PubMed

Am J Physiol Lung Cell Mol Physiol. 2025 Jan 17. doi: 10.1152/ajplung.00131.2024. Online ahead of print.ABSTRACTThe increasing shift from cannabis smoking to cannabis vaping is largely driven by the perception that vaping to form an aerosol represents a safer alternative to smoking and is a form of consumption appealing to youth. Herein, we compared the chemical composition and receptor-mediated activity of cannabis smoke extract (CaSE) to cannabis vaping extract (CaVE) along with the biological response in human bronchial epithelial cells. Chemical analysis using HPLC and GC/MS revealed that cannabis vaping aerosol contained fewer toxicants than smoke; CaSE and CaVE contained teratogens, carcinogens, and respiratory toxicants. A bioluminescence resonance energy transfer (BRET)-based biosensor detected the receptor-mediated activity of the extracts, primarily driven by Δ9-THC concentration. RNA- sequencing showed both CaSE and CaVE induced similar transcriptional responses, significantly upregulating genes within pathways related to inflammation, cancer, and cellular stress. This was paralleled by downregulation of pathways related to lipid synthesis and metabolism similarly from both CaSE and CaVE. Targeted metabolomics revealed significant changes in metabolites involved in lipid and membrane metabolism, energy production, nucleotide/DNA/RNA pathways, and oxidative stress response, suggesting potential impairment of lung epithelial cell repair and function. Additionally, the upregulation of 5-hydroxymethylcytosine (5hmC) indicates epigenetic changes potentially contributing to inflammation, oxidative stress, and an increased risk of cancer. These findings challenge the notion that cannabis vaping is risk-free, highlighting an urgent need for comprehensive research into its respiratory health effects. This comparison of cannabis consumption methods offers insights that could inform public health policies and raise consumer awareness regarding the potential risks of inhaling cannabis aerosol.PMID:39823205 | DOI:10.1152/ajplung.00131.2024

Open Life Sci. 2024 Dec 31;19(1):20220974. doi: 10.1515/biol-2022-0974. eCollection 2024.ABSTRACTIn this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventricular remodeling in DCM. A thorough analysis of global changes in genes and metabolites showed that amino acid metabolism, especially the breakdown of branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine, is highly dysregulated. Furthermore, the study identified the transcription factor Gata3 as a predicted negative regulator of the gene encoding the key enzyme for BCAA degradation. These findings suggest that the disruption of BCAA degradation is a critical characteristic of diabetic myocardial damage and indicate a potential role for Gata3 in the dysregulation of BCAA metabolism in the context of DCM.PMID:39822378 | PMC:PMC11736389 | DOI:10.1515/biol-2022-0974

J Extracell Vesicles. 2025 Jan;14(1):e70036. doi: 10.1002/jev2.70036.NO ABSTRACTPMID:39822156 | DOI:10.1002/jev2.70036

Physiol Plant. 2025 Jan-Feb;177(1):e70060. doi: 10.1111/ppl.70060.ABSTRACTHalophytes display distinctive physiological mechanisms that enable their survival and growth under extreme saline conditions. This makes them potential candidates for their use in saline agriculture. In this research, tomato (Solanum lycopersium Mill.) was cultivated in moderately saline conditions under two different managements involving Arthrocaulon macrostachyum L., a salt accumulator shrub: intercropping, i.e., co-cultivation of tomato/halophyte; and crop rotation, in which tomato is grown where the halophyte was previously cultivated. The effect of these crop managements was evaluated in tomato plants in comparison with tomato in monoculture, with regards to physiological and biochemical variables and metabolomic and proteomic profiles. Both halophyte-based managements reduced soil salinity. Crop rotation enhanced photosynthesis and protective mechanisms at the photosynthetic level. In addition, both crop managements altered the hormone profile and the antioxidant capacity, whereas a reactive oxygen species over-accumulation in leaf tissues indicated the establishment of a controlled mild oxidative stress. However, tomato production remained unchanged. Metabolomic and proteomic approaches suggest complex interactions at the leaf level, driven by the influence of the halophyte. In this regard, an interplay of ROS/lipid-based signalling pathways is proposed. Moreover, improved photosynthesis under crop rotation was associated with accumulation of sugar metabolism-related compounds and photosynthesis-related proteins. Likewise, acylamino acid-releasing enzymes, a class of serine-proteases, remarkably increased under both halophyte-based managements, which may act to modulate the antioxidant capacity of tomato plants. In summary, this work reveals common and distinctive patterns in tomato under intercropping and crop rotation conditions with the halophyte, supporting the use of A. macrostachyum in farming systems.PMID:39822104 | DOI:10.1111/ppl.70060

J Sci Food Agric. 2025 Jan 17. doi: 10.1002/jsfa.14099. Online ahead of print.ABSTRACTBACKGROUND: Dietary supplementation for beef cattle, using natural plant extracts, such as oregano essential oil (OEO), has proven effective in enhancing growth performance, beef production quantity and quality, and ensuring food safety. However, the precise mechanisms underlying these effects remain unclear. This study investigated the impact of OEO on carcass traits, muscle fiber structure, meat quality, oxidative status, flavor compounds, and gene regulatory mechanisms in the longissimus thoracis (LT) muscles of beef cattle. Eighteen steers were randomly assigned to two groups (n = 9 per group) and fed either a control diet (CK) or the same diet supplemented with 20 g of OEO per head per day for 300 days.RESULTS: Oregano essential oil supplementation improved the body weight, carcass weight, meat production, area and diameter of fiber, ether extract, and water-holding power of muscle. Increasing catalase (CAT), peroxidases (POD), glutathione peroxidase (GSH-Px) and by decreasing lipid droplets (LDs) reduced muscle lipid oxidation. However, the color (L*, a*, b*, C* and H°) and the flavor compounds of muscle were affected adversely by OEO. The transcriptome and metabolome indicated the OEO group enriched fat synthesis, proteo-metabolism, antioxidants, and growth significantly. Five key genes (SH2B2, CD209, LOC504773, C1QC, and HMOX) and ten downregulated metabolites (deoxyguanosine, d-melezitose, maltotriose, raffinose, melatonin, quinic acid, orotic acid, hydrocinnamic acid, 2-methylsuccinic acid, and pyridoxal 5'-phosphate) were identified as key biomarkers. These interacted to positively influence the growth, oxidative status, and meat quality of steers positively.CONCLUSION: These findings suggest that OEO, as a natural bioactive compound, can serve as an additive for beef cattle, with a daily dose of 20 g per steer improving growth and meat quality, although it may affect muscle color and flavor negatively. © 2025 Society of Chemical Industry.PMID:39821900 | DOI:10.1002/jsfa.14099

Sci China Life Sci. 2025 Jan 13. doi: 10.1007/s11427-024-2653-2. Online ahead of print.ABSTRACTAlthough disturbances in the gut microbiome have been implicated in multiple sclerosis (MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes affect disease-modifying therapy (DMT) in preventing the progression of MS. In this study, the structure and composition of the gut microbiota were evaluated using 16S rRNA gene sequencing and an untargeted metabolomics approach was used to compare the serum metabolite profiles from patients with relapsing-remitting MS (RRMS) and healthy controls (HCs). Results indicated that RRMS was characterized by phase-dependent α-phylogenetic diversity and significant disturbances in serum glycerophospholipid metabolism. Notably, α-phylogenetic diversity was significantly decreased in RRMS patients during the chronic phase (CMS) compared with those in the acute phase (AMS). A distinctive combination of two elevated genera (Slackia, Lactobacillus) and five glycerophospholipid metabolism-associated metabolites (four increased: GPCho(22:5/20:3), PC(18:2(9Z,12Z)/16:0), PE(16:0/18:2(9Z,12Z)), PE(18:1(11Z)/18:2(9Z,12Z)); one decreased: PS(15:0/22:1(13Z))) in RRMS patients when comparing to HCs. Moreover, a biomarker panel consisting of four microbial genera (three decreased: Lysinibacillus, Parabacteroides, UBA1819; one increased: Lachnoanaerobaculum) and two glycerophospholipid metabolism-associated metabolites (one increased: PE(P-16:0/22:6); one decreased: CL(i-12:0/i-16:0/i-17:0/i-12:0)) effectively discriminated CMS patients from AMS patients, which indicate correlation with higher disability. Additionally, DMTs appeared to attenuate MS progression by reducing UBA1819 and upregulating CL(i-12:0/i-16:0/i-17:0/i-12:0). These findings expand our understanding of the microbiome and metabolome roles in RRMS and may contribute to identifying novel diagnostic biomarkers and promising therapeutic targets.PMID:39821830 | DOI:10.1007/s11427-024-2653-2

Intensive Care Med Exp. 2025 Jan 17;13(1):6. doi: 10.1186/s40635-025-00715-1.ABSTRACTBACKGROUND: Sepsis-induced cardiomyopathy (SICM) often occurs in the acute phase of sepsis and is associated with increased mortality due to cardiac dysfunction. The pathogenesis remains poorly understood, and no specific treatments are available. Although SICM is considered reversible, emerging evidence suggests potential long-term sequelae. We hypothesized that metabolic and inflammatory cardiac changes, previously observed in acute sepsis as potential drivers of SICM, partially persist in prolonged sepsis.METHODS: In 24-week-old C57BL/6J mice, sepsis was induced by cecal ligation and puncture, followed by intravenous fluid resuscitation, subcutaneous analgesics and antibiotics, and, in the prolonged phase, by parenteral nutrition. Mice were killed after 5 days of sepsis (prolonged sepsis, n = 15). For comparison, we included acutely septic mice killed at 30 h (acute sepsis, n = 15) and healthy controls animals (HC, n = 15). Cardiac tissue was collected for assessment of inflammatory and metabolic markers through gene expression, metabolomic analysis and histological assessment.RESULTS: In prolonged sepsis, cardiac expression of IL-1β and IL-6 and macrophage infiltration remained upregulated (p ≤ 0.05). In contrast, tissue levels of Krebs cycle intermediates and adenosine phosphates were normal, whereas NADPH levels were low in prolonged sepsis (p ≤ 0.05). Gene expression of fatty acid transporters and of the glucose transporter Slc2a1 was upregulated in prolonged sepsis (p ≤ 0.01). Lipid staining and glycogen content were elevated in prolonged sepsis together with increased gene expression of enzymes responsible for lipogenesis and glycogen synthesis (p ≤ 0.05). Intermediate glycolytic metabolites (hexose-phosphates, GADP, DHAP) were elevated (p ≤ 0.05), but gene expression of several enzymes for glycolysis and mitochondrial oxidation of pyruvate, fatty-acyl-CoA and ketone bodies to acetyl-CoA were suppressed in prolonged sepsis (p ≤ 0.05). Key metabolic transcription factors PPARα and PGC-1α were downregulated in acute, but upregulated in prolonged, sepsis (p ≤ 0.05 for both). Ketone body concentrations were normal but ketolytic enzymes remained suppressed (p ≤ 0.05). Amino acid metabolism showed mild, mixed changes.CONCLUSIONS: Our results suggest myocardial lipid and glycogen accumulation and suppressed mitochondrial oxidation, with a functionally intact Krebs cycle, in the prolonged phase of sepsis, together with ongoing myocardial inflammation. Whether these alterations have functional consequences and predispose to long-term sequelae of SICM needs further research.PMID:39821755 | DOI:10.1186/s40635-025-00715-1

Front Med. 2025 Jan 17. doi: 10.1007/s11684-024-1116-0. Online ahead of print.ABSTRACTThe pursuit of healthy aging has long rendered aging and senescence captivating. Age-related ailments, such as cardiovascular diseases, diabetes, and neurodegenerative disorders, pose significant threats to individuals. Recent studies have shed light on the intricate mechanisms encompassing genetics, epigenetics, transcriptomics, and metabolomics in the processes of senescence and aging, as well as the establishment of age-related pathologies. Amidst these underlying mechanisms governing aging and related pathology metabolism assumes a pivotal role that holds promise for intervention and therapeutics. The advancements in metabolomics techniques and analysis methods have significantly propelled the study of senescence and aging, particularly with the aid of multiscale metabolomics which has facilitated the discovery of metabolic markers and therapeutic potentials. This review provides an overview of senescence and aging, emphasizing the crucial role metabolism plays in the aging process as well as age-related diseases.PMID:39821730 | DOI:10.1007/s11684-024-1116-0

Appl Biochem Biotechnol. 2025 Jan 17. doi: 10.1007/s12010-024-05136-6. Online ahead of print.ABSTRACTThis work aims to provide a basis for the enhancement of fucoxanthin (FCX) and eicosapentaenoic acid (EPA) biosynthesis in the microalga Phaeodactylum tricornutum using metabolomics and computational biology. To achieve this, both targeted (UHPLC and GC-FID) and untargeted (FTIR and NMR) analyses were conducted throughout various stages of cell cultivation. Targeted analyses revealed that EPA concentrations peaked at the end of the logarithmic growth phase, while fucoxanthin levels remained consistent from the onset of this phase through to the stationary phase. Untargeted analyses provided metabolic profiles by correlating FTIR absorbance bands with functional groups. When combined with cultivation strategies designed to improve EPA and FCX content, the optimal time for harvesting cells was identified as the end of the logarithmic phase. NMR further highlighted potentially key metabolic pathways for optimizing EPA and FCX production in Phaeodactylum tricornutum, particularly those involved in glyoxylate and dicarboxylate metabolism.PMID:39821501 | DOI:10.1007/s12010-024-05136-6

J Gerontol A Biol Sci Med Sci. 2025 Jan 16:glae280. doi: 10.1093/gerona/glae280. Online ahead of print.ABSTRACTChronological age is a major risk factor for numerous diseases. However, chronological age does not capture the complex biological aging process. the difference between the chronological age and biologically driven aging could be more informative in reflecting health status. Here, we set out to develop a metabolomic age prediction model by applying ridge regression and bootstrapping with 826 metabolites (678 endogenous and 148 xenobiotics) measured by an untargeted platform in relatively healthy blood donors aged 18-75 years from the INTERVAL study (N=11,977;50.2% men). After bootstrapping internal validation, the metabolomic age prediction models demonstrated high performance with an adjusted R2 of 0.83 using all metabolites and 0.82 using only endogenous metabolites. The former was significantly associated with obesity and cardiovascular disease (CVD) in the NEO study (N=599;47.0% men; age range=45-65) due to the contribution of medication derived metabolites-namely salicylate and ibuprofen-and environmental exposures such as cotinine. Additional metabolomic age prediction models using all metabolites were developed for men and women separately. The models had high performance (R²=0.85 and 0.86) but shared a moderate correlation of 0.72. Furthermore, we observed 163 sex-dimorphic metabolites, including threonine, glycine, cholesterol, and androgenic and progesterone-related metabolites. Our strongest predictors across all models were novel and included hydroxyasparagine (Model Endo+Xeno β=4.74), vanillylmandelate (β=4.07), and 5,6-dihydrouridine (β=-4.2). Our study presents a robust metabolomic age model that reveals distinct sex-based age-related metabolic patterns and illustrates the value of including xenobiotic to enhance metabolomic prediction accuracy.PMID:39821408 | DOI:10.1093/gerona/glae280

Sci China Life Sci. 2025 Jan 10. doi: 10.1007/s11427-024-2654-2. Online ahead of print.ABSTRACTMetabolites and metabolism-related gene expression profiles in skeletal muscle change dramatically under obesity, aging and metabolic disease. Since obese and lean pigs are ideal models for metabolic research. Here, we compared metabolome and transcriptome of Longissimus dorsi (LD) muscle between Taoyuan black (TB, obese) and Duroc (lean) pigs at different ages. We defined the "window phase" of intramuscular fat (IMF) deposition in TB pig, which has significantly higher IMF than Duroc pig. Our results displayed discrepant lipid composition and different expression genes (DEGs) enriched in lipid metabolism, and both metabolome and transcriptome analyses revealed stronger energy expenditure and more active amino acid and protein metabolism in Duroc pig. 10 up- and 51 down-regulated biomarker metabolites with age- and breed-specificity were identified. Potential secretory metabolites, including organic acid (fumaric acid, succinate, malic acid, and gamma-aminobutyric acid), amino acid (L-lysine, and L-glutamic acid), lipid (2-hydroxyisovaleric acid, and L-carnitine) were demonstrated a significant correlation with IMF deposition. Our research highlights the huge difference of metabolic spectrum in skeletal muscle between obese and lean model and muscle-derived secretory metabolites might act as an ambassador of intercellular communication to regulate systematic metabolism.PMID:39821160 | DOI:10.1007/s11427-024-2654-2

Plant Mol Biol. 2025 Jan 17;115(1):21. doi: 10.1007/s11103-024-01546-6.ABSTRACTPsa primarily utilises the type III secretion system (T3SS) to deliver effector proteins (T3Es) into host cells, thereby regulating host immune responses. However, the mechanism by which kiwifruit responds to T3SS remains unclear. To elucidate the molecular reaction of kiwifruit plants to Psa infection, M228 and mutant M228△hrcS strains were employed to inoculate Actinidia chinensis var. chinensis for performing comparative transcriptional and metabolomic analyses. Transcriptome analysis identified 973 differentially expressed genes (DEGs) related to flavonoid synthesis, pathogen interaction, and hormone signaling pathways during the critical period of Psa infection at 48 h post-inoculation. In the subsequent metabolomic analysis, flavonoid-related differential metabolites were significantly enriched after the loss of T3SS.Through multi-omics analysis, 22 differentially expressed genes related to flavonoid biosynthesis were identified. Finally, it was discovered that the transient overexpression of 3 genes significantly enhanced kiwifruit resistance to Psa. qRT-PCR analysis indicated that Ac4CL1, Ac4CL3 and AcHCT1 promote host resistance to disease, while Ac4CL3 negatively regulates host resistance to Psa. These findings enrich the plant immune regulation network involved in the interaction between kiwifruit and Psa, providing functional genes and directions with potential application for breeding kiwifruit resistance to canker disease.PMID:39821123 | DOI:10.1007/s11103-024-01546-6

Oncogene. 2025 Jan 16. doi: 10.1038/s41388-024-03266-z. Online ahead of print.ABSTRACTThe functional activation of the androgen receptor (AR) and its interplay with the aberrant Hh/Gli cascade are pivotal in the progression of castration-resistant prostate cancer (CRPC) and resistance to AR-targeted therapies. Our study unveiled a novel role of the truncated form of Gli (t-Gli3) in advancing CRPC. Investigation into Gli3 regulation revealed a Smo-independent mechanism for its activation. Despite lacking a transactivation domain, t-Gli3 relies on androgen receptor variant 7 (AR-V7) for its action. Mechanistically, Gsk3β activation led to the t-Gli3 generation, and inhibition of Gsk3β supported the accumulation of full-length Gli3 expression through a non-canonical mechanism. Knockdown of Gsk3β (Gsk3β KD) reduces CRPC cell proliferation, induces apoptosis via mitochondrial fragmentation, and triggers metabolomic reprogramming. The in vivo studies with Gsk3β KD cells in the mouse prostate resulted in tumor growth retardation compared to scramble cells. RNA-seq HALLMARK Gene Set Enrichment Analysis (GSEA) analysis of Gsk3β KD revealed a positive enrichment of apoptosis, tumor suppressor gene, and negative enrichment of oncogenic pathway. Furthermore, combinational use of a Gsk3β inhibitor with anti-Smo or Gli1 significantly inhibited the CRPC cell growth, which is resistant to individual Smo or Gli1 inhibitor targeting. Intriguingly, solely targeting Gli3 showed effectiveness in inhibiting CRPC cell growth. Overall, our study underscores the clinical significance of Gli3, emphasizing t-Gli3, and provides novel insights into the interplay of the Gsk3β/t-Gli3/AR-V7 axis in CRPC.PMID:39821099 | DOI:10.1038/s41388-024-03266-z

Physiol Plant. 2025 Jan-Feb;177(1):e70062. doi: 10.1111/ppl.70062.ABSTRACTEnsuring food security is one of the main challenges related to a growing global population under climate change conditions. The increasing soil salinity levels, drought, heatwaves, and late chilling severely threaten crops and often co-occur in field conditions. This work aims to provide deeper insight into the impact of single vs. combined abiotic stresses at the growth, biochemical and photosynthetic levels in Arabidopsis thaliana (L.). Reduced QY max was recorded in salinity-stressed plants, NPQ increased in heat and salinity single and combined stresses, and qP decreased in combined stresses. MDA and H2O2 content were consistently altered under all stress conditions, but higher values were recorded under salinity alone and in combination. Salinity alone and in stress combinations (especially with cold) provided a stronger hierarchical effect. Despite glycine and GABA osmolytes not significantly changing, proline highlighted the hierarchically stronger impact of salinity, while glycine-betaine was decreased under drought combinations. Untargeted metabolomics pointed out distinct metabolic reprogramming triggered by the different stress conditions, alone or in combination. Pathway analysis revealed that abiotic stresses significantly affected hormones, amino acids and derivates, and secondary metabolites. Flavonoids accumulated under drought (alone and combined with heat and cold stresses), while N-containing compounds decreased under all combined stresses. Looking at the interactions across the parameters investigated, antagonistic, additive, or synergistic effects could be observed depending on the biochemical process considered. Notwithstanding, these results contribute to delving into the impact of various stress combinations, hierarchically highlighting the stress-specific effects and pointing out different combinations.PMID:39821073 | DOI:10.1111/ppl.70062

Nat Methods. 2025 Jan 16. doi: 10.1038/s41592-024-02575-1. Online ahead of print.ABSTRACTSuper-resolution imaging of cell metabolism is hindered by the incompatibility of small metabolites with fluorescent dyes and the limited resolution of imaging mass spectrometry. We present ultrasensitive reweighted visible stimulated Raman scattering (URV-SRS), a label-free vibrational imaging technique for multiplexed nanoscopy of intracellular metabolites. We developed a visible SRS microscope with extensive pulse chirping to improve the detection limit to ~4,000 molecules and introduced a self-supervised multi-agent denoiser to suppress non-independent noise in SRS by over 7.2 dB, resulting in a 50-fold sensitivity enhancement over near-infrared SRS. Leveraging the enhanced sensitivity, we employed Fourier reweighting to amplify sub-100-nm spatial frequencies that were previously overwhelmed by noise. Validated by Fourier ring correlation, we achieved a lateral resolution of 86 nm in cell imaging. We visualized the reprogramming of metabolic nanostructures associated with virus replication in host cells and subcellular fatty acid synthesis in engineered bacteria, demonstrating its capability towards nanoscopic spatial metabolomics.PMID:39820753 | DOI:10.1038/s41592-024-02575-1

Plant Cell. 2025 Jan 16:koaf015. doi: 10.1093/plcell/koaf015. Online ahead of print.ABSTRACTPhotorespiration, often considered as a wasteful process, is a key target for bioengineering to improve crop yields. Several photorespiratory bypasses have been designed to efficiently metabolize 2-phosphoglycolate and increase the CO2 concentration in chloroplasts, thereby reducing photorespiration. However, the suppression of primary nitrate assimilation remains an issue when photorespiration is inhibited. In this study, we designed a carbon and nitrogen metabolism-coupled photorespiratory bypass, termed the GCBG bypass, in rice (Oryza sativa) chloroplasts. Our results demonstrated efficient assembly and expression of the GCBG bypass in rice chloroplasts, which affected the levels of typical metabolites and their derivatives of natural photorespiration and enhanced the photosynthetic efficiency. Metabolomic analyses revealed that oxaloacetate, produced from glycolate in chloroplasts, positively impacted amino acid synthesis, energy metabolism, and sugar synthesis. The engineered GCBG plants showed an average yield increase of 19.0% (17.8-20.2%) compared to wild-type plants under natural growth conditions, alongside improved nitrogen uptake, which compensated for 44.1% of yield losses under nitrogen-limited conditions. In summary, the GCBG bypass substantially improved the photosynthetic efficiency, biomass and yield in rice by integrating carbon and nitrogen metabolism. This study introduces a strategy for engineering high-yielding rice or other crops with improved photosynthetic efficiency and nitrogen uptake.PMID:39820482 | DOI:10.1093/plcell/koaf015

J Clin Endocrinol Metab. 2025 Jan 16:dgaf033. doi: 10.1210/clinem/dgaf033. Online ahead of print.ABSTRACTCONTEXT: When clinically stable, patients with A-β+ Ketosis-Prone Diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.OBJECTIVE: Compare serum metabolomics of KPD, T1D and T2D patients during hyperglycemic crises, and utilize Classification and Regression Tree (CART) modeling to distinguish these forms of diabetes.SETTING: Urban hospital emergency center.PARTICIPANTS: Adults with KPD, T1D and T2D during hyperglycemic crises (with or without diabetic ketoacidosis (DKA), and healthy controls.INTERVENTIONS: Comparisons of serum metabolite and hormonal profiles, and CART analysis.MAIN OUTCOME MEASURES: Group differences in concentrations of amino acids, their metabolites and relationship to glucose counterregulatory hormones; C-peptide cutoffs and analytes to distinguish KPD, T1D and T2D.RESULTS: Concentrations of most amino acids were similar in KPD and T1D and lower compared to T2D (P<0.05). Glucagon and cortisol concentrations were correlated with 3-methylhistidine and blood urea nitrogen in KPD but not in T1D. A C-peptide cutoff of 0.496 ng/mL differentiated T1D from KPD during DKA. CART revealed that a regression model based on the concentrations of β-hydroxybutyrate, C-peptide, glucagon, alpha-keto-β-methylvalerate, cystine and myristoyl-L-carnitine distinguished KPD from T1D and T2D.CONCLUSIONS: During DKA, KPD and T1D patients have similarly altered amino acid profiles that differentiate them from T2D patients. Elevated protein catabolic hormones drive altered amino acid metabolism in KPD, rather than insulin deficiency as with T1D. A combination of 6 analytes differentiates KPD from T1D and T2D during hyperglycemic crises.PMID:39820433 | DOI:10.1210/clinem/dgaf033

Sci Data. 2025 Jan 16;12(1):90. doi: 10.1038/s41597-025-04429-7.ABSTRACTLarge yellow croaker (Larimichthys crocea) is a highly economically important marine fish species in China. However, substantial individual variations in growth performance have emerged as a limiting factor for the sustainable development of the large yellow croaker industry. Gut microbiota plays a crucial role in fish growth and development by regulating metabolic processes. To explore these dynamics, we employed metagenomics, transcriptomics, and untargeted metabolomics to comprehensively analyze the structure of the intestinal microbiome and its relationship with intestinal metabolism and host gene expression. We constructed association models for "gut microbiota-differentially expressed genes", "differentially expressed genes-metabolites," and "gut microbiota-metabolites." Sequencing data and LC-MS/MS raw data have been deposited in NCBI and MetaboLights databases for public access. Our findings offer critical insights into the molecular mechanisms underlying growth variations in L. crocea and provide valuable data for the selective breeding of improved strains.PMID:39820425 | DOI:10.1038/s41597-025-04429-7

Environ Toxicol Chem. 2025 Jan 16:vgaf013. doi: 10.1093/etojnl/vgaf013. Online ahead of print.ABSTRACTThe combination of silver nanoparticles (AgNPs) and ciprofloxacin (CIP) can be considered an alternative to combat multidrug-resistant microbial infections. However, knowledge about their combined toxicity is scarce after being released in an aquatic environment. The present study evaluated the individual toxicity of AgNPs and CIP and their combined toxicity on the unicellular green microalga Chlorella vulgaris, evaluating cellular responses and conducting metabolomic analysis. The median effective concentrations at 96 h (EC50-96h) for AgNPs, CIP, and the mixture were 132 µg L-1, 7000 µg L-1, and 452 µg L-1, respectively. CIP exhibited a synergistic effect with AgNPs. The toxic ranking for C. vulgaris was AgNPs > AgNPs + CIP > CIP. The growth rate was the most evident parameter of toxicity. Cell diameter significantly increased (p < 0.001) at 96 hours for the highest concentrations tested of AgNPs, CIP, and the mixture, with increases of 24%, 41%, and 19%, respectively, compared to the control. Photosynthetic pigment analyses revealed that C. vulgaris upregulated chlorophyll, carotenoids, and pheophytin. Cell exposure to CIP caused an SOS response involving increased protein and carbohydrate concentrations to tolerate antibiotic stress. Exposure to AgNPs and CIP increased catalase and glutathione S-transferase activity, but the mixture decreased the activity. AgNPs increased malondialdehyde content in exposed cells due to fatty acid peroxidation. These pollutants revealed their potential risks in interfering with survival and metabolism. Our findings highlight the possible hazards of co-pollutants at environmentally relevant quantities, providing insights into the individual and combined ecotoxicity of AgNPs and CIP.PMID:39820261 | DOI:10.1093/etojnl/vgaf013

Sci Rep. 2025 Jan 16;15(1):2197. doi: 10.1038/s41598-024-79159-8.ABSTRACTThis study investigated the psychophysiological and metabolomic changes during horticultural activities involving the inhalation of volatile organic compounds (VOCs) in individuals experiencing depressive mood based on the presence or absence of the soil microbe Streptomyces rimosus, which emits VOCs. Thirty participants met the specific depression and anxiety criteria and engaged in horticultural activities using soil inoculated with S. rimosus (experimental group) or medium (control group). Electroencephalogram (EEG) was used to analyze the resulting psychophysiological response, and blood samples were collected after each activity. Significant increases were observed in the FZ channel of the central frontal lobe for relative theta, relative alpha, relative slow alpha, ratio of sensorimotor rhythm mid beta to theta, and ratio of alpha to high beta, whereas significant decreases were noted for relative beta, relative high beta, and relative gamma and spectral edge frequency 50% and 90%. GC-TOF-MS analysis identified 44 altered serum metabolites, showing an increasing trend in succinate, glycolate, glycerate, acetate, palmitate, myristate, laurate, caprynate, and octanoate, which are related to the citrate cycle, glyoxylate and dicarboxylate metabolism, and fatty acid biosynthesis. In conclusion, this study suggests that inhalation of VOCs during horticultural activities can help alleviate depression and depressive moods.PMID:39820093 | DOI:10.1038/s41598-024-79159-8