: the complexity of transcription in a chromatin context. Current Opinion in Plant Biology 14: 38-44.</Citation></Reference><Reference><Citation>Egloff S, Murphy S. 2008. Cracking the RNA polymerase II CTD code. Trends in Genetics 24: 280-288.</Citation></Reference><Reference><Citation>Fang X, Wang L, Ishikawa R, Li Y, Fiedler M, Liu F, Calder G, Rowan B, Weigel D, Li P et&#x2009;al. 2019. Arabidopsis FLL2 promotes liquid-liquid phase separation of polyadenylation complexes. Nature 569: 265-269.</Citation></Reference><Reference><Citation>Fujiwara S, Oda A, Yoshida R, Niinuma K, Miyata K, Tomozoe Y, Tajima T, Nakagawa M, Hayashi K, Coupland G et&#x2009;al. 2008. Circadian clock proteins LHY and CCA1 regulate SVP protein accumulation to control flowering in Arabidopsis. Plant Cell 20: 2960-2971.</Citation></Reference><Reference><Citation>Gu X, Le C, Wang Y, Li Z, Jiang D, Wang Y, He Y. 2013. Arabidopsis FLC clade members form flowering-repressor complexes coordinating responses to endogenous and environmental cues. Nature Communications 4: 1947.</Citation></Reference><Reference><Citation>Heidemann M, Hintermair C, Vo&#xdf; K, Eick D. 2012. Dynamic phosphorylation patterns of RNA polymerase II CTD during transcription. Biochimica et Biophysica Acta 1829: 55-62.</Citation></Reference><Reference><Citation>Hsin JP, Manley JL. 2012. The RNA polymerase II CTD coordinates transcription and RNA processing. Genes and Development 26: 2119-2137.</Citation></Reference><Reference><Citation>Imaizumi T, Kay SA. 2006. Photoperiodic control of flowering: not only by coincidence. Trends in Plant Science 11: 550-558.</Citation></Reference><Reference><Citation>Jarillo JA, Pineiro M. 2011. Timing is everything in plant development. The central role of floral repressors. Plant Science 181: 364-378.</Citation></Reference><Reference><Citation>Jiang D, Wang Y, Wang Y, He Y. 2008. Repression of FLOWERING LOCUS C and FLOWERING LOCUS T by the Arabidopsis Polycomb repressive complex 2 components. PLoS ONE 3: e3404.</Citation></Reference><Reference><Citation>Jung J-H, Barbosa AD, Hutin S, Kumita JR, Gao M, Derwort D, Silva CS, Lai X, Pierre E, Geng F et&#x2009;al. 2020. A prion-like domain in ELF3 functions as a thermosensor in Arabidopsis. Nature 585: 256-260.</Citation></Reference><Reference><Citation>Kim CY, Bove J, Assmann SM. 2008. Overexpression of wound-responsive RNA-binding proteins induces leaf senescence and hypersensitive-like cell death. New Phytologist 180: 57-70.</Citation></Reference><Reference><Citation>Kim DH, Doyle MR, Sung S, Amasino RM. 2009. Vernalization: winter and the timing of flowering in plants. Annual Review of Cell and Developmental Biology 25: 277-299.</Citation></Reference><Reference><Citation>Kim D, Paggi JM, Park C, Bennett C, Salzberg SL. 2019. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nature Biotechnology 37: 907-915.</Citation></Reference><Reference><Citation>Lambermon MH, Fu Y, Wieczorek Kirk DA, Dupasquier M, Filipowicz W, Lorkovi&#x107; ZJ. 2002. UBA1 and UBA2, two proteins that interact with UBP1, a multifunctional effector of pre-mRNA maturation in plants. Molecular and Cellular Biology 22: 4346-4357.</Citation></Reference><Reference><Citation>Lambermon MHL, Simpson GG, Wieczorek Kirk DA, Hemmings-Mieszczak M, Klahre U, Filipowicz W. 2000. UBP1, a novel hnRNP-like protein that functions at multiple steps of higher plant nuclear pre-mRNA maturation. EMBO Journal 19: 1638-1649.</Citation></Reference><Reference><Citation>Lee JH, Ryu HS, Chung KS, Pos&#xe9; D, Kim S, Schmid M, Ahn JH. 2013. Regulation of temperature-responsive flowering by MADS-box transcription factor repressors. Science 342: 628-632.</Citation></Reference><Reference><Citation>Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, Subgroup GPDP. 2009. The sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078-2079.</Citation></Reference><Reference><Citation>Li J, Kinoshita T, Pandey S, Ng CK, Gygi SP, Shimazaki K, Assmann SM. 2002. Modulation of an RNA-binding protein by abscisic-acid-activated protein kinase. Nature 418: 793-797.</Citation></Reference><Reference><Citation>Li Z, Peng J, Wen X, Guo H. 2012. Gene network analysis and functional studies of senescence-associated genes reveal novel regulators of Arabidopsis leaf senescence. Journal of Integrative Plant Biology 54: 526-539.</Citation></Reference><Reference><Citation>Liao Y, Smyth GK, Shi W. 2013. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30: 923-930.</Citation></Reference><Reference><Citation>Liu Z, Zhao N, Su Y, Chen S, He X. 2020. Exogenously overexpressed intronic long noncoding RNAs activate host gene expression by affecting histone modification in Arabidopsis. Scientific Reports 10: 3094.</Citation></Reference><Reference><Citation>Lorkovi&#x107; ZJ, Barta A. 2002. Genome analysis: RNA recognition motif (RRM)&#xa0;and K homology (KH) domain RNA-binding proteins from the&#xa0;flowering plant Arabidopsis thaliana. Nucleic Acids Research 30: 623-635.</Citation></Reference><Reference><Citation>Luo X, He Y. 2020. Experiencing winter for spring flowering: a molecular epigenetic perspective on vernalization. Journal of Integrative Plant Biology 62: 104-117.</Citation></Reference><Reference><Citation>Lutz U, Pos&#xe9; D, Pfeifer M, Gundlach H, Hagmann J, Wang C, Weigel D, Mayer KF, Schmid M, Schwechheimer C. 2015. Modulation of ambient temperature-dependent flowering in Arabidopsis thaliana by natural variation of FLOWERING LOCUS M. PLoS Genetics 11: e1005588.</Citation></Reference><Reference><Citation>Marondedze C, Thomas L, Gehring C, Lilley KS. 2019. Changes in the Arabidopsis RNA-binding proteome reveal novel stress response mechanisms. BMC Plant Biology 19: 139.</Citation></Reference><Reference><Citation>Marquardt S, Boss PK, Hadfield J, Dean C. 2006. Additional targets of the Arabidopsis autonomous pathway members, FCA and FY. Journal of Experimental Botany 57: 3379-3386.</Citation></Reference><Reference><Citation>Michaels SD, Amasino RM. 2001. Loss of FLOWERING LOCUS C activity eliminates the late-flowering phenotype of FRIGIDA and autonomous pathway mutations but not responsiveness to vernalization. Plant Cell 13: 935-941.</Citation></Reference><Reference><Citation>Mutasa-Gottgens E, Hedden P. 2009. Gibberellin as a factor in floral regulatory networks. Journal of Experimental Botany 60: 1979-1989.</Citation></Reference><Reference><Citation>Na JK, Kim JK, Kim DY, Assmann SM. 2015. Expression of potato RNA-binding proteins StUBA2a/b and StUBA2c induces hypersensitive-like cell death and early leaf senescence in Arabidopsis. Journal of Experimental Botany 66: 4023-4033.</Citation></Reference><Reference><Citation>Ng M, Yanofsky MF. 2001. Function and evolution of the plant MADS-box gene family. Nature Reviews Genetics 2: 186-195.</Citation></Reference><Reference><Citation>Nguyen CC, Nakaminami K, Matsui A, Kobayashi S, Kurihara Y, Toyooka K, Tanaka M, Seki M. 2016. Oligouridylate binding protein 1b plays an integral role in plant heat stress tolerance. Frontiers in Plant Science 7: 853.</Citation></Reference><Reference><Citation>Nguyen CC, Nakaminami K, Matsui A, Watanabe S, Kanno Y, Seo M, Seki M. 2017. Overexpression of oligouridylate binding protein 1b results in ABA hypersensitivity. Plant Signaling and Behavior 12: e1282591.</Citation></Reference><Reference><Citation>Pos&#xe9; D, Verhage L, Ott F, Yant L, Mathieu J, Angenent GC, Immink RG, Schmid M. 2013. Temperature-dependent regulation of flowering by antagonistic FLM variants. Nature 503: 414-417.</Citation></Reference><Reference><Citation>Quinlan AR, Hall IM. 2010. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26: 841-842.</Citation></Reference><Reference><Citation>Ramirez F, Ryan DP, Gruning B, Bhardwaj V, Kilpert F, Richter AS, Heyne S, Dundar F, Manke T. 2016. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Research 44: W160-W165.</Citation></Reference><Reference><Citation>Ratcliffe OJ, Riechmann JL. 2002. Arabidopsis transcription factors and the regulation of flowering time: a genomic perspective. Current Issues in Molecular Biology 4: 77-91.</Citation></Reference><Reference><Citation>Riback JA, Katanski CD, Kear-Scott JL, Pilipenko EV, Rojek AE, Sosnick TR, Drummond DA. 2017. Stress-triggered phase seperation is an adaptive, evolutionarily turned response. Cell 168: 1028-1040.</Citation></Reference><Reference><Citation>Riera M, Redko Y, Leung J. 2006. Arabidopsis RNA-binding protein UBA2a relocalizes into nuclear speckles in response to abscisic acid. FEBS Letter 580: 4160-4165.</Citation></Reference><Reference><Citation>Samach A, Onouchi H, Gold SE, Ditta GS, Schwarz-Sommer Z, Yanofsky MF, Coupland G. 2000. Distinct roles of CONSTANS target genes in reproductive development of Arabidopsis. Science 288: 1613-1616.</Citation></Reference><Reference><Citation>Santos-Pereira JM, Aguilera A. 2015. R loops: new modulators of genome dynamics and function. Nature Reviews Genetics 16: 583-597.</Citation></Reference><Reference><Citation>Schubert D, Primavesi L, Bishopp A, Roberts G, Doonan J, Jenuwein T, Goodrich J. 2006. Silencing by plant Polycomb-group genes requires dispersed trimethylation of histone H3 at lysine 27. EMBO Journal 25: 4638-4649.</Citation></Reference><Reference><Citation>Scortecci KC, Michaels SD, Amasino RM. 2003. Genetic interactions between FLM and other flowering-time genes in Arabidopsis thaliana. Plant Molecular Biology 52: 915-922.</Citation></Reference><Reference><Citation>Searle I, Coupland G. 2004. Induction of flowering by seasonal changes in photoperiod. EMBO Journal 23: 1217-1222.</Citation></Reference><Reference><Citation>Sheldon CC, Finnegan EJ, Rouse DT, Tadege M, Bagnall DJ, Helliwell CA, Peacock WJ, Dennis ES. 2000. The control of flowering by vernalization. Current Opinion in Plant Biology 3: 418-422.</Citation></Reference><Reference><Citation>Simpson GG. 2004. The autonomous pathway: epigenetic and post-transcriptional gene regulation in the control of Arabidopsis flowering time. Current Opinion in Plant Biology 7: 570-574.</Citation></Reference><Reference><Citation>Simpson G, Dean C. 2002. Arabidopsis, the Rosetta stone of flowering time? Science 296: 285-289.</Citation></Reference><Reference><Citation>Song YH, Ito S, Imaizumi T. 2013. Flowering time regulation: photoperiod- and temperature-sensing in leaves. Trends in Plant Science 18: 575-583.</Citation></Reference><Reference><Citation>Srikanth A, Schmid M. 2011. Regulation of flowering time: all roads lead to Rome. Cellular and Molecular Life Sciences 68: 2013-2037.</Citation></Reference><Reference><Citation>Sun Q, Csorba T, Skourti-Stathaki K, Proudfoot NJ, Dean C. 2013. R-loop stabilization represses antisense transcription at the Arabidopsis FLC locus. Science 340: 619-621.</Citation></Reference><Reference><Citation>Sureshkumar S, Dent C, Seleznev A, Tasset C, Balasubramanian S. 2016. Nonsense-mediated mRNA decay modulates FLM-dependent thermosensory flowering response in Arabidopsis. Nature Plants 2: 16055.</Citation></Reference><Reference><Citation>Theissen G, Rumpler F, Gramzow L. 2018. Array of MADS-box genes: facilitator for rapid adaptation? Trends in Plant Science 23: 563-576.</Citation></Reference><Reference><Citation>Wang Z, Xing H, Dong L, Zhang H, Han C, Wang X, Chen Q. 2015. Egg cell-specific promoter-controlled CRISPR/Cas9 efficiently generates homozygous mutants for multiple target genes in Arabidopsis in a single generation. Genome Biology 16: 144.</Citation></Reference><Reference><Citation>Werner JD, Borevitz JO, Warthmann N, Trainer GT, Ecker JR, Chory J, Weigel D. 2005. Quantitative trait locus mapping and DNA array hybridization identify an FLM deletion as a cause for natural flowering-time variation. Proceedings of the National Academy of Sciences, USA 102: 2460-2465.</Citation></Reference><Reference><Citation>Wu Z, Fang X, Zhu D, Dean C. 2020. Autonomous pathway: FLOWERING LOCUS C repression through an antisense-mediated chromatin-silencing mechanism. Plant Physiology 182: 27-37.</Citation></Reference><Reference><Citation>Wu Z, Ietswaart R, Liu F, Yang H, Howard M, Dean C. 2015. Quantitative regulation of FLC via coordinated transcriptional initiation and elongation. Proceedings of the National Academy of Sciences, USA 113: 218-223.</Citation></Reference><Reference><Citation>Xu W, Xu H, Li K, Fan Y, Liu Y, Yang X, Sun Q. 2017. The R-loop is a common chromatin feature of the Arabidopsis genome. Nature Plants 3: 704-714.</Citation></Reference><Reference><Citation>Yant L, Mathieu J, Schmid M. 2009. Just say no: floral repressors help Arabidopsis bide the time. Current Opinion in Plant Biology 12: 580-586.</Citation></Reference><Reference><Citation>Zang C, Schones DE, Zeng C, Cui K, Zhao K, Peng W. 2009. A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics 25: 1952-1958.</Citation></Reference><Reference><Citation>Zhou JX, Liu ZW, Li YQ, Li L, Wang B, Chen S, He XJ. 2018. Arabidopsis PWWP domain proteins mediate H3K27 trimethylation on FLC and regulate flowering time. Journal of Integrative Plant Biology 60: 362-368.</Citation></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">34585848</PMID><DateCompleted><Year>2021</Year><Month>11</Month><Day>22</Day></DateCompleted><DateRevised><Year>2023</Year><Month>11</Month><Day>08</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1757-4684</ISSN><JournalIssue CitedMedium="Internet"><Volume>13</Volume><Issue>11</Issue><PubDate><Year>2021</Year><Month>Nov</Month><Day>08</Day></PubDate></JournalIssue><Title>EMBO molecular medicine</Title><ISOAbbreviation>EMBO Mol Med</ISOAbbreviation></Journal><ArticleTitle>A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis.</ArticleTitle><Pagination><StartPage>e14563</StartPage><MedlinePgn>e14563</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">e14563</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.15252/emmm.202114563</ELocationID><Abstract><AbstractText>Semaphorin 7A (SEMA7A) is a membrane-bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis. WGS reveals a SEMA7A<sup>R148W</sup> homozygous mutation in a female child with elevated levels of serum ALT, AST, and total bile acid (TBA) of unknown etiology. This patient also carried a SLC10A1<sup>S267F</sup> allele, but Slc10a1<sup>S267F</sup> homozygous mice exhibited normal liver function. Similar to the child, Sema7a<sup>R145W</sup> homozygous mice displayed elevated levels of serum ALT, AST, and TBA. Remarkably, liver histology and LC-MS/MS analyses exhibited hepatocyte hydropic degeneration and increased liver bile acid (BA) levels in Sema7a<sup>R145W</sup> homozygous mice. Further mechanistic studies demonstrated that Sema7a<sup>R145W</sup> mutation reduced the expression of canalicular membrane BA transporters, bile salt export pump (Bsep), and multidrug resistance-associated protein-2 (Mrp2), causing intrahepatic cholestasis in mice. Administration with ursodeoxycholic acid and a dietary supplement glutathione improved liver function in the child. Therefore, Sema7a<sup>R145W</sup> homozygous mutation causes intrahepatic cholestasis by reducing hepatic Bsep and Mrp2 expression.</AbstractText><CopyrightInformation>&#xa9; 2021 The Authors Published under the terms of the CC BY 4.0 license.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Qiong</ForeName><Initials>Q</Initials><Identifier Source="ORCID">0000-0003-1033-3098</Identifier><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>Gang</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qu</LastName><ForeName>Jiaquan</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-0204-5646</Identifier><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Sheng</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiaoxun</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0002-3892-7464</Identifier><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Jingjing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Hong</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Mingqiao</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ling</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Xuan</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Qiaoling</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Qiao</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Xueqian</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zou</LastName><ForeName>Huiling</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, Changsha Hospital for Maternal &amp; Child Health Care, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Shijun</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zou</LastName><ForeName>Lingyun</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Bao'an Maternal and Child Health Hospital, Jinan University, Shenzhen, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Institute of Immunology, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deng</LastName><ForeName>Guohong</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shi-Ying</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, CT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyer</LastName><ForeName>James L</ForeName><Initials>JL</Initials><Identifier Source="ORCID">0000-0002-8959-6036</Identifier><AffiliationInfo><Affiliation>Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, CT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Jin</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-8543-4566</Identifier><AffiliationInfo><Affiliation>Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>09</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>EMBO Mol Med</MedlineTA><NlmUniqueID>101487380</NlmUniqueID><ISSNLinking>1757-4676</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018528">ATP-Binding Cassette Transporters</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015703">Antigens, CD</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D029363">Organic Anion Transporters, Sodium-Dependent</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C485571">Sema7a protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D039961">Semaphorins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D027981">Symporters</NameOfSubstance></Chemical><Chemical><RegistryNumber>145420-23-1</RegistryNumber><NameOfSubstance UI="C071908">sodium-bile acid cotransporter</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C535933">Cholestasis, progressive familial intrahepatic 1</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D018528" MajorTopicYN="N">ATP-Binding Cassette Transporters</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015703" MajorTopicYN="N">Antigens, CD</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002779" MajorTopicYN="Y">Cholestasis</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002780" MajorTopicYN="Y">Cholestasis, Intrahepatic</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002853" MajorTopicYN="N">Chromatography, Liquid</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D029363" MajorTopicYN="N">Organic Anion Transporters, Sodium-Dependent</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D039961" MajorTopicYN="Y">Semaphorins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D027981" MajorTopicYN="N">Symporters</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053719" MajorTopicYN="N">Tandem Mass Spectrometry</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">bile acid</Keyword><Keyword MajorTopicYN="N">bile salt export pump</Keyword><Keyword MajorTopicYN="N">liver injury</Keyword><Keyword MajorTopicYN="N">progressive familial intrahepatic cholestasis</Keyword><Keyword MajorTopicYN="N">semaphorin 7A</Keyword></KeywordList><CoiStatement>The authors declare that they have no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="revised"><Year>2021</Year><Month>9</Month><Day>3</Day></PubMedPubDate><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>5</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>9</Month><Day>7</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>9</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>11</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>9</Month><Day>29</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2021</Year><Month>11</Month><Day>8</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34585848</ArticleId><ArticleId IdType="pmc">PMC8573601</ArticleId><ArticleId IdType="doi">10.15252/emmm.202114563</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA (2010) A map of human genome variation from population&#x2010;scale sequencing. Nature 467: 1061&#x2013;1073</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3042601</ArticleId><ArticleId IdType="pubmed">20981092</ArticleId></ArticleIdList></Reference><Reference><Citation>Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7: 248&#x2013;249</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2855889</ArticleId><ArticleId IdType="pubmed">20354512</ArticleId></ArticleIdList></Reference><Reference><Citation>Alto L, Terman J (2017) Semaphorins and their signaling mechanisms. Methods Mol Biol 1493: 1&#x2013;25</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5538787</ArticleId><ArticleId IdType="pubmed">27787839</ArticleId></ArticleIdList></Reference><Reference><Citation>Amirneni S, Haep N, Gad MA, Soto&#x2010;Gutierrez A, Squires JE, Florentino RM (2020) Molecular overview of progressive familial intrahepatic cholestasis. World J Gastroenterol 26: 7470&#x2013;7484</Citation><ArticleIdList><ArticleId IdType="pmc">PMC7754551</ArticleId><ArticleId IdType="pubmed">33384548</ArticleId></ArticleIdList></Reference><Reference><Citation>Boyer JL, Phillips JM, Graf J (1990) Preparation and specific applications of isolated hepatocyte couplets. Methods Enzymol 192: 501&#x2013;516</Citation><ArticleIdList><ArticleId IdType="pubmed">1963665</ArticleId></ArticleIdList></Reference><Reference><Citation>Boyer JL (2013) Bile formation and secretion. Compr Physiol 3: 1035&#x2013;1078</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4091928</ArticleId><ArticleId IdType="pubmed">23897680</ArticleId></ArticleIdList></Reference><Reference><Citation>Boyer JL, Soroka CJ (2021) Bile formation and secretion: an update. J Hepatol 75: 190&#x2013;201</Citation><ArticleIdList><ArticleId IdType="pubmed">33617926</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL (2017) Bile acids initiate cholestatic liver injury by triggering a hepatocyte&#x2010;specific inflammatory response. JCI Insight 2: e90780</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5333973</ArticleId><ArticleId IdType="pubmed">28289714</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai S, Boyer J (2021) The role of bile acids in cholestatic liver injury. Ann Transl Med 9: 737</Citation><ArticleIdList><ArticleId IdType="pmc">PMC8106037</ArticleId><ArticleId IdType="pubmed">33987435</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai SY, Yu D, Soroka CJ, Wang J, Boyer JL (2021) Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis. J Hepatol 74: 550&#x2013;559</Citation><ArticleIdList><ArticleId IdType="pmc">PMC7897288</ArticleId><ArticleId IdType="pubmed">33039404</ArticleId></ArticleIdList></Reference><Reference><Citation>Chai J, Cai S&#x2010;Y, Liu X, Lian W, Chen S, Zhang L, Feng X, Cheng Y, He X, He YU et&#xa0;al (2015) Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. J Hepatol 63: 1440&#x2013;1448</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4686151</ArticleId><ArticleId IdType="pubmed">26212029</ArticleId></ArticleIdList></Reference><Reference><Citation>Chang M, Lin H, Fu H, Wang J, Yang Y, Wan Z, Han G (2020) CREB activation affects mesenchymal stem cell migration and differentiation in periodontal tissues due to orthodontic force. Int J Biochem Cell Biol 129: 105862</Citation><ArticleIdList><ArticleId IdType="pubmed">33045372</ArticleId></ArticleIdList></Reference><Reference><Citation>Chen H, Wu S, Hsu S, Liou B, Chen H, Chang M (2018) Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases. J Biomed Sci 25: 75</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6203212</ArticleId><ArticleId IdType="pubmed">30367658</ArticleId></ArticleIdList></Reference><Reference><Citation>Crocenzi FA, Sanchez Pozzi EJ, Ruiz ML, Zucchetti AE, Roma MG, Mottino AD, Vore M (2008) Ca(2+)&#x2010;dependent protein kinase C isoforms are critical to estradiol 17beta&#x2010;D&#x2010;glucuronide&#x2010;induced cholestasis in the rat. Hepatology 48: 1885&#x2013;1895</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3004396</ArticleId><ArticleId IdType="pubmed">18972403</ArticleId></ArticleIdList></Reference><Reference><Citation>DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, del Angel G, Rivas MA, Hanna M et&#xa0;al (2011) A framework for variation discovery and genotyping using next&#x2010;generation DNA sequencing data. Nat Genet 43: 491&#x2013;498</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3083463</ArticleId><ArticleId IdType="pubmed">21478889</ArticleId></ArticleIdList></Reference><Reference><Citation>El&#x2010;Guindi MA, Sira MM, Hussein MH, Ehsan NA, Elsheikh NM (2016) Hepatic immunohistochemistry of bile transporters in progressive familial intrahepatic cholestasis. Ann Hepatol 15: 222&#x2013;229</Citation><ArticleIdList><ArticleId IdType="pubmed">26845599</ArticleId></ArticleIdList></Reference><Reference><Citation>Fu W, O&#x2019;Connor TD, Jun G, Kang HM, Abecasis G, Leal SM, Gabriel S, Rieder MJ, Altshuler D, Shendure J et&#xa0;al (2013) Analysis of 6,515 exomes reveals the recent origin of most human protein&#x2010;coding variants. Nature 493: 216&#x2013;220</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3676746</ArticleId><ArticleId IdType="pubmed">23201682</ArticleId></ArticleIdList></Reference><Reference><Citation>Ghofrani J, Lucar O, Dugan H, Reeves RK, Jost S (2019) Semaphorin 7A modulates cytokine&#x2010;induced memory&#x2010;like responses by human natural killer cells. Eur J Immunol 49: 1153&#x2013;1166</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6679804</ArticleId><ArticleId IdType="pubmed">31016720</ArticleId></ArticleIdList></Reference><Reference><Citation>Gonzales E, Grosse B, Schuller B, Davit&#x2010;Spraul A, Conti F, Guettier C, Cassio D, Jacquemin E (2015) Targeted pharmacotherapy in progressive familial intrahepatic cholestasis type 2: evidence for improvement of cholestasis with 4&#x2010;phenylbutyrate. Hepatology 62: 558&#x2013;566</Citation><ArticleIdList><ArticleId IdType="pubmed">25716872</ArticleId></ArticleIdList></Reference><Reference><Citation>Kagawa T, Orii R, Hirose S, Arase Y, Shiraishi K, Mizutani A, Tsukamoto H, Mine T (2014) Ursodeoxycholic acid stabilizes the bile salt export pump in the apical membrane in MDCK II cells. J Gastroenterol 49: 890&#x2013;899</Citation><ArticleIdList><ArticleId IdType="pubmed">23722250</ArticleId></ArticleIdList></Reference><Reference><Citation>Koh J&#x2010;M, Oh B, Lee JY, Lee J&#x2010;K, Kimm K, Kim GS, Park BL, Cheong HS, Shin HD, Hong JM et&#xa0;al (2006) Association study of semaphorin 7a (sema7a) polymorphisms with bone mineral density and fracture risk in postmenopausal Korean women. J Hum Genet 51: 112&#x2013;117</Citation><ArticleIdList><ArticleId IdType="pubmed">16372136</ArticleId></ArticleIdList></Reference><Reference><Citation>K&#xf6;rner A, Bernard A, Fitzgerald J, Alarcon&#x2010;Barrera J, Kostidis S, Kaussen T, Giera M, Mirakaj V (2021) Sema7A is crucial for resolution of severe inflammation. Proc Natl Acad Sci USA 118: e2017527118</Citation><ArticleIdList><ArticleId IdType="pmc">PMC7936270</ArticleId><ArticleId IdType="pubmed">33637648</ArticleId></ArticleIdList></Reference><Reference><Citation>Kubitz R, Saha N, Kuhlkamp T, Dutta S, vom Dahl S, Wettstein M, Haussinger D (2004) Ca2+&#x2010;dependent protein kinase C isoforms induce cholestasis in rat liver. J Biol Chem 279: 10323&#x2013;10330</Citation><ArticleIdList><ArticleId IdType="pubmed">14679204</ArticleId></ArticleIdList></Reference><Reference><Citation>Lan W, Chen Z, Chen Y, Tan M, Chen Y, Chen J, Chi X, Chen Y (2020) Glycochenodeoxycholic acid impairs transcription factor E3&#x2010;dependent autophagy&#x2010;lysosome machinery by disrupting reactive oxygen species homeostasis in L02 cells. Toxicol Lett 331: 11&#x2013;21</Citation><ArticleIdList><ArticleId IdType="pubmed">32439580</ArticleId></ArticleIdList></Reference><Reference><Citation>Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O&#x2019;Donnell&#x2010;Luria AH, Ware JS, Hill AJ, Cummings BB et&#xa0;al (2016) Analysis of protein&#x2010;coding genetic variation in 60,706 humans. Nature 536: 285&#x2013;291</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5018207</ArticleId><ArticleId IdType="pubmed">27535533</ArticleId></ArticleIdList></Reference><Reference><Citation>Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25: 2078&#x2013;2079</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2723002</ArticleId><ArticleId IdType="pubmed">19505943</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu H, Juo ZS, Shim AH, Focia PJ, Chen X, Garcia KC, He X (2010) Structural basis of semaphorin&#x2010;plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1. Cell 142: 749&#x2013;761</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2936782</ArticleId><ArticleId IdType="pubmed">20727575</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu R, Chen C, Xia X, Liao Q, Wang Q, Newcombe PJ, Xu S, Chen M, Ding Y, Li X et&#xa0;al (2017) Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine. Sci Rep 7: 9214</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5569087</ArticleId><ArticleId IdType="pubmed">28835676</ArticleId></ArticleIdList></Reference><Reference><Citation>McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M et&#xa0;al (2010) The genome analysis toolkit: a MapReduce framework for analyzing next&#x2010;generation DNA sequencing data. Genome Res 20: 1297&#x2013;1303</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2928508</ArticleId><ArticleId IdType="pubmed">20644199</ArticleId></ArticleIdList></Reference><Reference><Citation>Merico D, Roifman M, Braunschweig U, Yuen RKC, Alexandrova R, Bates A, Reid B, Nalpathamkalam T, Wang Z, Thiruvahindrapuram B et&#xa0;al (2015) Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman syndrome by disrupting minor intron splicing. Nat Commun 6: 8718</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4667643</ArticleId><ArticleId IdType="pubmed">26522830</ArticleId></ArticleIdList></Reference><Reference><Citation>Pan Q, Zhang X, Zhang L, Cheng Y, Zhao N, Li F, Zhou X, Chen S, Li J, Xu S et&#xa0;al (2018) Solute carrier organic anion transporter family member 3A1 is a bile acid efflux transporter in cholestasis. Gastroenterology 155: 1578&#x2013;1592</Citation><ArticleIdList><ArticleId IdType="pmc">PMC6221191</ArticleId><ArticleId IdType="pubmed">30063921</ArticleId></ArticleIdList></Reference><Reference><Citation>Patel RK, Jain M (2012) NGS QC Toolkit: a toolkit for quality control of next generation sequencing data. PLoS One 7: e30619</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3270013</ArticleId><ArticleId IdType="pubmed">22312429</ArticleId></ArticleIdList></Reference><Reference><Citation>Perez LM, Milkiewicz P, Elias E, Coleman R, Sanchez Pozzi EJ, Roma MG (2006) Oxidative stress induces internalization of the bile salt export pump, Bsep, and bile salt secretory failure in isolated rat hepatocyte couplets: a role for protein kinase C and prevention by protein kinase A. Toxicol Sci 91: 150&#x2013;158</Citation><ArticleIdList><ArticleId IdType="pubmed">16452108</ArticleId></ArticleIdList></Reference><Reference><Citation>Robinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP (2011) Integrative genomics viewer. Nat Biotechnol 29: 24&#x2013;26</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3346182</ArticleId><ArticleId IdType="pubmed">21221095</ArticleId></ArticleIdList></Reference><Reference><Citation>Schulten HJ, Hussein D, Al&#x2010;Adwani F, Karim S, Al&#x2010;Maghrabi J, Al&#x2010;Sharif M, Jamal A, Bakhashab S, Weaver J, Al&#x2010;Ghamdi F et&#xa0;al (2016) Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma. Am J Cancer Res 6: 2140&#x2013;2161</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5088282</ArticleId><ArticleId IdType="pubmed">27822408</ArticleId></ArticleIdList></Reference><Reference><Citation>Schwarz JM, Cooper DN, Schuelke M, Seelow D (2014) MutationTaster2: mutation prediction for the deep&#x2010;sequencing age. Nat Methods 11: 361&#x2013;362</Citation><ArticleIdList><ArticleId IdType="pubmed">24681721</ArticleId></ArticleIdList></Reference><Reference><Citation>Song Y, Wang L, Zhang L, Huang D (2021) The involvement of semaphorin 7A in tumorigenic and immunoinflammatory regulation. J Cell Physiol 236: 6235&#x2013;6248</Citation><ArticleIdList><ArticleId IdType="pubmed">33611799</ArticleId></ArticleIdList></Reference><Reference><Citation>Suzuki K, Okuno T, Yamamoto M, Pasterkamp RJ, Takegahara N, Takamatsu H, Kitao T, Takagi J, Rennert PD, Kolodkin AL et&#xa0;al (2007) Semaphorin 7A initiates T&#x2010;cell&#x2010;mediated inflammatory responses through alpha1beta1 integrin. Nature 446: 680&#x2013;684</Citation><ArticleIdList><ArticleId IdType="pubmed">17377534</ArticleId></ArticleIdList></Reference><Reference><Citation>Vaser R, Adusumalli S, Leng SN, Sikic M, Ng PC (2016) SIFT missense predictions for genomes. Nat Protoc 11: 1&#x2013;9</Citation><ArticleIdList><ArticleId IdType="pubmed">26633127</ArticleId></ArticleIdList></Reference><Reference><Citation>Vaz FM, Paulusma CC, Huidekoper H, de Ru M, Lim C, Koster J, Ho&#x2010;Mok K, Bootsma AH, Groen AK, Schaap FG et&#xa0;al (2015) Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: conjugated hypercholanemia without a clear clinical phenotype. Hepatology 61: 260&#x2013;267</Citation><ArticleIdList><ArticleId IdType="pubmed">24867799</ArticleId></ArticleIdList></Reference><Reference><Citation>Wagner M, Trauner M (2016) Recent advances in understanding and managing cholestasis. F1000Res 5: 705</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4841200</ArticleId><ArticleId IdType="pubmed">27134744</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang W, Soroka CJ, Mennone A, Rahner C, Harry K, Pypaert M, Boyer JL (2006) Radixin is required to maintain apical canalicular membrane structure and function in rat hepatocytes. Gastroenterology 131: 878&#x2013;884</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1820831</ArticleId><ArticleId IdType="pubmed">16952556</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high&#x2010;throughput sequencing data. Nucleic Acids Res 38: e164</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2938201</ArticleId><ArticleId IdType="pubmed">20601685</ArticleId></ArticleIdList></Reference><Reference><Citation>Yamada A, Kubo K, Takeshita T, Harashima N, Kawano K, Mine T, Sagawa K, Sugamura K, Itoh K (1999) Molecular cloning of a glycosylphosphatidylinositol&#x2010;anchored molecule CDw108. J Immunol 162: 4094&#x2013;4100</Citation><ArticleIdList><ArticleId IdType="pubmed">10201933</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhao Y, Yang F, Qiu L, Wang L, Che H (2020) A novel heterozygous intron mutation in SEMA7A causing Kallmann syndrome in a female. Gynecol Endocrinol 36: 218&#x2013;221</Citation><ArticleIdList><ArticleId IdType="pubmed">31650878</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">34398202</PMID><DateCompleted><Year>2022</Year><Month>01</Month><Day>10</Day></DateCompleted><DateRevised><Year>2022</Year><Month>01</Month><Day>10</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2574-3805</ISSN><JournalIssue CitedMedium="Internet"><Volume>4</Volume><Issue>8</Issue><PubDate><Year>2021</Year><Month>Aug</Month><Day>02</Day></PubDate></JournalIssue><Title>JAMA network open</Title><ISOAbbreviation>JAMA Netw Open</ISOAbbreviation></Journal><ArticleTitle>Prevalence of Osteoporosis and Fracture in China: The China Osteoporosis Prevalence Study.</ArticleTitle><Pagination><StartPage>e2121106</StartPage><MedlinePgn>e2121106</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">e2121106</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1001/jamanetworkopen.2021.21106</ELocationID><Abstract><AbstractText Label="IMPORTANCE">The aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known.</AbstractText><AbstractText Label="OBJECTIVE">To assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years or older in mainland China.</AbstractText><AbstractText Label="DESIGN, SETTING. AND PARTICIPANTS">This cross-sectional study, the China Osteoporosis Prevalence Study, was conducted from December 2017 to August 2018. A random sample of individuals aged 20 years or older who represented urban and rural areas of China were enrolled, with a 99% participation rate.</AbstractText><AbstractText Label="MAIN OUTCOMES AND MEASURES">Weighted prevalence of osteoporosis, clinical fracture, and vertebral fracture by age, sex, and urban vs rural residence as determined by x-ray absorptiometry, questionnaire, and radiography.</AbstractText><AbstractText Label="RESULTS">A total of 20 416 participants were included in this study; 20 164 (98.8%; 11 443 women [56.7%]; mean [SD] age, 53 [13] years) had a qualified x-ray absorptiometry image and completed the questionnaire, and 8423 of 8800 (95.7%) had a qualified spine radiograph. The prevalence of osteoporosis among those aged 40 years or older was 5.0% (95% CI, 4.2%-5.8%) among men and 20.6% (95% CI, 19.3%-22.0%) among women. The prevalence of vertebral fracture was 10.5% (95% CI, 9.0%-12.0%) among men and 9.7% (95% CI, 8.2%-11.1%) among women. The prevalence of clinical fracture in the past 5 years was 4.1% (95% CI, 3.3%-4.9%) among men and 4.2% (95% CI, 3.6%-4.7%) among women. Among men and women, 0.3% (95% CI, 0.0%-0.7%) and 1.4% (95% CI, 0.8%-2.0%), respectively, with osteoporosis diagnosed on the basis of bone mineral density or with fracture were receiving antiosteoporosis treatment to prevent fracture.</AbstractText><AbstractText Label="CONCLUSIONS AND RELEVANCE">In this cross-sectional study of an adult population in mainland China, the prevalence of osteoporosis and vertebral fracture were high and the prevalence of vertebral fracture and clinical fracture was similarly high in men and women. These findings suggest that current guidelines for screening and treatment of fractures among patients in China should focus equally on men and women and should emphasize the prevention of vertebral fractures.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Linhong</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yin</LastName><ForeName>Xiangjun</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Division of Elderly Health, National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cui</LastName><ForeName>Lijia</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Shunyu</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Elderly Health, National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Ning</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cui</LastName><ForeName>Lu</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Elderly Health, National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Medical Sciences Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Qiang</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Lin</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, Army Medical University, Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Hua</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Orthopaedics, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jin</LastName><ForeName>Xiaolan</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Endocrinology, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dong</LastName><ForeName>Zhong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Beijing Center for Diseases Prevention and Control, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ren</LastName><ForeName>Zeping</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Shanxi Provincial Center for Disease Control and Prevention, Taiyuan, Shanxi Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hou</LastName><ForeName>Zhulin</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Jilin Provincial Center for Disease Control and Prevention, Changchun, Jilin Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Yongqing</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhong</LastName><ForeName>Jieming</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shunxiang</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Yuan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Hunan Provincial Center for Disease Control and Prevention, Changsha, Hunan Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meng</LastName><ForeName>Ruilin</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deng</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Xianbin</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Chongqing Center for Disease Control and Prevention, Chongqing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ma</LastName><ForeName>Jingang</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Shaanxi Provincial Center for Disease Control and Prevention, Xi'an, Shaanxi Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Zhongjian</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Lin</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Wen</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, Guangdong Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Mengmeng</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Osteoporosis, Jilin FAW General Hospital, Changchun, Jilin Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ying</LastName><ForeName>Qifeng</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Center of Osteoporosis, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zeng</LastName><ForeName>Yuhong</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Osteoporosis, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dong</LastName><ForeName>Jin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Endocrinology, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cummings</LastName><ForeName>Steven R</ForeName><Initials>SR</Initials><AffiliationInfo><Affiliation>San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Zhixin</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xia</LastName><ForeName>Weibo</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>08</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>JAMA Netw Open</MedlineTA><NlmUniqueID>101729235</NlmUniqueID><ISSNLinking>2574-3805</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002681" MajorTopicYN="N" Type="Geographic">China</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003430" MajorTopicYN="N">Cross-Sectional Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010024" MajorTopicYN="N">Osteoporosis</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="Y">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058866" MajorTopicYN="N">Osteoporotic Fractures</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="Y">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015995" MajorTopicYN="N">Prevalence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012111" MajorTopicYN="N">Residence Characteristics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016103" MajorTopicYN="N">Spinal Fractures</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading></MeshHeadingList><CoiStatement><b>Conflict of Interest Disclosures:</b> Drs Wang, Yu, Yin, Lijia Cui, Tang, and Jiang; Ms Lu Cui; Drs Zhao, Q. Lin, Chen, H. Lin, and Jin; Ms Z. Dong; Ms Ren; Mr Hou; Ms Y. Zhang; Mr Zhong; Mr Cai; Drs Liu, Meng, and Deng; Mr Ding; Drs Ma and Xie; Mr Wu; Ms M. Zhang; Drs Zeng and J. Dong; Mr Li; and Dr Xia reported receiving grants from the Chinese Central Government Key Project of Public Health Program and grants from the Chinese Red Cross Foundation during the conduct of the study. No other disclosures were reported.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>8</Month><Day>16</Day><Hour>12</Hour><Minute>56</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>8</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>1</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2021</Year><Month>8</Month><Day>16</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34398202</ArticleId><ArticleId IdType="pmc">PMC8369359</ArticleId><ArticleId IdType="doi">10.1001/jamanetworkopen.2021.21106</ArticleId><ArticleId IdType="pii">2783043</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>GBD 2017 Mortality Collaborators . Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1684-1735. doi:10.1016/S0140-6736(18)31891-9</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0140-6736(18)31891-9</ArticleId><ArticleId IdType="pmc">PMC6227504</ArticleId><ArticleId IdType="pubmed">30496102</ArticleId></ArticleIdList></Reference><Reference><Citation>National Bureau of Statistics of People&#x2019;s Republic of China . 2018 Statistical bulletin of national economic and social development. 2019. Accessed January 2, 2021. http://www.stats.gov.cn/tjsj/tjgb/ndtjgb/index.html</Citation></Reference><Reference><Citation>Yu F, Xia W. The epidemiology of osteoporosis, associated fragility fractures, and management gap in China. Arch Osteoporos. 2019;14(1):32. doi:10.1007/s11657-018-0549-y</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s11657-018-0549-y</ArticleId><ArticleId IdType="pubmed">30848398</ArticleId></ArticleIdList></Reference><Reference><Citation>Kung AW, Fan T, Xu L, et al. . Factors influencing diagnosis and treatment of osteoporosis after a fragility fracture among postmenopausal women in Asian countries: a retrospective study. BMC Womens Health. 2013;13:7. doi:10.1186/1472-6874-13-7</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/1472-6874-13-7</ArticleId><ArticleId IdType="pmc">PMC3637813</ArticleId><ArticleId IdType="pubmed">23410131</ArticleId></ArticleIdList></Reference><Reference><Citation>Cui L, Chen L, Xia W, et al. . Vertebral fracture in postmenopausal Chinese women: a population-based study. Osteoporos Int. 2017;28(9):2583-2590. doi:10.1007/s00198-017-4085-1</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-017-4085-1</ArticleId><ArticleId IdType="pubmed">28560474</ArticleId></ArticleIdList></Reference><Reference><Citation>Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993;8(9):1137-1148. doi:10.1002/jbmr.5650080915</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/jbmr.5650080915</ArticleId><ArticleId IdType="pubmed">8237484</ArticleId></ArticleIdList></Reference><Reference><Citation>2010 Population Census. 2013. Accessed Sep 28, 2019. http://www.stats.gov.cn/english/Statisticaldata/CensusData</Citation></Reference><Reference><Citation>Package survey, analysis of complex survey samples. Version 3.36: R package; 2019.</Citation></Reference><Reference><Citation>Kanis JA, Melton LJ III, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9(8):1137-1141. doi:10.1002/jbmr.5650090802</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/jbmr.5650090802</ArticleId><ArticleId IdType="pubmed">7976495</ArticleId></ArticleIdList></Reference><Reference><Citation>Li N, Ou P, Zhu H, Yang D, Zheng P. Prevalence rate of osteoporosis in the mid-aged and elderly in selected parts of China. Chin Med J (Engl). 2002;115(5):773-775.</Citation><ArticleIdList><ArticleId IdType="pubmed">12133555</ArticleId></ArticleIdList></Reference><Reference><Citation>Ling X, Cummings SR, Mingwei Q, et al. . Vertebral fractures in Beijing, China: the Beijing Osteoporosis Project. J Bone Miner Res. 2000;15(10):2019-2025. doi:10.1359/jbmr.2000.15.10.2019</Citation><ArticleIdList><ArticleId IdType="doi">10.1359/jbmr.2000.15.10.2019</ArticleId><ArticleId IdType="pubmed">11028456</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhu H, Fang J, Luo X, et al. . A survey of bone mineral density of healthy Han adults in China. Osteoporos Int. 2010;21(5):765-772. doi:10.1007/s00198-009-1010-2</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-009-1010-2</ArticleId><ArticleId IdType="pubmed">19597908</ArticleId></ArticleIdList></Reference><Reference><Citation>Zeng Q, Li N, Wang Q, et al. . The prevalence of osteoporosis in China, a nationwide, multicenter DXA survey. J Bone Miner Res. 2019;34(10):1789-1797. doi:10.1002/jbmr.3757</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/jbmr.3757</ArticleId><ArticleId IdType="pubmed">31067339</ArticleId></ArticleIdList></Reference><Reference><Citation>Cheng XG, Yang DZ, Zhou Q, et al. . Age-related bone mineral density, bone loss rate, prevalence of osteoporosis, and reference database of women at multiple centers in China. J Clin Densitom. 2007;10(3):276-284. doi:10.1016/j.jocd.2007.05.004</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jocd.2007.05.004</ArticleId><ArticleId IdType="pubmed">17604665</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang ZQ, Ho SC, Chen ZQ, Zhang CX, Chen YM. Reference values of bone mineral density and prevalence of osteoporosis in Chinese adults. Osteoporos Int. 2014;25(2):497-507. doi:10.1007/s00198-013-2418-2</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-013-2418-2</ArticleId><ArticleId IdType="pubmed">23800746</ArticleId></ArticleIdList></Reference><Reference><Citation>Looker AC, Sarafrazi Isfahani N, Fan B, Shepherd JA. Trends in osteoporosis and low bone mass in older US adults, 2005-2006 through 2013-2014. Osteoporos Int. 2017;28(6):1979-1988. doi:10.1007/s00198-017-3996-1</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-017-3996-1</ArticleId><ArticleId IdType="pmc">PMC7891684</ArticleId><ArticleId IdType="pubmed">28315954</ArticleId></ArticleIdList></Reference><Reference><Citation>Tenenhouse A, Joseph L, Kreiger N, et al. ; CaMos Research Group.Canadian Multicentre Osteoporosis Study . Estimation of the prevalence of low bone density in Canadian women and men using a population-specific DXA reference standard: the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int. 2000;11(10):897-904. doi:10.1007/s001980070050</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s001980070050</ArticleId><ArticleId IdType="pubmed">11199195</ArticleId></ArticleIdList></Reference><Reference><Citation>H&#xe4;ussler B, Gothe H, G&#xf6;l D, Glaeske G, Pientka L, Felsenberg D. Epidemiology, treatment and costs of osteoporosis in Germany&#x2014;the BoneEVA Study. Osteoporos Int. 2007;18(1):77-84. doi:10.1007/s00198-006-0206-y</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-006-0206-y</ArticleId><ArticleId IdType="pubmed">17048064</ArticleId></ArticleIdList></Reference><Reference><Citation>Holt G, Khaw KT, Reid DM, et al. . Prevalence of osteoporotic bone mineral density at the hip in Britain differs substantially from the US over 50 years of age: implications for clinical densitometry. Br J Radiol. 2002;75(897):736-742. doi:10.1259/bjr.75.897.750736</Citation><ArticleIdList><ArticleId IdType="doi">10.1259/bjr.75.897.750736</ArticleId><ArticleId IdType="pubmed">12200242</ArticleId></ArticleIdList></Reference><Reference><Citation>Park EJ, Joo IW, Jang MJ, Kim YT, Oh K, Oh HJ. Prevalence of osteoporosis in the Korean population based on Korea National Health and Nutrition Examination Survey (KNHANES), 2008-2011. Yonsei Med J. 2014;55(4):1049-1057. doi:10.3349/ymj.2014.55.4.1049</Citation><ArticleIdList><ArticleId IdType="doi">10.3349/ymj.2014.55.4.1049</ArticleId><ArticleId IdType="pmc">PMC4075366</ArticleId><ArticleId IdType="pubmed">24954336</ArticleId></ArticleIdList></Reference><Reference><Citation>Yoshimura N, Muraki S, Oka H, et al. . Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: the research on osteoarthritis/osteoporosis against disability study. J Bone Miner Metab. 2009;27(5):620-628. doi:10.1007/s00774-009-0080-8</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00774-009-0080-8</ArticleId><ArticleId IdType="pubmed">19568689</ArticleId></ArticleIdList></Reference><Reference><Citation>Balk EM, Adam GP, Langberg VN, et al. ; International Osteoporosis Foundation Calcium Steering Committee . Global dietary calcium intake among adults: a systematic review. Osteoporos Int. 2017;28(12):3315-3324. doi:10.1007/s00198-017-4230-x</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-017-4230-x</ArticleId><ArticleId IdType="pmc">PMC5684325</ArticleId><ArticleId IdType="pubmed">29026938</ArticleId></ArticleIdList></Reference><Reference><Citation>Jiang G, Eastell R, Barrington NA, Ferrar L. Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis. Osteoporos Int. 2004;15(11):887-896. doi:10.1007/s00198-004-1626-1</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-004-1626-1</ArticleId><ArticleId IdType="pubmed">15071725</ArticleId></ArticleIdList></Reference><Reference><Citation>Kwok AW, Gong JS, Wang YX, et al. . Prevalence and risk factors of radiographic vertebral fractures in elderly Chinese men and women: results of Mr. OS (Hong Kong) and Ms. OS (Hong Kong) studies. Osteoporos Int. 2013;24(3):877-885. doi:10.1007/s00198-012-2040-8</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-012-2040-8</ArticleId><ArticleId IdType="pubmed">22707064</ArticleId></ArticleIdList></Reference><Reference><Citation>Cosman F, Krege JH, Looker AC, et al. . Spine fracture prevalence in a nationally representative sample of US women and men aged &#x2265;40 years: results from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. Osteoporos Int. 2017;28(6):1857-1866. doi:10.1007/s00198-017-3948-9</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-017-3948-9</ArticleId><ArticleId IdType="pmc">PMC7422504</ArticleId><ArticleId IdType="pubmed">28175980</ArticleId></ArticleIdList></Reference><Reference><Citation>Cummings SR, Ferrari S, Eastell R, et al. . Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res. 2018;33(2):190-198. doi:10.1002/jbmr.3337</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/jbmr.3337</ArticleId><ArticleId IdType="pubmed">29105841</ArticleId></ArticleIdList></Reference><Reference><Citation>Gao C, Xu Y, Li L, et al. . Prevalence of osteoporotic vertebral fracture among community-dwelling elderly in Shanghai. Chin Med J (Engl). 2019;132(14):1749-1751. doi:10.1097/CM9.0000000000000332</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/CM9.0000000000000332</ArticleId><ArticleId IdType="pmc">PMC6759100</ArticleId><ArticleId IdType="pubmed">31261209</ArticleId></ArticleIdList></Reference><Reference><Citation>Kwok AW, Leung JC, Chan AY, et al. . Prevalence of vertebral fracture in Asian men and women: comparison between Hong Kong, Thailand, Indonesia and Japan. Public Health. 2012;126(6):523-531. doi:10.1016/j.puhe.2012.03.002</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.puhe.2012.03.002</ArticleId><ArticleId IdType="pubmed">22560410</ArticleId></ArticleIdList></Reference><Reference><Citation>Str&#xf6;m O, Borgstr&#xf6;m F, Kanis JA, et al. . Osteoporosis: burden, health care provision and opportunities in the EU: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2011;6:59-155. doi:10.1007/s11657-011-0060-1</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s11657-011-0060-1</ArticleId><ArticleId IdType="pubmed">22886101</ArticleId></ArticleIdList></Reference><Reference><Citation>Cosman F, de Beur SJ, LeBoff MS, et al. ; National Osteoporosis Foundation . Clinician&#x2019;s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2381. doi:10.1007/s00198-014-2794-2</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-014-2794-2</ArticleId><ArticleId IdType="pmc">PMC4176573</ArticleId><ArticleId IdType="pubmed">25182228</ArticleId></ArticleIdList></Reference><Reference><Citation>Kanis JA, McCloskey E, Johansson H, Oden A, Leslie WD. FRAX(&#xae;) with and without bone mineral density. Calcif Tissue Int. 2012;90(1):1-13. doi:10.1007/s00223-011-9544-7</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00223-011-9544-7</ArticleId><ArticleId IdType="pubmed">22057815</ArticleId></ArticleIdList></Reference><Reference><Citation>Cummings SR, Nevitt MC, Browner WS, et al. ; Study of Osteoporotic Fractures Research Group . Risk factors for hip fracture in white women. N Engl J Med. 1995;332(12):767-773. doi:10.1056/NEJM199503233321202</Citation><ArticleIdList><ArticleId IdType="doi">10.1056/NEJM199503233321202</ArticleId><ArticleId IdType="pubmed">7862179</ArticleId></ArticleIdList></Reference><Reference><Citation>Cummings SR. Are patients with hip fractures more osteoporotic? review of the evidence. Am J Med. 1985;78(3):487-494. doi:10.1016/0002-9343(85)90343-2</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/0002-9343(85)90343-2</ArticleId><ArticleId IdType="pubmed">3976707</ArticleId></ArticleIdList></Reference><Reference><Citation>Camacho PM, Petak SM, Binkley N, et al. . American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis&#x2014;2020 update. Endocr Pract. 2020;26(suppl 1):1-46. doi:10.4158/GL-2020-0524SUPPL</Citation><ArticleIdList><ArticleId IdType="doi">10.4158/GL-2020-0524SUPPL</ArticleId><ArticleId IdType="pubmed">32427503</ArticleId></ArticleIdList></Reference><Reference><Citation>Kanis JA, Cooper C, Rizzoli R, Reginster JY; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO); Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF) . European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2019;30(1):3-44. doi:10.1007/s00198-018-4704-5</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00198-018-4704-5</ArticleId><ArticleId IdType="pmc">PMC7026233</ArticleId><ArticleId IdType="pubmed">30324412</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">34159513</PMID><DateCompleted><Year>2022</Year><Month>04</Month><Day>08</Day></DateCompleted><DateRevised><Year>2022</Year><Month>04</Month><Day>08</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1554-3528</ISSN><JournalIssue CitedMedium="Internet"><Volume>54</Volume><Issue>1</Issue><PubDate><Year>2022</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Behavior research methods</Title><ISOAbbreviation>Behav Res Methods</ISOAbbreviation></Journal><ArticleTitle>Objective ages of acquisition for 3300+ simplified Chinese characters.</ArticleTitle><Pagination><StartPage>311</StartPage><EndPage>323</EndPage><MedlinePgn>311-323</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3758/s13428-021-01626-1</ELocationID><Abstract><AbstractText>We report the construction of two age-of-acquisition (AoA) norms for 3300+ characters in simplified Chinese, which make up about 99% of the texts used in daily life. We determined a character's AoA according to the time in which the character is formally learned in two sets of leading textbooks of Chinese in compulsory education, published respectively on the basis of the 2001 and 2011 national curriculum. Apart from having a significantly larger coverage of characters than previous norms, the current norms also outperformed them in explaining accuracy and reaction times in four large-scale databases for character decision, character naming, or character handwriting, even after controlling for the effects of frequency, number of meanings, and number of strokes. The explanatory advantage of the current norms suggests that, compared to earlier norms, the current norms capture more up-to-date character AoAs; these findings also highlight the diachronic nature of some lexical variables such as AoA and frequency. The developed objective AoA norms can be used for subsequent research on Chinese character recognition or production.</AbstractText><CopyrightInformation>&#xa9; 2021. The Psychonomic Society, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Zhenguang G</ForeName><Initials>ZG</Initials><AffiliationInfo><Affiliation>Department of Linguistics and Modern Languages, The Chinese University of Hong Kong, Sha Tin, N.T, Hong Kong, SAR, China. zhenguangcai@cuhk.edu.hk.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Brain and Mind Institute, The Chinese University of Hong Kong, Hong Kong, SAR, China. zhenguangcai@cuhk.edu.hk.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Shuting</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Linguistics and Modern Languages, The Chinese University of Hong Kong, Sha Tin, N.T, Hong Kong, SAR, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Zebo</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Linguistics and Modern Languages, The Chinese University of Hong Kong, Sha Tin, N.T, Hong Kong, SAR, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Translation, Interpreting and Intercultural Studies, Hong Kong Baptist University, Hong Kong, SAR, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>06</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Behav Res Methods</MedlineTA><NlmUniqueID>101244316</NlmUniqueID><ISSNLinking>1554-351X</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002681" MajorTopicYN="N" Type="Geographic">China</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006236" MajorTopicYN="Y">Handwriting</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007802" MajorTopicYN="Y">Language</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007858" MajorTopicYN="N">Learning</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011932" MajorTopicYN="N">Reading</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D021641" MajorTopicYN="N">Recognition, Psychology</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Age of acquisition</Keyword><Keyword MajorTopicYN="N">Character</Keyword><Keyword MajorTopicYN="N">Chinese</Keyword><Keyword MajorTopicYN="N">Lexical processing</Keyword><Keyword MajorTopicYN="N">Textbook</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>5</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>6</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>4</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>6</Month><Day>23</Day><Hour>7</Hour><Minute>30</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34159513</ArticleId><ArticleId IdType="doi">10.3758/s13428-021-01626-1</ArticleId><ArticleId IdType="pii">10.3758/s13428-021-01626-1</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Alonso, M. A., Fernandez, A., &amp; D&#xed;ez, E. (2015). Subjective age-of-acquisition norms for 7,039 Spanish words. Behavior Research Methods, 47(1), 268&#x2013;274.</Citation><ArticleIdList><ArticleId IdType="pubmed">24578152</ArticleId></ArticleIdList></Reference><Reference><Citation>&#xc1;lvarez, B., &amp; Cuetos, F. (2007). Objective age of acquisition norms for a set of 328 words in Spanish. Behavior Research Methods, 39(3), 377&#x2013;383.</Citation><ArticleIdList><ArticleId IdType="pubmed">17958148</ArticleId></ArticleIdList></Reference><Reference><Citation>Anderson, K. L., &amp; Cottrell, G. W. (2001). Age of Acquisition in Connectionist Networks. Paper presented at the Proceedings of the Annual Meeting of the Cognitive Science Society.</Citation></Reference><Reference><Citation>Arnon, I., McCauley, S. M., &amp; Christiansen, M. H. (2017). Digging up the building blocks of language: Age-of-acquisition effects for multiword phrases. Journal of Memory and Language, 92, 265&#x2013;280.</Citation></Reference><Reference><Citation>Barry, C., Hirsh, K. W., Johnston, R. A., &amp; Williams, C. L. (2001). Age of acquisition, word frequency, and the locus of repetition priming of picture naming. Journal of Memory and Language, 44(3), 350&#x2013;375.</Citation></Reference><Reference><Citation>Birchenough, J. M., Davies, R., &amp; Connelly, V. (2017). Rated age-of-acquisition norms for over 3,200 German words. Behavior Research Methods, 49(2), 484&#x2013;501.</Citation><ArticleIdList><ArticleId IdType="pubmed">26944578</ArticleId></ArticleIdList></Reference><Reference><Citation>Bird, H., Franklin, S., &amp; Howard, D. (2001). Age of acquisition and imageability ratings for a large set of words, including verbs and function words. Behavior Research Methods, Instruments, &amp; Computers, 33(1), 73&#x2013;79. https://doi.org/10.3758/BF03195349</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/BF03195349</ArticleId></ArticleIdList></Reference><Reference><Citation>Bonin, P., Barry, C., M&#xe9;ot, A., &amp; Chalard, M. (2004). The influence of age of acquisition in word reading and other tasks: A never ending story? Journal of Memory and Language, 50(4), 456&#x2013;476.</Citation></Reference><Reference><Citation>Bonin, P., Chalard, M., M&#xe9;ot, A., &amp; Fayol, M. (2002). The determinants of spoken and written picture naming latencies. British Journal of Psychology, 93(1), 89&#x2013;114.</Citation><ArticleIdList><ArticleId IdType="pubmed">11839103</ArticleId></ArticleIdList></Reference><Reference><Citation>Bonin, P., Fayol, M., &amp; Chalard, M. (2001). Age of acquisition and word frequency in written picture naming. The Quarterly Journal of Experimental Psychology Section A, 54(2), 469&#x2013;489. https://doi.org/10.1080/713755968</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/713755968</ArticleId></ArticleIdList></Reference><Reference><Citation>Bonin, P., &amp; M&#xe9;ot, A. (2002). Writing to dictation in real time in adults: What are the determinants of written latencies. Advances in psychology research, 16, 139&#x2013;165.</Citation></Reference><Reference><Citation>Brown, G. D., &amp; Watson, F. L. (1987). First in, first out: Word learning age and spoken word frequency as predictors of word familiarity and word naming latency. Memory &amp; Cognition, 15(3), 208&#x2013;216.</Citation></Reference><Reference><Citation>Brysbaert, M., &amp; Biemiller, A. (2017). Test-based age-of-acquisition norms for 44 thousand English word meanings. Behavior research methods, 49(4), 1520&#x2013;1523.</Citation><ArticleIdList><ArticleId IdType="pubmed">27659480</ArticleId></ArticleIdList></Reference><Reference><Citation>Brysbaert, M., &amp; Cortese, M. J. (2011). Do the effects of subjective frequency and age of acquisition survive better word frequency norms? Quarterly Journal of Experimental Psychology, 64(3), 545&#x2013;559.</Citation></Reference><Reference><Citation>Brysbaert, M., &amp; Ghyselinck, M. (2006). The effect of age of acquisition: Partly frequency related, partly frequency independent. Visual cognition, 13(7&#x2013;8), 992&#x2013;1011.</Citation></Reference><Reference><Citation>Brysbaert, M., Lange, M., &amp; Wijnendaele, I. V. (2000). The effects of age-of-acquisition and frequency-of-occurrence in visual word recognition: Further evidence from the Dutch language. European Journal of Cognitive Psychology, 12(1), 65&#x2013;85.</Citation></Reference><Reference><Citation>Brysbaert, M., &amp; New, B. (2009). Moving beyond Ku&#x10d;era and Francis: A critical evaluation of current word frequency norms and the introduction of a new and improved word frequency measure for American English. Behavior Research Methods, 41(4), 977&#x2013;990.</Citation><ArticleIdList><ArticleId IdType="pubmed">19897807</ArticleId></ArticleIdList></Reference><Reference><Citation>Brysbaert, M., Warriner, A. B., &amp; Kuperman, V. (2014). Concreteness ratings for 40 thousand generally known English word lemmas. Behavior Research Methods, 46(3), 904&#x2013;911.</Citation><ArticleIdList><ArticleId IdType="pubmed">24142837</ArticleId></ArticleIdList></Reference><Reference><Citation>Burgess, C., &amp; Livesay, K. (1998). The effect of corpus size in predicting reaction time in a basic word recognition task: Moving on from Ku&#x10d;era and Francis. Behavior Research Methods, Instruments, &amp; Computers, 30(2), 272&#x2013;277.</Citation></Reference><Reference><Citation>Bylund, E., Abrahamsson, N., Hyltenstam, K., &amp; Norrman, G. (2019). Revisiting the bilingual lexical deficit: The impact of age of acquisition. Cognition, 182, 45&#x2013;49.</Citation><ArticleIdList><ArticleId IdType="pubmed">30216899</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai, Q., &amp; Brysbaert, M. (2010). SUBTLEX-CH: Chinese Word and Character Frequencies Based on Film Subtitles. PLoS ONE, 5(6), e10729. https://doi.org/10.1371/journal.pone.0010729 .</Citation><ArticleIdList><ArticleId IdType="doi">10.1371/journal.pone.0010729</ArticleId><ArticleId IdType="pubmed">20532192</ArticleId><ArticleId IdType="pmc">2880003</ArticleId></ArticleIdList></Reference><Reference><Citation>Carroll, J. B., &amp; White, M. N. (1973). Word frequency and age of acquisition as determiners of picture-naming latency. The Quarterly Journal of Experimental Psychology, 25(1), 85&#x2013;95.</Citation></Reference><Reference><Citation>Catling, J., Dent, K., Preece, E., &amp; Johnston, R. (2013). Age-of-acquisition effects in novel picture naming: A laboratory analogue. Quarterly Journal of Experimental Psychology, 66(9), 1756&#x2013;1763.</Citation></Reference><Reference><Citation>Chalard, M., Bonin, P., M&#xe9;ot, A., Boyer, B., &amp; Fayol, M. (2003). Objective age-of-acquisition (AoA) norms for a set of 230 object names in French: Relationships with psycholinguistic variables, the English data from Morrison et al.(1997), and naming latencies. European Journal of Cognitive Psychology, 15(2), 209&#x2013;245.</Citation></Reference><Reference><Citation>Chang, Y. N., Hsu, C. H., Tsai, J. L., Chen, C. L., &amp; Lee, C. Y. (2016). A psycholinguistic database for traditional Chinese character naming. Behavior Research Methods, 48(1), 112&#x2013;122.</Citation><ArticleIdList><ArticleId IdType="pubmed">25630311</ArticleId></ArticleIdList></Reference><Reference><Citation>Chang, Y. N., &amp; Lee, C. Y. (2020). Age of Acquisition Effects on Traditional Chinese Character Naming and Lexical Decision. Psychonomic Bulletin &amp; Review, 27(6), 1317&#x2013;1324.</Citation></Reference><Reference><Citation>Chen, B., Dent, K., You, W., &amp; Wu, G. (2009). Age of acquisition affects early orthographic processing during Chinese character recognition. Acta Psychologica, 130(3), 196&#x2013;203.</Citation><ArticleIdList><ArticleId IdType="pubmed">19162255</ArticleId></ArticleIdList></Reference><Reference><Citation>Chen, B., Wang, L., Wang, L., &amp; Peng, D. (2004). The effect of age of word acquisition and frequency on the identification of Chinese double-character words (&#x8bcd;&#x6c47;&#x4e60;&#x5f97;&#x5e74;&#x9f84;&#x548c;&#x9891;&#x7387;&#x5bf9;&#x8bcd;&#x6c47;&#x8bc6;&#x522b;&#x7684;&#x5f71;&#x54cd;). Psychological Science, 27(5), 1060&#x2013;1064.</Citation></Reference><Reference><Citation>Chen, B., You, W., &amp; Zhou, H. (2007). Age of Acquisition Effects in Reading Chinese: Evidence in Favor of the Semantic Hypothesis (&#x6c49;&#x8bed;&#x8bcd;&#x6c47;&#x4e60;&#x5f97;&#x7684;&#x5e74;&#x9f84;&#x6548;&#x5e94;: &#x8bed;&#x4e49;&#x5047;&#x8bbe;&#x7684;&#x8bc1;&#x636e;). Acta Psychologica Sinica, 39(1), 9&#x2013;17.</Citation></Reference><Reference><Citation>Chen, B., Zhou, H., Dunlap, S., &amp; Perfetti, C. A. (2007). Age of acquisition effects in reading Chinese: Evidence in favour of the arbitrary mapping hypothesis. British Journal of Psychology, 98(3), 499&#x2013;516.</Citation><ArticleIdList><ArticleId IdType="pubmed">17705943</ArticleId></ArticleIdList></Reference><Reference><Citation>Cortese, M. J., &amp; Khanna, M. M. (2008). Age of acquisition ratings for 3,000 monosyllabic words. Behavior Research Methods, 40(3), 791&#x2013;794. https://doi.org/10.3758/BRM.40.3.791</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/BRM.40.3.791</ArticleId><ArticleId IdType="pubmed">18697675</ArticleId></ArticleIdList></Reference><Reference><Citation>Donnelly, S., &amp; Verkuilen, J. (2017). Empirical logit analysis is not logistic regression. Journal of Memory and Language, 94, 28&#x2013;42.</Citation></Reference><Reference><Citation>Ellis, A. W., Burani, C., Izura, C., Bromiley, A., &amp; Venneri, A. (2006). Traces of vocabulary acquisition in the brain: Evidence from covert object naming. Neuroimage, 33(3), 958&#x2013;968. https://doi.org/10.1016/j.neuroimage.2006.07.040</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.neuroimage.2006.07.040</ArticleId><ArticleId IdType="pubmed">16987673</ArticleId></ArticleIdList></Reference><Reference><Citation>Ellis, A. W., &amp; Lambon Ralph, M. A. (2000). Age of acquisition effects in adult lexical processing reflect loss of plasticity in maturing systems: Insights from connectionist networks. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26(5), 1103&#x2013;1123.</Citation><ArticleIdList><ArticleId IdType="pubmed">11009247</ArticleId></ArticleIdList></Reference><Reference><Citation>Fenson, L., Marchman, V.A., Thal, D., Dale, P.S., Reznick, J.S., &amp; Bates, E. (2007). MacArthur-Bates Communicative Development Inventories: User&#x2019;s guide and technical manual (2nd edn.). Brookes Publishing.</Citation></Reference><Reference><Citation>Ferrand, L., Brysbaert, M., Keuleers, E., New, B., Bonin, P., M&#xe9;ot, A., ... Pallier, C. (2011). Comparing word processing times in naming, lexical decision, and progressive demasking: Evidence from Chronolex. Frontiers in Psychology, 2, 306.</Citation></Reference><Reference><Citation>Fiebach, C. J., Friederici, A. D., M&#xfc;ller, K., von Cramon, D. Y., &amp; Hernandez, A. E. (2003). Distinct brain representations for early and late learned words. Neuroimage, 19(4), 1627&#x2013;1637. https://doi.org/10.1016/S1053-8119(03)00227-1</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S1053-8119(03)00227-1</ArticleId><ArticleId IdType="pubmed">12948717</ArticleId></ArticleIdList></Reference><Reference><Citation>Frank, M. C., Braginsky, M., Yurovsky, D., &amp; Marchman, V. A. (2017). Wordbank: An open repository for developmental vocabulary data. Journal of child language, 44(3), 677&#x2013;694.</Citation><ArticleIdList><ArticleId IdType="pubmed">27189114</ArticleId></ArticleIdList></Reference><Reference><Citation>Gerhand, S., &amp; Barry, C. (1998). Word frequency effects in oral reading are not merely age-of-acquisition effects in disguise. Journal of Experimental Psychology: Learning, Memory, and Cognition, 24(2), 267.</Citation></Reference><Reference><Citation>Gerhand, S., &amp; Barry, C. (1999a). Age-of-acquisition and frequency effects in speeded word naming. Cognition, 73(2), B27&#x2013;B36.</Citation><ArticleIdList><ArticleId IdType="pubmed">10580164</ArticleId></ArticleIdList></Reference><Reference><Citation>Gerhand, S., &amp; Barry, C. (1999b). Age of acquisition, word frequency, and the role of phonology in the lexical decision task. Memory &amp; Cognition, 27(4), 592&#x2013;602.</Citation></Reference><Reference><Citation>Ghyselinck, M., De Moor, W., &amp; Brysbaert, M. (2000). Age-of-acquisition ratings for 2816 Dutch four- and five-letter nouns. Psychologica Belgica, 40, 77&#x2013;98.</Citation></Reference><Reference><Citation>Ghyselinck, M., Lewis, M. B., &amp; Brysbaert, M. (2004). Age of acquisition and the cumulative-frequency hypothesis: A review of the literature and a new multi-task investigation. Acta Psychologica, 115(1), 43&#x2013;67. https://doi.org/10.1016/j.actpsy.2003.11.002</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.actpsy.2003.11.002</ArticleId><ArticleId IdType="pubmed">14734241</ArticleId></ArticleIdList></Reference><Reference><Citation>Gilhooly, K. J., &amp; Gilhooly, M. L. (1979). Age-of-acquisition effects in lexical and episodic memory tasks. Memory &amp; Cognition, 7(3), 214&#x2013;223. https://doi.org/10.3758/BF03197541 .</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/BF03197541</ArticleId></ArticleIdList></Reference><Reference><Citation>Gilhooly, K. J., &amp; Gilhooly, M. L. M. (1980). The validity of age-of-acquisition ratings. British Journal of Psychology 71, 105&#x2013;110.</Citation></Reference><Reference><Citation>Gilhooly, K. J., &amp; Logie, R. H. (1980). Age-of-acquisition, imagery, concreteness, familiarity, and ambiguity measures for 1,944 words. Behavior Research Methods &amp; Instrumentation, 12(4), 395&#x2013;427. https://doi.org/10.3758/BF03201693</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/BF03201693</ArticleId></ArticleIdList></Reference><Reference><Citation>Gilhooly, K. J., &amp; Watson, F. (1981). Word age-of-acquisition effects: A review. Current Psychological Reviews, 1(3), 269&#x2013;286.</Citation></Reference><Reference><Citation>G&#xf6;z, &#x130;., Tekcan, A. &#x130;., &amp; Erciyes, A. A. (2017). Subjective age-of-acquisition norms for 600 Turkish words from four age groups. Behavior Research Methods, 49(5), 1736&#x2013;1746.</Citation><ArticleIdList><ArticleId IdType="pubmed">27743317</ArticleId></ArticleIdList></Reference><Reference><Citation>Grigoriev, A., &amp; Oshhepkov, I. (2013). Objective age of acquisition norms for a set of 286 words in Russian: Relationships with other psycholinguistic variables. Behavior Research Methods, 45(4), 1208&#x2013;1217.</Citation><ArticleIdList><ArticleId IdType="pubmed">23435657</ArticleId></ArticleIdList></Reference><Reference><Citation>Hao, M., Liu, Y., Shu, H., &amp; Cheng, C. (2003). The role of age of acquisition on picture naming in Chinese (&#x6c49;&#x8bed;&#x56fe;&#x7247;&#x547d;&#x540d;&#x4e2d;&#x83b7;&#x5f97;&#x5e74;&#x9f84;&#x7684;&#x4f5c;&#x7528;). Studies of Psychology and Behavior, 1(4), 268&#x2013;273.</Citation></Reference><Reference><Citation>Huang, S., Lin, W., Xu, M., Wang, R., &amp; Cai, Z.G. (in press). On the tip of the pen: Effects of character-level lexical variables and handwriter-level individual differences on orthographic retrieval difficulties in Chinese handwriting. Quarterly Journal of Experimental Psychology. https://doi.org/10.1177/17470218211004385</Citation></Reference><Reference><Citation>Huang, S., Zhou, Y., Du, M., Wang, R., &amp; Cai, Z. G. (2021). Character amnesia in Chinese handwriting: A mega-study analysis. Language Sciences, 85, 101383.</Citation></Reference><Reference><Citation>Imbir, K. K. (2016). Affective norms for 4900 polish words reload (ANPW_R): assessments for valence, arousal, dominance, origin, significance, concreteness, imageability and, age of acquisition. Frontiers in Psychology, 7, 1081.</Citation><ArticleIdList><ArticleId IdType="pubmed">27486423</ArticleId><ArticleId IdType="pmc">4947584</ArticleId></ArticleIdList></Reference><Reference><Citation>Izura, C., P&#xe9;rez, M. A., Agallou, E., Wright, V. C., Mar&#xed;n, J., Stadthagen-Gonz&#xe1;lez, H., &amp; Ellis, A. W. (2011). Age/order of acquisition effects and the cumulative learning of foreign words: A word training study. Journal of Memory and Language, 64(1), 32&#x2013;58. https://doi.org/10.1016/j.jml.2010.09.002</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jml.2010.09.002</ArticleId></ArticleIdList></Reference><Reference><Citation>Jeffreys, H. (1998). The theory of probability. OUP Oxford.</Citation></Reference><Reference><Citation>Johnston, R. A., &amp; Barry, C. (2006). Age of acquisition and lexical processing. Visual Cognition, 13(7&#x2013;8), 789&#x2013;845. https://doi.org/10.1080/13506280544000066</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/13506280544000066</ArticleId></ArticleIdList></Reference><Reference><Citation>Juhasz, B. J., Yap, M. J., Dicke, J., Taylor, S. C., &amp; Gullick, M. M. (2011). Tangible Words are Recognized Faster: The Grounding of Meaning in Sensory and Perceptual Systems. Quarterly Journal of Experimental Psychology, 64(9), 1683&#x2013;1691. https://doi.org/10.1080/17470218.2011.605150</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/17470218.2011.605150</ArticleId></ArticleIdList></Reference><Reference><Citation>Juhasz, B. J., Yap, M. J., Raoul, A., &amp; Kaye, M. (2019). A further examination of word frequency and age-of-acquisition effects in English lexical decision task performance: The role of frequency trajectory. Journal of Experimental Psychology: Learning, Memory, and Cognition, 45(1), 82.</Citation><ArticleIdList><ArticleId IdType="pubmed">29683706</ArticleId></ArticleIdList></Reference><Reference><Citation>Kass, R. E., &amp; Raftery, A. E. (1995). Bayes factors. Journal of the American Statistical Association, 90(430), 773&#x2013;795.</Citation></Reference><Reference><Citation>Ku&#x10d;era, H., &amp; Francis, W. N. (1967). Computational analysis of present-day American English. Brown University Press</Citation></Reference><Reference><Citation>Kuperman, V., Stadthagen-Gonzalez, H., &amp; Brysbaert, M. (2012). Age-of-acquisition ratings for 30,000 English words. Behavior Research Methods, 44(4), 978&#x2013;990. https://doi.org/10.3758/s13428-012-0210-4</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/s13428-012-0210-4</ArticleId><ArticleId IdType="pubmed">22581493</ArticleId></ArticleIdList></Reference><Reference><Citation>Lachman, R., Shaffer, J. P., &amp; Hennrikus, D. (1974). Language and cognition: Effects of stimulus codability, name&#x2013;word frequency, and age of acquisition on lexical reaction time. Journal of Verbal Learning and Verbal Behavior, 13(6), 613&#x2013;625. https://doi.org/10.1016/S0022-5371(74)80049-6</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0022-5371(74)80049-6</ArticleId></ArticleIdList></Reference><Reference><Citation>Law, S., Weekes, B. S., Yeung, O., &amp; Chiu, K. (2009). Chapter 12: Age of acquisition effects on picture naming in Chinese anomia. In: Law, S. P., Weekes, B., &amp; Wong, A. M. (Eds.), Language disorders in speakers of Chinese. Multilingual Matters.</Citation></Reference><Reference><Citation>Law, S., Wong, W., Yeung, O., &amp; Weekes, B. S. (2008). A case study of the effect of age-of-acquisition on reading aloud in Chinese dyslexia. Neurocase, 14(3), 276&#x2013;289.</Citation><ArticleIdList><ArticleId IdType="pubmed">18704834</ArticleId></ArticleIdList></Reference><Reference><Citation>Law, S., &amp; Yeung, O. (2010). Effects of age of acquisition and semantic transparency on reading characters in Chinese dyslexia. Applied Psycholinguistics, 31(4), 711.</Citation></Reference><Reference><Citation>Lewis, M. B. (1999). Age of acquisition in face categorisation: is there an instance-based account? Cognition, 71(1), B23-B39. https://doi.org/10.1016/S0010-0277(99)00020-7</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0010-0277(99)00020-7</ArticleId><ArticleId IdType="pubmed">10394712</ArticleId></ArticleIdList></Reference><Reference><Citation>Lewis, M. B., Gerhand, S., &amp; Ellis, H. D. (2001). Re-evaluating age-of-acquisition effects: are they simply cumulative-frequency effects? Cognition, 78(2), 189&#x2013;205. https://doi.org/10.1016/S0010-0277(00)00117-7</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0010-0277(00)00117-7</ArticleId><ArticleId IdType="pubmed">11074250</ArticleId></ArticleIdList></Reference><Reference><Citation>Li, C., Zhang, Q., &amp; Huang, R. (2017). The Opposite Effects of Age of Acquisition in Object and Action Pictures Naming (&#x8bcd;&#x6c47;&#x83b7;&#x5f97;&#x5e74;&#x9f84;&#x5728;&#x7269;&#x4f53;&#x548c;&#x52a8;&#x4f5c;&#x56fe;&#x753b;&#x547d;&#x540d;&#x4e2d;&#x7684;&#x4e0d;&#x540c;&#x4f5c;&#x7528;). Psychological Exploration, 37(3), 220&#x2013;225.</Citation></Reference><Reference><Citation>Linguistics Institute of Chinese Academy of Social Sciences. (2011). Xinhua dictionary (&#x65b0;&#x534e;&#x5b57;&#x5178;, version 11). Commercial Press.</Citation></Reference><Reference><Citation>Liu, Y., Hao, M., Li, P., &amp; Shu, H. (2011). Timed picture naming norms for Mandarin Chinese. Plos one, 6(1), e16505.</Citation><ArticleIdList><ArticleId IdType="pubmed">21298065</ArticleId><ArticleId IdType="pmc">3027682</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu, Y., Hao, M., Shu, H., Tan, L. H., &amp; Weekes, B. S. (2008). Age-of-acquisition effects on oral reading in Chinese. Psychonomic Bulletin &amp; Review, 15(2), 344&#x2013;350.</Citation></Reference><Reference><Citation>Liu, Y., Shu, H., &amp; Li, P. (2007). Word naming and psycholinguistic norms: Chinese. Behavior Research Methods, 39(2), 192&#x2013;198. https://doi.org/10.3758/BF03193147</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/BF03193147</ArticleId><ArticleId IdType="pubmed">17695344</ArticleId></ArticleIdList></Reference><Reference><Citation>Lotto, L., Surian, L., &amp; Job, R. (2010). Objective age of acquisition for 223 Italian words: Norms and effects on picture naming speed. Behavior Research Methods, 42(1), 126&#x2013;133.</Citation><ArticleIdList><ArticleId IdType="pubmed">20160292</ArticleId></ArticleIdList></Reference><Reference><Citation>&#x141;uniewska, M., Haman, E., Armon-Lotem, S., Etenkowski, B., Southwood, F., An&#x111;elkovi&#x107;, D., ... de Abreu, P. E. (2016). Ratings of age of acquisition of 299 words across 25 languages: Is there a cross-linguistic order of words? Behavior Research Methods, 48(3), 1154&#x2013;1177.</Citation></Reference><Reference><Citation>McBride-Chang, C., &amp; Ho, C. S. H. (2000). Developmental issues in Chinese children's character acquisition. Journal of Educational Psychology, 92(1), 50&#x2013;55.</Citation></Reference><Reference><Citation>Mermillod, M., Bonin, P., M&#xe9;ot, A., Ferrand, L., &amp; Paindavoine, M. (2012). Computational evidence that frequency trajectory theory does not oppose but emerges from age-of-acquisition theory. Cognitive Science, 36(8), 1499&#x2013;1531.</Citation><ArticleIdList><ArticleId IdType="pubmed">22985438</ArticleId></ArticleIdList></Reference><Reference><Citation>Meschyan, G., &amp; Hernandez, A. (2002). Age of acquisition and word frequency: Determinants of object-naming speed and accuracy. Memory &amp; Cognition, 30(2), 262&#x2013;269.</Citation></Reference><Reference><Citation>Ministry of Education of the People's Republic of China (2011). Curriculum for Chinese in Compulsory Education (2011). [&#x4e49;&#x52a1;&#x6559;&#x80b2;&#x8bed;&#x6587;&#x8bfe;&#x7a0b;&#x6807;&#x51c6;(2011&#x5e74;&#x7248;)]. http://www.moe.gov.cn/srcsite/A26/s8001/201112/t20111228_167340.html . Retrieved on November 10, 2020.</Citation></Reference><Reference><Citation>Ministry of Education of the People's Republic of China (2013). Table of General Standard Chinese Characters [&#x901a;&#x7528;&#x89c4;&#x8303;&#x6c49;&#x5b57;&#x8868;]. http://www.gov.cn/gzdt/att/att/site1/20130819/tygfhzb.pdf . Retrieved on November 10, 2020.</Citation></Reference><Reference><Citation>Moors, A., De Houwer, J., Hermans, D., Wanmaker, S., Van Schie, K., Van Harmelen, A. L., ... &amp; Brysbaert, M. (2013). Norms of valence, arousal, dominance, and age of acquisition for 4,300 Dutch words. Behavior Research Methods, 45(1), 169&#x2013;177.</Citation></Reference><Reference><Citation>Morrison, C. M., Chappell, T. D., &amp; Ellis, A. W. (1997). Age of Acquisition Norms for a Large Set of Object Names and Their Relation to Adult Estimates and Other Variables. The Quarterly Journal of Experimental Psychology Section A, 50(3), 528&#x2013;559. https://doi.org/10.1080/027249897392017</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/027249897392017</ArticleId></ArticleIdList></Reference><Reference><Citation>Morrison, C. M., &amp; Ellis, A. W. (1995). Roles of word frequency and age of acquisition in word naming and lexical decision. Journal of Experimental Psychology: Learning, Memory, and Cognition, 21(1), 116.</Citation></Reference><Reference><Citation>Morrison, C. M., Hirsh, K. W., Chappell, T., &amp; Ellis, A. W. (2002). Age and age of acquisition: An evaluation of the cumulative frequency hypothesis. European Journal of Cognitive Psychology, 14(4), 435&#x2013;459. https://doi.org/10.1080/09541440143000159</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/09541440143000159</ArticleId></ArticleIdList></Reference><Reference><Citation>O&#x2019;Brien, R. M. (2007). A caution regarding rules of thumb for variance inflation factors. Quality &amp; quantity, 41(5), 673&#x2013;690.</Citation></Reference><Reference><Citation>Perez, M., &amp; Naval&#xf3;n, C. (2005). Objective&#x2013;AoA norms for 175 names in Spanish: Relationships with other psycholinguistic variables, estimated AoA, and data from other languages. European Journal of Cognitive Psychology, 17(2), 179&#x2013;206.</Citation></Reference><Reference><Citation>P&#xe9;rez, M. A. (2007). Age of acquisition persists as the main factor in picture naming when cumulative word frequency and frequency trajectory are controlled. Quarterly Journal of Experimental Psychology, 60(1), 32&#x2013;42. https://doi.org/10.1080/17470210600577423</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/17470210600577423</ArticleId></ArticleIdList></Reference><Reference><Citation>Shu, H., Chen, X., Anderson, R. C., Wu, N., &amp; Xuan, Y. (2003). Properties of School Chinese: Implications for Learning to Read. Child Development, 74(1), 27&#x2013;47. https://doi.org/10.1111/1467-8624.00519</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/1467-8624.00519</ArticleId><ArticleId IdType="pubmed">12625434</ArticleId></ArticleIdList></Reference><Reference><Citation>Stadthagen-Gonzalez, H., &amp; Davis, C. J. (2006). The Bristol norms for age of acquisition, imageability, and familiarity. Behavior Research Methods, 38(4), 598&#x2013;605. https://doi.org/10.3758/BF03193891</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/BF03193891</ArticleId><ArticleId IdType="pubmed">17393830</ArticleId></ArticleIdList></Reference><Reference><Citation>Stewart, N., &amp; Ellis, A. W. (2008). Order of acquisition in learning perceptual categories: A laboratory analogue of the age-of-acquisition effect? Psychonomic Bulletin &amp; Review, 15(1), 70&#x2013;74. https://doi.org/10.3758/PBR.15.1.70</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/PBR.15.1.70</ArticleId></ArticleIdList></Reference><Reference><Citation>Sze, W. P., Rickard Liow, S. J., &amp; Yap, M. J. (2014). The Chinese Lexicon Project: a repository of lexical decision behavioral responses for 2,500 Chinese characters. Behavior Research Methods, 46(1), 263&#x2013;273. https://doi.org/10.3758/s13428-013-0355-9</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/s13428-013-0355-9</ArticleId><ArticleId IdType="pubmed">23813237</ArticleId></ArticleIdList></Reference><Reference><Citation>Sze, W. P., Yap, M. J., &amp; Rickard Liow, S. J. (2015). The role of lexical variables in the visual recognition of Chinese characters: A megastudy analysis. Quarterly Journal of Experimental Psychology, 68(8), 1541&#x2013;1570.</Citation></Reference><Reference><Citation>Tsang, Y.-K., Huang, J., Lui, M., Xue, M., Chan, Y.-W. F., Wang, S., &amp; Chen, H.-C. (2018). MELD-SCH: A megastudy of lexical decision in simplified Chinese. Behavior Research Methods, 50(5), 1763&#x2013;1777. https://doi.org/10.3758/s13428-017-0944-0</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/s13428-017-0944-0</ArticleId><ArticleId IdType="pubmed">28779457</ArticleId></ArticleIdList></Reference><Reference><Citation>Urooj, U., Cornelissen, P. L., Simpson, M. I., Wheat, K. L., Woods, W., Barca, L., &amp; Ellis, A. W. (2014). Interactions between visual and semantic processing during object recognition revealed by modulatory effects of age of acquisition. Neuroimage, 87, 252&#x2013;264.</Citation><ArticleIdList><ArticleId IdType="pubmed">24212056</ArticleId></ArticleIdList></Reference><Reference><Citation>Valentine, V. M. T. (1998). The Effect of Age of Acquisition on Speed and Accuracy of Naming Famous Faces. The Quarterly Journal of Experimental Psychology Section A, 51(3), 485&#x2013;513. https://doi.org/10.1080/713755779</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/713755779</ArticleId></ArticleIdList></Reference><Reference><Citation>Wagenmakers, E.-J. (2007). A practical solution to the pervasive problems of p values. Psychonomic Bulletin &amp; Review, 14(5), 779&#x2013;804.</Citation></Reference><Reference><Citation>Wang, R., Huang, S., Zhou, Y., &amp; Cai, Z. G. (2020). Chinese character handwriting: A large-scale behavioral study and a database. Behavior Research Methods, 52(1), 82&#x2013;96. https://doi.org/10.3758/s13428-019-01206-4</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/s13428-019-01206-4</ArticleId><ArticleId IdType="pubmed">30805862</ArticleId></ArticleIdList></Reference><Reference><Citation>Warriner, A. B., Kuperman, V., &amp; Brysbaert, M. (2013). Norms of valence, arousal, and dominance for 13,915 English lemmas. Behavior Research Methods, 45(4), 1191&#x2013;1207.</Citation><ArticleIdList><ArticleId IdType="pubmed">23404613</ArticleId></ArticleIdList></Reference><Reference><Citation>Weekes, B. S., Chan, A. H., &amp; Tan, L. H. (2008). Effects of age of acquisition on brain activation during Chinese character recognition. Neuropsychologia, 46(7), 2086&#x2013;2090.</Citation><ArticleIdList><ArticleId IdType="pubmed">18325545</ArticleId></ArticleIdList></Reference><Reference><Citation>Wikse Barrow, C., Nilsson Bj&#xf6;rkenstam, K., &amp; Str&#xf6;mbergsson, S. (2019). Subjective ratings of age-of-acquisition: exploring issues of validity and rater reliability. Journal of Child Language, 46(2), 199&#x2013;213. https://doi.org/10.1017/S0305000918000363 .</Citation><ArticleIdList><ArticleId IdType="doi">10.1017/S0305000918000363</ArticleId><ArticleId IdType="pubmed">30348232</ArticleId></ArticleIdList></Reference><Reference><Citation>Xu, X., Li, J. &amp; Guo, S. (2021). Age of acquisition ratings for 19,716 simplified Chinese words. Behavior Research Methods, 53, 558&#x2013;573. https://doi.org/10.3758/s13428-020-01455-8 .</Citation><ArticleIdList><ArticleId IdType="doi">10.3758/s13428-020-01455-8</ArticleId><ArticleId IdType="pubmed">32748240</ArticleId></ArticleIdList></Reference><Reference><Citation>Yum, Y. N., &amp; Law, S.-P. (2019). Interactions of age of acquisition and lexical frequency effects with phonological regularity: An ERP study. Psychophysiology, 56(10), e13433. https://doi.org/10.1111/psyp.13433 .</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/psyp.13433</ArticleId><ArticleId IdType="pubmed">31264723</ArticleId></ArticleIdList></Reference><Reference><Citation>Zevin, J. D., &amp; Seidenberg, M. S. (2002). Age of acquisition effects in word reading and other tasks. Journal of Memory and language, 47(1), 1&#x2013;29.</Citation></Reference><Reference><Citation>Zevin, J. D., &amp; Seidenberg, M. S. (2004). Age-of-acquisition effects in reading aloud: Tests of cumulative frequency and frequency trajectory. Memory &amp; Cognition, 32(1), 31&#x2013;38.</Citation></Reference><Reference><Citation>Zhan, W., Guo, R., Chang, B., Chen, Y., &amp; Chen, L. (2019). The building of the CCL corpus: Its design and implementation, Corpus Linguistics, 6, 71&#x2013;86.</Citation></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33868140</PMID><DateRevised><Year>2021</Year><Month>04</Month><Day>21</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1664-2295</ISSN><JournalIssue CitedMedium="Print"><Volume>12</Volume><PubDate><Year>2021</Year></PubDate></JournalIssue><Title>Frontiers in neurology</Title><ISOAbbreviation>Front Neurol</ISOAbbreviation></Journal><ArticleTitle>Telitacicept Following Plasma Exchange in the Treatment of Subjects With Recurrent NMOSD: Study Protocol for a Single-Center, Single-Arm, Open-Label Study.</ArticleTitle><Pagination><StartPage>596791</StartPage><MedlinePgn>596791</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">596791</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3389/fneur.2021.596791</ELocationID><Abstract><AbstractText><b>Background:</b> Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease that recurrently relapses and leads to severe disability. The available choices for disease prevention are few or intolerable. Previous studies suggested that telitacicept may provide a promising therapeutic strategy for autoimmune diseases involving B cells. Therefore, this study aims to assess the effectiveness and safety of telitacicept for recurrent NMOSD. <b>Methods:</b> We will perform a single-arm, single-center, open-label, specialist study with a total enrollment of eight participants. The treatment regimen includes plasma exchange three times and subcutaneous injection of telitacicept for 46 cycles, with a total period of 48 weeks. The primary endpoint is the time to first recurrence after enrollment. Secondary endpoints are Expanded Disability Status Scale (EDSS) score, Opticospinal Impairment Scale (OSIS) score, Hauser Ambulation Index, number of lesions on MRI, and changes in visual evoked potential (VEP), optical coherence tomography (OCT) and immunologic status. All adverse events after medication will be documented and investigated. <b>Discussion:</b> This study will explore the safety and effectiveness of telitacicept following plasma exchange regarding the time to recurrence in neuromyelitis optica spectrum disorder (NMOSD) for the first time. <b>Clinical Trial Registration:</b> Chictr.org.cn, identifier ChiCTR1800019427.</AbstractText><CopyrightInformation>Copyright &#xa9; 2021 Ding, Cai, Deng, Jiang, Gao, Lin, Zhao, Wang, Yu, Lv, Zhang, Hao and Guan.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Jie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Yu</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deng</LastName><ForeName>Ye</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Xianguo</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Meichun</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Ze</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Haojun</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lv</LastName><ForeName>Wenwen</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Clinical Research Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hao</LastName><ForeName>Yong</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guan</LastName><ForeName>Yangtai</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>03</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Neurol</MedlineTA><NlmUniqueID>101546899</NlmUniqueID><ISSNLinking>1664-2295</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">clinical study</Keyword><Keyword MajorTopicYN="N">effectiveness</Keyword><Keyword MajorTopicYN="N">neuromyelitis optica spectrum disorders</Keyword><Keyword MajorTopicYN="N">plasma exchange</Keyword><Keyword MajorTopicYN="N">safety</Keyword><Keyword MajorTopicYN="N">study protocol</Keyword><Keyword MajorTopicYN="N">telitacicept</Keyword></KeywordList><CoiStatement>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>8</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>2</Month><Day>19</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>4</Month><Day>19</Day><Hour>6</Hour><Minute>21</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>4</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>4</Month><Day>20</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2021</Year><Month>3</Month><Day>18</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33868140</ArticleId><ArticleId IdType="pmc">PMC8044936</ArticleId><ArticleId IdType="doi">10.3389/fneur.2021.596791</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Hor JY, Asgari N, Nakashima I, Broadley SA, Leite MI, Kissani N, et al. . Epidemiology of Neuromyelitis Optica Spectrum Disorder and Its Prevalence and Incidence Worldwide. Front Neurol. (2020) 11:501. 10.3389/fneur.2020.00501</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fneur.2020.00501</ArticleId><ArticleId IdType="pmc">PMC7332882</ArticleId><ArticleId IdType="pubmed">32670177</ArticleId></ArticleIdList></Reference><Reference><Citation>Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. . International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. (2015) 85:177&#x2013;89. 10.1212/WNL.0000000000001729</Citation><ArticleIdList><ArticleId IdType="doi">10.1212/WNL.0000000000001729</ArticleId><ArticleId IdType="pmc">PMC4515040</ArticleId><ArticleId IdType="pubmed">26092914</ArticleId></ArticleIdList></Reference><Reference><Citation>Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol. (2014) 10:493&#x2013;506. 10.1038/nrneurol.2014.141</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrneurol.2014.141</ArticleId><ArticleId IdType="pmc">PMC4229040</ArticleId><ArticleId IdType="pubmed">25112508</ArticleId></ArticleIdList></Reference><Reference><Citation>Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, et al. . Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. (2014) 261:1&#x2013;16. 10.1007/s00415-013-7169-7</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00415-013-7169-7</ArticleId><ArticleId IdType="pmc">PMC3895189</ArticleId><ArticleId IdType="pubmed">24272588</ArticleId></ArticleIdList></Reference><Reference><Citation>Espiritu AI, Pasco PMD. Efficacy and tolerability of azathioprine for neuromyelitis optica spectrum disorder: a systematic review and meta-analysis. Mult Scler Relat Disord. (2019) 33:22&#x2013;32. 10.1016/j.msard.2019.05.011</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.msard.2019.05.011</ArticleId><ArticleId IdType="pubmed">31136907</ArticleId></ArticleIdList></Reference><Reference><Citation>Bonnan M, Valentino R, Debeugny S, Merle H, Ferge JL, Mehdaoui H, et al. . Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurol Neurosurg Psychiatry. (2018) 89:346&#x2013;51. 10.1136/jnnp-2017-316286</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/jnnp-2017-316286</ArticleId><ArticleId IdType="pubmed">29030418</ArticleId></ArticleIdList></Reference><Reference><Citation>Poupart J, Giovannelli J, Deschamps R, Audoin B, Ciron J, Maillart E, et al. . Evaluation of efficacy and tolerability of first-line therapies in NMOSD. Neurology. (2020) 94:e1645&#x2013;e56. 10.1212/WNL.0000000000009245</Citation><ArticleIdList><ArticleId IdType="doi">10.1212/WNL.0000000000009245</ArticleId><ArticleId IdType="pubmed">32170036</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang C, Zhang M, Qiu W, Ma H, Zhang X, Zhu Z, et al. . Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. (2020) 19:391&#x2013;401. 10.1016/S1474-4422(20)30070-3</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S1474-4422(20)30070-3</ArticleId><ArticleId IdType="pmc">PMC7935423</ArticleId><ArticleId IdType="pubmed">32333897</ArticleId></ArticleIdList></Reference><Reference><Citation>Duchow A, Chien C, Paul F, Bellmann-Strobl J. Emerging drugs for the treatment of neuromyelitis optica. Expert Opin Emerg Drugs. (2020) 25:285&#x2013;97. 10.1080/14728214.2020.1803828</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/14728214.2020.1803828</ArticleId><ArticleId IdType="pubmed">32731771</ArticleId></ArticleIdList></Reference><Reference><Citation>Melamed E, Levy M, Waters PJ, Sato DK, Bennett JL, John GR, et al. . Update on biomarkers in neuromyelitis optica. Neurology(R) neuroimmunology &amp; Neuroinflammation. (2015) 2:e134. 10.1212/NXI.0000000000000134</Citation><ArticleIdList><ArticleId IdType="doi">10.1212/NXI.0000000000000134</ArticleId><ArticleId IdType="pmc">PMC4516398</ArticleId><ArticleId IdType="pubmed">26236760</ArticleId></ArticleIdList></Reference><Reference><Citation>Dillon SR, Gross JA, Ansell SM, Novak AJ. An APRIL to remember: novel TNF ligands as therapeutic targets. Nat Rev Drug Discov. (2006) 5:235&#x2013;46. 10.1038/nrd1982</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrd1982</ArticleId><ArticleId IdType="pubmed">16474316</ArticleId></ArticleIdList></Reference><Reference><Citation>Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, et al. . BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. (1999) 285:260&#x2013;3. 10.1126/science.285.5425.260</Citation><ArticleIdList><ArticleId IdType="doi">10.1126/science.285.5425.260</ArticleId><ArticleId IdType="pubmed">10398604</ArticleId></ArticleIdList></Reference><Reference><Citation>Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, et al. . BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. The J Exp Med. (1999)189:1747&#x2013;56. 10.1084/jem.189.11.1747</Citation><ArticleIdList><ArticleId IdType="doi">10.1084/jem.189.11.1747</ArticleId><ArticleId IdType="pmc">PMC2193079</ArticleId><ArticleId IdType="pubmed">10359578</ArticleId></ArticleIdList></Reference><Reference><Citation>Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, Oregon-Romero E, Machado-Contreras JR, Munoz-Valle JF, et al. . Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus. (2016) 25:582&#x2013;92. 10.1177/0961203315608254</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/0961203315608254</ArticleId><ArticleId IdType="pubmed">26424128</ArticleId></ArticleIdList></Reference><Reference><Citation>Hegazy M, Darwish H, Darweesh H, El-Shehaby A, Emad Y. Raised serum level of APRIL in patients with systemic lupus erythematosus: correlations with disease activity indices. Clin Immunol. (2010) 135:118&#x2013;24. 10.1016/j.clim.2009.12.012</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.clim.2009.12.012</ArticleId><ArticleId IdType="pubmed">20116334</ArticleId></ArticleIdList></Reference><Reference><Citation>Shabgah AG, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohammadi M. The role of BAFF and APRIL in rheumatoid arthritis. J Cell Physiol. (2019) 234:17050&#x2013;63. 10.1002/jcp.28445</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/jcp.28445</ArticleId><ArticleId IdType="pubmed">30941763</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang H, Wang K, Zhong X, Qiu W, Dai Y, Wu A, et al. . Cerebrospinal Fluid BAFF and APRIL levels in neuromyelitis optica and multiple sclerosis patients during relapse. J Clin Immunol. (2012) 32:1007&#x2013;11. 10.1007/s10875-012-9709-9</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s10875-012-9709-9</ArticleId><ArticleId IdType="pubmed">22644841</ArticleId></ArticleIdList></Reference><Reference><Citation>McCarthy EM, Lee RZ, Ni Gabhann J, Smith S, Cunnane G, Doran MF, et al. . Elevated B lymphocyte stimulator levels are associated with increased damage in an Irish systemic lupus erythematosus cohort. Rheumatology. (2013) 52:1279&#x2013;84. 10.1093/rheumatology/ket120</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/rheumatology/ket120</ArticleId><ArticleId IdType="pubmed">23479724</ArticleId></ArticleIdList></Reference><Reference><Citation>Marsters SA, Yan M, Pitti RM, Haas PE, Dixit VM, Ashkenazi A. Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues BCMA and TACI. Curr Biol. (2000) 10:785&#x2013;8. 10.1016/s0960-9822(00)00566-2</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/s0960-9822(00)00566-2</ArticleId><ArticleId IdType="pubmed">10898980</ArticleId></ArticleIdList></Reference><Reference><Citation>Bossen C, Schneider P. BAFF, APRIL and their receptors: structure, function and signaling. Semin Immunol. (2006) 18:263&#x2013;75.10.1016/j.smim.2006.04.006</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.smim.2006.04.006</ArticleId><ArticleId IdType="pubmed">16914324</ArticleId></ArticleIdList></Reference><Reference><Citation>Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, et al. . TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. (2000) 404:995&#x2013;9. 10.1038/35010115</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/35010115</ArticleId><ArticleId IdType="pubmed">10801128</ArticleId></ArticleIdList></Reference><Reference><Citation>Kaegi C, Steiner UC, Wuest B, Crowley C, Boyman O. Systematic review of safety and efficacy of atacicept in treating immune-mediated disorders. Front Immunol. (2020) 11:433. 10.3389/fimmu.2020.00433</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fimmu.2020.00433</ArticleId><ArticleId IdType="pmc">PMC7105675</ArticleId><ArticleId IdType="pubmed">32265917</ArticleId></ArticleIdList></Reference><Reference><Citation>Merrill JT, Wallace DJ, Wax S, Kao A, Fraser PA, Chang P, et al. . Efficacy and safety of atacicept in patients with systemic lupus erythematosus: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm, phase iib study. Arthritis Rheumatol. (2018) 70:266&#x2013;76. 10.1002/art.40360</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.40360</ArticleId><ArticleId IdType="pmc">PMC6099253</ArticleId><ArticleId IdType="pubmed">29073347</ArticleId></ArticleIdList></Reference><Reference><Citation>Pena-Rossi C, Nasonov E, Stanislav M, Yakusevich V, Ershova O, Lomareva N, et al. . An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus. Lupus. (2009) 18:547&#x2013;55. 10.1177/0961203309102803</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/0961203309102803</ArticleId><ArticleId IdType="pmc">PMC3835146</ArticleId><ArticleId IdType="pubmed">19395457</ArticleId></ArticleIdList></Reference><Reference><Citation>van Vollenhoven RF, Kinnman N, Vincent E, Wax S, Bathon J. Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase II, randomized, placebo-controlled trial. Arthritis Rheum. (2011) 63:1782&#x2013;92. 10.1002/art.30372</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.30372</ArticleId><ArticleId IdType="pubmed">21452294</ArticleId></ArticleIdList></Reference><Reference><Citation>Huntington ND, Tomioka R, Clavarino C, Chow AM, Linares D, Mana P, et al. . A BAFF antagonist suppresses experimental autoimmune encephalomyelitis by targeting cell-mediated and humoral immune responses. Int Immunol. (2006) 18:1473&#x2013;85. 10.1093/intimm/dxl080</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/intimm/dxl080</ArticleId><ArticleId IdType="pubmed">16914508</ArticleId></ArticleIdList></Reference><Reference><Citation>Kappos L, Hartung H-P, Freedman MS, Boyko A, Rad&#xfc; EW, Mikol DD, et al. . Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Neurol. (2014) 13:353&#x2013;63. 10.1016/s1474-4422(14)70028-6</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/s1474-4422(14)70028-6</ArticleId><ArticleId IdType="pubmed">24613349</ArticleId></ArticleIdList></Reference><Reference><Citation>Sergott RC, Bennett JL, Rieckmann P, Montalban X, Mikol D, Freudensprung U, et al. . ATON: results from a Phase II randomized trial of the B-cell-targeting agent atacicept in patients with optic neuritis. J Neurol Sci. (2015) 351:174&#x2013;8. 10.1016/j.jns.2015.02.019</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jns.2015.02.019</ArticleId><ArticleId IdType="pubmed">25758472</ArticleId></ArticleIdList></Reference><Reference><Citation>Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, et al. . SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. (2013) 158:200&#x2013;7. 10.7326/0003-4819-158-3-201302050-00583</Citation><ArticleIdList><ArticleId IdType="doi">10.7326/0003-4819-158-3-201302050-00583</ArticleId><ArticleId IdType="pmc">PMC5114123</ArticleId><ArticleId IdType="pubmed">23295957</ArticleId></ArticleIdList></Reference><Reference><Citation>Munafo A, Priestley A, Nestorov I, Visich J, Rogge M. Safety, pharmacokinetics and pharmacodynamics of atacicept in healthy volunteers. Eur J Clin Pharmacol. (2007) 63:647&#x2013;56. 10.1007/s00228-007-0311-7</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s00228-007-0311-7</ArticleId><ArticleId IdType="pubmed">17473917</ArticleId></ArticleIdList></Reference><Reference><Citation>Willen D, Uhl W, Wolna P, Papasouliotis O, Yalkinoglu O. Safety, tolerability, pharmacokinetics, and pharmacodynamics of atacicept in a randomized trial in healthy caucasian and Japanese subjects. Eur J Drug Metab Pharmacokinet. (2020) 45:27&#x2013;40. 10.1007/s13318-019-00575-7</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s13318-019-00575-7</ArticleId><ArticleId IdType="pmc">PMC6994531</ArticleId><ArticleId IdType="pubmed">31529406</ArticleId></ArticleIdList></Reference><Reference><Citation>Gordon C, Bassi R, Chang P, Kao A, Jayne D, Wofsy D, et al. . Integrated safety profile of atacicept: an analysis of pooled data from the atacicept clinical trial programme. Rheumatol Adv Pract. (2019) 3:rkz021. 10.1093/rap/rkz021</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/rap/rkz021</ArticleId><ArticleId IdType="pmc">PMC6735746</ArticleId><ArticleId IdType="pubmed">31528843</ArticleId></ArticleIdList></Reference><Reference><Citation>Tak PP, Thurlings RM, Rossier C, Nestorov I, Dimic A, Mircetic V, et al. . Atacicept in patients with rheumatoid arthritis: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating, single- and repeated-dose study. Arthritis Rheum. (2008) 58:61&#x2013;72. 10.1002/art.23178</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.23178</ArticleId><ArticleId IdType="pubmed">18163485</ArticleId></ArticleIdList></Reference><Reference><Citation>Dall'Era M, Chakravarty E, Wallace D, Genovese M, Weisman M, Kavanaugh A, et al. . Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating trial. Arthritis Rheum. (2007) 56:4142&#x2013;50. 10.1002/art.23047</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.23047</ArticleId><ArticleId IdType="pubmed">18050206</ArticleId></ArticleIdList></Reference><Reference><Citation>Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. (2007) 6:805&#x2013;15. 10.1016/s1474-4422(07)70216-8</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/s1474-4422(07)70216-8</ArticleId><ArticleId IdType="pubmed">17706564</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33746886</PMID><DateRevised><Year>2021</Year><Month>03</Month><Day>23</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1664-2295</ISSN><JournalIssue CitedMedium="Print"><Volume>12</Volume><PubDate><Year>2021</Year></PubDate></JournalIssue><Title>Frontiers in neurology</Title><ISOAbbreviation>Front Neurol</ISOAbbreviation></Journal><ArticleTitle>Association Between Low-Density Lipoprotein Cholesterol and Platelet Distribution Width in Acute Ischemic Stroke.</ArticleTitle><Pagination><StartPage>631227</StartPage><MedlinePgn>631227</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">631227</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3389/fneur.2021.631227</ELocationID><Abstract><AbstractText><b>Objective:</b> Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for ischemic stroke; however, whether LDL-C affects the platelet deformation function in the peripheral blood circulation in patients with acute ischemic stroke (AIS) is unknown. The present study aimed to investigate the relationship between LDL-C and platelet distribution width (PDW) in AIS patients. <b>Methods:</b> We conducted a cross-sectional hospitalized-based study of consecutive 438 patients with AIS within 24 h. Blood samples were collected upon admission and prior to drug administration, and LDL-C and PDW (a parameter that reflects the heterogeneity of platelet volume) were assessed. The relationship between LDL-C and PDW were analyzed by linear curve fitting analyses. Crude and adjusted beta coefficients of LDL-C for PDW with 95% confidence intervals were analyzed using multivariate-adjusted linear regression models. <b>Results:</b> The PDW was significantly higher in the high LDL-C group compared with those in the normal LDL-C group (16.28 &#xb1; 0.37 fl vs. 16.08 &#xb1; 0.37 fl, <i>p</i> &lt; 0.001). Adjusted smoothed plots suggested that there are linear relationships between LDL-C and PDW, and the Pearson's correlation coefficient (95%) was 0.387 (0.304-0.464, <i>p</i> &lt; 0.001). The beta coefficients (95% CI) between LDL-C and PDW were 0.15 (0.12-0.18, <i>p</i> &lt; 0.001) and 0.14 (0.11-0.18, <i>p</i> &lt; 0.001), respectively, in AIS patients before and after adjusting for potential confounders. <b>Conclusion:</b> Our study suggested that the elevated LDL-C level was related to increased PDW among AIS patients.</AbstractText><CopyrightInformation>Copyright &#xa9; 2021 Yuan, Cai, Zhao, Zhao, Hong, Ding, Yang, Fan, Zhu, Zhou, Li, Zhu and Guan.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yuan</LastName><ForeName>Jian</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Jian</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Pei</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Neurology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hong</LastName><ForeName>Rong-Hua</ForeName><Initials>RH</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Jie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Jin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Qing-Lei</ForeName><Initials>QL</Initials><AffiliationInfo><Affiliation>Department of Neurology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Jian</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Xia-Jun</ForeName><Initials>XJ</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Ze-Zhi</ForeName><Initials>ZZ</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>De-Sheng</ForeName><Initials>DS</Initials><AffiliationInfo><Affiliation>Department of Neurology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guan</LastName><ForeName>Yang-Tai</ForeName><Initials>YT</Initials><AffiliationInfo><Affiliation>Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>03</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Neurol</MedlineTA><NlmUniqueID>101546899</NlmUniqueID><ISSNLinking>1664-2295</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">acute ischemic stroke</Keyword><Keyword MajorTopicYN="N">low-density lipoprotein</Keyword><Keyword MajorTopicYN="N">multivariate analysis</Keyword><Keyword MajorTopicYN="N">oxidative stress</Keyword><Keyword MajorTopicYN="N">platelet distribution width</Keyword></KeywordList><CoiStatement>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>11</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>2</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>3</Month><Day>22</Day><Hour>8</Hour><Minute>8</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>3</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>3</Month><Day>23</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2021</Year><Month>3</Month><Day>5</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33746886</ArticleId><ArticleId IdType="pmc">PMC7973264</ArticleId><ArticleId IdType="doi">10.3389/fneur.2021.631227</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Damani RH, Anand S, Asgarisabet P, Bissell C, Savitz S, Suarez JI. Regional intervention of stroke care to increase thrombolytic therapy for acute ischemic stroke. Stroke. (2018) 49:2008&#x2013;10. 10.1161/STROKEAHA.118.021109</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/STROKEAHA.118.021109</ArticleId><ArticleId IdType="pubmed">29991653</ArticleId></ArticleIdList></Reference><Reference><Citation>Nixon DE, Bosch RJ, Chan ES, Funderburg NT, Hodder S, Lake JE, et al. . Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1-infected individuals with low-density lipoprotein cholesterol &lt;130 mg/dL (AIDS Clinical Trials Group Study A5275). J. Clin. Lipidol. (2017) 11:61&#x2013;9. 10.1016/j.jacl.2016.09.017</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jacl.2016.09.017</ArticleId><ArticleId IdType="pmc">PMC5407297</ArticleId><ArticleId IdType="pubmed">28391912</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang Q, Liu S, Liu Y, Hua Y, Song H, Ren Y, et al. . Achieving low density lipoprotein-cholesterol &lt;70mg/dL may be associated with a trend of reduced progression of carotid artery atherosclerosis in ischemic stroke patients. J. Neurol. Sci. (2017) 378:26&#x2013;9. 10.1016/j.jns.2017.04.024</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jns.2017.04.024</ArticleId><ArticleId IdType="pmc">PMC5802361</ArticleId><ArticleId IdType="pubmed">28566171</ArticleId></ArticleIdList></Reference><Reference><Citation>Al RM, Martin SS, McEvoy JW, Nasir K, Blankstein R, Yeboah J, et al. . The prevalence and correlates of subclinical atherosclerosis among adults with low-density lipoprotein cholesterol &lt;70mg/dL: the multi-ethnic study of atherosclerosis (MESA) and Brazilian longitudinal study of adult health (ELSA-Brasil). Atherosclerosis. (2018) 274:61&#x2013;6. 10.1016/j.atherosclerosis.2018.04.021</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.atherosclerosis.2018.04.021</ArticleId><ArticleId IdType="pubmed">29751286</ArticleId></ArticleIdList></Reference><Reference><Citation>Ma C, Na M, Neumann S, Gao X. Low-density lipoprotein cholesterol and risk of hemorrhagic stroke: a systematic review and dose-response meta-analysis of prospective studies. Curr. Atheroscler. Rep. (2019) 21:52. 10.1007/s11883-019-0815-5</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s11883-019-0815-5</ArticleId><ArticleId IdType="pubmed">31748963</ArticleId></ArticleIdList></Reference><Reference><Citation>Safar ME, Blacher J, Mourad JJ, London GM. Stiffness of carotid artery wall material and blood pressure in humans: application to antihypertensive therapy and stroke prevention. Stroke. (2000) 31:782&#x2013;90. 10.1161/01.STR.31.3.782</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/01.STR.31.3.782</ArticleId><ArticleId IdType="pubmed">10700519</ArticleId></ArticleIdList></Reference><Reference><Citation>Karnad A, Poskitt TR. The automated complete blood cell count. Use of the red blood cell volume distribution width and mean platelet volume in evaluating anemia and thrombocytopenia. Arch. Intern. Med. (1985) 145:1270&#x2013;2. 10.1001/archinte.1985.00360070150025</Citation><ArticleIdList><ArticleId IdType="doi">10.1001/archinte.1985.00360070150025</ArticleId><ArticleId IdType="pubmed">4015277</ArticleId></ArticleIdList></Reference><Reference><Citation>Schmoeller D, Picarelli MM, Paz MT, Poli DFC, Staub HL. Mean platelet volume and immature platelet fraction in autoimmune disorders. Front. Med. (2017) 4:146. 10.3389/fmed.2017.00146</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fmed.2017.00146</ArticleId><ArticleId IdType="pmc">PMC5592196</ArticleId><ArticleId IdType="pubmed">28932736</ArticleId></ArticleIdList></Reference><Reference><Citation>Redfors B, Chen S, Ben-Yehuda O, Huang X, Witzenbichler B, Weisz G, et al. . Association between hypertension, platelet reactivity, and the risk of adverse events after percutaneous coronary intervention (From the ADAPT-DES study). Am. J. Cardiol. (2019) 124:1380&#x2013;8. 10.1016/j.amjcard.2019.07.044</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.amjcard.2019.07.044</ArticleId><ArticleId IdType="pubmed">31477234</ArticleId></ArticleIdList></Reference><Reference><Citation>Gao F, Chen C, Lyu J, Zheng J, Ma XC, Yuan XY, et al. . Association between platelet distribution width and poor outcome of acute ischemic stroke after intravenous thrombolysis. Neuropsychiatr. Dis. Treat. (2018) 14:2233&#x2013;9. 10.2147/NDT.S170823</Citation><ArticleIdList><ArticleId IdType="doi">10.2147/NDT.S170823</ArticleId><ArticleId IdType="pmc">PMC6126482</ArticleId><ArticleId IdType="pubmed">30214213</ArticleId></ArticleIdList></Reference><Reference><Citation>Pierot L, Jayaraman MV, Szikora I, Hirsch JA, Baxter B, Miyachi S, et al. . Standards of practice in acute ischemic stroke intervention: international recommendations. AJNR Am. J. Neuroradiol. (2018) 39:E112&#x2013;7. 10.3174/ajnr.A5853</Citation><ArticleIdList><ArticleId IdType="doi">10.3174/ajnr.A5853</ArticleId><ArticleId IdType="pmc">PMC7655359</ArticleId><ArticleId IdType="pubmed">30442688</ArticleId></ArticleIdList></Reference><Reference><Citation>Shen H, Herzog W, Drolet M, Pakyz R, Newcomer S, Sack P, et al. . Aspirin resistance in healthy drug-naive men versus women (from the heredity and phenotype intervention heart study). Am. J. Cardiol. (2009) 104:606&#x2013;12. 10.1016/j.amjcard.2009.04.027</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.amjcard.2009.04.027</ArticleId><ArticleId IdType="pmc">PMC3674572</ArticleId><ArticleId IdType="pubmed">19660620</ArticleId></ArticleIdList></Reference><Reference><Citation>Frisbee JC, Goodwill AG, Stapleton PA, Frisbee SJ, D'Audiffret AC. Aspirin resistance with genetic dyslipidemia: contribution of vascular thromboxane generation. Physiol. Genomics. (2010) 42:331&#x2013;41. 10.1152/physiolgenomics.00090.2010</Citation><ArticleIdList><ArticleId IdType="doi">10.1152/physiolgenomics.00090.2010</ArticleId><ArticleId IdType="pmc">PMC2929885</ArticleId><ArticleId IdType="pubmed">20530721</ArticleId></ArticleIdList></Reference><Reference><Citation>Spaans F, Quon A, Rowe SR, Morton JS, Kirschenman R, Sawamura T, et al. . Alterations in vascular function by syncytiotrophoblast extracellular vesicles via lectin-like oxidized low-density lipoprotein receptor-1 in mouse uterine arteries. Clin. Sci. (2018) 132:2369&#x2013;81. 10.1042/CS20180639</Citation><ArticleIdList><ArticleId IdType="doi">10.1042/CS20180639</ArticleId><ArticleId IdType="pubmed">30352791</ArticleId></ArticleIdList></Reference><Reference><Citation>Wen Y, Ahmad F, Mohri Z, Weinberg PD, Leake DS. Cysteamine inhibits lysosomal oxidation of low density lipoprotein in human macrophages and reduces atherosclerosis in mice. Atherosclerosis. (2019) 291:9&#x2013;18. 10.1016/j.atherosclerosis.2019.09.019</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.atherosclerosis.2019.09.019</ArticleId><ArticleId IdType="pmc">PMC6912160</ArticleId><ArticleId IdType="pubmed">31629988</ArticleId></ArticleIdList></Reference><Reference><Citation>Hsiai TK, Hwang J, Barr ML, Correa A, Hamilton R, Alavi M, et al. . Hemodynamics influences vascular peroxynitrite formation: implication for low-density lipoprotein apo-B-100 nitration. Free Radic. Biol. Med. (2007) 42:519&#x2013;29. 10.1016/j.freeradbiomed.2006.11.017</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.freeradbiomed.2006.11.017</ArticleId><ArticleId IdType="pmc">PMC2561143</ArticleId><ArticleId IdType="pubmed">17275684</ArticleId></ArticleIdList></Reference><Reference><Citation>Moriarty PM, Gibson CA, Kensey KR, Hogenauer W. Effect of low-density lipoprotein cholesterol apheresis on blood viscosity. Am. J. Cardiol. (2004) 93:1044&#x2013;6. 10.1016/j.amjcard.2003.12.059</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.amjcard.2003.12.059</ArticleId><ArticleId IdType="pubmed">15081454</ArticleId></ArticleIdList></Reference><Reference><Citation>Farias MG, Schunck EG, Dal Bo S, de Castro SM. Definition of reference ranges for the platelet distribution width (PDW): a local need. Clin. Chem. Lab. Med. (2010) 48:255&#x2013;7. 10.1515/CCLM.2010.035</Citation><ArticleIdList><ArticleId IdType="doi">10.1515/CCLM.2010.035</ArticleId><ArticleId IdType="pubmed">19958208</ArticleId></ArticleIdList></Reference><Reference><Citation>Cetin MS, Ozcan CE, Akdi A, Aras D, Topaloglu S, Temizhan A, et al. . Platelet distribution width and plateletcrit: novel biomarkers of ST elevation myocardial infarction in young patients. Kardiol. Pol. (2017) 75:1005&#x2013;12. 10.5603/KP.a2017.0135</Citation><ArticleIdList><ArticleId IdType="doi">10.5603/KP.a2017.0135</ArticleId><ArticleId IdType="pubmed">28715073</ArticleId></ArticleIdList></Reference><Reference><Citation>Akturk S, Buyukavci R. Evaluation of blood neutrophil-lymphocyte ratio and platelet distribution width as inflammatory markers in patients with fibromyalgia. Clin. Rheumatol. (2017) 36:1885&#x2013;9. 10.1007/s10067-017-3647-0</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s10067-017-3647-0</ArticleId><ArticleId IdType="pubmed">28466420</ArticleId></ArticleIdList></Reference><Reference><Citation>Estruch M, Sanchez-Quesada JL, Ordonez LJ, Benitez S. Electronegative LDL: a circulating modified LDL with a role in inflammation. Mediators Inflamm. (2013) 2013:181324. 10.1155/2013/181324</Citation><ArticleIdList><ArticleId IdType="doi">10.1155/2013/181324</ArticleId><ArticleId IdType="pmc">PMC3766570</ArticleId><ArticleId IdType="pubmed">24062611</ArticleId></ArticleIdList></Reference><Reference><Citation>Tekin IO, Orem A, Shiri-Sverdlov R. Oxidized LDL in inflammation: from bench to bedside. Mediators Inflamm. (2013) 2013:762759. 10.1155/2013/762759</Citation><ArticleIdList><ArticleId IdType="doi">10.1155/2013/762759</ArticleId><ArticleId IdType="pmc">PMC3857732</ArticleId><ArticleId IdType="pubmed">24347832</ArticleId></ArticleIdList></Reference><Reference><Citation>Lara-Guzman OJ, Gil-Izquierdo A, Medina S, Osorio E, Alvarez-Quintero R, Zuluaga N, et al. . Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages. Redox. Biol. (2018) 15:1&#x2013;11. 10.1016/j.redox.2017.11.017</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.redox.2017.11.017</ArticleId><ArticleId IdType="pmc">PMC5723280</ArticleId><ArticleId IdType="pubmed">29195136</ArticleId></ArticleIdList></Reference><Reference><Citation>Cimmino G, Cirillo P, Conte S, Pellegrino G, Barra G, Maresca L, et al. . Oxidized low-density lipoproteins induce tissue factor expression in T-Lymphocytes via activation of lectin-like oxidized low-density lipoprotein receptor-1. Cardiovasc. Res. (2020) 116:1125&#x2013;35. 10.1093/cvr/cvz230</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/cvr/cvz230</ArticleId><ArticleId IdType="pubmed">31504248</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhao B, Dierichs R, Miller FN, Dean WL. Oxidized low density lipoprotein inhibits platelet plasma membrane Ca(2+)-ATPase. Cell Calcium. (1996) 19:453&#x2013;8. 10.1016/S0143-4160(96)90118-9</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0143-4160(96)90118-9</ArticleId><ArticleId IdType="pubmed">8793185</ArticleId></ArticleIdList></Reference><Reference><Citation>Takahashi Y, Fuda H, Yanai H, Akita H, Shuping H, Chiba H, et al. . Significance of membrane glycoproteins in platelet interaction with oxidized low-density lipoprotein. Semin. Thromb. Hemost. (1998) 24:251&#x2013;3. 10.1055/s-2007-995850</Citation><ArticleIdList><ArticleId IdType="doi">10.1055/s-2007-995850</ArticleId><ArticleId IdType="pubmed">9701456</ArticleId></ArticleIdList></Reference><Reference><Citation>Abdullah AR, Hasan HA, Raigangar VL. Analysis of the relationship of leptin, high-sensitivity C-reactive protein, adiponectin, insulin, and uric acid to metabolic syndrome in lean, overweight, and obese young females. Metab Syndr Relat Disord. (2009) 7:17&#x2013;22. 10.1089/met.2008.0045</Citation><ArticleIdList><ArticleId IdType="doi">10.1089/met.2008.0045</ArticleId><ArticleId IdType="pubmed">19025443</ArticleId></ArticleIdList></Reference><Reference><Citation>Cicero A, Kuwabara M, Johnson R, Bove M, Fogacci F, Rosticci M, et al. . LDL-oxidation, serum uric acid, kidney function and pulse-wave velocity: data from the Brisighella Heart Study cohort. Int. J. Cardiol. (2018) 261:204&#x2013;8. 10.1016/j.ijcard.2018.03.077</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ijcard.2018.03.077</ArticleId><ArticleId IdType="pubmed">29572081</ArticleId></ArticleIdList></Reference><Reference><Citation>Marchio P, Guerra-Ojeda S, Vila JM, Aldasoro M, Victor VM, Mauricio MD. Targeting early atherosclerosis: a focus on oxidative stress and inflammation. Oxid. Med. Cell Longev. (2019) 2019:8563845. 10.1155/2019/8563845</Citation><ArticleIdList><ArticleId IdType="doi">10.1155/2019/8563845</ArticleId><ArticleId IdType="pmc">PMC6636482</ArticleId><ArticleId IdType="pubmed">31354915</ArticleId></ArticleIdList></Reference><Reference><Citation>Badrnya S, Butler LM, Soderberg-Naucler C, Volf I, Assinger A. Platelets directly enhance neutrophil transmigration in response to oxidised low-density lipoprotein. Thromb. Haemost. (2012) 108:719&#x2013;29. 10.1160/TH12-03-0206</Citation><ArticleIdList><ArticleId IdType="doi">10.1160/TH12-03-0206</ArticleId><ArticleId IdType="pubmed">22836389</ArticleId></ArticleIdList></Reference><Reference><Citation>Adam G, Kocak E, Ozkan A, Resorlu M, Cinar C, Bozkaya H, et al. . Evaluation of platelet distribution width and mean platelet volume in patients with carotid artery stenosis. Angiology. (2015) 66:375&#x2013;8. 10.1177/0003319714548682</Citation><ArticleIdList><ArticleId IdType="doi">10.1177/0003319714548682</ArticleId><ArticleId IdType="pubmed">25313243</ArticleId></ArticleIdList></Reference><Reference><Citation>Gao XM, Moore XL, Liu Y, Wang XY, Han LP, Su Y, et al. . Splenic release of platelets contributes to increased circulating platelet size and inflammation after myocardial infarction. Clin. Sci. (2016) 130:1089&#x2013;104. 10.1042/CS20160234</Citation><ArticleIdList><ArticleId IdType="doi">10.1042/CS20160234</ArticleId><ArticleId IdType="pubmed">27129192</ArticleId></ArticleIdList></Reference><Reference><Citation>Choi E, Im SM, Yoo HS, Nahm FS, Kim YH, Choe G, et al. . The neurological safety of an epidurally administered Lipo-PGE1 agonist in rats. Reg. Anesth. Pain Med. (2017) 42:75&#x2013;81. 10.1097/AAP.0000000000000520</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/AAP.0000000000000520</ArticleId><ArticleId IdType="pubmed">27922949</ArticleId></ArticleIdList></Reference><Reference><Citation>Alexandru N, Constantin A, Nemecz M, Comarita IK, Vilcu A, Procopciuc A, et al. . Hypertension associated with hyperlipidemia induced different MicroRNA expression profiles in plasma, platelets, and Platelet-Derived microvesicles; Effects of endothelial progenitor cell therapy. Front. Med. (2019) 6:280. 10.3389/fmed.2019.00280</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fmed.2019.00280</ArticleId><ArticleId IdType="pmc">PMC6901790</ArticleId><ArticleId IdType="pubmed">31850358</ArticleId></ArticleIdList></Reference><Reference><Citation>Paul M, Hemshekhar M, Kemparaju K, Girish KS. Aggregation is impaired in starved platelets due to enhanced autophagy and cellular energy depletion. Platelets. (2019) 30:487&#x2013;97. 10.1080/09537104.2018.1475630</Citation><ArticleIdList><ArticleId IdType="doi">10.1080/09537104.2018.1475630</ArticleId><ArticleId IdType="pubmed">29799304</ArticleId></ArticleIdList></Reference><Reference><Citation>Tan SK, Fong KP, Polizzi NF, Sternisha A, Slusky J, Yoon K, et al. . Modulating integrin alphaIIbbeta3 activity through mutagenesis of allosterically regulated intersubunit contacts. Biochemistry. (2019) 58:3251&#x2013;9. 10.1021/acs.biochem.9b00430</Citation><ArticleIdList><ArticleId IdType="doi">10.1021/acs.biochem.9b00430</ArticleId><ArticleId IdType="pmc">PMC7405930</ArticleId><ArticleId IdType="pubmed">31264850</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32281830</PMID><DateCompleted><Year>2020</Year><Month>04</Month><Day>28</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>28</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1079-7114</ISSN><JournalIssue CitedMedium="Internet"><Volume>124</Volume><Issue>12</Issue><PubDate><Year>2020</Year><Month>Mar</Month><Day>27</Day></PubDate></JournalIssue><Title>Physical review letters</Title><ISOAbbreviation>Phys Rev Lett</ISOAbbreviation></Journal><ArticleTitle>Magnetic Noise Enabled Biocompass.</ArticleTitle><Pagination><StartPage>128101</StartPage><MedlinePgn>128101</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1103/PhysRevLett.124.128101</ELocationID><Abstract><AbstractText>The discovery of magnetic protein provides a new understanding of a biocompass at the molecular level. However, the mechanism by which magnetic protein enables a biocompass is still under debate, mainly because of the absence of permanent magnetism in the magnetic protein at room temperature. Here, based on a widely accepted radical pair model of a biocompass, we propose a microscopic mechanism that allows the biocompass to operate without a finite magnetization of the magnetic protein in a biological environment. With the structure of the magnetic protein, we show that the magnetic fluctuation, rather than the permanent magnetism, of the magnetic protein can enable geomagnetic field sensing. An analysis of the quantum dynamics of our microscopic model reveals the necessary conditions for optimal sensitivity. Our work clarifies the mechanism by which magnetic protein enables a biocompass.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Xiao</LastName><ForeName>Da-Wu</ForeName><Initials>DW</Initials><AffiliationInfo><Affiliation>Beijing Computational Science Research Center, Beijing 100193, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>Wen-Hui</ForeName><Initials>WH</Initials><AffiliationInfo><Affiliation>Beijing Computational Science Research Center, Beijing 100193, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Yunfeng</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Cognitive Computing Lab, Baidu Research, Beijing 100085, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Beijing Computational Science Research Center, Beijing 100193, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Phys Rev Lett</MedlineTA><NlmUniqueID>0401141</NlmUniqueID><ISSNLinking>0031-9007</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007506">Iron-Sulfur Proteins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001703" MajorTopicYN="N">Biophysics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001717" MajorTopicYN="N">Birds</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007506" MajorTopicYN="N">Iron-Sulfur Proteins</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D060526" MajorTopicYN="Y">Magnetic Fields</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008962" MajorTopicYN="Y">Models, Theoretical</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065854" MajorTopicYN="N">Spatial Navigation</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>11</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>3</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>4</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>4</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>4</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32281830</ArticleId><ArticleId IdType="doi">10.1103/PhysRevLett.124.128101</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">30626478</PMID><DateCompleted><Year>2019</Year><Month>07</Month><Day>18</Day></DateCompleted><DateRevised><Year>2021</Year><Month>12</Month><Day>04</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1007-8738</ISSN><JournalIssue CitedMedium="Print"><Volume>34</Volume><Issue>12</Issue><PubDate><Year>2018</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology</Title><ISOAbbreviation>Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi</ISOAbbreviation></Journal><ArticleTitle>[Celastrol inhibits growth and increases apoptosis of human lung cancer A549 cells].</ArticleTitle><Pagination><StartPage>1111</StartPage><EndPage>1115</EndPage><MedlinePgn>1111-1115</MedlinePgn></Pagination><Abstract><AbstractText>Objective To investigate the inhibitory effect of celastrol on the proliferation of human lung cancer A549 cells and its possible mechanism. Methods A549 cells were treated with 0, 1, 2, 3, 4, 5, 6 &#x3bc;mol/L celastrol for 0, 24, 48, 72 hours. The effects of different concentrations and durations on the cell proliferation were evaluated by MTT assay to determine the optimal concentration and treatment time. In the subsequent experiments, A549 cells were treated with (0, 1, 3) &#x3bc;mol/L of celastrol for 48 hours. The effects of celastrol on the expression of BAX, B-cell lymphoma 2 (Bcl2), caspase-3, caspase-8, caspase-9 mRNA in A549 cells were detected by real-time quantitative PCR. The protein levels of BAX, Bcl-2, cleaved caspase-3(c-caspase-3), c-caspase-8, c-caspase-9 were assessed by Western blot analysis. Results Celastrol inhibited the viability of A549 cells in a concentration- and time-dependent manner. Compared with the group without celastrol treatment, the mRNA and protein level of Bcl2 in A549 cells treated with (1, 3) &#x3bc;mol/L celastrol decreased significantly, while the expression levels of BAX, caspase-3, caspase-8, caspase-9, c-caspase-3, c-caspase-8, c-caspase-9 increased significantly. Conclusion Celastrol could suppress the proliferation and induced the apoptosis of A549 cells through mitochondrial pathway.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Nan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Institute of Translational Medicine, First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Hong</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Institute of Translational Medicine, First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mu</LastName><ForeName>Chunqing</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institute of Translational Medicine, First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Qiuning</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, Jinzhou Medical University, Jinzhou 121000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Zhiyang</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Medicine Management, First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121000, China. *Corresponding author, E-mail: Zhiycai2015@outlook.com.</Affiliation></AffiliationInfo></Author></AuthorList><Language>chi</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi</MedlineTA><NlmUniqueID>101139110</NlmUniqueID><ISSNLinking>1007-8738</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C494826">BAX protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000595707">BCL2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053978">Pentacyclic Triterpenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019253">Proto-Oncogene Proteins c-bcl-2</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014315">Triterpenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051028">bcl-2-Associated X Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber><NameOfSubstance UI="D020169">Caspases</NameOfSubstance></Chemical><Chemical><RegistryNumber>L8GG98663L</RegistryNumber><NameOfSubstance UI="C050414">celastrol</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000072283" MajorTopicYN="N">A549 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="Y">Apoptosis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020169" MajorTopicYN="N">Caspases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008175" MajorTopicYN="N">Lung Neoplasms</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053978" MajorTopicYN="N">Pentacyclic Triterpenes</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019253" MajorTopicYN="N">Proto-Oncogene Proteins c-bcl-2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014315" MajorTopicYN="N">Triterpenes</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051028" MajorTopicYN="N">bcl-2-Associated X Protein</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>1</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>1</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>7</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30626478</ArticleId></ArticleIdList></PubmedData></PubmedArticle></PubmedArticleSet>trying2...<BR>

<!DOCTYPE html>
  <html dir="ltr" lang="en">
  <head>
    <!-- Google tag (gtag.js) -->
    <script async src="https://www.googletagmanager.com/gtag/js?id=G-442WFVFXCC"></script>
    <script>
      window.dataLayer = window.dataLayer || [];
      function gtag(){dataLayer.push(arguments);}
      gtag('js', new Date());
    
      gtag('config', 'G-442WFVFXCC');
    </script>
  <meta charset="utf-8">
  <meta http-equiv="X-UA-Compatible" content="IE=edge"><script type="text/javascript">(window.NREUM||(NREUM={})).init={privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]},distributed_tracing:{enabled:true}};(window.NREUM||(NREUM={})).loader_config={agentID:"601503912",accountID:"4767844",trustKey:"4767844",xpid:"UAEBVl5XDBAFXFhUBAEPVFI=",licenseKey:"NRJS-750ae8097b9f1344f1a",applicationID:"589630826"};;/*! For license information please see nr-loader-spa-1.277.0.min.js.LICENSE.txt */
(()=>{var e,t,r={8122:(e,t,r)=>{"use strict";r.d(t,{a:()=>i});var n=r(944);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.R)(3);if(!t||"object"!=typeof t)return(0,n.R)(4);const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{if(null===e[a]){r[a]=null;continue}Array.isArray(e[a])&&Array.isArray(t[a])?r[a]=Array.from(new Set([...e[a],...t[a]])):"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.R)(1,e)}return r}catch(e){(0,n.R)(2,e)}}},2555:(e,t,r)=>{"use strict";r.d(t,{Vp:()=>c,fn:()=>s,x1:()=>u});var n=r(384),i=r(8122);const o={beacon:n.NT.beacon,errorBeacon:n.NT.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){try{const t=c(e);return!!t.licenseKey&&!!t.errorBeacon&&!!t.applicationID}catch(e){return!1}}function c(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function u(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.a)(t,o);const r=(0,n.nY)(e);r&&(r.info=a[e])}},9417:(e,t,r)=>{"use strict";r.d(t,{D0:()=>p,gD:()=>m,xN:()=>g});var n=r(3333),i=r(993);const o=e=>{if(!e||"string"!=typeof e)return!1;try{document.createDocumentFragment().querySelector(e)}catch{return!1}return!0};var a=r(2614),s=r(944),c=r(384),u=r(8122);const d="[data-nr-mask]",l=()=>{const e={feature_flags:[],experimental:{marks:!1,measures:!1,resources:!1},mask_selector:"*",block_selector:"[data-nr-block]",mask_input_options:{color:!1,date:!1,"datetime-local":!1,email:!1,month:!1,number:!1,range:!1,search:!1,tel:!1,text:!1,time:!1,url:!1,week:!1,textarea:!1,select:!1,password:!0}};return{ajax:{deny_list:void 0,block_internal:!0,enabled:!0,harvestTimeSeconds:10,autoStart:!0},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},get feature_flags(){return e.feature_flags},set feature_flags(t){e.feature_flags=t},generic_events:{enabled:!0,harvestTimeSeconds:30,autoStart:!0},harvest:{tooManyRequestsDelay:60},jserrors:{enabled:!0,harvestTimeSeconds:10,autoStart:!0},logging:{enabled:!0,harvestTimeSeconds:10,autoStart:!0,level:i.p_.INFO},metrics:{enabled:!0,autoStart:!0},obfuscate:void 0,page_action:{enabled:!0},page_view_event:{enabled:!0,autoStart:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,autoStart:!0},performance:{get capture_marks(){return e.feature_flags.includes(n.$v.MARKS)||e.experimental.marks},set capture_marks(t){e.experimental.marks=t},get capture_measures(){return e.feature_flags.includes(n.$v.MEASURES)||e.experimental.measures},set capture_measures(t){e.experimental.measures=t},resources:{get enabled(){return e.feature_flags.includes(n.$v.RESOURCES)||e.experimental.resources},set enabled(t){e.experimental.resources=t},asset_types:[],first_party_domains:[],ignore_newrelic:!0}},privacy:{cookies_enabled:!0},proxy:{assets:void 0,beacon:void 0},session:{expiresMs:a.wk,inactiveMs:a.BB},session_replay:{autoStart:!0,enabled:!1,harvestTimeSeconds:60,preload:!1,sampling_rate:10,error_sampling_rate:100,collect_fonts:!1,inline_images:!1,fix_stylesheets:!0,mask_all_inputs:!0,get mask_text_selector(){return e.mask_selector},set mask_text_selector(t){o(t)?e.mask_selector="".concat(t,",").concat(d):""===t||null===t?e.mask_selector=d:(0,s.R)(5,t)},get block_class(){return"nr-block"},get ignore_class(){return"nr-ignore"},get mask_text_class(){return"nr-mask"},get block_selector(){return e.block_selector},set block_selector(t){o(t)?e.block_selector+=",".concat(t):""!==t&&(0,s.R)(6,t)},get mask_input_options(){return e.mask_input_options},set mask_input_options(t){t&&"object"==typeof t?e.mask_input_options={...t,password:!0}:(0,s.R)(7,t)}},session_trace:{enabled:!0,harvestTimeSeconds:10,autoStart:!0},soft_navigations:{enabled:!0,harvestTimeSeconds:10,autoStart:!0},spa:{enabled:!0,harvestTimeSeconds:10,autoStart:!0},ssl:void 0,user_actions:{enabled:!0}}},f={},h="All configuration objects require an agent identifier!";function p(e){if(!e)throw new Error(h);if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function g(e,t){if(!e)throw new Error(h);f[e]=(0,u.a)(t,l());const r=(0,c.nY)(e);r&&(r.init=f[e])}function m(e,t){if(!e)throw new Error(h);var r=p(e);if(r){for(var n=t.split("."),i=0;i<n.length-1;i++)if("object"!=typeof(r=r[n[i]]))return;r=r[n[n.length-1]]}return r}},5603:(e,t,r)=>{"use strict";r.d(t,{a:()=>c,o:()=>s});var n=r(384),i=r(8122);const o={accountID:void 0,trustKey:void 0,agentID:void 0,licenseKey:void 0,applicationID:void 0,xpid:void 0},a={};function s(e){if(!e)throw new Error("All loader-config objects require an agent identifier!");if(!a[e])throw new Error("LoaderConfig for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All loader-config objects require an agent identifier!");a[e]=(0,i.a)(t,o);const r=(0,n.nY)(e);r&&(r.loader_config=a[e])}},3371:(e,t,r)=>{"use strict";r.d(t,{V:()=>f,f:()=>l});var n=r(8122),i=r(384),o=r(6154),a=r(9324);let s=0;const c={buildEnv:a.F3,distMethod:a.Xs,version:a.xv,originTime:o.WN},u={customTransaction:void 0,disabled:!1,isolatedBacklog:!1,loaderType:void 0,maxBytes:3e4,onerror:void 0,ptid:void 0,releaseIds:{},appMetadata:{},session:void 0,denyList:void 0,timeKeeper:void 0,obfuscator:void 0},d={};function l(e){if(!e)throw new Error("All runtime objects require an agent identifier!");if(!d[e])throw new Error("Runtime for ".concat(e," was never set"));return d[e]}function f(e,t){if(!e)throw new Error("All runtime objects require an agent identifier!");d[e]={...(0,n.a)(t,u),...c},Object.hasOwnProperty.call(d[e],"harvestCount")||Object.defineProperty(d[e],"harvestCount",{get:()=>++s});const r=(0,i.nY)(e);r&&(r.runtime=d[e])}},9324:(e,t,r)=>{"use strict";r.d(t,{F3:()=>i,Xs:()=>o,Yq:()=>a,xv:()=>n});const n="1.277.0",i="PROD",o="CDN",a="^2.0.0-alpha.17"},6154:(e,t,r)=>{"use strict";r.d(t,{A4:()=>s,OF:()=>d,RI:()=>i,WN:()=>h,bv:()=>o,gm:()=>a,lR:()=>f,m:()=>u,mw:()=>c,sb:()=>l});var n=r(1863);const i="undefined"!=typeof window&&!!window.document,o="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),a=i?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),s="complete"===a?.document?.readyState,c=Boolean("hidden"===a?.document?.visibilityState),u=""+a?.location,d=/iPad|iPhone|iPod/.test(a.navigator?.userAgent),l=d&&"undefined"==typeof SharedWorker,f=(()=>{const e=a.navigator?.userAgent?.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),h=Date.now()-(0,n.t)()},7295:(e,t,r)=>{"use strict";r.d(t,{Xv:()=>a,gX:()=>i,iW:()=>o});var n=[];function i(e){if(!e||o(e))return!1;if(0===n.length)return!0;for(var t=0;t<n.length;t++){var r=n[t];if("*"===r.hostname)return!1;if(s(r.hostname,e.hostname)&&c(r.pathname,e.pathname))return!1}return!0}function o(e){return void 0===e.hostname}function a(e){if(n=[],e&&e.length)for(var t=0;t<e.length;t++){let r=e[t];if(!r)continue;0===r.indexOf("http://")?r=r.substring(7):0===r.indexOf("https://")&&(r=r.substring(8));const i=r.indexOf("/");let o,a;i>0?(o=r.substring(0,i),a=r.substring(i)):(o=r,a="");let[s]=o.split(":");n.push({hostname:s,pathname:a})}}function s(e,t){return!(e.length>t.length)&&t.indexOf(e)===t.length-e.length}function c(e,t){return 0===e.indexOf("/")&&(e=e.substring(1)),0===t.indexOf("/")&&(t=t.substring(1)),""===e||e===t}},1687:(e,t,r)=>{"use strict";r.d(t,{Ak:()=>c,Ze:()=>l,x3:()=>u});var n=r(7836),i=r(3606),o=r(860),a=r(2646);const s={};function c(e,t){const r={staged:!1,priority:o.P3[t]||0};d(e),s[e].get(t)||s[e].set(t,r)}function u(e,t){e&&s[e]&&(s[e].get(t)&&s[e].delete(t),h(e,t,!1),s[e].size&&f(e))}function d(e){if(!e)throw new Error("agentIdentifier required");s[e]||(s[e]=new Map)}function l(e="",t="feature",r=!1){if(d(e),!e||!s[e].get(t)||r)return h(e,t);s[e].get(t).staged=!0,f(e)}function f(e){const t=Array.from(s[e]);t.every((([e,t])=>t.staged))&&(t.sort(((e,t)=>e[1].priority-t[1].priority)),t.forEach((([t])=>{s[e].delete(t),h(e,t)})))}function h(e,t,r=!0){const o=e?n.ee.get(e):n.ee,s=i.i.handlers;if(!o.aborted&&o.backlog&&s){if(r){const e=o.backlog[t],r=s[t];if(r){for(let t=0;e&&t<e.length;++t)p(e[t],r);Object.entries(r).forEach((([e,t])=>{Object.values(t||{}).forEach((t=>{t[0]?.on&&t[0]?.context()instanceof a.y&&t[0].on(e,t[1])}))}))}}o.isolatedBacklog||delete s[t],o.backlog[t]=null,o.emit("drain-"+t,[])}}function p(e,t){var r=e[1];Object.values(t[r]||{}).forEach((t=>{var r=e[0];if(t[0]===r){var n=t[1],i=e[3],o=e[2];n.apply(i,o)}}))}},7836:(e,t,r)=>{"use strict";r.d(t,{P:()=>c,ee:()=>u});var n=r(384),i=r(8990),o=r(3371),a=r(2646),s=r(5607);const c="nr@context:".concat(s.W),u=function e(t,r){var n={},s={},d={},l=!1;try{l=16===r.length&&(0,o.f)(r).isolatedBacklog}catch(e){}var f={on:p,addEventListener:p,removeEventListener:function(e,t){var r=n[e];if(!r)return;for(var i=0;i<r.length;i++)r[i]===t&&r.splice(i,1)},emit:function(e,r,n,i,o){!1!==o&&(o=!0);if(u.aborted&&!i)return;t&&o&&t.emit(e,r,n);for(var a=h(n),c=g(e),d=c.length,l=0;l<d;l++)c[l].apply(a,r);var p=v()[s[e]];p&&p.push([f,e,r,a]);return a},get:m,listeners:g,context:h,buffer:function(e,t){const r=v();if(t=t||"feature",f.aborted)return;Object.entries(e||{}).forEach((([e,n])=>{s[n]=t,t in r||(r[t]=[])}))},abort:function(){f._aborted=!0,Object.keys(f.backlog).forEach((e=>{delete f.backlog[e]}))},isBuffering:function(e){return!!v()[s[e]]},debugId:r,backlog:l?{}:t&&"object"==typeof t.backlog?t.backlog:{},isolatedBacklog:l};return Object.defineProperty(f,"aborted",{get:()=>{let e=f._aborted||!1;return e||(t&&(e=t.aborted),e)}}),f;function h(e){return e&&e instanceof a.y?e:e?(0,i.I)(e,c,(()=>new a.y(c))):new a.y(c)}function p(e,t){n[e]=g(e).concat(t)}function g(e){return n[e]||[]}function m(t){return d[t]=d[t]||e(f,t)}function v(){return f.backlog}}(void 0,"globalEE"),d=(0,n.Zm)();d.ee||(d.ee=u)},2646:(e,t,r)=>{"use strict";r.d(t,{y:()=>n});class n{constructor(e){this.contextId=e}}},9908:(e,t,r)=>{"use strict";r.d(t,{d:()=>n,p:()=>i});var n=r(7836).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},3606:(e,t,r)=>{"use strict";r.d(t,{i:()=>o});var n=r(9908);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.d,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.d);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3878:(e,t,r)=>{"use strict";function n(e,t){return{capture:e,passive:!1,signal:t}}function i(e,t,r=!1,i){window.addEventListener(e,t,n(r,i))}function o(e,t,r=!1,i){document.addEventListener(e,t,n(r,i))}r.d(t,{DD:()=>o,jT:()=>n,sp:()=>i})},5607:(e,t,r)=>{"use strict";r.d(t,{W:()=>n});const n=(0,r(9566).bz)()},9566:(e,t,r)=>{"use strict";r.d(t,{LA:()=>s,ZF:()=>c,bz:()=>a,el:()=>u});var n=r(6154);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n.gm?.crypto||n.gm?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(30))),i.split("").map((e=>"x"===e?o(t,r++).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n.gm?.crypto||n.gm?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(e)));const a=[];for(var s=0;s<e;s++)a.push(o(r,i++).toString(16));return a.join("")}function c(){return s(16)}function u(){return s(32)}},2614:(e,t,r)=>{"use strict";r.d(t,{BB:()=>a,H3:()=>n,g:()=>u,iL:()=>c,tS:()=>s,uh:()=>i,wk:()=>o});const n="NRBA",i="SESSION",o=144e5,a=18e5,s={STARTED:"session-started",PAUSE:"session-pause",RESET:"session-reset",RESUME:"session-resume",UPDATE:"session-update"},c={SAME_TAB:"same-tab",CROSS_TAB:"cross-tab"},u={OFF:0,FULL:1,ERROR:2}},1863:(e,t,r)=>{"use strict";function n(){return Math.floor(performance.now())}r.d(t,{t:()=>n})},7485:(e,t,r)=>{"use strict";r.d(t,{D:()=>i});var n=r(6154);function i(e){if(0===(e||"").indexOf("data:"))return{protocol:"data"};try{const t=new URL(e,location.href),r={port:t.port,hostname:t.hostname,pathname:t.pathname,search:t.search,protocol:t.protocol.slice(0,t.protocol.indexOf(":")),sameOrigin:t.protocol===n.gm?.location?.protocol&&t.host===n.gm?.location?.host};return r.port&&""!==r.port||("http:"===t.protocol&&(r.port="80"),"https:"===t.protocol&&(r.port="443")),r.pathname&&""!==r.pathname?r.pathname.startsWith("/")||(r.pathname="/".concat(r.pathname)):r.pathname="/",r}catch(e){return{}}}},944:(e,t,r)=>{"use strict";function n(e,t){"function"==typeof console.debug&&console.debug("New Relic Warning: https://github.com/newrelic/newrelic-browser-agent/blob/main/docs/warning-codes.md#".concat(e),t)}r.d(t,{R:()=>n})},5284:(e,t,r)=>{"use strict";r.d(t,{t:()=>c,B:()=>s});var n=r(7836),i=r(6154);const o="newrelic";const a=new Set,s={};function c(e,t){const r=n.ee.get(t);s[t]??={},e&&"object"==typeof e&&(a.has(t)||(r.emit("rumresp",[e]),s[t]=e,a.add(t),function(e={}){try{i.gm.dispatchEvent(new CustomEvent(o,{detail:e}))}catch(e){}}({loaded:!0})))}},8990:(e,t,r)=>{"use strict";r.d(t,{I:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},6389:(e,t,r)=>{"use strict";function n(e,t=500,r={}){const n=r?.leading||!1;let i;return(...r)=>{n&&void 0===i&&(e.apply(this,r),i=setTimeout((()=>{i=clearTimeout(i)}),t)),n||(clearTimeout(i),i=setTimeout((()=>{e.apply(this,r)}),t))}}function i(e){let t=!1;return(...r)=>{t||(t=!0,e.apply(this,r))}}r.d(t,{J:()=>i,s:()=>n})},3304:(e,t,r)=>{"use strict";r.d(t,{A:()=>o});var n=r(7836);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())??""}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}return""}}},5289:(e,t,r)=>{"use strict";r.d(t,{GG:()=>o,sB:()=>a});var n=r(3878);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.sp)("load",e,t)}function a(e){if(i())return e();(0,n.DD)("DOMContentLoaded",e)}},384:(e,t,r)=>{"use strict";r.d(t,{NT:()=>o,US:()=>d,Zm:()=>a,bQ:()=>c,dV:()=>s,nY:()=>u,pV:()=>l});var n=r(6154),i=r(1863);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return n.gm.NREUM||(n.gm.NREUM={}),void 0===n.gm.newrelic&&(n.gm.newrelic=n.gm.NREUM),n.gm.NREUM}function s(){let e=a();return e.o||(e.o={ST:n.gm.setTimeout,SI:n.gm.setImmediate,CT:n.gm.clearTimeout,XHR:n.gm.XMLHttpRequest,REQ:n.gm.Request,EV:n.gm.Event,PR:n.gm.Promise,MO:n.gm.MutationObserver,FETCH:n.gm.fetch,WS:n.gm.WebSocket}),e}function c(e,t){let r=a();r.initializedAgents??={},t.initializedAt={ms:(0,i.t)(),date:new Date},r.initializedAgents[e]=t}function u(e){let t=a();return t.initializedAgents?.[e]}function d(e,t){a()[e]=t}function l(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},2843:(e,t,r)=>{"use strict";r.d(t,{u:()=>i});var n=r(3878);function i(e,t=!1,r,i){(0,n.DD)("visibilitychange",(function(){if(t)return void("hidden"===document.visibilityState&&e());e(document.visibilityState)}),r,i)}},8139:(e,t,r)=>{"use strict";r.d(t,{u:()=>f});var n=r(7836),i=r(3434),o=r(8990),a=r(6154);const s={},c=a.gm.XMLHttpRequest,u="addEventListener",d="removeEventListener",l="nr@wrapped:".concat(n.P);function f(e){var t=function(e){return(e||n.ee).get("events")}(e);if(s[t.debugId]++)return t;s[t.debugId]=1;var r=(0,i.YM)(t,!0);function f(e){r.inPlace(e,[u,d],"-",p)}function p(e,t){return e[1]}return"getPrototypeOf"in Object&&(a.RI&&h(document,f),c&&h(c.prototype,f),h(a.gm,f)),t.on(u+"-start",(function(e,t){var n=e[1];if(null!==n&&("function"==typeof n||"object"==typeof n)){var i=(0,o.I)(n,l,(function(){var e={object:function(){if("function"!=typeof n.handleEvent)return;return n.handleEvent.apply(n,arguments)},function:n}[typeof n];return e?r(e,"fn-",null,e.name||"anonymous"):n}));this.wrapped=e[1]=i}})),t.on(d+"-start",(function(e){e[1]=this.wrapped||e[1]})),t}function h(e,t,...r){let n=e;for(;"object"==typeof n&&!Object.prototype.hasOwnProperty.call(n,u);)n=Object.getPrototypeOf(n);n&&t(n,...r)}},3434:(e,t,r)=>{"use strict";r.d(t,{Jt:()=>o,YM:()=>c});var n=r(7836),i=r(5607);const o="nr@original:".concat(i.W);var a=Object.prototype.hasOwnProperty,s=!1;function c(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");const a="-"===n.charAt(0);for(let s=0;s<t.length;s++){const c=t[s],u=e[c];d(u)||(e[c]=r(u,a?c+n:n,i,c,o))}},r.flag=o,r;function r(t,r,n,s,c){return d(t)?t:(r||(r=""),nrWrapper[o]=t,function(e,t,r){if(Object.defineProperty&&Object.keys)try{return Object.keys(e).forEach((function(r){Object.defineProperty(t,r,{get:function(){return e[r]},set:function(t){return e[r]=t,t}})})),t}catch(e){u([e],r)}for(var n in e)a.call(e,n)&&(t[n]=e[n])}(t,nrWrapper,e),nrWrapper);function nrWrapper(){var o,a,d,l;try{a=this,o=[...arguments],d="function"==typeof n?n(o,a):n||{}}catch(t){u([t,"",[o,a,s],d],e)}i(r+"start",[o,a,s],d,c);try{return l=t.apply(a,o)}catch(e){throw i(r+"err",[o,a,e],d,c),e}finally{i(r+"end",[o,a,l],d,c)}}}function i(r,n,i,o){if(!s||t){var a=s;s=!0;try{e.emit(r,n,i,t,o)}catch(t){u([t,r,n,i],e)}s=a}}}function u(e,t){t||(t=n.ee);try{t.emit("internal-error",e)}catch(e){}}function d(e){return!(e&&"function"==typeof e&&e.apply&&!e[o])}},9300:(e,t,r)=>{"use strict";r.d(t,{T:()=>n});const n=r(860).K7.ajax},3333:(e,t,r)=>{"use strict";r.d(t,{$v:()=>u,TZ:()=>n,Zp:()=>i,kd:()=>c,mq:()=>s,nf:()=>a,qN:()=>o});const n=r(860).K7.genericEvents,i=["auxclick","click","copy","keydown","paste","scrollend"],o=["focus","blur"],a=4,s=1e3,c=["PageAction","UserAction","BrowserPerformance"],u={MARKS:"experimental.marks",MEASURES:"experimental.measures",RESOURCES:"experimental.resources"}},6774:(e,t,r)=>{"use strict";r.d(t,{T:()=>n});const n=r(860).K7.jserrors},993:(e,t,r)=>{"use strict";r.d(t,{ET:()=>o,TZ:()=>a,p_:()=>i});var n=r(860);const i={ERROR:"ERROR",WARN:"WARN",INFO:"INFO",DEBUG:"DEBUG",TRACE:"TRACE"},o="log",a=n.K7.logging},3785:(e,t,r)=>{"use strict";r.d(t,{R:()=>c,b:()=>u});var n=r(9908),i=r(1863),o=r(860),a=r(3969),s=r(993);function c(e,t,r={},c=s.p_.INFO){(0,n.p)(a.xV,["API/logging/".concat(c.toLowerCase(),"/called")],void 0,o.K7.metrics,e),(0,n.p)(s.ET,[(0,i.t)(),t,r,c],void 0,o.K7.logging,e)}function u(e){return"string"==typeof e&&Object.values(s.p_).some((t=>t===e.toUpperCase().trim()))}},3969:(e,t,r)=>{"use strict";r.d(t,{TZ:()=>n,XG:()=>s,rs:()=>i,xV:()=>a,z_:()=>o});const n=r(860).K7.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},6630:(e,t,r)=>{"use strict";r.d(t,{T:()=>n});const n=r(860).K7.pageViewEvent},782:(e,t,r)=>{"use strict";r.d(t,{T:()=>n});const n=r(860).K7.pageViewTiming},6344:(e,t,r)=>{"use strict";r.d(t,{BB:()=>d,G4:()=>o,Qb:()=>l,TZ:()=>i,Ug:()=>a,_s:()=>s,bc:()=>u,yP:()=>c});var n=r(2614);const i=r(860).K7.sessionReplay,o={RECORD:"recordReplay",PAUSE:"pauseReplay",REPLAY_RUNNING:"replayRunning",ERROR_DURING_REPLAY:"errorDuringReplay"},a=.12,s={DomContentLoaded:0,Load:1,FullSnapshot:2,IncrementalSnapshot:3,Meta:4,Custom:5},c={[n.g.ERROR]:15e3,[n.g.FULL]:3e5,[n.g.OFF]:0},u={RESET:{message:"Session was reset",sm:"Reset"},IMPORT:{message:"Recorder failed to import",sm:"Import"},TOO_MANY:{message:"429: Too Many Requests",sm:"Too-Many"},TOO_BIG:{message:"Payload was too large",sm:"Too-Big"},CROSS_TAB:{message:"Session Entity was set to OFF on another tab",sm:"Cross-Tab"},ENTITLEMENTS:{message:"Session Replay is not allowed and will not be started",sm:"Entitlement"}},d=5e3,l={API:"api"}},5270:(e,t,r)=>{"use strict";r.d(t,{Aw:()=>c,CT:()=>u,SR:()=>s});var n=r(384),i=r(9417),o=r(7767),a=r(6154);function s(e){return!!(0,n.dV)().o.MO&&(0,o.V)(e)&&!0===(0,i.gD)(e,"session_trace.enabled")}function c(e){return!0===(0,i.gD)(e,"session_replay.preload")&&s(e)}function u(e,t){const r=t.correctAbsoluteTimestamp(e);return{originalTimestamp:e,correctedTimestamp:r,timestampDiff:e-r,originTime:a.WN,correctedOriginTime:t.correctedOriginTime,originTimeDiff:Math.floor(a.WN-t.correctedOriginTime)}}},3738:(e,t,r)=>{"use strict";r.d(t,{He:()=>i,Kp:()=>s,Lc:()=>u,Rz:()=>d,TZ:()=>n,bD:()=>o,d3:()=>a,jx:()=>l,uP:()=>c});const n=r(860).K7.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState",l=1e3},3962:(e,t,r)=>{"use strict";r.d(t,{AM:()=>o,O2:()=>c,Qu:()=>u,TZ:()=>s,ih:()=>d,pP:()=>a,tC:()=>i});var n=r(860);const i=["click","keydown","submit","popstate"],o="api",a="initialPageLoad",s=n.K7.softNav,c={INITIAL_PAGE_LOAD:"",ROUTE_CHANGE:1,UNSPECIFIED:2},u={INTERACTION:1,AJAX:2,CUSTOM_END:3,CUSTOM_TRACER:4},d={IP:"in progress",FIN:"finished",CAN:"cancelled"}},7378:(e,t,r)=>{"use strict";r.d(t,{$p:()=>x,BR:()=>b,Kp:()=>R,L3:()=>y,Lc:()=>c,NC:()=>o,SG:()=>d,TZ:()=>i,U6:()=>p,UT:()=>m,d3:()=>w,dT:()=>f,e5:()=>E,gx:()=>v,l9:()=>l,oW:()=>h,op:()=>g,rw:()=>u,tH:()=>A,uP:()=>s,wW:()=>T,xq:()=>a});var n=r(384);const i=r(860).K7.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",l="remaining",f="interaction",h="spaNode",p="jsonpNode",g="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=(0,n.dV)().o.ST,w="-start",R="-end",x="-body",T="cb"+R,E="jsTime",A="fetch"},4234:(e,t,r)=>{"use strict";r.d(t,{W:()=>o});var n=r(7836),i=r(1687);class o{constructor(e,t){this.agentIdentifier=e,this.ee=n.ee.get(e),this.featureName=t,this.blocked=!1}deregisterDrain(){(0,i.x3)(this.agentIdentifier,this.featureName)}}},7767:(e,t,r)=>{"use strict";r.d(t,{V:()=>o});var n=r(9417),i=r(6154);const o=e=>i.RI&&!0===(0,n.gD)(e,"privacy.cookies_enabled")},425:(e,t,r)=>{"use strict";r.d(t,{j:()=>j});var n=r(860),i=r(2555),o=r(3371),a=r(9908),s=r(7836),c=r(1687),u=r(5289),d=r(6154),l=r(944),f=r(3969),h=r(384),p=r(6344);const g=["setErrorHandler","finished","addToTrace","addRelease","recordCustomEvent","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId","setApplicationVersion","start",p.G4.RECORD,p.G4.PAUSE,"log","wrapLogger"],m=["setErrorHandler","finished","addToTrace","addRelease"];var v=r(1863),b=r(2614),y=r(993),w=r(3785),R=r(2646),x=r(3434);const T=new Map;function E(e,t,r,n){if("object"!=typeof t||!t||"string"!=typeof r||!r||"function"!=typeof t[r])return(0,l.R)(29);const i=function(e){return(e||s.ee).get("logger")}(e),o=(0,x.YM)(i),a=new R.y(s.P);a.level=n.level,a.customAttributes=n.customAttributes;const c=t[r]?.[x.Jt]||t[r];return T.set(c,a),o.inPlace(t,[r],"wrap-logger-",(()=>T.get(c))),i}function A(){const e=(0,h.pV)();g.forEach((t=>{e[t]=(...r)=>function(t,...r){let n=[];return Object.values(e.initializedAgents).forEach((e=>{e&&e.api?e.exposed&&e.api[t]&&n.push(e.api[t](...r)):(0,l.R)(38,t)})),n.length>1?n:n[0]}(t,...r)}))}const S={};var N=r(9417),_=r(5603),O=r(5284);const I=e=>{const t=e.startsWith("http");e+="/",r.p=t?e:"https://"+e};let P=!1;function j(e,t={},g,R){let{init:x,info:T,loader_config:j,runtime:C={},exposed:k=!0}=t;C.loaderType=g;const L=(0,h.pV)();T||(x=L.init,T=L.info,j=L.loader_config),(0,N.xN)(e.agentIdentifier,x||{}),(0,_.a)(e.agentIdentifier,j||{}),T.jsAttributes??={},d.bv&&(T.jsAttributes.isWorker=!0),(0,i.x1)(e.agentIdentifier,T);const H=(0,N.D0)(e.agentIdentifier),M=[T.beacon,T.errorBeacon];P||(H.proxy.assets&&(I(H.proxy.assets),M.push(H.proxy.assets)),H.proxy.beacon&&M.push(H.proxy.beacon),A(),(0,h.US)("activatedFeatures",O.B),e.runSoftNavOverSpa&&=!0===H.soft_navigations.enabled&&H.feature_flags.includes("soft_nav")),C.denyList=[...H.ajax.deny_list||[],...H.ajax.block_internal?M:[]],C.ptid=e.agentIdentifier,(0,o.V)(e.agentIdentifier,C),e.ee=s.ee.get(e.agentIdentifier),void 0===e.api&&(e.api=function(e,t,h=!1){t||(0,c.Ak)(e,"api");const g={};var R=s.ee.get(e),x=R.get("tracer");S[e]=b.g.OFF,R.on(p.G4.REPLAY_RUNNING,(t=>{S[e]=t}));var T="api-",A=T+"ixn-";function N(t,r,n,o){const a=(0,i.Vp)(e);return null===r?delete a.jsAttributes[t]:(0,i.x1)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),I(T,n,!0,o||null===r?"session":void 0)(t,r)}function _(){}g.log=function(e,{customAttributes:t={},level:r=y.p_.INFO}={}){(0,a.p)(f.xV,["API/log/called"],void 0,n.K7.metrics,R),(0,w.R)(R,e,t,r)},g.wrapLogger=(e,t,{customAttributes:r={},level:i=y.p_.INFO}={})=>{(0,a.p)(f.xV,["API/wrapLogger/called"],void 0,n.K7.metrics,R),E(R,e,t,{customAttributes:r,level:i})},m.forEach((e=>{g[e]=I(T,e,!0,"api")})),g.addPageAction=I(T,"addPageAction",!0,n.K7.genericEvents),g.recordCustomEvent=I(T,"recordCustomEvent",!0,n.K7.genericEvents),g.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,o.f)(e).customTransaction=(r||"http://custom.transaction")+t,I(T,"setPageViewName",!0)()},g.setCustomAttribute=function(e,t,r=!1){if("string"==typeof e){if(["string","number","boolean"].includes(typeof t)||null===t)return N(e,t,"setCustomAttribute",r);(0,l.R)(40,typeof t)}else(0,l.R)(39,typeof e)},g.setUserId=function(e){if("string"==typeof e||null===e)return N("enduser.id",e,"setUserId",!0);(0,l.R)(41,typeof e)},g.setApplicationVersion=function(e){if("string"==typeof e||null===e)return N("application.version",e,"setApplicationVersion",!1);(0,l.R)(42,typeof e)},g.start=()=>{try{(0,a.p)(f.xV,["API/start/called"],void 0,n.K7.metrics,R),R.emit("manual-start-all")}catch(e){(0,l.R)(23,e)}},g[p.G4.RECORD]=function(){(0,a.p)(f.xV,["API/recordReplay/called"],void 0,n.K7.metrics,R),(0,a.p)(p.G4.RECORD,[],void 0,n.K7.sessionReplay,R)},g[p.G4.PAUSE]=function(){(0,a.p)(f.xV,["API/pauseReplay/called"],void 0,n.K7.metrics,R),(0,a.p)(p.G4.PAUSE,[],void 0,n.K7.sessionReplay,R)},g.interaction=function(e){return(new _).get("object"==typeof e?e:{})};const O=_.prototype={createTracer:function(e,t){var r={},i=this,o="function"==typeof t;return(0,a.p)(f.xV,["API/createTracer/called"],void 0,n.K7.metrics,R),h||(0,a.p)(A+"tracer",[(0,v.t)(),e,r],i,n.K7.spa,R),function(){if(x.emit((o?"":"no-")+"fn-start",[(0,v.t)(),i,o],r),o)try{return t.apply(this,arguments)}catch(e){const t="string"==typeof e?new Error(e):e;throw x.emit("fn-err",[arguments,this,t],r),t}finally{x.emit("fn-end",[(0,v.t)()],r)}}}};function I(e,t,r,i){return function(){return(0,a.p)(f.xV,["API/"+t+"/called"],void 0,n.K7.metrics,R),i&&(0,a.p)(e+t,[r?(0,v.t)():performance.now(),...arguments],r?null:this,i,R),r?void 0:this}}function P(){r.e(478).then(r.bind(r,8778)).then((({setAPI:t})=>{t(e),(0,c.Ze)(e,"api")})).catch((e=>{(0,l.R)(27,e),R.abort()}))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{O[e]=I(A,e,void 0,h?n.K7.softNav:n.K7.spa)})),g.setCurrentRouteName=h?I(A,"routeName",void 0,n.K7.softNav):I(T,"routeName",!0,n.K7.spa),g.noticeError=function(t,r){"string"==typeof t&&(t=new Error(t)),(0,a.p)(f.xV,["API/noticeError/called"],void 0,n.K7.metrics,R),(0,a.p)("err",[t,(0,v.t)(),!1,r,!!S[e]],void 0,n.K7.jserrors,R)},d.RI?(0,u.GG)((()=>P()),!0):P(),g}(e.agentIdentifier,R,e.runSoftNavOverSpa)),void 0===e.exposed&&(e.exposed=k),P=!0}},8374:(e,t,r)=>{r.nc=(()=>{try{return document?.currentScript?.nonce}catch(e){}return""})()},860:(e,t,r)=>{"use strict";r.d(t,{$J:()=>o,K7:()=>n,P3:()=>i});const n={ajax:"ajax",genericEvents:"generic_events",jserrors:"jserrors",logging:"logging",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",softNav:"soft_navigations",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.spa]:5,[n.ajax]:6,[n.sessionTrace]:7,[n.softNav]:8,[n.sessionReplay]:9,[n.logging]:10,[n.genericEvents]:11},o={[n.pageViewTiming]:"events",[n.ajax]:"events",[n.spa]:"events",[n.softNav]:"events",[n.metrics]:"jserrors",[n.jserrors]:"jserrors",[n.sessionTrace]:"browser/blobs",[n.sessionReplay]:"browser/blobs",[n.logging]:"browser/logs",[n.genericEvents]:"ins"}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>({212:"nr-spa-compressor",249:"nr-spa-recorder",478:"nr-spa"}[e]+"-1.277.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA-1.277.0.PROD:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d<u.length;d++){var l=u[d];if(l.getAttribute("src")==r||l.getAttribute("data-webpack")==t+o){s=l;break}}if(!s){c=!0;var f={478:"sha512-AgX6f6qOxyV4l/Fg8saiNsK37oY3qvFRTOkwua+LDBTL7KUv+eoUSnunEaP3OvjJ1ZiSn43xQyjf9TWbqq8FVQ==",249:"sha512-43TwsElpnwfBCx+EERv4zX5fDsbQLB0w+NTEOt/flpNK9wKjMch+SQIUgLVqaF8jJt5qUeNPsDi/Zk+jgt3SLw==",212:"sha512-/Y+2vKPi087MH5FY89Cw9ahyQ2qnbVj7M2MganYRhmEg4Xos9v/cFPZviY2a1m17D9zpXkOtPsycYXk2AV0huA=="};(s=document.createElement("script")).charset="utf-8",s.timeout=120,i.nc&&s.setAttribute("nonce",i.nc),s.setAttribute("data-webpack",t+o),s.src=r,0!==s.src.indexOf(window.location.origin+"/")&&(s.crossOrigin="anonymous"),f[a]&&(s.integrity=f[a])}e[r]=[n];var h=(t,n)=>{s.onerror=s.onload=null,clearTimeout(p);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},p=setTimeout(h.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=h.bind(null,s.onerror),s.onload=h.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.p="https://js-agent.newrelic.com/",(()=>{var e={38:0,788:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u<a.length;u++)o=a[u],i.o(e,o)&&e[o]&&e[o][0](),e[o]=0},r=self["webpackChunk:NRBA-1.277.0.PROD"]=self["webpackChunk:NRBA-1.277.0.PROD"]||[];r.forEach(t.bind(null,0)),r.push=t.bind(null,r.push.bind(r))})(),(()=>{"use strict";i(8374);var e=i(944),t=i(6344),r=i(9566);class n{agentIdentifier;constructor(e=(0,r.LA)(16)){this.agentIdentifier=e}#e(t,...r){if("function"==typeof this.api?.[t])return this.api[t](...r);(0,e.R)(35,t)}addPageAction(e,t){return this.#e("addPageAction",e,t)}recordCustomEvent(e,t){return this.#e("recordCustomEvent",e,t)}setPageViewName(e,t){return this.#e("setPageViewName",e,t)}setCustomAttribute(e,t,r){return this.#e("setCustomAttribute",e,t,r)}noticeError(e,t){return this.#e("noticeError",e,t)}setUserId(e){return this.#e("setUserId",e)}setApplicationVersion(e){return this.#e("setApplicationVersion",e)}setErrorHandler(e){return this.#e("setErrorHandler",e)}addRelease(e,t){return this.#e("addRelease",e,t)}log(e,t){return this.#e("log",e,t)}}class o extends n{#e(t,...r){if("function"==typeof this.api?.[t])return this.api[t](...r);(0,e.R)(35,t)}start(){return this.#e("start")}finished(e){return this.#e("finished",e)}recordReplay(){return this.#e(t.G4.RECORD)}pauseReplay(){return this.#e(t.G4.PAUSE)}addToTrace(e){return this.#e("addToTrace",e)}setCurrentRouteName(e){return this.#e("setCurrentRouteName",e)}interaction(){return this.#e("interaction")}wrapLogger(e,t,r){return this.#e("wrapLogger",e,t,r)}}var a=i(860),s=i(9417);const c=Object.values(a.K7);function u(e){const t={};return c.forEach((r=>{t[r]=function(e,t){return!0===(0,s.gD)(t,"".concat(e,".enabled"))}(r,e)})),t}var d=i(425);var l=i(1687),f=i(4234),h=i(5289),p=i(6154),g=i(5270),m=i(7767),v=i(6389);class b extends f.W{constructor(e,t,r=!0){super(e.agentIdentifier,t),this.auto=r,this.abortHandler=void 0,this.featAggregate=void 0,this.onAggregateImported=void 0,!1===e.init[this.featureName].autoStart&&(this.auto=!1),this.auto?(0,l.Ak)(e.agentIdentifier,t):this.ee.on("manual-start-all",(0,v.J)((()=>{(0,l.Ak)(e.agentIdentifier,this.featureName),this.auto=!0,this.importAggregator(e)})))}importAggregator(t,r={}){if(this.featAggregate||!this.auto)return;let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let o;try{if((0,m.V)(this.agentIdentifier)){const{setupAgentSession:e}=await i.e(478).then(i.bind(i,6526));o=e(t)}}catch(t){(0,e.R)(20,t),this.ee.emit("internal-error",[t]),this.featureName===a.K7.sessionReplay&&this.abortHandler?.()}try{if(t.sharedAggregator)await t.sharedAggregator;else{t.sharedAggregator=i.e(478).then(i.bind(i,9337));const{EventAggregator:e}=await t.sharedAggregator;t.sharedAggregator=new e}if(!this.#t(this.featureName,o))return(0,l.Ze)(this.agentIdentifier,this.featureName),void n(!1);const{lazyFeatureLoader:e}=await i.e(478).then(i.bind(i,6103)),{Aggregate:a}=await e(this.featureName,"aggregate");this.featAggregate=new a(t,r),n(!0)}catch(t){(0,e.R)(34,t),this.abortHandler?.(),(0,l.Ze)(this.agentIdentifier,this.featureName,!0),n(!1),this.ee&&this.ee.abort()}};p.RI?(0,h.GG)((()=>o()),!0):o()}#t(e,t){switch(e){case a.K7.sessionReplay:return(0,g.SR)(this.agentIdentifier)&&!!t;case a.K7.sessionTrace:return!!t;default:return!0}}}var y=i(6630);class w extends b{static featureName=y.T;constructor(e,t=!0){super(e,y.T,t),this.importAggregator(e)}}var R=i(384);var x=i(9908),T=i(2843),E=i(3878),A=i(782),S=i(1863);class N extends b{static featureName=A.T;constructor(e,t=!0){super(e,A.T,t),p.RI&&((0,T.u)((()=>(0,x.p)("docHidden",[(0,S.t)()],void 0,A.T,this.ee)),!0),(0,E.sp)("pagehide",(()=>(0,x.p)("winPagehide",[(0,S.t)()],void 0,A.T,this.ee))),this.importAggregator(e))}}var _=i(3969);class O extends b{static featureName=_.TZ;constructor(e,t=!0){super(e,_.TZ,t),this.importAggregator(e)}}var I=i(6774),P=i(3304);class j{constructor(e,t,r,n,i){this.name="UncaughtError",this.message="string"==typeof e?e:(0,P.A)(e),this.sourceURL=t,this.line=r,this.column=n,this.__newrelic=i}}function C(e){return H(e)?e:new j(void 0!==e?.message?e.message:e,e?.filename||e?.sourceURL,e?.lineno||e?.line,e?.colno||e?.col,e?.__newrelic)}function k(e){const t="Unhandled Promise Rejection";if(!e?.reason)return;if(H(e.reason))try{return e.reason.message=t+": "+e.reason.message,C(e.reason)}catch(t){return C(e.reason)}const r=C(e.reason);return r.message=t+": "+r?.message,r}function L(e){if(e.error instanceof SyntaxError&&!/:\d+$/.test(e.error.stack?.trim())){const t=new j(e.message,e.filename,e.lineno,e.colno,e.error.__newrelic);return t.name=SyntaxError.name,t}return H(e.error)?e.error:C(e)}function H(e){return e instanceof Error&&!!e.stack}class M extends b{static featureName=I.T;#r=!1;constructor(e,r=!0){super(e,I.T,r);try{this.removeOnAbort=new AbortController}catch(e){}this.ee.on("internal-error",((e,t)=>{this.abortHandler&&(0,x.p)("ierr",[C(e),(0,S.t)(),!0,{},this.#r,t],void 0,this.featureName,this.ee)})),this.ee.on(t.G4.REPLAY_RUNNING,(e=>{this.#r=e})),p.gm.addEventListener("unhandledrejection",(e=>{this.abortHandler&&(0,x.p)("err",[k(e),(0,S.t)(),!1,{unhandledPromiseRejection:1},this.#r],void 0,this.featureName,this.ee)}),(0,E.jT)(!1,this.removeOnAbort?.signal)),p.gm.addEventListener("error",(e=>{this.abortHandler&&(0,x.p)("err",[L(e),(0,S.t)(),!1,{},this.#r],void 0,this.featureName,this.ee)}),(0,E.jT)(!1,this.removeOnAbort?.signal)),this.abortHandler=this.#n,this.importAggregator(e)}#n(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}var D=i(8990);let K=1;const U="nr@id";function V(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===p.gm?0:(0,D.I)(e,U,(function(){return K++}))}function G(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,P.A)(e).length}catch(e){return}}}var F=i(8139),B=i(7836),W=i(3434);const z={},q=["open","send"];function Z(t){var r=t||B.ee;const n=function(e){return(e||B.ee).get("xhr")}(r);if(void 0===p.gm.XMLHttpRequest)return n;if(z[n.debugId]++)return n;z[n.debugId]=1,(0,F.u)(r);var i=(0,W.YM)(n),o=p.gm.XMLHttpRequest,a=p.gm.MutationObserver,s=p.gm.Promise,c=p.gm.setInterval,u="readystatechange",d=["onload","onerror","onabort","onloadstart","onloadend","onprogress","ontimeout"],l=[],f=p.gm.XMLHttpRequest=function(t){const r=new o(t),a=n.context(r);try{n.emit("new-xhr",[r],a),r.addEventListener(u,(s=a,function(){var e=this;e.readyState>3&&!s.resolved&&(s.resolved=!0,n.emit("xhr-resolved",[],e)),i.inPlace(e,d,"fn-",y)}),(0,E.jT)(!1))}catch(t){(0,e.R)(15,t);try{n.emit("internal-error",[t])}catch(e){}}var s;return r};function h(e,t){i.inPlace(t,["onreadystatechange"],"fn-",y)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,f),f.prototype=o.prototype,i.inPlace(f.prototype,q,"-xhr-",y),n.on("send-xhr-start",(function(e,t){h(e,t),function(e){l.push(e),a&&(g?g.then(b):c?c(b):(m=-m,v.data=m))}(t)})),n.on("open-xhr-start",h),a){var g=s&&s.resolve();if(!c&&!s){var m=1,v=document.createTextNode(m);new a(b).observe(v,{characterData:!0})}}else r.on("fn-end",(function(e){e[0]&&e[0].type===u||b()}));function b(){for(var e=0;e<l.length;e++)h(0,l[e]);l.length&&(l=[])}function y(e,t){return t}return n}var Y="fetch-",X=Y+"body-",J=["arrayBuffer","blob","json","text","formData"],Q=p.gm.Request,ee=p.gm.Response,te="prototype";const re={};function ne(e){const t=function(e){return(e||B.ee).get("fetch")}(e);if(!(Q&&ee&&p.gm.fetch))return t;if(re[t.debugId]++)return t;function r(e,r,n){var i=e[r];"function"==typeof i&&(e[r]=function(){var e,r=[...arguments],o={};t.emit(n+"before-start",[r],o),o[B.P]&&o[B.P].dt&&(e=o[B.P].dt);var a=i.apply(this,r);return t.emit(n+"start",[r,e],a),a.then((function(e){return t.emit(n+"end",[null,e],a),e}),(function(e){throw t.emit(n+"end",[e],a),e}))})}return re[t.debugId]=1,J.forEach((e=>{r(Q[te],e,X),r(ee[te],e,X)})),r(p.gm,"fetch",Y),t.on(Y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(Y+"done",[null,r],n)}else t.emit(Y+"done",[e],n)})),t}var ie=i(7485),oe=i(5603);class ae{constructor(e){this.agentIdentifier=e}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var t=(0,oe.o)(this.agentIdentifier);if(!t)return null;var n=(t.accountID||"").toString()||null,i=(t.agentID||"").toString()||null,o=(t.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,r.ZF)(),s=(0,r.el)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof p.gm?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,P.A)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var t=!1,r={};if((0,s.gD)(this.agentIdentifier,"distributed_tracing")&&(r=(0,s.D0)(this.agentIdentifier).distributed_tracing),e.sameOrigin)t=!0;else if(r.allowed_origins instanceof Array)for(var n=0;n<r.allowed_origins.length;n++){var i=(0,ie.D)(r.allowed_origins[n]);if(e.hostname===i.hostname&&e.protocol===i.protocol&&e.port===i.port){t=!0;break}}return t}isDtEnabled(){var e=(0,s.gD)(this.agentIdentifier,"distributed_tracing");return!!e&&!!e.enabled}excludeNewrelicHeader(){var e=(0,s.gD)(this.agentIdentifier,"distributed_tracing");return!!e&&!!e.exclude_newrelic_header}useNewrelicHeaderForCors(){var e=(0,s.gD)(this.agentIdentifier,"distributed_tracing");return!!e&&!1!==e.cors_use_newrelic_header}useTraceContextHeadersForCors(){var e=(0,s.gD)(this.agentIdentifier,"distributed_tracing");return!!e&&!!e.cors_use_tracecontext_headers}}var se=i(9300),ce=i(7295),ue=["load","error","abort","timeout"],de=ue.length,le=(0,R.dV)().o.REQ,fe=(0,R.dV)().o.XHR;class he extends b{static featureName=se.T;constructor(e,t=!0){super(e,se.T,t),this.dt=new ae(e.agentIdentifier),this.handler=(e,t,r,n)=>(0,x.p)(e,t,r,n,this.ee);try{const e={xmlhttprequest:"xhr",fetch:"fetch",beacon:"beacon"};p.gm?.performance?.getEntriesByType("resource").forEach((t=>{if(t.initiatorType in e&&0!==t.responseStatus){const r={status:t.responseStatus},n={rxSize:t.transferSize,duration:Math.floor(t.duration),cbTime:0};pe(r,t.name),this.handler("xhr",[r,n,t.startTime,t.responseEnd,e[t.initiatorType]],void 0,a.K7.ajax)}}))}catch(e){}ne(this.ee),Z(this.ee),function(e,t,r,n){function i(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=R,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){T(t,e)}),(0,E.jT)(!1)),p.lR||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,E.jT)(!1))}function o(e){this.params={method:e[0]},pe(this,e[1]),this.metrics={}}function s(t,r){e.loader_config.xpid&&this.sameOrigin&&r.setRequestHeader("X-NewRelic-ID",e.loader_config.xpid);var i=n.generateTracePayload(this.parsedOrigin);if(i){var o=!1;i.newrelicHeader&&(r.setRequestHeader("newrelic",i.newrelicHeader),o=!0),i.traceContextParentHeader&&(r.setRequestHeader("traceparent",i.traceContextParentHeader),i.traceContextStateHeader&&r.setRequestHeader("tracestate",i.traceContextStateHeader),o=!0),o&&(this.dt=i)}}function c(e,r){var n=this.metrics,i=e[0],o=this;if(n&&i){var a=G(i);a&&(n.txSize=a)}this.startTime=(0,S.t)(),this.body=i,this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof r.onload)&&"function"==typeof o.end)&&o.end(r)}catch(e){try{t.emit("internal-error",[e])}catch(e){}}};for(var s=0;s<de;s++)r.addEventListener(ue[s],this.listener,(0,E.jT)(!1))}function u(e,t,r){this.cbTime+=e,t?this.onloadCalled=!0:this.called+=1,this.called!==this.totalCbs||!this.onloadCalled&&"function"==typeof r.onload||"function"!=typeof this.end||this.end(r)}function d(e,t){var r=""+V(e)+!!t;this.xhrGuids&&!this.xhrGuids[r]&&(this.xhrGuids[r]=!0,this.totalCbs+=1)}function l(e,t){var r=""+V(e)+!!t;this.xhrGuids&&this.xhrGuids[r]&&(delete this.xhrGuids[r],this.totalCbs-=1)}function f(){this.endTime=(0,S.t)()}function h(e,r){r instanceof fe&&"load"===e[0]&&t.emit("xhr-load-added",[e[1],e[2]],r)}function g(e,r){r instanceof fe&&"load"===e[0]&&t.emit("xhr-load-removed",[e[1],e[2]],r)}function m(e,t,r){t instanceof fe&&("onload"===r&&(this.onload=!0),("load"===(e[0]&&e[0].type)||this.onload)&&(this.xhrCbStart=(0,S.t)()))}function v(e,r){this.xhrCbStart&&t.emit("xhr-cb-time",[(0,S.t)()-this.xhrCbStart,this.onload,r],r)}function b(e){var t,r=e[1]||{};if("string"==typeof e[0]?0===(t=e[0]).length&&p.RI&&(t=""+p.gm.location.href):e[0]&&e[0].url?t=e[0].url:p.gm?.URL&&e[0]&&e[0]instanceof URL?t=e[0].href:"function"==typeof e[0].toString&&(t=e[0].toString()),"string"==typeof t&&0!==t.length){t&&(this.parsedOrigin=(0,ie.D)(t),this.sameOrigin=this.parsedOrigin.sameOrigin);var i=n.generateTracePayload(this.parsedOrigin);if(i&&(i.newrelicHeader||i.traceContextParentHeader))if(e[0]&&e[0].headers)s(e[0].headers,i)&&(this.dt=i);else{var o={};for(var a in r)o[a]=r[a];o.headers=new Headers(r.headers||{}),s(o.headers,i)&&(this.dt=i),e.length>1?e[1]=o:e.push(o)}}function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function y(e,t){this.params={},this.metrics={},this.startTime=(0,S.t)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof le?r=i.url:p.gm?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),pe(this,r);var o=(""+(i&&i instanceof le&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.body=n.body,this.txSize=G(n.body)||0}function w(e,t){if(this.endTime=(0,S.t)(),this.params||(this.params={}),(0,ce.iW)(this.params))return;let n;this.params.status=t?t.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);const i={txSize:this.txSize,rxSize:n,duration:(0,S.t)()-this.startTime};r("xhr",[this.params,i,this.startTime,this.endTime,"fetch"],this,a.K7.ajax)}function R(e){const t=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(let t=0;t<de;t++)e.removeEventListener(ue[t],this.listener,!1);t.aborted||(0,ce.iW)(t)||(n.duration=(0,S.t)()-this.startTime,this.loadCaptureCalled||4!==e.readyState?null==t.status&&(t.status=0):T(this,e),n.cbTime=this.cbTime,r("xhr",[t,n,this.startTime,this.endTime,"xhr"],this,a.K7.ajax))}}function T(e,r){e.params.status=r.status;var n=function(e,t){var r=e.responseType;return"json"===r&&null!==t?t:"arraybuffer"===r||"blob"===r||"json"===r?G(e.response):"text"===r||""===r||void 0===r?G(e.responseText):void 0}(r,e.lastSize);if(n&&(e.metrics.rxSize=n),e.sameOrigin){var i=r.getResponseHeader("X-NewRelic-App-Data");i&&((0,x.p)(_.rs,["Ajax/CrossApplicationTracing/Header/Seen"],void 0,a.K7.metrics,t),e.params.cat=i.split(", ").pop())}e.loadCaptureCalled=!0}t.on("new-xhr",i),t.on("open-xhr-start",o),t.on("open-xhr-end",s),t.on("send-xhr-start",c),t.on("xhr-cb-time",u),t.on("xhr-load-added",d),t.on("xhr-load-removed",l),t.on("xhr-resolved",f),t.on("addEventListener-end",h),t.on("removeEventListener-end",g),t.on("fn-end",v),t.on("fetch-before-start",b),t.on("fetch-start",y),t.on("fn-start",m),t.on("fetch-done",w)}(e,this.ee,this.handler,this.dt),this.importAggregator(e)}}function pe(e,t){var r=(0,ie.D)(t),n=e.params||e;n.hostname=r.hostname,n.port=r.port,n.protocol=r.protocol,n.host=r.hostname+":"+r.port,n.pathname=r.pathname,e.parsedOrigin=r,e.sameOrigin=r.sameOrigin}const ge={},me=["pushState","replaceState"];function ve(e){const t=function(e){return(e||B.ee).get("history")}(e);return!p.RI||ge[t.debugId]++||(ge[t.debugId]=1,(0,W.YM)(t).inPlace(window.history,me,"-")),t}var be=i(3738);const{He:ye,bD:we,d3:Re,Kp:xe,TZ:Te,Lc:Ee,uP:Ae,Rz:Se}=be;class Ne extends b{static featureName=Te;constructor(e,t=!0){super(e,Te,t);if(!(0,m.V)(this.agentIdentifier))return void this.deregisterDrain();const r=this.ee;let n;ve(r),this.eventsEE=(0,F.u)(r),this.eventsEE.on(Ae,(function(e,t){this.bstStart=(0,S.t)()})),this.eventsEE.on(Ee,(function(e,t){(0,x.p)("bst",[e[0],t,this.bstStart,(0,S.t)()],void 0,a.K7.sessionTrace,r)})),r.on(Se+Re,(function(e){this.time=(0,S.t)(),this.startPath=location.pathname+location.hash})),r.on(Se+xe,(function(e){(0,x.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,a.K7.sessionTrace,r)}));try{n=new PerformanceObserver((e=>{const t=e.getEntries();(0,x.p)(ye,[t],void 0,a.K7.sessionTrace,r)})),n.observe({type:we,buffered:!0})}catch(e){}this.importAggregator(e,{resourceObserver:n})}}var _e=i(2614);class Oe extends b{static featureName=t.TZ;#i;#o;constructor(e,r=!0){let n;super(e,t.TZ,r),this.replayRunning=!1,this.#o=e;try{n=JSON.parse(localStorage.getItem("".concat(_e.H3,"_").concat(_e.uh)))}catch(e){}(0,g.SR)(e.agentIdentifier)&&this.ee.on(t.G4.RECORD,(()=>this.#a())),this.#s(n)?(this.#i=n?.sessionReplayMode,this.#c()):this.importAggregator(e),this.ee.on("err",(e=>{this.replayRunning&&(this.errorNoticed=!0,(0,x.p)(t.G4.ERROR_DURING_REPLAY,[e],void 0,this.featureName,this.ee))})),this.ee.on(t.G4.REPLAY_RUNNING,(e=>{this.replayRunning=e}))}#s(e){return e&&(e.sessionReplayMode===_e.g.FULL||e.sessionReplayMode===_e.g.ERROR)||(0,g.Aw)(this.agentIdentifier)}#u=!1;async#c(e){if(!this.#u){this.#u=!0;try{const{Recorder:t}=await Promise.all([i.e(478),i.e(249)]).then(i.bind(i,8589));this.recorder??=new t({mode:this.#i,agentIdentifier:this.agentIdentifier,trigger:e,ee:this.ee}),this.recorder.startRecording(),this.abortHandler=this.recorder.stopRecording}catch(e){}this.importAggregator(this.#o,{recorder:this.recorder,errorNoticed:this.errorNoticed})}}#a(){this.featAggregate?this.featAggregate.mode!==_e.g.FULL&&this.featAggregate.initializeRecording(_e.g.FULL,!0):(this.#i=_e.g.FULL,this.#c(t.Qb.API),this.recorder&&this.recorder.parent.mode!==_e.g.FULL&&(this.recorder.parent.mode=_e.g.FULL,this.recorder.stopRecording(),this.recorder.startRecording(),this.abortHandler=this.recorder.stopRecording))}}var Ie=i(3962);class Pe extends b{static featureName=Ie.TZ;constructor(e,t=!0){if(super(e,Ie.TZ,t),!p.RI||!(0,R.dV)().o.MO)return;const r=ve(this.ee);Ie.tC.forEach((e=>{(0,E.sp)(e,(e=>{a(e)}),!0)}));const n=()=>(0,x.p)("newURL",[(0,S.t)(),""+window.location],void 0,this.featureName,this.ee);r.on("pushState-end",n),r.on("replaceState-end",n);try{this.removeOnAbort=new AbortController}catch(e){}(0,E.sp)("popstate",(e=>(0,x.p)("newURL",[e.timeStamp,""+window.location],void 0,this.featureName,this.ee)),!0,this.removeOnAbort?.signal);let i=!1;const o=new((0,R.dV)().o.MO)(((e,t)=>{i||(i=!0,requestAnimationFrame((()=>{(0,x.p)("newDom",[(0,S.t)()],void 0,this.featureName,this.ee),i=!1})))})),a=(0,v.s)((e=>{(0,x.p)("newUIEvent",[e],void 0,this.featureName,this.ee),o.observe(document.body,{attributes:!0,childList:!0,subtree:!0,characterData:!0})}),100,{leading:!0});this.abortHandler=function(){this.removeOnAbort?.abort(),o.disconnect(),this.abortHandler=void 0},this.importAggregator(e,{domObserver:o})}}var je=i(7378);const Ce={},ke=["appendChild","insertBefore","replaceChild"];function Le(e){const t=function(e){return(e||B.ee).get("jsonp")}(e);if(!p.RI||Ce[t.debugId])return t;Ce[t.debugId]=!0;var r=(0,W.YM)(t),n=/[?&](?:callback|cb)=([^&#]+)/,i=/(.*)\.([^.]+)/,o=/^(\w+)(\.|$)(.*)$/;function a(e,t){if(!e)return t;const r=e.match(o),n=r[1];return a(r[3],t[n])}return r.inPlace(Node.prototype,ke,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var o=(s=e.src,c=s.match(n),c?c[1]:null);var s,c;if(!o)return;var u=function(e){var t=e.match(i);if(t&&t.length>=3)return{key:t[2],parent:a(t[1],window)};return{key:e,parent:window}}(o);if("function"!=typeof u.parent[u.key])return;var d={};function l(){t.emit("jsonp-end",[],d),e.removeEventListener("load",l,(0,E.jT)(!1)),e.removeEventListener("error",f,(0,E.jT)(!1))}function f(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",l,(0,E.jT)(!1)),e.removeEventListener("error",f,(0,E.jT)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",l,(0,E.jT)(!1)),e.addEventListener("error",f,(0,E.jT)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}const He={};function Me(e){const t=function(e){return(e||B.ee).get("promise")}(e);if(He[t.debugId])return t;He[t.debugId]=!0;var r=t.context,n=(0,W.YM)(t),i=p.gm.Promise;return i&&function(){function e(r){var o=t.context(),a=n(r,"executor-",o,null,!1);const s=Reflect.construct(i,[a],e);return t.context(s).getCtx=function(){return o},s}p.gm.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return i.toString()},Object.setPrototypeOf(e,i),["all","race"].forEach((function(r){const n=i[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=i[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=i.prototype;const o=i.prototype.then;i.prototype.then=function(...e){var i=this,a=r(i);a.promise=i,e[0]=n(e[0],"cb-",a,null,!1),e[1]=n(e[1],"cb-",a,null,!1);const s=o.apply(this,e);return a.nextPromise=s,t.emit("propagate",[i,!0],s,!1,!1),s},i.prototype.then[W.Jt]=o,t.on("executor-start",(function(e){e[0]=n(e[0],"resolve-",this,null,!1),e[1]=n(e[1],"resolve-",this,null,!1)})),t.on("executor-err",(function(e,t,r){e[1](r)})),t.on("cb-end",(function(e,r,n){t.emit("propagate",[n,!0],this.nextPromise,!1,!1)})),t.on("propagate",(function(e,r,n){this.getCtx&&!r||(this.getCtx=function(){if(e instanceof Promise)var r=t.context(e);return r&&r.getCtx?r.getCtx():this})}))}(),t}const De={},Ke="setTimeout",Ue="setInterval",Ve="clearTimeout",Ge="-start",Fe=[Ke,"setImmediate",Ue,Ve,"clearImmediate"];function Be(e){const t=function(e){return(e||B.ee).get("timer")}(e);if(De[t.debugId]++)return t;De[t.debugId]=1;var r=(0,W.YM)(t);return r.inPlace(p.gm,Fe.slice(0,2),Ke+"-"),r.inPlace(p.gm,Fe.slice(2,3),Ue+"-"),r.inPlace(p.gm,Fe.slice(3),Ve+"-"),t.on(Ue+Ge,(function(e,t,n){e[0]=r(e[0],"fn-",null,n)})),t.on(Ke+Ge,(function(e,t,n){this.method=n,this.timerDuration=isNaN(e[1])?0:+e[1],e[0]=r(e[0],"fn-",this,n)})),t}const We={};function ze(e){const t=function(e){return(e||B.ee).get("mutation")}(e);if(!p.RI||We[t.debugId])return t;We[t.debugId]=!0;var r=(0,W.YM)(t),n=p.gm.MutationObserver;return n&&(window.MutationObserver=function(e){return this instanceof n?new n(r(e,"fn-")):n.apply(this,arguments)},MutationObserver.prototype=n.prototype),t}const{TZ:qe,d3:Ze,Kp:Ye,$p:Xe,wW:$e,e5:Je,tH:Qe,uP:et,rw:tt,Lc:rt}=je;class nt extends b{static featureName=qe;constructor(e,t=!0){if(super(e,qe,t),!p.RI)return;try{this.removeOnAbort=new AbortController}catch(e){}let r,n=0;const i=this.ee.get("tracer"),o=Le(this.ee),a=Me(this.ee),s=Be(this.ee),c=Z(this.ee),u=this.ee.get("events"),d=ne(this.ee),l=ve(this.ee),f=ze(this.ee);function h(e,t){l.emit("newURL",[""+window.location,t])}function g(){n++,r=window.location.hash,this[et]=(0,S.t)()}function m(){n--,window.location.hash!==r&&h(0,!0);var e=(0,S.t)();this[Je]=~~this[Je]+e-this[et],this[rt]=e}function v(e,t){e.on(t,(function(){this[t]=(0,S.t)()}))}this.ee.on(et,g),a.on(tt,g),o.on(tt,g),this.ee.on(rt,m),a.on($e,m),o.on($e,m),this.ee.on("fn-err",((...t)=>{t[2]?.__newrelic?.[e.agentIdentifier]||(0,x.p)("function-err",[...t],void 0,this.featureName,this.ee)})),this.ee.buffer([et,rt,"xhr-resolved"],this.featureName),u.buffer([et],this.featureName),s.buffer(["setTimeout"+Ye,"clearTimeout"+Ze,et],this.featureName),c.buffer([et,"new-xhr","send-xhr"+Ze],this.featureName),d.buffer([Qe+Ze,Qe+"-done",Qe+Xe+Ze,Qe+Xe+Ye],this.featureName),l.buffer(["newURL"],this.featureName),f.buffer([et],this.featureName),a.buffer(["propagate",tt,$e,"executor-err","resolve"+Ze],this.featureName),i.buffer([et,"no-"+et],this.featureName),o.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),v(d,Qe+Ze),v(d,Qe+"-done"),v(o,"new-jsonp"),v(o,"jsonp-end"),v(o,"cb-start"),l.on("pushState-end",h),l.on("replaceState-end",h),window.addEventListener("hashchange",h,(0,E.jT)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",h,(0,E.jT)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){h(0,n>1)}),(0,E.jT)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#n,this.importAggregator(e)}#n(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}var it=i(3333);class ot extends b{static featureName=it.TZ;constructor(e,t=!0){super(e,it.TZ,t);const r=[e.init.page_action.enabled,e.init.performance.capture_marks,e.init.performance.capture_measures,e.init.user_actions.enabled,e.init.performance.resources.enabled];if(p.RI&&(e.init.user_actions.enabled&&(it.Zp.forEach((e=>(0,E.sp)(e,(e=>(0,x.p)("ua",[e],void 0,this.featureName,this.ee)),!0))),it.qN.forEach((e=>(0,E.sp)(e,(e=>(0,x.p)("ua",[e],void 0,this.featureName,this.ee)))))),e.init.performance.resources.enabled&&p.gm.PerformanceObserver?.supportedEntryTypes.includes("resource"))){new PerformanceObserver((e=>{e.getEntries().forEach((e=>{(0,x.p)("browserPerformance.resource",[e],void 0,this.featureName,this.ee)}))})).observe({type:"resource",buffered:!0})}r.some((e=>e))?this.importAggregator(e):this.deregisterDrain()}}var at=i(993),st=i(3785);class ct extends b{static featureName=at.TZ;constructor(e,t=!0){super(e,at.TZ,t);const r=this.ee;this.ee.on("wrap-logger-end",(function([e]){const{level:t,customAttributes:n}=this;(0,st.R)(r,e,n,t)})),this.importAggregator(e)}}new class extends o{constructor(t,r){super(r),p.gm?(this.features={},(0,R.bQ)(this.agentIdentifier,this),this.desiredFeatures=new Set(t.features||[]),this.desiredFeatures.add(w),this.runSoftNavOverSpa=[...this.desiredFeatures].some((e=>e.featureName===a.K7.softNav)),(0,d.j)(this,t,t.loaderType||"agent"),this.run()):(0,e.R)(21)}get config(){return{info:this.info,init:this.init,loader_config:this.loader_config,runtime:this.runtime}}run(){try{const t=u(this.agentIdentifier),r=[...this.desiredFeatures];r.sort(((e,t)=>a.P3[e.featureName]-a.P3[t.featureName])),r.forEach((r=>{if(!t[r.featureName]&&r.featureName!==a.K7.pageViewEvent)return;if(this.runSoftNavOverSpa&&r.featureName===a.K7.spa)return;if(!this.runSoftNavOverSpa&&r.featureName===a.K7.softNav)return;const n=function(e){switch(e){case a.K7.ajax:return[a.K7.jserrors];case a.K7.sessionTrace:return[a.K7.ajax,a.K7.pageViewEvent];case a.K7.sessionReplay:return[a.K7.sessionTrace];case a.K7.pageViewTiming:return[a.K7.pageViewEvent];default:return[]}}(r.featureName).filter((e=>!(e in this.features)));n.length>0&&(0,e.R)(36,{targetFeature:r.featureName,missingDependencies:n}),this.features[r.featureName]=new r(this)}))}catch(t){(0,e.R)(22,t);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,R.Zm)();delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.features,delete this.sharedAggregator;return r.ee.get(this.agentIdentifier).abort(),!1}}}({features:[he,w,N,Ne,Oe,O,M,ot,ct,Pe,nt],loaderType:"spa"})})()})();</script>
  <meta name="viewport" content="width=device-width, initial-scale=1">
  <meta name="keywords" content="">
  <meta name="description" content="LitMetric - Explore Scientific Literature">
  <!-- css file -->
  <link rel="stylesheet" href="https://www.litmetric.com/css/bootstrap.min.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/ace-responsive-menu.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/menu.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/fontawesome.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/flaticon.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/bootstrap-select.min.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/ud-custom-spacing.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/animate.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/jquery-ui.min.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/style.css?v=1.28">
  <!-- Responsive stylesheet -->
  <link rel="stylesheet" href="https://www.litmetric.com/css/responsive.css">
  <!-- Title -->
    <title>Publications by Zhao-Nan Cai | LitMetric</title>
  <!-- Favicon -->
  <link href="https://www.litmetric.com/images/favicon.ico?v=1.1" sizes="128x128" rel="shortcut icon" type="image/x-icon" />
  <link href="https://www.litmetric.com/images/favicon.ico?v=1.1" sizes="128x128" rel="shortcut icon" />
  <!-- Apple Touch Icon -->
  <link href="https://www.litmetric.com/images/apple-touch-icon-60x60.png?v=1.1" sizes="60x60" rel="apple-touch-icon">
  <link href="https://www.litmetric.com/images/apple-touch-icon-72x72.png?v=1.1" sizes="72x72" rel="apple-touch-icon">
  <link href="https://www.litmetric.com/images/apple-touch-icon-114x114.png?v=1.1" sizes="114x114" rel="apple-touch-icon">
  <link href="https://www.litmetric.com/images/apple-touch-icon-180x180.png?v=1.1" sizes="180x180" rel="apple-touch-icon">
  
  <!-- HTML5 shim and Respond.js for IE8 support of HTML5 elements and media queries -->
  <!-- WARNING: Respond.js doesn't work if you view the page via file:// -->
  <!--[if lt IE 9]>
  <script src="https://oss.maxcdn.com/html5shiv/3.7.3/html5shiv.min.js"></script>
  <script src="https://oss.maxcdn.com/respond/1.4.2/respond.min.js"></script>
  <![endif]-->

  </head>
  <body>
  <div class="wrapper ovh">
 <!--   <div class="preloader"></div> -->
    
    <!-- Main Header Nav -->
    <header class="header-nav nav-innerpage-style main-menu">
      <!-- Ace Responsive Menu -->
      <nav class="posr"> 
        <div class="container-fluid posr menu_bdrt1">
          <div class="row align-items-center justify-content-between">
            <div class="col-auto pe-0">
              <div class="d-flex align-items-center">
        <a class="header-logo bdrr1 pr30 pr5-xl" href="https://www.litmetric.com/home"><img src="https://www.litmetric.com/images/header-logo-dark.png" alt="LitMetric"></a>
                <div class="home1_style">
                  <div id="mega-menu">
                    <a class="btn-mega fw500" href="https://www.litmetric.com/categories"><span class="pl30 pl10-xl pr5 fz15 vam flaticon-menu"></span>Article  Categories</a>
                    
               <ul class="menu ps-0"><li> <a class="dropdown" href="https://www.litmetric.com/categories/Allergy+and+Immunology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Allergy and Immunology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Cardiology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Cardiology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Clinical+Procedures"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Clinical Procedures</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Critical+Care"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Critical Care</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Dermatology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Dermatology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Emergency+Medicine"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Emergency Medicine</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Endocrinology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Endocrinology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Gastroenterology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Gastroenterology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Genomic+Medicine"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Genomic Medicine</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Hematology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Hematology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Infectious+Diseases"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Infectious Diseases</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Nephrology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Nephrology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Neurology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Neurology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Obstetrics+and+Gynecology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Obstetrics and Gynecology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Oncology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Oncology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Pathology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Pathology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Perioperative+Care"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Perioperative Care</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Physical+Medicine+and+Rehabilitation"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Physical & Rehabilitation</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Psychiatry"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Psychiatry</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Pulmonology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Pulmonology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Radiology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Radiology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Rheumatology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Rheumatology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Sports+Medicine"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Sports Medicine</span> </a>
                   </li></ul>
                  
                  
                  
                  
                  </div>
                </div>
              </div>
            </div>
            <div class="col-auto">
              <div class="d-flex align-items-center">
                <!-- Responsive Menu Structure-->
                <ul id="respMenu" class="ace-responsive-menu" data-menu-style="horizontal">
                 
                
                <li> <a class="list-item" href="https://www.litmetric.com/categories">Browse Categories</a></li>
                <li> <a class="list-item" href="https://www.litmetric.com/drugs">Browse Drugs</a></li>
                <li> <a class="list-item" href="https://www.litmetric.com/journals">Browse Journals</a></li>
           <!--     <li> <a class="list-item" href="https://www.litmetric.com/authors">Browse Authors</a></li>-->
                </ul>
                <a class="login-info bdrl1 pl15-lg pl30" data-bs-toggle="modal" href="#exampleModalToggle" role="button"><span class="flaticon-loupe"></span></a>
                <div class="login-info mx15-lg mx30" class="login-info mr15-lg mr30"></div>
 <!--
                <a class="login-info mx15-lg mx30" class="login-info mr15-lg mr30" href="page-login.html">Sign in</a>
                <a class="ud-btn btn-thm add-joining" href="page-register.html">Join</a>
                
              -->
              </div>
            </div>
          </div>
        </div>
      </nav>
    </header>



            
            <!-- Search Modal -->
            <div class="search-modal">
              
              <form action="https://www.litmetric.com/search" method="post" >
              <div class="modal fade" id="exampleModalToggle" aria-hidden="true" aria-labelledby="exampleModalToggleLabel" tabindex="-1">
                <div class="modal-dialog modal-lg">
                  <div class="modal-content">
                    <div class="modal-header">
                      <h5 class="modal-title" id="exampleModalToggleLabel"></h5>
                      <button type="button" class="btn-close" data-bs-dismiss="modal" aria-label="Close"><i class="fal fa-xmark"></i></button>
                    </div>
                    <div class="modal-body">
                      <div class="popup-search-field search_area">
                        <input type="text" class="form-control border-0" placeholder="Article title or keywords" name="searchterm" >
                        <label><span class="far fa-magnifying-glass"></span></label>
                        <button class="ud-btn btn-thm" type="submit">Search</button>
                       
                      </div>
                    </div>
                  </div>
                </div>
              </div>
              </form>
            </div>
            
            <div class="hiddenbar-body-ovelay"></div>
            
       <!-- Mobile Nav  -->
<div id="page" class="mobilie_header_nav stylehome1">
  <div class="mobile-menu">
    <div class="header bdrb1">
      <div class="menu_and_widgets">
        <div class="mobile_menu_bar d-flex justify-content-between align-items-center">
          <a class="mobile_logo" href="https://www.litmetric.com/"><img src="https://www.litmetric.com/images/header-logo-dark.png" alt=""></a>
          <div class="right-side text-end">
            
              <a class="" href="https://www.litmetric.com/categories">Browse Categories</a>



            <a class="menubar ml30" href="#menu"><img src="https://www.litmetric.com/images/mobile-dark-nav-icon.svg" alt=""></a>
          </div>
        </div>
      </div>
      <div class="posr"><div class="mobile_menu_close_btn"><span class="far fa-times"></span></div></div>
    </div>
  </div>
  <!-- /.mobile-menu -->
  <nav id="menu" class="">
    <ul>
      <li><span><a href="https://www.litmetric.com/categories">Browse Categories</a></span>
        <ul>
	        <li><a  href="https://www.litmetric.com/categories/Allergy+and+Immunology">Allergy and Immunology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Cardiology">Cardiology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Clinical+Procedures">Clinical Procedures</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Critical+Care">Critical Care</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Dermatology">Dermatology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Emergency+Medicine">Emergency Medicine</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Endocrinology">Endocrinology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Gastroenterology">Gastroenterology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Genomic+Medicine">Genomic Medicine</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Hematology">Hematology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Infectious+Diseases">Infectious Diseases</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Nephrology">Nephrology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Neurology">Neurology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Obstetrics+and+Gynecology">Obstetrics and Gynecology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Oncology">Oncology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Pathology">Pathology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Perioperative+Care">Perioperative Care</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Physical+Medicine+and+Rehabilitation">Physical & Rehabilitation</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Psychiatry">Psychiatry</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Pulmonology">Pulmonology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Radiology">Radiology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Rheumatology">Rheumatology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Sports+Medicine">Sports Medicine</a></li>
	        </ul>
                   
      </li>
      <li><span><a href="https://www.litmetric.com/journals">Browse Journals</a></span>
      <ul>
	        <li></li>
	        </ul>
	        
      </li>
      <!-- Only for Mobile View -->
    </ul>
  </nav>
</div>


 
        
        
         
            <div class="body_content bgc-thm3">
              
               
     
              <!-- Breadcumb Sections -->
              <section class="breadcumb-section">
                <div class="container">
                  <div class="row">
                     
                                  
                  </div>
                </div>
              </section>
              
   
                        



   

<script type="application/ld+json">
    {
      "@context": "http://schema.org",
      "@type": "Person",

      "name": "Zhao-Nan Cai",


      "url": "https://www.litmetric.com/author/Zhao-Nan+Cai"

    }
    </script>


  
   
   <!-- Breadcumb Sections -->
   <section class="breadcumb-section pt-0">
     <div class="cta-service-v1 freelancer-single-style mx-auto maxw1700 pt20 pt60-sm pb20 pb60-sm bdrs16 position-relative overflow-hidden d-flex align-items-center mx20-lg px30-lg" style="height:auto">
       <img class="left-top-img wow zoomIn" src="https://www.litmetric.com/images/vector-img/left-top.png" alt="">
       <img class="right-bottom-img wow zoomIn" src="https://www.litmetric.com/images/vector-img/right-bottom.png" alt="">
       <div class="container">
         <div class="row wow fadeInUp">
           <div class="col-xl-10">
             <div class="position-relative">
               <h2>Publications by authors named "Zhao-Nan Cai"</h2>
               <div class="list-meta d-sm-flex align-items-center mt15">
             
          <!--       <div class="ml5 ml0-xs">
            
                    <p class="mb-0 dark-color fz15 fw500 list-inline-item ml15 mb5-sm ml0-xs"><i class="flaticon-contract vam fz20 me-2"></i> </p>
              
                   <p class="mb-0 dark-color fz15 fw500 list-inline-item mr15  mb5-sm ml0-xs"><i class="flaticon-place text-thm2 vam fz20 me-2"></i> </p>
                 </div>
               -->
               </div>
             </div>
           </div>
         </div>
       </div>
     </div>
   </section>
   
   
   
   <!-- Service Details -->
   <section class="pt10 pb90 pb30-md">
     <div class="container">
      
        
        
       <div class="row wow fadeInUp">
	       
    <div class="col-lg-12">
                     
                                     <div class="mbp_pagination text-right"><ul class="page_navigation" style="text-align:right"><li class="page-item" style="border:none;">Page <strong>1</strong> of <strong>2</strong></li><li class="page-item bg-white"><a href="https://www.litmetric.com/author/Zhao-Nan+Cai/2" class="page-link" style="height:auto" data-ci-pagination-page="2" rel="next"><span class="fas fa-angle-right"></span></a></li></ul></div> 
                          
                          <!--
                            <div class="publication-title-box">
                            <p><strong></strong>Reads</p>
                          </div>
                           <div class="publication-title-box">
                            <p><strong></strong>Profile Views</p>
                          </div>
                          -->
                     
                       </div>
                       
             
                                        
         <div class="col-lg-12">
                           
           <div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/39538854/Accurate-two-dimensional-simulation-model-and-experimental-demonstration-in-ultraviolet-picosecond-l">Accurate two-dimensional simulation model and experimental demonstration in ultraviolet picosecond laser scribing ablation.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zhiying+Xu" class="tag" style="margin-bottom: 5px;">Zhiying Xu</a> <a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Caijie+Zhang" class="tag" style="margin-bottom: 5px;">Caijie Zhang</a> <a href="https://www.litmetric.com/author/Shixian+Cai" class="tag" style="margin-bottom: 5px;">Shixian Cai</a> <a href="https://www.litmetric.com/author/Kai+Wang" class="tag" style="margin-bottom: 5px;">Kai Wang</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Opt Express</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> July 2024</p></div>
								 </div><p class="text mt10">Laser patterning of copper thin films is essential for the electronics manufacturing industry. In this work, to efficiently and accurately describe the physics process of UV-ps laser ablating copper thin film, a two-temperature model (TTM) consisting of the electron-lattice system and phase explosion mechanism was proposed. The process of electron heating and electron-lattice heat transfer in single pulse ablation were revealed.</p><a href="https://www.litmetric.com/detail/39538854/Accurate-two-dimensional-simulation-model-and-experimental-demonstration-in-ultraviolet-picosecond-l" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/39504356/Integrative-multiomic-analysis-identifies-distinct-molecular-subtypes-of-NAFLD-in-a-Chinese-populati">Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Jingjing+Ding" class="tag" style="margin-bottom: 5px;">Jingjing Ding</a> <a href="https://www.litmetric.com/author/Huaizheng+Liu" class="tag" style="margin-bottom: 5px;">Huaizheng Liu</a> <a href="https://www.litmetric.com/author/Xiaoxun+Zhang" class="tag" style="margin-bottom: 5px;">Xiaoxun Zhang</a> <a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Ying+Peng" class="tag" style="margin-bottom: 5px;">Ying Peng</a> <a href="https://www.litmetric.com/author/Shi-Ying+Cai" class="tag" style="margin-bottom: 5px;">Shi-Ying Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Sci Transl Med</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> November 2024</p></div>
								 </div><p class="text mt10">Nonalcoholic fatty liver disease (NAFLD) has become a common health care burden worldwide. The high heterogeneity of NAFLD remains elusive and impairs outcomes of clinical diagnosis and pharmacotherapy. Several NAFLD classifications have been proposed on the basis of clinical, genetic, alcoholic, or serum metabolic analyses.</p><a href="https://www.litmetric.com/detail/39504356/Integrative-multiomic-analysis-identifies-distinct-molecular-subtypes-of-NAFLD-in-a-Chinese-populati" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/38985995/Hepatic-GDP-fucose-transporter-SLC35C1-attenuates-cholestatic-liver-injury-and-inflammation-by-induc">Hepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Liangjun+Zhang" class="tag" style="margin-bottom: 5px;">Liangjun Zhang</a> <a href="https://www.litmetric.com/author/Pingfan+Xie" class="tag" style="margin-bottom: 5px;">Pingfan Xie</a> <a href="https://www.litmetric.com/author/Mingqiao+Li" class="tag" style="margin-bottom: 5px;">Mingqiao Li</a> <a href="https://www.litmetric.com/author/Xiaoxun+Zhang" class="tag" style="margin-bottom: 5px;">Xiaoxun Zhang</a> <a href="https://www.litmetric.com/author/Shuke+Fei" class="tag" style="margin-bottom: 5px;">Shuke Fei</a> <a href="https://www.litmetric.com/author/Shi-Ying+Cai" class="tag" style="margin-bottom: 5px;">Shi-Ying Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Hepatology</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> July 2024</p></div>
								 </div><p class="text mt10"><em>Background And Aims</em>: Inflammatory response is crucial for bile acid (BA)-induced cholestatic liver injury, but molecular mechanisms remain to be elucidated. Solute Carrier Family 35 Member C1 (SLC35C1) can transport Guanosine diphosphate-fucose into the Golgi to facilitate protein glycosylation. Its mutation leads to the deficiency of leukocyte adhesion and enhances inflammation in humans.</p><a href="https://www.litmetric.com/detail/38985995/Hepatic-GDP-fucose-transporter-SLC35C1-attenuates-cholestatic-liver-injury-and-inflammation-by-induc" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/37851699/Speech-errors-in-consecutive-interpreting-Effects-of-language-proficiency-working-memory-and-anxiety">Speech errors in consecutive interpreting: Effects of language proficiency, working memory, and anxiety.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Zhenguang+G+Cai" class="tag" style="margin-bottom: 5px;">Zhenguang G Cai</a> <a href="https://www.litmetric.com/author/Yanping+Dong" class="tag" style="margin-bottom: 5px;">Yanping Dong</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> PLoS One</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> October 2023</p></div>
								 </div><p class="text mt10">Interpreting can be seen as a form of language production, where interpreters extract conceptual information from the source language and express it in the target language. Hence, like language production, interpreting contains speech errors at various (e.g.</p><a href="https://www.litmetric.com/detail/37851699/Speech-errors-in-consecutive-interpreting-Effects-of-language-proficiency-working-memory-and-anxiety" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/37146714/Organic-Anion-Transporting-Polypeptide-OATP-1B3-is-a-Significant-Transporter-for-Hepatic-Uptake-of-C">Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Qiong+Pan" class="tag" style="margin-bottom: 5px;">Qiong Pan</a> <a href="https://www.litmetric.com/author/Guanyu+Zhu" class="tag" style="margin-bottom: 5px;">Guanyu Zhu</a> <a href="https://www.litmetric.com/author/Ziqian+Xu" class="tag" style="margin-bottom: 5px;">Ziqian Xu</a> <a href="https://www.litmetric.com/author/Jinfei+Zhu" class="tag" style="margin-bottom: 5px;">Jinfei Zhu</a> <a href="https://www.litmetric.com/author/Jiafeng+Ouyang" class="tag" style="margin-bottom: 5px;">Jiafeng Ouyang</a> <a href="https://www.litmetric.com/author/Shi-Ying+Cai" class="tag" style="margin-bottom: 5px;">Shi-Ying Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Cell Mol Gastroenterol Hepatol</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> July 2023</p></div>
								 </div><p class="text mt10"><em>Background & Aims</em>: OATP1B3/SLCO1B3 is a human liver-specific transporter for the clearance of endogenous compounds (eg, bile acid [BA]) and xenobiotics. The functional role of OATP1B3 in humans has not been characterized, as SLCO1B3 is poorly conserved among species without mouse orthologs.<BR><BR><em>Methods</em>: Slc10a1-knockout (Slc10a1), Slc10a1 (endogenous mouse Slc10a1 promoter-driven human-SLCO1B3 expression in Slc10a1 mice), and human SLCO1B3 liver-specific transgenic (hSLCO1B3-LTG) mice were generated and challenged with 0.</p><a href="https://www.litmetric.com/detail/37146714/Organic-Anion-Transporting-Polypeptide-OATP-1B3-is-a-Significant-Transporter-for-Hepatic-Uptake-of-C" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/37120214/Effects-of-endogenous-capsaicin-stress-and-fermentation-time-on-the-microbial-succession-and-flavor-">Effects of endogenous capsaicin stress and fermentation time on the microbial succession and flavor compounds of chili paste (a Chinese fermented chili pepper).</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Qiao+Shi" class="tag" style="margin-bottom: 5px;">Qiao Shi</a> <a href="https://www.litmetric.com/author/Huihua+Tang" class="tag" style="margin-bottom: 5px;">Huihua Tang</a> <a href="https://www.litmetric.com/author/Yuan+Mei" class="tag" style="margin-bottom: 5px;">Yuan Mei</a> <a href="https://www.litmetric.com/author/Junfei+Chen" class="tag" style="margin-bottom: 5px;">Junfei Chen</a> <a href="https://www.litmetric.com/author/Xinrui+Wang" class="tag" style="margin-bottom: 5px;">Xinrui Wang</a> <a href="https://www.litmetric.com/author/Yingli+Cai" class="tag" style="margin-bottom: 5px;">Yingli Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Food Res Int</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> June 2023</p></div>
								 </div><p class="text mt10">Chili paste, is a popular traditional product derived from chili pepper, and its fermentation system is affected by the variable concentration of capsaicin, which originates from the peppers. In the present study, the effects of capsaicin and fermentation time on the microbial community and flavor compounds of chili paste were investigated. After capsaicin supplementation, the total acid was significantly decreased (p < 0.</p><a href="https://www.litmetric.com/detail/37120214/Effects-of-endogenous-capsaicin-stress-and-fermentation-time-on-the-microbial-succession-and-flavor-" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/36834588/Gut-Microbiota-Deficiency-Exacerbates-Liver-Injury-in-Bile-Duct-Ligated-Mice-via-Inflammation-and-Li">Gut Microbiota Deficiency Exacerbates Liver Injury in Bile Duct Ligated Mice via Inflammation and Lipid Metabolism.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Xueqian+Zhou" class="tag" style="margin-bottom: 5px;">Xueqian Zhou</a> <a href="https://www.litmetric.com/author/Xiaoxun+Zhang" class="tag" style="margin-bottom: 5px;">Xiaoxun Zhang</a> <a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Liangjun+Zhang" class="tag" style="margin-bottom: 5px;">Liangjun Zhang</a> <a href="https://www.litmetric.com/author/Wen+Qiu" class="tag" style="margin-bottom: 5px;">Wen Qiu</a> <a href="https://www.litmetric.com/author/Shiying+Cai" class="tag" style="margin-bottom: 5px;">Shiying Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Int J Mol Sci</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> February 2023</p></div>
								 </div><p class="text mt10">Bile components play a critical role in maintaining gut microbiota homeostasis. In cholestasis, bile secretion is impaired, leading to liver injury. However, it remains to be elucidated whether gut microbiota plays a role in cholestatic liver injury.</p><a href="https://www.litmetric.com/detail/36834588/Gut-Microbiota-Deficiency-Exacerbates-Liver-Injury-in-Bile-Duct-Ligated-Mice-via-Inflammation-and-Li" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/36759512/Unique-DUOX2ACE2-small-cholangiocytes-are-pathogenic-targets-for-primary-biliary-cholangitis">Unique DUOX2ACE2 small cholangiocytes are pathogenic targets for primary biliary cholangitis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Xi+Li" class="tag" style="margin-bottom: 5px;">Xi Li</a> <a href="https://www.litmetric.com/author/Yan+Li" class="tag" style="margin-bottom: 5px;">Yan Li</a> <a href="https://www.litmetric.com/author/Jintao+Xiao" class="tag" style="margin-bottom: 5px;">Jintao Xiao</a> <a href="https://www.litmetric.com/author/Huiwen+Wang" class="tag" style="margin-bottom: 5px;">Huiwen Wang</a> <a href="https://www.litmetric.com/author/Yan+Guo" class="tag" style="margin-bottom: 5px;">Yan Guo</a> <a href="https://www.litmetric.com/author/Shi-Ying+Cai" class="tag" style="margin-bottom: 5px;">Shi-Ying Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Nat Commun</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> February 2023</p></div>
								 </div><p class="text mt10">Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease.</p><a href="https://www.litmetric.com/detail/36759512/Unique-DUOX2ACE2-small-cholangiocytes-are-pathogenic-targets-for-primary-biliary-cholangitis" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/36690641/Hepatic-TNFRSF12A-promotes-bile-acid-induced-hepatocyte-pyroptosis-through-NFκBCaspase-1GSDMD-signa">Hepatic TNFRSF12A promotes bile acid-induced hepatocyte pyroptosis through NFκB/Caspase-1/GSDMD signaling in cholestasis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Min+Liao" class="tag" style="margin-bottom: 5px;">Min Liao</a> <a href="https://www.litmetric.com/author/Junwei+Liao" class="tag" style="margin-bottom: 5px;">Junwei Liao</a> <a href="https://www.litmetric.com/author/Jiaquan+Qu" class="tag" style="margin-bottom: 5px;">Jiaquan Qu</a> <a href="https://www.litmetric.com/author/Pan+Shi" class="tag" style="margin-bottom: 5px;">Pan Shi</a> <a href="https://www.litmetric.com/author/Ying+Cheng" class="tag" style="margin-bottom: 5px;">Ying Cheng</a> <a href="https://www.litmetric.com/author/Shi-Ying+Cai" class="tag" style="margin-bottom: 5px;">Shi-Ying Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Cell Death Discov</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> January 2023</p></div>
								 </div><p class="text mt10">Tumor necrosis factor receptor superfamily member-12A (TNFRSF12A) plays a critical role in inflammation and cell death. It is expressed in multiple tissues yet extremely low in normal liver. To date, little is known about its role in cholestasis.</p><a href="https://www.litmetric.com/detail/36690641/Hepatic-TNFRSF12A-promotes-bile-acid-induced-hepatocyte-pyroptosis-through-NFκBCaspase-1GSDMD-signa" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/36647589/Runt-related-transcription-factor-1-ameliorates-bile-acid-induced-hepatic-inflammation-in-cholestasi">Runt-related transcription factor-1 ameliorates bile acid-induced hepatic inflammation in cholestasis through JAK/STAT3 signaling.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Liangjun+Zhang" class="tag" style="margin-bottom: 5px;">Liangjun Zhang</a> <a href="https://www.litmetric.com/author/Qiong+Pan" class="tag" style="margin-bottom: 5px;">Qiong Pan</a> <a href="https://www.litmetric.com/author/Lu+Zhang" class="tag" style="margin-bottom: 5px;">Lu Zhang</a> <a href="https://www.litmetric.com/author/Haihan+Xia" class="tag" style="margin-bottom: 5px;">Haihan Xia</a> <a href="https://www.litmetric.com/author/Junwei+Liao" class="tag" style="margin-bottom: 5px;">Junwei Liao</a> <a href="https://www.litmetric.com/author/Shi-Ying+Cai" class="tag" style="margin-bottom: 5px;">Shi-Ying Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Hepatology</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> June 2023</p></div>
								 </div><p class="text mt10"><em>Background And Aims</em>: Bile acids trigger a hepatic inflammatory response, causing cholestatic liver injury. Runt-related transcription factor-1 (RUNX1), primarily known as a master modulator in hematopoiesis, plays a pivotal role in mediating inflammatory responses. However, RUNX1 in hepatocytes is poorly characterized, and its role in cholestasis is unclear.</p><a href="https://www.litmetric.com/detail/36647589/Runt-related-transcription-factor-1-ameliorates-bile-acid-induced-hepatic-inflammation-in-cholestasi" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/36521151/Syntactic-encoding-in-written-language-production-by-deaf-writers-A-structural-priming-study-and-a-c">Syntactic encoding in written language production by deaf writers: A structural priming study and a comparison with hearing writers.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zhenguang+G+Cai" class="tag" style="margin-bottom: 5px;">Zhenguang G Cai</a> <a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Hao+Lin" class="tag" style="margin-bottom: 5px;">Hao Lin</a> <a href="https://www.litmetric.com/author/Zebo+Xu" class="tag" style="margin-bottom: 5px;">Zebo Xu</a> <a href="https://www.litmetric.com/author/Philip+Thierfelder" class="tag" style="margin-bottom: 5px;">Philip Thierfelder</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> J Exp Psychol Learn Mem Cogn</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> June 2023</p></div>
								 </div><p class="text mt10">In three structural priming experiments, we investigated whether deaf and hearing writers differ in the processes and representations underlying written language production. Experiment 1 showed that deaf writers of Mandarin Chinese exhibited comparable extents of structural priming and comparable lexical boosts, suggesting that syntactic encoding in written language production is similarly sensitive to prior lexical-syntactic experience in deaf and hearing writers. Experiment 2 showed that, while hearing writers showed a boost in structural priming when the prime and the target had homographic or heterographic homophone dative verbs compared to unrelated ones, deaf writers showed a homophone boost only with homographic homophone verbs but not with heterographic homophone verbs.</p><a href="https://www.litmetric.com/detail/36521151/Syntactic-encoding-in-written-language-production-by-deaf-writers-A-structural-priming-study-and-a-c" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/36354145/Arabidopsis-Trithorax-histone-methyltransferases-are-redundant-in-regulating-development-and-DNA-met">Arabidopsis Trithorax histone methyltransferases are redundant in regulating development and DNA methylation.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Ji-Yun+Shang" class="tag" style="margin-bottom: 5px;">Ji-Yun Shang</a> <a href="https://www.litmetric.com/author/Xue-Wei+Cai" class="tag" style="margin-bottom: 5px;">Xue-Wei Cai</a> <a href="https://www.litmetric.com/author/Yin-Na+Su" class="tag" style="margin-bottom: 5px;">Yin-Na Su</a> <a href="https://www.litmetric.com/author/Zhao-Chen+Zhang" class="tag" style="margin-bottom: 5px;">Zhao-Chen Zhang</a> <a href="https://www.litmetric.com/author/Xin+Wang" class="tag" style="margin-bottom: 5px;">Xin Wang</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> J Integr Plant Biol</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> December 2022</p></div>
								 </div><p class="text mt10">Although the Trithorax histone methyltransferases ATX1-5 are known to regulate development and stress responses by catalyzing histone H3K4 methylation in Arabidopsis thaliana, it is unknown whether and how these histone methyltransferases affect DNA methylation. Here, we found that the redundant ATX1-5 proteins are not only required for plant development and viability but also for the regulation of DNA methylation. The expression and H3K4me3 levels of both RNA-directed DNA methylation (RdDM) genes (NRPE1, DCL3, IDN2, and IDP2) and active DNA demethylation genes (ROS1, DML2, and DML3) were downregulated in the atx1/2/4/5 mutant.</p><a href="https://www.litmetric.com/detail/36354145/Arabidopsis-Trithorax-histone-methyltransferases-are-redundant-in-regulating-development-and-DNA-met" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/35938531/SEMA7AR148W-mutation-promotes-lipid-accumulation-and-NAFLD-progression-via-increased-localization-on">SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Xiaoxun+Zhang" class="tag" style="margin-bottom: 5px;">Xiaoxun Zhang</a> <a href="https://www.litmetric.com/author/Jingjing+Ding" class="tag" style="margin-bottom: 5px;">Jingjing Ding</a> <a href="https://www.litmetric.com/author/Qiong+Pan" class="tag" style="margin-bottom: 5px;">Qiong Pan</a> <a href="https://www.litmetric.com/author/Ming-Hua+Zheng" class="tag" style="margin-bottom: 5px;">Ming-Hua Zheng</a> <a href="https://www.litmetric.com/author/Shi-Ying+Cai" class="tag" style="margin-bottom: 5px;">Shi-Ying Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> JCI Insight</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> August 2022</p></div>
								 </div><p class="text mt10">Genetic polymorphisms are associated with the development of nonalcoholic fatty liver disease (NAFLD). Semaphorin7a (Sema7a) deficiency in mouse peritoneal macrophages reduces fatty acid (FA) oxidation. Here, we identified 17 individuals with SEMA7A heterozygous mutations in 470 patients with biopsy-proven NAFLD.</p><a href="https://www.litmetric.com/detail/35938531/SEMA7AR148W-mutation-promotes-lipid-accumulation-and-NAFLD-progression-via-increased-localization-on" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/35851754/Telitacicept-following-plasma-exchange-in-the-treatment-of-subjects-with-recurrent-neuromyelitis-opt">Telitacicept following plasma exchange in the treatment of subjects with recurrent neuromyelitis optica spectrum disorders: A single-center, single-arm, open-label study.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Jie+Ding" class="tag" style="margin-bottom: 5px;">Jie Ding</a> <a href="https://www.litmetric.com/author/Xianguo+Jiang" class="tag" style="margin-bottom: 5px;">Xianguo Jiang</a> <a href="https://www.litmetric.com/author/Yu+Cai" class="tag" style="margin-bottom: 5px;">Yu Cai</a> <a href="https://www.litmetric.com/author/Shuting+Pan" class="tag" style="margin-bottom: 5px;">Shuting Pan</a> <a href="https://www.litmetric.com/author/Ye+Deng" class="tag" style="margin-bottom: 5px;">Ye Deng</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> CNS Neurosci Ther</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> October 2022</p></div>
								 </div><p class="text mt10"><em>Introduction</em>: Neuromyelitis optica spectrum disorders (NMOSD), mainly mediated by B cells and AQP4 antibody, has a high rate of recurrence. Telitacicept is a novel drug specifically targeting the upstream signaling for the activation of B cell with its following production of autoimmune antibodies. Thus, it may be a promising approach.</p><a href="https://www.litmetric.com/detail/35851754/Telitacicept-following-plasma-exchange-in-the-treatment-of-subjects-with-recurrent-neuromyelitis-opt" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/35547390/Human-Umbilical-Cord-Mesenchymal-Stem-Cells-to-Treat-Neuromyelitis-Optica-Spectrum-Disorder-hUC-MSC-">Human Umbilical Cord Mesenchymal Stem Cells to Treat Neuromyelitis Optica Spectrum Disorder (hUC-MSC-NMOSD): A Study Protocol for a Prospective, Multicenter, Randomized, Placebo-Controlled Clinical Trial.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Xiao-Ying+Yao" class="tag" style="margin-bottom: 5px;">Xiao-Ying Yao</a> <a href="https://www.litmetric.com/author/Li+Xie" class="tag" style="margin-bottom: 5px;">Li Xie</a> <a href="https://www.litmetric.com/author/Yu+Cai" class="tag" style="margin-bottom: 5px;">Yu Cai</a> <a href="https://www.litmetric.com/author/Ying+Zhang" class="tag" style="margin-bottom: 5px;">Ying Zhang</a> <a href="https://www.litmetric.com/author/Ye+Deng" class="tag" style="margin-bottom: 5px;">Ye Deng</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Front Neurol</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> April 2022</p></div>
								 </div>		<div class="blockquote-style1 mb-4 mb-lg-5" ><h5 style="font-weight:bold">Article Synopsis</h5><div class="col-auto">
                <div class="ui-content">
                  <div class="list-style1">
                    <ul><li><i class='far fa-check text-thm3 bgc-thm3-light'></i>Neuromyelitis Optica spectrum disorder (NMOSD) is a serious autoimmune disease affecting the central nervous system, and the best initial treatment options are still uncertain.</li><li><i class='far fa-check text-thm3 bgc-thm3-light'></i>Researchers will conduct a clinical trial involving 430 NMOSD patients to assess the safety and efficacy of human umbilical cord mesenchymal stem cells (hUC-MSCs), looking for the optimal dosage.</li><li><i class='far fa-check text-thm3 bgc-thm3-light'></i>This trial is significant as it aims to provide the first systematic evaluation of hUC-MSCs' clinical safety and effectiveness for NMOSD, potentially identifying the best treatment dose for patients.</li> </ul>
                  </div>
                </div>
              </div></div><a href="https://www.litmetric.com/detail/35547390/Human-Umbilical-Cord-Mesenchymal-Stem-Cells-to-Treat-Neuromyelitis-Optica-Spectrum-Disorder-hUC-MSC-" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/35460276/Intestinal-peroxisome-proliferator-activated-receptor-α-fatty-acid-binding-protein-1-axis-modulates">Intestinal peroxisome proliferator-activated receptor α-fatty acid-binding protein 1 axis modulates nonalcoholic steatohepatitis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Tingting+Yan" class="tag" style="margin-bottom: 5px;">Tingting Yan</a> <a href="https://www.litmetric.com/author/Yuhong+Luo" class="tag" style="margin-bottom: 5px;">Yuhong Luo</a> <a href="https://www.litmetric.com/author/Nana+Yan" class="tag" style="margin-bottom: 5px;">Nana Yan</a> <a href="https://www.litmetric.com/author/Keisuke+Hamada" class="tag" style="margin-bottom: 5px;">Keisuke Hamada</a> <a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Jie+Cai" class="tag" style="margin-bottom: 5px;">Jie Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Hepatology</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> January 2023</p></div>
								 </div><p class="text mt10"><em>Background And Aims</em>: Peroxisome proliferator-activated receptor α (PPARα) regulates fatty acid transport and catabolism in liver. However, the role of intestinal PPARα in lipid homeostasis is largely unknown. Here, intestinal PPARα was examined for its modulation of obesity and NASH.</p><a href="https://www.litmetric.com/detail/35460276/Intestinal-peroxisome-proliferator-activated-receptor-α-fatty-acid-binding-protein-1-axis-modulates" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/35339795/How-do-people-interpret-implausible-sentences">How do people interpret implausible sentences?</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zhenguang+G+Cai" class="tag" style="margin-bottom: 5px;">Zhenguang G Cai</a> <a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Martin+J+Pickering" class="tag" style="margin-bottom: 5px;">Martin J Pickering</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Cognition</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> August 2022</p></div>
								 </div><p class="text mt10">People sometimes interpret implausible sentences nonliterally, for example treating The mother gave the candle the daughter as meaning the daughter receiving the candle. But how do they do so? We contrasted a nonliteral syntactic analysis account, according to which people compute a syntactic analysis appropriate for this nonliteral meaning, with a nonliteral semantic interpretation account, according to which they arrive at this meaning via purely semantic processing. The former but not the latter account postulates that people consider not only a literal-but-implausible double-object (DO) analysis in comprehending The mother gave the candle the daughter, but also a nonliteral-but-plausible prepositional-object (PO) analysis (i.</p><a href="https://www.litmetric.com/detail/35339795/How-do-people-interpret-implausible-sentences" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/34724229/The-RNA-recognition-motif-containing-protein-UBA2c-prevents-early-flowering-by-promoting-transcripti">The RNA recognition motif-containing protein UBA2c prevents early flowering by promoting transcription of the flowering repressor FLM in Arabidopsis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Xiao-Min+Su" class="tag" style="margin-bottom: 5px;">Xiao-Min Su</a> <a href="https://www.litmetric.com/author/Zhang-Wei+Liu" class="tag" style="margin-bottom: 5px;">Zhang-Wei Liu</a> <a href="https://www.litmetric.com/author/Jin-Xing+Zhou" class="tag" style="margin-bottom: 5px;">Jin-Xing Zhou</a> <a href="https://www.litmetric.com/author/Yin-Na+Su" class="tag" style="margin-bottom: 5px;">Yin-Na Su</a> <a href="https://www.litmetric.com/author/Xue-Wei+Cai" class="tag" style="margin-bottom: 5px;">Xue-Wei Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> New Phytol</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> January 2022</p></div>
								 </div><p class="text mt10">FLOWERING LOCUS M (FLM) is a well-known MADS-box transcription factor that is required for preventing early flowering under low temperatures in Arabidopsis thaliana. Alternative splicing of FLM is involved in the regulation of temperature-responsive flowering. However, how the basic transcript level of FLM is regulated is largely unknown.</p><a href="https://www.litmetric.com/detail/34724229/The-RNA-recognition-motif-containing-protein-UBA2c-prevents-early-flowering-by-promoting-transcripti" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/34585848/A-homozygous-R148W-mutation-in-Semaphorin-7A-causes-progressive-familial-intrahepatic-cholestasis">A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Qiong+Pan" class="tag" style="margin-bottom: 5px;">Qiong Pan</a> <a href="https://www.litmetric.com/author/Gang+Luo" class="tag" style="margin-bottom: 5px;">Gang Luo</a> <a href="https://www.litmetric.com/author/Jiaquan+Qu" class="tag" style="margin-bottom: 5px;">Jiaquan Qu</a> <a href="https://www.litmetric.com/author/Sheng+Chen" class="tag" style="margin-bottom: 5px;">Sheng Chen</a> <a href="https://www.litmetric.com/author/Xiaoxun+Zhang" class="tag" style="margin-bottom: 5px;">Xiaoxun Zhang</a> <a href="https://www.litmetric.com/author/Shi-Ying+Cai" class="tag" style="margin-bottom: 5px;">Shi-Ying Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> EMBO Mol Med</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> November 2021</p></div>
								 </div><p class="text mt10">Semaphorin 7A (SEMA7A) is a membrane-bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis.</p><a href="https://www.litmetric.com/detail/34585848/A-homozygous-R148W-mutation-in-Semaphorin-7A-causes-progressive-familial-intrahepatic-cholestasis" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/34398202/Prevalence-of-Osteoporosis-and-Fracture-in-China-The-China-Osteoporosis-Prevalence-Study">Prevalence of Osteoporosis and Fracture in China: The China Osteoporosis Prevalence Study.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Linhong+Wang" class="tag" style="margin-bottom: 5px;">Linhong Wang</a> <a href="https://www.litmetric.com/author/Wei+Yu" class="tag" style="margin-bottom: 5px;">Wei Yu</a> <a href="https://www.litmetric.com/author/Xiangjun+Yin" class="tag" style="margin-bottom: 5px;">Xiangjun Yin</a> <a href="https://www.litmetric.com/author/Lijia+Cui" class="tag" style="margin-bottom: 5px;">Lijia Cui</a> <a href="https://www.litmetric.com/author/Shunyu+Tang" class="tag" style="margin-bottom: 5px;">Shunyu Tang</a> <a href="https://www.litmetric.com/author/Shunxiang+Cai" class="tag" style="margin-bottom: 5px;">Shunxiang Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> JAMA Netw Open</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> August 2021</p></div>
								 </div><p class="text mt10"><em>Importance</em>: The aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known.<BR><BR><em>Objective</em>: To assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years or older in mainland China.</p><a href="https://www.litmetric.com/detail/34398202/Prevalence-of-Osteoporosis-and-Fracture-in-China-The-China-Osteoporosis-Prevalence-Study" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/34159513/Objective-ages-of-acquisition-for-3300-simplified-Chinese-characters">Objective ages of acquisition for 3300+ simplified Chinese characters.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zhenguang+G+Cai" class="tag" style="margin-bottom: 5px;">Zhenguang G Cai</a> <a href="https://www.litmetric.com/author/Shuting+Huang" class="tag" style="margin-bottom: 5px;">Shuting Huang</a> <a href="https://www.litmetric.com/author/Zebo+Xu" class="tag" style="margin-bottom: 5px;">Zebo Xu</a> <a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Behav Res Methods</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> February 2022</p></div>
								 </div><p class="text mt10">We report the construction of two age-of-acquisition (AoA) norms for 3300+ characters in simplified Chinese, which make up about 99% of the texts used in daily life. We determined a character's AoA according to the time in which the character is formally learned in two sets of leading textbooks of Chinese in compulsory education, published respectively on the basis of the 2001 and 2011 national curriculum. Apart from having a significantly larger coverage of characters than previous norms, the current norms also outperformed them in explaining accuracy and reaction times in four large-scale databases for character decision, character naming, or character handwriting, even after controlling for the effects of frequency, number of meanings, and number of strokes.</p><a href="https://www.litmetric.com/detail/34159513/Objective-ages-of-acquisition-for-3300-simplified-Chinese-characters" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/33868140/Telitacicept-Following-Plasma-Exchange-in-the-Treatment-of-Subjects-With-Recurrent-NMOSD-Study-Proto">Telitacicept Following Plasma Exchange in the Treatment of Subjects With Recurrent NMOSD: Study Protocol for a Single-Center, Single-Arm, Open-Label Study.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Jie+Ding" class="tag" style="margin-bottom: 5px;">Jie Ding</a> <a href="https://www.litmetric.com/author/Yu+Cai" class="tag" style="margin-bottom: 5px;">Yu Cai</a> <a href="https://www.litmetric.com/author/Ye+Deng" class="tag" style="margin-bottom: 5px;">Ye Deng</a> <a href="https://www.litmetric.com/author/Xianguo+Jiang" class="tag" style="margin-bottom: 5px;">Xianguo Jiang</a> <a href="https://www.litmetric.com/author/Meichun+Gao" class="tag" style="margin-bottom: 5px;">Meichun Gao</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Front Neurol</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> March 2021</p></div>
								 </div><p class="text mt10"> Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease that recurrently relapses and leads to severe disability. The available choices for disease prevention are few or intolerable. Previous studies suggested that telitacicept may provide a promising therapeutic strategy for autoimmune diseases involving B cells.</p><a href="https://www.litmetric.com/detail/33868140/Telitacicept-Following-Plasma-Exchange-in-the-Treatment-of-Subjects-With-Recurrent-NMOSD-Study-Proto" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/33746886/Association-Between-Low-Density-Lipoprotein-Cholesterol-and-Platelet-Distribution-Width-in-Acute-Isc">Association Between Low-Density Lipoprotein Cholesterol and Platelet Distribution Width in Acute Ischemic Stroke.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Jian+Yuan" class="tag" style="margin-bottom: 5px;">Jian Yuan</a> <a href="https://www.litmetric.com/author/Jian+Cai" class="tag" style="margin-bottom: 5px;">Jian Cai</a> <a href="https://www.litmetric.com/author/Pei+Zhao" class="tag" style="margin-bottom: 5px;">Pei Zhao</a> <a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Rong-Hua+Hong" class="tag" style="margin-bottom: 5px;">Rong-Hua Hong</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Front Neurol</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> March 2021</p></div>
								 </div><p class="text mt10"> Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for ischemic stroke; however, whether LDL-C affects the platelet deformation function in the peripheral blood circulation in patients with acute ischemic stroke (AIS) is unknown. The present study aimed to investigate the relationship between LDL-C and platelet distribution width (PDW) in AIS patients.  We conducted a cross-sectional hospitalized-based study of consecutive 438 patients with AIS within 24 h.</p><a href="https://www.litmetric.com/detail/33746886/Association-Between-Low-Density-Lipoprotein-Cholesterol-and-Platelet-Distribution-Width-in-Acute-Isc" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/32281830/Magnetic-Noise-Enabled-Biocompass">Magnetic Noise Enabled Biocompass.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Da-Wu+Xiao" class="tag" style="margin-bottom: 5px;">Da-Wu Xiao</a> <a href="https://www.litmetric.com/author/Wen-Hui+Hu" class="tag" style="margin-bottom: 5px;">Wen-Hui Hu</a> <a href="https://www.litmetric.com/author/Yunfeng+Cai" class="tag" style="margin-bottom: 5px;">Yunfeng Cai</a> <a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Phys Rev Lett</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> March 2020</p></div>
								 </div><p class="text mt10">The discovery of magnetic protein provides a new understanding of a biocompass at the molecular level. However, the mechanism by which magnetic protein enables a biocompass is still under debate, mainly because of the absence of permanent magnetism in the magnetic protein at room temperature. Here, based on a widely accepted radical pair model of a biocompass, we propose a microscopic mechanism that allows the biocompass to operate without a finite magnetization of the magnetic protein in a biological environment.</p><a href="https://www.litmetric.com/detail/32281830/Magnetic-Noise-Enabled-Biocompass" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/30626478/Celastrol-inhibits-growth-and-increases-apoptosis-of-human-lung-cancer-A549-cells">[Celastrol inhibits growth and increases apoptosis of human lung cancer A549 cells].</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Nan+Zhao" class="tag" style="margin-bottom: 5px;">Nan Zhao</a> <a href="https://www.litmetric.com/author/Hong+Wang" class="tag" style="margin-bottom: 5px;">Hong Wang</a> <a href="https://www.litmetric.com/author/Chunqing+Mu" class="tag" style="margin-bottom: 5px;">Chunqing Mu</a> <a href="https://www.litmetric.com/author/Qiuning+Wang" class="tag" style="margin-bottom: 5px;">Qiuning Wang</a> <a href="https://www.litmetric.com/author/Zhiyang+Cai" class="tag" style="margin-bottom: 5px;">Zhiyang Cai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> December 2018</p></div>
								 </div><p class="text mt10">Objective To investigate the inhibitory effect of celastrol on the proliferation of human lung cancer A549 cells and its possible mechanism. Methods A549 cells were treated with 0, 1, 2, 3, 4, 5, 6 μmol/L celastrol for 0, 24, 48, 72 hours. The effects of different concentrations and durations on the cell proliferation were evaluated by MTT assay to determine the optimal concentration and treatment time.</p><a href="https://www.litmetric.com/detail/30626478/Celastrol-inhibits-growth-and-increases-apoptosis-of-human-lung-cancer-A549-cells" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div>           <div class="row">
           
              <div class="mbp_pagination text-center"><ul class="page_navigation"><li class="page-item active" aria-current="page">
<a class="page-link" href="#">1 <span class="sr-only">(current)</span></a>
  </li><li class="page-item"><a href="https://www.litmetric.com/author/Zhao-Nan+Cai/2" class="page-link" style="height:auto" data-ci-pagination-page="2">2</a></li><li class="page-item bg-white"><a href="https://www.litmetric.com/author/Zhao-Nan+Cai/2" class="page-link" style="height:auto" data-ci-pagination-page="2" rel="next"><span class="fas fa-angle-right"></span></a></li></ul></div>            </div>
         </div>

              
                         
     </div>
   </section>
   
   

          



    <!-- Our Footer --> 
    <section class="footer-style1 pt25 pb-0">
      <div class="container">
        <div class="row  pb10">
          <div class="col-md-7">
            <div class="d-block text-center text-md-start justify-content-center justify-content-md-start d-md-flex align-items-center mb-3 mb-md-0">
              <a class="fz17 fw500 text-white mr15-md mr30" href="https://www.litmetric.com/privacypolicy">Privacy Policy</a>
              <a class="fz17 fw500 text-white" href="https://www.litmetric.com/sitemap">Site Map</a>
            </div>
          </div>
          <div class="col-md-5">
            <div class="social-widget text-center text-md-end">
              <div class="social-style1">
                <a class="text-white me-2 fw500 fz17" href="mailto:info@litmetric.com">Contact Us</a>
                <!--
                <a href=""><i class="fab fa-facebook-f list-inline-item"></i></a>
                <a href=""><i class="fab fa-twitter list-inline-item"></i></a>
                <a href=""><i class="fab fa-instagram list-inline-item"></i></a>
                <a href=""><i class="fab fa-linkedin-in list-inline-item"></i></a>
              -->
              </div>
            </div>
          </div>
        </div>
              </div>
      <div class="container white-bdrt1 py-4">
        <div class="row align-items-center">
          <div class="col-md-12">
            <div class="text-center text-lg-start">
              <p class="copyright-text mb-2 mb-md-0 text-white-light ff-heading">© LitMetric 2024. All rights reserved.</p>
            </div>
          </div>
    
        </div>
      </div>
    </section>
    <a class="scrollToHome" href="#"><i class="fas fa-angle-up"></i></a>
  </div>
</div>
<!-- Wrapper End --> 
<script src="https://www.litmetric.com/js/jquery-3.6.4.min.js"></script>
<script src="https://www.litmetric.com/js/jquery-migrate-3.0.0.min.js"></script>
<script src="https://www.litmetric.com/js/popper.min.js"></script>
<script src="https://www.litmetric.com/js/bootstrap.min.js"></script>
<script src="https://www.litmetric.com/js/bootstrap-select.min.js"></script>
<script src="https://www.litmetric.com/js/jquery.mmenu.all.js"></script>
  
  

<script src="https://www.litmetric.com/js/ace-responsive-menu.js"></script>
<script src="https://www.litmetric.com/js/jquery-scrolltofixed-min.js"></script>
<script src="https://www.litmetric.com/js/wow.min.js"></script>
<script src="https://www.litmetric.com/js/scrollbalance.js"></script>
<!-- Custom script for all pages --> 
<script src="https://www.litmetric.com/js/script.js?v=1.47"></script>
</body>
</html>

      <script type="text/javascript">  
	    
	    
	    
	      


      

      

      
    
    
</script>

<script>
//  Fixed sidebar Custom Script For That 
$(function() {
  var cols = $('.wrap .column');
  var enabled = true;
  var scrollbalance = new ScrollBalance(cols, {
    minwidth: 1199
  });
  // bind to scroll and resize events
  scrollbalance.bind();
}); 



</script>




<script type="text/javascript">window.NREUM||(NREUM={});NREUM.info={"beacon":"bam.nr-data.net","licenseKey":"NRJS-750ae8097b9f1344f1a","applicationID":"589630826","transactionName":"ZVZbN0FZXEtUAENfV1wcbBFaF1tWUQZPGEhaQw==","queueTime":0,"applicationTime":1189,"atts":"SRFYQQlDT0U=","errorBeacon":"bam.nr-data.net","agent":""}</script></body>
</html>