Assessment of Five-Year Relative Survival of Patients With Endometrial Cancer: A Period Analysis.

Background: Endometrial cancer is one of the most common female cancers globally and in China. Although timely assessment of 5-year relative survival is crucial for guiding secondary prevention and early screening programs for endometrial cancer patients, those kinds of data are scarce in China. We aimed to provide a timely and accurate assessment of 5-year relative survival for patients with endometrial cancer from eastern China.

Use of Period Analysis to Timely Assess Five-Year Relative Survival for the Patients With Bone Cancer.

Background: While timely assessment of long-term survival for patients with bone cancer is essential for evaluation on early detection and prognosis level of treatment of bone cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for patients with bone cancer in Eastern China.

Methods: Patients diagnosed with bone cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included.

lncRNA read-through regulates the BX-C insulator .

Though long non-coding RNAs (lncRNAs) represent a substantial fraction of the Pol II transcripts in multicellular animals, only a few have known functions. Here we report that the blocking activity of the Bithorax complex (BX-C) boundary is segmentally regulated by its own lncRNA. The boundary is located between the () gene and the regulatory domain, which is responsible for regulating expression in parasegment PS6/segment A1.

Implantation of hydrogel-liposome nanoplatform inhibits glioblastoma relapse by inducing ferroptosis.

Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults. However, the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment. Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.

Use of Period Analysis to Timely Assess Five-Year Relative Survival for Patients with Ovarian Cancer from Taizhou, Eastern China.

Objective: Ovarian cancer is a deadly gynecologic malignancy with a poor prognosis. It is essential to evaluate the early detection and screening programs of ovarian cancer via timely assessment of long-time survival, particularly in China where those data are incredibly limited. Here, we aimed to provide timely and accurately assessment of long-term survival estimate of ovarian cancer patients from eastern China.

H1N1 influenza virus infection through NRF2-KEAP1-GCLC pathway induces ferroptosis in nasal mucosal epithelial cells.

Influenza A virus can induce nasal inflammation by stimulating the death of nasal mucosa epithelium, however, the mechanism is not clear. In this study, to study the causes and mechanisms of nasal mucosa epithelial cell death caused by Influenza A virus H1N1, we isolated and cultured human nasal epithelial progenitor cells (hNEPCs) and exposed them to H1N1 virus after leading differentiation. Then we performed high-resolution untargeted metabolomics and RNAseq analysis of human nasal epithelial cells (hNECs) infected with H1N1 virus.

Shp2 Deficiency in Kupffer Cells and Hepatocytes Aggravates Hepatocarcinogenesis by Recruiting Non-Kupffer Macrophages.

Background & Aims: Complex communications between hepatocytes and Kupffer cells (KCs) are known to drive or suppress hepatocarcinogenesis, with controversial data in the literature. In previous experiments that aimed to decipher hepatocyte/KC interactions, we unexpectedly unveiled a tumor-suppressing effect of polyinosinic-polycytidylic acid, a widely used inducer of MX dynamin like GTPase 1 (Mx1)-cre expression, which questioned a theory of interleukin 1a/6 cytokine circuit in hepatocyte/KC communication. The goal of this study was to clarify the controversy and decipher unique functions of KCs and non-KC macrophages in liver tumorigenesis.

Obstructive sleep apnea-increased DEC1 regulates systemic inflammation and oxidative stress that promotes development of pulmonary arterial hypertension.

Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is a common risk factor for pulmonary arterial hypertension (PAH). As a hypoxia-induced transcription factor, differentially expressed in chondrocytes (DEC1) negatively regulates the transcription of peroxisome proliferative activated receptor-γ (PPARγ), a recognized protective factor of PAH. However, whether and how DEC1 is associated with PAH pathogenesis remains unclear.

Circadian clock disruptions link oxidative stress and systemic inflammation to metabolic syndrome in obstructive sleep apnea patients.

Obstructive sleep apnea (OSA) is an independent risk factor for metabolic syndrome (MetS). Recent studies have indicated that circadian clock genes were dysregulated in OSA. In addition, it is clear that the impairment of circadian clocks drives the progression of MetS.

N-Methyladenosine-modified lncRNA LINREP promotes Glioblastoma progression by recruiting the PTBP1/HuR complex.

Glioblastoma multiforme (GBM) is acknowledged as the most aggressive primary brain tumor in adults. It is typically characterized by the high heterogeneity which corresponds to extensive genetic mutations and complex alternative splicing (AS) profiles. Known as a major repressive splicing factor in AS, polypyrimidine tract-binding protein 1 (PTBP1) is involved in the exon skipping events of multiple precursor mRNAs (pre-mRNAs) in GBM.

The effects of obstructive sleep apnea-hypopnea syndrome (OSAHS) on learn and memory function of 6-12 years old children.

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep disorder causing cognitive impairments.

Aims: We use the auditory verbal learning test (AVLT), clock drawing test (CDT), Wechsler intelligence scale for children (WISC) and Montreal cognitive assessment (MoCA) to evaluate the memory and spatial impairments of OSHAS in 6-12 years old children patients with different severity.

Material And Methods: A total of 137 children of snoring were enrolled following the inclusion criteria of this study.

Tfh Exosomes Derived from Allergic Rhinitis Promote DC Maturation Through miR-142-5p/CDK5/STAT3 Pathway.

Background: Dendritic cells (DCs) play an important role in allergen signal presentation. Many studies showed that follicular helper T cells (Tfhs) are related to allergic rhinitis (AR). However, the relationship between Tfhs and DCs and the mechanism of their interaction with AR remain unclear.

Essential Regression: A generalizable framework for inferring causal latent factors from multi-omic datasets.

High-dimensional cellular and molecular profiling of biological samples highlights the need for analytical approaches that can integrate multi-omic datasets to generate prioritized causal inferences. Current methods are limited by high dimensionality of the combined datasets, the differences in their data distributions, and their integration to infer causal relationships. Here, we present Essential Regression (ER), a novel latent-factor-regression-based interpretable machine-learning approach that addresses these problems by identifying latent factors and their likely cause-effect relationships with system-wide outcomes/properties of interest.

H1N1 Influenza Virus-Infected Nasal Mucosal Epithelial Progenitor Cells Promote Dendritic Cell Recruitment and Maturation.

The barrier function of nasal mucosal epithelial cells plays an irreplaceable role in the spread and expansion of viruses in the body. This study found that influenza A virus H1N1 could induce apoptosis of nasal mucosal epithelial progenitor cells, cause an inflammatory response, and trigger the maturation and recruitment of nasal submucosal dendritic cells (DCs), but the mechanism remained unclear. Therefore, we used RNA sequencing and high-resolution untargeted metabolomics to sequence and perform combined bioinformatic analysis of H1N1 virus-infected nasal mucosal epithelial cells from 6 different patients.

Transcriptional coupling of distant regulatory genes in living embryos.

The prevailing view of metazoan gene regulation is that individual genes are independently regulated by their own dedicated sets of transcriptional enhancers. Past studies have reported long-range gene-gene associations, but their functional importance in regulating transcription remains unclear. Here we used quantitative single-cell live imaging methods to provide a demonstration of co-dependent transcriptional dynamics of genes separated by large genomic distances in living Drosophila embryos.

Pharmaceutical SH2 domain-containing protein tyrosine phosphatase 2 inhibition suppresses primary and metastasized liver tumors by provoking hepatic innate immunity.

Background And Aims: SH2 domain-containing protein tyrosine phosphatase 2 (Shp2) is the first identified pro-oncogenic tyrosine phosphatase that acts downstream of receptor tyrosine kinases (RTKs) to promote Ras-extracellular signal-regulated kinase signaling. However, this phosphatase was also shown to be antitumorigenic in HCC. This study is aimed at deciphering paradoxical Shp2 functions and mechanisms in hepatocarcinogenesis and at exploring its value as a pharmaceutical target in HCC therapy.

S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling.

Epithelial-mesenchymal transition (EMT) is thought to be involved in the tissue remodeling and long-term inflammatory process of chronic sinusitis (CRS), but the driving mechanism is still unclear. Using high-resolution mass spectrometry, we performed a proteomic screen of CRS nasal mucosal tissue to identify differentially expressed proteins. Data are available ProteomeXchange with identifier PXD030884.

Temporal analyses of postnatal liver development and maturation by single-cell transcriptomics.

The postnatal development and maturation of the liver, the major metabolic organ, are inadequately understood. We have analyzed 52,834 single-cell transcriptomes and identified 31 cell types or states in mouse livers at postnatal days 1, 3, 7, 21, and 56. We observe unexpectedly high levels of hepatocyte heterogeneity in the developing liver and the progressive construction of the zonated metabolic functions from pericentral to periportal hepatocytes, which is orchestrated with the development of sinusoid endothelial, stellate, and Kupffer cells.

Genome organization controls transcriptional dynamics during development.

Past studies offer contradictory claims for the role of genome organization in the regulation of gene activity. Here, we show through high-resolution chromosome conformation analysis that the genome is organized by two independent classes of regulatory sequences, tethering elements and insulators. Quantitative live imaging and targeted genome editing demonstrate that this two-tiered organization is critical for the precise temporal dynamics of Hox gene transcription during development.

Enhancing the therapeutic efficacy of programmed death ligand 1 antibody for metastasized liver cancer by overcoming hepatic immunotolerance in mice.

Background And Aims: Immunotherapy with programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade has shown low response rates in liver cancer patients, with the underlying mechanisms unclear. To decipher a specific impact of the liver microenvironment, we compared the effects of anti-PD-L1 antibody (αPD-L1) blockade on the same tumor grown s.c.

Generation of combined hepatocellular-cholangiocarcinoma through transdifferentiation and dedifferentiation in p53-knockout mice.

The two principal histological types of primary liver cancers, hepatocellular carcinoma (HCC) and cholangiocarcinoma, can coexist within a tumor, comprising combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Although the possible involvement of liver stem/progenitor cells has been proposed for the pathogenesis of cHCC-CCA, the cells might originate from transformed hepatocytes that undergo ductular transdifferentiation or dedifferentiation. We previously demonstrated that concomitant introduction of mutant HRAS (HRAS) and Myc into mouse hepatocytes induced dedifferentiated tumors that expressed fetal/neonatal liver genes and proteins.

Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning.

The relationship between chromatin organization and gene regulation remains unclear. While disruption of chromatin domains and domain boundaries can lead to misexpression of developmental genes, acute depletion of regulators of genome organization has a relatively small effect on gene expression. It is therefore uncertain whether gene expression and chromatin state drive chromatin organization or whether changes in chromatin organization facilitate cell-type-specific activation of gene expression.

NFAT Overexpression Correlates with CA72-4 and Poor Prognosis of Ovarian Clear-Cell Carcinoma Subtype.

Current biomarkers did not overcome the limitations of clinical application due to the heterogeneity of ovarian tumors. The role of nuclear factor of activated T cells (NFAT) in the prognosis of different histological subtypes of ovarian cancer remains unclear. NFAT expression was analyzed in 302 ovarian tumors from The Cancer Genome Atlas (TCGA) dataset and was further confirmed by 88 ovarian tumor specimens, including 30 clear-cell carcinoma, 34 serous carcinoma, and 24 papillary serous cystadenocarcinoma.

Hepatocyte Mitogen-Activated Protein Kinase Kinase 7 Contributes to Restoration of the Liver Parenchyma Following Injury in Mice.

Background And Aims: Mitogen-activated protein kinase kinase (MKK) 7 and MKK4 are upstream activators of c-Jun NH -terminal kinases (JNKs) and have been shown to be required for the early development of the liver. Although it has been suggested that MKK7 might be involved in the regulation of hepatocyte proliferation, the functional role of MKK7 in the liver has remained unclear.

Approach And Results: Here, we examined phenotypic alterations in liver-specific or hepatocyte/hematopoietic cell-specific MKK7 knockout (KO) mice, which were generated by crossing MKK7 with albumin-cyclization recombination (Alb-Cre) or myxovirus resistance protein 1-Cre mice, respectively.