PubMed

Environ Res. 2025 May 8:121798. doi: 10.1016/j.envres.2025.121798. Online ahead of print.ABSTRACTEutrophication is the main factor for the degradation of lake ecosystems. More than exogenous input, endogenous N and P nutrients are responsible for it. Although the P passivation technology with functional materials is common for alleviating endogenous P pollution, will it have the same effect for endogenous N removal? In this study, a novel MgFe-LDHs/Vallisneria natans (V. natans) combined system was established for effective eliminating endogenous N and P simultaneously. During remediation periods, MgFe-LDHs/V. natans combined system with the most obvious improvement for overlying water quality that was reflected by DO, ORP, and SS, and TP, TN, and NH4+-N removal efficiency were up to 99%. In sediments, TP and TN removal rate was approximately 68% and 63%, where the reduction of Org-P and NH4+-N accounted for the majority of it, respectively. Under stimulation of MgFe-LDHs, NH4+-N assimilation in V. natans could be promoted through improving the metabolizing enzymes activity. In turn, V. natans contributed to Org-P mineralization by secreting organic acid, further facilitating IP enrichment on MgFe-LDHs. Additionally, owing to the synergism between V. natans allelopathy and MgFe-LDHs, the symbiotic relationship between microbial communities was much closer and more stable, the expression of functional genes that relate to denitrification, assimilatory nitrate reduction, phosphorylation and organophosphorus mineralization processes were up-regulated prominently. That is, microorganisms acted synergistically were important for endogenous N and P elimination performance. This study proposed a high-efficiency and environmentally friendly materials/plants combined remediation technology for eutrophication, especially those where with much high endogenous N and P loading.PMID:40348264 | DOI:10.1016/j.envres.2025.121798

Int J Biol Macromol. 2025 May 8:143932. doi: 10.1016/j.ijbiomac.2025.143932. Online ahead of print.ABSTRACTBile Arisaema, a traditional Chinese medicine, has been previously identified by our team to possess antipyretic properties attributed to its polysaccharide component. Recently, we have confirmed that bile Arisaema played a significantly lipid-lowering effect on hyperlipidemia rats. Building upon this discovery, the present study aimed to investigate the unexplored hypolipidemic potential of its polysaccharide component and elucidate the underlying mechanisms. A soluble polysaccharide fraction devoid of free proteins, named BAPs, was extracted from bile Arisaema using a combination of hot water extraction, alcohol precipitation, and the Sevage method. The structural characteristics of BAPs were preliminarily elucidated through monosaccharide composition analysis (mainly composed of glucose), molecular weight distribution (38.74 kDa and 2.87 kDa), and glycosyl linkage analysis via methylation. The results of animal experiment demonstrated that oral administration of BAPs (400 mg/kg/day) for four weeks significantly improved abnormal serum lipid levels, hepatic function and histopathological injury on high-fat diet-induced hyperlipidemia rats. Mechanistically, the results of high throughput sequencing indicated that BAPs intake markedly altered the hepatic and fecal metabolome and lipidome, while also modulating gut microbiota composition and improving intestinal barrier integrity. Spearman's correlation analysis unveiled closely associations between the altered microbes, lipids, metabolites and serum biochemical indicators. Western blotting and qRT-PCR analyses further confirmed that these metabolic improvements were mediated by the regulation of key genes involved in lipid metabolism. Collectively, this study demonstrated that BAP supplementation effectively improved serum lipid profiles in hyperlipidemia rats by modulating metabolic disorders and restoring gut homeostasis.PMID:40348213 | DOI:10.1016/j.ijbiomac.2025.143932

Life Sci. 2025 May 8:123692. doi: 10.1016/j.lfs.2025.123692. Online ahead of print.ABSTRACTAIMS: Ubiquitin-specific peptidase 18 (USP18) is an important member of the deubiquitinating enzyme family, which has received much attention in recent years for its role in microglia regulation. The aim of this study was to investigate the role of USP18 in midbrain and its potential molecular mechanisms.METHODS: In this study, we assessed behavioural phenotypes and pathological changes by adeno-associated virus (AAV)-mediated midbrain-specific USP18 high-expression mouse model. RNA sequencing and untargeted metabolomics were used for multi-omics analysis, and protein expression was detected by Western blot, and ELISA was used to detect neuroinflammatory factor levels.RESULTS: Our analyses suggest that USP18 is a key regulator of immune activity in the midbrain. USP18 helps maintain the resting state of microglia and exerts neuroprotective effects by promoting TH protein expression. In the midbrain, interference with USP18 expression resulted in significant changes in neuroimmune responses, gene expression associated with inflammation, and metabolite levels. Notably, the TLR signalling pathway was significantly enriched. Loss of USP18 led to a significant increase in the expression of TLR2, Iba-1, and GFAP proteins and a significant decrease in TH levels, and this change was particularly pronounced in microglia. Importantly, the changes observed in USP18 silencing were also reflected in brain tissues of human neurodegenerative diseases.SIGNIFICANCE: This study reveals the critical role of USP18 in midbrain and microglia, and suggests it can finely regulate neuroinflammatory and immune responses by modulating TLR2 protein levels. The findings provide new ideas for understanding mechanisms of neurodegenerative diseases and developing therapeutic strategies.PMID:40348176 | DOI:10.1016/j.lfs.2025.123692

Phytomedicine. 2025 Apr 28;143:156817. doi: 10.1016/j.phymed.2025.156817. Online ahead of print.ABSTRACTBACKGROUND: Ocular neovascularization, a hallmark of several vision-threatening diseases, including retinopathy of prematurity (ROP) and wet age-related macular degeneration (wet AMD), is commonly treated with intravitreal injections of anti-VEGF agents. However, these treatments are limited by invasiveness and drug resistance, highlighting the need for alternative therapies. Sclareol (SCL), a labdane diterpenoid derived from Salvia sclarea, exhibits various biological activities, but its potential role in angiogenesis and pharmacokinetics after oral administration remain unexplored.METHODS: Hypoxia-induced endothelial cells (ECs) were used as an in vitro model, while mouse oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) were used as in vivo models. The pharmacokinetics of SCL in plasma, retina, and choroid were analyzed after oral administration in mice. Furthermore, the underlying mechanisms were elucidated through an integrative approach combining transcriptomics, metabolomics, network pharmacology, molecular docking, and molecular dynamics simulation.RESULTS: SCL inhibited hypoxia-induced EC proliferation, permeability, migration, tube formation, sprouting, glycolysis, mitochondrial respiration, and oxidative stress by modulating the PI3K-AKT-FOXO1 pathway. Additionally, Oral administration of SCL significantly inhibited OIR and CNV progression in mice, demonstrating enhanced therapeutic efficacy when combined with intravitreal aflibercept (Eylea) injection.CONCLUSION: SCL is a promising orally administered natural compound for ocular neovascularization, offering a potential alternative or adjunctive therapy to existing anti-VEGF treatments.PMID:40347925 | DOI:10.1016/j.phymed.2025.156817

Food Chem. 2025 May 5;486:144644. doi: 10.1016/j.foodchem.2025.144644. Online ahead of print.ABSTRACTSelenium (Se) plays a crucial role in maintaining human health, but traditional methods of incorporating Se into food products have certain limitations. Recently, Se-enriched fermented foods have emerged as a promising, safe and efficient source of Se supplementation. Paocai, a traditional Chinese fermented vegetable, is particularly popular due to its nutritional benefits and distinctive flavor. Herein, this study explored the physicochemical properties, flavor quality and microbial community composition of Paocai inoculated with various types of Se-enriched lactic acid bacteria (LAB). The results showed that the Se contents of Se-enriched fermented Paocai ranged from 39.02 μg/L to 68.26 μg/L, which were closely related to the strain of LAB. Synergistic fermentation of Se and LAB reduced nitrite contents and pH in Paocai by promoting organic acid formation. Additionally, variations in the flavor quality of Paocai across different treatments were primarily attributed to the differing levels of 21 aroma compounds. Furthermore, both abiotic factors and aroma compounds jointly influenced the microbiota structure of Paocai. Most LAB exhibited significant correlations with organic acids and specific aroma compounds. Functional predictions further reconstructed metabolic pathways and key enzyme distributions in organic acid and isothiocyanate metabolism. These findings offer a novel approach to enhancing Paocai quality while addressing daily Se intake requirements.PMID:40347818 | DOI:10.1016/j.foodchem.2025.144644

J Pharm Biomed Anal. 2025 May 8;263:116956. doi: 10.1016/j.jpba.2025.116956. Online ahead of print.ABSTRACTAging leads to deterioration of the liver and kidney. Metabolic research on aging organs, including liver and kidney and metabolic studies of caloric restriction (CR), which delay aging and extends lifespan, are not well understood. In this study, we monitored metabolic changes associated with aging and explored potential biomarkers in kidney and liver of young (Y, 8 months), old (O, 23 months), and old calorie-restricted (OCR, 23 months) rats by metabolic profiling of organic acids (OA), free fatty acids (FFA), amino acids (AA) using gas chromatography-tandem mass spectrometry. Optimization of OA, FFA, and AA profiling methods were useful for quantifying these metabolites in kidney and liver. Profile analysis identified 48 and 45 metabolites in the kidney and liver, respectively. In the kidney, malic acid was significantly higher when comparing the Y and O groups, whereas 3-hydroxybutyric acid was significantly higher when comparing the O and OCR groups. In the liver, four metabolites (phenylacetic acid, valine, isoleucine, and tyrosine) were significantly evaluated as potential biomarker when comparing the Y and O groups, whereas 3-hydroxybutyric acid was significantly increased when comparing the O and OCR groups. Metabolomics results indicate that aging leads to mitochondrial dysfunction, phenylalanine metabolism disorders, and kidney dysfunction, whereas CR may regulate renal aging by reducing oxidative stress, inflammation, and lipid accumulation, while improving energy metabolism and resistance to oxidative stress in the liver. This result may explain some changes in the metabolism of aged kidney and liver during aging and CR.PMID:40347762 | DOI:10.1016/j.jpba.2025.116956

Comp Biochem Physiol Part D Genomics Proteomics. 2025 May 7;55:101529. doi: 10.1016/j.cbd.2025.101529. Online ahead of print.ABSTRACTThe influences of different bamboo species on the microbiome and metabolome of giant pandas (Ailuropoda melanoleuca) remain understudied. The aim of this study was to investigate the effects of different Phyllostachys species on the gut microbial communities and fecal metabolite profiles in giant pandas. Metagenome and metabolome were performed on the feces of giant pandas fed with different Phyllostachys species (P. edulis, P. iridescens, P. glauca, and P. violascens). The results of metagenome showed that dietary with P. glauca could notably decrease the microbial Shannon index. The relative abundances of both Cellulosilyticum and Pseudomonas were enhanced after dietary with P. iridescens, suggesting P. iridescens could enhance the cellulose-degrading function in giant pandas. However, dietary with P. glauca or P. violascens could increase the relative abundances of certain pathogenic bacteria (Escherichia, Shigella, and Klebsiella). Metabolomics analysis further revealed that all experimental groups exhibited notably elevated levels of fecal flavonoids and fatty acids. In addition, the correlation analysis showed that certain nutrients of bamboo leaves (mainly crude protein and Cu) were significantly correlated with several differential gut bacteria and fecal metabolites. Based on the present results, P. iridescens might be a substitute for the routinely used Phyllostachys species (P. edulis) in the captive management of giant pandas. The results have revealed that bamboo species is an important factor affecting the gut microbiota and fecal metabolites in giant pandas. Our results could provide important information about bamboo species-induced alterations on the microbiome and metabolome in giant pandas.PMID:40347566 | DOI:10.1016/j.cbd.2025.101529

Bioinformatics. 2025 May 10:btaf290. doi: 10.1093/bioinformatics/btaf290. Online ahead of print.ABSTRACTNontargeted LC-MS metabolomics datasets contain a wealth of information but present many challenges during analysis and processing. Often, two or more independently processed datasets must be aligned to form a complete dataset, but existing software does not fully meet our needs. For this, we have created an open-source Python package called Eclipse. Eclipse uses a novel graph-based approach to handle complex matching scenarios that arise from n > 2 datasets.AVAILABILITY AND IMPLEMENTATION: Eclipse is open source (https://github.com/broadinstitute/bmxp) and can be installed via "pip install bmxp".SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:40347466 | DOI:10.1093/bioinformatics/btaf290

Eur J Immunol. 2025 May;55(5):e202451595. doi: 10.1002/eji.202451595.ABSTRACTIn severe malaria, dysregulated metabolism and excessive inflammatory responses contribute to fatal outcomes. Therapeutic strategies that address both metabolic and inflammatory balances are thus required. Itaconate, a metabolite produced by aconitate decarboxylase 1 (ACOD1), is a potent inhibitor of both inflammation and glycolysis with protective effects in various inflammatory diseases. Although elevated itaconate levels have been observed in Plasmodium-infected individuals, its role in malaria is still poorly understood, making further investigation essential for assessing its therapeutic potential. We investigated the role of itaconate in both severe and mild malaria using Plasmodium berghei NK65 (PbNK65) and Plasmodium chabaudi AS (PcAS) models, respectively. Using 13C-tracer metabolomics, we detected increased itaconate levels in various organs during infection and identified inflammatory monocytes as the source of this production. Nevertheless, ACOD1 knockout mice displayed no significant changes in phenotype after PbNK65 infection, and treatment of PbNK65-infected mice with 4-octyl itaconate did not affect disease severity either. However, in the PcAS model, ACOD1 deficiency worsened the disease, as indicated by increased weight loss, higher clinical scores, and elevated parasitemia. Therefore, in contrast to the findings in recent literature, our study shows that itaconate does not contribute to susceptibility, but rather provides limited protection to malaria.PMID:40346757 | DOI:10.1002/eji.202451595

Antonie Van Leeuwenhoek. 2025 May 10;118(6):77. doi: 10.1007/s10482-025-02087-8.ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) is one of the most alarming antibiotic-resistant pathogens causing nosocomial and community-acquired infections. Actinomycetes, particularly Streptomycetes, have historically been a major source of natural products including anti-MRSA agents. Hence, we designed this study to isolate new anti-MRSA natural products from Streptomycetes aided by liquid chromatography-electrospray ionization-high resolution mass spectrometry (LC-ESI-HRMS)-based metabolomics data analysis and dereplication study to select the best fractions for isolation work. Following this approach, two new natural products, namely, (4-propylphenyl) methane-diazonium (1) and (4E)-6-oxooctadec-4-enoic acid (2) and three known compounds, 8-methyl-5-oxononanoic acid (4), 15-methylhexadecanoic acid (5), and (Z)-14-methylpentadecenoic acid (6) were isolated from two soil Streptomyces sp. Additionally, (9E)-11-hydroxyoctadec-9-enoic acid (3) was recovered for the first time from Streptomycetes. The minimum inhibitory concentration (MIC) of compounds 1, 5, and 6 against MRSA were 128, 64, and 64 µg/mL respectively. The compounds were slightly more active against B. subtilis with MIC values of 64, 64, and 32 µg/mL, respectively. Our research adds to the growing knowledge about the importance of combining sophisticated analytical methods in the chemical profiling of the fractions with the outcomes of the bioassays throughout the subsequent fractionation processes to help isolate new secondary metabolites from natural sources.PMID:40347296 | DOI:10.1007/s10482-025-02087-8

Nat Prod Res. 2025 May 10:1-9. doi: 10.1080/14786419.2025.2500738. Online ahead of print.ABSTRACTAn in-depth genomic and metabolomic investigation was conducted on the endophytic fungus Penicillium turbatum BLH34, isolated from Macleaya cordata. Hybrid sequencing (Illumina-Nanopore) generated a high-quality 27.9 Mb genome (GC 48.6%) encoding 9798 proteins, with functional annotation linking 5350 genes to the NCBI non-redundant database and 3404 to KEGG pathways. AntiSMASH analysis uncovered 35 biosynthetic gene clusters (BGCs), 23 of which lacked homology to known pathways, highlighting BLH34's potential for novel metabolite discovery. Molecular networking (GNPS) and LC-MS/MS identified 19 specialised metabolites, including antimicrobial polyketides. Bioassays demonstrated potent inhibition against Staphylococcus aureus (36 mm), Bacillus subtilis (28 mm) and Escherichia coli (24 mm), underscoring its pharmaceutical relevance.PMID:40347091 | DOI:10.1080/14786419.2025.2500738

Integr Cancer Ther. 2025 Jan-Dec;24:15347354251335599. doi: 10.1177/15347354251335599. Epub 2025 May 9.ABSTRACTSolanum lycopersicum L. Moench (Tomato) is a rich source of bioactive compounds. This study investigated the anticancer potential of S. lycopersicum roots methanol extract (TMESLR) and their nanocrystals (TMESLR-NCs) against breast (MCF-7), hepatocellular (HepG2), and colon (Caco-2) cancer cell lines, for the first time. TMESLR exhibited significant cytotoxicity against all 3 cell lines, with the nanocrystals demonstrating enhanced activity, Caco-2, MCF-7, and HepG2 cells with IC50 values of 9.69 ± 0.6, 12.52 ± 0.58, and 14.34 ± 0.62 µg/mL, respectively. Whereas, the prepared TMESLR-NCs displayed significantly the highest cytostatic potential against Caco-2 with IC50 value of 5.733 ± 0.29 µg/mL. Metabolomic profiling revealed 17 secondary metabolites, including flavonoids, phenolic acids, and terpenoids. In silico analyses, including PPI network construction, GO enrichment, and KEGG pathway analysis, highlighted the involvement of apoptotic pathways, p53 signaling, and TNF signaling in the anticancer effects of TMESLR. Molecular docking studies identified chlorogenic acid and inosine as potential inhibitors of Histone Deacetylase 2 (HDAC2). Inosine (6) displayed a superior docking score of -7.86 kcal/mol, interacting with critical residues GLY154, ASP269, and HIS146. On the other hand, chlorogenic acid (12) achieved a docking score of -7.32 kcal/mol, forming stable interactions with TYR308, PHE210, and LEU276 residues. These findings suggest that TMESLR and TMESLR-NCs possess promising anticancer activity and warrant further investigation as potential therapeutic agents.PMID:40346830 | DOI:10.1177/15347354251335599

Sci Rep. 2025 May 9;15(1):16204. doi: 10.1038/s41598-025-00734-8.ABSTRACTAlthough synthetic UV filters are widely used for skin photoprotection, growing concerns about their environmental and health impacts underscore the need for new, effective photoprotective products. This study aimed to develop a screening methodology for selecting brown macroalgae extracts with potential photoprotective activity. The approach integrates in vitro photoprotection assays, antioxidant TLC-DPPH assays, and HPLC-DAD metabolic profiling of 17 algal samples from the Dictyota, Canistrocarpus, Stypopodium, Sargassum, Lobophora, Padina, and Turbinaria genera. The results revealed concentration-dependent sun protection factor (SPF) values ranging from 0.403 to 2.915, UVA ratios (UVAr) ranging from 0.167 to 3.623, critical wavelengths (λc) ranging from 335 to 393 nm, and antioxidant DPPH-TLC activity in 10 of the evaluated extracts. These findings were correlated with the HPLC-DAD metabolic profile using the Multivariate Curve Resolution- Alternating Least Squares (MCR-ALS) algorithm and multivariate data analysis tools. Extracts from Canistrocarpus cervicornis (CCe) and Stypopodium zonale (SS) presented the most promising photoprotective activity. Through NMR and MS analysis, 2,5,7-trihydroxy-2-pentadecylchroman-4-one (1), fucoxanthin, pheophytin a, and pheophorbide a were identified as the main contributors to this activity. This methodology was successfully implemented and could be further used to screen for photoprotective activity in algal species.PMID:40346135 | DOI:10.1038/s41598-025-00734-8

J Oral Rehabil. 2025 May 9. doi: 10.1111/joor.14003. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: Burning mouth syndrome (BMS) is considered a multifactorial condition. The study aimed to investigate the association between BMS and cognitive impairment (CI), as well as the proteomic and metabolomic characteristics.MATERIALS AND METHODS: A total of 42 BMS patients and 23 healthy controls were recruited from August 2022 to August 2024 to analyse the relationship between BMS, psychological factors and cognitive function. Saliva samples were collected for comprehensive proteomic and metabolomic analyses, followed by validation studies.RESULTS: The mini-mental state examination (MMSE) indicated a significantly higher prevalence of CI in the BMS group (50.00%) compared to the healthy control group (8.70%) (p = 0.001). Logistic regression analysis revealed that BMS incidence was negatively correlated with MMSE scores and positively correlated with depression scores (both p < 0.05). Proteomics and metabolomics identified 197 differential proteins and 208 differential metabolites in the BMS group relative to the healthy control group. Additionally, there were 407 differential proteins and 344 differential metabolites in the BMS with cognitive impairment (BC) group compared to the BMS with noncognitive impairment (BnC) group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of combined proteomics and metabolomics data revealed the involvement of the arachidonic acid metabolic pathway and salivary secretion pathway in BMS and CI respectively.CONCLUSION: Higher levels of depression and lower cognitive function appear to be more closely associated with BMS. The pathways of arachidonic acid metabolism and salivary secretion may play significant roles in the pathogenesis of BMS and CI respectively.PMID:40346710 | DOI:10.1111/joor.14003

J Exp Clin Cancer Res. 2025 May 9;44(1):141. doi: 10.1186/s13046-025-03404-9.ABSTRACTBACKGROUND: Tumors often evade immune surveillance by limiting T cell infiltration. In non-small cell lung cancer (NSCLC), increased infiltration of CD8+ T cells is associated with a favorable response to immunotherapy. While BIN1 is recognized as a tumor suppressor gene, its role in shaping the tumor microenvironment in NSCLC has yet to be fully clarified.METHODS: To investigate the relationship between BIN1 expression and CD8+T cell infiltration in NSCLC, we performed a comprehensive data analysis utilizing clinical information from NSCLC patients. BIN1 expression levels in NSCLC tissues were evaluated, and their correlation with CD8+T cells infiltration and patient survival outcomes was examined. Loss-of-function strategies targeting BIN1 were applied in syngeneic NSCLC mouse models to assess its functional significance. Tumor growth was monitored, and immune cell populations were analyzed in terms of frequency and functionality through mass cytometry and flow cytometry techniques. Cytokine secretion was profiled using multiplex assays. Additionally, RNA sequencing, immunoprecipitation-mass spectrometry, and molecular docking were employed to confirm direct interactions between BIN1 and cytokine-encoding genes. Finally, the regulatory role of BIN1 in ferroptosis in NSCLC cells were explored using metabolomics analysis, ROS measurement, and MDA detection.RESULTS: We observed that BIN1 expression is downregulated in NSCLC tumor tissues, with its reduced expression strongly associated with advanced disease progression and poor prognosis. Bioinformatics analysis of immune infiltration in human NSCLC samples revealed a positive correlation between BIN1 expression in NSCLC tissues and CD8+ T cell infiltration. Furthermore, the prognostic impact of BIN1 on NSCLC patients is strongly linked to the level of CD8+ T cell infiltration. In syngeneic mouse models, the knockout of BIN1 in NSCLC cells significantly inhibited CD8+ T cell infiltration and impaired their cytotoxic function, facilitating tumor immune evasion. Mechanistically, we demonstrated that BIN1 directly interacts with G3BP1, and its knockout stabilizes G3BP1. This, in turn, promotes STAT1 degradation and reduces the secretion of T cell-recruiting chemokines such as CXCL10 and CCL5. Finally, our findings reveal that BIN1 influences ferroptosis in NSCLC cells through the G3BP1/STAT1/GSH pathway, thereby regulating NSCLC cell proliferation, migration, and invasion.CONCLUSION: This study highlights the crucial role of the BIN1/G3BP1/STAT1/CD8+ tumor-infiltrating lymphocyte signaling pathway in the progression of NSCLC and its mechanisms of immune evasion. This fundings lay a foundation for the development of BIN1-targeted therapies aimed at improving tumor immunogenicity and transforming immunologically "cold" NSCLC into a more responsive disease.PMID:40346580 | DOI:10.1186/s13046-025-03404-9

BMC Musculoskelet Disord. 2025 May 9;26(1):457. doi: 10.1186/s12891-025-08703-y.ABSTRACTBACKGROUND: Skeletal muscle possesses a robust regenerative capacity and can effectively repair itself following injury. However, research on the metabolic changes during skeletal muscle regeneration in large animals remains relatively limited. Therefore, in this study, we used pigs as a model and applied non-targeted LC-MS/MS metabolomic technology to reveal the metabolic changes during skeletal muscle regeneration, and conducted an in-depth exploration of important signaling pathways, which can provide a reference for further research on the mechanisms promoting skeletal muscle regeneration.METHODS: In this study, we used 18 piglets aged 35 days and weighing 7.10 ± 0.90 kg to construct a skeletal muscle regeneration model. These piglets were randomly divided into three treatment groups (n = 6) and injected with cardiotoxins (CTX) in the right longissimus dorsi muscle. They were euthanized on the 1st, 4th, and 16th days post-injection to collect right longissimus dorsi muscle samples as the treatment group. Additionally, the left longissimus dorsi muscle of piglets on the 4th day post-injection was selected as the control group. Phenotypic changes in skeletal muscle regeneration were determined through H&E staining, immunofluorescence, and Western Blot analysis, and LC-MS/MS untargeted metabolomics technology was utilized to explore the differential expressed metabolites (DEMs) involved in skeletal muscle regeneration.RESULTS: Phenotyping results showed that the regeneration model showed 3 stages of inflammation, regeneration and remodeling, which indicated successful model construction. Non-targeted LC-MS/MS metabolomics analysis showed significant differences in the structure of metabolites in these 3 stages. (1) In the inflammatory stage, a total of 198 DEMs were identified, which were mainly enriched in the pathways regulating the inflammatory response. (2) in the repair stage, 264 DEMs were identified, which were mainly enriched in pathways that inhibit inflammatory response and promote protein synthesis. (3) During the remodeling stage, 102 DEMs were identified, which were mainly enriched in the pathways that inhibit protein depletion and promote protein deposition. Temporal expression analysis revealed metabolites consistent with changes in the skeletal muscle regeneration process and found that these metabolite functions were mainly enriched in inhibiting inflammatory responses, alleviating myofibrillar lysis, and promoting muscle growth. Among them, (R)-Lipoic acid, 8-Hydroxyguanosine, and Uridine 5'-monophosphate maybe key metabolites associated with skeletal muscle regeneration.CONCLUSION: The skeletal muscle regeneration mechanism was systematically explored, and the metabolite time series analysis during skeletal muscle regeneration revealed some key metabolites that reflect the degree of skeletal muscle damage.PMID:40346552 | DOI:10.1186/s12891-025-08703-y

Cell Mol Biol Lett. 2025 May 9;30(1):58. doi: 10.1186/s11658-025-00737-3.ABSTRACTBACKGROUND: Testicular aging has profound effects on spermatogenesis, sperm function, and the spermatogenic microenvironment, contributing to reduced male fertility. However, the precise molecular mechanisms by which mitochondria influence spermiogenesis during aging still remain largely unclear.METHODS: Vha68-3 KO flies were generated using the CRISPR/Cas9 technique. Testicular phenotypes and functions were mainly observed through immunofluorescence staining and transmission electron microscopy. Multi-omics study was mainly conducted through single-cell RNA sequencing and transcriptome-metabolomics association analysis. Vha68-3 binding proteins were identified via liquid chromatography-tandem mass spectrometry. The therapeutic potential of modulating mitochondrial metabolism for testicular aging mainly relied on the dietary intake of related compounds in fruit flies.RESULTS: In this study, we identified Vha68-3, a testis-specific subunit of the V-type adenosine triphosphate (ATP) synthase, predominantly localized in the tails of elongated spermatids, as a key age-related regulator of male fertility and spermatid elongation in Drosophila testes. Crucially, Vha68-3 deficiency impaired mitochondrial homeostasis in elongated spermatids during testicular aging. Through a multi-omics approach, including single-cell transcriptomics, protein interaction mapping of Vha68-3, and transcriptome-metabolome integration, we identified pyruvate metabolism as a critical pathway disrupted by Vha68-3 deficiency. Moreover, dietary supplementation with pyruvate (PA), S-lactoylglutathione (SLG), and phosphoenolpyruvate (PEP) effectively alleviated mitochondrial dysfunction and testicular aging linked to Vha68-3 deficiency.CONCLUSIONS: Our findings uncover novel mechanisms by which mitochondrial metabolism regulates spermatid elongation and propose potential therapeutic strategies to combat mitochondrial metabolic disorders in aging testes.PMID:40346547 | DOI:10.1186/s11658-025-00737-3

Cardiovasc Diabetol. 2025 May 9;24(1):195. doi: 10.1186/s12933-025-02746-0.ABSTRACTBACKGROUND: Gestational diabetes mellitus (GDM), characterized by insulin resistance (IR) and β-cell dysfunction, is one of the most common complications of pregnancy with unmet needs of prevention methods.OBJECTIVE: To investigate the causal role of insulin resistance and metabolic pathways in the pathogenesis of GDM with our proposed high-dimensional systematic Mendelian randomization (hdsMR) framework.METHODS: Cases with GDM and controls with normal glucose tolerance were recruited at the University of Hong Kong-Shenzhen Hospital from 2015 to 2018. A total of 566 participants (aged > 18 years), including 274 with GDM, were enrolled after excluding subjects with major chronic diseases or long-term use of medications affecting glycolipid metabolism. Clinical characteristics and serum samples were collected during the GDM screening stage, and the genome and metabolome were tested. A novel hdsMR framework was proposed to estimate the causal role of IR index (Homeostasis Model Assessment of Insulin Resistance, HOMA-IR) and metabolic pathways in the pathogenesis of GDM.RESULTS: Our hdsMR method confirmed that HOMA-IR was causal to GDM (odds ratio, 1.17; 95% confidence interval, 1.04-1.32) and revealed that two metabolic pathways (glyoxylate and dicarboxylate metabolism pathway and lysine degradation pathway) mediated 14.6% and 8.4%, respectively, between HOMA-IR and GDM. In an independent validation cohort comprising 255 pre-diabetic individuals, we showed that both pathways could be intervened through diet (P < 0.05). Furthermore, glyoxylate and dicarboxylate metabolism pathway was significantly associated with adverse pregnancy outcomes in GDM.CONCLUSIONS: These results indicated that targeting specific metabolic pathways through dietary intervention is worth exploring as a possible GDM prevention approach, and hdsMR is more efficient in finding causal mediating metabolic pathways than traditional MR methods.PMID:40346526 | DOI:10.1186/s12933-025-02746-0

BMC Plant Biol. 2025 May 9;25(1):611. doi: 10.1186/s12870-025-06375-3.ABSTRACTBACKGROUND: Storage conditions affect the metabolome composition and quality of tobacco leaf and, therefore, its economic value. The present study was designed to reveal tobacco leaves' dynamic phytochemical and metabolite profile changes under three different storage conditions: natural (NT), mechanical (MC), and air-conditioning (AC). The 210,003 grade (Hubei Central Tobacco) was selected as the experimental material, and the changes in iodine value absorbance (IV), pH, polyphenols, plastid pigments, conventional chemical compositions, and metabolite profile were analyzed at different times (T0, starting day; T1, three months; T2, five months; and T3, nine months) during storage.RESULTS: The IV significantly increased with the storage duration, while the pH, polyphenols, and stromal pigments had the opposite trends. Lutein, β-carotene, and chlorogenic acid were significantly less degraded under MC and AC than NT. Neoxanthin and chlorophyll b were completely degraded at T3. The nicotine, total sugar, reducing sugar, and chlorine content significantly varied along with the storage duration, reaching their maximum values at T2 under MC and AC. The sugar/base ratio at T3 under MC and AC was 8.53 and 8.44, respectively, higher than in NT (5.85). LC-MS-based untargeted metabolomics analysis identified 124‒224, 138‒180, and 110‒153 significant differential accumulated metabolites (DAMs) under NT, MC, and AC, respectively. Biosynthesis of secondary metabolites was significantly induced under the three storage conditions between T0 and T3. Glutathione metabolism and oxidative phosphorylation were induced under NT. Biosynthesis of terpenoids and steroids was highly induced under AC.CONCLUSIONS: Our findings may facilitate the optimization of the storage conditions for better preservation of tobacco leaves.CLINICAL TRIAL NUMBER: Not applicable.PMID:40346464 | DOI:10.1186/s12870-025-06375-3

BMC Plant Biol. 2025 May 9;25(1):612. doi: 10.1186/s12870-025-06576-w.ABSTRACTThe ERF transcription factor can regulate the biosynthesis of various secondary metabolites, including triterpenoid saponins, in plants. DaERF9 has been found to be a potential regulatory factor in the accumulation of asperosaponin VI in Dipsacus asper. However, its underlying molecular mechanisms remain unclear. Here, we cloned the transcription factor DaERF9, which promotes the accumulation of asperosaponin VI in D.asper. Metabolomic analysis showed that wound stress significantly increased the content of asperosaponin VI and jasmonic acid, while the expression level of DaERF9 was markedly enhanced during this process, suggesting that DaERF9 plays a regulatory role in the wound-induced synthesis of asperosaponin VI by JA signaling pathway. Transgenic DaERF9 promoted the synthesis of precursor compounds of asperosaponin VI in Arabidopsis, activating the triterpenoid saponin biosynthesis pathway. MeJA induction enhanced the expression of the key enzyme gene DaHMGCR, which is involved in the synthesis of asperosaponin VI in transgenic DaERF9. Wound treatment markedly increased the transcriptional level of DaERF9 and the content of JA, and DaERF9 was able to interact with the DaHMGCR promoter, activating the activity of DaHMGCR. Overall, our findings suggest that DaERF9 plays a crucial role in the synthesis of asperosaponin VI in D. asper and elucidate the transcriptional regulatory mechanism of JA-induced accumulation of asperosaponin VI.PMID:40346454 | DOI:10.1186/s12870-025-06576-w