PubMed

J Transl Med. 2025 Jan 31;23(1):143. doi: 10.1186/s12967-025-06168-0.ABSTRACTBACKGROUND: Despite the success of antiretroviral therapy (ART) in suppressing HIV-1 replication, some people living with HIV-1 (PLWH) fail to achieve an optimal recovery of CD4 T cells, and precise metabolic regulation underlying immune recovery remained poorly understood.METHODS: In this cross-sectional study, mass spectrometry was used for quantitative analysis of plasma metabolome and lipidome in 24 treatment-naïve PLWH (TNs), 33 immunological responders (IRs), 35 immunological non-responders (INRs), and 16 healthy controls (HCs). The data were analyzed using the Mann-Whitney U-test, Kruskal-Wallis test, Spearman correlation, and LASSO regression analysis.RESULTS: Significant metabolic dysregulation was observed in TNs, IRs and INRs compared to HCs. In TNs, metabolomic analysis revealed increased levels of 3-hydroxyoctanoic acid, 3-oxododecanoic acid, 5-hydroxy-L-tryptophan, 5-hydroxyindoleacetic acid, L-kynurenine, oleoylcarnitine, and pseudouridine that were positively correlated with CD8 T cell activation and inflammation-related markers, and decreased levels of phosphorylcholine, ribothymidine, and thymine that were negatively correlated. Notably, 3-hydroxyoctanoic acid and thymine were consistently associated with CD4 T cell counts and inflammation-related markers in PLWH, regardless of ART. Pathway analysis uncovered the biosynthesis of unsaturated fatty acids as the major dysregulated pathway in TNs, IRs, and INRs, while primary bile acid biosynthesis was the dysregulated pathway specifically in INRs. Lipidomic analysis indicated higher plasma triacylglycerols, free fatty acids, ceramide, and monosialodihexosyl gangliosides (GM3) in TNs, IRs, and INRs compared to HCs. Pathway enrichment and differential correlation analyses underscore perturbed systemic lipid metabolism in treatment response to ART, possibly mediated by host-commensal metabolic interactions. Ultimately, we identified two panels, one consisting of 9 metabolites and another of 8 lipids, that can effectively distinguish INRs from IRs.CONCLUSIONS: Metabolic aberrations induced by chronic HIV-1 infection persist and do not recover with ART. Abnormal primary bile acid biosynthesis pathway and levels of DHA-containing lipids are closely associated with CD4 T cell recovery. These finding provide new intervention targets to achieve better immune recovery in PLWH.PMID:39891216 | DOI:10.1186/s12967-025-06168-0

BMC Genomics. 2025 Jan 31;26(1):96. doi: 10.1186/s12864-025-11272-y.ABSTRACTThe walnut (Juglans regia) is an important oilseed tree species characterized by its extensive distribution, high oil yield, and nutrient-dense kernels, which provide substantial economic benefits. However, the rising incidence of late-spring frosts, exacerbated by global climate change, has adversely affected walnut yields. A comprehensive understanding of the regulatory mechanisms involved in bud dormancy, germination, and development is essential for developing strategies to mitigate the effects of late-spring frosts and for breeding frost-resistant cultivars. This study focused on W13, a protogynous walnut variety with early germination of dormant buds in spring, employing a combination of transcriptomic and hormone metabolomic analyses. Our results emphasized four key biological processes-cellular response to ethylene stimulus, phenylpropanoid metabolic process, ethylene-activated signaling pathway, and monooxygenase activity-along with several relevant pathways, including plant hormone signal transduction, flavone and flavonol biosynthesis, biosynthesis of secondary metabolites, and MAPK signaling pathway, all crucial for walnut bud germination. Additionally, bud germination is closely associated with alterations in various hormone signaling pathways, including abscisic acid, auxin, cytokinin, ethylene, gibberellins, jasmonic acid, and salicylic acid. By assessing hormone levels and gene expression at different developmental stages, we pinpointed potential regulatory genes and critical hormones associated with bud germination. Furthermore, through weighted correlation network analysis, we constructed a co-expression network, identifying gene modules specifically expressed during dormancy, germination, budding, and leafing phases. The hub genes within these modules are likely pivotal in regulating walnut bud germination. Our analysis also revealed that genes from various transcription factor families are central within the co-expression network, indicating their significant roles in the bud germination process. Correlation network analysis of hormone and gene further illuminated the mechanisms through which genes and hormones jointly influence walnut bud germination. These findings establish a crucial molecular basis for a more comprehensive understanding of the mechanisms governing germination and development in dormant walnut buds.PMID:39891068 | DOI:10.1186/s12864-025-11272-y

BMJ Open. 2025 Jan 30;15(1):e089206. doi: 10.1136/bmjopen-2024-089206.ABSTRACTINTRODUCTION: Type 1 diabetes (T1D) is an autoimmune-mediated disorder caused by the destruction of pancreatic beta cells. Although there is an underlying genetic predisposition to developing T1D, the trigger is multifactorial and likely includes environmental factors. The intestinal microbiome has been identified as one such factor. Previous studies have illustrated differences in the microbiota of people with T1D compared with healthy controls. This study aims to describe the evolution of the microbiome and metabolome during the first year of clinical T1D, or stage 3 T1D diagnosis, and investigate whether there are differences in the microbiome and metabolome of children who present with and without diabetic ketoacidosis. The study will also explore possible associations between the microbiome, metabolome, glycaemic control and beta cell reserve.METHODS AND ANALYSIS: This prospective cohort study will include children with newly diagnosed T1D and sibling controls (n=100, males and females) and their faecal microbiome will be characterised using shotgun metagenomic sequencing at multiple time points during the first year of diagnosis. We will develop a microbial culture biobank based on culturomic studies of stool samples from the healthy controls that will support future investigation. Metabolomic analysis will aim to identify additional biomarkers which may be involved in disease presentation and progression. Through this initial exploratory study, we aim to identify specific microbial biomarkers which may be used as future interventional targets throughout the various stages of T1D progression.ETHICS AND DISSEMINATION: This study has been approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. Study results will be available to patients with T1D and their families, carers, support networks and microbiome societies and other researchers.TRIAL REGISTRATION NUMBER: The clinicaltrials.gov registration number for this trial is NCT06157736.PMID:39890137 | DOI:10.1136/bmjopen-2024-089206

Neoreviews. 2025 Feb 1;26(2):e100-e114. doi: 10.1542/neo.26-2-011.ABSTRACTThe metabolome and lipidome comprise the thousands of molecular compounds in an organism. Molecular compounds consist of the upstream metabolic components of intracellular reactions or the byproducts of cellular pathways. Molecular and biochemical perturbations are associated with disorders in newborns and infants. The diagnosis of inborn errors of metabolism has relied on targeted metabolomics for several decades. Newer approaches offer the potential to identify novel biomarkers for common diseases of the newborn and infant. They may also elucidate novel predictive or diagnostic measures for a variety of health trajectories. Here, we review the relevance of the metabolome and lipidome for common disorders and highlight challenges and opportunities for future investigations.PMID:39889768 | DOI:10.1542/neo.26-2-011

Food Chem. 2025 Jan 23;473:143015. doi: 10.1016/j.foodchem.2025.143015. Online ahead of print.ABSTRACTThis study presents metabolome profiling of milk-derived exosomes (MDE) from cows of different genetic origins that is Sahiwal (Bos indicus), Holstein Friesian (Bos taurus) and Karan Fries (crossbred: cross of Bos indicus and Bos taurus) using 1H NMR spectroscopy. Diverse arrays of 41 metabolites were identified in all MDE groups. Comparative profiling across the three MDE groups revealed 16 metabolites to be differentially abundant (p < 0.01; log 2(FC) > 1; VIP >1) and all of these were enriched in SW-MDE. On pairwise comparison, 19 metabolites showed differential abundance (p < 0.01) between SW-HF and 10 each in SW-KF and KF-HF MDE. All the metabolites except citrate and lactose exhibited abundance in SW-MDE followed by KF and HF-MDE. Most of the metabolites (alanine, leucine, isoleucine, valine, phenylalanine, O-acetyl carnitine and 3-hydroxybutyrate) enriched in SW-MDE have positive health attributes and are involved in key metabolic pathways associated with energy production, growth, intestinal proliferation, and immune regulation. The differential quantification highlighted the source specific metabolome of MDE and also the advantageous nutritional and therapeutic potential of indicus cow milk derived exosomes.PMID:39889637 | DOI:10.1016/j.foodchem.2025.143015

Microbiol Res. 2025 Jan 24;293:128077. doi: 10.1016/j.micres.2025.128077. Online ahead of print.ABSTRACTThe interplay between Parkinson's disease (PD) and sleep disturbances suggests that sleep problems constitute a risk factor for PD progression, but the underlying mechanisms remain unclear. Microglial activation and oxidative stress are considered to play an important role in the pathogenesis of aging and neurodegenerative diseases. We hypothesized that sleep deprivation (SD) could exacerbate PD progression via modulating microglial activation and oxidative stress. To test this hypothesis, we established a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), then subjected the mice to SD. A battery of behavioral tests, including rotarod, pole, adhesive removal, and open field tests, were used to assess motor function. Our study showed that SD exacerbated motor deficits, loss of tyrosine hydroxylase (TH), microglial activation and oxidative stress damage in PD model mice. Fecal microbiota transplantation experiments revealed that SD mediated PD progression, microglial activation and oxidative stress via the gut microbiota. 16S rRNA sequencing analysis indicated that SD increased the abundances of bacteria such as Bacteroidaceae, while decreasing the abundances of bacteria including Lactobacillus. Non-targeted metabolomic analysis of gut microbiota-derived metabolites revealed that SD significantly increased the production of adenosine (ADO), a purine metabolite. Probiotic supplementation reversed the effects of SD on motor deficits, dopaminergic neuron loss, microglial activation and oxidative stress damage in PD mice; it also decreased SD-induced ADO production. Administration of Adenosine A2A receptor (A2AR) inhibitors, Istradefylline (Ist), attenuated the roles of SD and ADO in promoting microglial activation, oxidative stress and PD progression. Taken together, our findings indicate that SD accelerates PD progression via regulating microbiota associated microglial activation and oxidative stress, suggesting that efforts to improve sleep quality can be used to prevent and treat PD.PMID:39889629 | DOI:10.1016/j.micres.2025.128077

Comp Biochem Physiol Part D Genomics Proteomics. 2025 Jan 24;54:101429. doi: 10.1016/j.cbd.2025.101429. Online ahead of print.ABSTRACTThe liver is simultaneously impacted by environmental challenges and modulates the response to these insults. Efforts to understand the effects of stressors on the activity of the liver typically consider one type of challenge (e.g., nutrition, toxin, disease), profile targeted molecules, or study the hepatic disruptions in one sex. The present study characterized hepatic changes in the metabolome of females and males exposed to the nutritional challenge of fasting and inflammatory signals elicited by the viral mimetic Poly(I:C). The hepatic metabolome of pigs was profiled using untargeted liquid chromatography-mass spectrometry analysis enabling the quantification of metabolites. The analysis of pathways enriched among metabolites showing sex-by-distress interactions revealed molecular processes affected by fasting and immune stresses in a sex-specific manner, including SLC-mediated transmembrane transport, the urea cycle, and G-protein coupled receptor signaling. Metabolites differentially abundant across sex-distress groups in the previous pathways included creatine, taurine, and glycine derivatives. Pathways over-represented among metabolites significantly affected by distress included glucose homeostasis, the Krebs cycle, and the metabolism of water-soluble vitamins, with key metabolites including S-adenosylmethionine, histidine, glycerophosphocholine, and lactic acid. These results indicate that 24-h fasting, and low-grade systemic inflammation modulate the liver metabolism. The detection of metabolic disruption that varies with sex enforces the need to develop therapies that can restore hepatic homeostasis in females and males.PMID:39889585 | DOI:10.1016/j.cbd.2025.101429

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