PubMed

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

J Heart Lung Transplant. 2025 Mar 19:S1053-2498(25)01834-0. doi: 10.1016/j.healun.2025.02.1699. Online ahead of print.ABSTRACTBACKGROUND: Controlled hypothermic preservation of donor hearts is associated with decreased post-transplant primary graft dysfunction compared to conventional cold storage. However, mechanisms underlying this benefit in human subjects are unclear.METHODS: We randomized 20 heart transplant recipients at a single institution to receive donor hearts preserved with either controlled hypothermic preservation or standard cold storage. Right ventricular biopsies were obtained at donor heart recovery, immediately before implantation, and 7 days after transplantation. Protein expression profiles at each time point were evaluated using mass spectrometry, Protein Interaction Network Extractor analysis, and Ingenuity Pathway Analysis.RESULTS: Immediately before implantation, controlled hypothermic preservation was associated with increased protein expression related to fatty acid metabolism, mitochondrial intermembrane space, and contractile fiber machinery. Pathway analysis indicated increased cell viability, autophagy, and upregulation of AMP-activated protein kinase pathway with controlled hypothermic preservation. By post-transplant day 7, the protein expression profiles of the two groups were similar. However, controlled hypothermic preservation was associated with increased expression in the peroxisome proliferator-activated receptor signaling pathway and fatty acid oxidation.CONCLUSIONS: Controlled hypothermic preservation of donor hearts shows beneficial time-dependent variability in protein expression that may confer improved organ quality at the time of transplantation.PMID:40118307 | DOI:10.1016/j.healun.2025.02.1699

Microb Pathog. 2025 Mar 19:107446. doi: 10.1016/j.micpath.2025.107446. Online ahead of print.ABSTRACTBACKGROUND: Gallstone disease, arising from the interplay between host metabolism and gut microbiota, represents a significant health concern. Dysbiosis of the gut microbiome and disruptions in circadian rhythm contribute to the pathogenesis of gallstones. This study conducted a comprehensive analysis of gut microbiota and metabolites derived from stool and serum samples of 28 patients with cholesterol gallstones (CGS) and 19 healthy controls, employing methodologies such as 16S rRNA sequencing, metaproteomics, metabolomics, and host genetic analysis. Additionally, a retrospective cohort study was utilized to assess the efficacy of probiotics or ursodeoxycholic acid (UDCA) in preventing CGS formation post- bariatric surgery.RESULTS: In CGS patients, gut microbiota diversity shifted, with harmful bacteria rising and beneficial ones declining. The altered microbiota primarily affected amino acid, lipid, nucleotide, and carbohydrate metabolism. Metabolic abnormalities were noted in amino acids, glucose, lipids, and bile acids with decreased levels of ursodeoxycholic, glycosodeoxycholic, and glycolithocholic acids, and increased glycohyodeoxycholic and allocholic acids. Glutamine and alanine levels dropped, while phenylalanine and tyrosine rosed. Animal studies confirmed gene changes in gallbladder tissues related to bile acid, energy, glucose, and lipid metabolism. Importantly, UDCA and probiotics effectively reduced CGS risk post-bariatric surgery, especially when combined.CONCLUSIONS: Multi-omics can clarify CGS pathology, by focusing on the gut-metabolism-gene axis,paving the way for future studies on CGS prevention and treatment through gut microbiota or metabolic interventions.PMID:40118296 | DOI:10.1016/j.micpath.2025.107446

Bone. 2025 Mar 19:117460. doi: 10.1016/j.bone.2025.117460. Online ahead of print.ABSTRACTOBJECTIVES: The study aimed to explore associations of metabolomic data based on nuclear magnetic resonance (NMR) with the risk of fractures and bone mineral density (BMD).METHODS: We included 69,963 participants without fractures at baseline in the UK Biobank. Cox proportional hazard models were used to estimate the associations of metabolomic biomarkers measured by NMR technology with the risk of all fractures and hip fracture. We used principal component analysis (PCA) to obtain uncorrelated principal components (PC), which were further used to estimate the associations of each PC with BMD, all fractures, and hip fracture separately.RESULTS: During a median follow-up of 12.6 years, 3840 incidents of all fractures and 666 incidents of hip fracture were documented. Ninety-four of the 143 metabolomic biomarkers were significantly associated with incident all fractures, and 81 were significantly associated with incident hip fracture. The very low-density lipoprotein (VLDL) subclasses in different lipid constituents were associated with increased BMD at multiple sites, whereas high-density lipoprotein (HDL) subclasses were associated with decreased BMD. Higher concentrations of small (HR per SD increment: 0.92; 95 % CI: 0.88-0.97), medium (HR per SD increment: 0.91; 95 % CI: 0.88-0.94), and large (HR per SD increment: 0.93; 95 % CI: 0.90-0.96) low-density lipoprotein (LDL) particles were associated with a lower risk of all fractures. Similarly, higher VLDL subclasses (excluding very small VLDL particles) were associated with a lower risk of all fractures. Besides, higher levels of lipid constituents (including total lipids, cholesteryl esters, cholesterol, and free cholesterol) of very large and large HDL were associated with an increased risk of all fractures. PC1 (mainly contributed by lipid subclasses of LDL and VLDL), which explained the most variance of individual biomarkers, showed a negative association with the risk of all fractures (P = 7.80E-08). Similar associations were observed for hip fracture.CONCLUSIONS: Higher levels of large and very large HDL were associated with an increased risk of fractures, whereas higher lipid subclasses of LDL and VLDL were associated with a lower risk of fracture. Higher levels of VLDL subclasses in different lipid constituents were associated with increased BMD at multiple sites, while higher level of HDL was associated with decreased BMD.PMID:40118262 | DOI:10.1016/j.bone.2025.117460

Gastroenterology. 2025 Mar 19:S0016-5085(25)00526-8. doi: 10.1053/j.gastro.2025.02.035. Online ahead of print.ABSTRACTThe gut microbiome is involved in human health and disease, and its comprehensive understanding is necessary to exploit it as a diagnostic or therapeutic tool. Multi-omics approaches, including metagenomics, metatranscriptomics, metabolomics, and metaproteomics, enable depicting the complexity of the gut microbial ecosystem. However, these tools generate a large data stream, which integration is needed to produce clinically useful readouts but, in turn, might be difficult to carry out with conventional statistical methods. Artificial intelligence and machine learning have been increasingly applied to multi-omics datasets in several conditions associated with microbiome disruption, from chronic disorders to cancer. Such tools show potential for clinical implementation, including the discovery of microbial biomarkers for disease classification or prediction, the prediction of response to specific treatments, the fine-tuning of microbiome-modulating therapies. Here we discuss the state of the art, potential, and limits, of artificial intelligence and machine learning in the multi-omics approach to gut microbiome.PMID:40118220 | DOI:10.1053/j.gastro.2025.02.035

Cell Genom. 2025 Mar 19:100810. doi: 10.1016/j.xgen.2025.100810. Online ahead of print.ABSTRACTDifferential susceptibilities to various diseases and corresponding metabolite variations have been documented across diverse ethnic populations, but the genetic determinants of these disparities remain unclear. Here, we performed large-scale genome-wide association studies of 171 directly quantifiable metabolites from a nuclear magnetic resonance-based metabolomics platform in 10,792 Han Chinese individuals. We identified 15 variant-metabolite associations, eight of which were successfully replicated in an independent Chinese population (n = 4,480). By cross-ancestry meta-analysis integrating 213,397 European individuals from the UK Biobank, we identified 228 additional variant-metabolite associations and improved fine-mapping precision. Moreover, two-sample Mendelian randomization analyses revealed evidence that genetically predicted levels of triglycerides in high-density lipoprotein were associated with a higher risk of coronary artery disease and that of glycine with a lower risk of heart failure in both ancestries. These findings enhance our understanding of the shared and specific genetic architecture of metabolites as well as their roles in complex diseases across populations.PMID:40118068 | DOI:10.1016/j.xgen.2025.100810

Cell. 2025 Mar 14:S0092-8674(25)00209-0. doi: 10.1016/j.cell.2025.02.021. Online ahead of print.ABSTRACTUnderstanding how proteins in different mammalian tissues are regulated is central to biology. Protein abundance, turnover, and post-translational modifications such as phosphorylation are key factors that determine tissue-specific proteome properties. However, these properties are challenging to study across tissues and remain poorly understood. Here, we present Turnover-PPT, a comprehensive resource mapping the abundance and lifetime of 11,000 proteins and 40,000 phosphosites in eight mouse tissues and various brain regions using advanced proteomics and stable isotope labeling. We reveal tissue-specific short- and long-lived proteins, strong correlations between interacting protein lifetimes, and distinct impacts of phosphorylation on protein turnover. Notably, we discover a remarkable pattern of turnover changes for peroxisome proteins in specific tissues and that phosphorylation regulates the stability of neurodegeneration-related proteins, such as Tau and α-synuclein. Thus, Turnover-PPT provides fundamental insights into protein stability, tissue dynamic proteotypes, and functional protein phosphorylation and is accessible via an interactive web-based portal at https://yslproteomics.shinyapps.io/tissuePPT.PMID:40118046 | DOI:10.1016/j.cell.2025.02.021

Nutr Res. 2025 Feb 26;136:15-27. doi: 10.1016/j.nutres.2025.02.004. Online ahead of print.ABSTRACTYeast mannans (YM) are potential prebiotics that may improve laxation. The aim was to evaluate the effects of YM on gastrointestinal symptoms, with a hypothesis of high tolerance. A secondary aim assessed stool frequency. Fecal microbiota composition (16S rRNA gene amplicon sequencing) and targeted urine metabolites (LC-MS/MS) were explored. An ex vivo simulation of digestion and fermentation (6 donors) compared YM to the reference prebiotic inulin followed by an open-label pilot study, with a 1-week baseline and 2-week intervention of 15 g/d of YM. Ex vivo findings showed increased Bacteroides faecis, B. ovatus, Parabacteroides merdae, P. distasonis, Blautia faecis, and Bifidobacterium spp. in response to YM. Participants (n = 20, 71.4 ± 11.0 y) reported no change with YM for burping, constipation, diarrhea, flatulence/gas, nausea, reflux/heartburn, or rumblings/noise, rated from 0 for none to 3 for severe symptoms. Cramping/pain marginally increased from baseline (0.02 ± 0.01) to intervention (0.05 ± 0.02; P = .046), as did distention/bloating (baseline, 0.07 ± 0.03; intervention week 2, 0.15 ± 0.05; P = .037). This high tolerability was explained by the ex vivo finding that YM induced less gas production than inulin (-45%). Stool frequency trended higher with YM (1.53 ± 0.15 stools/d) compared to baseline (1.35 ± 0.11) (P = .079); participants with ≤1 stools/d (n = 8) showed an increase (0.84 ± 0.14 to 1.19 ± 0.32; P = .016). In vivo compositional changes in fecal microbiota suggest increased B. faecis, B. ovatus, P. merdae, and P. distasonis levels in response to YM. Overall, YM elicited specific microbiota modulation with minimal gastrointestinal symptoms and the potential to increase stool frequency, supporting its prebiotic potential. This trial was registered at clinicaltrials.gov (NCT05939336).PMID:40117931 | DOI:10.1016/j.nutres.2025.02.004

Redox Biol. 2025 Mar 8;82:103579. doi: 10.1016/j.redox.2025.103579. Online ahead of print.ABSTRACTBronchopulmonary dysplasia (BPD) is a prevalent chronic respiratory condition in preterm infants with an increasing incidence, severely affecting their survival rate and quality of life. Exploring the underlying mechanisms of BPD helps to develop novel effective therapeutic strategies. In this study, integrated metabolomic analyses of tracheal aspirates (TAs) from BPD infants and non-BPD infants, along with lung tissues from hyperoxia-induced experimental BPD neonatal rats and control rats, demonstrated that BPD was associated with a significant reduction in 3-hydroxyanthranilic acid (3-HAA), which was confirmed to be partly caused by tryptophan-metabolizing enzyme disorders. In vivo and in vitro models were subsequently established to assess the efficacy and underlying mechanisms of 3-HAA in relation to BPD. Compared with the BPD group, 3-HAA nebulization improved lung development and suppressed inflammation in rats. Limited proteolysis-small molecule mapping (LiP-SMap) proteomic analysis revealed the involvement of the ferroptosis pathway in the underlying mechanism by which 3-HAA alleviated hyperoxia-induced BPD injury. Ferroptosis was identified by detecting Fe2+ levels, malondialdehyde (MDA), 4-HNE, total aldehydes, mitochondrial morphology, ferroptosis-associated protein and mRNA expression, and this dysregulation was indeed ameliorated by 3-HAA nebulization in vivo. Furthermore, a combination of LiP-SMap, molecular docking, SPR and Co-IP analyses confirmed that 3-HAA can bind directly to FTH1 and disrupt the nuclear receptor coactivator 4 (NCOA4)-FTH1 interaction. In conclusion, our study is the first to reveal that BPD is linked to the reduction of 3-HAA, and 3-HAA could inhibit the ferroptosis pathway by targeting FTH1, thereby alleviating hyperoxia-induced injury in rats and alveolar type II epithelial cells, highlighting the potential of targeting 3-HAA and ferroptosis for clinical applications in BPD.PMID:40117887 | DOI:10.1016/j.redox.2025.103579

Food Chem. 2025 Mar 14;480:143892. doi: 10.1016/j.foodchem.2025.143892. Online ahead of print.ABSTRACTWhite mold is one of the most common and serious fungal diseases of morel affecting the entire growth cycle. Studies show that when infected, plants defend against pathogens by regulating metabolic responses within their systems. A total of 310 metabolites for infecting Paecilomyces penicillatus in morel mushrooms were identified by UPLC-MS/MS. Most metabolites showed an intuitive downward trend during infection and reached their lowest levels at the third stage. For PCA and HCA, infection period had a significant effect on metabolites, and the second stage was the key turning point for metabolite accumulation in response to disease. Correlation analysis of the top 50 differential metabolites with the highest VIP values screened by OPLS-DA suggested that lipids, nucleotides and their derivatives, sugars, organic acids, phenolic acids and alkaloids may respond synergistically to disease during infection. Taken together, this study provided an entry point for studying white mold pathogenesis in morel.PMID:40117821 | DOI:10.1016/j.foodchem.2025.143892

J Hazard Mater. 2025 Mar 18;491:137989. doi: 10.1016/j.jhazmat.2025.137989. Online ahead of print.ABSTRACTThis study aimed to explore the metabolite profiles of populations engaged in intensive vegetable cultivation and their exposure to pesticides. As urbanization progresses and eating habits evolve, intensive vegetable farming has rapidly expanded; however, this cultivation method poses potential health risks to farmers, particularly due to long-term exposure to "greenhouse gases" in enclosed environments. The study investigated the demographic characteristics of individuals in vegetable-growing areas, collected relevant biological samples, and assessed exposure levels by analyzing pesticide metabolites in urine. The results indicated that the types and concentrations of pesticide metabolites detected in the urine of the exposed group were significantly higher than those in the control group, with notable increases in neonicotinoid metabolites such as dinotefuran (DIN) and thiacloprid. Furthermore, the impact of these pesticides on mammalian organisms was examined through animal experiments, which revealed dynamic changes in the concentration of DIN in mouse serum and urine, providing valuable data on its biological metabolic characteristics. These findings underscore the importance of ongoing disease prevention, pollution control, and the need for enhanced health monitoring and protective measures for agricultural workers.PMID:40117779 | DOI:10.1016/j.jhazmat.2025.137989

Comp Biochem Physiol Part D Genomics Proteomics. 2025 Mar 18;55:101486. doi: 10.1016/j.cbd.2025.101486. Online ahead of print.ABSTRACTAnimals frequently suffer from starvation throughout their life cycle; however, the mobilization and utilization of energy sources can differ. To clarify the fundamental mechanisms underlying energy mobilization and metabolic adjustment in response to food deprivation in the soft-shelled turtle (Pelodiscus sinensis), eighty turtles (initial body weight, 51.81 ± 0.29 g) were subjected to starvation periods of 1 d, 4 d, 8 d, 16 d, and 32 d (referred to as S1, S4, S8, S16, and S32). The results showed that the greatest absolute loss in body composition occurred in moisture, followed by protein and lipid, respectively. Hepatic glycogen contents significantly decreased after 4 days of starvation and then remained stable. Notably, plasma glucose, cholesterol, and free fatty acid contents exhibited significant decreases from S8, while plasma triacylglycerol levels dramatically declined from S4. Gluconeogenesis-related genes (pepck, g6pase) were upregulated in the starving turtles to maintain glucose homeostasis. Comparative analyses between S32 and S1 groups identified a total of 6051 differential genes and 150 differential metabolites, highlighting three overlapping metabolic pathways: glycerophospholipid metabolism, alanine, aspartate, and glutamate metabolism, and taurine and hypotaurine metabolism. Integrative analyses further revealed increased levels of specific metabolites, including phosphatidylcholine, phosphatidylethanolamine, glycerophosphocholine, L-2-aminoethyl seryl phosphate, l-serine-phosphatidylethanolamine, adenyiosuccinate, 5-phosphoribosylamine, and taurine. These metabolites are vital for amino acid-driven gluconeogenesis, cell membrane stability, and mitigating cellular damage resulting from food deprivation. In conclusion, glucose homeostasis was maintained by enhancing gluconeogenesis in P. sinensis during extended periods of starvation, and the activation of lipid and amino acid metabolism represents an adaptive metabolic strategy employed by P. sinensis to cope with starvation conditions.PMID:40117751 | DOI:10.1016/j.cbd.2025.101486

Free Radic Res. 2025 Mar 21:1-13. doi: 10.1080/10715762.2025.2483454. Online ahead of print.ABSTRACTChronic kidney disease (CKD) is a progressive condition marked by persistent kidney damage, leading to high mortality rates and economic burden in advanced stages. Ozone therapy has emerged as a complementary alternative capable of mitigating oxidative stress involved in CKD progression. Ozonated saline solution (OSS) prepared via microbubbling offers enhanced efficacy due to greater ozone dissolution, homogeneity, and stability compared to conventional methods. This study compared the biosafety and efficacy of OSS prepared through bubbling and microbubbling methods in advanced CKD patients. In vitro, hydrogen peroxide (H2O2) concentrations were measured at various doses and times for both methods. In healthy volunteer, biosafety was assessed using TMRE and Annexin V in leukocytes. In CKD patients, TMRE, Annexin V, redox markers (catalase, superoxide dismutase, glutathione system, H2O2, lipoperoxidation), and renal function markers (urea, creatinine, glomerular filtration rate) were evaluated. Microbubbling produced lower H2O2 concentrations in vitro, depending on time and ozone dose. In vivo, both methods increased mitochondrial activity and apoptosis in CKD patient leukocytes. However, microbubbling notably enhanced antioxidant capacity, catalase and superoxide dismutase activity, and redox balance (elevated reduced-to-oxidized glutathione ratio) compared to conventional bubbling. It also showed slight improvements in serum clinical parameters. In conclusion, the microbubbling method demonstrated superior biosafety and therapeutic efficacy in advanced CKD patients, highlighting its potential as a preferred approach in ozone therapy.PMID:40117653 | DOI:10.1080/10715762.2025.2483454