PubMed

Metabolites. 2025 Jan 26;15(2):75. doi: 10.3390/metabo15020075.ABSTRACTBackground: Incidence of cardiometabolic disease among U.S. Hispanics/Latinos is higher than in non-Hispanic Whites. Prolonged sitting duration is prevalent in older adults, and compounded with menopause, greatly increases cardiometabolic risk in postmenopausal women. Metabolomic analyses of interventions to reduce sitting are lacking and mechanistic understanding of health-promoting behavior change in postmenopausal Latinas is needed. Methods: To address this knowledge gap, an exploratory analysis investigated the plasma metabolome impact of a 12-week increased standing intervention among sedentary postmenopausal Latinas with overweight or obesity. From a parent-randomized controlled trial, a subset of Best Responders (n = 43) was selected using parameters of highest mean change in sitting bout duration and total sitting time; baseline variable-Matched Controls (n = 43) were selected using random forest modeling. Targeted LC-MS/MS analysis of archived baseline and 12-week plasma samples was conducted. Metabolite change was determined using a covariate-controlled general linear model and multivariate testing was performed. A false discovery rate correction was applied to all analyses. Results: Best Responders significantly changed time sitting (-110.0 ± 11.0 min; -21%), standing (104.6 ± 10.1 min; 40%), and sitting in bouts >30 min (-102.3 ± 13.9 min; -35%) compared to Matched Controls (7.1 ± 9.8 min, -7.8 ± 9.0 min, and -4.6 ± 12.7 min, respectively; all p < 0.001). Twelve-week metabolite change was significantly different between the two groups for 24 metabolites (FDR < 0.05). These were primarily related to amino acid metabolism, improved blood flow, and ATP production. Enzyme enrichment analysis predicted significant changes regulating glutamate, histidine, phenylalanine, and mitochondrial short-chain fatty acid catabolism. Pathway analysis showed significant intervention effects on glutamate metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis, potentially indicating reduced cardiometabolic disease risk. Conclusions: Replacing nearly two hours of daily sitting time with standing and reduced prolonged sitting bouts significantly improved metabolomic profiles associated with cardiometabolic risk among postmenopausal Latinas.PMID:39997700 | DOI:10.3390/metabo15020075

Metabolites. 2025 Jan 24;15(2):73. doi: 10.3390/metabo15020073.ABSTRACTBACKGROUND: Among abiotic stresses to agricultural crops, drought stress is the most prolific and has worldwide detrimental impacts. The soybean (Glycine max) is one of the most important sources of nutrition to both livestock and humans. Different plant introductions (PI) of soybeans have been identified to have different drought tolerance levels.OBJECTIVES: Here, two soybean lines, Pana (drought sensitive) and PI 567731 (drought tolerant) were selected to identify chemical compounds and pathways which could be targets for metabolomic analysis induced by abiotic stress.METHODS: Extracts from the two lines are analyzed by direct infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The high mass resolution and accuracy of the method allows for identification of ions from hundreds of different compounds in each cultivar. The exact m/z of these species were filtered through SoyCyc and the Human Metabolome Database to identify possible molecular formulas of the ions. Next, the exact m/z values were converted into Kendrick masses and their Kendrick mass defects (KMD) computed, which were then sorted from high to low KMD. This latter process assists in identifying many additional molecular formulas, and is noted to be particularly useful in identifying formulas whose mass difference corresponds to two hydrogen atoms.RESULTS: In this study, more than 460 ionic formulas were identified in Pana, and more than 340 ionic formulas were identified in PI 567731, with many of these formulas reported from soybean for the first time.CONCLUSIONS: Using the SoyCyc matches, the metabolic pathways from each cultivar were compared, providing lists of molecular targets available to profile effects of abiotic stress on these soybean cultivars. Key metabolites include chlorophylls, pheophytins, mono- and diacylglycerols, cycloeucalenone, squalene, and plastoquinones and involve pathways which include the anabolism and catabolism of chlorophyll, glycolipid desaturation, and biosynthesis of phytosterols, plant sterols, and carotenoids.PMID:39997698 | DOI:10.3390/metabo15020073

Metabolites. 2025 Jan 22;15(2):68. doi: 10.3390/metabo15020068.ABSTRACTBACKGROUND/OBJECTIVES: Salt-based density gradient ultracentrifugation (SBUC) is frequently used to isolate lipoproteins for their subsequent analysis. However, the addition of salts may disrupt their molecular composition. Therefore, the aim of the present study was to assess the impact of SBUC upon the molecular composition of low-density lipoprotein (LDL) particles, compared to a validated non-salt method involving iodixanol gradient ultracentrifugation (IGUC).METHODS: Whole human plasma was analysed for various lipid parameters before LDL particles were isolated using both SBUC and IGUC methods. Each fraction was then filtered to obtain low-molecular-weight compounds. The LDL molecular content of the resulting fractions from both methods was determined using untargeted liquid chromatography-mass spectrometry (LC-MS) in positive and negative modes.RESULTS: A total of 1041 and 401 features were putatively identified using positive and negative modes, respectively. Differences were shown in the molecular composition of LDL prepared using SBUC and IGUC; in positive mode ionisation, the PLS-DA model showed reasonable fit and discriminatory power (R2 = 0.63, Q2 = 0.58, accuracy 0.88) and permutation testing was significant (p < 0.001).CONCLUSIONS: The findings reveal distinct differences in the small molecule composition of LDL prepared using the two methods, with IGUC exhibiting greater variation. In negative mode, both methods detected phospholipids, long-chain sphingolipids, and ceramides, but IGUC showed higher fold differences for some phospholipids. However, in positive mode, non-native brominated adducts were found in LDL isolated using SBUC and evidence of potential bacterial contamination was discovered in samples prepared using IGUC, both of which have the capacity to affect in vitro experiments.PMID:39997693 | DOI:10.3390/metabo15020068

Neurol Int. 2025 Feb 18;17(2):30. doi: 10.3390/neurolint17020030.ABSTRACTIntroduction: Serum metabolome changes after acute ischemic stroke (AIS), but the significance of this is poorly understood. We evaluated whether this change is associated with AIS outcomes in patients with large vessel occlusion (LVO). To improve validity, we combined cross-sectional and longitudinal designs and analyzed serum using Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS). Methodology: In the cross-sectional part, we compared serum metabolome from 48 LVO strokes, collected at 48-72 h, and analyzed with NMR, while in the longitudinal part, we compared metabolome from 15 LVO strokes, collected at <24 h, 48-72 h, 5-7 days, and 80-120 days, and analyzed with LC-MS between patients with modified Rankin Scores (mRS) of 0-3 and 4-6 at 90 days. We hypothesized that compounds elevated in patients with mRS 0-3 in the cross-sectional part would also be elevated in the longitudinal part, and vice versa. We used regression for the analysis and TSBH for multiple testing. Results: In the cross-sectional part, cholesterol, choline, phosphoglycerides, sphingomyelins, and phosphatidylethanolamines had lower levels in patients with an mRS of 0-3 compared to an mRS of 4-6. In the longitudinal part, lower levels of sphingomyelin (d18:1/19:0, d19:1/18:0)* significantly correlated with an mRS of 0-3 in patients with small infarction volume, while lower levels of sphingolipid N-palmitoyl-sphingosine (d18:1/16:0), 1-palmitoyl-2-docosahexaenoyl-GPC (16:0/22:6), 1-palmitoyl-2-docosahexaenoyl-GPE, palmitoyl-docosahexaenoyl-glycerol (16:0/22:6), campesterol, and 3beta-hydroxy-5-cholestenoate correlated with an mRS of 0-3 in patients with large infarction volume. Conclusions: This pilot study showed that lower levels of lipidomic components nerve cell membrane correlate with good AIS outcomes. If proven on large-scale studies, these compounds may become important AIS outcome markers.PMID:39997661 | DOI:10.3390/neurolint17020030

J Fungi (Basel). 2025 Feb 8;11(2):129. doi: 10.3390/jof11020129.ABSTRACTOlive trees are a cornerstone of Mediterranean agriculture but face significant threats from diseases such as Verticillium wilt and olive anthracnose. These diseases, caused by Verticillium dahliae and Colletotrichum spp., respectively, result in significant economic losses and degrade olive oil quality. While traditional chemical treatments present environmental risk, sustainable alternatives such as biological control agents (BCAs) are gaining attention. Epicoccum nigrum, an antagonistic fungus, has shown potential as a BCA due to its production of antimicrobial secondary metabolites. This study aimed to observe whether E. nigrum has an antagonistic ability against V. dahliae and C. acutatum, and to elucidate the metabolic interactions between these fungi using NMR-based metabolomics. E. nigrum showed inhibitory effects on the growth of C. acutatum and V. dahlia of 44.97% and 38.73% respectively. Metabolomic profiling revealed distinct biochemical responses in E. nigrum, V. dahliae, and C. acutatum under mono- and dual-culture. Multivariate statistical analysis highlighted the metabolic shifts in mycelia and identified the primary metabolites, such as glutamine, 4-aminobutyrate, and phenylalanine that are involved in adaption for survival in stress conditions such as the presence of a competitor. The results could be important for a better understanding of the primary fungal metabolism, which is still poorly characterized. Further investigation is needed, but these results suggest that E. nigrum could serve as a BCA, offering a more sustainable approach to managing olive diseases.PMID:39997423 | DOI:10.3390/jof11020129

J Fungi (Basel). 2025 Feb 4;11(2):115. doi: 10.3390/jof11020115.ABSTRACTDaldinia carpinicola is a newly identified species of wood-rotting fungi, with substantial aspects of its biology and ecological function yet to be clarified. A Nanopore third-generation sequencer was employed for de novo genome assembly to examine the genetic characteristics. The genome consisted of 35.93 Mb in 46 contigs with a scaffold N50 of 4.384 Mb. Glycoside hydrolases and activities enzymes accounted for a large proportion of the 522 identified carbohydrate-active enzymes (CAZymes), suggesting a strong wood degradation ability. Phylogenetic and comparative analysis revealed a close evolutionary relationship between D. carpinicola and D. bambusicola. D. carpinicola and Hypoxylon fragiforme exhibited significant collinear inter-species genome alignment. Based on transcriptome and metabolomic analyses, D. carpinicola showed a greater ability to utilize sucrose over sawdust as a carbon source, enhancing its growth by activating glycolysis/gluconeogenesis and the citrate cycle. However, compared with sucrose, sawdust as a carbon source activated D. carpinicola amino acid biosynthesis and the production of various secondary metabolites, including diterpenoid, indole alkaloid, folate, porphyrin, and biotin metabolism. The study establishes a theoretical basis for research and applications in biological processes, demonstrating a strategy to modulate the production of secondary metabolites by altering its carbon sources in D. carpinicola.PMID:39997409 | DOI:10.3390/jof11020115

J Fungi (Basel). 2025 Jan 24;11(2):93. doi: 10.3390/jof11020093.ABSTRACTMetabolomics has emerged as a transformative tool in the study of microbes, including pathogenic fungi, facilitating the identification of unique metabolic profiles that elucidate their pathogenic mechanisms, host interactions, and treatment resistance. This review highlights key applications of metabolomics in understanding fungal metabolites essential for human virulence, such as mycotoxins produced by various fungal species, including Aspergillus fumigatus (gliotoxin, fumagillins) and Candida species (phenylethyl alcohol, TCA cycle metabolites), and secondary metabolites that contribute to pathogenicity. It also explores the metabolic adaptations of fungi in relation to drug resistance and biofilm formation, revealing alterations in key metabolic pathways during infection, as seen in C. albicans and C. auris. Furthermore, metabolomics aids in deciphering host-pathogen interactions, showcasing how fungi like Cryptococcus neoformans and Candida modify host metabolism to promote survival and evade immune responses. The study of antifungal resistance mechanisms has also benefited from metabolomic approaches, identifying specific metabolite patterns that signify resistance, such as in Candida albicans and Candidozyma (Candida) auris, and informing new therapeutic strategies. The integration of metabolomics with other omics technologies is paving the way for a comprehensive understanding of fungal biology and pathogenesis. Such multi-omics approaches are crucial for discovering new therapeutic targets and developing innovative antifungal treatments. Thus, the purpose of this review is to provide an overview of how metabolomics is revolutionizing our understanding of fungal pathogenesis, drug resistance, and host interactions, and to highlight its potential for identifying new therapeutic targets and improving antifungal strategies.PMID:39997385 | DOI:10.3390/jof11020093

Mar Drugs. 2025 Feb 7;23(2):74. doi: 10.3390/md23020074.ABSTRACTThe rising prevalence of Alzheimer's disease (AD) underscores the urgent need for novel therapeutic agents derived from natural sources. Among flavonoids, 3',4',5,7-tetramethoxyflavone (TMF), a structural analog of luteolin, has gained attention for its favorable pharmacokinetics and potential neuroprotective properties. Despite the significant neuroprotective effects and favorable pharmacokinetics of TMF, its efficacy and mechanism of action in AD remain unclear. This study explored TMF's pharmacological effects in AD models, highlighting its ability to improve memory and cognitive deficits in APP/PS1 mice. TMF reduced Aβ plaques, NFTs formation, and glial activation while suppressing neuroinflammation through the MAPK/NF-κB pathway. Further analysis in LPS-induced BV2 cells revealed TMF's ability to reduce microglial activation. These findings highlight the anti-neuroinflammatory activity of TMF, suggesting its potential as a treatment for AD.PMID:39997198 | DOI:10.3390/md23020074

Mar Drugs. 2025 Feb 7;23(2):73. doi: 10.3390/md23020073.ABSTRACTInflammatory bowel disease remains a significant challenge in clinical settings. This study investigated the therapeutic potential of sea cucumber ovum hydrolysates (SCH) in a dextran sulfate sodium (DSS)-induced colitis mouse model. SCH, defined by its elevated stability and solubility, with a molecular weight below 1000 Da, significantly alleviated DSS-induced colitis, as evidenced by enhanced splenic index, reduced colonic damage, and diminished serum pro-inflammatory cytokines. Furthermore, macrogenomic analysis demonstrated that SCH increased beneficial gut microbes and decreased pro-inflammatory bacteria. Furthermore, metabolomic analysis of colonic tissues identified elevated levels of anti-inflammatory metabolites, such as Phenyllactate, 2-Hydroxyglutarate, and L-Aspartic acid, in colitis mice after oral administration of SCH. In conclusion, SCH represents a promising candidate for the treatment of colitis.PMID:39997197 | DOI:10.3390/md23020073

Curr Issues Mol Biol. 2025 Feb 11;47(2):117. doi: 10.3390/cimb47020117.ABSTRACTBasil, renowned for its aromatic properties, exhibits commendable drought tolerance and holds significant value as an edible and medicinal plant. Recognizing the scarcity of studies addressing basil's response to drought stress, we performed physiological experiments and omics analyses of sweet basil across four distinct levels of drought stress. During drought stress, basil showed increased activity of antioxidant enzymes and accumulated more osmoregulatory compounds. Our metabolic analysis meticulously identified a total of 830 metabolites, among which, 215 were differentially accumulated. The differentially accumulated metabolites under drought stress were predominantly esters and terpenes; however, none were identified as the primary volatile compounds of basil. Transcriptome analyses highlighted the pivotal roles of phenylpropanoid and flavonoid biosynthesis and lipid metabolism in fortifying the resistance of sweet basil against drought stress. α-linolenic acid, lignin, flavonoid, and flavonol contents significantly increased under stress; the essential genes involved in the production of these compounds were confirmed through quantitative real-time PCR (qRT-PCR), and their variations aligned with the outcomes from sequencing. This holistic approach not only enriches our understanding of the molecular intricacies underpinning basil's drought resistance but also furnishes valuable insights for the molecular breeding of basil varieties endowed with enhanced drought tolerance.PMID:39996838 | DOI:10.3390/cimb47020117

Curr Issues Mol Biol. 2025 Feb 1;47(2):94. doi: 10.3390/cimb47020094.ABSTRACTAlthough the pod color was one of the seven characteristics Mendel studied in peas, the mechanism of color variation in peas with purple pods has not been reported. This study systemically analyzed the difference between two pea accessions with green pods (GPs) and purple pods (PPs) at two pod developmental stages from the metabolome and transcriptome levels, aiming to preliminarily explore the mechanism and of color variation in PPs and screen out the candidate genes. A total of 180 differentially accumulated metabolites (DAMs) belonged to seven flavonoid subgroups and 23 flavonoid-related differentially expressed genes (DEGs) were identified from the analysis of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment, respectively. Among the 180 flavonoid metabolites, ten anthocyanin compounds, which were the principal pigments in PPs and might be the major reason for the purple color formation, were significantly up-accumulated in both of the different pod development stages of PPs. A transcriptome analysis revealed that eight genes encoding enzymes (C4H, CHI, F3H, F3'H, F3'5'H, DFR, ANS, and FLS) involved in the flavonoid synthesis pathway were significantly upregulated in PPs and finally resulted in the significant accumulation of flavonoid and anthocyanin metabolites. The joint analysis of two omics and a weighted gene co-expression network analysis (WGCNA) also screened out that the WD-40 protein-encoding gene, one WRKY and three MYB transcription factor genes exhibited significant upregulation in PPs, and highly correlated with several structural genes in flavonoid synthesis pathways, indicating that these genes are involved in the regulation of pod color formation in PPs. Overall, the results of this study first explored the mechanism underlying the purple color variation between PPs and GPs, and then preliminarily screened out some candidate genes responsible for the pod color formation in PPs.PMID:39996815 | DOI:10.3390/cimb47020094

Curr Issues Mol Biol. 2025 Jan 25;47(2):77. doi: 10.3390/cimb47020077.ABSTRACT(1) This study investigates the association of plasma concentrations of various cytokines and chemokines with the disease activity of idiopathic nephrotic syndrome (INS) in children in Slovenia. (2) In a prospective single-center study lasting 18 months, we took sequential plasma samples from children with INS at disease onset or relapse (prior to corticosteroid (CS) therapy), at remission, and after discontinuation of CS therapy. The Olink®Target 48 Cytokine Panel was applied to analyze 45 analytes in the plasma samples, adhering to the manufacturer's protocol. We performed a statistical analysis with a paired samples analysis with a t-test as well as with a non-parametric Wilcoxon correction test. (3) We included 18 pediatric patients with INS in the study. We demonstrated statistically significant differences in the concentrations of CSF1, IL4, FLT3LG, CCL19, and MMP12 in the patients at disease onset or relapse compared to those in remission, differences in the concentrations of CSF1 and IL17F in the patients at disease onset or relapse compared to those in remission after CS treatment, and differences in the concentrations of CCL19, MMP12, and CCL13 in the patients in remission compared to those in remission after CS treatment. (4) The findings support potential roles of certain cytokines and chemokines, especially CSF1, CCL19, and MMP12, in influencing the disease activity of INS.PMID:39996798 | DOI:10.3390/cimb47020077

Ann Clin Transl Neurol. 2025 Feb 25. doi: 10.1002/acn3.52299. Online ahead of print.ABSTRACTOBJECTIVES: This study sought to evaluate proteomic, metabolomic, and immune signatures in the cerebrospinal fluid of individuals with Down Syndrome Regression Disorder (DSRD).METHODS: A prospective case-control study comparing proteomic, metabolomic, and immune profiles in individuals with DSRD was performed. Samples were obtained from a biorepository of affected individuals and compared to clinically available data and previously obtained neurodiagnostic studies. Individuals with DSRD were compared to individuals with established neuroinflammatory conditions (e.g., multiple sclerosis), and neurotypical controls undergoing a lumbar puncture for headaches. Samples underwent high-throughput proteomic, metabolomic, and immune marker profiling. Data was compared across groups and clinical phenotypes. Gene set enrichment analysis and pathway analyses were utilized to analyze the data.RESULTS: In total, 34 individuals with DSRD, 22 neuroinflammatory controls, and 27 neurotypical controls were enrolled in the study. We observed a highly significant concordance in dysregulated proteomics signatures in DSRD and neuroinflammatory controls versus healthy controls, most prominently upregulation of many immunoglobulin sequences. In addition, individuals with DSRD displayed strong upregulation of liver-derived plasma proteins and erythrocyte proteins in the CSF, indicating poor blood-brain barrier integrity. The immune marker profile of DSRD is clearly similar to other neuroimmunological conditions, including strong elevation of MIP3-α, eotaxin, and IFN-γ.INTERPRETATION: Individuals with DSRD have unique CSF proteomic and metabolomic signatures consistent with neuroinflammation and increased blood-brain barrier permeability. The CSF of individuals with DSRD was more comparable to individuals with neuroinflammatory disorders than neurotypical controls, indicating the potential for an immune etiology of disease.PMID:39996411 | DOI:10.1002/acn3.52299

Plant Physiol. 2025 Feb 7;197(2):kiaf027. doi: 10.1093/plphys/kiaf027.ABSTRACTWild citrus (Citrus L.) exhibits high disease resistance accompanied by high-acidity fruit, whereas cultivated citrus produces tastier fruit but is more susceptible to disease. This is a common phenomenon, but the underlying molecular mechanisms remain unknown. Citrus PH4 (CitPH4) is a key transcription factor promoting citric acid accumulation in fruits. Accordingly, CitPH4 expression decreased during citrus domestication, along with a reduction in citric acid levels. Here, we demonstrate that a CitPH4-knockout mutant exhibits an acidless phenotype and displays substantially lower resistance to citrus diseases. Metabolome and transcriptome analyses of CitPH4-overexpressing citrus callus, Arabidopsis, and CitPH4-knockout citrus fruits revealed that quercetin, pipecolic acid (Pip), and N-hydroxypipecolic acid (NHP) are pivotal defense-related metabolites. Application of quercetin and Pip inhibited the growth of Xcc and Penicillium italicum, while NHP inhibited the growth of P. italicum and Huanglongbing. Biochemical experiments demonstrated that CitPH4 enhances the expression of quercetin and NHP biosynthesis genes by binding to their promoters. Moreover, Pip and quercetin contents were positively associated with citric acid content in the pulp of fruits from natural citrus populations. Finally, the heterologous expression of CitPH4 in Arabidopsis promoted the expression of stress response genes and enhanced its resistance to the fungal pathogen Botrytis cinerea. The overexpression of CitPH4 in tobacco (Nicotiana tabacum) enhanced disease resistance. This study reveals the mechanism by which CitPH4 regulates disease resistance and fruit acidity, providing a conceptual strategy to control fruit acidity and resistance to devastating diseases.PMID:39996402 | DOI:10.1093/plphys/kiaf027

J Mass Spectrom. 2025 Mar;60(3):e5117. doi: 10.1002/jms.5117.ABSTRACTDiabetes mellitus (DM) is a prevalent metabolic disorder attributed to insulin secretion and action defects, affecting a growing adult population with hyperglycemia expected to reach 578 million by 2030. This study explores the antidiabetic potential of 25% aqueous methanol extract of Cupressus torulosa needles, utilizing in vitro and in vivo assays. In the α-glucosidase inhibition assay, the extract exhibited significant in vitro antidiabetic activity with an IC50, 123.45 ± 1.8 μg/mL, comparable to the standard drug acarbose (IC50, 58.21 ± 3.1 μg/mL). Toxicity assessment indicated non-toxic nature of the extract at 2000 mg/kg b.w. In STZ-induced diabetic mice, it displayed dose-dependent antihyperglycemic effects, evident at the fourth hour and 14th day, paralleling the positive control glibenclamide. In the chemical profiling of the extract using UPLC-QTOF-MS, the mobile phases consisted of 0.1% formic acid in water (Solvent A) and 100% methanol (Solvent B). The gradient elution started with 5% B (0 to 2 min) and gradually increased to 95% B by 25 min, followed by a post-run time of 2 min. Preliminarily, 50 constituents were identified, predominantly phenolics, with hypoglycemic effects attributed to flavonoids like (-)-epicatechin, amentoflavone, and cupressuflavone, as well as iridoid O-glycoside, exemplified by haprpagoside. Further studies are needed to assess the long-term efficacy, safety, and molecular mechanisms of the extract of C. torulosa needles in diabetes management.PMID:39996299 | DOI:10.1002/jms.5117

Front Microbiol. 2025 Feb 10;16:1534809. doi: 10.3389/fmicb.2025.1534809. eCollection 2025.ABSTRACTThe alternating planting of corn and soybeans is regarded as an effective strategy in addressing the challenges faced in soybean cultivation. However, the precise mechanisms that control the bacterial microbiome in soybean roots in the soil, particularly in continuous cropping and rotational corn-soybean farming rotations, are remain unclear. This study employed both field and pot positioning experiments, using high-throughput and generic metabolomics sequencing techniques to explore the dynamics between soybean plants, root microflora, and soil metabolites, especially in the context of continuous cropping and fluctuating corn-soybean crop rotation. The process that included rotating corn soybeans significantly enhanced their grain yield, dry weight, soil nitrogen concentration, urease activity, as well as the accumulation of nitrogen, phosphorus, and potassium in various plant organs, compared to the traditional practice of continuous soybean cultivation. There is a significant reduction in the transit of bacterial operational taxonomic units (OTUs) from the rhizosphere to the endosphere through rhizoplane. The number of bacterial OTUs that are consumed and enriched on rhizoplane is greater than those that are enriched and absorbed in the endosphere. Continuous cropping practices significantly boost Burkholderiales, whereas chloroplast microorganisms significantly improve crop rotation techniques. Soil environmental factors, such as urease and accessible phosphorus, are crucial in establishing the relative prevalence of Rhodanobacter and other bacterial groups. Soil metabolites, such as benzyl alcohol, show a positive correlation with Cyanobacteria, while acidic compounds, such as D-arabinitol, are positively linked with Burkholderiales. This study indicates that the rotation of corn and soybean crops facilitates the growth of soybeans, increases nutrient accumulation in both plants and soil, enhances the presence of beneficial bacteria, and improves soybean yields.PMID:39996076 | PMC:PMC11847879 | DOI:10.3389/fmicb.2025.1534809

Front Microbiol. 2025 Feb 10;16:1531212. doi: 10.3389/fmicb.2025.1531212. eCollection 2025.ABSTRACTINTRODUCTION: Continuous cropping is the main cause of cassava yield reduction. To find an effective method to alleviate the obstacle of cassava continuous cropping and explore the effect of cassava-soybean intercropping, this study analysed the differences in cassava agronomic traits, yield, soil physicochemical properties, microbial community structure, and metabolites between cassava single cropping (M) and cassava-soybean intercropping (MD) and its effects on continuous cassava cropping soil.METHODS: The correlations between yield, agronomic traits, soil physicochemical properties, microbial diversity, and metabolites were explored, and the effect of the cassava-soybean intercropping model on cassava soil was revealed.RESULTS: The results showed that compared with group M, soil pH, porosity, organic matter, available nitrogen, and fresh potato yield in the MD group significantly increased by 8.59, 13.66, 20.68, 23.29, and 50.61%, respectively, and soil bulk density significantly decreased by 9.68%. Soil bacterial community diversity in the MD group did not change significantly but had significant effects on soil fungal community diversity. The relative abundances of Trichoderma and Micropsalliota in the MD group were significantly upregulated. The contents of phenol glucuronide, 2,3-butanediol, L-phenylalanine, deoxyguanosine, other carbohydrates, alcohols, purine nucleotides, and amino acids in the soil of the MD group were significantly upregulated. Organic acids, such as fumaric acid, succinic acid, phosphoenolpyruvic acid, decreased significantly. Correlation analysis showed that Trichoderma was significantly negatively correlated with fumaric acid, succinic acid, phosphoenolpyruvic acid, and soil bulk density. However, there was significant positive correlation with phenol glucuronide, alpha-CEHC deoxyguanosine and other carbohydrates, nucleotide substances, organic matter, and pH. Phenol glucuronide, 2,3-butanediol, L-phenylalanine, deoxyguanosine and other carbohydrates, alcohols, purine nucleotides, and amino acids were significantly positively correlated with organic matter, available nitrogen, soil porosity, and pH.DISCUSSION: Therefore, cassava-soybean intercropping can effectively alleviate the obstacles of continuous cassava cropping by affecting the accumulation of metabolites and microbial community structure in continuous cropping soil, thereby improving the adverse factors of severe soil acidification, soil compaction, and nutrient decline.PMID:39996072 | PMC:PMC11847900 | DOI:10.3389/fmicb.2025.1531212

Heliyon. 2025 Jan 23;11(3):e42197. doi: 10.1016/j.heliyon.2025.e42197. eCollection 2025 Feb 15.ABSTRACTBACKGROUND AND OBJECTIVE: Obesity is intricately linked with metabolic disturbances. The comprehensive exploration of metabolomes is important in unravelling the complexities of obesity development. This study was aimed to discern unique metabolite signatures in obese and lean individuals using liquid chromatography-mass spectrometry quadruple time-of-flight (LC-MS/Q-TOF), with the goal of elucidating their roles in obesity.METHODS: A total of 160 serum samples (Discovery, n = 60 and Validation, n = 100) of obese and lean individuals with stable Body Mass Index (BMI) values were retrieved from The Malaysian Cohort biobank. Metabolic profiles were obtained using LC-MS/Q-TOF in dual-polarity mode. Metabolites were identified using a molecular feature and chemical formula algorithm, followed by a differential analysis using MetaboAnalyst 5.0. Validation of potential metabolites was conducted by assessing their presence through collision-induced dissociation (CID) using a targeted tandem MS approach.RESULTS: A total of 85 significantly differentially expressed metabolites (p-value <0.05; -1.5 < FC > 1.5) were identified between the lean and the obese individuals, with the lipid class being the most prominent. A stepwise logistic regression revealed three metabolites associated with increased risk of obesity (14-methylheptadecanoic acid, 4'-apo-beta,psi-caroten-4'al and 6E,9E-octadecadienoic acid), and three with lower risk of obesity (19:0(11Me), 7,8-Dihydro-3b,6a-dihydroxy-alpha-ionol 9-[apiosyl-(1->6)-glucoside] and 4Z-Decenyl acetate). The model exhibited outstanding performance with an AUC value of 0.95. The predictive model underwent evaluation across four machine learning algorithms consistently demonstrated the highest predictive accuracy of 0.821, aligning with the findings from the classical logistic regression statistical model. Notably, the presence of 4'-apo-beta,psi-caroten-4'-al showed a statistically significant difference between the lean and obese individuals among the metabolites included in the model.CONCLUSIONS: Our findings highlight the significance of lipids in obesity-related metabolic alterations, providing insights into the pathophysiological mechanisms contributing to obesity. This underscores their potential as biomarkers for metabolic dysregulation associated with obesity.PMID:39995923 | PMC:PMC11848079 | DOI:10.1016/j.heliyon.2025.e42197

iScience. 2025 Jan 25;28(2):111903. doi: 10.1016/j.isci.2025.111903. eCollection 2025 Feb 21.ABSTRACTSix-transmembrane protein of prostate 4 (Steap4), highly expressed in adipose tissue, is associated with metabolic homeostasis. Dysregulated adipose and mitochondrial metabolism contributes to obesity, highlighting the need to understand their interplay. Whether and how Steap4 influences mitochondrial function, adipocytes, and energy expenditure remain unclear. Adipocyte-specific Steap4-deficient mice exhibited increased fat mass and severe insulin resistance in our high-fat diet model. Mass spectrometry identified two classes of Steap4 interactomes: mitochondrial proteins and proteins involved in splicing. RNA sequencing (RNA-seq) analysis of white adipose tissue demonstrated that Steap4 deficiency altered RNA splicing patterns with enriched mitochondrial functions. Indeed, Steap4 deficiency impaired respiratory chain complex activity, causing mitochondrial dysfunction in white adipose tissue. Consistently, brown adipocyte-specific Steap4 deficiency impaired mitochondrial function, increased brown fat whitening, reduced energy expenditure, and exacerbated insulin resistance in a high-fat model. Overall, our study highlights Steap4's critical role in modulating adipocyte mitochondrial function, thereby controlling thermogenesis, energy expenditure, and adiposity.PMID:39995871 | PMC:PMC11848796 | DOI:10.1016/j.isci.2025.111903

iScience. 2025 Jan 22;28(2):111874. doi: 10.1016/j.isci.2025.111874. eCollection 2025 Feb 21.ABSTRACTBrain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Toward this goal, we explored the contribution of the gut microbiome to BrM development by using in vivo breast-BrM models under germ-free conditions or antibiotic treatment. This revealed a detrimental role of gut microbiota in fostering BrM initiation. We thus evaluated the impact of antibiotics and BrM outgrowth on the gut-brain axis. We found the bacterial genus Alistipes was differentially present under antibiotic treatment and BrM progression. In parallel, we quantified circulating metabolites, revealing kynurenic acid as a differentially abundant molecule that impaired the interaction between cancer cells and the brain vasculature in ex vivo functional assays. Together, these results illuminate the potential role of gut microbiota in modulating breast-BrM via the gut-to-brain axis.PMID:39995854 | PMC:PMC11848439 | DOI:10.1016/j.isci.2025.111874