Search Results (926)

Pancreatic cancer is among the most aggressive malignancies, and late diagnosis remains a key challenge. For a systematic review of pancreatic cancer diagnosis and prognosis, Scopus and Web of Science databases were used for the period from 2016 to 2026. The search query included the following keywords and their combinations: pancreatic cancer, diagnosis, early detection, prognosis, biomarkers, metabolomic profiling, CA19-9, microbiome, metagenomic changes, circulating tumor DNA, genomic analysis. Inclusion criteria included only articles published in English. Exclusion criteria included case reports and studies that did not examine pancreatic cancer. Our analysis demonstrates that integrating multi-omics data, particularly combining traditional CA19-9 with circulating tumor DNA (ctDNA) and metabolomic profiles (lipids, amino acids, carbohydrates), significantly improves diagnostic accuracy. Microbiome composition and genomic alterations further refine risk stratification and prognostic assessment. The synergistic use of these biomarkers may facilitate the development of screening, early diagnosis, risk stratification, and treatment optimization. However, the introduction of new diagnostic approaches into clinical practice requires additional verification, standardization and prospective clinical studies. Full article

Background: Autoimmune diseases such as primary Sjögren’s syndrome and type 1 diabetes are frequently complicated by hepatic injury, yet therapies that simultaneously target inflammation and parenchymal damage remain limited. Mitochondrial dysfunction with excessive reactive oxygen species (ROS) production drives a self-amplifying pathogenic loop by activating the cGAS-STING innate immune pathway. We previously observed that a Chinese herbal formula preserved mitochondrial ultrastructure in autoimmune NOD mice, and computational screening identified trifolirhizin—a natural pterocarpan flavonoid—as the candidate active constituent mediating this protection. Here, we investigated the hepatoprotective effects and underlying mechanisms of trifolirhizin in autoimmune-associated liver injury. Methods: Female NOD mice received trifolirhizin (5, 10, or 20 mg/kg/day) for four weeks, with C57BL/6J mice as healthy controls. Hepatic histopathology, inflammatory cytokines, mitochondrial ultrastructure (TEM), mitochondrial membrane potential (ΔΨm), and ROS levels were evaluated. Integrated transcriptomic and metabolomic profiling was performed to unbiasedly characterize protective mechanisms. In vitro, H₂O₂-induced oxidative stress was established in HepG2 cells. Cells were treated with trifolirhizin (15–25 µM) and assessed for antioxidant enzyme activities, ΔΨm, ROS production, glycolytic and mitochondrial respiration (Seahorse analysis), and cGAS-STING pathway protein expression. Pharmacological rescue experiments using the cGAS agonist cGAMP were conducted to test pathway dependency. Results: Trifolirhizin dose-dependently alleviated hepatic pathological damage and reduced pro-inflammatory cytokine levels in NOD mice. Multi-omics profiling revealed that oxidative stress responses, the mitochondrial electron transport chain, and glutathione metabolism were the most significantly restored pathways. Trifolirhizin preserved mitochondrial ultrastructure, restored ΔΨm, and attenuated ROS accumulation both in vivo and in vitro. Functionally, Seahorse analysis demonstrated that trifolirhizin rescued overall cellular bioenergetics, restoring both glycolytic capacity and mitochondrial respiratory parameters (basal respiration, ATP production, maximal respiration, and spare respiratory capacity). Mechanistically, trifolirhizin suppressed the cGAS-STING-TBK1-IRF3 axis, as evidenced by reduced expression of cGAS, p-STING, ZBP1, p-TBK1, and p-IRF3. Importantly, the cGAS agonist cGAMP abrogated the protective effects of trifolirhizin, confirming that the cGAS-STING pathway is functionally required for its action downstream of mitochondrial protection. Conclusion: Trifolirhizin attenuates liver injury in the nod mouse by preserving mitochondrial integrity, maintaining cellular energy metabolism, and thereby suppressing the ROS/cGAS-STING inflammatory cascade. These findings position trifolirhizin as a promising mitochondria-targeted therapeutic candidate for pSS-related hepatic complications and provide a mechanistic framework for discovering active compounds from mitochondrially active herbal formulations. Full article

High-yielding dairy cows are highly susceptible to lactational oxidative stress, which compromises mammary barrier integrity and elevates mastitis risk. This study investigated the potential biological mechanisms by which dietary hydroxy-selenomethionine (HMSeBA) alleviates oxidative stress and improves health in dairy cows. Forty Holstein cows were assigned to a basal control group (0.32 mg Se/kg DM) or an HMSeBA-supplemented group (0.64 mg Se/kg DM) for 105 days. HMSeBA significantly enhanced selenium bioavailability in both milk and blood, comprehensively strengthening antioxidant defenses (increased glutathione peroxidase activity, decreased malondialdehyde) and elevated serum immunoglobulins (IgA, IgM, IgG), accompanied by a reduction in milk somatic cell count, without significantly affecting milk yield, feed intake, or milk production efficiency. Multi-omics analysis revealed that HMSeBA supplementation altered the rumen microenvironment by enriching fiber-degrading genera (Prevotellaceae_Ga6A1_group, Xylanibacter, Segatella) and shifting metabolites, including feed flavonoids, peptides, 1-deoxy-D-xylulose-5-phosphate, and 3-OH-C6-HSL. The positive correlation of ruminal 3-OH-C6-HSL with both blood selenium and these enriched taxa suggests a potential link between microbial activity and host selenium status. These findings indicate that HMSeBA supplementation improves the antioxidant and immune status of dairy cows, accompanied by exploratory, hypothesis-generating shifts in the ruminal microbiome and metabolome. Collectively, these findings highlight HMSeBA as a promising nutritional strategy to produce selenium-enriched milk while safeguarding udder health. Full article

Osteosarcoma remains the most common primary malignant bone tumor in adolescents and is characterized by aggressive metastasis, resistance to therapy, and extensive bone microenvironment remodeling. Therefore, the identification of novel multi-target therapeutic agents capable of simultaneously inducing ferroptosis and disrupting tumor-supportive signaling is urgently needed. This study employed a multi-omics-guided approach to investigate the anti-osteosarcoma potential of metabolites derived from the sea cucumber Holothuria scabra. LC–MS/MS profiling identified major bioactive constituents, including holothurins, scabrasides, fucosterol, desmosterol, and 24-methylenecholesterol. Integrated transcriptomic analysis of the GSE42352 dataset revealed key ferroptosis- and bone microenvironment-associated targets, including CXCR4, CTSK, RUNX2, VEGFA, and TFRC. In silico pharmacological prediction and molecular docking demonstrated favorable anticancer properties and strong binding affinities of several metabolites toward these targets, with fucosterol and holothurin A exhibiting the most promising interactions. Functional validation in MG-63 osteosarcoma cells showed concentration-dependent reductions in cell viability and migration following H. scabra treatment. Furthermore, treatment decreased GPX4, NRF2, and GSH levels while increasing TFRC and MDA, indicating activation of ferroptotic cell death. In a MG-63/RAW264.7 co-culture model, H. scabra suppressed RANKL, VEGFA, MMP9, and TRAP-positive osteoclast formation, suggesting inhibition of osteoclastogenesis, angiogenesis, and metastatic potential. Collectively, these findings identify H. scabra as a promising marine source of multi-target compounds for osteosarcoma management through coordinated induction of ferroptosis and remodeling of the bone tumor microenvironment. Full article

Nicotinamide (NAM), a precursor of nicotinamide adenine dinucleotide (NAD⁺), and NAD⁺ are integral to a variety of cellular processes. NAM supplementation has been shown to have benefits for cellular senescence. However, the mechanism by which NAM improves skin photoaging remains unclear. In this study, the multi-omics analysis revealed that insufficient nicotinamide metabolism may be associated with a decrease in NAD⁺ synthesis during skin aging. Importantly, we found that NAM has an ameliorating effect on the skin photoaging in mice. Supplementation with NAM restored the expression of the salvage-pathway enzymes and NAD⁺ consumers. In addition, the supplementation with NAM was shown to restore the expression of skin barrier-related proteins (ZO1 and E-cadherin) and collagen I, while reducing the expression of senescence markers (γ-H2AX, p53, and p21). Furthermore, we found that NAM effectively suppresses the senescence-associated secretory phenotype (SASP) factors’ expression in skin photoaging. Our research reveals the dual role of NAM in attenuating skin photoaging, acting not only to delay cellular senescence but also to suppress the SASP. Full article

Background and Objectives: Identifying regulatory genes that integrate epigenetic, transcriptional, immune, and non-coding RNA networks may improve prognostic stratification in hepatocellular carcinoma (HCC). ZBTB40 is a poorly characterized transcription factor whose clinical relevance and multi-layered regulatory role in HCC remain unclear. This study systematically investigated the prognostic significance, molecular regulatory networks, and toxicogenomic interactions of ZBTB40 in HCC. Materials and Methods: Comprehensive multi-omics analyses were conducted utilizing TCGA-HCC datasets and various public bioinformatics platforms. We systematically evaluated ZBTB40 expression patterns, survival outcomes, clinicopathological associations, DNA methylation status, immune cell infiltration, and competing endogenous RNA (ceRNA) networks. Additionally, chemical–gene interactions were analyzed using the Comparative Toxicogenomics Database (CTD). Results: ZBTB40 was significantly overexpressed in HCC, closely correlating with advanced clinicopathological features and poor survival outcomes. This upregulation was significantly associated with promoter hypomethylation. Furthermore, ZBTB40 expression was associated with specific immune infiltration patterns. A ZBTB40-centered ceRNA network identified key regulatory miRNAs, including miR-24-3p, miR-34a-5p, miR-132-3p, and miR-222-3p, along with prognostically relevant lncRNAs and circRNAs. CTD analysis identified 39 key chemical modulators of ZBTB40 (e.g., sorafenib, aflatoxin B1) and revealed RNF13 and CHD3 as functionally related genes sharing substantial chemical interaction profiles. Functional analyses suggested ZBTB40’s involvement in chromatin remodeling, the cell cycle, and immune-related pathways. Conclusions: ZBTB40 expression is associated with multi-layered molecular features involving epigenetic, post-transcriptional, immune-related, and toxicogenomic signatures in HCC. Full article

Against the background of the ongoing transition toward green livestock production and the implementation of “dual-carbon” goals, reducing the environmental footprint of ruminant production while maintaining animal performance has become a key focus in nutritional regulation research. This review summarizes and critically discusses the mechanisms and recent progress of nutritional strategies for emission mitigation and improved nutrient utilization in ruminants, with particular emphasis on major environmental challenges, including enteric methane emissions and nitrogen and phosphorus losses. The review discusses the underlying mechanisms through which nutritional interventions contribute to emission reduction, focusing on ruminal hydrogen flux allocation, microbial community remodeling, host metabolic responses, and changes in nutrient utilization efficiency. In addition, by integrating functional feed additives, diet formulation optimization, precision protein supply, and mineral nutrition regulation, this review compares the application characteristics and practical challenges of different strategies in mitigating methane emissions, reducing nutrient excretion, and sustaining production performance. Furthermore, research approaches such as in vitro screening, multi-omics analysis, and evidence synthesis approaches are discussed to highlight the shift of green nutritional technologies from single-target interventions toward integrated and system-level regulation. This review provides a theoretical basis and technical reference for developing green ruminant production systems that balance productivity, animal health, and environmental sustainability. Full article

Cold stress is a key environmental constraint in aquaculture, but integrated host responses linking oxidative status, intestinal microbiota, and hepatic metabolism remain insufficiently characterized in Luciobarbus capito. This study aimed to evaluate the biochemical, microbial, and metabolic responses of L. capito to acute low-temperature exposure. Fish were exposed to 12 °C for 96 h, with fish maintained at 22 °C as controls; hepatic antioxidant indices, serum biochemical parameters, intestinal microbiota based on 16S rRNA gene sequencing, and liver metabolomic profiles were analyzed. Cold exposure reduced hepatic total superoxide dismutase (T-SOD) and catalase (CAT) activities and increased malondialdehyde (MDA) content, while serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities increased and acid phosphatase (ACP) activity decreased. The intestinal microbiota showed reduced richness and compositional shifts, including decreased Cetobacterium and increased Pseudomonas. Liver metabolomics identified 172 differential metabolites, with enriched pathways related to glycerophospholipid metabolism, α-linolenic acid metabolism, pantothenate and CoA biosynthesis, and ascorbate and aldarate metabolism. Correlation analysis indicated significant associations between altered bacterial genera and hepatic metabolites. These results suggest that acute cold stress disrupts oxidative balance, intestinal microbial composition, and hepatic metabolism in L. capito, providing an integrated view of associated physiological and metabolic responses to low-temperature stress. Full article

Direct sea discharge outlets served as critical conduits for urban sewage and industrial wastewater disposal, playing dual roles as pollutant dilution channels and hotspots for pathogens and antibiotic resistance genes. Traditional monitoring approaches relying on physicochemical parameters and fecal indicator bacteria failed to capture the latent and cumulative risks posed by complex microbial communities. In this review, a holistic microbiome perspective was adopted to systematically synthesize current knowledge on the bacterial community dynamics, assembly mechanisms, resistome–virulome coupling patterns, mobilome-associated risk characteristics, and emerging biomonitoring strategies in direct sea discharge outlets. By integrating high-throughput multi-omics technologies with ecological network analysis and machine learning, we delineated a paradigm shift from cataloging microbial presence to deciphering functional interactions, risk propagation dynamics, and proactive surveillance strategies. Furthermore, under the “One Health” framework, we discussed emerging research frontiers and future challenges in managing pollution at discharge outlets, aiming to provide a scientific basis for environmental risk management in coastal zones. Full article

Single-cell omics technologies have transformed the study of cellular heterogeneity, enabling high-resolution analysis of tissue development and complex traits. In sheep and goats, these approaches have been applied to skin, hair follicles, reproductive organs, metabolic tissues, and adipose tissue, revealing cell type-specific regulatory programs underlying traits such as wool quality, fertility, growth, and fat deposition. However, most studies rely on single-cell RNA sequencing (scRNA-seq) and are limited by incomplete genome annotation, insufficient coverage of production traits, and weak integration with population genetics, restricting their application in molecular breeding. This review summarizes advances in single-cell omics in sheep and goats, focusing on tissue development and trait formation. We further discuss emerging strategies that integrate single-cell multi-omics, spatial transcriptomics, and population genetics to resolve regulatory mechanisms in a cell type-specific and spatially informed context. Finally, we discuss CRISPR/Cas9-based validation to link genotype and phenotype, accelerating gene discovery and precision breeding in small ruminants. Full article

Climate change and soil degradation pose a challenge to grape quality, motivating the development of integrated monitoring approaches combining soil analysis with remote sensing techniques. However, harmonized information addressing this multidisciplinary challenge remains scarce. Therefore, this systematic review synthesizes the scientific literature published since 2020 with the aim of (i) identifying key soil properties and techniques applied, (ii) evaluating remote sensing approaches and their integration with soil data, and (iii) highlighting knowledge gaps and challenges for sustainable precision viticulture. A search in Scopus yielded 197 full-text articles classified into three thematic groups and analyzed using a standardized extraction protocol. Our synthesis reveals that pH, electrical conductivity, soil organic matter, and cation exchange capacity are the most consistently reported physicochemical parameters across the reviewed studies, while next-generation sequencing and multi-omics approaches are increasingly adopted in microbiological research to characterize rhizosphere communities and their links to terroir expression. In remote sensing, multispectral UAV platforms and satellite missions (Sentinel-2, Landsat) combined with vegetation indices, principally NDVI, dominate the toolset for monitoring vine vigor and water status. Nevertheless, genuine integration of remote-sensing outputs with root-zone soil measurements remains uncommon, with most studies treating both data streams independently. The principal knowledge gaps identified concern the absence of standardized sustainability assessment frameworks, limited cross-terroir transferability of predictive models, and insufficient long-term multi-site datasets to underpin climate change adaptation in vineyard management. Full article

Lipophilic marine toxins (LMTs) are important toxic risk factors in marine ecosystems and seafood safety, yet the comparative cytotoxicity-associated molecular responses of different LMT classes remain unclear. Here, Neuro-2a cells were exposed to four representative LMTs—dinophysistoxin-1 (DTX1), azaspiracid-3 (AZA3), yessotoxin (YTX), and pectenotoxin-2 (PTX2)—and acute cytotoxicity was evaluated together with integrated transcriptomic, proteomic, and metabolomic analyses. Cell viability assays showed a cytotoxic potency order of DTX1 > AZA3 > YTX > PTX2. Integrated multi-omics analysis revealed that DTX1, the most cytotoxic toxin, caused the broadest molecular perturbations, mainly involving mitochondrial energy metabolism, p53-mediated stress responses, and multilayered metabolic networks. AZA3 and YTX induced intermediate cytotoxicity and showed partially similar perturbation patterns, particularly affecting cytoskeleton-related, immune-related, and metabolism-related processes. In contrast, PTX2, the least cytotoxic toxin, produced more limited responses mainly involving tyrosine metabolism and the cGMP–PKG signaling network. Overall, molecular perturbation patterns generally corresponded to acute cytotoxic potencies, while each toxin exhibited distinct key pathways and functional modules. These findings provide a multi-omics basis for cytotoxic responses of representative LMT classes and guide subsequent functional validation. Full article

Ovine pulmonary adenocarcinoma (OPA), caused by the exogenous Jaagsiekte sheep retrovirus (JSRV), shares several pathological and molecular features with human lung adenocarcinoma, providing an important model for comparative oncology. JSRV pathogenesis is mostly studied at the transcriptome level, with systematic proteomic and metabolomic studies remaining insufficient. Therefore, this study aimed to systematically characterise the molecular alterations associated with JSRV-induced OPA by integrating direct data-independent acquisition proteomics and untargeted metabolomics. We established an OPA model by infecting lambs with JSRV and performed multi-omics analyses on the lesion and control lung tissues (n = 3 per group for both proteomic and metabolomic analyses). In total, 1631 differentially expressed proteins and 748 differential metabolites were identified, and the two omics datasets exhibited highly coordinated variations. Integrated analyses suggested that adhesion remodelling (with downregulated LIMCH1), endoplasmic reticulum stress (with upregulated HYOU1), and metabolic and immune-related alterations (accompanied by elevated GFPT1 and PTGS2) represent major biological processes associated with JSRV infection. Western blot analysis confirmed the expression changes in these proteins. Overall, this study provides a multidimensional molecular landscape of OPA and expands current understanding of the molecular alterations associated with JSRV infection. These findings provide candidate pathways and molecular targets for future mechanistic studies and comparative investigations of lung adenocarcinoma. Full article

Sperm cryopreservation is important for livestock breeding and germplasm conservation, but freeze–thaw injury can impair ram sperm quality through oxidative stress, membrane damage, and metabolic disturbance. This study evaluated the concentration-dependent effects of kaempferol supplementation on the cryopreservation quality of semen from Yuansheng Aite dairy rams. Qualified ejaculates were pooled and randomly allocated to five equally spaced kaempferol treatment groups: 0, 25, 50, 75, and 100 μg/mL. Post-thaw sperm motility, oxidative stress status, ATP-related energy metabolism, acrosome integrity, and multi-omics profiles were evaluated. Data were analyzed using appropriate parametric or non-parametric tests after assessment of normality and homogeneity of variance. Orthogonal polynomial analysis was performed to evaluate linear and nonlinear dose–response patterns across the tested kaempferol concentrations. Kaempferol supplementation significantly affected PM, VCL, and VAP, while RPM, LIN, WOB, and VSL were not significantly affected. No significant linear effect was observed for the motility parameters, whereas VCL exhibited a significant quadratic response to kaempferol concentration. Based on the observed overall responses of sperm motility, antioxidant capacity, oxidative stress markers, ATP content, and acrosome integrity, 25 μg/mL kaempferol showed the most favorable overall profile among the tested concentrations and was selected for subsequent mechanistic analyses. Proteomic and metabolomic analyses suggested that the protective effects of kaempferol may be associated with pathways related to focal adhesion, cytoskeletal organization, oxidative phosphorylation-related energy metabolism, and central carbon metabolism. These findings indicate that moderate kaempferol supplementation may improve the post-thaw quality of Yuansheng Aite dairy ram semen, although further fertility-oriented studies are needed to confirm its practical reproductive benefits. Full article

Background/Objectives: Telomeres are critical biomarkers of biological aging, with shortened leukocyte telomere length strongly linked to all-cause mortality and age-related disease risk. Although exercise modulates telomere dynamics, the field’s evolution from descriptive measurements to mechanistic inquiries involving redox biology and epigenetics remains incompletely mapped. This study systematically characterized the global research landscape of telomere–exercise science over 25 years to establish a strategic evidence base for precision exercise prescription. Methods: A bibliometric analysis was conducted on 858 publications from the Web of Science Core Collection (2000–2025). CiteSpace and VOSviewer were used for keyword co-occurrence analysis, strategic thematic mapping, and citation burst detection to visualize global research trends and identify emerging frontiers. Results: Annual publication volume grew from 2 (2000) to 71 (2025), with a compound annual growth rate of 15.4%. China emerged as one of the leading global contributors. Thematic analysis revealed a paradigm shift from descriptive leukocyte telomere length studies toward mechanistic investigations of oxidative stress, mitochondrial homeostasis, and epigenetic clocks. Keyword network analysis confirmed oxidative stress and inflammation as central hubs, mediating telomere protection via redox regulation and non-canonical telomerase functions. Conclusions: Exercise preserves telomere integrity primarily through redox–mitochondrial homeostasis, hormesis-driven antioxidant upregulation, and non-canonical telomerase activation. For aging populations and individuals at metabolic risk, aerobic training and high-intensity interval training (HIIT) are recommended as first-line non-pharmacological interventions for healthspan extension. Leukocyte telomere length and telomerase activity should be integrated as biomarkers in preventive medicine practice. Future large-scale randomized controlled trials incorporating multi-omics approaches and sex-stratified analyses are warranted to establish individualized dose–response guidelines for precision exercise prescription. Full article