PubMed

Front Vet Sci. 2025 Apr 2;12:1554771. doi: 10.3389/fvets.2025.1554771. eCollection 2025.ABSTRACTPreservation of sperm significantly contributes to the advancement of assisted reproductive technologies, genetic conservation and improvement efforts, and precision breeding of livestock. This review distills knowledge from the existing information and emerging patterns in the field of buck sperm cryopreservation. The primary focus is on the challenges and opportunities associated with improving extender formulations and freezing techniques in order to enhance the vitality of sperm after thawing and to increase the potential for conception. This review assesses the efficacy and limitations of conventional extenders derived from egg yolk or soybean lecithin, and the adverse impacts of seminal plasma enzymes on sperm quality during the processes of chilling and cryopreservation. Significant progress has been made in the fields of molecular biology namely lipidomics, proteomics, metabolomics, DNA methylation providing valuable knowledge regarding the unique reactions of sperm to cryopreservation. The utilization of the "omics" technologies has shown intricate molecular transformation that occur in sperm during freezing and thawing. Moreover, detection of molecular biomarkers that indicate the quality of sperm and their ability to withstand freezing provides opportunities to choose the best sperm samples for cryopreservation. This, in turn, enhances the results of artificial insemination and genetic conservation endeavors. This review emphasizes the necessity for adopting a comprehensive approach that combines molecular and cellular knowledge with practical methods in the field of sperm cryopreservation to ensure production of goats as major food animals in the global scale.PMID:40241808 | PMC:PMC12001040 | DOI:10.3389/fvets.2025.1554771

Food Chem X. 2025 Mar 28;27:102424. doi: 10.1016/j.fochx.2025.102424. eCollection 2025 Apr.ABSTRACTRipened Pu-erh tea (RPT) is renowned for its distinctive flavor and health benefits. However, its complex fermentation process poses challenges in ensuring consistency in production. This study investigated RPT flavor formation through sensory evaluation, multi-omics analysis, and multivariate statistical approaches. By day 24, the tea exhibited a reddish-brown infusion and a mellow, thick taste (MT_RPT), achieving the highest sensory score (94.0, P < 0.05). Sixteen flavor-related chemical components exhibited significant changes (P < 0.05). The contents of free amino acids, L-theanine, tea polyphenols, flavonoids, catechins, and thearubigins decreased. In contrast, the contents of total soluble sugars, caffeine, theobromine, epicatechin, and theabrownins (TBs) increased, reaching 74.1 mg/g, 65.38 mg/g, 3.13 mg/g, 3.33 mg/g, and 134.84 mg/g, respectively. Additionally, 33 nonvolatile metabolites (e.g., pelargonidin 3-O-glucoside, dihydroisorhamnetin, and puerarin) were significantly correlated with MT_RPT flavor (VIP > 1, |r| ≥ 0.8, P < 0.05) and influenced by key functional microbes, including Pantoea, Aspergillus, Brachybacterium, and Staphylococcus. By day 30, the infusion darkened, and sensory scores declined (81.4, P < 0.05), attributed to the dominance of Brevibacterium. This microbial shift reduced water-soluble pectin, free amino acids, and 11 metabolites while increasing TBs and theophylline (219.33 mg/g and 0.09 mg/g, respectively). Therefore, TBs were identified as a crucial indicator of optimal fermentation. Moreover, redundancy analysis indicated that the tea pile's central temperature, moisture content, and pH were essential fermentation parameters (P < 0.05). These findings deepen our understanding of MT_RPT flavor development mechanisms and provide valuable insights into precise fermentation control.PMID:40241696 | PMC:PMC12002954 | DOI:10.1016/j.fochx.2025.102424

Anim Biosci. 2025 Apr 11. doi: 10.5713/ab.24.0861. Online ahead of print.ABSTRACTOBJECTIVE: The development of pre-hierarchical follicles (PHFs), especially small yellow follicles (SYFs), directly affects the recruitment of dominant follicles and thus affects the egg-laying performance of chickens. However, the development of PHFs, especially SYFs, and their regulatory mechanism remain unclear.METHODS: We performed transcriptomic and metabolomic analyses of large white follicles (LWFs) and SYFs in chickens.RESULTS: Transcriptome sequencing revealed 258 differentially expressed genes (DEGs) between SYFs and LWFs, of which 172 were upregulated and 86 were downregulated. The DEGs were mapped to 17 KEGG pathways, including Glutathione metabolism, Ferroptosis, Calcium signaling pathway, and Neuroactive ligand-receptor interactions, etc. The metabolome analysis revealed 129 significant differential metabolites (DMs), including 36 upregulated DMs and 93 downregulated DMs. The DMs were mapped to nine KEGG pathways, including Glutathione metabolism, alpha-Linolenic acid metabolism, and Linoleic acid metabolism, etc. The combined transcriptional and metabolic analysis revealed significantly enriched pathways. Five KEGG pathways associated with follicular development were identified, including Glutathione metabolism, Ferroptosis, alpha-Linolenic acid metabolism, Linoleic acid metabolism, and Pyrimidine metabolism.CONCLUSION: Glutathione metabolism may directly inhibit Ferroptosis, which can induce apoptosis of granulosa cells (GCs), thereby regulating SYFs development in chickens. These findings provided a reference for improving the egg-laying performance of Tengchong snow chickens.PMID:40241591 | DOI:10.5713/ab.24.0861

ACS Biomater Sci Eng. 2025 Apr 16. doi: 10.1021/acsbiomaterials.4c02148. Online ahead of print.ABSTRACTThe successful replication of the intricate architecture of human tissues remains a major challenge in the biomedical area. Three-dimensional (3D) bioprinting has emerged as a promising approach for the biofabrication of living tissue analogues, taking advantage of the use of adequate bioinks and printing methodologies. Here, a hydrogel bioink based on gelatin (Gel) and nanofibrillated cellulose (NFC), cross-linked with genipin, was developed for the 3D extrusion-based bioprinting of hepatocarcinoma cells (HepG2). This formulation combines the biological characteristics of Gel with the exceptional mechanical and rheological attributes of NFC. Gel/NFC ink formulations with different Gel/NFC mass compositions, viz., 90:10, 80:20, 70:30, and 60:40, were prepared and characterized. The corresponding cross-linked hydrogels were obtained using 1.5% (w/w) genipin as the cross-linking agent. The rheological and mechanical performances of the inks were enhanced by the addition of NFC, as evidenced by the rise in the yield stress from 70.9 ± 28.6 to 627.9 ± 74.8 Pa, compressive stress at 80% strain from 0.5 ± 0.1 to 1.5 ± 0.2 MPa, and Young's modulus from 4.7 ± 0.9 to 12.1 ± 1.1 MPa, for 90:10 and 60:40 inks, respectively. Moreover, higher NFC contents translated into 3D structures with better shape fidelity and the possibility of printing more intricate structures. These hydrogels were noncytotoxic toward HepG2 cells for up to 48 h, with cell viabilities consistently above 80%. The ink 70:30 was loaded with HepG2 cells (2 × 106 cells mL-1) and bioprinted. Cell viability remained elevated (90 ± 4%) until day 14 postbioprinting, with cells maintaining their metabolic activity shown by 1H NMR metabolomics, proving the enormous potential of Gel/NFC-based bioinks for bioprinting HepG2 cells without jeopardizing their viability and metabolism.PMID:40241282 | DOI:10.1021/acsbiomaterials.4c02148

Cell Biosci. 2025 Apr 16;15(1):47. doi: 10.1186/s13578-025-01385-y.ABSTRACTIn recent years, advancements in metagenomics, metabolomics, and single-cell sequencing have enhanced our understanding of the intricate relationships between gut microbiota and their hosts. Gut microbiota colonize humans from birth, with their initial composition significantly influenced by the mode of delivery and feeding method. During the transition from infancy to early childhood, exposure to a diverse diet and the maturation of the immune system lead to the gradual stabilization of gut microbiota's composition and distribution. Numerous studies have demonstrated that gut microbiota can influence a wide range of physiological functions and pathological processes by interacting with various tissues and organs through the gut-organ axis. Different intestinal segments exhibit unique physical and chemical conditions, which leads to the formation of vertical gradients along the intestinal tract: aerobes and facultative aerobes mainly live in the small intestine and anaerobic bacteria mainly live in the large intestine, and horizontal gradients: mucosa-associated microbiota and lumen-associated microbiota. In this review, we systematically summarize the distribution characteristics of gut microbiota across six intestinal segments: duodenum, jejunum, ileum, cecum, colon, and rectum. We also draw a conclusion that gut microbiota distributed in different intestinal segments affect the progression of different diseases. We hope to elucidate the role of microbiota at specific anatomic sites within the gut in precisely regulating the processes of particular diseases, thereby providing a solid foundation for developing novel diagnostic and therapeutic strategies for related diseases.PMID:40241220 | DOI:10.1186/s13578-025-01385-y

BMC Vet Res. 2025 Apr 17;21(1):279. doi: 10.1186/s12917-025-04742-8.ABSTRACTBACKGROUND: Long breeding cycle, long calving intervals and typical single calves limit the potential for improving their economic benefits. Ensuring the reproductive performance and efficiency of cows are crucial to increasing their economic value. Factors affecting the reproductive performance of cows include breed, pre-pregnancy maternal preparation, nutrition during pregnancy, and perinatal management. The gene editing of MSTN gene can improve the development of skeletal muscles and provide a new way for the promotion of existing beef cattle breeds. However, little has been reported about the reproductive performance and pregnancy state of MSTN gene-edited animals. In order to evaluate the reproductive safety and physiological changes during pregnancy of MSTN gene-edited cows, this study compared the sizes of reproductive organs, reproductive hormones, blood metabolic indicators, and metabolomic profiles at different stages of pregnancy, including period to be insemination, first trimester, second trimester, and late third trimester in MSTN gene-edited Luxi cattle (MT) and non-edited Luxi cattle (WT).RESULTS: The results showed no significant differences in ovary and uterus sizes between MT and WT cows. However, MT cattle exhibited a larger pelvic area and higher calf birth weight. Compared to WT cattle, MT cattle showed enhanced glucose metabolism, reduced lipid synthesis, increased protein synthesis and absorption capacity, and decreased tryptophan synthesis at different stages of pregnancy. The hormone levels showed decreased E2 and increased P4 in MT cattle.CONCLUSION: The study demonstrates that MSTN gene editing has no significant impact on the reproductive safety of dairy cows and provides a deeper understanding of the feasibility of MSTN mutations for beef cattle breeding.PMID:40241099 | DOI:10.1186/s12917-025-04742-8

Cardiovasc Diabetol. 2025 Apr 16;24(1):166. doi: 10.1186/s12933-025-02718-4.ABSTRACTBACKGROUND: Metabolites are pivotal in the biological process underlying type 2 diabetes (T2D) and its cardiovascular complications. Nevertheless, their contributions to these diseases have not been comprehensively evaluated, particularly in East Asian ancestry. This study aims to elucidate the metabolic underpinnings of T2D and its cardiovascular complications and leverage multi-omics integration to uncover the molecular pathways involved.METHOD: This study included 1180 Chinese participants from the Zhejiang Metabolic Syndrome Cohort (ZMSC). A total of 1912 metabolites were profiled using high-coverage widely targeted and non-targeted metabolic techniques. Multivariable logistic regression models and orthogonal partial least squares discriminant analysis were used to identify T2D-related metabolites. A metabolome-wide genome-wide association study (GWAS) in ZMSC, followed by two-sample Mendelian randomization (MR) analyses, was conducted to explore potential causal metabolite-T2D associations. To enhance cross-ancestry generalizability, MR analyses were conducted in European ancestry to explore the potential causal effects of serum metabolites on T2D and its cardiovascular complications. Furthermore, multi-omics evidence was integrated to explore the underlying molecular mechanisms.RESULTS: We identified six metabolites associated with T2D in Chinese, supported by metabolome analysis and genetic-informed causal inference. These included two potential protective factors (PC [O-16:0/0:0] and its derivative LPC [O-16:0]) and four potential risk factors ([R]-2-hydroxybutyric acid, 2-methyllactic acid, eplerenone, and rauwolscine). Cross-ancestry metabolome-wide analysis further revealed four shared potential causal metabolites, highlighting the potential protective role of creatine for T2D. Through multi-omics integration, we revealed a potential regulatory path initialized by a genetic variant near CPS1 (coding for a urea cycle-related mitochondrial enzyme) influencing serum creatine levels and subsequently modulating the risk of T2D. MR analyses further demonstrated that nine urea cycle-related metabolites significantly influence cardiovascular complications of T2D.CONCLUSION: Our study provides novel insights into the metabolic underpinnings of T2D and its cardiovascular complications, emphasizing the role of urea cycle-related metabolites in disease risk and progression. These findings advance our understanding of circulating metabolites in the etiology of T2D, offering potential biomarkers and therapeutic targets for future research.RESEARCH INSIGHTS: WHAT IS CURRENTLY KNOWN ABOUT THIS TOPIC?: Metabolites are crucial for understanding diabetes biology.Multi-omics integration aids in revealing complex mechanisms. WHAT IS THE KEY RESEARCH QUESTION?: How do serum metabolites affect diabetes and its cardiovascular outcomes? WHAT IS NEW?: Novel diabetes-related metabolites identified in Chinese populations.Consistent metabolites associated with diabetes and glycemic traits in East Asians and Europeans.Emphasizing the role of urea cycle pathway in cardiometabolic disease. HOW MIGHT THIS STUDY INFLUENCE CLINICAL PRACTICE?: Findings could guide diabetes prevention and personalized management strategies.PMID:40241080 | DOI:10.1186/s12933-025-02718-4

BMC Musculoskelet Disord. 2025 Apr 16;26(1):374. doi: 10.1186/s12891-025-08622-y.ABSTRACTBACKGROUND: Osteoporotic bone defects significantly affect patient health and quality of life. The gut-bone axis plays a crucial role in osteoporosis, and disruptions in gut microbiota are linked to systemic inflammation and compromised bone metabolism. Irisin, a myokine, has shown potential in protecting against osteoporosis, but its mechanisms of action on the gut-bone axis remain unclear. This study aimed to investigate the role of irisin in mitigating osteoporotic bone defects by examining its effects on gut microbiota, related metabolites, and intestinal barrier integrity.METHODS: An osteoporosis model was created using ovariectomized (OVX) mice. The mice were divided into Sham, OVX, and r-irisin groups. Mice in the r-irisin group received intraperitoneal injections of 100 μg/kg irisin twice weekly for five weeks. Bone parameters were analyzed by micro-CT and histological staining. Gut microbiota composition was examined via 16S rDNA sequencing. Intestinal cytokines and barrier proteins were measured using immunohistochemistry and ELISA. Fecal metabolomic profiling was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and correlations between gut microbiota, metabolites, and bone metabolism markers were evaluated.RESULTS: Irisin treatment improved bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and trabecular number (Tb.N), and reduced trabecular separation (Tb.Sp) in OVX mice. It enhanced new bone formation and collagen deposition. Irisin restored intestinal barrier integrity by increasing tight junction protein expression and reducing inflammatory cytokines in intestinal tissues. It also modulated gut microbiota diversity, reducing Firmicutes and increasing Verrucomicrobiota abundance. Key fecal metabolites, including atractylon (r = - 0.60, P < 0.01) and enterodiol (r = + 0.83, P < 0.01), showed strong correlations with BMD.CONCLUSION: Irisin mitigates osteoporotic bone defects by enhancing bone formation, restoring intestinal barrier integrity, modulating gut microbiota composition, and influencing fecal metabolites. These preclinical findings highlight irisin's potential to mitigate osteoporosis via the gut-bone axis.PMID:40241040 | DOI:10.1186/s12891-025-08622-y

BMC Plant Biol. 2025 Apr 17;25(1):491. doi: 10.1186/s12870-025-06453-6.ABSTRACTBACKGROUND: Persistent lead contamination and the absence of natural remediation elements exacerbate the long-term toxicity of plants. Nevertheless, it has been consistently shown that selenium has a protective effect against heavy metal toxicity in plants. Consequently, it is imperative to identify the metabolic pathways that selenium employs to enhance the resistance of plants to lead stress. This study aimed to investigate the metabolomic alterations induced by selenium priming of Vicia faba seeds to enhance their tolerance to lead stress.RESULTS: Selenium seed priming significantly improved the growth parameter and mitigated the adverse growth consequences observed under lead stress. Nuclear magnetic resonance-based metabolomic analysis identified 58 metabolites in the polar extracts of the shoots, with the metabolites composed of amino acids (40%), carboxylic acids (12%), fatty acids (11%), carbohydrates (5%), alkaloids (5%), and phenols (4%). The addition of Pb facilitated the biosynthesis of unique metabolites, including 2-methylglutarate, 3-methyladipate, and epinephrine, which were absent in control and selenium-treated samples. Conversely, 4-aminobutyrate and 2-methylglutarate were entirely absent in Pb samples. Selenium-treated plants accumulated trigonelline and AMP at levels 1.4 and 6.0 times, respectively, more than the control samples. Selenium-primed plants exposed to lead stress exhibited higher levels of asparagine, tryptophan, and xanthine compared to other treatments. As determined by both enrichment analysis and pathway analysis, the most significantly altered pathways were alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis; and valine, leucine, and isoleucine biosynthesis pathways.CONCLUSION: The results demonstrate the crucial role of selenium priming in enhancing the growth and lead stress resistance of Vicia faba plants by significantly altering the concentrations of key metabolites and metabolic pathways, particularly those involved in amino acid metabolism, offering a promising strategy for improving plant resilience to heavy metal contamination.PMID:40240979 | DOI:10.1186/s12870-025-06453-6

Genes Nutr. 2025 Apr 16;20(1):9. doi: 10.1186/s12263-025-00768-7.ABSTRACTBACKGROUND: The mammalian liver executes its vital functions through intricate hepatic biochemistry. However, the complexity of the liver metabolome and its dynamic alterations during metabolic dysfunction-associated steatotic liver disease (MASLD) remain poorly understood.METHODS: We established progressive MASLD mouse models through high-fat diet (HFD) and high-fat/high-cholesterol (HFHC) dietary-feeding across multiple time points. Utilizing liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and lipidomics, we systematically mapped the metabolome atlas of the mouse liver across five anatomical segments during the progression of MASLD.RESULTS: By integration of data from two assays, we structurally annotated 426 lipids and 118 polar metabolites. The temporal progression of HFD feeding (0, 8, and 16 weeks) resulted in gradual metabolic deterioration across various liver segments. In HFHC-fed mice, metabolic alterations surged sharply from 0 to 8 weeks, followed by moderate progression until 16 weeks in different liver segments. Elevated levels of glycerolipids and cholesteryl esters, along with fluctuating acylcarnitine and fatty acid levels across various liver segments, suggested impaired energy metabolism and disrupted fatty acid oxidation. As MASLD progresses, a shift in sphingolipid metabolism, linked to inflammation, was observed, accompanied by significant alterations in phospholipid turnover patterns. Additionally, amino acid profiles in the livers of HFD-fed and HFHC-fed mice were altered, potentially influencing the regulation of energy metabolism, inflammation, and oxidative stress. These metabolic changes in lipids and amino acids displayed segment-specific patterns, indicating varying sensitivities to inflammation and mitochondrial β-oxidation across different liver lobes. Notably, the left lateral lobe showed heightened sensitivity to metabolic disturbances during MASLD progression.CONCLUSION: Our findings provided in-depth understanding in hepatic metabolites of MASLD, offering a comprehensive resource for further investigation.PMID:40240942 | DOI:10.1186/s12263-025-00768-7

BMC Bioinformatics. 2025 Apr 16;26(1):105. doi: 10.1186/s12859-025-06118-z.ABSTRACTBACKGROUND: Metabolomics describes the metabolic profile of an organism at a given time by the concentrations of its constituent metabolites. When studied over time, metabolite concentrations can help understand the dynamical evolution of a biological process. However, metabolites are involved into sequences of chemical reactions, called metabolic pathways, related to a given biological function. Accounting for these pathways into statistical methods for metabolomic data is thus a relevant way to directly express results in terms of biological functions and to increase their interpretability.METHODS: We propose a new method, phoenics, to perform differential analysis for longitudinal metabolomic data at the pathway level. In short, phoenics proceeds in two steps: First, the matrix of metabolite quantifications is transformed by a dimension reduction approach accounting for pathway information. Then, a mixed linear model is fitted on the transformed data.RESULTS: This method was applied to semi-synthetic NMR data and two real NMR datasets assessing the effects of antibiotics and irritable bowel syndrome on feces. Results showed that phoenics properly controls the Type I error rate and has a better ability to detect differential metabolic pathways and to extract new impacted biological functions than alternative methods. The method is implemented in the R package phoenics available on CRAN.PMID:40240918 | DOI:10.1186/s12859-025-06118-z

Nature. 2025 Apr;640(8059):623-633. doi: 10.1038/s41586-025-08710-y. Epub 2025 Apr 16.ABSTRACTThe rapid advent of high-throughput omics technologies has created an exponential growth in biological data, often outpacing our ability to derive molecular insights. Large-language models have shown a way out of this data deluge in natural language processing by integrating massive datasets into a joint model with manifold downstream use cases. Here we envision developing multimodal foundation models, pretrained on diverse omics datasets, including genomics, transcriptomics, epigenomics, proteomics, metabolomics and spatial profiling. These models are expected to exhibit unprecedented potential for characterizing the molecular states of cells across a broad continuum, thereby facilitating the creation of holistic maps of cells, genes and tissues. Context-specific transfer learning of the foundation models can empower diverse applications from novel cell-type recognition, biomarker discovery and gene regulation inference, to in silico perturbations. This new paradigm could launch an era of artificial intelligence-empowered analyses, one that promises to unravel the intricate complexities of molecular cell biology, to support experimental design and, more broadly, to profoundly extend our understanding of life sciences.PMID:40240854 | DOI:10.1038/s41586-025-08710-y

Rice (N Y). 2025 Apr 17;18(1):28. doi: 10.1186/s12284-025-00779-3.ABSTRACTFructose-1,6-bisphosphate aldolase (FBA) stands as a pivotal enzyme involved within the Calvin cycle and glycolytic pathways in bacteria and higher plants, but the specific function of OsFBA in rice is still unclear. Here, we identified a chloroplast and mitochondria dual-localized FBA protein, OsFBA1, in rice. Experimental evidence showed that the functionally deficient osfba1 mutants featured a notable decline in chlorophyll content, photosynthetic rate, and severe growth impediment by the three-leaf stage, leading to eventual plant demise. Up-regulation of photosynthetic-pathway genes in the osfba1 mutants indicated the essential role of OsFBA1 in chloroplast development and suggested a compensatory mechanism of other genes in the process. Furthermore, the absence of OsFBA1 impaired the carbon assimilation in young rice seedlings, and supplying exogenous glucose could partially sustain the survival of osfba1 mutant for a few more days. Pathway-specific metabolomics analysis revealed a systemic change of metabolites in the glycolytic pathway, and consequential carbohydrates accumulation due to OsFBA1 disruption. Transcriptomics profiling corroborated the expression changes of photosynthesis, and carbon metabolism pathway genes. We further demonstrated that OsFBA1 serves as the primary FBA enzyme governing energy generation, photosynthesis and carbon metabolism. These results prove that OsFBA1 is an essential core gene in supporting the life cycle of rice, its expression has to be tightly regulated.PMID:40240707 | DOI:10.1186/s12284-025-00779-3

Sci Rep. 2025 Apr 16;15(1):13172. doi: 10.1038/s41598-025-94839-9.ABSTRACTCopy number variants (CNVs) are an important class of genomic variation known to be important for human physiology and diseases. Here we present genome-wide metabolomic signatures for CNVs in two Finnish cohorts-The Northern Finland Birth Cohort 1966 (NFBC 1966) and NFBC 1986. We have analysed and reported CNVs in over 9,300 individuals and characterised their dosage effect (CNV-metabolomic QTL) on 228 plasma lipoproteins and metabolites. We have reported reference (normal physiology) metabolomic signatures for up to ~ 2.6 million COVID-19 GWAS results from the National Institutes of Health (NIH) GRASP database, including for outcomes related to COVID-19 death, severity, and hospitalisation. Furthermore, by analysing two exemplar genes for COVID-19 severity namely LZTFL1 and OAS1, we have reported here two additional candidate genes for COVID-19 severity biology, (1) NFIX, a gene related to viral (adenovirus) replication and hematopoietic stem cells and (2) ACSL1, a known candidate gene for sepsis and bacterial inflammation. Based on our results and current literature we hypothesise that (1) charge imbalance across the cellular membrane between cations (Fe2+, Mg2+ etc.) and anions (e.g. ROS, hydroxide ion from cellular Fenton reactions, superoxide etc.), (2) iron trafficking within and between different cell types e.g., macrophages and (3) systemic oxidative stress response (e.g. lipid peroxidation mediated inflammation), together could be of relevance in severe COVID-19 cases. To conclude, our unique atlas of univariate and multivariate metabolomic signatures for CNVs (~ 7.2 million signatures) with deep annotations of various multi-omics data sets provide an important reference knowledge base for human metabolism and diseases.PMID:40240424 | DOI:10.1038/s41598-025-94839-9

J Appl Microbiol. 2025 Apr 16:lxaf090. doi: 10.1093/jambio/lxaf090. Online ahead of print.ABSTRACTAIMS: Glutamine (Gln), present within potato root exudates, stimulates germination of resting spores and chemotactic attraction of zoospores of the plasmodiophorid pathogen, Spongospora subterranea. We hypothesised that rhizosphere bacteria could alter the rhizosphere metabolome by diminishing occurrence of Gln with the eventual aim of reducing pathogen activation, attraction and infection. This study aimed to isolate and characterize bacteria capable of substantially degrading Gln within the potato rhizosphere.METHODS AND RESULTS: Eleven bacteria were isolated from potato rhizosphere samples using Gln as a sole carbon source. Of these Pantoea sp. (RR15) and Rhodococcus sp. (RR09) showed superior Gln degradation potential. Both isolates established within the potato rhizosphere and reduced Gln concentrations in situ. Further analysis of the rhizosphere metabolome showed significant treatment effects for a range of other organic compounds including some known to stimulate or inhibit S. subterranea germination and/or taxis.CONCLUSIONS: We demonstrate that establishing selected bacteria in the rhizosphere of potatoes can successfully modify the root rhizosphere metabolome.PMID:40240295 | DOI:10.1093/jambio/lxaf090

Circ J. 2025 Apr 15. doi: 10.1253/circj.CJ-24-0953. Online ahead of print.ABSTRACTBACKGROUND: In large clinical trials, sodium-glucose cotransporter 2 (SGLT2) inhibitors have improved prognosis in heart failure with preserved ejection fraction (HFpEF). Although several beneficial pharmacological effects of SGLT2 inhibitors for HFpEF have been suggested, their presumed metabolic pathways remain insufficiently proven.METHODS AND RESULTS: We compared the metabolomic profile, determined using liquid chromatography-mass spectrometry, of 16 patients with HFpEF before and after empagliflozin therapy. Only citrulline levels (expressed as a ratio to methionine sulfone levels) were significantly elevated after therapy (3.57±1.88 vs. 6.47±3.78; P=0.006).CONCLUSIONS: Empagliflozin significantly increased citrulline levels in HFpEF patients. Although further studies are needed, it would be intriguing if this metabolite change were related to the cardiovascular protective effects of empagliflozin.PMID:40240153 | DOI:10.1253/circj.CJ-24-0953

Bioresour Technol. 2025 Apr 14:132544. doi: 10.1016/j.biortech.2025.132544. Online ahead of print.ABSTRACTFermentation technology presents promising opportunities for food waste valorization. Pomegranate peel (PP), a food by-product, has potential applications in fermented feed. This study examined the effects of a 6 % dry PP additive on the ensiling characteristics, antioxidant activity, metabolites, bacterial community, and in vitro ruminal fermentation, methane (CH4) emission of corn silage ensiled for 7 days and 60 days using microbiome and metabolome analyses. PP-treated silage inhibited (P < 0.05) protein degradation by reducing ammonia nitrogen and non-protein nitrogen concentrations during ensiling. The PP additive increased (P < 0.05) water-soluble carbohydrate content and reduced ethanol production in corn silage. Lactiplantibacillus dominated PP-treated silage at the initial ensiling stage, while Levilactobacillus prevailed at the final stage. Notably, the PP additive exhibited strong antioxidant activity by modulating antioxidant enzymes and flavonoid biosynthesis mediated by key metabolites (epigallocatechin and catechin). Correlation analysis identified Lactiplantibacillus, Citrobacter, Phytobacter and Burkholderia as key microbes in the production of antioxidant metabolites and enzymes in PP-treated silage. Additionally, PP supplementation reduced (P < 0.05) in vitro ruminal CH4 and nitrogen losses, while decreasing dry matter (DM) digestibility in corn silage. In summary, PP-treated corn silage enhanced antioxidant properties and reduced the nitrogen losses and in vitro ruminal CH4 emissions, but lowered DM digestibility. Thus, PP can be recommended as a silage additive, though the dry PP level should be lower than that used in this study.PMID:40239901 | DOI:10.1016/j.biortech.2025.132544

Vascul Pharmacol. 2025 Apr 14:107496. doi: 10.1016/j.vph.2025.107496. Online ahead of print.ABSTRACTAtherosclerosis remains a leading cause of morbidity and mortality worldwide, driven by complex molecular mechanisms involving gene regulation and post-transcriptional processes. Emerging evidence highlights the critical role of epitranscriptomics, the study of chemical modifications occurring on RNA molecules, in atherosclerosis development. Epitranscriptomics provides a new layer of regulation in vascular health, influencing cellular functions in endothelial cells, smooth muscle cells, and macrophages, thereby shedding light on the pathogenesis of atherosclerosis and presenting new opportunities for novel therapeutic targets. This review provides a comprehensive overview of the epitranscriptomic landscape, focusing on key RNA modifications such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), pseudouridine (Ψ), RNA editing mechanisms including A-to-I and C-to-U editing and RNA isoforms. The functional implications of these modifications in RNA stability, alternative splicing, and microRNA biology are discussed, with a focus on their roles in inflammatory signaling, lipid metabolism, and vascular cell adaptation within atherosclerotic plaques. We also highlight how these modifications influence the generation of RNA isoforms, potentially altering cellular phenotypes and contributing to disease progression. Despite the promise of epitranscriptomics, significant challenges remain, including the technical limitations in detecting RNA modifications in complex tissues and the need for deeper mechanistic insights into their causal roles in atherosclerotic pathogenesis. Integrating epitranscriptomics with other omics approaches, such as genomics, proteomics, and metabolomics, holds the potential to provide a more holistic understanding of the disease.PMID:40239855 | DOI:10.1016/j.vph.2025.107496

Adv Nutr. 2025 Apr 14:100420. doi: 10.1016/j.advnut.2025.100420. Online ahead of print.ABSTRACTMetabolomics is a post-genomic, systems-based discipline offering valuable applications in nutrition research, including the use of objective biomarkers to characterise dietary intake and metabolic responses more accurately. A scoping review identified the need for reporting guidance on dietary information in the form of a checklist to ensure reproducibility of human feeding studies that are measuring the diet-related metabolome. Here, we aimed to gain consensus on a core outcome set (COS) pertaining to diet-related item details (DID) and recommendations for reporting DIDs to inform development of a reporting checklist. The goal of this checklist is to guide researchers on the minimum level of content and detail required for reporting dietary information in human feeding studies measuring the metabolome. A two-stage online Delphi process encompassing five survey rounds with international experts in clinical trial design, feeding study intervention implementation, metabolomics, and/or human biospecimen analyses was conducted. A COS encompassing twenty-nine core DIDs and accompanying recommendations was developed across 5 domains: Dietary Intervention - Modelling (8 DIDs), Dietary Intervention - Implementation (3 DIDs), Dietary Assessment (9 DIDs), Adherence and Compliance Monitoring (4 DIDs), and Bias (5 DIDs). The reporting guideline (DID-METAB Checklist) was generated and accepted by the international expert working group in the final survey round. All experts agreed that relevant journals should include the checklist as a suggested reporting tool for relevant studies and/or used alongside existing reporting tools. This report provides examples, explanations and elaboration for each recommendation including examples from published literature and references. The DID-METAB Checklist will be a key tool to advance the standardised reporting for feeding studies assessing the metabolome. Implementation of this tool will enable the ability to better interpret data and ensure global utility of results for furthering the advancement of metabolomics in nutrition research and future precision and personalised nutrition strategies.PMID:40239809 | DOI:10.1016/j.advnut.2025.100420

Cell. 2025 Apr 14:S0092-8674(25)00256-9. doi: 10.1016/j.cell.2025.02.029. Online ahead of print.ABSTRACTMicrobiota-derived bile acids (BAs) are associated with host biology/disease, yet their causal effects remain largely undefined. Herein, we speculate that characterizing previously undefined microbiota-derived BAs would uncover previously unknown BA-sensing receptors and their biological functions. We integrated BA metabolomics and microbial genetics to functionally profile >200 putative microbiota BA metabolic genes. We identified 56 less-characterized BAs, many of which are detected in humans/mammals. Notably, a subset of these BAs are potent antagonists of the human androgen receptor (hAR). They inhibit AR-related gene expression and are human-relevant. As a proof-of-principle, we demonstrate that one of these BAs suppresses tumor progression and potentiates the efficacy of anti-PD-1 treatment in an AR-dependent manner. Our findings show that an approach combining bioinformatics, BA metabolomics, and microbial genetics can expand our knowledge of the microbiota metabolic potential and reveal an unexpected microbiota BA-AR interaction and its role in regulating host biology.PMID:40239649 | DOI:10.1016/j.cell.2025.02.029