Bupleurum marginatum Wall.: A comprehensive review of the traditional uses, phytochemistry, pharmacology, and quality control.

Animal tuberculosis (TB) is a zoonosis maintained by various domestic and wild mammals in complex episystems. Higher competent host species richness at the community level promotes infection maintenance. Consequently, it has been proposed to go beyond the classic one- or two-host systems, where only certain species were considered maintenance hosts, to address "maintenance communities" of multiple hosts with different levels of contribution to infection maintenance. A further factor in TB epidemiology is the environment. In the Iberian Peninsula, water availability has a strong influence on TB in wildlife and livestock. However, the relative importance of any single host species, the richness and network of interactions in each community, or the environment in driving infection maintenance is unknown. We addressed this complexity using structural equation modelling (SEM), a framework to analyze complex relationships between multiple variables. We analyzed 18 multi-host communities and assessed the effects of climate (humidity), mammal diversity, and host (cattle, wild boar, and red deer) abundance and connectedness on TB prevalence in wild boar and cattle. Red deer abundance and connectedness and wild boar connectedness were positively correlated with TB prevalence in wild boar. Humidity was negatively correlated with TB prevalence in wild boar and cattle. Red deer connectedness and the diversity of the mammal community were positively correlated with TB prevalence in cattle, while wild boar abundance was negatively correlated. Through SEM, we integrated host abundance with community network parameters, mammal diversity, and climate to reveal the drivers of TB maintenance in multi-host systems. Climate effects were stronger on cattle TB than on wild boar TB and these effects were superimposed to other risk factors such as red deer abundance and host community structure. Our findings suggest that TB eradication in cattle could be particularly challenging in regions with high competent host species richness and arid climate, with implications for livestock health, economic sustainability of cattle farms, and reduction of zoonotic risk in rural areas.

Single-cell profiling of T/NK cell glycosylation and interaction networks during liver cirrhosis.

Twin cross contrastive learning with multi-modality fusion for drug-target affinity prediction.

Glycoside hydrolases (GHs) achieve glycan breakdown through glycosidic bond hydrolysis. Some retaining GHs can also transglycosylate, which could be useful for glycosynthesis. Improving GHs for either glycan degradation or synthesis requires a deep understanding of the residues involved in catalysis and substrate binding. This study characterizes in detail the activity and structure of Ta_Cel5A, a cellulase in glycoside hydrolase family 5, subfamily 5 (GH5_5) from the thermophilic ascomycete Thermoascus aurantiacus. While its hydrolytic activity was confirmed, Ta_Cel5A was also found to exhibit a weak transglycosylase activity with cellopentaose as a substrate. Transglycosylation products were detected within the first minutes of reaction at 25°C, far below its optimal temperature. The structures of catalytically impaired variants were solved in complex with oligosaccharides. The entire catalytic cleft was defined, consisting of seven glucose-binding subsites, five negative subsites and two positive subsites, from the nonreducing end to the reducing end. The fifth negative subsite could not be inferred in silico, showing the limitation in predicting distal subsites based on structural analogy. The structure of the glycosyl-enzyme intermediate was also obtained, revealing the displacement of key residues in the active site. The covalent binding of a glycosidic molecule triggers a major displacement of the nucleophilic residue, Glu244, changing its interaction network. The acid/base residue, Glu133, and a conserved tyrosine residue, Tyr201, are also displaced during glycosyl-enzyme intermediate formation, hinting at their role in the deglycosylation step.

ACAT1-mediated lactylation reprogramming governs immune-stromal crosstalk in ulcerative colitis.

Integrated single‑cell and spatial transcriptomics reveal the colorectal cancer microenvironment.

Emerging data indicate that the lung microbiota contribute to the initiation and progression of lung cancer. Here, we investigate a wide range of immune checkpoint genes (ICGs) in the pulmonary microenvironment across lung carcinogenesis and explore the interplay between these immunoregulatory genes, the intratumoral microbiota, and inflammatory processes in the lungs. First, we establish that ICGs can considerably impact host immunity and efficacy of immunotherapy. Second, we identify CD160, HLA-DOA, and VTCN1 to significantly downregulate as tumors progress from early-stage to advanced-stage. In addition, the expression of CD86, HLA-DPB1, and HAVCR2 are significantly positively correlated with pulmonary inflammation. Finally, HLA-A, HLA-B, and HLA-E levels positively correlate to immune- and inflammation-associated Lachnoclostridium dominance. Taken together, our study uncovers ICG signatures linked to tumor progression and sheds light on the complex network of microbiota-host immunity interactions within the lung microenvironment. This study lays the groundwork for future mechanistic studies and underscores the significance of microbiota-host immunity interactions for predicting and tracking the response to cancer treatment.NEW & NOTEWORTHY This study uncovers a dynamic link between the evolving lung microbiota and the expression of specific immune checkpoint genes during cancer progression. We identify key genes that correlate with tumor advancement or inflammation and, notably, reveal a novel positive association between HLA molecules and a proinflammatory bacterial genus. These findings illuminate the microbiota-immune interplay in the lung tumor microenvironment, offering new potential targets and biomarkers for therapy.

Recent research has shown that the biosphere harbors an immense diversity of large and complex DNA viruses that infect a wide range of hosts. This is best exemplified by giant viruses of eukaryotes (phylum Nucleocytoviricota) and large phages, also referred to as jumbo phages, that infect bacteria (class Caudoviricetes). Both groups independently evolved large genomes and complex infection strategies, and recent research reveals striking convergences between these viral groups despite their distinct evolutionary origins. Virus factories and phage nuclei separate transcription from translation, mediate spatiotemporal regulation of infection, and involve elaborate interactions with host cytoskeletal systems. Moreover, both viral groups harbor an expanded repertoire of genes acquired from cellular hosts, including transcription and translation-related genes and metabolic enzymes, suggesting convergent strategies to optimize host takeover. Additionally, both lineages are embedded in networks of hyperparasitic interactions, including viral parasites and phage satellites, as well as other selfish genetic elements such as transposons and homing endonucleases, which may, in some cases, facilitate genome innovation and provide fitness benefits. The repeated emergence of genome gigantism across diverse viral clades within both the Nucleocytoviricota and Caudoviricetes suggests that selective pressures favoring gene gain, potentially through a genomic accordion mechanism, are widespread. Yet, genome expansions also harbor many features that are lineage-specific and highly context-dependent. This review explores the mechanistic, functional, and evolutionary parallels that shape the biology of genome gigantism in the virosphere.

Mechanistic insights into cardiovascular toxicity induced by polycyclic aromatic hydrocarbons using Benzo[a]pyrene (BaP) as an example.

Transcriptomic profiling reveals T cell-mediated Glutamine immunomodulation via CD8A / LCK / LAT signaling in the liver model of piglets.

Recombinant IL-38 Alleviates Temporomandibular Joint Synovial Inflammation via IL-1R1-NF-κB-IL1β Pathway.

Cross-omics interpretable neural network for discovery of molecular markers in prostate cancer.

Late-feathering phenotype can be classified into subtypes based on the difference in length between primary and primary-covert feathers of 1-day-old chicks. In this study, a chick with its primary feathers shorter than its primary-covert feathers is identified as Subtype 1 (T1), and a chick with its primary feathers as long as its primary-covert feathers is identified as Subtype 2 (T2). The objective of this study was to obtain candidate genes for late-feathering subtypes in Shouguang chickens. Fifty-three Shouguang chickens were genotyped using a 600 K SNP chip, and two genomic regions on Chromosome 3 and 10 were identified as being associated with late-feathering subtypes by Genome-wide association study (GWAS). Twelve hair follicle samples of flight feathers from 12 1-day-old Shouguang chicks, including 6 of each subtype, were collected. RNA sequencing analysis was performed, and no overlapping genes were found between differentially expressed genes (DEGs) identified by differential expression analysis and candidate genes by GWAS. In order to find the relationship between the two sets of genes, a protein-protein interaction (PPI) network was constructed using all protein-coding genes in the two sets, and the result showed that four genes (CDC40, EFL1, AK9, and ZBTB24) from GWAS and 21 DEGs were enriched in the largest subnetwork associated with muscle function. Considering the spatiotemporal characteristics of gene differential expression and the fact that the two most significant SNP loci in GWAS were located on EFL1 and CDC40, we propose that the two genes are more suitable as candidate genes for late-feathering subtypes.

Breast cancer (BC) remains one of the leading causes of cancer-related mortality among women worldwide, with distant metastasis being the primary contributor to poor prognosis. However, the molecular mechanisms driving BC metastasis are not yet fully understood. We integrated three public microarray datasets (GSE14776, GSE103357, and GSE32489) to identify the differentially expressed genes (DEGs) associated with breast cancer metastasis. Functional enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene identification were performed using bioinformatics tools including DAVID, STRING, Cytoscape, and R. The prognostic significance of hub genes was assessed using Kaplan-Meier plotter and GEPIA. Expression validation was conducted through UALCAN, immunohistochemistry (IHC), and single-cell RNA sequencing (scRNA-seq) analysis from the GSE180286 dataset. A total of 295 co-DEGs were identified across the three datasets, enriched in pathways such as MAPK signaling, Rap1 signaling, and cell adhesion molecules. Twenty hub genes were identified from the PPI network, with eight showing strong prognostic value. Among them, PRC1 and POLR3H emerged as potential novel biomarkers. IHC confirmed the differential protein expression of PRC1, CDCA8, KIF14, and POLR3H. scRNA-seq analysis revealed that these hub genes were predominantly expressed in malignant epithelial and EMT (epithelial-mesenchymal transition) cells, particularly those from metastatic lymph node sites. This integrative analysis combining bulk and single-cell transcriptomic data identified key metastasis-associated genes in breast cancer. PRC1 and POLR3H, in particular, may serve as novel prognostic biomarkers and potential therapeutic targets.

Downregulated ECHS1 and HADH-mediated fatty acid β-oxidation contributes to mitochondrial dysfunction in salivary glands of Sjögren's syndrome.

Antidepressant effects of combined eucommia-gastrodia extract via modulation of the HIF-1α-EPO/cAMP-CREB-BDNF pathway: An integrated network pharmacology and in vivo study.

Study on chronic toxicity, metabolic profiles and potential mechanisms of Aristolochiae Fructus in rats.

Coronary artery disease (CAD) causes irreversible myocardial dysfunction and progressive heart failure due to loss of contractile function and limited endogenous regenerative capacity. Current therapeutic strategies fail to restore lost myocardium or regenerate damaged cardiac tissue. Identifying dysregulated contractility-related genes may reveal actionable targets for stem cell engineering, iPSC-derived cardiomyocyte design, and tissue regeneration aimed at restoring myocardial contractility and function. Transcriptomic data from the GSE20680 dataset (195 total samples; 87 CAD cases versus 52 healthy controls, N=139; 56 intermediate stenosis subjects used for sensitivity analyses) were analyzed. Functional enrichment was performed with clusterProfiler, and protein-protein interaction (PPI) networks were constructed with STRING/Cytoscape. Protein validation was conducted in peripheral blood mononuclear cells (PBMCs) from 64 angiographically confirmed CAD patients and 55 matched healthy controls by Western blotting, with diagnostic accuracy assessed by receiver operating characteristic (ROC) analysis. Mechanistic studies employed human coronary artery smooth muscle cells (HCASMCs) transduced with lentiviral overexpression vectors or transfected with siRNA constructs targeting selected DEGs; proliferation (colony formation assay) and apoptosis (Annexin V/PI flow cytometry) were evaluated to establish regenerative targeting rationale. Differential expression analysis identified 319 DEGs (226 downregulated, 93 upregulated). Nine myocardial contractility-related genes were prioritized: UQCRQ, COX7C, COX6C, SLC8A1, COX7B, COX7A2, TNNT2, CACNB2, and CACNB1. Protein expression changes in PBMC lysates were directionally consistent with mRNA dysregulation: eight genes were significantly downregulated at the protein level, while COX7B was upregulated (P<0.05). ROC analysis demonstrated robust diagnostic performance (AUC 0.799-0.900). In HCASMCs, correcting dysregulation of the eight downregulated genes (by lentiviral overexpression) suppressed proliferation and enhanced apoptosis, suggesting restoration of contractile phenotype. COX7B exhibited the reverse pattern, supporting its distinct detrimental role. These expression patterns suggest that gene correction in engineered cardiomyocytes could restore contractile function and improve cell survival post-transplantation. This nine-gene contractility-related signature represents a set of CAD-associated biomarkers with plausible links to myocardial excitation-contraction pathways. Our integrated PBMC and HCASMC data suggest that these genes may influence vascular remodeling, and they highlight candidate targets for future regenerative studies, but direct validation in human myocardial tissue and cardiomyocytes will be required before firm conclusions about myocardial contractility or regenerative efficacy can be drawn.

Disposable plastic-alcohol leachates as emerging Neurotoxicants: Evidence for the mir-330-3p/Acsl1 pathway in cognitive performance.