SARS-CoV-2 spike protein acts as a β-adrenergic receptor agonist: A potential mechanism for cardiac sequelae of long COVID.

Background: Currently, pathophysiological mechanisms of post-acute sequelae of coronavirus disease-19-cardiovascular syndrome (PASC-CVS) remain unknown.

Methods And Results: Patients with PASC-CVS exhibited significantly higher circulating levels of severe acute respiratory syndrome-coronavirus-2 spike protein S1 than the non-PASC-CVS patients and healthy controls. Moreover, individuals with high plasma spike protein S1 concentrations exhibited elevated heart rates and normalized low frequency, suggesting cardiac β-adrenergic receptor (β-AR) hyperactivity.

Anti-CTLA-4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5-Neutrophil Infiltration.

The risk for suffering immune checkpoint inhibitors (ICIs)-associated myocarditis increases in patients with pre-existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single-cell RNA sequencing, and flow cytometry are used to decipher how anti-cytotoxic T lymphocyte antigen-4 m2a antibody (anti-CTLA-4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti-CTLA-4 m2a antibody increases cardiac fibroblast-derived C-X-C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1-Cxcr2 chemotaxis.

Cytochrome P450 Mining for Bufadienolide Diversification.

Bufadienolides are a class of steroids with a distinctive α-pyrone ring at C17, mostly produced by toads and consisting of over 100 orthologues. They exhibit potent cardiotonic and antitumor activities and are active ingredients of the traditional Chinese medicine Chansu and Cinobufacini. Direct extraction from toads is costly, and chemical synthesis is difficult, limiting the accessibility of active bufadienolides with diverse modifications and trace content.

Four decades of full-scale nitrous oxide emission inventory in China.

China is among the top nitrous oxide (NO)-emitting countries, but existing national inventories do not provide full-scale emissions including both natural and anthropogenic sources. We conducted a four-decade (19802020) of comprehensive quantification of Chinese NO inventory using empirical emission factor method for anthropogenic sources and two up-to-date process-based models for natural sources. Total NO emissions peaked at 2287.

Vemurafenib induces senescence in acute myeloid leukemia and myelodysplastic syndrome by activating the HIPPO signaling pathway: implications for potential targeted therapy.

Background: The outcome of Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remain dismal despite the development of treatment. Targeted therapy is gaining more and more attention in improving prognosis.

Methods: Expression of BRAF was analyzed by RT-qPCR in AML and MDS patients.

Predicting T Cell-Inflamed Gene Expression Profile in Hepatocellular Carcinoma Based on Dynamic Contrast-Enhanced Ultrasound Radiomics.

Purpose: The T cell-inflamed gene expression profile (GEP) quantifies 18 genes' expression indicative of a T-cell immune tumor microenvironment, playing a crucial role in the immunotherapy of hepatocellular carcinoma (HCC). Our study aims to develop a radiomics-based machine learning model using contrast-enhanced ultrasound (CEUS) for predicting T cell-inflamed GEP in HCC.

Methods: The primary cohort of HCC patients with preoperative CEUS and RNA sequencing data of tumor tissues at the single center was used to construct the model.

Identification and validation of a plasma metabolomics-based model for risk stratification of intrahepatic cholangiocarcinoma.

Background: Liver resection is the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC) while the postoperative prognosis varies greatly, with no recognized biomarker. We aimed to identify the plasma metabolomic biomarkers that could be used for preoperative risk stratification of ICC patients.

Methods: 108 eligible ICC patients who underwent radical surgical resection between August 2012 and October 2020 were enrolled.

Effects of connection-based physician-patient relationships on perceptions of outcome: A vignette experiment.

Objectives: To investigate the effects of media reports of medical outcomes and connection-based medicine on trust in physicians. In "connection-based medicine," people use personal connections to obtain better medical resources.

Methods: Vignette experiments were used to investigate attitudes toward physicians among 230 cancer patients and their families (Sample 1) and a cross-validated sample of 280 employees from various industries (Sample 2).

Integration of Artificial Intelligence Decision Aids to Reduce Workload and Enhance Efficiency in Thyroid Nodule Management.

Importance: To optimize the integration of artificial intelligence (AI) decision aids and reduce workload in thyroid nodule management, it is critical to incorporate personalized AI into the decision-making processes of radiologists with varying levels of expertise.

Objective: To develop an optimized integration of AI decision aids for reducing radiologists' workload while maintaining diagnostic performance compared with traditional AI-assisted strategy.

Design, Setting, And Participants: In this diagnostic study, a retrospective set of 1754 ultrasonographic images of 1048 patients with 1754 thyroid nodules from July 1, 2018, to July 31, 2019, was used to build an optimized strategy based on how 16 junior and senior radiologists incorporated AI-assisted diagnosis results with different image features.

Therapeutic efficacy of a MMAE-based anti-DR5 drug conjugate Oba01 in preclinical models of pancreatic cancer.

Pancreatic cancer (PC) is among the most aggressive malignancies associated with a 5-year survival rate of <9%, and the treatment options remain limited. Antibody-drug conjugates (ADCs) are a new class of anticancer agents with superior efficacy and safety profiles. We studied the antitumor activity of Oba01 ADC and the mechanism underlying the targeting of death receptor 5 (DR5) in preclinical PC models.

Aldosterone-stimulated endothelial epithelial sodium channel (EnNaC) plays a role in cold exposure-induced hypertension in rats.

Previous studies have demonstrated that activated endothelial epithelial sodium channel (EnNaC) impairs vasodilatation, which contributes to salt-sensitive hypertension. Here, we investigate whether mesenteric artery (MA) EnNaC is involved in cold exposure-induced hypertension (CIH) and identify the underlying mechanisms in SD rats. One group of rats was housed at room temperature and served as control.

Using Systemic Inflammatory Markers to Predict Microvascular Invasion Before Surgery in Patients With Hepatocellular Carcinoma.

Background: Mounting studies reveal the relationship between inflammatory markers and post-therapy prognosis. Yet, the role of the systemic inflammatory indices in preoperative microvascular invasion (MVI) prediction for hepatocellular carcinoma (HCC) remains unclear.

Patients And Methods: In this study, data of 1,058 cases of patients with HCC treated in the First Affiliated Hospital of Sun Yat-sen University from February 2002 to May 2018 were collected.

Racial/Ethnic Disparities on the Risk of Second Malignant Neoplasm Among Hodgkin Lymphoma Survivors.

Background: Hodgkin lymphoma survivors are at risk for second malignant neoplasm (SMN). How race/ethnicity affects the risk remains unclear.

Methods: This retrospective cohort study included 22,415 patients diagnosed with primary Hodgkin lymphoma from January 1992 to December 2015 in 13 Surveillance, Epidemiology, and End Results-based registries and divided patients into four groups: non-Hispanic whites, non-Hispanic blacks, Hispanics, and Asian/others.

The pivotal role of the NLRC4 inflammasome in neuroinflammation after intracerebral hemorrhage in rats.

The NLRC4 inflammasome, a member of the nucleotide-binding and oligomerization domain-like receptor (NLR) family, amplifies inflammation by facilitating the processing of caspase-1, interleukin (IL)-1β, and IL-18. We explored whether NLRC4 knockdown alleviated inflammatory injury following intracerebral hemorrhage (ICH). Furthermore, we investigated whether NLRC4 inflammasome activation can be adjusted by the regulator of G protein signaling 2/leucine-rich repeat kinase-2 pathway.

Paeonol Suppresses Vasculogenesis Through Regulating Vascular Smooth Muscle Phenotypic Switching.

Objective: Smooth muscle cell (SMC) phenotypic switching is associated with development of a variety of occlusive vascular diseases. Paeonol has been reported to be involved in suppressing SMC proliferation. However, it is still unknown whether paeonol can regulate SMC phenotypic switching, and which eventually result in suppressing vasculogenesis.

EZH2 regulates the malignancy of human glioblastoma cells via modulation of Twist mRNA stability.

Glioblastoma multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. However, the effects and mechanisms of epigenetic factors on the development of GBM were still not well illustrated. We found that expression of enhancer of zeste homolog 2 (EZH2), which can catalyze histone H3K27me3 to modulate gene expression, was increased in GBM cells.

Deep learning-based artificial intelligence model to assist thyroid nodule diagnosis and management: a multicentre diagnostic study.

Background: Strategies for integrating artificial intelligence (AI) into thyroid nodule management require additional development and testing. We developed a deep-learning AI model (ThyNet) to differentiate between malignant tumours and benign thyroid nodules and aimed to investigate how ThyNet could help radiologists improve diagnostic performance and avoid unnecessary fine needle aspiration.

Methods: ThyNet was developed and trained on 18 049 images of 8339 patients (training set) from two hospitals (the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, and Sun Yat-sen University Cancer Center, Guangzhou, China) and tested on 4305 images of 2775 patients (total test set) from seven hospitals (the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the Guangzhou Army General Hospital, Guangzhou, China; the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the First Affiliated Hospital of Sun Yat-sen University; Sun Yat-sen University Cancer Center; and the First Affiliated Hospital of Guangxi Medical University, Nanning, China) in three stages.

Tyrosine kinase Fyn promotes apoptosis after intracerebral hemorrhage in rats by activating Drp1 signaling.

Tyrosine kinase Fyn is a member of the Src kinase family, which is involved in neuroinflammation, apoptosis, and oxidative stress. Its role in intracerebral hemorrhage (ICH) is not fully understood. In this study, we found that Fyn was significantly elevated in human brain tissue after ICH.

Current Research Landscape of Marine-Derived Anti-Atherosclerotic Substances.

Atherosclerosis is a chronic disease characterized by lipid accumulation and chronic inflammation of the arterial wall, which is the pathological basis for coronary heart disease, cerebrovascular disease and thromboembolic disease. Currently, there is a lack of low-cost therapeutic agents that effectively slow the progression of atherosclerosis. Therefore, the development of new drugs is urgently needed.

NLRP6 contributes to inflammation and brain injury following intracerebral haemorrhage by activating autophagy.

Inflammation is a crucial factor contributing to secondary brain injury after intracerebral haemorrhage (ICH). NLRP6, a member of nod-like receptors (NLRs) family, has been reported to participate in inflammation and host-defence in multiple diseases. Distinct from the other NLR family members, NLRP6 regulates inflammation in an inflammasome-dependent as well as an inflammasome-independent pathway.

The Influence of Immune Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors in Multifocal Hepatocellular Carcinomas.

Purpose: Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms.

Experimental Design: We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing.

Competing endogenous RNA regulation in hematologic malignancies.

The clinical application of cytogenetic analysis and molecular-targeted drugs has dramatically improved the prognosis for many patients with hematologic malignancy, especially for those with chronic myeloid leukemia (CML) and acute promyelocytic leukemia (APL). Nevertheless, the treatment of hematologic malignancies is still faced with problems, such as disease recurrence and drug resistance, so further exploring the underlying molecular mechanism is urgent. With the discovery of different RNA species, the mechanism of RNA-RNA interaction has caught more and more attention.

Cera alba-assisted ultraclean graphene transfer for high-performance PbI UV photodetectors.

Large polymer residues introduced by the graphene transfer process is still a major obstacle limiting the integration of chemical vapor deposition (CVD)-grown graphene into next-generation electronic and photoelectronic devices. Here we use cera alba, a natural and environmental-friendly material that derives from honeycomb, as the supporting layer for ultraclean graphene transfer. The transferred graphene has a low surface roughness with a surface height fluctuation within 5 nm and an only 80.