PubMed

Am J Transplant. 2025 Mar 20:S1600-6135(25)00147-9. doi: 10.1016/j.ajt.2025.03.018. Online ahead of print.ABSTRACTOptimized static cold storage has the potential to improve preservation of organs most vulnerable to ischemia reperfusion injury. Data from lung transplantation suggest that storage at 10°C improves mitochondrial preservation and subsequent allograft function compared to conventional storage on ice. Using a porcine model of donation after circulatory death (DCD), we compared static storage of livers at 10°C to ice. Livers (N=5 per group) underwent ten hours of storage followed by four hours of normothermic machine perfusion (NMP) for real-time allograft assessment. Allografts were compared using established NMP viability criteria, tissue immunostaining, and tissue metabolomics. 10°C stored livers demonstrated lower portal venous vascular resistance and greater hepatic artery vasoresponsiveness. Lactate clearance during NMP was similar between groups. 10°C stored livers showed favorable biochemical parameters of biliary viability, including greater bile volume, pH, and bicarbonate. Metabolomics analysis revealed increased aerobic respiration, improved electron transport chain function, and less DNA damage after reperfusion of livers stored at 10°C. Static storage of DCD livers with extended cold ischemic time at 10°C demonstrates superior allograft function with evidence of improved biliary viability and mitochondrial function compared to ice. These data suggest that storage at 10°C should be considered for translation to clinical practice.PMID:40120647 | DOI:10.1016/j.ajt.2025.03.018

Cell Stem Cell. 2025 Mar 20:S1934-5909(25)00088-8. doi: 10.1016/j.stem.2025.02.017. Online ahead of print.ABSTRACTNon-energetic roles for glucose are largely unclear, as is the interplay between transcription factors (TFs) and ubiquitous biomolecules. Metabolomic analyses uncovered elevation of intracellular glucose during differentiation of diverse cell types. Human and mouse tissue engineered with glucose sensors detected a glucose gradient that peaked in the outermost differentiated layers of the epidermis. Free glucose accumulation was essential for epidermal differentiation and required the SGLT1 glucose transporter. Glucose affinity chromatography uncovered glucose binding to diverse regulatory proteins, including the IRF6 TF. Direct glucose binding enabled IRF6 dimerization, DNA binding, genomic localization, and induction of IRF6 target genes, including essential pro-differentiation TFs GRHL1, GRHL3, HOPX, and PRDM1. These data identify a role for glucose as a gradient morphogen that modulates protein multimerization in cellular differentiation.PMID:40120584 | DOI:10.1016/j.stem.2025.02.017

Chemosphere. 2025 Mar 21;377:144263. doi: 10.1016/j.chemosphere.2025.144263. Online ahead of print.ABSTRACTErythromycin (ERY) is a commonly used antibiotic found in wastewater effluents and the environment globally. Due to the bioactivity by which they kill and prevent bacterial growth, ERY and other antibiotics may have significant unwanted impacts on the gut microbiome of fishes. The overall objective of this project was to assess effects on the gut microbiome in response to exposure to ERY alone or in a mixture with other common antibiotics, which was accomplished in two experiments. The objectives of experiment 1 as a pilot study were to understand uptake and depuration of ERY in juvenile rainbow trout (RBT) over a 7-d exposure to three concentrations of ERY followed by a 7-d depuration period. Furthermore, throughout the study changes in gut microbiome were assessed. In experiment 2, an identical experimental design was used to assess the effects of a mixture of antibiotics containing, in addition to ERY, 100 μg/g each of ampicillin, metronidazole, and ciprofloxacin. In that study, three matrices were analyzed, with gut collected for 16S rRNA metabarcoding, blood plasma for non-targeted metabolomics, and brain tissue for mRNA-seq analysis. ERY was relatively quickly depurated from fish and gut microbiome dysbiosis was observed at 7 d after exposure, with a slight recovery after the 7-d depuration period. A greater number of plasma metabolites was dysregulated at 14 d compared to 7 d revealing distinct temporal dynamics compared to gut microbiome dysbiosis. Furthermore, several transformation products of antibiotics and biomarker metabolites were observed in plasma due to antibiotic exposure. The transcriptome of the brain was only slightly altered due to antibiotic exposure. Results of these studies will help inform aquaculture practitioners and risk assessors when assessing the potential impacts of antibiotics present in fish feed and the environment, with implications for host health.PMID:40120561 | DOI:10.1016/j.chemosphere.2025.144263

Phytomedicine. 2025 Mar 15;141:156655. doi: 10.1016/j.phymed.2025.156655. Online ahead of print.ABSTRACTBACKGROUND: Obesity, characterized by excessive adipose tissue accumulation, has become a global health challenge with rapidly increasing prevalence. It contributes significantly to metabolic disorders including insulin resistance (IR). Renshen-zhuye decoction (RZD), a traditional Chinese medicine formula historically used for diabetes, shows potential for improving metabolic parameters, but its effects and mechanisms in obesity and insulin resistance remain unclear.PURPOSE: This study aimed to evaluate the therapeutic benefits of RZD on obesity and insulin resistance, and to elucidate the underlying mechanisms through which it improves glucose and lipid metabolism.METHODS: The role of RZD was evaluated in a high-fat diet (HFD) mouse model. The formula was characterized using UPLC-MS. Comprehensive analyses including histopathological staining, immunofluorescence, biochemical assays, 16S rRNA gene sequencing of gut microbiota, and non-targeted metabolomic analysis were performed. To validate the role of gut microbiota, we employed antibiotic treatment (ABX) to deplete intestinal flora and conducted fecal microbiota transplantation (FMT) experiments.RESULTS: RZD treatment dose-dependently alleviated HFD-induced dyslipidemia and insulin resistance, improving glucose tolerance, insulin sensitivity, and energy expenditure. Gut microbiota analysis revealed that RZD significantly modulated the composition of intestinal flora and their metabolic profiles. Additionally, RZD reduced intestinal and systemic inflammation by enhancing intestinal barrier integrity, particularly through increased expression of tight junction proteins such as Occludin. Importantly, the beneficial effects of RZD on weight management and glucose homeostasis were antagonized by antibiotic intervention, while FMT experiments confirmed that these improvements were mediated through gut microbiota modulation.CONCLUSION: This study provides new insights into RZD's modulatory effects on gut microbiota and subsequent improvements in obesity-related metabolic parameters. RZD alleviates HFD-induced obesity and insulin resistance in mice by modulating gut microbiota composition and function, which subsequently improves intestinal barrier integrity, reduces inflammation, and enhances metabolic homeostasis.PMID:40120542 | DOI:10.1016/j.phymed.2025.156655

Phytomedicine. 2025 Mar 11;141:156569. doi: 10.1016/j.phymed.2025.156569. Online ahead of print.ABSTRACTBACKGROUND: Diabetic skin ulcer is a clinical disorder of glucose metabolism that has a long treatment period and is prone to recurrent episodes. Huiyang Shengji decoction (HYSJD) is an effective traditional Chinese medicine for its clinical treatment, but its metabolic effects in patients with diabetic skin ulcers have not been well studied.PURPOSE: Our study aimed to investigate the mechanism of pharmacological treatment of HYSJD in treating diabetic skin ulcers.METHODS: The potential mechanism underlying diabetic wound treatment by HYSJD was screened using network pharmacology. Ultra-high performance liquid chromatography-MS/MS metabolomics analysis and correlation analysis were performed to investigate potential target pathways and genes. Furthermore, the db/db diabetic wound tissues and RAW264.7 macrophage inflammation model verified the mechanism using molecular biology experiments.RESULTS: In network pharmacology, HYSJD played a mainly therapeutic effect by regulating PI3K/AKT signaling pathway, EGFR tyrosine kinase inhibitor resistance, metabolic pathway, and other related metabolic-related pathways. Metabolomics analysis disclosed that L-lysine content increased, while those of linoleic and deoxycholic acids decreased in plasma between the HYSJD-treated group and the control group, participating in biotin metabolism. Among them, PPARγ played an important role. The experiments conducted in db/db mice indicated that HYSJD facilitates VEGF secretion and PPARγ expression. In vitro experiments have revealed that HYSJD inhibits macrophage ROS production, augments mitochondrial ATP production, elevates mitochondrial membrane potential, and diminishes the mitochondrial ECAR rate. Furthermore, these effects culminate in promoting M2 macrophage polarization through PPARγ activation. The molecular docking results revealed that the active compounds from HYSJD were capable of binding to PPARγ protein primarily through hydrogen bonding interactions. Notably, all binding energies were found to be lower than -3 kcal/mol, indicating strong and favorable interactions between the active compounds and the target receptor.CONCLUSIONS: The findings suggested that HYSJD regulates biotin metabolism by reducing excess levels of linoleic and deoxycholic acids and increasing levels of L-lysine, which in turn promotes diabetic wound healing by promoting M2 macrophage polarization through PPARγ up-regulation. These findings indicated that HYSJD is a decoction that can effectively treat diabetic skin ulcers.PMID:40120541 | DOI:10.1016/j.phymed.2025.156569

Phytomedicine. 2025 Mar 16;141:156642. doi: 10.1016/j.phymed.2025.156642. Online ahead of print.ABSTRACTBACKGROUND: Gastrointestinal diseases are global health issues. Current drugs for gastrointestinal diseases cause discomfort and toxicity; consequently, the use of traditional medicines and their extracts has gained attention in recent years. Physochlaina physaloides (L) G. Don. (P. physaloides) is traditionally used for diarrhoea and gastroenteritis; however, its material basis and mechanism of action for gastric injury have not been fully studied.PURPOSE: This study aims to explore P. physaloides and their protective effects on gastric injury, together with the potential mechanisms.STUDY DESIGN AND METHODS: We constructed chronic gastritis and gastric ulcer models in rats using 56 % ethanol and anhydrous ethanol, respectively. Additionally, we screened gastric injury pathways via transcriptomics and the gene expression omnibus (GEO) database. Subsequently, we constructed an ethanol-stimulated GES-1 cell model and screened the active fraction of P. physaloides based on the cell survival rate and antioxidant activity. The effect of the active fraction of P. physaloides was investigated via tissue structure (HE staining), mucus secretion (PAS staining), anti-inflammatory activity, antioxidant activity, and gastric acid secretion levels. We employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the active components of P. physaloides and the drug components in blood, before investigating the mechanisms via immunofluorescence, transcriptomic, metabolomics, network pharmacology, molecular docking, qRT-PCR, western blotting, and flow cytometry.RESULTS: The occurrence of gastritis, gastric ulcer, and gastric cancer is related to the PPAR/NF-κB signalling pathway, with decreased expression of FABP3 and PPARγ, and increased expression of Bcl-2 and TNF-α. The n-butanol fraction of P. physaloides (BPP) showed significant improvement in cell survival and antioxidant activity in vitro. BPP also alleviated inflammation and oxidative stress in rat models, including by upregulating CAT, GSH, SOD, IL-10, PGE2; downregulating VEGFA, IL-6, IL-8, TNF-α, and NO; improving pathological damage; restoring mucus levels; and reducing gastric acid secretion and macrophage expression. BPP and its active components, anisodamine and hyoscyamine, upregulated the expression of PPARα, PPARγ, CPT1, and FABP3, and downregulated NF-κB p65, thereby regulating the PPAR/NF-κB signalling pathway for gastroprotection. The BPP and its active components did not significantly increase the expression of GPX4 and SLC7A11, nor did they reduce the production of ROS. Therefore, their effects are unrelated to ferroptosis.CONCLUSION: This study provides the first evidence of the effectiveness of BPP in the prevention of gastric ulcers and treatment of chronic gastritis. We adopted a multidisciplinary approach to demonstrate that BPP and its active components, anisodamine and hyoscyamine, protect against ethanol-induced gastric injury by regulating the PPAR/NF-κB and non-ferroptotic cell death pathways. BPP and its active components can target PPARγ and FABP3 and may have clinical application prospects to prevent gastric injury, which has unique advantages. These findings provide a scientific foundation for gastroprotection and expand the clinical applications of BPP.PMID:40120539 | DOI:10.1016/j.phymed.2025.156642

Ultrason Sonochem. 2025 Mar 15;116:107313. doi: 10.1016/j.ultsonch.2025.107313. Online ahead of print.ABSTRACTTender coconut water (TCW) refers to the liquid endosperm of coconut developed in 6-9 months, which is prone to deterioration during postharvest storage. This study explored the impact of ultrasound (20 kHz, 2400 w and 20 min) on the quality of TCW during postharvest storage. Results showed that ultrasound was effective in preserving the quality of TCW. Especially at the end of storage (15 d), TSS value was increased by 18.38%, titratable acid was increased by 25.17%, turbidity was decreased by 10.58%, and soluble sugar and reducing sugar content were increased by 23.36% and 45.77%, respectively. According to HS-SPME-GC-MS results, a total of 28 volatile organic compounds were identified and the content of volatile organic compounds in TCW showed no significant difference before and after ultrasonic treatment. The E-tongue data demonstrated that ultrasound could effectively affect the taste of TCW, especially enhanced the astringency, aftertaste-A and aftertaste-B values. A total of 56 compounds were identified as differentially expressed metabolites by LC-MS based metabolomics, which were mainly connected with the tricarboxylic acid cycle and flavonoid biosynthesis pathway. These findings provide valuable insights into the potential use of ultrasound in the storage and preservation of other fruits.PMID:40120342 | DOI:10.1016/j.ultsonch.2025.107313

J Hazard Mater. 2025 Mar 17;491:137959. doi: 10.1016/j.jhazmat.2025.137959. Online ahead of print.ABSTRACTThe increasing cadmium (Cd) contamination in the environment poses a serious threat to ecosystem health and human safety. This study investigated the roles of quorum sensing (QS) genes luxI/R, key components of the QS system, in the Cd accumulation and detoxification in Aeromonas. Pan-genome analysis showed that luxI/R and Cd resistance genes were highly conserved in Aeromonas species. Strains of luxI/R knockout, complementation and overexpression were constructed via homologous recombination. The luxI/R deletion significantly reduced Cd removal by up to 32 %, decreased extracellular protein (18-36 %) and polysaccharide (19-33 %) contents, whereas luxI/R overexpression enhanced Cd removal capacity by 11 %. Transcriptomic and metabolomic analyses further revealed coordinated changes. In the ΔluxI/R strain, genes involved in assimilatory sulfate reduction and arginine biosynthesis were downregulated, accompanied by reduced levels of glycerophospholipid, vitamin, and cytochrome P450-related metabolites. In contrast, luxI/R overexpression upregulated arginine synthesis (2.0-3.5 fold) and sulfate assimilation (1.4-2.4 fold) genes, with corresponding increases of metabolites. Together these findings demonstrate that luxI/R genes may play a crucial role in regulation of EPS production and Cd resistance gene expression, thus enhancing our understanding of microbial Cd detoxification mechanisms.PMID:40120273 | DOI:10.1016/j.jhazmat.2025.137959

Environ Int. 2025 Mar 16;198:109380. doi: 10.1016/j.envint.2025.109380. Online ahead of print.ABSTRACTThis study examined the effects of branched perfluorohexanesulfonic acid (PFHxS) and perfluoroheptanoic acid (PFHpA), two alternatives to per- and polyfluoroalkyl substances (PFASs), on gut microbiota and metabolic function in Chinese children aged 6-9 years. A total of 336 children were enrolled, providing plasma and fecal samples. Gut microbiota composition was assessed through 16S rRNA gene sequencing, and fecal metabolites and short-chain fatty acids (SCFAs) were analyzed using targeted metabolomics profiling and high-performance liquid chromatography (HPLC), respectively. PFASs in plasma samples were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results revealed that exposure to PFHpA significantly reduced microbial diversity and richness in the gut microbiota. Specific bacterial genera were found to be positively or negatively associated with branched PFHxS and PFHpA exposures (β = -0.008---0.009, P_fdr = <0.001---0.048), with Parabacteroides positively correlated with branched PFHxS and Lachnospiraceae FCS020 group negatively correlated with PFHpA. Metabolomic analysis showed that branched PFHxS and PFHpA exposures were associated with distinct changes in fecal metabolite profiles (β = -0.182---0.177, P_fdr = 0.015---0.172), particularly reducing fatty acids and amino acids. Additionally, higher exposure to PFHpA was linked to a reduction in SCFA profiles, such as valeric acid (β = -0.691 - -0.341, P = 0.011---0.030). This study offers new insights into the potential adverse effects of PFASs alternatives, specifically branched PFHxS and PFHpA, on the gut microbiome and metabolic health in children.PMID:40120233 | DOI:10.1016/j.envint.2025.109380

Comp Biochem Physiol Part D Genomics Proteomics. 2025 Mar 1;55:101462. doi: 10.1016/j.cbd.2025.101462. Online ahead of print.ABSTRACTWhite faeces syndrome (WFS) has always been one of the main intestinal diseases of Litopenaeus vannamei, which has caused huge economic losses to shrimp farming. WFS infection is known to result from a combination of pathogens, but the changes in intestinal metabolites following WFS infection are unknown. In this study, morphological sections of the hepatopancreas and intestine of WFS infected shrimp were analyzed, and lesions were found in the hepatopancreas and intestine of infected shrimp. The hepatopancreatic bodies of shrimp infected with WFS were arranged and scattered, and the stellate cavity was deformed. The connective tissue within the intestinal fold's atrophies to the point where the muscular layer almost disappeared. The enzyme linked kit results showed that lysozyme activity in hepatopancreas was significantly increased, total antioxidant capacity was significantly decreased, intestinal total antioxidant capacity and superoxide dismutase activities were significantly decreased in WFS infected shrimp, indicating that the antioxidant capacity of hepatopancreas and intestine were impaired. The intestinal metabolites of WFS shrimp and healthy shrimp were analyzed by non-targeted metabolic technology, and 10 differential metabolites and 7 differential metabolic pathways were screened. Among them, arginine, a significant differential metabolite, may positively activate the mTOR pathway, leading to the high expression of mTOR pathway, which is closely related to intestinal health. This indicates that when L. vannamei. is infected with WFS, the arginine content in the intestine is up-regulated, which positively activates the mTOR signaling pathway leading to pathway disorder, thereby destroying the intestinal health of L. vannamei. Through this study, we can not only understand the intestinal metabolic characteristics of WFS, but also provide a theoretical reference for the prevention and treatment of WFS in L. vannamei.PMID:40120225 | DOI:10.1016/j.cbd.2025.101462

Water Res. 2025 Mar 13;279:123497. doi: 10.1016/j.watres.2025.123497. Online ahead of print.ABSTRACTThis study developed a novel strategy combining a nanoscale zero-valent iron (nZVI)/peracetic acid (PAA) pretreatment and hydrochar regulation to enhance anaerobic digestion of waste activated sludge (WAS) under ammonia-stressed conditions. The strategy significantly enhanced methane production at ammonia concentrations below 3000 mg/L, with the regulation groups (AN3000/REG) achieving a 50.1 % increase in cumulative methane yield. Metagenomic analysis demonstrated a 14.2 % enrichment of key functional microorganisms, including syntrophic fatty acid-oxidizing bacteria and hydrogenotrophic methanogens, in the AN3000/REG groups. Some of them promote the conversion of butyrate and valerate to acetate through the upregulation of key genes in the fatty acid β-oxidation pathway, thereby supplying sufficient substrates for acetoclastic methanogenesis. Beyond enhancing acetoclastic methanogenesis, the AN3000/REG groups exhibited significant upregulation of other metabolic pathways, with a 34.2 % increase in syntrophic acetate oxidation-hydrogenotrophic methanogenesis genes and a 17.1 % increase in methanol/methylotrophic methanogenesis-related genes. These findings were further validated by the metatranscriptomic and metaproteomic combination analyses. Furthermore, the AN3000/REG groups exhibited a significant enhancement in direct interspecies electron transfer, with functional microbes (e.g., Geobacter, Methanosarcina, and Methanobacterium), pili, and cytochrome c showing significant increases of 1.38-fold, 12.7-fold, and 5.6-fold, respectively. This might be due to the synergistic effects of nZVI and hydrochar in the regulation groups. Additionally, metabolomic analyses revealed that the regulation strategy improved the microbial adaptability to ammonia stress by modulating metabolic products, such as alkaloids. Our study not only provides a promising strategy for alleviating ammonia inhibition during the anaerobic digestion of WAS but also provides a strong basis for understanding the underlying mechanism under ammonia-stressed conditions.PMID:40120189 | DOI:10.1016/j.watres.2025.123497

Plant Biol (Stuttg). 2025 Mar 22. doi: 10.1111/plb.70013. Online ahead of print.ABSTRACTPlants produce an astonishingly diverse array of specialized metabolites. A crucial step in understanding the origin of such chemodiversity is describing how chemodiversity manifests across the spatial and ontogenetic scales relevant to plant-biotic interactions. Focusing on 21 sympatric species of Psychotria and Palicourea sensu lato (Rubiaceae), we describe patterns of specialized metabolite diversity across spatial and ontogenetic scales using a combination of field collections, untargeted metabolomics, and ecoinformatics. We compare α, β, and γ diversity of specialized metabolites in expanding leaves, unripe pulp, immature seed, ripe pulp, mature seed, and fine roots. Within species, fruit tissues from across ontogenetic stages had ≥α diversity than leaves, and ≤β diversity than leaves. Pooled across species, fruit tissues and ontogenetic stages had the highest γ diversity of all organs, and fruit tissues and ontogenetic stages combined had a higher incidence of organ-specific mass spectral features than leaves. Roots had ≤α diversity than leaves and the lowest β and γ diversity of all organs. Phylogenetic correlations of chemical distance varied by plant organ and chemical class. Our results describe patterns of specialized metabolite diversity across organs and species and provide support for organ-specific contributions to plant chemodiversity. This study contributes to the growing understanding within plant evolutionary ecology of the biological scales of specialized metabolite diversification. Future studies combining our data on specialized metabolite diversity with biotic interaction data and experiments can test existing hypotheses on the roles of ecological interactions in the evolution of chemodiversity.PMID:40120124 | DOI:10.1111/plb.70013

Sci China Life Sci. 2025 Mar 19. doi: 10.1007/s11427-024-2794-4. Online ahead of print.ABSTRACTLactobacillus johnsonii is a microbial biomarker associated with lipid deposition, but the mechanism by which it accelerates fatty acid absorption and deposition remains unclear. In this study, we isolated a strain of L. johnsonii MS0621 from the feces of Ningxiang pigs, an obese animal model, and evaluated its probiotic properties with high resistance to temperature and intestinal fluids. Colonization by L. johnsonii MS0621 increased the abundance of gut Lactobacillus in lean DLY pigs, concomitant with increases in fatty acid absorption in the intestine and lipid depositions in the fat and muscle tissues. The lipid absorption-promoting effect was further detected in IPEC-J2 cells treated with live L. johnsonii MS0621 and the bacteria-free supernatants, as evidenced by high triglyceride synthesis and the expression of CD36, a key lipid transporter. Metabolomics analysis showed that (R)-leucic acid is a potential metabolite targeting CD36 expression to guarantee lipid absorption and deposition. The mechanism might involve direct interaction with CD36, as molecular docking and inhibition of CD36 blocked L. johnsonii MS0621 or derived metabolite-mediated lipid absorption. In conclusion, we uncovered an important role of L. johnsonii MS0621 derived (R)-leucic acid in regulating the absorption and deposition of intestinal fatty acids via regulation of CD36 expression.PMID:40120026 | DOI:10.1007/s11427-024-2794-4

Anal Chem. 2025 Mar 22. doi: 10.1021/acs.analchem.4c06471. Online ahead of print.ABSTRACTTop-down proteomics (TDP) is emerging as a vital tool for the comprehensive characterization of proteoforms. However, as its core technology, top-down mass spectrometry (TDMS) still faces significant analytical challenges. While data-independent acquisition (DIA) has revolutionized bottom-up proteomics and metabolomics, they are rarely employed in TDP. The unique feature of protein ions in an electrospray mass spectrum as well as the data complexity require the development of new DIA strategies. This study introduces a machine learning-assisted Full Window DIA (FW-DIA) method that eliminates precursor ion isolation, making it compatible with a wide range of commercial mass spectrometers. Moreover, FW-DIA leverages all precursor protein ions to generate high-quality tandem mass spectra, enhancing signal intensities by ∼50-fold and protein sequence coverage by 3-fold in a modular protein analysis. The method was successfully applied to the analysis of a five-protein mixture under native conditions and Escherichia coli ribosomal proteoform characterization.PMID:40119838 | DOI:10.1021/acs.analchem.4c06471

J Agric Food Chem. 2025 Mar 22. doi: 10.1021/acs.jafc.4c12283. Online ahead of print.ABSTRACTHumic acids (HAs), tea polyphenols (TPs), and fulvic acids (FAs) are bioactive substances known for their antimicrobial, antioxidant, and plant growth-promoting properties. However, the chemical structures and molecular mechanisms underlying their growth-promoting effects remain unclear. Solid-state 13C nuclear magnetic resonance analysis reveals that FA has the most aromatic and oxygen-containing groups, followed by HA and TP, with a molecular weight ranking of HA > TP > FA. Transcriptomic and metabolomic analyses reveal that these biostimulants unregulated genes related to IAA, C and N metabolism, and pathogen resistance, leading to enhanced synthesis of amino acids, lipids, vitamins, and sugars while improving N and P utilization efficiency. Small molecular weight and aromatic compounds with carboxyl groups and phenolic hydroxyl (especially those with high O/C or (O + H)/C ratios) are crucial for stimulating hormone synthesis and nutrient uptake. These findings provide valuable insights into developing novel fertilizers and artificially regulating humic substances.PMID:40119812 | DOI:10.1021/acs.jafc.4c12283

Anal Chem. 2025 Mar 22. doi: 10.1021/acs.analchem.4c04480. Online ahead of print.ABSTRACTThis study introduces the ΔΔG method, a novel approach to analyzing metabolic regulation using relative quantification metabolome data. The method calculates shifts in the Gibbs free energy change (ΔG) in two different metabolic states. Subsequently, key reactions controlling the metabolic flux can be identified by comparing the ΔΔG values to the reaction rates. Two case studies demonstrated the applicability of this method. First, a metabolome data set was obtained from the wild-type and single-gene-deletion mutant strains of Saccharomyces cerevisiae. The ΔΔG values of the glycolytic reactions were calculated between those of the wild-type and each mutant strain. A positive correlation was observed between the ΔΔG values of phosphofructokinase (PFK) and the approximate glycolytic flux levels. These results suggested that PFK regulates glycolytic flux. Moreover, a comparison between S. cerevisiae (Crabtree-positive yeast) and Kluyveromyces marxianus (Crabtree-negative yeast) revealed that S. cerevisiae primarily regulates glycolysis through PFK, whereas K. marxianus employs a more distributed control. The ΔΔG method provides insights into metabolic regulation that are not apparent from metabolite profiles alone and is applicable to various biological systems, particularly for analyzing glycolysis. Furthermore, the simplicity of this method makes it a valuable tool for metabolic engineering and medical research.PMID:40119797 | DOI:10.1021/acs.analchem.4c04480

Cancer Med. 2025 Mar;14(6):e70819. doi: 10.1002/cam4.70819.ABSTRACTOBJECTIVE: Lipid metabolic reprogramming is closely intertwined with the development and progression of thyroid carcinoma (TC); however, its specific mechanism remains elusive. This study aimed to investigate the association between lipid metabolism and TC progression.METHODS: We employed liquid chromatography-mass spectrometry (LC/MS) for an untargeted metabolomics analysis, comparing 12 TC patients and 12 healthy controls (HC). Additionally, we conducted the screening of differentially expressed genes (DEGs) and identified differentially expressed lipid metabolism genes (LMGs). Multi-omic findings related to lipid metabolism were integrated to establish a prognostic risk model. The resulting risk score stratified TC patients into high- and low-risk groups. Overall survival (O.S.) was assessed using Kaplan-Meier (K-M) analysis. The immune landscape was evaluated using the CIBERSORT algorithm, and chemotherapeutic response was predicted utilizing the "pRRophetic" R package.RESULTS: Our metabolomic analysis revealed heightened lipid metabolic activity in TC, corroborated by similar findings in transcriptomic analysis. Multi-omic analysis identified key LMGs (FABP4, PPARGC1A, AGPAT4, ALDH1A1, TGFA, and GPAT3) associated with fatty acids and glycerophospholipids metabolism. A novel risk model, incorporating these LMGs, confirmed significantly worse O.S. (p = 0.0045) in the high-risk group based on TCGA_THCA. Furthermore, high-risk TC patients exhibited lower immune cell infiltration, and predictive outcomes indicated the efficacy of potential therapeutic drugs across risk groups.CONCLUSION: This multi-omic analysis underscores the potential utility of the lipid metabolism risk model in guiding clinical treatment and improving outcomes for TC patients.PMID:40119647 | DOI:10.1002/cam4.70819

Anim Microbiome. 2025 Mar 21;7(1):30. doi: 10.1186/s42523-025-00394-z.ABSTRACTBACKGROUND: The gut microbiota exerts a critical influence on energy metabolism homeostasis and productive performance in avian species. Given the diminishing availability of arable land and intensifying competition for finite resources between livestock production and human populations, the agricultural sector faces dual imperatives to enhance productive efficiency while mitigating ecological footprints. Within this paradigm, optimizing nutrient assimilation efficiency in commercial waterfowl operations emerges as a strategic priority. This investigation employs an integrated multi-omics approach framework (metagenomic, metabolomic, and transcriptomic analyses) to elucidate the mechanistic relationships between cecal microbial consortia and feed conversion ratios in Shan Partridge ducks.RESULTS: Based on the analysis of metagenome data, a total of 34 phyla, 1033 genera and 3262 species of bacteria were identified by metagenomic sequencing analysis. At the phylum level, 31 phylums had higher mean abundance in the low residual feed intake ( LRFI) group than in the high residual feed intake (HRFI) group. Among them, the expression of microbiome Elusimicrobiota was significantly higher in the LRFI group than in the HRFI group (P < 0.05). And we also found a significant differences in secondary metabolites biosynthesis, transport, and catabolism pathways between the two groups in microbial function (P < 0.05). Based on metabolomic analysis, 17 different metabolites were found. Among them, Lipids and lipid molecules accounted for the highest proportion. Whereas the liver is very closely related to lipid metabolism, we are close to understanding whether an individual's energy utilization efficiency is related to gene expression in the liver. We selected six ducks from each group of six ducks each for liver transcriptome analysis. A total of 322 differential genes were identified in the transcriptome analysis results, and 319 genes were significantly down-regulated. Among them, we found that prostaglandin endoperoxide synthase 2 (PTGS2) might be a key hub gene regulating RFI by co-occurrence network analysis. Interestingly, the differential gene PTGS2 was enriched in the arachidonic acid pathway at the same time as the differential metabolite 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2). In addition, the results of the association analysis of differential metabolites with microorganisms also revealed a significant negative correlation between 15d-PGJ2 and Elusimicrobiota.CONCLUSION: Based on comprehensive analysis of the research results, we speculate that the Elusimicrobiota may affect the feed utilization efficiency in ducks by regulating the expression of the PTGS2 gene.PMID:40119394 | DOI:10.1186/s42523-025-00394-z

BMC Genomics. 2025 Mar 21;26(1):278. doi: 10.1186/s12864-025-11465-5.ABSTRACTBACKGROUND: Although it has been demonstrated that gastrointestinal microorganisms greatly influence livestock performance, the effect of gastrointestinal microorganisms on the growth performance of crossbred cattle remains unclear. Due to their superior production characteristics, understanding the impact of gastrointestinal microorganisms on the growth performance of crossbred beef cattle is of significant importance for improving farming efficiency.RESULT: In this study, healthy Simmental with similar birth date and weight were selected as dams, Simmental (Combination I), Belgian Blue (Combination II) and Red Angus (Combination III) were used as parents for crossbreeding. The progeny of the three combination crosses were measured for growth performance under identical conditions from birth rearing to 18 months of age (n = 30). Rumen fluid and plasma were collected for macro-genomic and non-targeted metabolomic analysis (n = 8). The results showed that Combination II was superior to Combination I and Combination III in body weight (BW) and body height (BH) (P < 0.05). Mycoplasma, Succinivibrio, Anaerostipes, Methanosphaera, Aspergillus, and Acidomyces were significantly increased in the rumen of Combination II (P < 0.05), whereas differentially expressed metabolites (DEMs) 9,10,13-Trihome (11), 9,12,13-Trihome and 9(10)-Epome, and 9(S)-Hpode were reduced in abundance. In addition, plasma DEM PC (14:0/P-18:1(11Z)), PC (16:0/0:0), and PC (17:0/0:0) were down-regulated in combination II. Correlation analysis revealed that Anaerostipes, Methanosphaera, and Succinivibrio were associated with PC (14:0/P-18:1(11Z)), 9(10)-Epome, 9,10,13-Trihome (11), 9(S)-Hpode, 9,10,13-Trihome, PC (17:0/0:0), and PC (16:0/0:0). Growth traits were significantly positively correlated with the three dominant genera, Anaerostipes, Methanosphaera, and Succinivibrio, while significantly negatively correlated with key rumen metabolites and plasma metabolites (P < 0.05).CONCLUSIONS: Our study reveals the role of rumen microorganisms and its metabolites with host metabolism in the regulation of growth performance of crossbred cattle, which will contribute to the development of modern cattle breeding.PMID:40119296 | DOI:10.1186/s12864-025-11465-5

Sci Rep. 2025 Mar 21;15(1):9811. doi: 10.1038/s41598-025-94766-9.ABSTRACTThe role of amino acids (AAs) with bone health is still controversial. We examined the association between AAs and osteoporosis in a cross-sectional study of 135 participants aged 45 years or older from the Second Hospital of Jilin University. Plasma AAs were measured with targeted quantitative methodology. We measured bone mineral density (BMD) with dual energy x-ray absorptiometry, and osteoporosis was defined as a T-score ≤ -2.5. We estimated odds ratios (OR) and corresponding 95% confidence intervals (CIs) for the associations between AAs (per 1 standard deviation increase) with osteoporosis. Approximately 18.5% of participants (n = 25) had osteoporosis. Total (adjusted β = 0.052; P = 0.002) and non-essential AA (adjusted β = 0.064; P = 0.002) levels were associated with femoral neck BMD T-scores. Greater levels of total (adjusted OR: 0.734; 95% CI: 0.655-0.821), essential (adjusted OR: 0.763; 95% CI: 0.623-0.934) and non-essential AAs (adjusted OR: 0.721; 95% CI: 0.629-0.826) were associated with lower odds of osteoporosis. Higher tryptophan (adjusted OR: 0.498; 95% CI: 0.281-0.882), cysteine (adjusted OR: 0.561; 95% CI: 0.321-0.983), glycine (adjusted OR: 0.513; 95% CI: 0.285-0.922), and ornithine levels (adjusted OR: 0.581; 95% CI: 0.345-0.978) were associated with reduced osteoporosis risk. Higher AA levels were associated with higher femoral neck BMD, and lower odds of osteoporosis.PMID:40119126 | DOI:10.1038/s41598-025-94766-9