Metabolites最新文献

Background: Endolichenic fungi represent an emerging source of bioactive secondary metabolites; however, the genomic basis of their chemical diversity remains largely poorly characterized. Specifically, the metabolic capabilities of Cladosporium limoniforme have not been explored at the genomic level. Objectives: This study aimed to characterize the biosynthetic potential of C. limoniforme by presenting its first whole-genome sequence and conducting a comparative analysis of its biosynthetic gene clusters (BGCs), with a specific focus on the evolutionary conservation of the DHN-melanin pathway. Methods: Genome mining was performed using antiSMASH and fungiSMASH tools. Comparative genomics involved heatmap-based distribution analysis across the Cladosporium genus, synteny profiling using Clinker to assess gene order conservation, and Maximum Likelihood phylogenetic analysis of the polyketide synthase (T1PKS) domain. Results: We identified 26 putative BGCs, revealing a largely untapped metabolic repertoire. Comparative analysis demonstrated a high degree of conservation for the metachelin C (siderophore) and 1,3,6,8-tetrahydroxynaphthalene (T4HN) clusters across the genus. Notably, synteny and phylogenetic analyses showed that while C. limoniforme retains a conserved, ancestral T1PKS core essential for stress survival, it exhibits a significant reduction in accessory genes compared to plant-pathogenic congeners. Conclusions: These findings support a "metabolic streamlining" hypothesis driven by the endolichenic lifestyle, where the fungus retains essential protective machinery while shedding costly accessory genes unnecessary in the buffered lichen niche. This study establishes C. limoniforme as a valuable genomic resource for future biotechnological research.

Lactic acid accumulates in the tumour microenvironment (TME) at concentrations reaching up to 40 mM. Initially, lactic acid was considered merely a metabolic by-product of aerobic glycolysis, a phenomenon commonly referred to as the Warburg effect and observed in the majority of tumours. Recent evidence, however, has demonstrated that lactic acid is not merely a waste product; rather, it plays a pivotal role in tumour biology. High plasma lactic acid levels correlate with increased metastatic potential and lower survival rates. Elevated lactic acid levels in the TME have been shown to suppress antitumour immune responses, facilitate both metastasis and cellular senescence, and might modulate gene expression through novel epigenetic mechanisms such as histone lactylation. This review aims to summarize current knowledge on the multifaceted impact of elevated lactic acid in the TME on tumour progression and biology.

Background: The Metabolomics Workbench (MW) is a public scientific data repository consisting of experimental data and metadata from metabolomics studies collected with mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses. Although not as rapidly as in the past, MW has steadily evolved, updating its mwTab and JSON deposition text file formats and its web-based infrastructure. However, the growth of MW has been exponential since its inception in 2013 and continues to be exponential, with the number of datasets hosted on the repository increasing by 50% since April 2024. As part of regular maintenance to keep up with changes to the mwTab file format and an earnest effort to use MW datasets in meta-analyses, the mwtab Python package has been updated. Methods: Updates include better error handling for batch processing, better parsing to read more files without error, and extensive improvements to the validation capabilities of the package. These updates also required our mwFileStatusWebsite to be updated and improved. Results: We used the enhanced validation features of the mwtab package to evaluate all available datasets in MW to facilitate improved curation, FAIRness of the repository, and reuse for meta-analyses. Conclusions: Version 2.0.0 of the mwtab Python package is now officially released and freely available on GitHub and the Python Package Index (PyPI) under a Clear Berkeley Software Distribution (BSD) license, with documentation available on GitHub. The updated mwFileStatusWebsite is also officially in its 2.0.0 version.

Background/objectives: This review integrates evolutionary, metabolic, genetic, and nutritional perspectives to explain how sterol-derived vitamin D pathways shape human physiology and inter-individual variability in vitamin D status.

Methods: The literature on sterol and vitamin D metabolism across animals, plants, fungi, and algae was synthesized with data from metabolomics databases, genome-wide association studies, RNA-seq resources (including GTEx), structural biology, and functional genomics.

Results: Vitamin D₂ and vitamin D₃ likely emerged early in evolution as non-enzymatic photochemical sterol derivatives and were later co-opted into a tightly regulated endocrine system in vertebrates. In humans, cytochrome P450 enzymes coordinate vitamin D activation and degradation and intersect with oxysterol production, thereby linking vitamin D signaling to cholesterol and bile acid metabolism. Tissue-specific gene expression and regulatory genetic variants, particularly in the genes DHCR7, CYP2R1, CYP27B1, and CYP27A1, contribute to population-level differences in vitamin D status and metabolic outcomes. Structural analyses reveal selective, high-affinity binding of 1,25-dihydroxyvitamin D₃ to VDR, contrasted with broader, lower-affinity ligand recognition by LXRs. Dietary patterns modulate nuclear receptor signaling through distinct yet convergent ligand sources, including cholesterol-derived oxysterols, oxidized phytosterols, and vitamin D₂ versus vitamin D₃.

Conclusions: Sterol and vitamin D metabolism constitute an evolutionarily conserved, adaptable network shaped by UV exposure, enzymatic control, genetic variation, and diet. This framework explains inter-individual variability in vitamin D biology and illustrates how evolutionary and dietary modulation of sterol-derived ligands confers functional flexibility to nuclear receptor signaling in human health.

Background/Objectives: Replacing fish oil with vegetable oil is an important measure for aquaculture to relieve the pressure of fish oil, but it is also easy to cause the growth decline and metabolic disorder of farmed animals, mainly due to the change in dietary fatty acids. This study investigated the regulatory effects of dietary fatty acid composition on glucose metabolism in large yellow croaker (Larimichthys crocea) with an initial weight of 30.51 ± 0.16 g. Methods: Three isonitrogenous (~43% crude protein) and isolipid (~11% crude lipid) diets were formulated as follows: control (CON, DHA/EPA-rich oil as primary lipid), moderate palmitic acid (MPA, 50% of DHA+EPA-rich oil was replaced by glyceryl palmitate), and high palmitic acid (HPA, 100% of DHA+EPA-rich oil was replaced by glyceryl palmitate). Results: After 10 weeks of feeding, the HPA significantly reduced the liver/muscle glycogen contents, increased the liver lipid content, decreased the serum leptin/insulin level, and increased the adiponectin level. The levels of DHA and EPA in liver were decreased significantly. Transcriptionally, HPA upregulated hepatic glucokinase (gk, glycolysis) but down-regulated glycogen synthase (gys) and insulin/irs2 (insulin pathway) while inhibiting muscle ampk and leptin receptor (lepr). Conclusions: This study showed that high dietary PA/(DHA + EPA) impacted glycolipid homeostasis through endocrine and transcriptional regulation, leading to increased crude lipid and decreased glycogen levels, which provides a theoretical basis for scientific aquatic feed fatty acid formulation.

Background: Early molecular changes on the facial skin surface during early adulthood remain insufficiently characterized. We integrated biophysical readouts with untargeted skin surface lipid (SSL) profiling to identify region-dependent, age-associated features in women with combination skin. Methods: Eighty healthy Chinese women were stratified into 22-28 years (n = 40) and 29-35 years (n = 40). Sebum was measured on the cheek and forehead; cheek elasticity, hydration (CM), transepidermal water loss (TEWL), pH, and tone indices were assessed under standardized conditions. SSLs from both regions were profiled by UPLC-QTOF-MS. Differential features were prioritized using OPLS-DA (VIP > 1) with univariate screening (p < 0.05; fold change > 2 or <0.5). Results: TEWL, CM, and pH were comparable between age groups, whereas the older group showed lower cheek elasticity and reduced sebum. Lipidomics revealed clearer remodeling on the cheek than the forehead: 30 and 59 differential SSL features were identified in the cheek and forehead, respectively. Cheek changes in the older group were characterized by lower ceramides (including acylceramides), TG/DG and long-chain fatty acids, alongside relatively higher cholesteryl esters. Conclusions: Conventional barrier indices remained largely stable across this age window, while cheek SSL profiles captured earlier molecular shifts, providing candidates for targeted validation and longitudinal follow-up.

Background: Metabolic syndrome (MetS) comprises interrelated metabolic abnormalities that collectively confer increased risk of cardiovascular disease and hepatic morbidity. The MAF-5 score is a non-invasive prognostic marker of liver fibrosis and mortality, while Cystatin C (CysC) is a sensitive indicator of renal function that also reflects inflammation, atherosclerosis, and metabolic dysfunction. Although both MetS and CysC have been widely studied, their potential interplay via MAF-5 remains unclear. We aimed to investigate the relationship between MAF-5 scores and CysC levels in MetS patients for the first time.

Materials and methods: Adults (≥18 years) with MetS were included in this study. MAF-5 scores (based on waist circumference, BMI, diabetes status, AST, and platelet count) and CysC levels were recorded. The MAF-5-CysC relationship was assessed via Pearson correlation. Participants were grouped into MAF-5 quartiles, and continuous variables were compared using ANOVA with Bonferroni-corrected pairwise tests.

Results: We included 347 MetS patients (54.8% female, median age 54 years). The median MAF-5 score was 1.25, and MAF-5 correlated positively with CysC (r = 0.357, p < 0.001). CysC levels differed significantly across MAF-5 quartiles (Q1 = 0.96, Q2 = 0.99, Q3 = 1.06, Q4 = 1.09; p < 0.001), with Q4 showing higher values than Q1 and Q2.

Conclusions: A significant correlation was found between MAF-5 scores and CysC in patients with MetS. CysC levels differed significantly across MAF-5 quartiles, suggesting a potential link between systemic inflammation, liver fibrosis, and CysC. These results highlight shared inflammatory and fibrotic pathways, underlying metabolic dysfunction. Clinically, combined assessment of MAF-5 and CysC may improve risk stratification, identifying patients at higher risk for hepatic fibrosis and adverse outcomes.

Background: Proteasomes are protein complexes that mediate proteolysis to degrade unneeded or damaged proteins, and they play an indispensable role in plant growth and development. However, their regulatory effects on tomato fruit quality and the underlying metabolic mechanisms remain largely elusive. This study aimed to elucidate the metabolic regulatory mechanisms of proteasomes in tomato fruits through untargeted metabolome analysis. Methods: An untargeted metabolomics approach was employed to profile the metabolic changes in tomato fruits. Metabolites were detected and identified under both positive and negative ion modes. Metabolic profiles were compared between wild-type (WT) tomato fruits and SlPBB2 RNA interference (SlPBB2-RNAi) lines. Specifically, the SlPBB2-RNAi line refers to a transgenic tomato line constructed via Agrobacterium-mediated transformation, where the expression of the proteasome component gene SlPBB2 was stably downregulated by RNA interference technology to clarify its regulatory role in fruit metabolism. KEGG enrichment analysis was performed to annotate the functions of differential metabolites. Results: A total of 568 and 333 metabolites were identified in positive and negative ion modes, respectively. Comparative analysis revealed 43 differentially abundant metabolites between WT and SlPBB2-RNAi fruits, including D-glucose, pyruvic acid, leucine, and naringenin. KEGG enrichment analysis further identified key metabolites involved in the carbon fixation pathway of photosynthetic organisms, with L-malic acid being a prominent representative. Reduced accumulation of D-glucose and pyruvic acid in SlPBB2-RNAi fruits suggested the inhibition of the citrate cycle, a core pathway in cellular energy metabolism. This metabolic perturbation was associated with decreased chlorophyll content in SlPBB2-RNAi plants, implying impaired photosynthetic carbon fixation and energy metabolism. Conclusions: This study uncovers the metabolic regulatory role of SlPBB2-mediated proteasome function in tomato fruits, providing novel insights into the link between proteasomal activity and fruit metabolic homeostasis from a metabolomic perspective. These findings offer new theoretical foundations for developing strategies to improve tomato nutritional quality.

Background/objectives: Silicosis remains a major occupational health concern worldwide and is characterized by notable clinical heterogeneity in terms of disease progression and complications. However, the underlying metabolic mechanisms contributing to this heterogeneity remain poorly understood.

Methods: We conducted a case-control study involving 156 silicosis patients and 132 silica-exposed controls. The plasma samples were analyzed via untargeted metabolomics based on liquid chromatography-mass spectrometry (LC-MS/MS). To explore disease subtypes and potential biomarkers, we applied non-negative matrix factorization (NMF) clustering, weighted gene co-expression network analysis (WGCNA), and machine learning approaches.

Results: A total of 860 differentially abundant metabolites, including elevated pathogen-associated compounds, were identified in silicosis patients. Unsupervised NMF clustering revealed two distinct metabolic subtypes with different clinical features. Patients in the NMF2 subgroup had a 5.3-fold greater risk of pulmonary infections (p = 0.026) than those in the NMF1 subgroup. Metabolomic analysis revealed that NMF2 was enriched in arachidonic acid and unsaturated fatty acid metabolism pathways, with prominent LysoPC accumulation, suggesting inflammation-related lipid peroxidation. In contrast, NMF1 was characterized by increased spermidine biosynthesis and urea cycle activity, along with suppressed saturated fatty acid metabolism and reduced LysoPC processing, potentially affecting membrane integrity and promoting fibrosis. A machine learning-derived dual-metabolite panel, tyrosocholic acid and PI (20:4/0:0), achieved AUC values above 0.85 for both silicosis detection and subtype classification.

Conclusions: These findings highlight metabolic heterogeneity in silicosis and suggest clinically relevant subtypes, providing a foundation for improved stratification, early detection, and targeted interventions.

Background/Objectives: Itaconic acid (ITA) is an immunometabolite with anti-inflammatory and metabolic regulatory functions, but its cellular source and role in brown adipose tissue (BAT) remain unclear. This study aims to reveal the expression patterns of the key ITA synthesis gene Irg1 in BAT at different developmental stages and to investigate the effects of cold exposure and exogenous ITA on BAT metabolic function and cardioprotection. Methods: Single-cell RNA sequencing was used to analyze the gene expression profiles of stromal vascular fraction (SVF) cells in BAT from P7 neonatal and adult mice. Bioinformatic methods were applied to identify cell types expressing Irg1. Cold exposure (4 °C) and exogenous ITA treatment were employed to evaluate BAT morphology, and the ITA content in BAT was detected using gas chromatography-triple quadrupole mass spectrometry, UCP1 protein expression, and body temperature changes. A transverse aortic constriction (TAC) surgery model was established to induce cardiac dysfunction, and BAT excision was performed to explore the BAT-dependent effects of ITA on myocardial hypertrophy, fibrosis, and cardiac function. Results: In P7 neonatal mouse BAT, Irg1 was predominantly expressed in a subset of interferon-responsive activated macrophages (macrophage27), while in adult mice, it was mainly expressed in neutrophils and a functionally similar macrophage subset (macrophage25). Cold exposure significantly suppressed Irg1 expression in neutrophils but did not affect its expression in macrophages, also resulting in a significant decrease in ITA content in BAT. Exogenous ITA significantly enhanced BAT thermogenesis under cold conditions, which manifested as reduced lipid droplets, upregulated UCP1 expression, and increased body temperature. In the TAC model, ITA treatment markedly improved cardiac function, attenuated myocardial hypertrophy and fibrosis, and these protective effects were significantly diminished after BAT excision. Conclusions: ITA promotes cold adaptation and ameliorates cardiac injury by enhancing BAT metabolic function, and its effects depend on the presence of BAT. This study provides new insights for the treatment of metabolic cardiovascular diseases.