METTL5 deficiency induces oligoasthenoteratozoospermia via impaired 18S rRNA mA methylation in humans and mice.

Recent studies have highlighted RNA modifications as integral regulators of gene expression during spermatogenesis. Ribosomal RNAs (rRNAs) are the most abundant RNA in cells, while the function and clinical relevance of rRNA modifications in spermatogenesis remain poorly understood. Here, we identified 4 pathogenic heterozygous variants of METTL5 in 1,427 patients with male infertility characterized as oligoasthenoteratozoospermia (OAT).

The exacerbating effects of stable pulmonary tuberculosis on the deterioration of inflammatory response, coagulation function, and pulmonary function in COPD: A propensity score-matched retrospective study.

Chronic obstructive pulmonary disease (COPD) and tuberculosis pose significant public health challenges, particularly in tuberculosis-endemic developing regions where their co-prevalence may exacerbate the disease burden of chronic airflow obstruction. This study aimed to investigate the impact of stable pulmonary tuberculosis on inflammatory status, coagulation function, and pulmonary function in COPD patients during acute exacerbations.We conducted a retrospective analysis of 68 COPD patients with acute exacerbation and stable pulmonary tuberculosis (observation group) admitted between December 2019 and December 2023.

Rational Enzyme Evolution by Facilitating Correlated Motion along the Reaction.

Enzymes are highly efficient and specific protein catalysts that play an essential role in regulating metabolic processes in living organisms. By modulating the rates of chemical reactions, enzymes tune fundamental crucial biological functions. Directed evolution is a widely used strategy to enhance protein functionality by selecting variants with desirable traits through random mutation and recombination.

An iterative and automatic collective variable optimization scheme via unsupervised feature selection with CUR matrix decomposition.

Phase transitions frequently involve surmounting significant energy barriers, necessitating the construction of collective variables (CVs) to facilitate enhanced sampling of high-energy structures in molecular dynamics simulations. However, optimizing CVs remains a formidable challenge, particularly when limited prior knowledge about the transition process is available. This study presents an unsupervised approach for optimizing the CVs by iteratively applying the principal component analysis algorithm on the representative feature variables generated with the CUR method (an efficient feature space contraction algorithm that can be employed to seek the representative feature variables).

Microplastics enhance laccase-driven bisphenol A removal in multipollutant wastewater.

Bisphenol A (BPA) is recognized as a significant constituent of environmental pollutants and could be efficiently removed from wastewater by laccase (Lac). Microplastics (MPs) was found to be present in wastewater contained BPA. This work was to realize BPA removal from wastewater in the presence of MPs by Lac and to reveal the possible mechanism for MPs enhancing Lac-driven BPA removal.

FEP-SPell-ABFE: An Open-Source Automated Alchemical Absolute Binding Free-Energy Calculation Workflow for Drug Discovery.

The binding affinity between a drug molecule and its target, measured by the absolute binding free energy (ABFE), is a crucial factor in the lead discovery phase of drug development. Recent research has highlighted the potential of in silico ABFE predictions to directly aid drug development by allowing for the ranking and prioritization of promising candidates. This work introduces an open-source Python workflow called FEP-SPell-ABFE, designed to automate ABFE calculations with minimal user involvement.

In situ architecture of the intercellular organelle reservoir between epididymal epithelial cells by volume electron microscopy.

Mammalian epididymal epithelial cells are crucial for sperm maturation. Historically, vacuole-like ultrastructures in epididymal epithelial cells were observed via transmission electron microscopy but were undefined. Here, we utilize volume electron microscopy (vEM) to generate 3D reconstructions of epididymal epithelial cells and identify these vacuoles as intercellular organelle reservoirs (IORs) in the lateral intercellular space (LIS), which contains protein aggregates, autophagosomes, lysosome-related organelles and mitochondrial residues.

MHR as a promising predictor for coronary artery disease in COPD patients: Insights from a retrospective nomogram study.

Background And Objective: Chronic obstructive pulmonary disease (COPD) frequently co-occurs with coronary artery disease (CAD), adversely affecting patients morbidity and mortality. Identifying new risk factors for CAD in COPD patients is essential for improving clinical management and patients outcomes.

Methods: This retrospective case-control study analyzed 406 COPD patients who underwent coronary artery computed tomography angiography (CCTA).

Analyzes of pan-genome and resequencing atlas unveil the genetic basis of jujube domestication.

Jujube (Ziziphus jujuba Mill.), belonging to the Rhamnaceae family, is gaining increasing prominence as a perennial fruit crop with significant economic and medicinal values. Here, we conduct de novo assembly of four reference-grade genomes, encompassing one wild and three cultivated jujube accessions.

A enhancer transcriptionally regulates Wnt signaling dosage to balance homeostasis and tumorigenesis of intestinal epithelia.

The β-catenin-dependent canonical Wnt signaling is pivotal in organ development, tissue homeostasis, and cancer. Here, we identified an upstream enhancer of - the coding gene for β-catenin, named ieCtnnb1 (ntestinal nhancer of ), which is crucial for intestinal homeostasis. ieCtnnb1 is predominantly active in the base of small intestinal crypts and throughout the epithelia of large intestine.

Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition.

As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Here we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.

A retrospective study of anlotinib in patients with persistent, recurrent or metastatic cervical and endometrial cancer.

Background: The prognosis of persistent, recurrent or metastatic cervical and endometrial cancer is poor. Anlotinib is a novel multitarget tyrosine kinase inhibitor (TKI). The efficacy and safety of anlotinib in patients with cervical and endometrial cancer need to be evaluated.

Convergence criteria for single-step free-energy calculations: the relation between the Π bias measure and the sample variance.

Free energy calculations play a crucial role in simulating chemical processes, enzymatic reactions, and drug design. However, assessing the reliability and convergence of these calculations remains a challenge. This study focuses on single-step free-energy calculations using thermodynamic perturbation.

Identification of Key Disulfidptosis-Related Genes and Their Association with Gene Expression Subtypes in Crohn's Disease.

Background: Crohn's disease (CD) is a persistent inflammatory condition that impacts the gastrointestinal system and is characterized by a multifaceted pathogenesis involving genetic, immune, and environmental components. This study primarily investigates the relationship between gene expression and immune cell infiltration in CD, focusing on disulfidptosis-a novel form of cell death caused by abnormal disulfide accumulation-and its impact on various immune cell populations. By identifying key disulfidptosis-related genes (DRGs) and exploring their association with distinct gene expression subtypes, this research aims to enhance our understanding of CD and potentially other autoimmune diseases.

PANoptosis and Autophagy-Related Molecular Signature and Immune Landscape in Ulcerative Colitis: Integrated Analysis and Experimental Validation.

Background: Ulcerative colitis (UC) is an autoimmune inflammatory disorder of the gastrointestinal tract. Programmed cell death (PCD), including PANoptosis and autophagy, plays roles in inflammation and immunity. This study aimed to investigate the molecular signature and immune landscape of the PANoptosis- and autophagy-related differentially expressed genes (DEGs) in UC.

Large regions of homozygosity in prenatal diagnosis.

Chromosomal microarrays (CMA) incorporate single nucleotide polymorphisms to enable the detection of regions of homozygosity (ROH). Here, we retrospectively analyzed 6288 prenatal cases who performed CMA to explored the clinical implications of large ROH in prenatal diagnosis. We analyzed cases with ROH larger than 10 megabases and reviewed the ultrasound findings; karyotype results and pregnancy follow-up data.

Imaging manifestations of papillary glioneuronal tumors.

To analyse the imaging findings of papillary glioneuronal tumors (PGNTs), in order to improve the accuracy of preoperative diagnosis of this tumor. The clinical and imaging manifestations of 36 cases of PGNT confirmed by pathology were analyzed retrospectively. A total of 17 males and 19 females, averaging 22.

Potent inhibitors targeting cyclin-dependent kinase 9 discovered virtual high-throughput screening and absolute binding free energy calculations.

Due to the crucial regulatory mechanism of cyclin-dependent kinase 9 (CDK9) in mRNA transcription, the development of kinase inhibitors targeting CDK9 holds promise as a potential treatment strategy for cancer. A structure-based virtual screening approach has been employed for the discovery of potential novel CDK9 inhibitors. First, compounds with kinase inhibitor characteristics were identified from the ZINC15 database virtual high-throughput screening.

Structures of the essential efflux pump EfpA from reveal the mechanisms of substrate transport and small-molecule inhibition.

As the first identified multidrug efflux pump in (), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Herein we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.

YAP represses intestinal inflammation through epigenetic silencing of JMJD3.

Background: Epigenetics plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Some studies have reported that YAP is involved in inflammatory response and can regulate target genes through epigenetic modifications. JMJD3, a histone H3K27me3 demethylase, is associated with some inflammatory diseases.

Effect of uniparental disomy in parentage testing.

Uniparental disomy (UPD) is a rare type of chromosomal aberration that may hinder the analysis of kinship during forensic identification. Here, we investigated these genetic findings to avoid false exclusions during parentage testing. Thirty-nine fluorescently labeled, autosomal short tandem repeats (STR) were amplified in three cases, to detect parent-child relationships.