PubMed

Food Chem X. 2025 Apr 10;27:102453. doi: 10.1016/j.fochx.2025.102453. eCollection 2025 Apr.ABSTRACTWhile selenium (Se) fortification significantly influences plant secondary metabolism, there has been limited research on its effects on the phenolic profile of kiwifruit. This study aimed to characterize and compare the phenolic profile of Se-enriched and conventional kiwifruit. A total of 463 phenolic compounds were identified. Among these, nine common differential metabolites, including six flavonoids, two phenolic acids, and one lignan (massoniresinol), were identified between Se-enriched and conventional kiwifruit of the same variety. Further comparative analysis of diverse varieties indicated that massoniresinol was the sole differential metabolite. This metabolite was found to be significantly up-regulated in Se-enriched kiwifruit compared to conventional kiwifruit. In addition, correlation analysis showed that the total Se, phenol, and flavonoids content were highly significantly positively correlated with antioxidant activities in kiwifruit. These findings enhance our understanding of the phenolic composition in Se-enriched and conventional kiwifruit and provide a potential biomarker for distinguishing Se-enriched from conventional kiwifruit.PMID:40276232 | PMC:PMC12018201 | DOI:10.1016/j.fochx.2025.102453

Front Microbiol. 2025 Apr 10;16:1470731. doi: 10.3389/fmicb.2025.1470731. eCollection 2025.ABSTRACTINTRODUCTION: Post-weaning Diarrhea (PWD) is a kind of physiological stress diarrhea in Rex rabbits after weaning, which can lead to death in severe cases. Traditional Chinese medicine (TCM) has been widely used in animal due to its advantages of natural origin, diverse functions, safety, reliability, economy and environmental protection. Modified Yupingfeng Granule (MYPFG) is an improved Yupingfeng prescription based on the famous traditional Chinese prescription Yupingfeng (YPF), which is combined with other TCM and has obvious synergistic and additive activity in order to obtain an excellent natural medicine for PWD.METHODS: In this study, 120 weaned Rex rabbits were randomly allocated to 4 treatment groups, including control (CON), low dose (LD), medium dose (MD), high dose (HD). Rabbits were fed a control diet or a different MYPFG proportions of diet for 30 days. The study combined 16S rRNA analysis of intestinal microbiota and cecal contents metabolomics to explore the MYPFG effect on weaned Rex rabbits.RESULTS: MYPFG increased average daily gain, villus length to crypt depth ratio and decreased the feed to meat ratio, diarrhea frequency, mortality rate, depth of crypt (p < 0.05). The intestinal microbiota test found that MYPFG could change the abundances of Patescibacteria, Sphingobium, Ruminococcus, and Oxalobacter. Metabolomics analysis found that effect may be related to its regulation of Glycine, serine and threonine metabolism, Arginine and proline metabolism. Nicotinate and nicotinamide metabolism.DISCUSSION: MYPFG could regulate intestinal microbiota and change the metabolic pathway of some amino acids to alleviate the PWD in Rex rabbits.PMID:40276219 | PMC:PMC12020438 | DOI:10.3389/fmicb.2025.1470731

J Appl Microbiol. 2025 Apr 24:lxaf095. doi: 10.1093/jambio/lxaf095. Online ahead of print.ABSTRACTAIM: To search for active compounds produced by microorganisms isolated from the Antarctic environment, against biofilms of pathogenic bacteria Pseudomonas aeruginosa.METHODS AND RESULTS: Seven different bacteria from Antarctic were cultivated, and their secretome (supernatants of the culture media) extracted using liquid/liquid partition, rendering 41 fractions of different polarities. Assays were performed to quantify P. aeruginosa pathogenic bacterial growth and inhibition of biofilm formation. From the tested Antarctic isolates the apolar hexane extract fraction of N52R1 strain, identified as Bacillus siamensis, showed activity against P. aeruginosa biofilm formation and was fractionated by reverse phase chromatography, corroborated by Confocal Laser Scanning Microscopy images. Applying LC-MS/MS untargeted metabolomics it is suggested that these results were obtained by the action of lipopeptide molecules, particularly plipastatin and surfactin which has no previous report of activity upon the important pathogen P. aeruginosa. In vivo toxicity assays of the antibiofilm fraction of N52R1 upon the invertebrate G. mellonella was performed, showing no toxicity at up to 200 mg/kg.CONCLUSION: we demonstrate the relevance and diversity of compounds from Antarctic microorganisms, in order to find bioactive agents against P. aeruginosa biofilm formation.PMID:40275521 | DOI:10.1093/jambio/lxaf095

Lett Appl Microbiol. 2025 Apr 24:ovaf064. doi: 10.1093/lambio/ovaf064. Online ahead of print.ABSTRACTThe overuse of antibiotics has accelerated the emergence of antibiotic-resistant bacteria, necessitating alternative treatment options. Micromonospora spp., known for producing bioactive metabolites, is a promising source of novel antimicrobials. This study evaluated the antimicrobial potential of metabolic ethyl-acetate extracts from three Micromonospora strains against multidrug-resistant (MDR) Gram-negative clinical isolates of enteric origin.. Using the Kirby-Bauer modified disc diffusion method, following Clinical and Laboratory Standards Institute (CLSI) guidelines, the extract from Micromonospora strain 65SH exhibited the most potent activity, with minimum inhibitory concentrations (MICs) of 25 µg/ml against Enterobacter aerogenes and 12.5 µg/ml against Escherichia coli. 16S rRNA gene sequencing identified the strain as closely related to Micromonospora fluminis (99.6% similarity). Further analysis using LC-QTOF-MS/MS non-targeted metabolomics identified six bioactive compounds-melibiose, oligomycin A, queuine, heptelidic acid, diethyl phthalate, and 2'-deoxyguanosine-linked to the inhibition of bacterial enzymes essential for proliferation. Molecular modeling suggested these compounds disrupt E. coli ATP synthase and inhibit ATP-dependent bacterial topoisomerases. This study integrates metabolomics, molecular docking, and genomics, offering robust mechanistic insights into ATP synthase inhibition. Future research will include fecal isolate testing, detailed structural elucidation using NMR, and experimental validation to explore the therapeutic potential of Micromonospora-derived compounds.PMID:40275498 | DOI:10.1093/lambio/ovaf064

Stem Cell Res Ther. 2025 Apr 24;16(1):207. doi: 10.1186/s13287-025-04317-2.ABSTRACTBACKGROUND: Extracellular vesicles (EVs) derived from human organoids are phospholipid bilayer-bound nanoparticles that carry therapeutic cargo. However, the low yield of EVs remains a critical bottleneck for clinical translation. Vertical-Wheel bioreactors (VWBRs), with unique design features, facilitate the scalable production of EVs secreted by human blood vessel organoids (BVOs) under controlled shear stress, using aggregate- and microcarrier-based culture systems.METHODS: Human induced pluripotent stem cell-derived BVOs cultured as aggregates or on Synthemax II microcarriers within VWBRs (40 and 80 rpm) were compared to static controls. The organoids were characterized by metabolite profiling, flow cytometry, and gene expression of EV biogenesis markers. EVs were characterized by nanoparticle tracking analysis, electron microscopy, and Western blotting. Lipidomics provided insights into EV lipid composition, while functional assays assessed the impact of EVs in a D-galactose-induced senescence model.RESULTS: VWBR cultures showed more aerobic metabolism and higher expression of EV biogenesis genes compared to the static control. EVs from different conditions were comparable in size, but the yields were significantly higher for microcarrier and dynamic cultures than static aggregates. Lipidomic profiling revealed minimal variation (< 0.36%) in total lipid content; however, distinct differences were identified in lipid chain lengths and saturation levels, affecting key pathways such as sphingolipid and neurotrophin signaling. Human BVO EVs demonstrated the abilities of reducing oxidative stress and increasing cell proliferation in vitro.CONCLUSIONS: Human BVOs differentiated in VWBRs (in particular 40 rpm) produce 2-3 fold higher yield of EVs (per mL) than static control. The bio manufactured EVs from VWBRs have exosomal characteristics and therapeutic cargo, showing functional properties in in vitro assays. This innovative approach establishes VWBRs as a scalable platform for producing functional EVs with defined lipid profiles and therapeutic potential, paving the way for future in vivo studies.PMID:40275401 | DOI:10.1186/s13287-025-04317-2

Acta Neuropathol Commun. 2025 Apr 24;13(1):83. doi: 10.1186/s40478-025-01997-y.ABSTRACTVPS13A disease (chorea-acanthocytosis), is an ultra-rare autosomal recessive neurodegenerative disorder caused by mutations of the VPS13A gene encoding Vps13A. Increased serum levels of the muscle isoform of creatine kinase associated with often asymptomatic muscle pathology are among the poorly understood early clinical manifestations of VPS13A disease. Here, we carried out an integrated analysis of skeletal muscle from Vps13a-/- mice and from VPS13A disease patient muscle biopsies. The absence of Vps13A impaired autophagy, resulting in pathologic metabolic remodeling characterized by cellular energy depletion, increased protein/lipid oxidation and a hyperactivated unfolded protein response. This was associated with defects in myofibril stability and the myofibrillar regulatory proteome, with accumulation of the myocyte senescence marker, NCAM1. In Vps13a-/- mice, the impairment of autophagy was further supported by the lacking effect of starvation alone or in combination with colchicine on autophagy markers. As a proof of concept, we showed that rapamycin treatment rescued the accumulation of terminal phase autophagy markers LAMP1 and p62 as well as NCAM1, supporting a connection between impaired autophagy and accelerated aging in the absence of VPS13A. The premature senescence was also corroborated by local activation of pro-inflammatory NF-kB-related pathways in both Vps13a-/- mice and patients with VPS13A disease. Our data link for the first time impaired autophagy and inflammaging with muscle dysfunction in the absence of VPS13A. The biological relevance of our mouse findings, supported by human muscle biopsy data, shed new light on the role of VPS13A in muscle homeostasis.PMID:40275365 | DOI:10.1186/s40478-025-01997-y

Sci Rep. 2025 Apr 24;15(1):14317. doi: 10.1038/s41598-025-95357-4.ABSTRACTGut microbiota variations in response to environmental and nutritional factors are of great significance as gut microbiota plays an integral role in nutrient metabolism, immunity, health, and disease conditions. In this context, limited studies investigated variations of gut microbiota in response to different feeding systems and environmental conditions. The current study obtained fresh fecal samples from house-fed (LS) and grazing yaks (LF) from Linzhou County. 16 S rRNA amplicon sequencing of the V3-V4 and internal transcribed spacer 2 (ITS2) domains generated 16,332 bacterial and 2345 fungus amplicon sequence variants (ASVs). Alpha and beta diversity indices revealed significant variations (p > 0.05) in gut microflora between the two groups. At the phylum level, Firmicutes, Actinobacteriota, Bacteroidota, and Patescibacteria regarding bacteria, and Ascomycota and Basidiomycota regarding fungi dominated. At the genus level, UCG-005, Rikenellaceae_RC9_gut_group, Clostridium_sensu_stricto_1, g__Muribaculaceae, UCG-010, [Eubacterium]_coprostanoligenes_group, Turicibacter, Alistipes, Prevotellaceae_UCG-003, UCG-009, Blautia, dgA-11_gut_group, Candidatus_Saccharimonas dominated in LS, while Anthrobacter and Terrisporobacter dominated in the LF group. Fungal genera like Myrothecium and Plectosphaerella dominated the LS group, while Neoascochyta, Paraphaeosphaeria, and Hypocreales dominated the LF group. Also, significant variations (p > 0.05) in gene expressions were found between the two groups. These findings provide insights into yak gut microbiota adaptations and metabolic changes in response to varied environmental conditions and can provide valuable information, optimizing feeding strategies after identifying specific differences between grazing and house-fed yaks, reducing environmental impacts, and improving yaks' health and productivity in specific geographical settings.PMID:40274860 | DOI:10.1038/s41598-025-95357-4

Nat Commun. 2025 Apr 24;16(1):3867. doi: 10.1038/s41467-025-59307-y.ABSTRACTThe ability of cancer cells to evade immune destruction is governed by various intrinsic factors including their metabolic state. Here we demonstrate that inactivation of dihydroorotate dehydrogenase (DHODH), a pyrimidine synthesis enzyme, increases cancer cell sensitivity to T cell cytotoxicity through induction of ferroptosis. Lipidomic and metabolomic analyses reveal that DHODH inhibition reduces CDP-choline level and attenuates the synthesis of phosphatidylcholine (PC) via the CDP-choline-dependent Kennedy pathway. To compensate this loss, there is increased synthesis from phosphatidylethanolamine via the phospholipid methylation pathway resulting in increased generation of very long chain polyunsaturated fatty acid-containing PCs. Importantly, inactivation of Dhodh in cancer cells promotes the infiltration of interferon γ-secreting CD8+ T cells and enhances the anti-tumor activity of PD-1 blockade in female mouse models. Our findings reveal the importance of DHODH in regulating immune evasion through a CDP-choline dependent mechanism and implicate DHODH as a promising target to improve the efficacy of cancer immunotherapies.PMID:40274823 | DOI:10.1038/s41467-025-59307-y

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 25. doi: 10.1007/s00210-025-04186-9. Online ahead of print.ABSTRACTDepression is a serious mental disease, and its accompanying abnormal changes in peripheral organs, including the kidney, are easy to be ignored. The metabolic abnormalities of the kidney and other organs will inevitably affect the progress of depression through the circulatory system. Quercetin has attracted much attention as a flavonoid with anti-inflammatory, antioxidant, neuroprotective, and antidepressant potential. Chronic unpredictable mild stress (CUMS) model is a reliable and effective animal model of depression. We hypothesize that quercetin has the potential to alleviate the abnormalities in renal metabolic profile induced by CUMS. An ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) platform was used to analyze renal metabolites, and the obtained data were analyzed using the Progenesis QI software for peak alignment, peak picking, and data normalization. Based on the data processing method with fold change > 2 or < 0.5, the false discovery rate corrected was p < 0.05, and a variable importance in projection score was > 1; a total of 16 differential metabolites were identified, including L-histidine, D-glucose 1-phosphate, cytidine, D-Ribulose 5-phosphate, D-xylulose 5-phosphate, uridine monophosphate (UMP), uracil, glucuronide, prostaglandin-F2α (PGF2ɑ), arachidonic acid, 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), 14,15-epoxyeicosatrienoic acid (14,15-EET), deoxycytidine, anserine, carnosine, and PC (14:0). Among them, the intensities of anserine, carnosine, L-histidine, and 14,15-EET were significantly reduced (p < 0.01), while the intensities of other metabolites were significantly increased in the CUMS group compared with the control group (p < 0.01). When CUMS model rats received high-dose quercetin treatment, the intensities of above differential metabolites were significantly restored (p < 0.05 or p < 0.01). Further, pathway enrichment analysis revealed abnormalities in arachidonic acid (AA) metabolism, pyrimidine metabolism, amino acid metabolism, and pentose and glucuronide acid interconversion in the kidney. The renal histopathological examination revealed CUMS induced renal tubular epithelial cell shedding and glomerular atrophy. High-dose quercetin can improve renal metabolic disorders and renal pathological changes caused by CUMS. Mechanistically, quercetin improves renal metabolic disorders by enhancing the antioxidant capacity and inhibiting the secretion of inflammatory factors. Moreover, quercetin can regulate renal AA metabolism disorder by inhibiting soluble epoxide hydrolase activity. High-dose quercetin (50 mg/kg bw) has a certain protective effect on kidney damage induced by CUMS, providing new strategies for quercetin to prevent depression.PMID:40274622 | DOI:10.1007/s00210-025-04186-9

Zhonghua Liu Xing Bing Xue Za Zhi. 2025 Apr 10;46(4):557-565. doi: 10.3760/cma.j.cn112338-20241209-00780.ABSTRACTObjective: To investigate the prospective associations between plasma metabolites and the risks of all-cause and cause-specific mortality among Chinese adults. Methods: This study analyzed plasma metabolomics data from 2 183 healthy adults in the China Kadoorie Biobank (CKB), measured using targeted mass spectrometry. Cox proportional hazards regression models were used to examine the associations between 630 metabolites and the risk of all-cause mortality. Cause-specific hazard regression models evaluated the associations between metabolites and cardiovascular disease (CVD) risks, cancer, and other-cause mortality. Stepwise regression was used to identify key metabolites independently associated with all-cause mortality, and the area under the receiver operating characteristic curve (AUC) was calculated to assess the improvement in predictive performance when these metabolites were added to traditional risk prediction models. Results: The mean age of the participants was (53.2±9.8) years, 65.1% of whom were female. During a median follow-up of 14.5 years, 231 deaths occurred. A total of 44 metabolites were significantly associated with the risk of all-cause mortality [false discovery rate (FDR)-adjusted P<0.05], primarily including triglycerides, ceramides, and amino acids. Additionally, 29 and 15 metabolites were found to be associated with cancer and other-cause mortality, respectively, but no metabolites were significantly associated with CVD mortality after FDR corrections. Adding 14 metabolites independently associated with all-cause mortality into the traditional prediction model significantly improved its predictive performance. Specifically, incorporating metabolites into the traditional model, which already included laboratory biomarkers, increased the AUC to 0.798 (95%CI: 0.755-0.843), an improvement of 0.088 compared to the traditional model (P<0.001). Conclusions: Multiple metabolites are significantly associated with mortality risk and can substantially improve the accuracy of mortality risk prediction models. These findings provide new insights into the physiological mechanisms of aging and offer valuable clues for personalized health risk assessment.PMID:40274560 | DOI:10.3760/cma.j.cn112338-20241209-00780

Anal Chim Acta. 2025 Jun 15;1355:344005. doi: 10.1016/j.aca.2025.344005. Epub 2025 Apr 2.ABSTRACTBACKGROUND: Isotope tracing experiments in cellular metabolomics are challenged by the multiple isomers and in-source fragments, which need to be considered to obtain unbiased isotopologue ratio measurements. Thus, both, selectivity and sensitivity are key requirements for customized workflows. Trapped ion mobility spectrometry (TIMS) introduces an additional separation dimension to mass spectrometry, separating otherwise co-eluting isomers by measuring the ion mobility of a molecule. This study shows for the first time, the potential of this MS platform for accurate isotopologue assessment as showcased in isotope tracer experiments using mammalian cells.RESULTS: The validation exercise focused on spectral accuracy, precision, and metabolite detection capabilities and comprised independent measurements on an orbitrap-based platform. Hydrophilic interaction chromatography, in combination with TIMS-TOF-MS delivered excellent results, with a minimum trueness bias and excellent precision (CV%) between 0.3 % and 6.4 %. The ion mobility separation allowed for differentiation of the otherwise co-eluting isomers fructose-6-phosphate (F6P) and glucose-1-phosphate (G1P). Overall, isotopologue distributions were in good agreement upon crossvalidation with the orbitrap platform. Finally, a proof-of-concept tracer study addressed the activity of the glycolysis and the pentose phosphate pathway (PPP) in resting and endotoxin activated macrophages. We confirmed an activation of glycolysis and PPP in LPS activated macrophages, but found a potentially reduced relative contribution of glucose-6-phosphate (G6P) to increased F6P pools. Our findings imply that TIMS is a powerful technology for the reliable measurements of isotope distribution analysis in metabolic tracing experiments.SIGNIFICANCE: By implementation of ion mobility, it is now possible to generate distinct isotopologue patterns for G1P and F6P in isotope tracer experiments. F6P plays a crucial role in glycolysis and PPP, highlighting the importance of precise analytical measurements. This is particularly true for metabolic studies in immunology and cancer research.PMID:40274332 | DOI:10.1016/j.aca.2025.344005

J Invest Dermatol. 2025 Apr 22:S0022-202X(25)00414-2. doi: 10.1016/j.jid.2025.02.157. Online ahead of print.ABSTRACTHyperproliferative inflammatory skin disease (HISD) is frequently seen in rare monogenic diseases of cholesterol metabolism and responds to topical cholesterol/statin. We hypothesised that aberrant cholesterol metabolism within keratinocytes could be important in HISD more generally, driven by either immunological or lipid pathway genetic variation. Whilst other epidermal lipids have been well characterised in HISDs, cholesterol and its metabolites have not. Using GCxGC 3D mass spectrometry we find here that primary keratinocytes from diverse monogenic HISDs (Inflammatory Linear Verruvous Epidermal Naevus ILVEN n=14, CHILD syndrome n=2), and from plaque psoriasis (n=2), demonstrate significantly reduced mean cholesterol across all patient groups compared to controls. This striking abnormality appears causally implicated, as treatment in vitro with cholesterol and statin rescues the cellular hyperproliferation. Using SNPsea and burden analysis of large international psoriasis cohorts we go on to show that GWAS hits are significantly enriched in proximity to genes encoding lipid metabolic pathways, and that rare variants in lipid metabolic pathway genes are significantly enriched in psoriasis patients. These data identify a final common pathway of aberrant keratinocyte cholesterol metabolism in HISD, which should be drugged topically to avoid first pass metabolism. In parallel we implicate genetic variation in lipid pathway genes in psoriasis susceptibility, potentially explaining the co-morbidity of abnormal serum lipid profile and psoriasis.PMID:40274221 | DOI:10.1016/j.jid.2025.02.157

Environ Toxicol Pharmacol. 2025 Apr 22:104704. doi: 10.1016/j.etap.2025.104704. Online ahead of print.ABSTRACTPolystyrene microplastics (PS-MPs) pose significant risks to honeybee health. However, how microplastics (MPs) adversely influence honeybee survival through the gut pathway, especially the metabolic processes, remains poorly understood. To conduct the experiment, the honeybees (Apis mellifera L.) were exposed to PS-MPs (0.5 μm and 5 μm) at environmental concentrations of 25mg/L and 50mg/L for 21 days. Results revealed that PS-MPs reduced honeybee survival rates and food consumption. The accumulation of PS-MPs in honeybee guts caused structural damage to gut walls and elevated oxidative stress levels. Additionally, MPs altered gut microbial communities, with a decrease in Lactobacillus and an increase in Bartonella. Gut metabolomics analysis indicated that PS-MPs disrupted metabolic pathways, upregulated amino acid and carbohydrate metabolism, and downregulated alpha-linolenic acid and lipid metabolism. Our study offers important insights into the physiological effects of accumulated MPs on honeybees, highlighting the critical need for effective strategies to manage environmental pollutants.PMID:40274082 | DOI:10.1016/j.etap.2025.104704

Mol Genet Metab. 2025 Apr 18;145(2):109113. doi: 10.1016/j.ymgme.2025.109113. Online ahead of print.ABSTRACTBOLA3 is one of the proteins involved in the assembly and transport of [4Fe-4S] clusters, which are incorporated into mitochondrial respiratory chain complexes I and II, aconitase, and lipoic acid synthetase. Pathogenic variants in the BOLA3 gene cause a rare condition known as multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia, characterized by life-threatening lactic acidosis, nonketotic hyperglycinemia, and hypertrophic cardiomyopathy. The aim of this study was to elucidate the biochemical characteristics of patients with BOLA3 variants and to clarify the role of BOLA3 protein in humans. The characteristics, clinical course, and biochemical data of eight Japanese patients with BOLA3 pathogenic variants were collected. In addition, metabolomic analyses were performed using capillary electrophoresis time-of-flight mass spectrometry, blue native polyacrylamide gel electrophoresis (BN-PAGE)/Western blot analysis of mitochondrial respiratory chain complexes, and in-gel enzyme staining of mitochondrial respiratory chain complexes of fibroblasts from all eight patients. Metabolomic data were compared between the eight patients with BOLA3 variants and three control samples using Welch's t-test. In the metabolomic analysis, levels of lactic acid, pyruvic acid, alanine, tricarboxylic acid (TCA) cycle intermediates (such as α-ketoglutaric acid and succinic acid), branched-chain amino acids, and metabolites of lysine and tryptophan were significantly elevated in the BOLA3 group. Data collected during the patients' lives showed increased lactic acid and glycine levels. In BN-PAGE/Western blot analysis and in-gel enzyme staining, bands for complexes I and II were barely detectable in all eight cases. These results indicate that BOLA3 variants decrease the activity of lipoic acid-dependent proteins (pyruvate dehydrogenase complex, α-ketoglutarate dehydrogenase, 2-oxoadipate dehydrogenase, branched-chain ketoacid dehydrogenase, and the glycine cleavage system), as well as mitochondrial respiratory chain complexes I and II, but do not affect aconitase. Thus, it is believed that BOLA3 is involved in transporting [4Fe-4S] clusters to respiratory chain complexes I and II and lipoic acid synthetase, but does not interfere with aconitase. These findings suggest that while lipoic acid supplementation or vitamin cocktails may provide benefits, the impaired [4Fe-4S] cluster pathway itself should be targeted for treatment to improve the extensive metabolic abnormalities caused by BOLA3 deficiency.PMID:40273865 | DOI:10.1016/j.ymgme.2025.109113

J Hazard Mater. 2025 Apr 22;493:138371. doi: 10.1016/j.jhazmat.2025.138371. Online ahead of print.ABSTRACTMicroplastics comprise a heterogeneous group of polymer particles that vary in chemical properties, size, and shape, that may influence their environmental and in vivo behavior. Numerous in vitro and in vivo studies show induction of oxidative stress and metabolic disturbances. Valid critique regarding unrealistically high concentrations or additives within standard materials calls some results into question. Here, we present a novel protocol for the detergent-free production of polyethylene terephthalate (PET) and biodegradable poly(butylenadipat-co-terephthalat) (PBAT) micro- and nanoplastic particles (MNPs) as model microplastics for research. The particles were produced by dissolution precipitation from trifluoroacetic acid (TFA) for PET or tetrahydrofuran (THF)/ethanol for PBAT. Different PET sources were investigated for MNPs production. PET MNPs in the size range of 170-1000 nm with up to 80 % yield were produced from pellets as starting material. Particle size can be adjusted by ultrasounding. The non-toxic concentration range for two commonly used detergents was assessed by means of MTT assay. PET particles with a Zeta-potential of -45 were stable in aqueous suspension with and without detergents at neutral pH. Biodegradable PBAT particles in the micro- and nanometer range were produced by adapting the PET precipitation protocol. These high-yield production protocols provide additive-free authentic PET and PBAT MNPs for research.PMID:40273850 | DOI:10.1016/j.jhazmat.2025.138371

Poult Sci. 2025 Apr 20;104(7):105180. doi: 10.1016/j.psj.2025.105180. Online ahead of print.ABSTRACTThe low fertility of geese has long constrained the development of the geese industry. Sperm quality plays a critical role in fertility, and sperm mobility (SM) serves as a key indicator of sperm quality. However, the molecular mechanisms underlying SM remain largely unexplored. The objective of this study was to identify molecular markers associated with SM in the epididymis of Zi geese (Anser cygnoides L.). The SM of 40 one-year-old ganders was assessed. Based on SM values, six ganders were selected: three with the highest SM (H group: n = 3, SM = 0.43 ± 0.02) and three with the lowest SM (L group: n = 3, SM = 0.10 ± 0.01, P < 0.001). Semen quality parameters, fertility, and hormone levels were measured in both groups. Epididymal tissues from the six ganders were subjected to transcriptomic and metabolomic analyses. Results identified 438 differentially expressed genes (DEGs) between the groups, primarily associated with transmembrane transport of proteins and ions. These DEGs were enriched in pathways such as "alanine, aspartate and glutamate metabolism," "butanoate metabolism," and the "PPAR signaling pathway." Among these, ATP12A, ATP1B4, and CNDP1 were identified as key genes regulating SM. Additionally, 486 metabolites showed significant differences between the groups in both positive and negative ion modes. Integration of transcriptomic and metabolomic data revealed critical gene-metabolite pairs, including CNDP1-citric acid, implicated in SM regulation. Notably, the "arginine biosynthesis" pathway was significantly enriched by both DEGs and differential metabolites. In conclusion, this study provides novel insights into the molecular mechanisms regulating SM in the epididymis and lays a theoretical foundation for geese breeding programs.PMID:40273680 | DOI:10.1016/j.psj.2025.105180

Hum Vaccin Immunother. 2025 Dec;21(1):2493539. doi: 10.1080/21645515.2025.2493539. Epub 2025 Apr 24.ABSTRACTThis study aims to fill the knowledge gap in systematically mapping the evolution of omics-driven tumor immunotherapy research through a bibliometric lens. While omics technologies (genomics, transcriptomics, proteomics, metabolomics)provide multidimensional molecular profiling, their synergistic potential with immunotherapy remains underexplored in large-scale trend analyses. A comprehensive search was conducted using the Web of Science Core Collection for literature related to omics in tumor immunotherapy, up to August 2024. Bibliometric analyses, conducted using R version 4.3.3, VOSviewer 1.6.20, and Citespace 6.2, examined publication trends, country and institutional contributions, journal distributions, keyword co-occurrence, and citation bursts. This analysis of 9,494 publications demonstrates rapid growth in omics-driven tumor immunotherapy research since 2019, with China leading in output (63% of articles) yet exhibiting limited multinational collaboration (7.9% vs. the UK's 61.8%). Keyword co-occurrence and citation burst analyses reveal evolving frontiers: early emphasis on "PD-1/CTLA-4 blockade" has transitioned toward "machine learning," "multi-omics," and "lncRNA," reflecting a shift to predictive modeling and biomarker discovery. Multi-omics integration has facilitated the development of immune infiltration-based prognostic models, such as TIME subtypes, which have been validated across multiple tumor types, which inform clinical trial design (e.g. NCT06833723). Additionally, proteomic analysis of melanoma patients suggests that metabolic biomarkers, particularly oxidative phosphorylation and lipid metabolism, may stratify responders to PD-1 blockade therapy. Moreover, spatial omics has confirmed ENPP1 as a potential novel therapeutic target in Ewing sarcoma. Citation trends underscore clinical translation, particularly mutation-guided therapies. Omics technologies are transforming tumor immunotherapy by enhancing biomarker discovery and improving therapeutic predictions. Future advancements will necessitate longitudinal omics monitoring, AI-driven multi-omics integration, and international collaboration to accelerate clinical translation. This study presents a systematic framework for exploring emerging research frontiers and offers insights for optimizing precision-driven immunotherapy.PMID:40275437 | DOI:10.1080/21645515.2025.2493539

Exp Hematol Oncol. 2025 Apr 24;14(1):60. doi: 10.1186/s40164-025-00657-0.ABSTRACTBACKGROUND: Ferroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, is associated with chemoresistance in lung adenocarcinoma (LUAD). This study aims to investigate the role of sarcosine in ferroptosis and its underlying mechanisms.METHODS: An RSL3-induced ferroptosis model was used to screen a library of 889 human endogenous metabolites and metabolomic profiling was harnessed to identify metabolites associated with ferroptosis. Cell viability, lipid-reactive oxygen species (ROS), ferrous iron, malondialdehyde (MDA), and mitochondrial integrity were assessed to evaluate sarcosine's effects on ferroptosis. Metabolic fate was studied using 15N-labeled sarcosine. Next, we used untargeted metabolomic profiling and next-generation sequencing to dissect metabolic and transcriptomic changes upon sarcosine supplementation. The effects of sarcosine on ferroptosis and chemotherapy were further validated in patient-derived organoids (PDOs), xenograft models, and LUAD tissues.RESULTS: Sarcosine emerged as a potent ferroptosis inducer in the metabolic library screening, which was further confirmed via cell viability, lipid-ROS, ferrous iron, and MDA measurements. Metabolic flux analysis showed limited conversion of sarcosine to other metabolites in LUAD cells, while untargeted metabolomic profiling and seahorse assays indicated a metabolic shift from glycolysis to oxidative phosphorylation. Sarcosine enhanced pyruvate dehydrogenase activity to generate more ROS by interacting with PDK4, reducing PDHA1 phosphorylation. As a co-activator of N-methyl-D-aspartate receptor (NMDAR), sarcosine also exerted its pro-ferroptosis effect via regulating ferrous export through the NMDAR/MXD3/SLC40A1 axis. Given the significance of ferroptosis in chemotherapy, we validated that sarcosine enhanced the sensitization of cisplatin by promoting ferroptosis in LUAD cells, PDOs, and xenograft models.CONCLUSION: Sarcosine promotes ferroptosis and enhances chemosensitivity, suggesting its potential as a therapeutic agent in treating LUAD.PMID:40275333 | DOI:10.1186/s40164-025-00657-0

Sci Rep. 2025 Apr 24;15(1):14401. doi: 10.1038/s41598-025-98754-x.ABSTRACTSubarachnoid hemorrhage (SAH) is a disease with high mortality and morbidity, and its pathophysiology is complex but poorly understood. To investigate the potential therapeutic targets post-SAH, the SAH-related feature genes were screened by the combined analysis of transcriptomics and metabolomics of rat cortical tissues following SAH and proteomics of cerebrospinal fluid from SAH patients, as well as WGCNA and machine learning. The competitive endogenous RNAs (ceRNAs) and transcription factors (TFs) regulatory networks of the feature genes were constructed and further validated by molecular biology experiments. A total of 1336 differentially expressed proteins were identified, including 729 proteins downregulated and 607 proteins upregulated. The immune microenvironment changed after SAH and the changement persisted at SAH 7d. Through multi-omics and bioinformatics techniques, five SAH-related feature genes (A2M, GFAP, GLIPR2, GPNMB, and LCN2) were identified, closely related to the immune microenvironment. In addition, ceRNAs and TFs regulatory networks of the feature genes were constructed. The increased expression levels of A2M and GLIPR2 following SAH were verified, and co-localization of A2M with intravascular microthrombus was demonstrated. Multiomics and bioinformatics tools were used to predict the SAH associated feature genes confirmed further through the ceRNAs and TFs regulatory network development. These molecules might play a key role in SAH and may serve as potential biological markers and provide clues for exploring therapeutic options.PMID:40274967 | DOI:10.1038/s41598-025-98754-x

NPJ Sci Food. 2025 Apr 24;9(1):57. doi: 10.1038/s41538-025-00411-0.ABSTRACTCitri Grandis Exocarpium (CGE), is renowned for its dual use in medicine and food, being well-known for its beneficial antioxidant and anti-inflammatory effects. However, the changes of chemical composition and antioxidant activity of CGE during the storage (aging) process are still unclear. In this study, We examined the changes in metabolites of CGE samples aged for 1 year (CG1), 3 years (CG3) and 5 years (CG5), mainly through comprehensive metabolomics techniques. The results indicated that analysis of CGE extracts by ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UHPLC-QTOF-MS/MS) resulted in the detection of 1249 metabolites. A total of 57 differential metabolites were identified as potential markers for distinguishing CGEs of different aging years by chemometrics methods, including naringin, among others. The KEGG annotation, enrichment and topology analysis revealed that the biosynthesis of flavonoids was a key metabolic pathway during the aging process of CEG, involving 14 flavonoids determined as differential metabolites. Total flavonoids, naringin, naringenin, butin, 7',4-dihydroxyflavone, and phlorizin have been identified as potential metabolites associated with antioxidant activity. These results clarified the effects of aging time on the flavonoids accumulation and antioxidant activity of CGE, and provided a scientific basis for understanding the mechanism of CGE aging process.PMID:40274825 | DOI:10.1038/s41538-025-00411-0