PubMed

Food Res Int. 2025 Feb;201:115549. doi: 10.1016/j.foodres.2024.115549. Epub 2024 Dec 30.ABSTRACTBrochothrix thermophcta (B. thermophcta) is a pathogenic microorganism associated with food contamination. Linalyl alcohol, owing to its broad spectrum and exceptional antibacterial properties, is regarded as a potent natural antimicrobial agent. This is to elucidate the cellular-level mechanism of linalyl alcohol on B. thermophacta and investigate, for the first time, its regulatory effect on the metabolic pathway of B. thermophacta through metabonomics analysis. The results demonstrated that treatment with linalyl alcohol led to a reduction in bacterial metabolic capacity, while simultaneously promoting an increase in membrane fluidity through damage to the bacterial cell membrane. A total of 201 differential metabolites were identified at the metabolic level, with 50 showing significant up-regulation and 151 displaying significant down-regulation. The differential metabolites primarily participate in the tRNA cycle, amino acid metabolism, nucleotide metabolism, and aminoacyl-tRNA biosynthesis, with a particular emphasis on the significant impairment of amino acid metabolism. The application results demonstrated that linalyl alcohol exhibited a significant antibacterial effect on B. thermosphacta, as evidenced by the negligible changes observed in the color, smell, and tissue state of pork even after 8 days of treatment. In summary, linalyl alcohol exhibits multi-target and multi-pathway inhibition against B. thermosphacta, leading to disruption of cell morphology and metabolic processes. These findings provide a novel theoretical foundation for understanding the inhibitory mechanism of linalyl alcohol on B. thermosphacta, highlighting its potential as an effective alternative to food additives in the preservation industry of livestock products.PMID:39849689 | DOI:10.1016/j.foodres.2024.115549

Stem Cell Res Ther. 2025 Jan 23;16(1):19. doi: 10.1186/s13287-024-04121-4.ABSTRACTBACKGROUND: Understanding how enteric neural crest cells (ENCCs) differentiate into neurons is crucial for neurogenesis therapy and gastrointestinal disease research. This study explores how magnesium ions regulate the glycolytic pathway to enhance ENCCs differentiation into neurons.MATERIALS AND METHODS: We used polymerase chain reaction, western blot, immunofluorescence, and multielectrode array techniques to assess magnesium ions' impact on ENCCs differentiation. Non-targeted metabolomic sequencing, cellular acidification rate, oxygen consumption, and western blot analyzed sugar metabolism changes. D-glucose-13C6 isotope tracing identified key glucose flux changes. Surface plasmon resonance was used to detect the binding affinity of magnesium ions with key glycolysis genes. The elastic modulus of the hydrogel was measured using a universal testing machine, while pore size and porosity were assessed with scanning electron microscopy. Swelling ratios were determined using gravimetric analysis. In vivo, ENCCs in hydrogels were transplanted into renal capsule and subcutaneously, and magnesium ions' effects on ENCCs differentiation were evaluated.RESULTS: Magnesium ions increased glycolysis levels during ENCCs differentiation into neurons, along with significant upregulation of neuronal markers β-Tubulin and ubiquitin C-terminal hydrolase L1, and enhanced functional neuronal properties. D-glucose-13C6 tracing results showed increased carbon flux in the glycolytic pathway after magnesium supplementation. The binding affinity of magnesium ions with the glycolytic key enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 was found to be 1.08 μM. Inhibiting glycolysis suppressed ENCCs differentiation into neurons, emphasizing its crucial role. The double-cross-linked hydrogel gelatin methacryloyl-alginate (gelMA-ALMA), cross-linked with magnesium ions, showed promise in enhancing ENCCs differentiation in vivo without causing systemic hypermagnesemia.CONCLUSION: Magnesium ions promote ENCCs differentiation into neurons by activating the Warburg effect. The GelMA-ALMA hydrogel serves as an effective localized magnesium delivery system, supporting neuronal differentiation in vivo.PMID:39849616 | DOI:10.1186/s13287-024-04121-4

Stem Cell Res Ther. 2025 Jan 23;16(1):21. doi: 10.1186/s13287-025-04138-3.ABSTRACTBACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is still a growing concern in the field of antimicrobial resistance due to its resistance to conventional antibiotics and its association with high mortality rates. Mesenchymal stromal cells (MSCs) have been shown as a promising and attractive alternative treatment for bacterial infections, due to their antibacterial properties and potential to bypass traditional resistance mechanisms. This study aims to shed light on the antibacterial potential of adipose-derived mesenchymal stromal cell (AD-MSC) secretome against clinical isolates of Staphylococcus spp., including MRSA strains.METHODS: Using the Kirby-Bauer disk diffusion method, broth microdilution assays, and colony-forming unit (CFU) counting, the antibacterial activity of AD-MSC secretome was assessed. These tests were first conducted on Staphylococcus (S.) aureus ATCC 25923, then on 73 clinical isolates including MRSA strains. Further molecular analysis was performed to identify resistant genes in MRSA isolates.RESULTS: The AD-MSC secretome demonstrated significant antibacterial activity against S. aureus ATCC with a 32 mm inhibition zone. 96% of the collected staphylococcal clinical isolates showed susceptibility to the secretome with 87.5% inhibition observed in MRSA isolates, along with 100% in MSSA, MSSE, and MRSE strains. Molecular analysis revealed that MRSA strains resistant to the secretome harbored mecA, ermA, and ermB genes. Additionally, the mecA-negative MRSA strains remained susceptible to the secretome, suggesting alternative resistance mechanisms.CONCLUSION: These findings emphasize the ability of AD-MSCs secretome as a promising alternative for treating antibiotic-resistant infections, with potential applications in combating MRSA. However, further research is required to explore its clinical applications as a complementary or standalone therapy for resistant infections.PMID:39849590 | DOI:10.1186/s13287-025-04138-3

BMC Ophthalmol. 2025 Jan 23;25(1):43. doi: 10.1186/s12886-025-03875-6.ABSTRACTBACKGROUND: Herpes simplex keratitis (HSK) is a recurrent inflammatory disease of cornea primarily initiated by type I herpes simplex virus infection of corneal epithelium. However, early diagnosis of HSK remains challenging due to the lack of specific biomarkers. This study aims to identify biomarkers for HSK through tear metabolomics analysis between HSK and healthy individuals.METHODS: We conducted a cross-sectional study enrolling 33 participants. Tear samples were collected from one eye of 18 HSK patients and 15 healthy volunteers using Schirmer-strips. Tear metabolomic profiling was performed using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Metabolites were quantified and matched against entries in the human metabolome database (HMDB) and small molecule pathway database (SMPDB) to identify metabolites and metabolic pathways, respectively. Metabolic differences between HSK and control group were determined using multivariate statistical analysis.RESULTS: A total of 329 metabolites were identified, of which 18 were significantly altered in HSK patients. Notably, 12 metabolites were significantly increased, and 6 were significantly decreased in HSK patients. The changed metabolites were enriched in these pathways: arginine and proline metabolism, phospholipid biosynthesis, alpha linolenic acid and linoleic acid metabolism, retinol metabolism. To assess the potential utility of tear biomarkers, a predictive model was developed combining 4 metabolites (AUC = 0.998 [95%CI: 0.975, 1]): D-proline, linoelaidic acid, plantagonine, and phosphorylcholine.CONCLUSIONS: Our study establishes that HSK has a distinctive metabolomic profile, with 4 key elements maybe emerging as potential biomarkers for diagnostic purposes. These findings may provide novel insights into early and rapid diagnosis of HSK.PMID:39849402 | DOI:10.1186/s12886-025-03875-6

BMC Genomics. 2025 Jan 23;26(1):65. doi: 10.1186/s12864-025-11229-1.ABSTRACTBACKGROUND: There is increasing need for effective incorporation of high-dimensional genetics data from individuals with varied ancestry in genome-wide association (GWAS) analyses. Classically, multi-ancestry GWAS analyses are performed using statistical meta-analysis to combine results conducted within homogeneous ancestry groups. The emergence of cosmopolitan reference panels makes collective preprocessing of GWAS data possible, but impact on downstream GWAS results in a mega-analysis framework merits investigation. We utilized GWAS data from the multi-national Hyperglycemia and Adverse Pregnancy Outcome Study to investigate differences in GWAS findings using a homogeneous ancestry meta-analysis versus a heterogeneous ancestry mega-analysis pipeline. Maternal fasting and 1-hr glucose and metabolomics measured during a 2-hr 75-gram oral glucose tolerance test during early third trimester pregnancy were evaluated as phenotypes.RESULTS: For the homogeneous ancestry meta-analysis pipeline, variant data were prepared by identifying sets of individuals with similar ancestry and imputing to ancestry-specific reference panels. GWAS was conducted within each ancestry group and results were combined using random-effects meta-analysis. For the heterogeneous ancestry mega-analysis pipeline, data for all individuals were collectively imputed to the Trans-Omics for Precision Medicine (TOPMed) cosmopolitan reference panel, and GWAS was conducted using a unified mega-analysis. The meta-analysis pipeline identified genome-wide significant associations for 15 variants in a region close to GCK on chromosome 7 with maternal fasting glucose and no significant findings for 1-hr glucose. Associations in this same region were identified using the mega-analysis pipeline, along with a well-documented association at MTNR1B on chromosome 11 with both fasting and 1-hr maternal glucose. For metabolomics analyses, the number of significant findings in the heterogeneous ancestry mega-analysis far exceeded those from the homogeneous ancestry meta-analysis and confirmed many previously documented associations, but genomic inflation factors were much more variable.CONCLUSIONS: For multi-ancestry GWAS, heterogeneous ancestry mega-analysis generates a rich set of variants for analysis using a cosmopolitan reference panel and results in vastly more significant, biologically credible and previously documented associations than a homogeneous ancestry meta-analysis approach. Genomic inflation factors do indicate that findings from the mega-analysis pipeline may merit cautious interpretation and further follow-up.PMID:39849370 | DOI:10.1186/s12864-025-11229-1

Life Sci. 2025 Jan 21:123411. doi: 10.1016/j.lfs.2025.123411. Online ahead of print.ABSTRACTAs a pivotal branch of metabolomics, lipidomics studies global changes in lipid metabolism under different physiological and pathological conditions or drug interventions, discovers key lipid markers, and elaborates the associated lipid metabolism network. There are a considerable number of lipids in the host, which act on various functional networks such as metabolism and immune regulation. As an indispensable research method, lipidomics plays a key character in the analysis of lipid composition in organisms, the elaboration of the physiological mechanism of lipids, and the decoding of their character in the occurrence and development of diseases by exploring the character of lipids in the host environmental network. As an essential means of driving lipidomics research, High-throughput and High-resolution mass spectrometry is helpful in exploring disease phenotypic characteristics, diagnosing disease biomarkers, regulating related metabolic pathways, and discovering related active components. In this paper, we discuss the specific role of lipidomics in the analysis of disease diagnosis, prognosis and treatment, which is conducive to the realization of accurate and personalized medicine.PMID:39848598 | DOI:10.1016/j.lfs.2025.123411

Metab Eng. 2025 Jan 21:S1096-7176(25)00004-7. doi: 10.1016/j.ymben.2025.01.004. Online ahead of print.ABSTRACTPolyhydroxyalkanoate (PHA) is an attractive bio-degradable plastic alternative to petrochemical plastics. Photosynthetic cyanobacteria accumulate biomass by fixing atmospheric CO2, making them promising hosts for sustainable PHA production. Conventional PHA production in cyanobacteria requires prolonged cultivation under nutrient limitation to accumulate cellular PHA. In this study, we developed a system for growth-coupled production of the PHA poly-hydroxybutyrate (PHB), using the marine cyanobacterium Synechococcus sp. PCC 7002. A recombinant strain termed KB1 expressing a set of heterologous PHB biosynthesis genes (phaA/phaB from Cupriavidus necator H16 and phaE/phaC from Synechocystis sp. PCC 6803) accumulated substantial PHB during growth (11.4% of dry cell weight). To improve PHB accumulation, we introduced the Pseudomonas aeruginosa phosphoketolase gene (pk) into strain KB1, rewiring intermediates of the Calvin-Benson-Bassham (CBB) cycle (xyluose-5-phosphate, sedoheptulose 7-phosphate, and fructose-6-phosphate) to acetyl-CoA. The pk-expressing strain, KB15, accumulated 2.1-fold enhanced levels of PHB (23.8% of dried cell weight), relative to the parent strain, KB1. The highest PHB titer of KB15 strain supplemented with acetate was about 1.1 g L-1 and the yield was further enhanced by 2.6-fold following growth at 38°C (0.21 g L-1 d-1), relative to growth at 30°C. Metabolome analysis revealed that pool sizes of CBB intermediates decreased, while levels of acetyl-CoA increased in strain KB15 compared with strain KB1, and this increase was further enhanced following growth at 38°C. Our data demonstrate that acetyl-phosphate generated by Pk was converted into acetyl-CoA via acetate by hitherto unidentified enzymes. In conclusion, expression of heterologous PHB biosynthesis genes enabled growth-coupled PHB production in strain PCC 7002, which was increased through acetyl-CoA supplementation by bypassing acetyl-phosphate and elevating culture temperature.PMID:39848486 | DOI:10.1016/j.ymben.2025.01.004

Int J Biol Macromol. 2025 Jan 21:140193. doi: 10.1016/j.ijbiomac.2025.140193. Online ahead of print.ABSTRACTIn the fiber industry, cotton (Gossypium hirsutum L.) is an important crop. One of the most important morphology traits of plants is the color of the anthers, is closely related to pollen fertility and stress resistance. Upland cotton anthers appear white, while island cotton and many wild cotton species have yellow anthers. Carotenoids are natural pigments in plants which involved in many metabolic processes, including photosynthesis, photoprotection, photomorphogenesis, growth and development. Here, we characterized the yellow anther trait of G. hirsutum. Carotenoid and flavonoid profiles in the yellow anthers were greatly altered compared to that in the white anthers, indicating that both carotenoids and flavonoids contribute to the yellow anther phenotype. Map-based cloning identified GhYA (GH_A05G4013) encoding a phytoene synthase to be the candidate gene responsible for anther coloration. GhYA is predominantly expressed in anthers, with its expression level gradually decreasing with the development of anthers. Haplotype analysis revealed that white anthers are associated with two haplotypes, with X74 belonging to HAP1. Through evolutionary analysis, it was found that although there are many white anther Germplasm in upland cotton, the two types of white anther haplotypes were mutated from yellow anthers respectively. Comparative transcriptome analysis between the yellow anther and white anther accessions revealed differentially expressed genes related to both the carotenoid and flavonoid biosynthesis pathways, in line with the changed profiles of the two types of metabolites in yellow anthers; meanwhile, it also indicates potential cross-talk between the flavonoid and carotenoid pathways. According to the results, the PSY gene is critical for the regulation of carotenoids accumulation in cotton anthers.PMID:39848383 | DOI:10.1016/j.ijbiomac.2025.140193

Cell Rep Med. 2025 Jan 16:101924. doi: 10.1016/j.xcrm.2024.101924. Online ahead of print.ABSTRACTHormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common type of breast cancer, with continuous recurrence remaining an important clinical issue. Current relapse predictive models in HR+/HER2- breast cancer patients still have limitations. The integration of multidimensional data represents a promising alternative for predicting relapse. In this study, we leverage our multi-omics cohort comprising 579 HR+/HER2- breast cancer patients (200 patients with complete data across 7 modalities) and develop a machine-learning-based model, namely CIMPTGV, which integrates clinical information, immunohistochemistry, metabolomics, pathomics, transcriptomics, genomics, and copy number variations to predict recurrence risk of HR+/HER2- breast cancer. This model achieves concordance indices (C-indices) of 0.871 and 0.869 in the train and test sets, respectively. The risk population predicted by the CIMPTGV model encompasses those identified by single-modality models. Feature analysis reveals that synergistic and complementary effects exist in different modalities. Simultaneously, we develop a simplified model with a mean area under the curve (AUC) of 0.840, presenting a useful approach for clinical applications.PMID:39848244 | DOI:10.1016/j.xcrm.2024.101924

Poult Sci. 2025 Jan 14;104(2):104814. doi: 10.1016/j.psj.2025.104814. Online ahead of print.ABSTRACTTo investigate the effect of fresh corn extract (FCE) on chicken meat quality, 135-day-old Jingyuan chicken hens were fed diets containing different doses of FCE (CON, 0.3% FCE, 0.6% FCE and 0.9% FCE) until 180 day-old in this study. Meat performance measurements showed that the 0.6% FCE group of Jingyuan chickens had higher intramuscular fat (IMF), pressing loss (PL), amino acid and fatty acid contents (P < 0.05). Their breasts were collected for transcriptomic and metabolomic analyses (n=8), and 210 Differentially expressed genes (DEGs) and 29 Differentially expressed genes (DEMs) were obtained. Gene Ontology (GO) analyses of DEGs indicate multiple entries involved in IMF synthesis such as skeletal system development and cellular response to amino acid stimulation. Kyoto Encyclopedia of Genes and Genomes (GSEA-KEGG) analysis identified sphingolipid_metabolism and multiple genes affecting IMF deposition including SPHK1, CERS1, CERS6, GLB1L, SGMS2, UGT8, and UGCG. KEGG and metabolite correlation analyses of DEMs identified Aspartate, PI 38:5; PI(18:1/20:4), PI 36:3; PI(18:1/18:2), PI 36:2; PI(18:0/18:2), and PI 34:1; PI(16:0/18:1) as the likely major influences on IMF deposition in the DEMs. Correlation analysis revealed that shear force (SF) was significantly and positively correlated with Aspartate and CERS6; PL was significantly and positively correlated with SPHK1 and UGCG (P < 0.05). IMF was significantly and positively correlated with PI 34:1; PI (16:0/18:1), SPHK1 and UGCG; and flesh colour yellowness b* was significantly and positively correlated with SGMS2 (P < 0.05). The above results indicate that feeding a basal diet containing 0.6% FCE can improve the meat quality of Jingyuan chicken, which provides a theoretical basis for improving the meat quality of Jingyuan chicken.PMID:39848207 | DOI:10.1016/j.psj.2025.104814

Phytomedicine. 2025 Jan 7;138:156375. doi: 10.1016/j.phymed.2025.156375. Online ahead of print.ABSTRACTBACKGROUND: The prevalence of obesity and its associated diseases has sharply increased, becoming a global health issue. White adipose tissue (WAT), responsible for lipid storage via hyperplasia and hypertrophy, and brown adipose tissue (BAT), which facilitates energy dissipation, have increasingly been recognized as critical regulators of weight loss. Shouhui Tongbian Capsule (SHTB) has traditionally been used for detoxification, weight loss, and lipid reduction, and clinical evidence supports its use for relieving constipation. In traditional Chinese medicine (TCM), "dissipating turbidity" is seen as a shared approach to treating both constipation and obesity. Our evidence suggests that SHTB improves obesity and metabolic disorders, but the underlying mechanisms remain unclear.PURPOSE: This study aimed to evaluate the pharmacological effects of SHTB on obesity and to explore the underlying mechanisms involved.METHODS: Obese mice induced by a high-fat diet were treated with SHTB, and effects on body weight, adipose tissue, and metabolism were assessed. Active ingredients were identified through UPLC-MS, while metabolomics and RNA sequencing were performed to explore the mechanisms of SHTB in obesity, and molecular biology techniques validated its effects on energy consumption and lipolysis in adipose tissue. Finally, rescue experiments in vivo and in vitro confirmed the proposed mechanisms.RESULTS: SHTB significantly reduced body weight, body fat percentage, and WAT mass while increasing BAT weight, and enhancing energy expenditure. Metabolomics and RNA sequencing indicated activation of the G-protein coupled receptor signaling and cAMP-PKA pathway, leading to increased lipolysis in WAT and enhanced thermogenesis in BAT. H89, a PKA agonist, counteracted these effects, supporting the involvement of cAMP-PKA signaling.CONCLUSION: SHTB may prevent obesity by promoting lipolysis and enhancing BAT thermogenesis via the cAMP-PKA pathway, offering a potential therapeutic approach for obesity management.PMID:39848021 | DOI:10.1016/j.phymed.2025.156375

Phytomedicine. 2025 Jan 20;138:156405. doi: 10.1016/j.phymed.2025.156405. Online ahead of print.ABSTRACTBACKGROUND: Prostate cancer (PCa) is a significant malignancy in men, particularly challenging in the metastatic stage due to poor prognosis and limited treatment efficacy. Traditional Chinese Medicine, particularly Modified Shenqi Dihuang Decoction (MSDD), has demonstrated promise in inhibiting PCa metastasis, although its mechanisms remain unclear.METHODS: The efficacy of MSDD was evaluated using migration assays and a nude mouse model. Metabolomics was employed to identify the biological processes affected by MSDD. Systematic pharmacology, bioinformatics, and molecular dynamics were utilized to determine direct action targets of MSDD. Additionally, luciferase reporter assays, ChIP-qPCR, and gene editing were applied to elucidate the pharmacological mechanisms.RESULTS: MSDD effectively inhibited prostate metastasis both in vivo and in vitro, without significant adverse events reported. Metabolomics and molecular biology experiments indicated that MSDD transcriptionally represses OGDH, affecting energy metabolism associated with the tricarboxylic acid cycle (TCA) in PCa. The active components of MSDD were found to potentially bind to the transcription factor RELA (NF-kB-p65), and further experiments demonstrated that RELA regulates OGDH transcription. Further experiments revealed that the anti-metastatic effects of MSDD are RELA-dependent, indicating the crucial role of the NF-kB/OGDH axis in this process.CONCLUSIONS: These findings support the clinical use of MSDD in metastatic PCa, emphasizing its potential to address current treatment gaps. The identified NF-kB/OGDH-dependent mechanism not only underpins MSDD's anti-metastatic effects but also reflects OGDH as a potential therapeutic target. Further research into the role of TCA in PCa progression is imperative.PMID:39848017 | DOI:10.1016/j.phymed.2025.156405

Ecotoxicol Environ Saf. 2025 Jan 22;290:117774. doi: 10.1016/j.ecoenv.2025.117774. Online ahead of print.ABSTRACTEffective environmental risk assessments of chemical plant protection products, such as benzoylurea pesticides, are crucial for safeguarding ecosystems. These pesticides, including teflubenzuron, target chitin synthesis in arthropods but also pose risks to non-target soil fauna like Collembola, which play essential roles in decomposition and nutrient cycling. This study combines traditional toxicity tests with a metabolomic approach to examine the interspecies specific sensitivity of three Collembola species - Sinella curviseta, Ceratophysella denticulata, and Folsomia candida - to teflubenzuron. The investigation focused on reproduction, bioaccumulation, and changes in chitin-related metabolites as indicators of pesticide impacts. Results revealed significant interspecies specific variability in sensitivity, with F. candida showing higher susceptibility towards teflubenzuron, possibly due to greater bioaccumulation factors. Metabolomic analysis highlighted distinct patterns in chitin metabolite alterations among the species, correlating with their differential sensitivity. Notably, metabolites like trehalose and glucose, crucial for chitin synthesis, were significantly affected by teflubenzuron within seven days of exposure. Despite high soil concentrations of the pesticide, S. curviseta demonstrated resilience in traditional life-history endpoints, such as reproduction and survival. However, metabolomics indicated a biochemical response to even low internal concentrations of teflubenzuron, underscoring the complexity of their interactions with environmental stressors. This study emphasizes the importance of incorporating metabolomics to understand the differential responses of non-target organisms to pesticides and advocates for species-specific risk assessments in pesticide regulation. The distinct metabolic responses among Collembola species to chitin synthesis inhibitors provide critical insights into their ecological resilience or vulnerability, enhancing our understanding of ecosystem dynamics and the potential ramifications of chemical exposure.PMID:39847884 | DOI:10.1016/j.ecoenv.2025.117774

Aquat Toxicol. 2025 Jan 16;279:107252. doi: 10.1016/j.aquatox.2025.107252. Online ahead of print.ABSTRACTThe hepatotoxicity of microplastics (MPs) has garnered increasing attention, but their effects on elderly organisms remain inadequately characterized, particularly concerning hepatic stress response patterns in environmental conditions. In this study, a 10-day exposure period of elderly zebrafish to polystyrene microplastics (PS-MPs, 1 µm) was conducted, with exposure concentrations set at 5.6 × 10-7 µg/L, 5.6 × 10-4 µg/L, and 5.6 × 10-1 µg/L. PS-MPs-induced toxicity varied with concentration: superoxide dismutase (SOD), complement 3 (C3), and complement 4 (C4) initially decreased before rising; 8‑hydroxy-2-deoxyguanosine (8-OhdG), interleukin-6 (IL-6), and interleukin-8 (IL-8) increased at high concentrations. Additionally, catalase (CAT) activity and thiobarbituric acid reactive substances (TBARS) contents rose with concentration. The aged zebrafish liver exhibited differentiation driven by responsiveness; low levels cause homeostatic disruption, and high levels induce genotoxicity and immune activation. LC-MS identified twelve crucial metabolites involved in 18 metabolic pathways, including amino acids (L-tyrosine, l-arginine), lipids (phospholipids, 12(S)-leukotriene B4 and triglycerides), and N-acetylneuraminic acid, related to energy, immunity, and neurological health. Overall, elderly zebrafish exhibited clear dose-dependent thresholds and distinct physiological stress responses under varying concentrations of PS-MPs. These findings reveal how PS-MP exposure can affect physiological health and metabolism, offering critical insights into the ecological risks faced by aging organisms.PMID:39847840 | DOI:10.1016/j.aquatox.2025.107252

STAR Protoc. 2025 Jan 21;6(1):103582. doi: 10.1016/j.xpro.2024.103582. Online ahead of print.ABSTRACTGut-microbiome-combined metabolomics studies in cerebrovascular disease highlight the microbiota-gut-brain axis in neurological disorders. Here, we present a protocol for correlating the gut microbiome and metabolomics in patients with intracranial aneurysms. We describe steps for sample collection, fecal genomic DNA extraction, rRNA PCR amplification, sequencing library construction, and rRNA sequencing. We then detail procedures for metabolite extraction, liquid chromatography-tandem mass spectrometry (LC-MS/MS) non-targeted metabolomics sequencing, and ELISA for cerebrospinal fluid and plasma samples. Finally, we perform combined multi-omics analysis. For complete details on the use and execution of this protocol, please refer to Xu et al.1.PMID:39847486 | DOI:10.1016/j.xpro.2024.103582

J Am Soc Nephrol. 2025 Jan 23. doi: 10.1681/ASN.0000000626. Online ahead of print.ABSTRACTBACKGROUND: Cardiac surgery-associated acute kidney injury is a common serious complication after cardiac surgery. Currently, there are no specific pharmacological therapies. Our understanding of its pathophysiology remains preliminary.METHODS: A total of 2504 patients with and without acute kidney injury (AKI) following cardiac surgery were enrolled. High-performance liquid chromatography coupled with mass spectrometry was used for untargeted analysis of metabolites in plasma, identifying significant differential metabolites. Subsequently, a tandem liquid chromatography-mass spectrometry-based approach using isotope-labeled standard addition was performed for targeted analysis of the metabolic marker N-acetyl-tryptophan. The function of N-acetyl-tryptophan was determined using different kidney injury mouse models and epithelial cellular models. Transcriptome sequencing, surface plasmon resonance and protein mutation were employed to explore the mechanism of N-acetyl-tryptophan on the kidney.RESULTS: We identified a total of 32 differential metabolites related to AKI occurrence based on a cohort of 1042 patients. Among them, N-acetyl-tryptophan was elevated in plasma of patients with cardiac surgery-associated acute kidney injury compared with those who do not develop AKI after cardiac surgery. The higher level of N-acetyl-tryptophan in plasma was confirmed by accurate targeted quantification. N-acetyl-tryptophan exhibited kidney protective effects in ischemia/reperfusion-, cisplatin-, and unilateral ureteral obstruction-induced kidney injury mouse models. Mechanistically, N-acetyl-tryptophan exerted kidney protective effects by interacting with KEAP1 at 483 and 508 sites, resulting in Nrf2 nuclear translocation and the transcription of proteasome genes.CONCLUSIONS: N-acetyl-tryptophan plays a key role in kidney protection.PMID:39847454 | DOI:10.1681/ASN.0000000626

Proc Natl Acad Sci U S A. 2025 Jan 28;122(4):e2414434122. doi: 10.1073/pnas.2414434122. Epub 2025 Jan 23.ABSTRACTChemical communication between marine bacteria and their algal hosts drives population dynamics and ultimately determines the fate of major biogeochemical cycles in the ocean. To gain deeper insights into this small molecule exchange, we screened niche-specific metabolites as potential modulators of the secondary metabolome of the roseobacter, Roseovarius tolerans. Metabolomic analysis led to the identification of a group of cryptic lipids that we have termed roseoceramides. The roseoceramides are elicited by iron-binding algal flavonoids, which are produced by macroalgae that Roseovarius species associate with. Investigations into the mechanism of elicitation show that iron limitation in R. tolerans initiates a stress response that results in lowered oxidative phosphorylation, increased import and catabolism of algal exudates, and reconfiguration of lipid ynthesis to prioritize production of roseoceramides over phospholipids, likely to fortify membrane integrity as well as promote a sessile and symbiotic lifestyle. Our findings add new small molecule words and their "meanings" to the algal-bacterial lexicon and have implications for the initiation of these interactions.PMID:39847340 | DOI:10.1073/pnas.2414434122

Rice (N Y). 2025 Jan 23;18(1):2. doi: 10.1186/s12284-025-00757-9.ABSTRACTEnhancing nitrogen (N) fixation in rice plants can reduce N fertilizer application and contribute to sustainable rice production, particularly under low-N conditions. However, detailed microbial and metabolic characterization of N fixation in rice stems, unlike in the well-studied roots, has not been investigated. Therefore, the aim of this study was to determine the active N-fixing sites, their diazotroph communities, and the usability of possible carbon sources in stems compared with roots. The N-fixing activity and copy number of the nitrogenase gene in the rice stem were high in the outer part of the unelongated stem (basal node), especially in the epidermis. N fixation, estimated using the acetylene reduction assay, was also higher in the leaf sheath and root than in the inner part of the unelongated stem and culm. Amplicon sequence variants (ASVs) close to sugar-utilizing heterotrophic diazotrophs belonging to Betaproteobacteria and type II methanotrophic diazotrophs belonging to Alphaproteobacteria were abundant in the outer part of the unelongated stems. Media containing crushed unelongated stems exhibited N-fixing activity when sucrose, glucose, and methane were added as the sole carbon sources. This suggested that N fixation in the unelongated stems was at least partly supported by sugars (sucrose and glucose) and methane as carbon sources. ASVs close to sugar-utilizing heterotrophs belonging to Actinobacteria were also highly abundant in the unelongated stem; however, their functions need to be further elucidated. The present finding that diazotrophs in rice stems can use sugars such as sucrose and glucose synthesized by rice plants provides new insights into enhancing N fixation in rice stems.PMID:39847236 | DOI:10.1186/s12284-025-00757-9

Protoplasma. 2025 Jan 23. doi: 10.1007/s00709-025-02030-8. Online ahead of print.ABSTRACTEclipta prostrata belongs to the Asteraceae family. The plant contains bioactive compounds like wedelolactone (WDL) and demethylwedelolactone (DW). Its transcriptomic information engaged with secondary metabolite biosynthesis is not available. Based on differential accumulation of WDL and DW in root, shoot of the mature plant, we performed comparative de novo transcriptome of root and shoot tissue in three independent biological replicates and generated 49820 unique transcripts. Annotation resulted in significant matches for 43,015 unigenes. Based on differential gene expression data, we found WDL biosynthesis-related transcripts, which were mainly upregulated in shoot. Finally, 13 selected differentially expressed transcripts related to WDL biosynthesis that were validated by qRT-PCR. Detailed tissue-specific metabolite and transcript profiling revealed that DW highly accumulated in root and WDL accumulation was high in aerial part along with transcripts. For WDL pathway exploration, we did integrated profiling of 08 metabolites and 13 transcripts and witnessed that only naringenin, apigenin, DW, and WDL were detected in different developmental stages. Taking leads from the findings, we postulated that naringenin to apigenin pathway is one potential route for WDL biosynthesis. Moreover, wound stress led to accumulation of DW and WDL and related biosynthetic transcripts. Furthermore, the selected enzymes were subjected to molecular docking and binding studies for the predicted substrates involved in crucial and advance steps of WDL biosynthesis. A comprehensive analysis integrating de novo transcriptomics, metabolomics, and molecular docking of targeted proteins paves the way for the elucidation of the putative wedelolactone biosynthesis pathway from E. prostrata.PMID:39847090 | DOI:10.1007/s00709-025-02030-8

Plant Cell Rep. 2025 Jan 23;44(2):34. doi: 10.1007/s00299-024-03384-8.ABSTRACTIntegration of resistance indicators, metabolomes, and transcriptomes to elucidate that there is a positive correlation between disease susceptibility and cold tolerance in tea plants. The flavonoid pathway was found to be the major metabolic and transcriptional enrichment pathway. A key domain NB-ARC was identified through joint analysis, along with analysis of key domains within the NB-ARC protein. Tea is a healthy beverage and the tea plant is a woody plant rich in secondary metabolites. In the face of abnormal climate change year by year, it is important to investigate the mechanisms by which tea plants resist both biotic and abiotic stresses. In this study, we found different tea plant cultivars were evaluated for cold and disease resistance have highly correlated. Subsequently, two cold and fungal resistant cultivars were screened from a Shuixian population that had been cold domesticated for 50 years, and transcriptome and metabolome assays were performed on the two materials under cold and anthracnose stresses, using Baiye Dancong as a control. The analyses found that differential metabolites were most enriched in the flavonoid pathway and differentially expressed genes were most enriched in the pathway related to disease course after pathogen stress and cold stress. Combined metabolome and transcriptome analyses identified 30 genes that were positively correlated with flavonoid content after pathogen stress and cold stress, of which the number of genes with NB-ARC structural domains was 11, which accounted for the largest proportion. These 11 genes with NB-ARC structural domains were analyzed by family analysis and found to be highly involved in different tissues transcriptomes of tea plants, indicating the importance of the NB-ARC structural domains in biotic and abiotic stresses, and providing a theoretical basis of analysis for the subsequent related studies. In this study, through the identification of resistance in different varieties of tea plant and the multi-omics approach, we found the genes related to the key structural domain NB-ARC, which lays the foundation for the study of biologically and abiologically important mechanisms in response to the disease in tea plant.PMID:39847084 | DOI:10.1007/s00299-024-03384-8