PubMed

Theriogenology. 2025 Jan 17;235:262-274. doi: 10.1016/j.theriogenology.2025.01.015. Online ahead of print.ABSTRACTSeminal plasma composition has important role in sperm functionality and its freezability. The objective of this study was to test the hypothesis that seminal plasma (SP) oxidative status and metabolome are associated with fresh semen characteristics and freezability of bull sperm. To accomplish this objective, oxidative status markers and metabolome of SP of ejaculates obtained from 20 Holstein bulls (3 for each bull) were analyzed using spectrophotometry and nuclear magnetic resonance (1H NMR). The ejaculates were classified into higher motility fresh semen (HMF) and lower motility fresh semen (LMF), according to total motility (TM) and progressive motility (PM) values of fresh semen. Then the ejaculates was cryopreserved and assigned to higher motility thawed group (HMT) or lower motility thawed group (LMT) according to TM and PM at 0 h post-thawing. Multivariate analyses were performed to identify the association between the functional characteristics of fresh and thawed semen and the SP parameters, in terms of the oxidative status and the metabolomic composition. According to our results, the advanced oxidative protein products (AOPP) and thiol concentrations in SP are significantly related to some physiological characteristics of the thawed sperm, such as higher viability, TM, PM and LIN and lower mitochondrial and cytoplasmic superoxide production in viable thawed cells. In contrast, a higher amount of C in the SP was negatively related to TM and PM of thawed semen and was associated with higher mitochondrial and cytoplasmic superoxide production. In addition, partial least squares-discriminant analysis (PLS-DA) performed on the 1H NMR spectra indicated a discrete separation between HMF and LMF groups, and good discrimination between HMT and LMT groups. Higher levels of formic acid, lactate, glycerol and phosphocholine, were found in the SP of the HMF group than in the LMF group. On the other hand, alanine, phenylalanine, and tyrosine were higher in the SP of the LMF group than in the HMF group. GABA, glutamate, histidine and glycerol were found in higher concentrations in the HMT group than in the LMT group, while fructose decreased in the HMT group. Our results showed that the oxidative and metabolomic status of SP is related to the physiological properties of semen and its freezability and open new fields in research of SP biomarkers of bull semen preservation and fertility.PMID:39889331 | DOI:10.1016/j.theriogenology.2025.01.015

Microbiome. 2025 Jan 31;13(1):32. doi: 10.1186/s40168-024-02013-6.ABSTRACTBACKGROUND: Gut microbiota has been extensively demonstrated to modulate host lipid metabolism. Higher intramuscular fat (IMF) accumulation in Chinese indigenous breed pigs is associated with their special gut microbiota structure. However, the specific microbes and metabolic pathways responsible for lipid deposition are still poorly understood.RESULTS: In the present study, a comparative analysis of the gut microbiota and metabolome in obese Ningxiang (NX) pigs and lean Duroc × Landrace × Yorkshire (DLY) pigs was conducted. The results revealed a higher abundance of gut lactobacilli and a correlation of branched-chain amino acid (BCAA) metabolism pathway in NX pigs. We proceeded to verify the roles of various lactobacilli strains originating from NX pigs in BCAA metabolism and lipids deposition in SD rats. We demonstrated that L. reuteri is a fundamental species responsible for modulating lipid deposition in NX pigs and that increased circulating levels of BCAA are positively linked to greater lipid deposition. Additionally, it has been verified that L. reuteri originating from NX pigs has the ability to improve BCAA synthesis in the gut and enhance IMF content in lean DLY pigs. The expression of genes related to lipid synthesis was also significantly upregulated.CONCLUSIONS: Taken together, our results imply that NX pig-derived L. reuteri regulates BCAA metabolism and plays a potential role in improving the meat quality of lean pig breeds through modulation of host intramuscular lipid deposition. The results provide a new strategy for improving the meat quality of commercial pigs by influencing host metabolism through supplementing dietary additives. Video Abstract.PMID:39891238 | DOI:10.1186/s40168-024-02013-6

Environ Microbiome. 2025 Jan 31;20(1):15. doi: 10.1186/s40793-025-00676-8.ABSTRACTBACKGROUND: Arbuscular mycorrhizal fungi (AMF) are beneficial root symbionts contributing to improved plant growth and development and resistance to abiotic and biotic stresses. Commercial bioinoculants containing AMF are widely considered as an alternative to agrochemicals in vineyards. However, their effects on grapevine plants grown in soil containing native communities of AMF are still poorly understood. In a greenhouse experiment, we evaluated the influence of five different bioinoculants on the composition of native AMF communities of young Cabernet Sauvignon vines grown in a non-sterile soil. Root colonization, leaf nitrogen concentration, plant biomass and root morphology were assessed, and AMF communities of inoculated and non-inoculated grapevine roots were profiled using high-throughput sequencing.RESULTS: Contrary to our predictions, no differences in the microbiome of plants exposed to native AMF communities versus commercial AMF bioinoculants + native AMF communities were detected in roots. However, inoculation induced positive changes in root traits as well as increased AMF colonization, plant biomass, and leaf nitrogen. Most of these desirable functional traits were positively correlated with the relative abundance of operational taxonomic units identified as Glomus, Rhizophagus and Claroideoglomus genera.CONCLUSION: These results suggest synergistic interactions between commercial AMF bioinoculants and native AMF communities of roots to promote grapevine growth. Long-term studies with further genomics, metabolomics and physiological research are needed to provide a deeper understanding of the symbiotic interaction among grapevine roots, bioinoculants and natural AMF communities and their role to promote plant adaptation to current environmental concerns.PMID:39891198 | DOI:10.1186/s40793-025-00676-8

Br J Pharmacol. 2025 Jan 31. doi: 10.1111/bph.17435. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is closely associated with immune dysfunction, where nutrient-mediated metabolic flux dictates immune cell fate and function. Thiamine is a central water-soluble vitamin involved in cellular energy metabolism, and its deficiency has been reported in IBD patients. However, whether thiamine deficiency is a cause or consequence of IBD pathogenesis remains unclear. The current study aimed to reveal the immunometabolic regulation of macrophages and underlying mechanism of thiamine deficiency in colitis development.EXPERIMENTAL APPROACH: Thiamine deficiency was induced in C57BL/6 mice and bone marrow-derived macrophages (BMDMs), by administering a thiamine-deficient diet/medium together with pyrithiamine hydrobromide. The frequency of macrophage phenotypes and their intracellular metabolism were detected using flow cytometry and non-targeted metabolomics, respectively.KEY RESULTS: Thiamine deficiency aggravated ulcerative colitis in mice and promoted the infiltration of proinflammatory M1 macrophages in colonic lamina propria. Our mechanistic study revealed that thiamine deficiency impaired pyruvate dehydrogenase (PDH) activity, thereby reprogramming cellular glucose metabolism to enhance glycolysis and lactic acid accumulation in M1 macrophages. Using a well-established PDH inhibitor (CPI-613) and lactic acid dehydrogenase inhibitor (galloflavin), we further demonstrated that PDH inhibition mimics, while lactate dehydrogenase inhibition partially rescues, thiamine deficiency-induced proinflammatory macrophage infiltration and experimental colitis in mice.CONCLUSION AND IMPLICATIONS: Our study provides evidence linking thiamine deficiency with proinflammatory macrophage activation and colitis aggravation, suggesting that monitoring thiamine status and adjusting thiamine intake is necessary to protect against colitis.PMID:39890689 | DOI:10.1111/bph.17435

FEMS Microbiol Lett. 2025 Jan 31:fnaf011. doi: 10.1093/femsle/fnaf011. Online ahead of print.ABSTRACTUnderstanding bacterial responses to antibiotics is essential for identifying resistance mechanisms and developing novel therapies. This study evaluated the resistance of Staphylococcus aureus (S. aureus) to fusidic acid (FD) in 100 patients with skin and soft tissue infections (SSTIs), revealing susceptibility to FD despite resistance to other antibiotics. Through adaptive laboratory evolution, we developed a highly FD-resistant strain, E10, and identified three gene mutations (fusA, BPENGOFF-00211, and rplF) using whole-genome sequencing. The fusA mutation was the primary contributor to resistance. Furthermore, the evolved fusA mutant strain (H457Y) displayed impaired coagulation function and reduced growth rates. We also analyzed the metabolomic profiles of ancestral ATCC 25923 and evolved E10 strains, both treated and untreated with FD, revealing that the fusA gene can independently induce metabolic reprogramming. These changes primarily impacted pathways involved in central carbon metabolism, nucleotide metabolism, and amino acid synthesis. This study highlights the complexity of FD resistance in S. aureus and offers insights into the metabolic pathways associated with antibiotic resistance.PMID:39890598 | DOI:10.1093/femsle/fnaf011

Toxicol Appl Pharmacol. 2025 Jan 29:117246. doi: 10.1016/j.taap.2025.117246. Online ahead of print.ABSTRACTCytochrome P450 1B1 (CYP1B1) metabolizes endogenous and xenobiotic substrates, including steroids and fatty acids. It is implicated in the metabolism of compounds essential for eye development and is a causative gene in primary congenital glaucoma (PCG). However, CYP1B1's role in PCG and related eye disorders and neurobehavioral function is poorly understood. To investigate the role of Cyp1b1 this study used a novel CRISPR-Cas9 generated Cyp1b1 mutant zebrafish (Danio rerio) line. Behavioral, metabolomic, and transcriptomic analyses were performed to determine the molecular and behavioral consequences of the mutant Cyp1b1. Further we aimed to distinguish a visual defect from other neurological effects. Larval mutant zebrafish were hyperactive during the vision-based larval photomotor response assay but behaved normally in the sound-based larval startle response assay. Adult mutants exhibited normal locomotion but altered interactions with other fish. In vision and hearing-based assays, mutant fish showed altered behavior to visual stimuli and reduced auditory responses. Mass spectrometry-based metabolomics analysis revealed 26 differentially abundant metabolites in the eye and 49 in the brain between the genotypes, with perturbed KEGG pathways related to lipid, nucleotide, and amino acid metabolism. RNA sequencing identified 95 differentially expressed genes in the eye and 45 in the brain. Changes in arachidonic and retinoic acid abundance were observed and potentially modulated by altered expression of CYP 1, 2, and 3 family enzymes. While these findings could not point to specific ocular defects over other neurobehavioral phenotypes, behavioral assays and omics analyses highlighted the role of Cyp1b1 in maintaining metabolic homeostasis and the behavioral consequences due to its loss.PMID:39890032 | DOI:10.1016/j.taap.2025.117246

Cell Metab. 2025 Jan 29:S1550-4131(24)00491-1. doi: 10.1016/j.cmet.2024.12.009. Online ahead of print.ABSTRACTLactate is among the highest flux circulating metabolites. It is made by glycolysis and cleared by both tricarboxylic acid (TCA) cycle oxidation and gluconeogenesis. Severe lactate elevations are life-threatening, and modest elevations predict future diabetes. How lactate homeostasis is maintained, however, remains poorly understood. Here, we identify, in mice, homeostatic circuits regulating lactate production and consumption. Insulin induces lactate production by upregulating glycolysis. We find that hyperlactatemia inhibits insulin-induced glycolysis, thereby suppressing excess lactate production. Unexpectedly, insulin also promotes lactate TCA cycle oxidation. The mechanism involves lowering circulating fatty acids, which compete with lactate for mitochondrial oxidation. Similarly, lactate can promote its own consumption by lowering circulating fatty acids via the adipocyte-expressed G-protein-coupled receptor hydroxycarboxylic acid receptor 1 (HCAR1). Quantitative modeling suggests that these mechanisms suffice to produce lactate homeostasis, with robustness to noise and perturbation of individual regulatory mechanisms. Thus, through regulation of glycolysis and lipolysis, lactate homeostasis is maintained.PMID:39889702 | DOI:10.1016/j.cmet.2024.12.009

J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Jan 27;1253:124486. doi: 10.1016/j.jchromb.2025.124486. Online ahead of print.ABSTRACTA novel range-divided data dependent acquisition (DDA) strategy was proposed for the screening of diterpenoid alkaloids in Aconitum pendulum roots. In range-divided DDA, the low-range was set between m/z 340-500 and the high-range was set between m/z 500-700 according to the molecular weight range of the diterpenoid alkaloids. The combined identification approach including MS1 molecular weight, MS2 spectrum interpretation, literature comparison, and standard verification was applied to the results. The range-divided DDA identified 15 more diterpenoid alkaloids than the full-range DDA under the same LC conditions. A total of 47 diterpenoid alkaloids were identified. Among them, brachyaconitines A-D were screened for the first time in Aconitum pendulum. This screening strategy can serve as a powerful tool for the discovery of novel metabolites in the field of plant metabolomics.PMID:39889611 | DOI:10.1016/j.jchromb.2025.124486

J Hazard Mater. 2025 Jan 25;488:137354. doi: 10.1016/j.jhazmat.2025.137354. Online ahead of print.ABSTRACTThe viability and tolerance of individual ureolytic bacteria are a bottleneck in the remediation of cadmium (Cd) by microbially induced carbonate precipitation (MICP) technology. To solve this issue, strains of Bacillus thuringiensis (B. thuringiensis, BT) and Citrobacter freundii (C. freundii, CF) were isolated from soil and studied for their growth characteristics and metabolism. A cooperation system (BT+CF, 1:1, v/v) was constructed and exposed to 20 mg/kg Cd2 + for 7 days, compared with individual bacteria. The synergistic mechanism of strains that immobilize Cd2+ was explored using characterization techniques. Results showed that the main metabolic pathways leading to urea up-regulation were pyrimidine metabolism, urea cycle, and lysine degradation by metabolomic analysis. The cooperation system can effectively remove Cd2+ with an efficiency of 97.68 %, which is higher than BT (66.66 %) and CF (88.61 %). The SEM-EDS, TEM, and XPS results revealed that the calcium carbonate polycrystals (vaterite and calcite) were formed during the MICP process, and the XRD and FTIR confirmed that the BT+CF produces more stable carbonate crystals. The BT+CF cooperation system was efficient at immobilizing Cd2+ by synergizing the molecular mechanisms of ureolytic bacteria. These results provide a novel perspective for the application of MICP.PMID:39889604 | DOI:10.1016/j.jhazmat.2025.137354

Int J Food Microbiol. 2025 Jan 25;431:111087. doi: 10.1016/j.ijfoodmicro.2025.111087. Online ahead of print.ABSTRACTThe aim of this study was to explore the alterations in physicochemical characteristics, bioactivity, flavor and metabolic profiles of mango juice fermented by Limosilactobacillus reuteri FJG2526 (L. reuteri FJG2526). The results exhibited that L. reuteri FJG2526 had strong adaptability in mango juice, and reduced the total sugar, polyphenolics and flavonoids content of mango juice. L. reuteri FJG2526 fermentation ameliorated the flavor profiles of mango juice, particularly promoted the production of acids, alcohols, and esters. Moreover, 107 metabolites in the mango juice were drastically altered after 48 h L. reuteri FJG2526 fermentation by metabolomic analysis, including 73 remarkably upregulated metabolites and 34 remarkably downregulated metabolites, primarily involving amino acid metabolism. In addition, L. reuteri FJG2526 fermentation also enhanced the ability to scavenge DPPH and OH free radicals of mango juice, and inhibited lipase and α-glucosidase activities. This study offers new insights into the mango juice fermentation and will contribute to the application of L. reuteri in functional juices.PMID:39889581 | DOI:10.1016/j.ijfoodmicro.2025.111087

Phytomedicine. 2025 Jan 20;138:156412. doi: 10.1016/j.phymed.2025.156412. Online ahead of print.ABSTRACTBACKGROUND: Vascular dementia (VaD), a significant cognitive disorder, is caused by reduced cerebral blood flow. Unraveling the metabolic heterogeneity and reprogramming in VaD is essential for understanding its molecular pathology and developing targeted therapies. However, the in situ metabolic regulation within the specific brain regions affected by VaD has not been thoroughly investigated, and the therapeutic mechanisms of Erigeron breviscapus injection (EBI), a traditional Chinese medicine, require further elucidation.PURPOSE: To investigate the region-specific metabolic alterations in a VaD rat model, explore the therapeutic effects of EBI at a microregional level, identify the key metabolic pathways and metabolites involved in VaD, and elucidate how EBI modulates these pathways to exert its therapeutic effects.METHODS: Air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), a novel technique, was employed to investigate the metabolic changes in the brain microregions. We used a bilateral common carotid artery occlusion model to induce VaD in rats. Network analysis and network pharmacology were used to assess the local metabolic effects of the EBI treatment (3.6 mL/kg/day for 2 weeks).RESULTS: The EBI treatment significantly ameliorated the neurological deficits in VaD rats. AFADESI-MSI revealed 31 key metabolites with significant alterations in the VaD model, particularly within the pathways related to neurotransmitter metabolism, redox homeostasis, and osmoregulation. The metabolic disturbances were primarily observed in the striatum (ST), pyriform cortex (PCT), hippocampus (HP), and other critical brain regions. The EBI treatment effectively reversed these metabolic imbalances, especially in neurotransmitter metabolism, suggesting its potential in mitigating VaD-related cognitive decline.CONCLUSION: Our findings not only shed light on the molecular underpinnings of VaD but also highlight the potential of EBI as a therapeutic agent in neurodegenerative disorders. Moreover, this study demonstrates the power of advanced mass spectrometry imaging techniques in phytomedicine, offering new insights into the spatial metabolic changes induced by botanical treatments.PMID:39889490 | DOI:10.1016/j.phymed.2025.156412

J Environ Manage. 2025 Jan 30;375:124292. doi: 10.1016/j.jenvman.2025.124292. Online ahead of print.ABSTRACTBiosolids, derived from wastewater treatment processes, are valuable resources for soil amendment in agriculture due to their nutrient-rich composition. However, various contaminants of concern (CEC) such as pharmaceuticals, per-and poly-fluoroalkyl substances, endocrine disruptive chemicals, surfactants, pathogens, nanoplastics, and microplastics, are also reported in biosolids. The use of biosolids for agriculture may introduce these CEC into the soil, which raises concerns about their environmental and human health impacts. Moreover, the presence of pathogens (Escherichia coli, Salmonella sp., Shigella, Giardia, Rotavirus, etc.) even after treatment calls for microbial profiling of biosolids, especially in developing countries. Multi-omics approaches can be used as powerful tools for characterizing microbial communities and highlighting metabolic pathways. Moreover, these approaches also help in predicting the ecological and agronomic effects of biosolids application in agricultural soils. This review discusses the advantages and challenges of using biosolids in agriculture, considering the range of different CEC reported in biosolids. Moreover, the current legislation for the use of biosolids in agriculture is also presented, highlighting the limitations with respect to guidelines for emerging contaminants in biosolids. Furthermore, the role of the multi-omics approach in biosolids management, focusing on genomics, transcriptomics, proteomics, and metabolomics is also assessed. Multi-omics also allows for real-time monitoring, ensuring continuous optimization of biosolids towards changing environmental conditions. This dynamic approach not only enhances the safe use, but also enhances the sustainability of waste management practices, minimizing the negative effects. Finally, the future research directions for integrating the multi-omics approach into biosolid management practices are also suggested. The need for updating the legislative framework, continued innovation to promote sustainable and robust agricultural systems, bringing the process closer to the principles of a circular bioeconomy is also empahasized.PMID:39889433 | DOI:10.1016/j.jenvman.2025.124292

Hum Immunol. 2025 Jan 30;86(2):111247. doi: 10.1016/j.humimm.2025.111247. Online ahead of print.ABSTRACTDonor Specific Antibodies (DSAs) are associated with a higher risk of Antibody Mediated Rejection (AMR). However, not all DSAs are pathogenic, and patients that raise DSAs have a wide spectrum of outcomes ranging from the complete absence of graft injury to severe AMR. Hence, characterization of both the qualitative features and titer of DSAs has the potential to predict AMR risk and treatment outcome for sensitized patients. Here, using HLA-A2+ cell-based assays, we investigate the qualitative features of immunoglobulin G (IgG) alloantibodies including Fc receptor binding properties and Fc-mediated effector function over time. Compared to seronegative controls, reactive antibodies in seropositive participants were predominantly IgG1, and exhibited elevated levels of binding to the receptors involved in Antibody Dependent Cellular Phagocytosis (ADCP) and Antibody Dependent Cellular Cytotoxicity (ADCC) activity. Further analysis of seropositive individuals revealed that these activities were predictive ofAMR status. Collectively, these results suggest a role for phagocytic and cytotoxic antibody effector functions of DSA in contributing to graft injury.PMID:39889319 | DOI:10.1016/j.humimm.2025.111247

PLoS One. 2025 Jan 31;20(1):e0318026. doi: 10.1371/journal.pone.0318026. eCollection 2025.ABSTRACTA noteworthy group of culinary and medicinal plants is Polygonatum species. They are known for their abundant flavonoid compound-rich rhizomes, which have antioxidative and anticancer activities. Using Polygonatum sibiricum Red (SXHZ) and Polygonatum kingianum var. grandifolium (HBES), we conducted transcriptome and metabolomic investigations to look into the molecular processes that control the manufacture of these flavonoids in Polygonatum plants. Seven distinct flavonoid metabolites were identified by the analytical data, with phloretin exhibiting a notable differential expression in the biosynthetic pathway. 30 genes with differential expression were found in both plants after further investigation, five of which are members of the transcription factor family associated with MBW. Thus, we suggest that Phloretin and the genes belonging to the MYB-related transcription factor family play a crucial role in controlling the flavonoid biosynthesis pathway in Polygonatum. This work lays the groundwork for a deeper comprehension of the biosynthesis and metabolic processes of flavonoids in Polygonatum, serving as an invaluable resource for the development of the polygonatum-related pharmaceutical industries as well as for the future breeding of Polygonatum plants with higher flavonoid content.PMID:39888911 | DOI:10.1371/journal.pone.0318026

Sleep. 2025 Jan 31:zsaf030. doi: 10.1093/sleep/zsaf030. Online ahead of print.ABSTRACTSTUDY OBJECTIVES: Insomnia with objective short sleep duration is associated with increased hypertension risk. We aimed to explore the mechanism underlying the association between objective short sleep duration and hypertension in patients with chronic insomnia disorder (CID) by multi-omics.METHODS: CID was defined according to International Classification of Sleep Disorders-3, and objective short sleep was based on the median value of total sleep time of the overall subjects during an overnight polysomnography. We used the mean values of measured nighttime and morning systolic (SBP) and diastolic blood pressure (DBP) for analysis. Serum metabolomics and fecal 16S rDNA amplicon sequencing were used to explore characteristic metabolites and analyze gut microbiota distribution, respectively.RESULTS: One hundred three patients with CID and 70 normal sleepers were included. We found 52 objective short sleep duration insomnia phenotype (ISSD)-related serum metabolites. Among the 52 ISSD-related serum metabolites, indoxyl sulfate was positively correlated with BP after adjusting for confounding factors (SBP: β=0.250, p=0.028; DBP: β=0.256, p=0.030) in ISSD. In addition, the level of serum indoxyl sulfate was significantly correlated with the genera Prevotella 9 (r=0.378, p=0.027), CAG-56 (r=-0.359, p=0.037), Ruminiclostridium 9 (r=-0.340, p=0.049) and Ruminococcus 2 (r=-0.356, p=0.039) in ISSD.CONCLUSIONS: Our study suggests that the ISSD phenotype is associated with significant changes in serum metabolic profile, including high levels of indoxyl sulfate. The latter molecule correlates both with BP and gut microbiota in patients with the ISSD phenotype, suggesting that indoxyl sulfate may be the molecular path resulting in increased hypertension risk in this phenotype.PMID:39888642 | DOI:10.1093/sleep/zsaf030

Diabetes Obes Metab. 2025 Jan 30. doi: 10.1111/dom.16213. Online ahead of print.ABSTRACTAIMS: The utilization of targeted metabolomics technology promises to facilitate the identification of novel metabolic markers in women with gestational diabetes mellitus (GDM), which may in turn facilitate a more comprehensive investigation of the underlying mechanisms of gestational diabetes GDM.MATERIALS AND METHODS: In this study, we used targeted metabolomics to identify serum metabolites from women with or without GDM. The differential metabolites were categorized and analysed using pathway analyses, correlated with maternal glucose level, and assessed as predictors of GDM by receiver operating characteristics analysis.RESULTS: Notably, we detected 46 differential metabolites (24 upregulated and 22 downregulated) between GDM and normal pregnancy, which were catalogued into amino acids, peptides and analogues, and organic acids and derivatives, and others. Pathway analysis showed that amino acid metabolites were abnormally active. In addition, most of the metabolites were closely related to maternal glucose level. Of these, two metabolites were associated with fasting blood glucose, 22 correlated with 1-h postprandial plasma glucose and 13 were related to 2-h postprandial plasma glucose. Next, we identified metabolites that could better diagnose GDM with the area under the receiver operating characteristics above 0.75, including 2-hydroxybutyric acid, itaconic acid, O-acetylcarnitine, glutathione disulfide, P-cresolsulfate, 2-furoic acid, l-asparagine, d-biotin, choline and homovanillic acid.CONCLUSION: We identified abnormal serum metabolites caused by GDM, which may contribute to our understanding of the pathomechanisms of GDM.PMID:39888318 | DOI:10.1111/dom.16213

Rapid Commun Mass Spectrom. 2025 Jan 31:e9996. doi: 10.1002/rcm.9996. Online ahead of print.ABSTRACTSourcing in chemical forensic science refers to the attribution of a sample to a specific source using a characteristic signature. It relies on the identification of chemical attribution signatures (CAS), including chemical markers such as residual synthetic precursors, impurities, reaction by-products and degradation products, or even metabolites. Undertaking CAS for chemical threat agents (CTA) can be used to provide an evidentiary link between the use of a given chemical and its precursor(s) to support forensic investigations. Organophosphorus compounds, a class of nerve agents, can be produced by different, more or less complex synthesis routes that can lead to specific CAS. Chlorpyrifos (CPF), an organophosphorus pesticide, was selected as model compound. To assess the specificity of impurity markers originated from a chemical synthesis, untargeted fingerprints of crude CPF from different synthesis pathways were analyzed as a first use-case using metabolomics-based trace discovery strategies. Seven different CPF synthesis routes were considered, and their crude mixtures were analyzed with a minimal sample preparation. Analyses were performed on a trapped ion mobility spectrometry (TIMS) coupled to liquid chromatography (LC) and high-resolution mass spectrometry (HRMS). Chemometrics analyses were conducted with multivariate methods to extract discriminating features (i.e., relevant impurities), annotate, and identify them. Then, unknown samples were analyzed in blind conditions without any information of the synthesis pathway employed. The aim is to validate the methodology seeking some discriminating impurities identified in the first section to attribute and classify them according to the synthesis route.PMID:39888204 | DOI:10.1002/rcm.9996

Physiol Plant. 2025 Jan-Feb;177(1):e70096. doi: 10.1111/ppl.70096.ABSTRACTCombined cold and high moisture stress (CHS) is a prevalent abiotic stress during maize sowing in northeast China, severely affecting the growth of seedlings and seed germination. However, the mechanism underlying seed growth responses to CHS remains unclear. We used Jidan441 (JD441, CHS-resistant) and Jidan558 (JD558, CHS-sensitive) as experimental materials. Treatments of 5-day cold (4°C, CS), high moisture (25%, gravimetric water content, HH), and CHS were initiated at sowing, followed by a return to normal growth conditions (20°C during light/ 15°C during dark, 15%) at 7 days after sowing (DAS). CS, HH, and CHS decreased seed root length and surface area. The reduction in root length and surface area in JD441 due to CHS was less severe than in JD558. We found that the difference between CHS and control in JD441was less than that in JD558 at transcriptional and metabolic levels at 7 DAS. After CHS removal, JD441 exhibited a greater increase in α-amylase activity and antioxidant content than JD558, which facilitated starch decomposition and the rapid removal of O2 - and H2O2 in seeds. The rapid recovery of soluble sugar and soluble protein in JD441 helped maintain osmotic balance. Amino acids and genes related to amino acid metabolism were upregulated in response to combined stress in JD441, whereas they were downregulated in JD558. In conclusion, the stress tolerance of JD441 was attributed to its efficient recovery ability from CHS. This study provides a scientific foundation for exploring seed stress tolerance pathways and developing cold and high-moisture-tolerant hybrids.PMID:39887997 | DOI:10.1111/ppl.70096

Br J Pharmacol. 2025 Jan 31. doi: 10.1111/bph.17440. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Kidney disease (KD) is a leading cause of mortality worldwide, affecting 〉10% of the global population. Two of the most common causes of KD are diabetes and acute kidney injury (AKI), both of which induce mitochondrial dysfunction resulting in renal proximal tubular damage/necrosis. Thus, pharmacological induction of mitochondrial biogenesis (MB) may provide a therapeutic strategy to block the onset/progression of KD. Here, we evaluated the pharmacological and potential therapeutic effects of a novel MB-inducing oxindole agent, MC16.EXPERIMENTAL APPROACH: Primary cultures of rabbit renal proximal tubule cells (RPTCs) were used to evaluate the cellular signalling and MB-inducing effects of MC16. Mice were used to determine the MB-inducing effects of MC16 in vivo, and the metabolic effects of MC16 on the renal cortical metabolome. Mouse models of AKI and diabetic kidney disease (DKD) were used to demonstrate the therapeutic potential of MC16 to ameliorate acute and diabetic nephropathy.KEY RESULTS: MC16 activated the PI3K-AKT-eNOS-FOXO1 axis and induced MB in RPTCs. MC16 induced MB and altered the renal cortical metabolome of mice. MC16 accelerated renal recovery, reduced vascular permeability, and diminished mitochondrial dysfunction following AKI. MC16 decreased diabetes-induced renal swelling, improved renal and mitochondrial function, and diminished interstitial fibrosis in DKD mouse models.CONCLUSION AND IMPLICATIONS: MC16 is a novel compound that induces MB and ameliorates acute and diabetic nephropathy in mice. This study underscores that targeting MB following the onset of renal/metabolic insults may provide a therapeutic strategy to mitigate the onset and/or progression of KD.PMID:39887970 | DOI:10.1111/bph.17440

Microb Biotechnol. 2025 Jan;18(1):e70045. doi: 10.1111/1751-7915.70045.ABSTRACTAscomycetes fungi are often prone to degeneration. Agricultural production of the prized ascomycete mushroom Morchella importuna (black morel) typically suffers from reduced yield and malformed ascocarps owing to culture degeneration. This study compared M. importuna cultures subjected to five different long-term preservation treatments, using transcriptomics and metabolomics. Avoiding repeated subculturing in combination with nutrient-limited conditions was found to be the most beneficial method for maintaining the fruiting capability of morels. The expression of the gene sets involved in cysteine and methionine metabolism and nucleocytoplasmic transport was upregulated under nutrient-limited and nutrient-rich conditions, respectively. This increased expression was accompanied by differential accumulation of metabolites involved in nucleobase metabolism. Repeated subculturing triggered dissimilar changes in the functional modules under nutrient-rich and nutrient-limited conditions. A diverse set of cellular biochemical processes related to carbon metabolism were altered by repeated subculturing under nutrient-rich conditions, whereas glycerophospholipid and purine metabolism were key functions affected by repeated subculturing under nutrient-limited conditions. Altogether, metabolic alterations related to sulfur-containing amino-acid biosynthesis, DNA repair, and cellular structural maintenance contributed to improved preservation outcomes in terms of morel fruiting capability. Our findings contribute to a more detailed understanding of the molecular mechanisms related to subculturing and fruiting of ascomycete macrofungi after long-term preservation.PMID:39887921 | DOI:10.1111/1751-7915.70045