PubMed

Ecotoxicol Environ Saf. 2025 May 14;298:118302. doi: 10.1016/j.ecoenv.2025.118302. Online ahead of print.ABSTRACTClomazone (CMZ) is a pesticide widely used for weed control in soybean fields. However, its persistence in the environment, including soil, surface water, and groundwater, poses potential risks to subsequent crops and human health. To evaluate the ecotoxicological impacts of CMZ residues on maize growth, a comprehensive study was conducted using integrated transcriptomic and metabolomic analyses of maize seedlings. The results showed that maize seedlings absorb CMZ through the roots and translocate it to the shoots, which led to inhibited growth, reduced chlorophyll content, decreased dry weight, increased electrolyte leakage, and elevated antioxidant enzyme activities. Differentially expressed metabolites (DEMs) and genes (DEGs) were significantly altered in CMZ-stressed maize seedlings, with 1456 DEGs and 1461 DEMs in roots, and 2946 DEGs and 2999 DEMs in shoots. Metabolomic profiling revealed the accumulation of key metabolites involved in CMZ catabolism, including carbohydrates, amino acids, glutathione, and flavonoids. UPLC-Q-TOF/MS analysis identified twelve CMZ transformation products (TPs), which correlated with the activities of DEGs, DEMs, and antioxidant enzymes. These findings indicate that maize seedlings detoxify absorbed CMZ through specific pathways, including decarboxylation, and primarily via canonical phase I and phase II reactions. This study suggests that crops like maize can mitigate the toxicity and residues of CMZ, providing insights for strategies to manage and control CMZ ecotoxicity.PMID:40373711 | DOI:10.1016/j.ecoenv.2025.118302

Food Chem. 2025 May 9;486:144706. doi: 10.1016/j.foodchem.2025.144706. Online ahead of print.ABSTRACTLotus seed juice has significant potential in the plant-based beverage market owing to its distinctive flavor. However, its sensory quality is significantly influenced by processing and storage conditions. This study examined the effects and underlying mechanisms of fresh squeezing, sterilization, and refrigeration at 4 °C (for 1-6 months) on the aroma profile of lotus seed juice using an electronic nose, gas chromatography-ion mobility spectrometry (GC-IMS), and non-targeted metabolomics. Sterilization processes resulted in vanilla, mint, and ammonia-like flavors due to the accumulation of hexanal, pentanal, and pyrrolidine. One month of refrigeration enhanced fruity and minty flavors, attributed to increased acetone and 6-ethyl acetate-D from fatty acid oxidation and esterification, respectively. However, prolonged refrigeration (six months) introduced undesirable alcoholic and pungent off-flavors caused by slow oxidative degradation (such as 2-propanol and 1-hydroxy-2-propanone). These findings provide valuable insights for improving the preservation methods and quality control strategies for plant-based beverages.PMID:40373601 | DOI:10.1016/j.foodchem.2025.144706

J Hazard Mater. 2025 May 12;494:138598. doi: 10.1016/j.jhazmat.2025.138598. Online ahead of print.ABSTRACTEtomidate (ETO), a widely used anesthetic, has emerged as a concerning environmental contaminant due to its increasing misuse and demonstrated neurotoxicity in aquatic organisms. This study employed an integrated multi-omics strategy to investigate the developmental neurotoxic effects of ETO in zebrafish (Danio rerio). ETO exposure induced dose-dependent toxicity in zebrafish embryos, characterized by decreased hatching rates (10-20 %), elevated mortality (up to 30 %), and morphological abnormalities such as scoliosis and pericardial edema. Behavioral assays revealed marked locomotor suppression (40-65 % reduction) and disrupted circadian rhythmicity. Neurochemical profiling indicated a 2.1-fold increase in dopamine levels, accompanied by significant reductions in GABAergic (38 %) and serotonergic (42 %) signaling, consistent with transcriptomic downregulation of related pathway genes. Metabolomic analysis revealed dysregulated lipid metabolism, including a 3.2-fold increase in eicosapentaenoic acid (EPA), and perturbations in phenylalanine metabolism. Transgenic zebrafish models (Tg(hb9:eGFP), Tg(coro1a:DsRed), Tg(elavl3:GCaMP6f)) further demonstrated motor neuron damage, inflammatory cell infiltration in the brain, and disrupted Ca2 + dynamics, indicating blood-brain barrier disruption and neuroinflammation responses. Molecular docking analysis confirmed ETO's binding affinity for GABA-A receptors, aligning with observed neurotransmitter imbalances. These findings elucidate ETO's neurotoxic mechanisms, involving neurotransmitter imbalance, metabolic disruption, and neuroinflammatory. The results underscore the dual threat of ETO as both an emerging aquatic pollutant and a developmental neurotoxicant, highlighting the urgent need for stricter environmental monitoring and a reevaluation of its safety profile, particularly during critical developmental windows.PMID:40373404 | DOI:10.1016/j.jhazmat.2025.138598

J Hazard Mater. 2025 May 6;494:138523. doi: 10.1016/j.jhazmat.2025.138523. Online ahead of print.ABSTRACTPlants require a fine balance of zinc (Zn) for proper growth and development. This fine-tuning of Zn metabolism is tightly regulated and often challenging task for plants. Hyperaccumulating ecotype of Sedum alfredii Hance, a Zn hyperaccumulator form the Crassulaceae family, offers a unique model to study Zn homeostasis. To date, their complex molecular mechanisms underlying Zn regulation remain largely unknown. Here, we present a large-scale comparative investigation of Zn homeostasis networks in Zn hyperaccumulating and non-hyperaccumulating ecotypes of S. alfredii. By integrating transcriptomics, proteomics, metabolomics, and ionomics, we uncovered that transcriptional and translational changes play critical roles in maintaining Zn homeostasis. These adaptations include enhanced photosynthetic efficiency, improved Zn ion binding in shoots, and increased antioxidative capacities. Additionally, carbon and sulfur metabolic pathways were found to respond significantly to Zn treatment. Key components of the tricarboxylic acid (TCA) cycle, along with stress-related amino acids, fatty acids, sugars, antioxidants, and Zn-binding phenolics, were coordinately modulated under Zn exposure. This multi-omics integration provides novel insights into the functional genomics and metabolic adaptations of the Zn hyperaccumulator S. alfredii and will facilitate biotechnological applications of Zn hyperaccumulation traits for biofortification, phytoremediation and food crop safety.PMID:40373399 | DOI:10.1016/j.jhazmat.2025.138523

Comp Biochem Physiol Part D Genomics Proteomics. 2025 May 8;55:101530. doi: 10.1016/j.cbd.2025.101530. Online ahead of print.ABSTRACTBile acids (BAs) are cholesterol derivatives synthesized by the liver, exhibit variation between different species. Researchers have long appreciated that microbiota play the roles in the biotransformation of BAs. However, relatively few studies have been reported on microbial-mediated production and transformation of BAs in amphibians. Our focus here is principally on difference of intestinal microbial diversity and BAs profiles between two common amphibians, Bufo gargarizans (B. gargarizans) and Rana chensinensis (R. chensinensis) tadpoles, through intestinal targeted BAs metabolomics and fecal metagenomic sequencing. The results demonstrated that B. gargarizans possessed higher levels of total BAs and higher ratio of unconjugated / conjugated BAs. In addition, the relative abundance of microbiota with bile salt hydrolase (BSH) activity in B. gargarizans was significantly higher than that of R. chensinensis, which may facilitate the conversion of conjugated to unconjugated BAs. Meanwhile the higher prevalence of bile-acid-induced (BAI) gene encoding microbiota in R. chensinensis may promote the synthesis of deoxycholic acid (DCA). Furthermore, discrepancies in virulence factors (VFs) and energy metabolism were observed between the two species, which may be linked to differences in the microbiota. This study revealed substantial differences in intestinal microbes and BAs across amphibian species, emphasizing the significant impact of intestinal microbes on BAs metabolism.PMID:40373385 | DOI:10.1016/j.cbd.2025.101530

Obstet Gynecol. 2025 Jun 1;145(6):721-731. doi: 10.1097/AOG.0000000000005922. Epub 2025 May 1.ABSTRACTOBJECTIVE: To perform metabolomic and lipidomic profiling with plasma samples from patients with placenta accreta spectrum (PAS) to identify possible biomarkers for PAS and to predict PAS with machine learning methods that incorporated clinical characteristics with metabolomic and lipidomic profiles.METHODS: This was a multicenter case-control study of patients with placenta previa with PAS (case group n=33) and previa alone (control group n=21). Maternal third-trimester plasma samples were collected and stored at -80°C. Untargeted metabolomic and targeted lipidomic assays were measured with flow-injection mass spectrometry. Univariate analysis provided an association of each lipid or metabolite with the outcome. The Benjamini-Hochberg procedure was used to control for the false discovery rate. Elastic net machine learning models were trained on patient characteristics to predict risk, and an integrated elastic net model of lipidome or metabolome with nine clinical features was trained. Performance using the area under the receiver operating characteristic curve (AUC) was determined with Monte Carlo cross-validation. Statistical significance was defined at P<.05.RESULTS: The mean gestational age at sample collection was 33 3/7 weeks (case group) and 35 5/7 weeks (control group) (P<.01). In total, 786 lipid species and 2,605 metabolite features were evaluated. Univariate analysis revealed 31 lipids and 214 metabolites associated with the outcome (P<.05). After false discovery rate adjustment, these associations no longer remained statistically significant. When the machine learning model was applied, prediction of PAS with only clinical characteristics (AUC 0.685, 95% CI, 0.65-0.72) performed similarly to prediction with the lipidome model (AUC 0.699, 95% CI, 0.60-0.80) and the metabolome model (AUC 0.71, 95% CI, 0.66-0.76). However, integration of metabolome and lipidome with clinical features did not improve the model.CONCLUSION: Metabolomic and lipidomic profiling performed similarly to, and not better than, clinical risk factors using machine learning to predict PAS among patients with PAS with previa and previa alone.PMID:40373320 | DOI:10.1097/AOG.0000000000005922

Cell Rep. 2025 May 13;44(5):115684. doi: 10.1016/j.celrep.2025.115684. Online ahead of print.ABSTRACTDespite broad knowledge of the pathogenesis, our understanding of the origin of allergy and asthma remains poor, preventing etiotropic treatments. The gut microbiome is seen to be altered in asthmatics; however, proof of causality of the microbiome alterations is lacking. We report on gut microbiome transplantation (GMT) from mice predisposed to asthma by maternal exposure to pro-allergy environmental particles into naive recipients. This GMT confers asthma predisposition, and the effect is abrogated by gamma sterilization of the transplant material or by co-administration of antibacterials, indicating that viable bacteria are mediating the effect. Metagenomics identifies key changes in the "pro-asthma" microbiome, and metabolomics links the identified species to altered production of butyrate known to act on immune cells and epigenetic mechanisms. We further show that transplant recipients develop DNA methylation alterations in dendritic cells. Finally, dendritic cells with an altered methylome present allergen to T cells, and this effect is abrogated by an epigenetically acting drug in vitro.PMID:40372916 | DOI:10.1016/j.celrep.2025.115684

Environ Sci Technol. 2025 May 15. doi: 10.1021/acs.est.5c01550. Online ahead of print.ABSTRACTPerfluorooctanesulfonate (PFOS) is a persistent environmental endocrine disruptor that poses severe threats to mammalian reproductive health upon accumulation in organisms. Therefore, elucidating the mechanisms of PFOS-induced damage and identifying effective protective strategies are of critical importance. In this study, an untargeted metabolomic analysis revealed that PFOS exposure significantly disrupted metabolic homeostasis in oocytes. Using public databases to predict potential target proteins of PFOS and performing KEGG pathway enrichment analysis, we identified the tryptophan metabolism pathway as a key target of PFOS. Molecular docking and molecular dynamics simulations demonstrated specific binding between PFOS and proteins involved in the tryptophan metabolism pathway, leading to dynamic structural alterations in these proteins. Furthermore, supplementation with tryptophan was shown to significantly enhance mitochondrial function in oocytes, regulate the glutathione (GSH)/oxidized glutathione (GSSG) ratio, reduce reactive oxygen species (ROS) levels, and alleviate oxidative stress, thereby mitigating the decline in oocyte quality caused by PFOS exposure. These findings provide novel theoretical insights and research directions for using tryptophan as a protective agent against PFOS-induced reproductive toxicity.PMID:40372800 | DOI:10.1021/acs.est.5c01550

Drug Deliv Transl Res. 2025 May 15. doi: 10.1007/s13346-025-01875-z. Online ahead of print.ABSTRACTAtopic dermatitis (AD) is a chronic inflammatory skin condition characterized by immune dysregulation and a disrupted gut-skin axis. Emerging evidence suggests that the gut microbiota and their metabolites play a critical role in pathogenesis and potential treatment of AD. However, therapeutic strategies targeting the gut microbiota that aim to alleviate AD remain underexplored. Therefore, this study investigated the potential of bovine colostrum-derived extracellular vesicles (BCEVs) to ameliorate AD symptoms by modulating the gut microbiota and intestinal metabolites. AD was induced in mice using 2,4-dinitrochlorobenzene, followed by the oral administration of BCEVs. Skin lesions were assessed histologically to evaluate disease severity. Allergic and immune responses were measured by analyzing serum immunoglobulin E (IgE) levels and cytokine profiles, including interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α). Gut microbiota composition was determined using 16 S rRNA gene sequencing, and the metabolomic profiling of intestinal samples was performed using gas chromatography-mass spectrometry to identify metabolites. BCEV treatment significantly alleviated skin lesions and reduced the serum IgE levels and the imbalance in IL-4 and TNF-α levels associated with AD induction. Gut microbiota analysis revealed that BCEVs restored microbial dysbiosis and improved the abundance of beneficial bacteria, and metabolomic analysis demonstrated elevated levels of lactic acid and other metabolites. These findings suggest that BCEVs alleviate AD symptoms by rebalancing the gut microbiota and intestinal metabolomes. This study emphasizes the importance of targeting the gut-skin axis as a novel strategy for AD treatment and provides evidence for the therapeutic potential of BCEVs in skin-related immune disorders.PMID:40372696 | DOI:10.1007/s13346-025-01875-z

Mol Neurobiol. 2025 May 15. doi: 10.1007/s12035-025-05015-z. Online ahead of print.ABSTRACTIschemic stroke (IS) is emerging as an increasingly serious social issue with elusive etiology, few diagnostic markers, and limited treatment methods. Another concern in contemporary society is the prevalence of obesity, which is indicative of suboptimal well-being. Despite its association with established risk factors for stroke (such as hypertension and diabetes), several studies have reported a controversial phenomenon known as the "obesity paradox," whereby certain obese patients with stroke exhibited unexpectedly positive outcomes. In this study, a total of 68 plasma samples were collected including 36 controls and 32 IS patients, with further differentiation between obese and non-obese individuals in each group. A quantitative metabonomic approach based on 1H nuclear magnetic resonance (1H NMR) was employed to identify differential metabolic markers of IS, and elucidate the impact of obesity on IS. The final results demonstrated that obesity did not have a significant impact on metabolites. It is important to note, however, that reliance on BMI as the sole indicator of obesity may be insufficient. Additional parameters, such as waist-to-hip ratio and waist circumference, should be considered. Furthermore, the impact of obesity on stroke is probably mediated through metabolic health, making it an intermediate factor rather than a direct cause. Additionally, the study identified approximately 30 metabolites exhibiting significant alterations in IS patients, with the primary metabolic pathways being energy metabolism, amino acid metabolism, lipid metabolism, and folic acid deficiency. These findings are significant for comprehending the potential mechanisms of IS and facilitating its rapid and early diagnosis for effective treatment.PMID:40372670 | DOI:10.1007/s12035-025-05015-z

Plant Physiol. 2025 May 15:kiaf163. doi: 10.1093/plphys/kiaf163. Online ahead of print.ABSTRACTIn Arabidopsis thaliana, the POWDERY MILDEW RESISTANT4 (PMR4)/GLUCAN SYNTHASE LIKE5 (GSL5) callose synthase is required for pathogen-induced callose deposition in cell wall defense. Paradoxically, pmr4/gsl5 mutants exhibit strong resistance to both powdery and downy mildew. The powdery mildew resistance of pmr4/gsl5 has been attributed to up-regulated salicylic acid (SA) signaling based on its dependence on PHYTOALEXIN DEFICIENT4 (PAD4), which controls SA accumulation, and its abolishment by bacterial NahG salicylate hydroxylase. Our study revealed that disruption of PMR4/GSL5 also leads to early senescence. Suppressor analysis uncovered that PAD4 and N-hydroxypipecolic acid (NHP) biosynthetic genes ABERRANT GROWTH AND DEATH2-LIKE DEFENSE RESPONSE PROTEIN1 (ALD1) and FLAVIN-DEPENDENT MONOXYGENASE1 (FMO1) are required for early senescence of pmr4/gsl5 mutants. The critical role of NHP in the early senescence of pmr4/gsl5 was supported by greatly increased accumulation of pipecolic acid in pmr4/gsl5 mutants. In contrast, disruption of the SA biosynthetic gene ISOCHORISMATE SYNTHASE1/SA-INDUCTION DIFFICIENT 2 (ICS1/SID2), which greatly reduces SA accumulation, had little effect on impaired growth of pmr4/gsl5. Furthermore, while disruption of PAD4 completely abolished the powdery mildew resistance in pmr4/gsl5, mutations in ICS1/SID2, ALD1, or FMO1 had only a minor effect on the resistance of the mutant plants. However, disruption of both ICS1/SID2 and FMO1 abolished the enhanced immunity of the callose synthase mutants against the fungal pathogen. Therefore, while NHP plays a crucial role in the early senescence of pmr4/gsl5 mutants, both SA and NHP have important roles in the strong powdery mildew resistance induced by the loss of the callose synthase.PMID:40372133 | DOI:10.1093/plphys/kiaf163

Arch Physiol Biochem. 2025 May 15:1-11. doi: 10.1080/13813455.2025.2500651. Online ahead of print.ABSTRACTINTRODUCTION: Among the dietary factors, glucose, and fatty acids are known to trigger fatty liver disease, while butyrate attenuates steatosis.OBJECTIVE: To decipher the hepatocellular altered metabolome under nutrient perturbation relevant to fatty liver disease.METHODS: HepG2 cells were cultured under the influence of sub-lethal doses of glucose, palmitic acid (PA), and butyrate. Following the treatment, intracellular metabolites were extracted and derivatized for GCMS analysis. Chemical class enrichment, metabolic pathway analysis, and metabolomic interactome analysis were undertaken.RESULTS: Glucose, PA and butyrate caused loss of cell viability at 160 mM, 1600 µM, and 40 mM concentration, respectively. A total of 39, 47, 52, and 51 metabolites were identified in control, glucose, PA, and butyrate, respectively, among which 2-ethylhexanoic acid in control and 2-ethylhexan-1-ol in glucose, PA and butyrate were the most abundant metabolites. Pathways related to the mitochondrial electron transport chain were highly enriched in glucose and PA treatments, leading to increased free radicals. The metabolites identified under glucose and PA treatment were linked to the metabolomic markers of metabolic liver diseases.CONCLUSION: Our data showed that the hepatocellular metabolome of HepG2 cells under glucose and PA treatment is closely related, while the metabolome and pathways associated with butyrate treatment are associated with energy metabolism and alleviation of fatty liver.PMID:40372011 | DOI:10.1080/13813455.2025.2500651

J Am Heart Assoc. 2025 May 15:e040042. doi: 10.1161/JAHA.124.040042. Online ahead of print.ABSTRACTBACKGROUND: Lifestyle factors toward diet and physical activity (PA) may directly influence the pathophysiology of dyslipidemia. However, the associations of the specific macronutrient-to-PA ratio with dyslipidemia, and the underlying mechanisms regarding gut microbiota and metabolites, remain largely unexplored.METHODS: Dietary and PA information from 273 participants with or at risk of metabolic syndrome was collected via a food frequency questionnaire and the International Physical Activity Questionnaire. Gut microbial genera and fecal metabolites were profiled through 16S rRNA sequencing and untargeted LC-MS metabolomics, respectively. Machine-learning algorithms were applied to identify gut microbiome features of macronutrient-to-PA ratios and to construct microbiome risk score.RESULTS: Higher macronutrient-to-PA ratios, especially for high saturated fatty acid intake, were associated with increased risks of dyslipidemia, with adjusted odds ratio (95% CIs) of 2.87 (1.41-5.99) for hypercholesteremia, 2.21 (1.11-4.48) for hypertriglyceridemia, and 2.52 (1.26-5.16) for high low-density lipoprotein cholesterol. Microbiome risk scores were significantly associated with elevated levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Additionally, for each macronutrient-to-PA ratio, a core group of gut microbial genera were identified (eg, Phocaeicola, Lachnoclostridium, Limosilactobacillus, and Tyzzerella), exhibiting positive associations with lipid disorders and superior discrimination capacities for hypercholesterolemia, hypertriglyceridemia, and high low-density lipoprotein cholesterol. Furthermore, we identified 9 metabolites (eg, acetyl phosphate, glycerol, and pyruvic acid), predominantly enriched in dyslipidemia-related pathways and associated with both core gut microbial taxa and macronutrient-to-PA ratios.CONCLUSIONS: This study identified varied associations between macronutrient-to-PA ratios and dyslipidemia and depicted the potential modulatory roles of gut microbiota and fecal metabolites.PMID:40371613 | DOI:10.1161/JAHA.124.040042

Hortic Res. 2025 Mar 25;12(7):uhaf092. doi: 10.1093/hr/uhaf092. eCollection 2025 Jul.ABSTRACTPlant-metabolite-microbe interactions play essential roles in disease suppression. Most studies focus on the root exudates and rhizosphere microbiota to fight soil-borne pathogens, but it is poorly understood whether the changes in phyllosphere metabolites can actively recruit beneficial microbes to enhance disease resistance. In this study, the differences of phyllosphere microbial communities and key leaf metabolites were systematically explored in resistant and susceptible black currant cultivars related to powdery mildew (PM) by integrating microbiome and metabolomic analyses. The results showed that the diversity and composition of microbiome changed, as highlighted by a reduction in microbial alpha-diversity and beta-diversity of susceptible cultivars. An increasing fungal network complexity and a decreasing bacterial network complexity occurred in resistant cultivar. Bacillus, Burkholderia (bacteria), and Penicillium (fungi) were identified as keystone microorganisms and resistance effectors in resistant cultivar. Metabolites such as salicylic acid, trans-zeatin, and griseofulvin were more abundant in resistant cultivar, which had a positive regulatory effect on the abundance of bacterial and fungal keystones. These findings unravel that resistant cultivar can enrich beneficial microorganisms by adjusting leaf metabolites, thus showing the external disease-resistant response. Moreover, the reduced stomatal number and increased tissue thickness were observed in resistant cultivar, suggesting inherent physical structure also provides a basic defense against PM pathogens. Therefore, resistant black currant cultivar displayed multilevel defense responses of physical structures, metabolites, and microorganisms to PM pathogens. Collectively, our study highlights the potential for utilizing phyllosphere microbiome dynamics and metabolomic adjustments in agricultural practices, plant breeding, and microbiome engineering to develop disease-resistant crops.PMID:40371437 | PMC:PMC12077297 | DOI:10.1093/hr/uhaf092

Anal Sci Adv. 2025 May 14;6(1):e70012. doi: 10.1002/ansa.70012. eCollection 2025 Jun.NO ABSTRACTPMID:40371267 | PMC:PMC12077755 | DOI:10.1002/ansa.70012

Front Oncol. 2025 Apr 30;15:1530487. doi: 10.3389/fonc.2025.1530487. eCollection 2025.ABSTRACTINTRODUCTION: Aberrant fatty acid (FA) metabolism is increasingly recognized as a significant factor in ovarian cancer (OC) progression, although the comprehensive metabolic alterations across different body tissues remain unclear.METHODS: In this study, sixteen OC patients and twenty-nine non-cancer (NC) patients were recruited for metabolic profiling using a global and targeted metabolomic strategy based on a gas chromatography-hydrogen flame ionization detector (GC-FID). The patient survival was followed up to 3 years, and PFS was calculated.RESULTS: Our findings revealed distinct metabolite profiles that differentiate OC from NC groups across all sample types. We found seven, nine, and thirteen significant metabolites in subcutaneous fat, plasma, and ovarian tissue respectively. In particular, docosahexaenoic acid (DHA) and arachidonic acid (AA) levels were notably elevated in all sample types of OC patients. Furthermore, receiver operating characteristic (ROC) analysis highlight that three plasma FA showed the best specificity and sensitivity in differentiating the OC group from the NC group (Area Under The Curve, AUC > 0.89), including caprylic acid, myristoleic acid, and tetracosaenoic acid. Most of the significant FA in subcutaneous fat and ovarian tissue showed a high risk of OC. However, caprylic acid and tetracosanoic acid were identified as protective factors in the plasma sample. We also found that high levels of linoelaidic acid in subcutaneous fat and palmitelaidic acid in ovarian tissue were associated with poor prognosis. Pathway analysis indicated upregulation of fatty acid synthesis, inflammatory signaling, and ferroptosis pathways in OC patients.DISCUSSION: This study reveals a coordinated reprogramming of FA metabolism across multiple biospecimens in OC patients. Our results suggest that specific fatty acids may contribute to OC progression through dysregulation of fatty acid synthesis, inflammatory signaling, and ferroptosis. These findings offer mechanistic insights into OC progression and highlighting potential biomarkers and targeted therapeutic interventions.PMID:40371224 | PMC:PMC12074969 | DOI:10.3389/fonc.2025.1530487

Front Microbiol. 2025 Apr 30;16:1538746. doi: 10.3389/fmicb.2025.1538746. eCollection 2025.ABSTRACTINTRODUCTION: Di-n-butyl phthalate (DBP) is one of the most widely used phthalate esters (PAEs) and is considered an emerging global pollutant. It may pose a significant threat to ecosystem and human health due to its residual hazards and accumulation in the environment. Bacteria-driven PAE biodegradation is considered an economical and effective strategy for remediating such polluted environments.METHODS: A DBP-degrading bacterium (P-7), was isolated from long-term film mulched cotton field soil. Its identity was confirmed via physiological, biochemical, and 16S rRNA gene analyses. The degradation conditions were optimized through single-factor experiments and response surface methodology (RSM).Furthermore, the whole-genome sequencing coupled with metabolomics was employed to elucidate metabolic mechanisms.RESULTS: Priestia megaterium P-7 (P. megaterium P-7) achieved 100% DBP removal within 20 h under optimal conditions and exhibited broad substrate specificity for other PAEs. Genomic analysis identified key genes (lip, aes, ybfF, estA, and yvaK) encoding esterases/hydrolases that initiate DBP catabolism, converting it to phthalic acid (PA). Subsequent decarboxylation (pdc, bsdCD, mdcACDH, and lysA) and dioxygenase-mediated steps integrated PA into the TCA cycle. Metabolomics revealed three degradation pathways: decarboxylation (DBP → MBP → BB → BA→Catechol), hydrolysis (DBP → MBP → PA → PCA → Catechol) and direct β-oxidation (DBP → DEP → MEP → PA → Catechol).CONCLUSION: P. megaterium P-7 demonstrates exceptional degradation efficiency, substrate versatility, and environmental stress tolerance, making it a promising candidate for bioremediation of organic pollutants in contaminated soil.PMID:40371103 | PMC:PMC12075219 | DOI:10.3389/fmicb.2025.1538746

Front Neurol. 2025 Apr 30;16:1524412. doi: 10.3389/fneur.2025.1524412. eCollection 2025.ABSTRACTBACKGROUND: Insomnia (difficulty falling or staying asleep) is a common issue among breast cancer survivors, significantly impacting their quality of life. Current treatments, primarily pharmacological and psychological, have limitations: the former often causes side effects, while the latter faces accessibility barriers. Long-snake moxibustion (LSM), a traditional Chinese medicine (TCM) technique, involves applying moxibustion along the governor vessel, which is an important meridian in TCM that plays a key role in regulating brain function. LSM is characterized by its minimal side effects, ease of application, and cost-effectiveness, with preliminary studies supporting its potential for treating insomnia. This study aims to further investigate the therapeutic effectiveness of LSM in alleviating insomnia among breast cancer survivors and to explore its underlying mechanisms.METHODS: This single-center, rater-masked, randomized controlled trial will enroll 100 breast cancer survivors with chronic insomnia, who will be randomly assigned in a 1:1 ratio to either the LSM group or a waitlist control group. During the 4-week treatment period, all participants will receive standard care, with the LSM group additionally receiving LSM treatment twice a week. The primary efficacy outcome is the change in Insomnia Severity Index (ISI) score at the end of the intervention. Secondary outcomes include changes in hypnotic medication use, Pittsburgh Sleep Quality Index (PSQI) scores, Piper Fatigue Scale (PFS) scores, and Functional Assessment of Cancer Therapy-Breast (FACT-B) scores. Mechanistic evaluations will assess serum biochemical markers, gut microbiota composition, and metabolomic profiles.DISCUSSION: If proven effective, this trial will provide critical clinical evidence supporting LSM as a viable and accessible treatment for insomnia among breast cancer survivors. The findings could influence clinical practice by offering a non-pharmacological treatment option, improving patient outcomes, and reducing dependence on pharmacological interventions. Furthermore, exploring the underlying mechanisms may enhance our understanding of how LSM works, paving the way for future research.CLINICAL TRIAL REGISTRATION: http://itmctr.ccebtcm.org.cn/, identifier ITMCTR2024000578.PMID:40371071 | PMC:PMC12074938 | DOI:10.3389/fneur.2025.1524412

Front Vet Sci. 2025 Apr 30;12:1552045. doi: 10.3389/fvets.2025.1552045. eCollection 2025.ABSTRACTSuperovulation and embryo transfer technologies provide strong support for improving the productivity of cattle population. A non-invasive diagnostic method for superovulation prediction is necessary to improve its efficiency. Compared to macromolecular substances, there has been an increasing number of studies on small molecular metabolites as biomarkers. This study aimed to identify key biomarkers associated with superovulation outcomes in cows through serum metabolomics analysis. In this study, 36 induced estrus cows were selected, and the blood samples were collected at three time points: before FSH injection, before artificial insemination, and before embryo collection. Then, the cows were classified into high embryonic yield (HEY) and low embryonic yield (LEY) groups based on the total number of embryos. Furthermore, a serum untargeted metabolomics analysis of the two groups was conducted using liquid chromatography with tandem mass spectrometry (LC-MS/MS). A total of 372 embryos were collected. The metabolomics analysis revealed that 1,158 metabolites were detected, and 617 were annotated. In the before FSH injection samples, 121 differential metabolites were identified between the two groups. In the before artificial insemination samples, 129 differential metabolites were identified. In the before embryo collection samples, 201 differential metabolites were identified. A total of 11 differential metabolites were shared between the before FSH injection and before artificial insemination samples, while five differential metabolites were shared across all three samples. The majority of the differential metabolites were significantly enriched in pathways related to amino acid and fatty acid metabolism, digestive system secretion, and ovarian steroidogenesis. This study showed that phosphatidylcholine [PC; 14:0/22:1(13Z)], phosphatidylethanolamine [PE; DiMe (11, 3)], triacylglycerol [TG; 15:0/16:0/22:4 (7Z, 10Z, 13Z, 16Z)], phosphatidylinositol [PI; 16:0/22:2 (13Z, 16Z)], and phosphatidylserine [PS; 18:0/20:4(8Z, 11Z, 14Z, 17Z)] were differentially expressed in the serum during the superovulation period. These could serve as potential biomarkers for embryonic yield prediction in bovine superovulation. The lipid and amino acid metabolic pathways may have an impact on the ovarian response. The results of this study could provide novel screening indexes of donors for bovine superovulation, although the accuracy of the relevant factors requires further investigation.PMID:40370823 | PMC:PMC12076740 | DOI:10.3389/fvets.2025.1552045

Front Endocrinol (Lausanne). 2025 Apr 30;16:1539797. doi: 10.3389/fendo.2025.1539797. eCollection 2025.ABSTRACTBACKGROUND: Growth Hormone Deficiency (GHD) is marked by insufficient growth hormone (GH) production, leading to disruptions in growth and metabolism. Its diagnosis is challenging due to the lack of sensitive, specific tests. To address this, we used a novel mouse model with a POU1F1 (Pit-1) gene mutation (K216E). This study aimed to identify metabolic biomarkers of GHD and assess their responsiveness to GH therapy, alongside pathway analysis to uncover disrupted metabolic pathways.METHODS: The Pit-1^K216E mouse model was validated for GHD through assessments of GH production, growth, and body composition. Metabolomic profiling was conducted to identify biomarkers, while pathway analysis examined disrupted metabolic pathways and their response to GH treatment. This approach aimed to improve understanding of GHD's metabolic impact and potential therapeutic strategies.RESULTS: The assessment of the Pit-1^K216E mouse confirmed GHD, as evidenced by reduced GH production and altered body composition. Metabolomic profiling identified three distinct biomarker groups associated with GHD: (1) GHD Biomarkers, found exclusively in GH-deficient mutant mice but absent in WT controls; (2) GH Treatment Responsive Biomarkers, which were altered in GH-deficient mutant mice (GHD) and further modulated following GH treatment, reflecting a response specific to the GHD condition and its treatment, but not observed in WT mice; and (3) GH Treatment-Specific Responsive Biomarkers, observed exclusively in the GHD condition after GH therapy. Pathway analysis revealed significant disruptions in purine metabolism, amino acid metabolism, and protein synthesis, with notable sex-specific differences. Male mice exhibited imbalances in taurine and hypotaurine metabolism, while female mice showed disruptions in tyrosine metabolism and mitochondrial function, highlighting sex-dependent metabolic responses to GHD and GH therapy.CONCLUSION: The Pit-1^K216E mouse model offers a robust platform for exploring GHD's molecular mechanisms. The identification of distinct, sex-specific metabolic biomarkers provides insights into GHD-related metabolic disruptions and supports personalized management strategies. These findings establish a framework for leveraging metabolic biomarkers to enhance the diagnosis and monitoring of GHD, with promising applications for future human studies and therapeutic strategies.PMID:40370773 | PMC:PMC12074916 | DOI:10.3389/fendo.2025.1539797