PubMed

J Neurosurg. 2025 Jul 11:1-12. doi: 10.3171/2025.3.JNS242330. Online ahead of print.ABSTRACTOBJECTIVE: Spatial metabolic differences recently found in glioblastoma (GBM) have been linked to the infiltrating nature of the tumor edge tissue, which is mostly unresectable, and to the tumor core tissue, which resists therapy. The impact of metabolic dysregulation in core and edge GBM tissues on patient survival remains unclear. This study evaluated metabolites obtained from core and edge GBM tissues at the time of resection as biomarkers to risk stratify patients in terms of overall survival (OS).METHODS: Paired core and edge tumor samples from 27 patients with glioma obtained after craniotomy were evaluated postsurgery with high-resolution 2D liquid chromatography-mass spectrometry/mass spectrometry, and metabolomic data for grade IV samples (n = 21) were analyzed by Kaplan-Meier survival analysis and univariable and multivariable Cox proportional hazard regression models. GBM patients were stratified into low- and high-risk groups via a linear equation based on log-transformed signal intensities of key metabolites. Risk scores were generated by summing the product of weights and metabolite signal intensities for each patient's tumor. Weights for significant metabolites were calculated by scaling the univariable Cox proportional hazard ratio for each metabolite by the standard error. For risk score validation, OS events were predicted using an Extreme Gradient Boosting model with Linear Booster (XGBL).RESULTS: Kaplan-Meier survival analysis identified 6 significant metabolites in core tissue and 5 in edge tissue, respectively. Key metabolites in core and edge tissue identified through univariable Cox regression analyses combined with covariates were used to generate multivariable Cox regression models, with edge metabolites remaining significant after correction by patient sex and age at resection. Risk scores based on either 4 core or 11 edge metabolites, or the combination of both, with covariates, generated multivariable Cox regression models significantly associated with OS. Risk score derived from core metabolites remained significant after correction by covariates and was validated with XGBL classification model (area under the receiver operating characteristic curve = 0.876).CONCLUSIONS: OS of patients with GBM can be stratified based on metabolomic differences between core and edge tumor tissues.PMID:40644725 | DOI:10.3171/2025.3.JNS242330

Chem Biodivers. 2025 Jul 11:e00548. doi: 10.1002/cbdv.202500548. Online ahead of print.ABSTRACTSida rhombifolia belongs to the Malvaceae and is known to have bioactive compounds. The chemical composition and concentration of S. rhombifolia could be affected by several factors, including its growth locations. This research aims to determine the metabolite profile of S. rhombifolia extracts based on different locations of growth on Java Island, Indonesia, namely, Sukabumi, Malang, Tawangmangu, and Yogyakarta, as well as classify them based on their growth locations using principal component analysis (PCA). The total phenolic content was determined using the Folin-Ciocalteau methods, and antioxidant activity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC) methods. The ethanol extract of S. rhombifolia from Tawangmangu had the highest yield and antioxidant activity compared to samples from other regions. The PCA score plot using Fourier transform infrared (FTIR) and LC-HRMS data showed cumulative total variances of PC-1 and PC-2 are 96% and 91%, respectively. These results indicate that S. rhombifolia leaf extracts from different growth locations could be distinguished. This study proves that different growing areas affected the metabolite profile and antioxidant activity of S. rhombifolia.PMID:40644693 | DOI:10.1002/cbdv.202500548

Arch Microbiol. 2025 Jul 11;207(9):192. doi: 10.1007/s00203-025-04392-2.ABSTRACTThe study of fungal genetics has undergone transformative advancements in recent decades, profoundly reshaping our understanding of fungal diversity, evolution, and pathogenesis. This review synthesizes cutting-edge molecular techniques revolutionizing fungal diagnostics, with a focus on DNA fingerprinting, next-generation sequencing (NGS), and third-generation sequencing (TGS), alongside their applications in species identification, phylogenetic reconstruction, and disease management. We critically evaluated the utility of molecular markers such as the Internal Transcribed Spacer (ITS), Large Subunit (LSU), and protein-coding genes (e.g., RPB1, RPB2, TEF1-α), which have emerged as indispensable tools for resolving taxonomic ambiguities and cryptic species complexes. While ITS remains the gold standard for fungal barcoding due to its high interspecific variability, multi-locus strategies integrating loci like β-tubulin and CaM enhance resolution in challenging genera such as Aspergillus, Fusarium, and Penicillium. The review underscores the limitations of traditional morphology-based taxonomy, particularly its inability to address cryptic speciation or non-reproductive fungal phases. Advances in NGS platforms (e.g., Illumina, PacBio, Oxford Nanopore) have overcome these barriers, enabling high-throughput genomic analyses that reveal unprecedented fungal diversity in environmental and clinical samples. TGS technologies, with their long-read capabilities (> 10 kb), now facilitate the assembly of complex genomes, identification of structural variants, and exploration of horizontal gene transfer events, offering new insights into fungal adaptation and pathogenicity. Despite these breakthroughs, challenges persist in resolving intragenomic variation, reconciling gene tree discordance, and standardizing workflows for large-scale fungal population studies. The integration of multi-omics approaches (transcriptomics, proteomics, metabolomics) and machine learning algorithms promises to address these gaps, enabling predictive modeling of antifungal resistance and host-pathogen interactions. Collaborative efforts among mycologists, clinicians, and bioinformaticians are critical to harmonizing data sharing, refining diagnostic pipelines, and translating genomic insights into precision therapies. Fungal-related diseases pose escalating threats to global agriculture, healthcare, and ecosystem stability. Climate change further exacerbates pathogen spread and antifungal resistance, necessitating innovative management strategies. Emerging tools such as CRISPR-based diagnostics, portable sequencers (MinION), and synthetic biology platforms hold promise for real-time pathogen surveillance and engineered biocontrol solutions. By bridging genomic innovation with interdisciplinary collaboration, this review charts a roadmap for advancing fungal diagnostics, enhancing taxonomic clarity, and mitigating the socio-economic impacts of fungal diseases in an era of rapid environmental change.PMID:40643763 | DOI:10.1007/s00203-025-04392-2

Metabolomics. 2025 Jul 11;21(4):100. doi: 10.1007/s11306-025-02306-3.ABSTRACTINTRODUCTION: Post-stroke depression (PSD) pathophysiology involves glutamate excitotoxicity mediated through 'postsynaptic density protein95-neuronal nitric oxide synthase' (PSD95-nNOS) coupling. However, the therapeutic mechanisms of targeting this complex remain incompletely understood.OBJECTIVE: To elucidate the antidepressant mechanisms of the PSD95-nNOS decoupler ZL006 using an innovative integrated metabolomics approach.METHODS: We developed an innovative integrated metabolomics approach to investigate the antidepressant mechanisms of ZL006, a selective PSD95-nNOS decoupler. Using a rat model of PSD, we employed untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics combined with a novel analytical framework that distinguished treatment efficacy-associated metabolites from drug bias-associated ones. This classification enabled identification of primary drug mechanisms versus secondary responses. Pathway analyses focused on proteins interacting with drug-specific metabolites, with key findings validated through quantitative polymerase chain reaction (qPCR).RESULTS: ZL006 demonstrated dose-dependent antidepressant effects while modulating multiple neurotransmitter pathways, including tryptophan, tyrosine, and arginine metabolism, along with steroid hormone synthesis. Our integrated metabolomics approach revealed vascular endothelial growth factor (VEGF) signaling, hypoxia-inducible factor (HIF) pathway, and tight junction regulation as primary mechanisms of action.CONCLUSION: This novel metabolomics strategy, by discriminating between treatment-associated and compound-intrinsic pathways, provided unprecedented mechanistic insights into ZL006's therapeutic effects. The findings suggest that ZL006 alleviates PSD through coordinated modulation of neuroplasticity, angiogenesis, and stress responses via PSD95-nNOS targeting. This integrated analytical approach presents a valuable framework for mechanistic investigation of therapeutic compounds.PMID:40643722 | DOI:10.1007/s11306-025-02306-3

Curr Opin Pulm Med. 2025 Jul 14. doi: 10.1097/MCP.0000000000001199. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Interstitial lung disease (ILD) presents significant diagnostic and therapeutic challenges due to underlying biological heterogeneity and variable clinical course. Traditional diagnostic and prognostic tools are limited in their ability to capture this heterogeneity or guide personalized treatment. Advances in biological phenotyping have set the stage for precision medicine in ILD, improving diagnosis, prognosis, and therapeutic decision-making in ILD. This review highlights recent advances in biological phenotyping technologies and their potential to reshape ILD care.RECENT FINDINGS: Emerging evidence supports the use of genomic, transcriptomic, and proteomic, and metabolomic biomarkers to identify distinct ILD subgroups with prognostic or therapeutic relevance. Several biomarkers are being evaluated prospectively, including TOLLIP genotype and eNose technology. Machine learning enables the integration of high-dimensional multiomics data, offering insights beyond what single biomarkers can provide.SUMMARY: Precision medicine in ILD is advancing rapidly and holds promise for more individualized care. Future efforts should prioritize multimodal integration, prospective validation across diverse ILD subtypes, and translating research into clinical practice. Continued innovation and collaboration will be essential to fully realize the potential of precision medicine in transforming ILD care and research.PMID:40643570 | DOI:10.1097/MCP.0000000000001199

Cells. 2025 Jul 1;14(13):1006. doi: 10.3390/cells14131006.ABSTRACTWe have previously shown that the mitochondrial respiratory chain (RC) can switch between the following two states: (i) an "ATP-producing" state characterized by the low production of reactive oxygen species (ROS), the vigorous translocation of hydrogen ions (H+), and the storage of energy from the H+ gradient in the form of ATP, and (ii) an "ROS-producing" state, where the translocation of H+ is slow but the production of ROS is high. Here, we suggest that the RC transition from an ATP-producing to an ROS-producing state initiates a mitochondrial permeability transition (MPT) by generating a burst of ROS. Numerous MPT activators induce the transition of the RC to an ROS-producing state, and the ROS generated in this state activate the MPT. The MPT, in turn, induces changes in conditions that are necessary for the RC to return to an ATP-producing state, decreasing the ROS production rate and restoring the normal permeability of the inner membrane. In this way, the transient MPT prevents cell damage from oxidative stress that would occur if the RC remained in an ROS-producing state. It is shown that an overload of glutamate, which enters through excitatory amino acid transporters (EAATs), induces the RC to switch to an ROS-producing state. Subsequent MPT activation causes a transition back to an ATP-producing state. The model was used to predict the spatial-temporal dynamics of glutamate concentrations and H2O2 production rates in a three-dimensional digital phantom of nervous tissue.PMID:40643527 | DOI:10.3390/cells14131006

Cells. 2025 Jul 1;14(13):1004. doi: 10.3390/cells14131004.ABSTRACTHexokinase catalyzes the first rate-limiting step glycolysis. However, the roles of hexokinase 2 (HK2) in asthma remain incompletely understood. This study aimed to investigate metabolic alterations in asthma, focusing on the expression, function and regulation of HK2. In this study, non-targeted metabolomics analysis of 20 asthma patients and 15 healthy controls identified metabolic alterations in asthma, particularly in the glycolytic pathways. Consistently, HK2 expression was elevated in both asthma individuals and mice with allergic airway inflammation. Airway epithelium-specific HK2 knockdown and pharmacological inhibition with 2-deoxy-D-glucose (2-DG) significantly attenuated airway inflammation and hyperresponsiveness in mice induced by ovalbumin/ lipopolysaccharide. Mechanistic analyses demonstrated that HK2 regulates epithelial apoptosis and inflammation via interaction with peptidylprolyl isomerase F (PPIF), independent of voltage-dependent anion channel 1 (VDAC1). Asthma is associated with metabolic reprogramming, characterized by alterations in lipid and glucose metabolism. These findings establish HK2 plays a crucial role in asthma pathogenesis by promoting airway epithelial apoptosis and inflammation in asthma, suggesting its potential as a therapeutic target.PMID:40643524 | DOI:10.3390/cells14131004

Cells. 2025 Jun 27;14(13):987. doi: 10.3390/cells14130987.ABSTRACTBackground. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world population. Progression to its inflammatory state, MASH, is associated with increasing liver fibrosis, leading to end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). SW033291, an inhibitor of 15-PGDH (the PGE2 degradation enzyme), has been shown to increase in vivo regeneration of liver parenchyma, ameliorating oxidative stress and inflammation. We hypothesized that SW033291 abrogates MASH progression by inducing a paucity of the initial apoptotic switch and restoring physiological collagen's microenvironment. Methods. The expression levels of the cell metabolic proteins FOXO1, mTOR, and SIRT7 were determined in a diet-induced MASH-mouse model at 16, 20, and 24 weeks. Non-targeted metabolomics in mouse plasma were measured by LC-MS/MS. Liver morphology and apoptotic activity were quantified by the NAS score and TUNEL assay, respectively. Statistical analyses between groups (NMC, HFD, and SW033291) were determined by ANOVA, t-test/Tukey's post hoc test using GraphPad Prism. Metabolomics data were analyzed using R-lab. Results. The treated group showed significant decreases in total body fat, cellular oxidative stress, and inflammation and an increase in total lean mass with improved insulin resistance and favorable modulation of metabolic protein expressions (p < 0.05). SW033291 significantly decreased GS:SG, citric acid, and corticosterone, NAS scores (9.4 ± 0.2 vs. 6.2 ± 0.1, p < 0.05), liver fibrosis scores (1.3 ± 0.5 vs. 0.25 ± 0.1, p < 0.05), and apoptotic activity (43.9 ± 4.6 vs. 0.38 ± 0.1%, p < 0.05) compared with controls at 24W. Conclusions. The inhibition of 15-PGDH appears to normalize the metabolic and morphological disturbances during MASH progression with a paucity of the initial apoptotic switch, restoring normal collagen architecture. SW033291 warrants further investigation for its translation.PMID:40643509 | DOI:10.3390/cells14130987

Elife. 2025 Jul 11;13:RP97130. doi: 10.7554/eLife.97130.ABSTRACTThe gut microbiome plays a key role in the maintenance of host metabolic homeostasis and health. Most metabolic processes cycle with a 24-hour rhythm, but the extent to which the microbiome influences metabolite cycling under different conditions, such as variations in dietary composition, remains largely unknown. In this study, we utilized high temporal resolution metabolite profiling of the Drosophila gut to investigate the role of the microbiome in metabolite cycling. We find that the microbiome increases the number of oscillating metabolites despite the previous finding that it dampens transcript cycling in the gut. Time-restricted feeding also promotes metabolite cycling and does so to a larger extent in germ-free flies, thereby increasing cycling in these flies to levels comparable to those in microbiome-containing flies. Enhancement of cycling by the microbiome depends upon a circadian clock, which also maintains phase in the face of changes in the microbiome. Interestingly, a high protein diet increases microbiome-dependent metabolite cycling, while a high sugar diet suppresses it. Gene Ontology identifies amino acid metabolism as the metabolic pathway most affected by changes in the gut microbiome, the circadian clock, and timed feeding, suggesting that it is subject to regulation by multiple inputs. Collectively, our observations highlight a key role of the gut microbiome in host metabolite cycling and reveal a complex interaction with internal and external factors.PMID:40643220 | DOI:10.7554/eLife.97130

Aging Cell. 2025 Jul 11:e70166. doi: 10.1111/acel.70166. Online ahead of print.ABSTRACTGut microbiota delays aging by regulating the immune, metabolic, and neurological functions of the host. However, current research on novel probiotics with antiaging properties significantly lags, impacting their application in clinical treatments. In this study, metagenomics, culturomics, and probiotic property screening were used to identify Bifidobacterium pseudocatenulatum NCU-08 as a potential probiotic with anti-aging properties. In addition, B. pseudocatenulatum NCU-08 effectively improved the behavioral characteristics, significantly reduced the levels of the age-related protein β-galactosidase (β-gal) (BP: M = 0.81 vs. 1.13, p < 0.05), attenuated neuronal damage in the hippocampus, and improved the composition of the gut microbiota of senescence-accelerated mouse tendency-8 (SAMP8) mice. The targeted metabolomics suggested that L-tryptophan (L-Trp) may be a key substance for B. pseudocatenulatum NCU-08 to exert anti-aging effects (BP: M = 14878.6 ng/mL vs. 5464.99 ng/mL, p < 0.01). Mechanistically, using the aging model of SAMP8 mice and HT22 mouse hippocampal neuronal cells, it was found that B. pseudocatenulatum NCU-08 might enter the intestine to regulate L-Trp, and then transport it to the brain. In the brain, L-Trp was metabolized to NAD+, which activated the Sirt1/P53/P21/Rb signaling pathway, thereby exerting antiaging effects. Interestingly, this antiaging effect was inhibited after the intervention of the Sirt1 inhibitor EX-527. This study is the first to confirm the antiaging properties of NCU-08 isolated from the fecal samples of seven centenarians in Jiangxi Province, providing data support for the future development of probiotic preparations with antiaging effects.PMID:40643197 | DOI:10.1111/acel.70166

Arch Endocrinol Metab. 2025 Jul 11;69(3):e240441. doi: 10.20945/2359-4292-2024-0441.ABSTRACTOBJECTIVE: To assess whether plasma irisin is associated with anthropometric, body composition, and metabolic parameters according to body mass index.METHODS: A prospective cohort study was conducted at a tertiary referral hospital in Southern Brazil. Patients were divided according to body mass index: Group 1 (body mass index = 18.5 - 29.9 kg/m2; n = 15), Group 2 (body mass index = 30 - 39.9 kg/m2; n = 36), and Group 3 (body mass index ≥ 40 kg/m2; n = 30). Groups 1 and 2 underwent cholecystectomy, while Group 3 underwent Roux-en-Y gastric bypass. All groups were evaluated at baseline, and Groups 2 and 3 were re-evaluated 6 months later. Body composition was assessed using X-ray absorptiometry, and resting energy expenditure was measured by indirect calorimetry.RESULTS: The study subjects were predominantly female (75%), white (82%), with a mean age of 46 ± 14 years. Group 3 had lower irisin levels compared to Group 2: 9.1 ± 2.2 versus 10.7 ± 2.8 ng/mL; p = 0.038). Irisin was negatively correlated with weight (r = -0.246; p = 0.042), waist circumference (r = -0.272; p = 0.024), glucose (r = -0.259; p = 0.039), glycated hemoglobin (r = -0.283; p = 0.024), triglycerides (r = -0.414; p = 0.024), and positively correlated with HDL (r = 0.280; p = 0.029).CONCLUSION: Irisin showed an inverse correlation with insulin-related metabolic pathways, suggesting its potential involvement in insulin resistance states such as obesity and type 2 diabetes.PMID:40643080 | DOI:10.20945/2359-4292-2024-0441

Am J Physiol Lung Cell Mol Physiol. 2025 Jul 11. doi: 10.1152/ajplung.00322.2024. Online ahead of print.ABSTRACTIntrauterine inflammation is associated with lung injury in offspring and long-term adverse pulmonary outcomes, but the underlying mechanism remains elusive. This study aimed to investigate the underlying molecular mechanism from the perspective of metabolites. Pregnant C57BL/6 mice received an intraperitoneal injection of LPS on gestational day 12.5 to establish an intrauterine inflammation model. The results showed that prenatal LPS exposure induced BPD-like alveolar simplification. Then, by LC/MS untargeted metabolomics analysis, succinic acid was found to be elevated in murine placentas and preterm human umbilical cord blood with intrauterine inflammation. Besides, the expression of succinate dehydrogenase B subunit (Sdhb), a key catalytic enzyme of succinic acid, was downregulated in the murine placentas with intrauterine inflammation. Tail intravenous administration of Sdhb siRNA led to the accumulation of succinic acid in the placenta and aggravated LPS-induced lung injury in the offspring. In offspring mice, intrauterine inflammation decreased E-cadherin levels in lung tissue, which were further reduced by Sdhb siRNA injection. Conversely, overexpression of E-cadherin alleviated inflammation-induced lung injury. In vitro experiments revealed that succinic acid downregulated E-cadherin expression in alveolar epithelial cells through the PI3K/Akt/Hif-1α pathway. Succinic acid also indirectly downregulated the E-cadherin expression in alveolar epithelial cells by inducing macrophage M2 polarization and the production of Tgf-β1. In conclusion, this study demonstrates that succinic acid is a critical mediator of intrauterine inflammation-induced lung injury in offspring.PMID:40643013 | DOI:10.1152/ajplung.00322.2024

Microbiol Spectr. 2025 Jul 11:e0084725. doi: 10.1128/spectrum.00847-25. Online ahead of print.ABSTRACTDrought poses considerable challenges to the sustainable development of crops, highlighting the urgent need to improve plant resistance to drought stress. Rhizosphere mycobiota roles in Eucommia ulmoides drought adaptation remain uncharacterized. This study examines E. ulmoides' rhizosphere mycobiota diversity, its changes, and interactions with plant physiology and metabolites under drought stress using amplicon sequencing, plant physiological assessments, and non-targeted root metabolomics. Our data indicate that drought stress considerably altered the species richness and community composition of the E. ulmoides seedling rhizosphere mycobiota, affecting the co-occurrence patterns and the composition of core fungal taxa within the mycobiota. Additionally, Sordariomycetes were notably enriched in the rhizosphere of E. ulmoides under drought stress and showed a notable positive correlation with the physiological indicator soluble sugar (SS). During drought stress mid-stages, rhizosphere core fungal taxa of E. ulmoides exhibit higher diversity, increased network connectivity, and a tighter network structure. Correlation analyses show that core fungal taxa are significantly linked to malondialdehyde (MDA) content. The root metabolome's phosphatidylcholines (o-16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)) and 8-demethyltetracenomycin C are also notably affected by the core microbial taxa. In summary, drought stress drives changes in the E. ulmoides rhizosphere mycobiota, plant physiology, and root metabolites, with MDA, SS, and 8-demethyltetracenomycin C possibly mediating the selection of specific rhizosphere fungal communities. Taken together, these data provide notable insights into plant-microbe interactions under drought stress and have important implications for improving the drought adaptability of E. ulmoides.IMPORTANCEDrought presents substantial challenges to the sustainability of crops, highlighting the need to enhance their resistance to arid conditions. Although the rhizosphere microbiome plays a crucial role in bolstering crop resilience, the dynamics and mechanisms of Eucommia ulmoides' rhizosphere mycobiota under drought conditions remain poorly understood. This study provides valuable insights into the interactions between plants and microbes under drought stress and has significant implications for improving the drought adaptability of E. ulmoides.PMID:40642984 | DOI:10.1128/spectrum.00847-25

Phytother Res. 2025 Jul 11. doi: 10.1002/ptr.8076. Online ahead of print.ABSTRACTThe potential effects of Puerariae Lobatae Radix (Gegen in Chinese) water extract (GWE) on overactive bladder (OAB) were previously demonstrated through ex vivo examination of detrusor contraction. However, the mechanisms were not fully understood. The current aim was to investigate the therapeutic mechanisms of GWE against OAB in spontaneously hypertensive rats (SHR) with bladder ischemia. The therapeutic effect of GWE against OAB was evaluated by urodynamics. Hematoxylin & eosin (H&E) staining, Masson staining, and Doppler ultrasonic blood stream detector were utilized to observe bladder structures and local blood flow, respectively. To elucidate the mechanisms, an integrated omics approach was employed. The key proteins and metabolites were validated using Western Blotting and ELISA. A 3-week treatment of GWE demonstrated a significant improvement in urodynamic parameters. The results from Doppler detector, H&E staining, and Masson staining indicated that GWE improved vasodilation of bladder microvessels. Transcriptomic analysis revealed changes in genes such as Ptgfr and Ntsr1, which were involved in regulating intracellular Ca2+ concentration. Proteomic analysis suggested that the downregulation of epoxide hydrolase 2 (EPHX2), maintaining the balance of epoxyeicosatrienoic acids (EETs), was responsible for GWE-induced vasodilation. Metabolomic analysis further supported alterations in arachidonic acid (AA) metabolism. It is concluded that GWE treated OAB in SHR rats by improving bladder blood flow through the inhibition of EPHX2 and upregulation of EETs. This inhibition resulted in the improvement of bladder structure and the suppression of AA metabolism-mediated PTGES/PTGFR/PLCβ1/phospho-MLC signaling pathway.PMID:40642956 | DOI:10.1002/ptr.8076

J Agric Food Chem. 2025 Jul 11. doi: 10.1021/acs.jafc.5c03576. Online ahead of print.ABSTRACTExcessive nitrogen application reduces nitrogen use efficiency (NUE) and exacerbates environmental risks. Nanoselenium (nano-Se) has been shown to enhance plant nitrogen uptake efficiency. This study investigated nano-Se influences potato (Solanum tuberosum L.) tuber yield, quality, rhizosphere soil enzyme activity, and inorganic nitrogen content under different nitrogen application levels, integrating metabolomic, metagenomic, and soil metabolomic analyses. Results showed that the N2 + Se treatment matched the yield of the N3 + Se treatment but notably boosted vitamin C (Vc), starch content, and NUE. Metabolomic analysis showed that nano-Se promoted the accumulation of d-glucose-1-phosphate (a starch precursor) and amino acids (raw materials for protein) in tubers. Multiomics data indicated that nano-Se recruited beneficial rhizobacteria such as Flavobacterium and Pseudoxanthomonas by exuding l-tyrosine, l-valine, and 4-oxoproline. In addition, It promoted nitrate assimilation genes (narB and nirB) and suppressed nitrification genes (amoA and hao), reducing nitrogen losses.PMID:40642907 | DOI:10.1021/acs.jafc.5c03576

J Agric Food Chem. 2025 Jul 11. doi: 10.1021/acs.jafc.5c03530. Online ahead of print.ABSTRACTArbuscular mycorrhizal fungi (AMF) influence plant-insect interactions, yet how they modulate volatile organic compounds (VOCs) to affect insect behavior remains unclear. This study integrates physiological assays, GC-MS volatile metabolomics, and insect bioassays to investigate how Funneliformis mosseae (Fm) and Rhizophagus intraradices (Ri) inoculation affects Perilla frutescens growth and its resistance to Spodoptera exigua. The results showed that Fm and Ri inoculation both promoted plant growth but differed in defense strategies. Ri inoculation increased the tannin content (16.98%) and polyphenol oxidase activity (40.52%), whereas Fm inoculation showed neutral effects. VOC profiling revealed that Ri inoculation upregulated leaf monoterpenes and phenylpropanoids, while Fm inoculation reduced sesquiterpenes (e.g., β-selinene). Insect bioassays showed that Ri inoculation inhibited the insect growth, whereas Fm inoculation promoted the insect growth and enhanced its feeding preference. These results revealed that AMF triggers a plant growth-defense trade-off, with sesquiterpenoid regulation critical for insect behavioral shifts. The findings provide a basis for sustainable pest management using AMF-plant symbiosis.PMID:40642887 | DOI:10.1021/acs.jafc.5c03530

Quintessence Int. 2025 Jul 11;0(0):0. doi: 10.3290/j.qi.b6362487. Online ahead of print.ABSTRACTOBJECTIVE: This study aimed to investigate the causal relationship between metabolites and periodontitis using Mendelian randomization (MR) and validate findings through gingival crevicular fluid (GCF) metabolomic profiling.METHODS AND MATERIALS: A two-sample MR analysis used genetic data from 486 metabolite Genome-Wide Association Study (GWAS) and periodontitis statistics, with IVW as the primary method, supported by MR-Egger, weighted median, and weighted mode. Sensitivity analyses included Cochran's Q, MR-Egger, and MR-PRESSO tests. GCF metabolomics compared 5 periodontitis patients and 5 controls, identifying differential metabolites via t-tests and PLS-DA, with KEGG pathway enrichment.RESULTS: MR analysis identified 17 metabolites causally linked to periodontitis, spanning amino acids, lipids, energy metabolism, and cofactors/vitamins. Protective metabolites included betaine (OR: 0.478, 95% CI:0.235-0.975), laurate (0.51, 0.267-0.974), and glycerol 3-phosphate (0.312, 0.105-0.926), while phenylalanine (39.651, 2.173-723.565), pelargonate (2.527, 1.059-6.03), and 3-methylhistidine (1.481, 1.074-2.042) increased risk. Sensitivity analyses confirmed minimal heterogeneity, no pleiotropy (except 4-acetamidobutanoate), and no reverse causation. GCF metabolomics revealed 75 upregulated and 245 downregulated metabolites, with pathway enrichment in lipid, amino acid, and vitamin metabolism. Notably, betaine-protective in MR analysis-was significantly reduced in periodontitis, aligning with its anti-inflammatory role.CONCLUSION: This study indicates that some circulating metabolites (e.g., betaine) may protect against periodontitis. Integrating MR and GCF analyses, we identified key metabolic risk factors. Clinically, metabolites like betaine and glycerol 3-phosphate could serve as non-invasive early biomarkers, providing new avenues for personalized periodontitis prevention and treatment.PMID:40642796 | DOI:10.3290/j.qi.b6362487

Food Chem X. 2025 Jun 19;29:102681. doi: 10.1016/j.fochx.2025.102681. eCollection 2025 Jul.ABSTRACTThis study aimed to investigated metabolism and browning-related enzyme differences of Fuji apples in fresh (FC), browning pulp (BR), and browning inhibition pulp (CM) at 0, 4, 6, and 8 months of storage. Apples stored for 4-months exhibited the highest browning rate and color differences, with browning inhibition effectiveness decreasing over time. PPO and POD activity increased, while CAT and SOD decreased. Untargeted metabolomics revealed differential metabolites (445, 468, 265) in FC, BR, and CM among four-storage, mainly related to carbohydrate, lipid, and amino acid metabolism. In BR vs. FC, differential metabolites were primarily enriched in secondary metabolite biosynthesis (within 6-months) and energy metabolism (after 8-months). In CM vs. FC, differential metabolites were significantly enriched in nitrogen metabolism. Nitrogen metabolite accumulation induces browning, which can be mitigated by CaCl2 through alleviating nitrosative stress and oxidative damage. These findings provide metabolic insights into quality control during apple storage and processing.PMID:40642524 | PMC:PMC12242009 | DOI:10.1016/j.fochx.2025.102681

Curr Res Food Sci. 2025 Jun 19;11:101121. doi: 10.1016/j.crfs.2025.101121. eCollection 2025.ABSTRACTCardamine violifolia is an emerging cruciferous vegetable rich in nutrients and bioactive components. This study investigated the microbial community and metabolite profiles in C. violifolia leaf pickles prepared using three fermentation methods: natural fermentation (NF), inoculation with Lactiplantibacillus plantarum (LP), and inoculation with Leuconostoc mesenteroides (LM). Results revealed that fermentation significantly altered the microbial composition, with Firmicutes becoming the dominant phylum. Lactococcus and Weissella were predominant in both the NF and LM groups, while Lactiplantibacillus dominated in the LP group. Metabolomic analysis identified 865 metabolites in total, with amino acids, lipids, and alkaloids representing the most abundant classes. Fermentation enhanced the production of bioactive compounds (e.g., alkaloids, phenolic acid, flavonoids), particularly in the LP group. Correlation analysis indicated a strong relationship between specific microorganisms and active metabolites. These findings suggest that fermentation not only improved the edible and nutritional value of C. violifolia leaf pickles but also enhanced their potential health benefits.PMID:40642499 | PMC:PMC12241996 | DOI:10.1016/j.crfs.2025.101121

Chin J Cancer Res. 2025 Jun 30;37(3):316-336. doi: 10.21147/j.issn.1000-9604.2025.03.03.ABSTRACTOBJECTIVE: Triple-negative breast cancer (TNBC) is a highly aggressive subtype that lacks targeted therapies, leading to a poorer prognosis. However, some patients achieve long-term recurrence-free survival (RFS), offering valuable insights into tumor biology and potential treatment strategies.METHODS: We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer (AJCC) stage III TNBC, comprising 36 long-term survivors (RFS≥8 years), 62 moderate-term survivors (RFS: 3-8 years), and 34 short-term survivors (RFS<3 years). Analyses investigated clinicopathological factors, whole-exome sequencing, germline mutations, copy number alterations (CNAs), RNA sequences, and metabolomic profiles.RESULTS: Long-term survivors exhibited fewer metastatic regional lymph nodes, along with tumors showing reduced stromal fibrosis and lower Ki67 index. Molecularly, these tumors exhibited multiple alterations in genes related to homologous recombination repair, with higher frequencies of germline mutations and somatic CNAs. Additionally, tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway. Metabolomic profiling revealed decreased levels of lipids and carbohydrate, particularly those involved in glycerophospholipid, fructose, and mannose metabolism, in long-term survival group. Multivariate Cox analysis identified fibrosis [hazard ratio (HR): 12.70, 95% confidence interval (95% CI): 2.19-73.54, P=0.005] and RAC1 copy number loss/deletion (HR: 0.22, 95% CI: 0.06-0.83, P=0.026) as independent predictors of RFS. Higher fructose/mannose metabolism was associated with worse overall survival (HR: 1.30, 95% CI: 1.01-1.68, P=0.045). Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.CONCLUSIONS: Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC, suggesting potential therapeutic targets to improve patient outcomes.PMID:40642486 | PMC:PMC12240250 | DOI:10.21147/j.issn.1000-9604.2025.03.03