PubMed

Front Endocrinol (Lausanne). 2025 Feb 25;16:1501305. doi: 10.3389/fendo.2025.1501305. eCollection 2025.ABSTRACTAs a multidimensional metabolic disorder, the disability and death rate of type 2 diabetes mellitus (T2DM) has increased over time. T2DM covers a wide range of pathological manifestations ranging from hyperglycemia to multi-organ failure, and it has the potential to evolve into acute complications, including ketosis and chronic complications such as peripheral neuropathy, retinopathy, and nephropathy. T2DM mainly occurs in microvascular and large vessels and thus it is restricted for the clinician to diagnose and prescribe. However, the pathological mechanism and clinical diagnosis are inadequate. High-throughput metabolomics, characterized by non-invasive diagnostic techniques to identify potential biomarkers and distinct stages of T2DM, has been increasingly recognized as a vigorous tool with latent capacity for clinical translation. The pathological stratification of T2DM can significantly reduce disability and mortality rates. By tracing the metabolome and associated pathways from impaired fasting blood glucose or impaired glucose tolerance to severe organ failure, the chief contributions of large, independent population-based cohorts are summarized herein. These results facilitate understanding the pathophysiology and mechanism and supports research in accurate diagnosis, risk prediction, curative effect, distinct stages, and prognosis judgment of T2DM.PMID:40070584 | PMC:PMC11893406 | DOI:10.3389/fendo.2025.1501305

Front Pharmacol. 2025 Feb 25;16:1552228. doi: 10.3389/fphar.2025.1552228. eCollection 2025.ABSTRACTINTRODUCTION: Vascular dementia (VD) is a neurodegenerative disease caused by chronic cerebral hypoperfusion (CCH), which considerably impact patients' quality of life. Ethanol extraction from Rubia yunnanensis (RY-A) has gained attention for its potential neuroprotective effects, but its effects and mechanisms of action on CCH are unknown.METHODS: After 30 days of RY-A gavage treatment in a CCH rat model, its effects were evaluated using the Morris water maze test, cerebral blood flow measurements, and HE staining of the brain. These findings, combined with serum medicinal chemistry, RNA-seq, and metabolomics analyses, revealed the active compounds and mechanisms of RY-A in CCH rats. The results were further validated using assay kits and Western blot techniques.RESULTS: RY-A treatment significantly attenuated neurological damage and improved cognitive function in CCH rats. Ultra-high-performance liquid chromatography high-resolution mass spectrometry identified 511 blood-entry compounds of RY-A. RNA-seq and metabolomic analysis showed that RY-A might help to normalize changes in gene and metabolite expression caused by CCH. RY-A induced neuroprotective effects by increasing the production of key proteins involved in ferroptosis inhibition, such as SLC7A11, SLC3A2, GSS, and GPX4, while increasing antioxidant enzyme activities and alleviating oxidative stress.CONCLUSION: RY-A inhibited oxidative stress and ferroptosis by activating the System Xc-/GSH/GPX4 pathway and balancing iron metabolism, thereby attenuating CCH-induced neurological damage and cognitive deficits.PMID:40070574 | PMC:PMC11893507 | DOI:10.3389/fphar.2025.1552228

Physiol Mol Biol Plants. 2025 Feb;31(2):173-197. doi: 10.1007/s12298-025-01554-w. Epub 2025 Mar 3.ABSTRACTThe substantial economic impact of thrips on crop yield and productivity enthused us to review comprehensive research findings associated with plant-thrips interaction. An attempt has been made to summarize a broad spectrum of knowledge on thrips infestation in different crops regarding defensive traits including plant morphological features, biochemical alterations and transcriptional profiling of defensive genes along with effective thrips management strategies. Thrips feeding mechanism involves puncturing the outer (epidermal) layer of host tissue and evoking the plant defence mechanism. Plants respond to thrips attacks by activating the defensive genes, which lead to the production of physical barriers (trichomes, waxes, and papillae) and biochemical compounds (primary and secondary metabolites). It is imperative to appreciate the physiological responses, metabolic changes, and regulation at the transcriptional level of various phytoconstituents during thrips feeding. The literature survey revealed that leaf size, papillae and trichome density, total phenols, tannins and genes associated with phenylalanine metabolism and flavonoid biosynthesis contribute to plant resistance against thrips infestation. Thus, this comprehensive overview will serve as a roadmap for researchers, guiding future studies and the development of sustainable pest management practices to mitigate thrips-related damage and enhance crop resilience.PMID:40070534 | PMC:PMC11890886 | DOI:10.1007/s12298-025-01554-w

Front Nutr. 2025 Feb 25;12:1522429. doi: 10.3389/fnut.2025.1522429. eCollection 2025.ABSTRACTOBJECTIVE: Our study aim is to explore the mechanisms of short peptide passages on intestinal dysfunction in septic mice utilizing a metabolomics approach, which provides a new scientific basis for the clinical study of sepsis.METHODS: Mices were allocated at random into four groups: control (Con), cecal ligation and puncture followed by one, three or 7 day short-peptide-based enteral nutrition group (CLP + SPEN1), (CLP + SPEN3), and (CLP + SPEN7) groups. A liquid chromatography-mass spectrometry-based metabolomics method was used to analyze changes in serum metabolites in septic mice.RESULTS: Short peptides showed effectiveness in reducing symptoms, mucosal inflammation, and intestinal function damage scores in septic mice. The 16sRNA analysis showcased significant variances in the distribution of bacterial communities between the CLP + SPEN1, CLP + SPEN3, and CLP + SPEN7 groups. At the phylum level, statistically significant variances in the relative abundance of Proteobacteria, Firmicutes, and Bacteroidetes were recognized. The metabolomics analysis results showed significant separation of metabolites between the CLP + SPEN1 and CLP + SPEN3 groups, as well as significant differences in metabolite profiles between the CLP + SPEN3 and CLP + SPEN7 groups. Utilizing a differential Venn diagram, four metabolites were commonly different; 10-heptadecanoic and dodecanoic acids had statistical significance. The abundance of both dodecanoic and lactic acid bacteria was negatively associated at the genus level.CONCLUSION: Short peptides were found to promote the growth of beneficial bacteria, Lactobacillus and uncultured_bacterium_f_Muribaculaceae, while reducing intestinal metabolites such as Dodecanoic acid and 10-Heptadecenoic acid. Moreover the Lactobacillus may play a significant therapeutic role in the treatment of sepsis. However, due to the limited number of experimental samples, the exact mechanism of action of short peptides awaits further confirmation.PMID:40070479 | PMC:PMC11893400 | DOI:10.3389/fnut.2025.1522429

Front Physiol. 2025 Feb 25;16:1537099. doi: 10.3389/fphys.2025.1537099. eCollection 2025.ABSTRACTThe liver-gut axis plays a central role in maintaining the health and productivity of poultry. In addition, the liver-gut axis serves as a key regulator of digestion, metabolism, immunity, and detoxification. The gut, with its diverse microbiota, is the primary site for nutrient absorption and immune modulation, while the liver metabolizes nutrients, detoxifies harmful substances, and acts as a frontline defense against pathogens translocated from the gut. Disruptions in this interconnected system, including gut dysbiosis or liver inflammation, can lead to compromised immunity and reduced productivity. This mini-review explores integrated nutritional and immunological strategies aimed at optimizing the liver-gut axis to enhance poultry performance. Nutritional interventions, such as the use of flavonoids, vitamins, amino acids, micronutrients, probiotics, prebiotics, and synbiotics, have demonstrated their potential to support liver and gut health. Dietary components such as phytogenic additives, fiber, and fatty acids further contribute to immune modulation and systemic health. Immunological approaches, such as beta-glucans and in ovo stimulation, and molecular approaches, including advanced genetic techniques, offer additional avenues for improving disease resistance and organ function. Despite notable advancements, challenges including antibiotic resistance, environmental stressors, and implementation costs persist. Emerging technologies like metagenomics, metabolomics, and precision breeding offer innovative solutions to enhance liver-gut interactions. This review underscores recent advancements in understanding the liver-gut axis and calls for holistic strategies to improve sustainable poultry production. Future research should integrate these approaches to enhance resilience, productivity, and sustainability in the poultry industry.PMID:40070462 | PMC:PMC11893858 | DOI:10.3389/fphys.2025.1537099

Postep Psychiatr Neurol. 2024 Dec;33(1):201-212. doi: 10.5114/ppn.2024.144224. Epub 2024 Nov 27.ABSTRACTPURPOSE: Young adults experience high stress levels, leading to mood disorders. This study investigates the associations between specific fatty acid levels, lipid profiles, inflammatory markers, and emotional well-being among young adults.METHODS: Seventy-two young adults aged 18-35 participated in this study. Participants completed self-assessments of depression severity (PHQ-9), stress (PSS-10), insomnia (ISI), and anxiety (GAD-7). Blood samples were collected and analyzed for plasma fatty acid profiles, lipid profiles, C-reactive protein (CRP) and kynurenine pathway metabolites. Classification and Regression Tree (C&RT) and multivariate stepwise regression analyses were employed to identify potential predictors of mental health outcomes.RESULTS: The analyses revealed significant associations between certain fatty acids, lipid markers, and mental health conditions. Lauric acid, myristic acid, and eicosatrienoic acid were identified as potential indicators of mental health issues. Higher levels of palmitoleic acid were linked to increased depressive symptoms, while higher oleic acid levels were associated with reduced depression. Anxiety was influenced by myristoleic acid and docosahexaenoic acid. Stress and sleep disturbances correlated with specific fatty acids. The models explained a significant percentage of variability in mental health outcomes, accounting for 25% in both depressive symptoms and anxiety, 23% in stress, and 43% in sleep disturbances.CONCLUSIONS: Specific fatty acids, associated with lipid profiles, kynurenic acid, and CRP, significantly impact the mental health of young adults. Monitoring biomarkers may assist in managing mental health disorders. Personalized dietary interventions could improve well-being and sleep quality. Further research is needed to confirm these findings and establish causal relationships.PMID:40070427 | PMC:PMC11891755 | DOI:10.5114/ppn.2024.144224

Front Cell Infect Microbiol. 2025 Feb 25;15:1484144. doi: 10.3389/fcimb.2025.1484144. eCollection 2025.ABSTRACTBACKGROUND: Post-neurosurgical bacterial meningitis (PNBM) is a severe complication in patients receiving neurosurgical treatments. Pathogens and neuroinflammation have been reported to influence metabolites in the microenvironment of the central nervous system. However, information about the relationship between neurotransmitter levels and PNBM is still limited. In this study, we aimed to investigate the diagnostic potential of neurotransmitters for PNBM in the patients with stroke.METHODS: In this study, a total of 66 stroke patients were recruited. Among them, 40 patients were complicated with PNBM. We profiled cerebrospinal fluid (CSF) levels of neurotransmitter precursors and metabolites using the targeted metabolomics method, which contained 26 precursors and metabolites of neurotransmitters, using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC/MS).RESULTS: We found that 14 biomarkers were downregulated but 3,4-dihydroxyphenylacetic acid (DOPAC) was upregulated in the CSF of PNBM patients. Among the biomarkers, D-glutamine (AUC=1.000), Boc-D-Tyr-OH (AUC=0.9447), L(+)-arginine (AUC=0.9418), and DOPAC (AUC=0.9173) had strong diagnostic efficiency for PNBM. Bioinformatic analysis showed that tyrosine metabolism, butanoate metabolism, histidine metabolism, alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and tryptophan metabolism might be involved in the pathogenesis of PNBM. After reviewing previous studies, we found a probable diverse pathophysiological alteration between PNBM and community-acquired bacterial meningitis.CONCLUSIONS: In summary, we identified downregulated levels of D-glutamine, Boc-D-Tyr-OH, L(+)-arginine, and phenprobamate, and an upregulated level of DOPAC in CSF to have strong diagnostic efficiencies. The results also offered potential targets for the treatment of PNBM.PMID:40070373 | PMC:PMC11893869 | DOI:10.3389/fcimb.2025.1484144

Curr Protein Pept Sci. 2025 Mar 11. doi: 10.2174/0113892037350167250121112656. Online ahead of print.ABSTRACTRotator cuff injury is a disease in which the muscle and tendon that constitute the rotator cuff are torn causing shoulder pain and limited function. Osteoporosis (OP) is a systemic metabolic bone disease characterized by decreased bone mass, destruction of bone microstructure, decreased bone strength, and increased bone fragility. Both are common musculoskeletal diseases that occur in middle-aged and elderly people, and their prevalence gradually increases with age. Clinically, rotator cuff injury and OP comorbidity are very common, especially in terms of bone metabolism. In recent years, plant natural products have gradually become a research hotspot. Icariin (ICA) is one of the naturally present active ingredients derived from the Berberaceae herb Epimedium. It has various pharmacological effects, such as anti-inflammatory, antioxidant, and anti- tumor properties, and is involved in the regulation of bone metabolism, which can play multiple therapeutic effects through a variety of proteins, receptors, and signaling pathways. Therefore, ICA, as a potential natural drug, is being gradually applied in the treatment of rotator cuff injury combined with OP, which has achieved great clinical efficacy. This study mainly discusses the pharmacological action and action mechanism of ICA in order to explore the potential of ICA to prevent and treat rotator cuff injury combined with OP and provide a theoretical basis for the subsequent clinical application of ICA.PMID:40070332 | DOI:10.2174/0113892037350167250121112656

Plant Cell Environ. 2025 Mar 12. doi: 10.1111/pce.15471. Online ahead of print.ABSTRACTPlant growth-promoting rhizobacteria (PGPR) are widely recognized for enhancing the absorption of mineral nutrients by crops. While Sphingobium species have been reported as PGPRs, their capacity to improve nitrogen use efficiency (NUE) and the underlying regulatory mechanisms are not yet fully understood. Here, a strain 41R9, isolated from the rhizosphere of N-deficient rapeseed, was found to significantly enhance the growth performance of rapeseed under both low and normal N conditions. Genomic analysis revealed that strain 41R9 was closely related to Sphingobium yanoikuyae. 15N isotope tracer experiments confirmed that inoculation with strain 41R9 significantly boosted N uptake and translocation in rapeseed roots. Transcriptome profiling demonstrated that strain 41R9 directly upregulated N transporter genes (NRT2.5 and SLAH1/3), facilitating efficient N acquisition. Furthermore, strain 41R9 maintained jasmonic acid (JA) homoeostasis via JAZ-mediated negative feedback, balancing defense responses and root development, thereby improving the plant's N acquisition capacity in the roots. Metabolomic and in vitro assays further demonstrated that strain 41R9 displayed strong chemotaxis towards kaempferol, a N-deficiency-induced root exudate, suggesting kaempferol might as a chemical effector for S. yanoikuyae recruitment. These findings advance our understanding of PGPR-driven mechanisms in enhancing crop NUE and highlight the potential of harnessing PGPRs for sustainable agriculture.PMID:40070320 | DOI:10.1111/pce.15471

Plant Physiol Biochem. 2025 Feb 28;222:109726. doi: 10.1016/j.plaphy.2025.109726. Online ahead of print.ABSTRACTPlants have evolved a variety of regulatory mechanisms to adapt to changing environment conditions. Secondary metabolites play a crucial role in these adaptive processes. However, little is known about whether specific secondary metabolites confer broad-spectrum resistance to various biotic and abiotic stresses. In this study, we compared the cultivated tomato Solanum lycopersicum L. Ailsa Craig (AC) with the wild tomato Solanum habrochaites S.Knapp & D.M.Spooner LA1777. We found that wild tomato LA1777 exhibited stronger resistance than cultivated tomato AC under cold, drought, salt stresses, and attack by the insect Helicoverpa armigera. Comparative metabolomic analysis of cultivated tomato AC and wild tomato LA1777 revealed significantly higher levels of terpenoid compounds, particularly sesquiterpenes in wild tomato LA1777. Transcriptomic analysis of the terpenoid synthase gene family, combined with virus-induced gene silencing, identified β-Caryophyllene synthase 1 (ShCAS1) as essential for β-Caryophyllene production in wild tomato LA1777 under cold stress. Silencing ShCAS1 compromised the plant's resistance to cold, drought, salt stresses and H. armigera attack in wild tomato LA1777, while exogenous application of β-Caryophyllene enhanced resistance to these stresses in cultivated tomato AC. These findings underscore the significant role of ShCAS1-synthesized β-Caryophyllene in conferring broad-spectrum resistance in tomatoes, suggesting that this compound could be a key target for breeding or biotechnological approaches aimed at improving the resilience of crops to diverse environmental challenges.PMID:40069972 | DOI:10.1016/j.plaphy.2025.109726

Physiol Plant. 2025 Mar-Apr;177(2):e70151. doi: 10.1111/ppl.70151.ABSTRACTThe increasing impacts of climate change and intensified human activities exacerbate soil salinization, posing significant challenges to agricultural productivity. Therefore, addressing salt stress in crops is a critical area of research. In this study, strawberry seedlings (Fragaria×ananassa Duch. 'Benihoppe') were used to investigate the alleviating effects of hydrogen-rich water (HRW) on salt stress through integrated transcriptomic and metabolomic analyses. HRW treatment was found to significantly enhance plant growth, notably increasing root biomass by 49.50%. Additionally, HRW modulated key parameters, including the levels of soluble sugars, malondialdehyde (MDA), and antioxidant enzyme activities, while promoting K+ uptake and Na+ exclusion. Transcriptomic analysis revealed that HRW induced the expression of genes associated with ion transport, antioxidant defence, and cell wall biosynthesis in roots. Metabolomic profiling identified phenolic acids, flavonoids, and amino acids as critical metabolites in HRW-mediated salt stress mitigation. Integrated multi-omics analysis highlighted two key metabolic pathways, phenylpropanoid biosynthesis and amino and nucleoside sugar metabolism, pivotal to the observed protective effects. This study provides molecular insights into the mechanisms by which HRW alleviates salt stress in strawberry seedlings, underscoring the potential of hydrogen gas applications in sustainable agriculture.PMID:40069937 | DOI:10.1111/ppl.70151

Lipids Health Dis. 2025 Mar 11;24(1):89. doi: 10.1186/s12944-025-02512-x.ABSTRACTINTRODUCTION: This systematic review explores the hypothesis that various lipid categories and lipid metabolism-related genomic variations link to mental disorders, seeking potential clinically useful markers.METHODS: We searched PubMed, Scopus, and PsycInfo databases until October 12th, 2024, using terms related to lipidomics, lipid-related genomics, and different mental disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia (SCZ), and Obsessive-Compulsive Disorder (OCD). Eligible studies were assessed. Extracted data included author, year, methodology, outcomes, genes, and lipids linked to disorders. Bias and evidence certainty were evaluated. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and a registered protocol (PROSPERO: CRD42023438862).RESULTS: A total of 27 studies were included. SCZ showed alterations in 77 lipids, including triglycerides (TG), ceramides, and phosphatidylcholine, while MDD and BD exhibited 97 and 47 altered lipids, respectively, with overlap among disorders. Shared genes, such as ABCA13, DGKZ, and FADS, and pathways involving inflammation, lipid metabolism, and mitochondrial function were identified. OCD was associated with sphingolipid signaling and peroxisomal metabolism.DISCUSSION: Lipid signatures in MDD, BD, and SCZ shed light on underlying processes. Further research is needed to validate biomarkers and refine their clinical applications in precision psychiatry.PMID:40069786 | DOI:10.1186/s12944-025-02512-x

Biotechnol Biofuels Bioprod. 2025 Mar 11;18(1):32. doi: 10.1186/s13068-025-02628-3.ABSTRACTBACKGROUND: Given the global rise in antimicrobial resistance, the discovery of novel antimicrobial agents and production processes thereof are of utmost importance. To this end we have activated the gene cluster encoding for the biosynthesis of the potent antifungal compound ilicicolin H in the fungus Trichoderma reesei. While the biosynthetic gene cluster (BGC) is silent under standard cultivation conditions, we achieved BGC activation by genetically overexpressing the transcription factor TriliR.RESULTS: Successful activation was confirmed by RT-qPCR, proteomic and metabolomic analyses. Metabolomic profiling upon BGC expression revealed high-yield production of ilicicolin H. To elucidate the enzymatically highly diverse functionality of this BGC, we employed a combination of overexpression and deletions of individual genes in the BGC. While we hardly observed any of the previously reported side- or shunt products associated with heterologous ilicicolin H expression, we discovered that Trichoderma reesei produces a novel member of the ilicicolin family using a metabolomic molecular networking approach. This new compound, ilicicolin K, is expressed in substantial amounts in the genetically engineered Trichoderma reesei. Ilicicolin K differs from ilicicolin H in its structure by a second hydroxylation of the tyrosine derived phenol and an additional ring formed by an intramolecular ether bridge of the hydroxyl group at the pyridone towards the tyrosine moiety of the molecule. Bioactivity tests of ilicicolin K revealed a strong antifungal activity against Saccharomyces cerevisiae and a moderate activity against the human pathogen Candida auris, an emerging multi-drug resistant fungus.CONCLUSIONS: By activating a silent BGC in T. reesei, we obtained a high-yielding strain for the production of the antifungal compounds ilicicolin H and the novel ilicicolin K. These two compounds share some structural properties and are thus highly likely to act on the fungal cytochrome bc1 complex, a component of the mitochondrial repository chain. However, they possess different bioactive properties, which might suggest that ilicicolin K may overcome certain limitations of ilicicolin H.PMID:40069746 | DOI:10.1186/s13068-025-02628-3

BMC Cancer. 2025 Mar 11;25(1):438. doi: 10.1186/s12885-025-13866-x.ABSTRACTBACKGROUND: Esophageal squamous cell carcinoma (ESCC), the most common type of esophageal cancer, characterized by low five-year survival rate, and concurrent chemoradiotherapy (CCRT) has been proposed to treat ESCC, while potential biomarkers for prognostic monitoring after optimized CCRT remains unknown.METHODS: Serum samples from 45 patients with ESCC were collected and categorized into three groups: Control (pre-CCRT), CCRT (during CCRT), and CCRT-1 M (one-month post-CCRT). The therapeutic effect was evaluated using CT imaging and established evaluation criteria. Untargeted metabolomic analysis was performed on the serum samples to identify differential metabolites caused by CCRT treatment, assessing their potential for prognostic monitoring.RESULTS: CCRT had significant therapeutic efficacy in patients with ESCC, as indicated by CT imaging and RECIST 1.1 solid tumor evaluation criteria. Notably, several metabolic markers were identified through non-targeted metabolomic analysis, highlighting changes following CCRT treatment. These differential metabolites are involved in the dysregulation of phenylalanine, tyrosine, and tryptophan biosynthesis, as well as histidine, arginine, and proline metabolism, and glycine, serine, and threonine metabolism, suggesting a reduction in glucose metabolism in patients with ESCC after CCRT. Additionally, ROC analysis indicated that the AUC of these metabolites exceeded 0.661, underscoring their diagnostic value for assessing CCRT efficacy and their potential use in prognostic monitoring. Comparative metabolomic analysis identified L-phenylalanine and lysine as promising serum biomarkers for predicting therapeutic outcomes.CONCLUSIONS: CCRT shows considerable therapeutic benefit in patients with ESCC, with observed reductions in glucose metabolism post-treatment. L-phenylalanine and lysine may serve as potential serum biomarkers to predict CCRT efficacy.PMID:40069698 | DOI:10.1186/s12885-025-13866-x

BMC Plant Biol. 2025 Mar 11;25(1):312. doi: 10.1186/s12870-025-06337-9.ABSTRACTBACKGROUND: Tobacco is an important economic crop and a model plant for molecular biology research. It exists in various cultivars and is processed using different curing methods. Fatty acids play a crucial role in the quality and flavor of tobacco leaves. However, there is limited information on the fatty acid composition across different cultivars, developmental stages, and curing methods. This study employed targeted metabolomics and transcriptomics to investigate the fatty acids and related pathway genes in tobacco leaves from different cultivars, developmental stages, and curing methods.RESULTS: This study focused on four tobacco cultivars: K326, Basma, Samsun, and Cuba1, and investigated fatty acid differences in the leaves at four developmental stages (seedling, transplanting, budding, and topping) under two curing methods (air-curing and flue-curing). K326 was used as the main cultivar for comparison with the other three. The analysis included short-chain fatty acids (C2-C6), free fatty acids (C8-C24), and gene expression differences. The fatty acid metabolic profile of different tissue types in K326 at the budding stage was also examined. The results showed significant differences in fatty acid content among the different tissues of K326 at the budding stage, with the highest levels of short-chain fatty acids found in flower buds and upper leaves. At the seedling stage, there were marked variations in short-chain fatty acid content across different periods. Three key genes Nta01g31980, Nta08g22780, and Nta23g11140 were identified as major differential genes in fatty acid-related pathways in K326 compared to the other three cultivars during this stage. Regarding the four cultivars, the total short-chain fatty acid content at the budding stage was ranked as Basma > Samsun > Cuba1 > K326 before topping, but the order was reversed after topping. At the budding stage, 35 fatty acid pathway-related genes showed similar expression levels in Basma and Samsun, differing from K326 and Cuba1. Among the two curing methods, air-curing resulted in higher short-chain fatty acid content than flue-curing. Under air-curing, Samsun and Basma showed more downregulation of differential fatty acids compared to K326, while the opposite was observed under flue-curing.CONCLUSION: This study expands our understanding of fatty acids in tobacco across different cultivars and developmental stages, providing a molecular basis for the study of fatty acids and genes related to their biosynthesis and metabolism.PMID:40069610 | DOI:10.1186/s12870-025-06337-9

BMC Genomics. 2025 Mar 11;26(1):231. doi: 10.1186/s12864-025-11409-z.ABSTRACTWater spinach (Ipomoea aquatica Forsk.) is an important leaf vegetable affected by salt stress, however, little is known about its salt adaption mechanism. Here, we integrated physiomics, ionomics, transcriptomics, and metabolomics to analyze the root adaptation response of two water spinach varieties, BG (salt-tolerant) and MF (salt-sensitive), at 150 mM NaCl. The results showed that compared with MF, BG significantly reduced the content of malondialdehyde (MDA) and H2O2, and increased catalase (CAT) activity and proline content. Ionome analysis demonstrated that BG significantly reduced Na+ accumulation and increased K+ level to reduce the toxicity of Na+, compared to MF. Weighted gene co-expression network analysis (WGCNA) revealed that key transcription factors such as HSFA4A, bHLH093, and IDD7, which were only up-regulated in BG. Multi-omics revealed that BG reprogrammed key pathways: starch and sucrose metabolism, as well as galactose metabolism, leading to decreased amylose production and increased sucrose and galactose levels, helping to maintain cellular osmotic balance in response to salt stress. These findings provide insight into transcriptional regulation in response to salt stress, which could advance the genetic enhancement of water spinach.PMID:40069607 | DOI:10.1186/s12864-025-11409-z

Physiol Plant. 2025 Mar-Apr;177(2):e70146. doi: 10.1111/ppl.70146.ABSTRACTToona sinensis, a plant species renowned for its culinary and medicinal properties, exhibits diverse colour variations that contribute to its aesthetic appeal and commercial value. Understanding the molecular mechanisms underlying colour and aroma traits in Toona sinensis is crucial for breeding programs and quality regulation in agriculture and the food industry. The present investigation included a comprehensive analysis of the transcriptomic and metabolomic profiles of Toona sinensis with different colours, including green, red, and red leaves with green stems. Metabolic analysis revealed that the flavonoid biosynthesis pathway governs the colour distinction between green and red Toona sinensis. The top 10 metabolites influenced by transcriptome include terpenoids (5), heterocyclic compounds (1), phenol (1), ketone (1), aldehyde (1), and alcohol (1). Fifteen highly expressed genes impacted by phenylpropanoid, sesquiterpenoid, and triterpenoid biosynthesis in coloured Toona sinensis. Functional annotation and pathway analysis revealed that terpene metabolites are predominantly synthesized via terpene metabolic pathway, involving eight key gene families. This study underscores the importance of multi-omics approaches in unravelling the genetic and metabolic basis of phenotypic traits in plant species aimed at improving colour, aroma, and nutritional quality in plants and derived products. HIGHLIGHTS: Flavonoid biosynthesis pathway governs the colour distinction between green and red Toona sinensis. The top 10 metabolites influenced by transcriptome include five terpenoids, one heterocyclic compound, one phenol, one ketone, one aldehyde, and one alcohol. Fifteen highly expressed genes impacted by phenylpropanoid, sesquiterpenoid, and triterpenoid biosynthesis in coloured Toona sinensis. Terpene metabolites are predominantly synthesized via the terpene metabolic pathway, involving eight key gene families. The net photosynthetic rate and intercellular CO2 concentration are relatively high in the red Toon sinensis morph.PMID:40069569 | DOI:10.1111/ppl.70146

Commun Biol. 2025 Mar 11;8(1):415. doi: 10.1038/s42003-025-07808-3.ABSTRACTWater kefir (WK) is an artisanal fermented beverage made from sugary water, optional fruits and WK grains. WK grains can be reused to start new fermentations. Here we investigate the microbial composition and function of 69 WK grains and their ferments by shotgun metagenomics. A subset of samples was subjected to metabolomic, including volatilomic, analysis. The impact of different fermentation practices on microbial composition and fermentation characteristics was analysed and it was noted that, for example, the common practice of drying water kefir grains significantly reduces microbial diversity and negatively impacts subsequent grain growth. Metagenomic analysis allowed the detection of 96 species within WK, the definition of core genera and the detection of different community states after 48 h of fermentation. A total of 485 bacterial metagenome assembled genomes were obtained and 18 putatively novel species were predicted. Metabolite and volatile analysis show associations between key species with flavour compounds. We show the complex microbial composition of WK and links between fermentation practices, microbes and the fermented product. The results can be used as a foundation for the selection of species for large scale WK production with desired flavour profiles and to guide the regulatory framework for commercial WK production.PMID:40069560 | DOI:10.1038/s42003-025-07808-3

Nat Metab. 2025 Mar 11. doi: 10.1038/s42255-025-01243-8. Online ahead of print.ABSTRACTLung adenocarcinoma (LUAD) is an aggressive cancer defined by oncogenic drivers and metabolic reprogramming. Here we leverage next-generation spatial screens to identify glycogen as a critical and previously underexplored oncogenic metabolite. High-throughput spatial analysis of human LUAD samples revealed that glycogen accumulation correlates with increased tumour grade and poor survival. Furthermore, we assessed the effect of increasing glycogen levels on LUAD via dietary intervention or via a genetic model. Approaches that increased glycogen levels provided compelling evidence that elevated glycogen substantially accelerates tumour progression, driving the formation of higher-grade tumours, while the genetic ablation of glycogen synthase effectively suppressed tumour growth. To further establish the connection between glycogen and cellular metabolism, we developed a multiplexed spatial technique to simultaneously assess glycogen and cellular metabolites, uncovering a direct relationship between glycogen levels and elevated central carbon metabolites essential for tumour growth. Our findings support the conclusion that glycogen accumulation drives LUAD cancer progression and provide a framework for integrating spatial metabolomics with translational models to uncover metabolic drivers of cancer.PMID:40069440 | DOI:10.1038/s42255-025-01243-8

Transl Stroke Res. 2025 Mar 11. doi: 10.1007/s12975-025-01342-4. Online ahead of print.ABSTRACTIntracerebral hemorrhage (ICH) is characterized by the rupture of blood vessels, allowing components from peripheral circulation to infiltrate the brain and impair central immune functions. This study employs non-targeted metabolomics to compare cerebrospinal fluid (CSF) metabolites between acute-phase and recovery-phase of ICH, aiming to identify metabolites associated with ICH central inflammation. CSF and plasma samples were collected from a retrospective observational cohort of participants with ICH (n = 38). Additionally, we obtained CSF samples from patients who underwent lower limb surgery due to accidental injuries, serving as healthy controls (n = 12). Non-targeted metabolomics analysis was performed, and inflammatory factors in the CSF were measured. The association between these metabolites and inflammation in the CSF was validated using a collagenase-induced ICH mouse model and microglial cultures in vitro. Our results demonstrate that the levels of certain metabolites in the cerebrospinal fluid of ICH patients changed significantly from the acute phase to the recovery phase (P < 0.05, VIP > 1). Furthermore, the concentration of inflammatory factors in the acute-phase CSF was significantly higher compared to both the recovery phase of ICH and healthy control levels. Correlation analyses of inflammatory factors and the patients' CSF metabolites revealed several metabolites associated with central inflammation. Notably, kynurenic acid (Kyna) exhibited a positive correlation with central inflammation and a negative correlation with the Glasgow Coma Scale (GCS). In the collagenase-induced ICH mouse model, elevated levels of Kyna were also associated with increased inflammation in the CSF. Additionally, in vitro studies demonstrated that Kyna regulates inflammatory cytokines by activating microglia. Our study highlights a significant relationship between metabolites in the CSF of ICH patients and central inflammation. Specifically, Kyna promotes inflammation by activating microglia, suggesting its potential as a promising target for therapeutic intervention in ICH central inflammation. Registration: 2023-KY-155-02.PMID:40069432 | DOI:10.1007/s12975-025-01342-4