Search Results (1,554)

Background: Aberrant glycosylation is closely associated with tumor progression, changes in the tumor microenvironment, and chemoresistance. This study aimed to identify prognostic sialylation-related genes in bladder cancer and define the role of ST3GAL6 in gemcitabine–cisplatin resistance. Methods: Molecular subtype analysis, prognostic analysis, and risk model construction were performed for sialylation-related genes using transcriptomic data and clinical information from the TCGA database. GC-resistant bladder cancer cell models were established for transcriptomic sequencing and untargeted metabolomic analysis. Cell proliferation and drug sensitivity assays were performed to evaluate the function of ST3GAL6. The regulatory relationship between IGF2BP3, ST3GAL6, and the PI3K pathway was further assessed by combining database analysis with molecular experiments. Results: Sialylation-related molecular patterns were associated with patient prognosis and tumor microenvironment features, particularly fibroblast-related characteristics, in bladder cancer. The key model gene ST3GAL6 was upregulated in bladder cancer tissues and was closely associated with prognosis. In GC-resistant bladder cancer cells, ST3GAL6 expression was significantly increased and accompanied by enhanced sialylation activity. ST3GAL6 promoted bladder cancer cell proliferation and reduced sensitivity to cisplatin and gemcitabine, at least in part through the PI3K-AKT-mTOR pathway. IGF2BP3 was also upregulated in resistant cells, is positively correlated with ST3GAL6, and may help maintain ST3GAL6’s expression by stabilizing its mRNA. Conclusions: Our findings suggest that aberrant sialylation is involved in bladder cancer progression and GC resistance. The IGF2BP3-ST3GAL6-PI3K/AKT/mTOR signaling axis may contribute to this process and may serve as a potential biomarker and therapeutic target in bladder cancer. Full article

Spatholobus suberectus is a traditional edible, ornamental, and medicinal vine with an abundant flavonoid content in its dried stems. An integrated metabolomic and transcriptomic analysis was conducted on its vegetative organs to identify flavonoid biosynthesis pathways. The results showed that: (1) a total of 268 flavonoids could be identified among all the vegetative organs, and stems accumulated most of them; (2) a total of 449,569,220 clean reads were retained from all the vegetative organs (many genes related to key enzymes of flavonoid biosynthesis and transcription factors were found in all the compared groups between different organs; among them, 77 genes showed high correlations with key flavonoids in different pathways); and (3) PAL (encoding phenylalanine ammonia-lyase), 4CL (encoding 4-coumarate: CoA ligase), C4H (encoding cinnamate-4-hydroxylase), CHS (encoding chalcone synthase), DFR (encoding dihydroflavonol 4-reductase) and others showed positive correlations with L-phenylalanine and various flavonoids, while FLS (encoding flavonol synthase) showed negative correlations with many flavonols and flavonoids, as revealed through integrated analysis. This study reveals the flavonoid biosynthesis characteristics in S. suberectus and provides new insights into the utilization of its biological resources. Full article

Precision nano-fertilization offers transformative potential for sustainable improvement of grape quality, yet the underlying molecular mechanisms remain poorly understood. Here, we investigated the effects of foliar-applied nano zero-valent iron (nZVI) and potassium dihydrogen phosphate (KH₂PO₄), in combination, on berry quality and secondary metabolic reprogramming in Vitis vinifera cv. Marselan. The combined nZVI/KH₂PO₄ treatment improved photosynthetic capacity, Fe/P co-accumulation, and berry quality traits including soluble solid content, sugar–acid ratio, and phenolic and aroma metabolite profiles. Crucially, integrated transcriptomic and metabolomic profiling identified 631 differentially expressed genes and 838 differentially accumulated metabolites, converging on flavonoid biosynthesis and glutathione metabolism as the dominant regulatory axes. Correlation network analysis pinpointed five hub regulatory genes—VvHCT, VvFLS1, VvLAR1/2, VvUGT88F5, and VvODC—as central orchestrators of nanomaterial-driven metabolic reprogramming: VvHCT and VvFLS1 coordinately redirected carbon flux toward hydroxycinnamic acid conjugates and flavonol accumulation, while VvLAR1/2 governed proanthocyanidin polymerization, and VvUGT88F5 modulated glycosylation-dependent metabolite stabilization. Notably, VvODC linked polyamine metabolism to glutathione-mediated stress buffering, revealing a previously uncharacterized crosstalk between nano-iron signaling and antioxidant reprogramming. These findings establish a mechanistic framework in which nZVI and KH₂PO₄ synergistically remodel the secondary metabolome through discrete yet interconnected transcriptional nodes, providing molecular targets for nano-enabled precision viticulture and broader applications of engineered nanomaterials in high-value crop improvement. Full article

Heat stress is a major constraint to productivity and physiological homeostasis in laying hens. This study investigated integrated responses to acute heat stress using a multi-omics approach, including performance traits, serum biochemical parameters, histology, hepatic transcriptomics, cecal metagenomics, and metabolomics. Acute heat stress impaired productive performance, as reflected by changes in egg production and reduced eggshell strength, and induced systemic physiological disturbances, including increased stress- and injury-related blood indicators and disrupted metabolic and electrolyte balance. Histological analysis confirmed liver and intestinal tissue damage. Hepatic transcriptomics revealed inflammatory activation and suppression of metabolic pathways, particularly those involved in lipid metabolism, energy production, and redox homeostasis. Cecal metagenomic and metabolomic analyses showed altered microbial composition and functional potential, along with disruptions in amino acid, lipid, and energy metabolism. Collectively, these findings suggest that acute heat stress is associated with coordinated inflammatory responses and metabolic reprogramming, together with liver and intestinal injury and gut microbiota–metabolite alterations. The study provides a framework for understanding early heat stress responses and highlights potential targets for nutritional and microbiota-based interventions in poultry production. Importantly, serum biochemical indicators such as D-lactic acid and aspartate aminotransferase may serve as potential early biomarkers for monitoring heat-stress-induced physiological disturbances. Full article

In the human reproductive system, extracellular vesicles (EVs) have been recognized as playing a vital role in mediating cell–cell communication. They are considered critical for embryo development, implantation, gamete interaction, and fertilization. The various cargoes carried by EVs, depending on the physiological and pathological state of the cell, include proteins, lipids, nucleic acids, and mitochondrial components. EVs are recognized as critical carriers of redox-related signals and mitochondrial components, linking oxidative stress (OS) to reproductive failure and influencing gamete quality and embryo competence. Although considerable progress has been made, research remains poorly integrated, despite individual omics technologies providing valuable molecular insights. The use of multi-omics technologies, including transcriptomics, proteomics, metabolomics, and microbiome analysis, has been proposed as a global approach to understanding the complexities associated with EVs and discovering new biomarkers associated with infertility. ML and AI have been proposed to identify predictive signatures linked to ART effectiveness and reproductive outcomes, with a strong capacity to handle high-dimensional data. The review aims to provide an overview of current knowledge on EV-mediated redox–mitochondrial signaling in human reproduction, while highlighting the importance of emerging multi-omics and AI technologies for EV-mediated biomarker development. The review discusses the promise of EVs in the development of minimally invasive diagnostic approaches and therapeutic interventions, as well as the challenges in the standardization, integration, and clinical translation of EV-mediated research. In addition, the review proposes integrating computational approaches to better understand molecular pathways involved in the development of next-generation precision medicine in human reproduction. Full article

Squalene, a high-value triterpenoid precursor widely used in pharmaceuticals and vaccine adjuvants, is primarily sourced from shark liver oil—an unsustainable practice that has driven interest in developing plant-based production alternatives. The first committed reaction in triterpenoid biosynthesis is catalyzed by squalene synthase (SQS), yet no SQS gene has been characterized in Amaranthus tricolor, a species recognized for its high squalene content. Here, we cloned and functionally characterized AtrSQS, a novel squalene synthase gene isolated from A. tricolor for the first time. Sequence analysis revealed that AtrSQS contains conserved domains and six characteristic motifs shared among plant SQSs, with high homology to orthologs from dicotyledonous species. To investigate its functional role in squalene biosynthesis, AtrSQS was overexpressed in Nicotiana tabacum under the CaMV 35S promoter. Transgenic lines exhibited significantly increased AtrSQS expression and accumulated squalene up to 6.81 μg/g dry weight, a 4.76-fold increase over wild-type plants. Additionally, the content of downstream product 2,3-oxidosqualene was also significantly elevated in the transgenic lines. Integrated transcriptomic and metabolomic analyses revealed that AtrSQS overexpression upregulated key mevalonate pathway genes (AACT, HMGS, MVD) and FPPS. Meanwhile, it suppressed competitive carotenoid biosynthesis and the production of an SQS-specific inhibitor, indicating a successful redirection of metabolic flux toward squalene production. These findings demonstrate that AtrSQS is crucial for squalene biosynthesis and provide both a valuable genetic resource and mechanistic insights for engineering plant-based squalene production systems. Full article

Age-related changes in the gut significantly impact host health, yet the multi-omics dynamics during the maturation of Tibetan pigs remain unclear. This study aimed to investigate the morphological, microbial, metabolic, and transcriptomic transformations in the intestines of aging Tibetan pigs. We analyzed the ileum and colon of 1-year-old and 3-year-old Tibetan pigs using histological evaluation, 16S rRNA sequencing, metabolomics, and transcriptomics. Aging to 3 years significantly improved ileal architecture, notably increasing the villus height to crypt depth ratio. Older pigs exhibited higher colonic microbial diversity, a decreased Firmicutes to Bacteroidota ratio, and enrichment of homeostasis-associated taxa, including Lactobacillus, Prevotellaceae, and Ruminococcaceae. Metabolomics revealed higher abundance of certain metabolites, including docosahexaenoic and arachidonic acids, enriching lipid metabolism and bile secretion pathways. Transcriptomics identified 2363 differentially expressed genes in the ileum, primarily involved in immune regulation and nutrient digestion. Integrated analysis showed strong positive correlations between enriched microbes (Lactobacillus porci) and up-regulated host genes (UGT2B31, CCL28) governing intestinal homeostasis. The transition from 1 to 3 years of age in Tibetan pigs fosters a synergistic host-microbiome environment, enhancing intestinal barrier function, immune capacity, and metabolic efficiency. Full article

Grape seeds are a major by-product of grape processing and a rich source of polyphenolic compounds, yet their value remains underutilized. In this study, 12 lactic acid bacteria (LAB) strains were evaluated in a grape seed-based fermentation system to compare their tolerance, metabolic performance, and ability to promote polyphenol release. Among them, Lactiplantibacillus plantarum FBL002 showed the best overall performance. The strain maintained strong viability and metabolic activity at 5% grape seed concentration and released polyphenols more effectively than the other tested strains. The resulting fermentation broth also showed pronounced intracellular antioxidant activity. To clarify the basis of this phenotype, we further combined metabolomic, genomic, and transcriptomic analyses. Fermentation caused substantial shifts in phenolic metabolites, characterized by a decrease in glycosylated forms and an increase in more bioactive aglycones. Genome annotation revealed an enrichment of β-glucosidase-related genes in FBL002, and transcriptomic analysis showed that these genes were markedly upregulated during fermentation. This pattern was closely associated with the enhanced release of polyphenols. Together, these findings identify β-glucosidase as a key driver of grape seed polyphenol biotransformation by FBL002 and support the sustainable, high-value use of grape seeds in functional foods and cosmetic applications. Full article

This study aimed to identify candidate molecular pathways mediating dopaminergic dysfunction induced by PFAS mixture exposure, with a focus on the TM/5-HT signaling axis and calcium-linked lipid metabolites, and to explore potential gut-brain axis involvement. Adult mice were exposed to a PFAS mixture. Behavioral tests assessed spatial memory, spontaneous activity, and motor coordination. Histopathological and ultrastructural analyses examined neuronal atrophy, mitochondrial damage, α-synuclein (α-syn), and tyrosine hydroxylase (TH). Transcriptomics, metabolomics, and gut microbiota profiling (16S rRNA sequencing) were performed, followed by integrated multi-omics and correlation analyses. PFAS exposure was associated with PD-relevant motor and cognitive impairments, including impaired spatial memory, reduced spontaneous activity, and motor coordination deficits. Neuronal atrophy, mitochondrial structural damage, upregulation of α-syn, and downregulation of TH were observed. Transcriptomics identified 315 differentially expressed genes (DEGs) enriched in ciliary movement, neuroactive ligand-receptor interactions, and serotonergic synapses. Metabolomics identified 130 differentially abundant metabolites involved in arachidonic acid metabolism and serotonergic synapses. Integrated analysis highlighted correlative changes in the TM/5-HT signaling pathway. Phosphatidylinositol PI(16:0/20:2(11Z,14Z)) showed a strong positive correlation with Dbh gene expression, suggesting a candidate association between Dbh expression and phosphatidylinositol alterations. Gut microbiota analysis revealed compositional alterations (e.g., Muribaculaceae, Ileibacterium) and predicted functional shifts (e.g., tryptophan metabolism–related modules) were observed; these findings are exploratory. This study identifies multi-omics signatures associated with PFAS mixture-induced dopaminergic dysfunction in mice. The TM/5-HT pathway emerges as a candidate molecular axis requiring further investigation. Gut microbiota alterations suggest a potential peripheral component, but causality and gut-brain axis involvement remain hypothetical and need direct experimental validation. Full article

Soil salinity is a major environmental constraint limiting plant productivity and modulating secondary metabolism. Triterpenoid saponins play crucial roles in plant stress adaptation, yet their biosynthetic regulation in Cyclocarya paliurus under salt stress remains poorly understood. This research integrated transcriptomic and metabolomic analyses to investigate triterpenoid saponin metabolism in C. paliurus leaves at four NaCl concentrations and two sampling times. Salt stress altered ion homeostasis, suppressed growth, and induced distinct triterpenoid saponins accumulation patterns, with cyclocaric acid B and oleanolic acid showing significant increases. Weighted gene co-expression network analysis identified two modules significantly correlated with triterpenoid saponin accumulation and highlighted transcription factors including WRKY18, bHLH121, ERF4, and ERF1 as regulators of key biosynthetic genes (DXS, SQS, and HMGR). Molecular docking further validated these regulatory interactions, demonstrating that bHLH35, MYC2, ERF113, and MED26B form stable complexes with target gene promoters through extensive hydrogen-bond networks. These findings elucidate the regulatory framework of triterpenoid saponin metabolism under salinity and provide a foundation for molecular breeding and cultivation of C. paliurus in saline regions. Full article

Water stress is a major abiotic constraint limiting the growth and productivity of alfalfa (Medicago sativa L.). To elucidate the adaptive mechanisms and identify key drought-tolerance genes, physiological measurements were integrated with multi-omics analyses of cultivar ‘Tamu 1’ under three water treatments: waterlogging (100% field water capacity), normal irrigation (80% FWC), and drought (light: 60% FWC, moderate: 40% FWC, severe: 20% FWC). Water stress markedly inhibited plant growth, induced oxidative stress, and reduced the photosynthetic capacity. Compared with waterlogging stress (DAMs: n = 71; DEGs: n = 313), drought stress resulted in a substantially greater number of differentially accumulated metabolites (DAMs, n = 1504) and differentially expressed genes (DEGs, n = 8006). Weighted gene co-expression network analysis (WGCNA) identified six key modules and ten hub genes associated with stress responses. Integrated transcriptomic and metabolomic analyses further revealed four major responsive pathways: starch and sucrose metabolism, phenylpropanoid and flavonoid metabolism, glutathione metabolism, and zeatin biosynthesis. Based on integrative criteria, including differential expression (|log₂FC| ≥ 1, adjusted p < 0.05), WGCNA modules significantly associated with drought-related traits (R² > 0.6), as well as functional annotation and protein–protein interaction (PPI) network topology, 28 candidate genes associated with drought tolerance were identified, of which six were further validated by quantitative real-time PCR (qRT-PCR). These findings highlight key metabolic pathways and regulatory modules underlying alfalfa responses to water stress and provide valuable candidate gene resources for improving drought tolerance. Full article

Soybean (Glycine max [L.] Merr.) seed hardness is a critical physical trait that dictates processing efficiency and end-product quality, yet the underlying genetic and metabolic regulatory networks remain poorly elucidated. To systematically decipher the mechanisms governing this complex quantitative trait, a multi-omics approach integrating a genome-wide association study (GWAS), transcriptomics, and metabolomics was conducted on a panel of 162 soybean germplasm accessions from Northeast China. Four significant quantitative trait nucleotides (QTNs) on chromosomes 15 and 19 were identified by GWAS. Subsequent RNA-seq and liquid chromatography–mass spectrometry (LC-MS) analyses comparing extreme phenotypes identified 573 differentially expressed genes (DEGs) and 784 differentially accumulated metabolites (DAMs). Joint multi-omics analysis revealed 14 consistently enriched pathways, highlighting the crucial role of secondary metabolite biosynthesis. Notably, Glyma.19G030500, which encodes an isoflavone malonyltransferase, was identified as the primary hub gene. These findings offer valuable genomic targets for the marker-assisted breeding of soybean varieties with optimized processing qualities. Full article

Goose blood has anticancer properties and was recorded in ancient China, but the specific molecular mechanisms underlying this effect still require further exploration. In this study, SW1990 cells were treated with goose serum or plasma, and transcriptome analysis was performed to explore the function of goose blood on cancer cells. Metabolomic profiling was also performed on goose serum, goose plasma, chicken serum, and chicken plasma to identify the bioactive substances responsible for the anticancer effect. The study examined the effects of goose plasma and serum on SW1990 cells and compared the metabolites between goose and chicken blood. Wound scratch, CCK-8, and Annexin V-PI assays showed that goose plasma and serum inhibited SW1990 cell proliferation at 24 and 48 h. Both treatments reduced cell viability, with serum inducing early and late apoptosis and plasma inducing late apoptosis. RNA sequencing (RNA-seq) identified 2259 (1418 upregulated, 841 downregulated) and 2731 (1844 upregulated, 887 downregulated) differentially expressed genes (DEGs) in the plasma and serum groups versus the negative control (NC), respectively, and 689 DEGs between the plasma and serum groups. Gene Ontology (GO) and KEGG pathway analyses revealed that the DEGs were enriched in processes such as lipid metabolism, JAK-STAT, and IL-17 pathways. Untargeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis identified distinct metabolites in goose and chicken blood, with unique metabolites and differential ones between groups. In SW1990 cells, four metabolite subclusters matched the plasma and serum effects. In summary, goose blood can suppress cancer cells by regulating gene expression to affect the key signaling pathways involved in cancer cell apoptosis and autophagy. Certain metabolites present at high concentrations in goose blood, such as cucurbitacin D and Oleoyl-L-carnitine, may also contribute to the inhibition of cancer cell proliferation and migration. These findings suggest that goose blood holds broad application prospects as a future auxiliary drug for cancer treatment, and this study provides a theoretical basis for the further application of goose products. Full article

Carotenoids are an important class of natural compounds, essential for human nutrition, acting in plants as pigments and apocarotenoid precursors. Tomato is a key model for carotenoid metabolism, as genetic variation strongly affects carotenoid composition during fruit ripening. To date, most of the enzymes involved in the carotenoid pathway were mainly characterized by linking gain- or loss-of-function phenotypes to their genetic basis (e.g., mutation in a single gene), with limited integration into pathway-wide analyses. Here we report an extensive biochemical and molecular characterization of a collection of tomato carotenoid mutants—apricot (at), yellow flesh (r), tangerine (t), Delta (Del) and Beta (B)—throughout three different stages of fruit ripening (mature green, breaker, red ripe). Using correlation-based integrative analyses, we integrated targeted isoprenoid metabolomics (carotenoids, chlorophylls, tocochromanols, quinones, abscisic acid) with gene expression profiling and correlation-based analyses. The pronounced, stage-dependent remodeling of the isoprenoid profiles exceeded the expected changes in substrates/products and was accompanied by significant transcriptional changes, largely independent of the position of the mutated step in the pathway. This integration highlighted metabolite/transcript regulatory links and the central role of lycopene cyclization in isoprenoid metabolism rewiring, thus improving our understanding of mechanisms controlling their accumulation during tomato fruit ripening. Full article

The amino acid composition of hazelnut seeds is a critical determinant of nutritional value and flavor. Understanding the biosynthesis mechanisms during seed development is essential for breeding functional varieties. In this study, we analyzed the seed quality characteristics of three Corylus heterophylla × Corylus avellana cultivars (DW, YZ, and B-21) using extensive targeted metabolomics and transcriptomics at the seed enrichment and fruit maturity stages. A total of 273 amino acid-related metabolites—including free proteinogenic amino acids, non-proteinogenic amino acids, small peptides, and their derivatives— were identified. While all cultivars contained a complete profile of essential amino acids, their accumulation patterns varied significantly. Notably, B-21 exhibited significantly higher total amino acid content compared with DW and YZ, although its content decreased during ripening. Integrated metabolomics and transcriptomics analysis, facilitated by Pearson correlation network analysis (PCA), identified 16 key structural genes strongly associated with amino acid synthesis, including PK, ENO, PHGDH, aroA, and trpE. Specifically, IMDH was significantly positively correlated with arginine synthesis, while ilvH, rpiA, and lysC were potential contributors to the synthesis of methionine, histidine, and tryptophan. These findings highlight a putative regulatory network of amino acid biosynthesis in hybrid hazelnuts and provide candidate genes for future functional validation and the genetic improvement of hazelnut nutritional quality. Full article