Single-cell sequencing uncovers disrupted stromal-macrophage communication as a driver of intrauterine adhesion progression.

Intrauterine adhesions (IUA), characterized by endometrial fibrosis, pose a serious threat to women's reproductive health, yet their molecular mechanisms remain poorly understood. Here, we use single-cell RNA sequencing (scRNA-seq) to profile 139,395 single cells from nine individuals in the proliferative phase. We identify seven stromal and five macrophage subsets, revealing increased immune cell infiltration and a profibrotic shift in macrophage states.

Development and Application of a Senolytic Predictor for Discovery of Novel Senolytic Compounds and Herbs.

The accumulation of senescent cells is a major contributor to aging and various age-related diseases, making developing senolytic compounds that are capable of clearing these cells an important area of research. However, progress has been hampered by the limited number of known senolytics and the incomplete understanding of their mechanisms. This study presents a powerful senolytic predictor built using phenotypic data and machine learning techniques to identify compounds with potential senolytic activity.

Integrative single-cell and cell-free plasma RNA transcriptomics identifies biomarkers for early non-invasive AD screening.

Introduction: Data-driven omics approaches have rapidly advanced our understanding of the molecular heterogeneity of Alzheimer's disease (AD). However, limited by the unavailability of brain tissue, there is an urgent need for a non-invasive tool to detect alterations in the AD brain. Cell-free RNA (cfRNA), which crosses the blood-brain barrier, could reflect AD brain pathology and serve as a diagnostic biomarker.

A novel Tc17 population recruited by tumor cells promotes tumor progression in gastric cancer.

Objective: The tumor microenvironment (TME) plays a crucial role in tumor progression. Recent advancements in single-cell sequencing technology have identified Tc17 cells, a newfound subset of CD8 T cells with a phenotype similar to Th17, within the gastric cancer (GC) microenvironment. However, the role of Tc17 cells are unclear.

Aging-related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1,255 human blood samples.

This study aimed to identify age-related genes and alternative splicing (AS) events by comprehensive transcriptome analysis of 1,255 healthy blood samples from individuals aged 8-87 years. We identified 1,029 up-regulated and 1,186 down-regulated genes in older individuals, including 17 genes overlapped with known aging-associated genes, such as TFAP2A and Klotho. Gene set enrichment analysis revealed significant alterations in immunoregulatory and metabolic pathways during aging.

Proteome-Wide Identification and Comparison of Drug Pockets for Discovering New Drug Indications and Side Effects.

Drug development faces significant financial and time challenges, highlighting the need for more efficient strategies. This study evaluated the druggability of the entire human proteome using Fpocket. We identified 15,043 druggable pockets in 20,255 predicted protein structures, significantly expanding the estimated druggable proteome from 3000 to over 11,000 proteins.

Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment.

A highly immunosuppressive tumor microenvironment (TME) and the presence of the blood‒brain barrier are the two major obstacles to eliciting an effective immune response in patients with high-grade glioma (HGG). Here, we tried to enhance the local innate immune response in relapsed HGG by intracranially injecting poly(I:C) to establish a robust antitumor immune response in this registered clinical trial (NCT03392545). During the follow-up, 12/27 (44.

In Silico Identification of Anti-SARS-CoV-2 Medicinal Plants Using Cheminformatics and Machine Learning.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, is spreading rapidly and has caused hundreds of millions of infections and millions of deaths worldwide. Due to the lack of specific vaccines and effective treatments for COVID-19, there is an urgent need to identify effective drugs. Traditional Chinese medicine (TCM) is a valuable resource for identifying novel anti-SARS-CoV-2 drugs based on the important contribution of TCM and its potential benefits in COVID-19 treatment.

scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory.

The tumor microenvironment (TME) in gastric cancer (GC) has been shown to be important for tumor control but the specific characteristics for GC are not fully appreciated. We generated an atlas of 166,533 cells from 10 GC patients with matched paratumor tissues and blood. Our results show tumor-associated stromal cells (TASCs) have upregulated activity of Wnt signaling and angiogenesis, and are negatively correlated with survival.

Carma3 Protects from Liver Injury by Preserving Mitochondrial Integrity in Liver Sinusoidal Endothelial Cells.

Carma3 is an intracellular scaffolding protein that can form complex with Bcl10 and Malt1 to mediate G protein-coupled receptor- or growth factor receptor-induced NF-κB activation. However, the in vivo function of Carma3 has remained elusive. Here, by establishing a Con A-induced autoimmune hepatitis model, we show that liver injury is exacerbated in mice.

Knockout of immunotherapy prognostic marker genes eliminates the effect of the anti-PD-1 treatment.

The efficacy of immunotherapy is largely patient-specific due to heterogeneity in tumors. Combining statistic power from a variety of immunotherapies across cancer types, we found four biological pathways significantly correlated with patient survival following immunotherapy. The expression of immunotherapy prognostic marker genes (IPMGs) in these pathways can predict the patient survival with high accuracy not only in the TCGA cohort (89.

Malt1 Protease Is Critical in Maintaining Function of Regulatory T Cells and May Be a Therapeutic Target for Antitumor Immunity.

The paracaspase Malt1 is a key molecule in mediating Ag receptor-induced NF-κB activation in lymphocytes, but the role of Malt1 in the function of regulatory T (Treg) cells is still unclear. In this article, we reported that specific deletion of Malt1 in Treg cells would lead to -like lethal autoimmune disease, which was caused by Treg cell dysfunction but not number loss. Interestingly, mice, in which Malt1 protease was specifically inactivated in Treg cells, also displayed spontaneous inflammatory disorders, with severe hair loss and skin hyperplasia.