PubMed

Mol Cell Proteomics. 2024 Nov 26:100887. doi: 10.1016/j.mcpro.2024.100887. Online ahead of print.ABSTRACTThe foundation of all biological processes is the network of diverse and dynamic protein interactions with other molecules in cells known as the interactome. Understanding the interactome is crucial for elucidating molecular mechanisms but has been a longstanding challenge. Recent developments in mass spectrometry (MS)-based techniques, including affinity purification, proximity labeling, cross-linking, and co-fractionation mass spectrometry (MS), have significantly enhanced our abilities to study the interactome. They do so by identifying and quantifying protein interactions, yielding profound insights into protein organizations and functions. This review summarizes recent advances in MS-based interactomics, focusing on the development of techniques that capture protein-protein, protein-metabolite, and protein-nucleic acid interactions. Additionally, we discuss how integrated MS-based approaches have been applied to diverse biological samples, focusing on significant discoveries that have leveraged our understanding of cellular functions. Finally, we highlight state-of-the-art bioinformatic approaches for predictions of interactome and complex modeling, as well as strategies for combining experimental interactome data with computation methods, thereby enhancing the ability of MS-based techniques to identify protein interactomes. Indeed, advances in MS technologies and their integrations with computational biology provide new directions and avenues for interactome research, leveraging new insights into mechanisms that govern the molecular architecture of living cells and, thereby, our comprehension of biological processes.PMID:39608603 | DOI:10.1016/j.mcpro.2024.100887

Int J Biol Macromol. 2024 Nov 26:138122. doi: 10.1016/j.ijbiomac.2024.138122. Online ahead of print.ABSTRACTOral intake of probiotics is a promising approach to alleviate colitis. However, environmental sensitivity of the gastrointestinal tract and poor adhesion of probiotics to the intestine hamper the remedial effects. In this study, a simple yet effective novel probiotic multilayer coating consisting of Fe3+-protocatechuic acid (PCA) crosslinked network and Ca2+-induced sodium alginate (SA) for arming Lactiplantibacillus plantarum (LP) was developed. In the dextran sulfate sodium-induced colitis mouse model, SA-PCA-LP effectively alleviated colitis by regulating the expression of inflammatory cytokines, and repairing gut barriers. In addition, SA-PCA-LP regulated the gut microbiota and promoted the production of short-chain fatty acids, which further promoted the remission of colitis. Untargeted metabolomics also revealed that the scymnol, adenosine 5'-monophosphat, guanidylic acid, and 9H-purine-9-ol were significantly up-regulated in SA-PCA-LP group. In general, the novel coating strategies developed in the present study will motivate researchers to arm probiotics with various prebiotics to effectively alleviate colitis.PMID:39608540 | DOI:10.1016/j.ijbiomac.2024.138122

Microb Pathog. 2024 Nov 26:107162. doi: 10.1016/j.micpath.2024.107162. Online ahead of print.ABSTRACTXanthomonas campestris pathovar campestris (Xcc) is the pathogen responsible for causing black rot in cruciferous plants. In this study, we show that mutation of AAW18_RS04175 (pacR, encodes a hypothetical protein containing a domain of unknown function, DUF1631) of Xcc strain Xc17 had decreased bacterial attachment, exopolysaccharide production, hypersensitive response and virulence. Furthermore, the pacR mutant exhibited reduced cell membrane integrity and outer membrane vesicle production. Transcriptomic analysis indicated that 225 genes were differentially expressed following pacR mutation. These genes can be classified into various functional categories, such as the type three secretion system and membrane component. Among them, genes associated with attachment, exopolysaccharide synthesis, the type three secretion system, and nucleotide metabolism were further verified by quantitative RT-PCR. Metabolomic analysis showed that 81 and 132 metabolites in positive and negative modes, respectively, were altered after pacR mutation. Among the identified metabolites, some are known to belong to different pathways, such as biosynthesis of secondary metabolites, microbial metabolism in diverse environments, and nucleotide and purine metabolism, while others have not been previously documented in microbial systems. Additionally, the transcription initiation point of pacR was mapped, and promoter analysis indicated that pacR expression is influenced by different conditions. Taken together, our findings advance the understanding of PacR function and expression in Xcc and offer new insights into the role of the DUF1631-containing hypothetical protein in bacterial physiology.PMID:39608507 | DOI:10.1016/j.micpath.2024.107162

Metabolism. 2024 Nov 26:156085. doi: 10.1016/j.metabol.2024.156085. Online ahead of print.ABSTRACTBACKGROUND: Evidence is limited regarding the association of circulating metabolites with decline of kidney function, letting alone their value in prediction of development of chronic kidney disease (CKD).METHODS: This study included 3802 participants aged 64.1 ± 7.4 years from the Dongfeng-Tongji cohort, among whom 3327 were CKD-free at baseline (estimated glomerular filtration rate [eGFR] > 60 ml/min per 1.73 m2). We measured baseline levels of 211 metabolites with liquid chromatography coupled with mass spectrometry, including 25 amino acids, 12 acyl-carnitines, 161 lipids, and 13 other metabolites.RESULTS: The mean (SD) absolute annual change in eGFR was -0.14 ± 4.11 ml/min per 1.73 m2 per year, and a total of 472 participants who were free of CKD at baseline developed incident CKD during follow-up of 4.6 ± 0.2 years (14.2 %). We identified a total of 22 metabolites associated with annual eGFR change and survived Bonferroni correction for multiple testing, including seven metabolites associated with eGFR increase (six being docosahexaenoic acid [DHA]-containing lipids) and 15 associated with eGFR decline (nine being phosphatidylcholines [PCs]). Among them, eight metabolites obtained non-zero coefficients in least absolute shrinkage and selection operator (LASSO) regression on incident CKD, indicating predictive potential, including one amino acid (arginine), one acyl-carnitine (C2), one lysophosphatidylcholine (LPC 22:6), two PCs (32:1 and 34:3), one triacylglycerol (TAG 56:8 [22:6]) and two other metabolites (inosine, niacinamide), and the composite score of these eight metabolites showed an odds ratio (OR) of 8.79 (95 % confidence interval [CI]: 7.49, 10.32; P < 0.001) per SD increase in association with incident CKD. The addition of the metabolite score increased the c-statistic of the reference model of traditional risk factors (including baseline eGFR) by 0.065 (95 % CI: 0.046 to 0.084; P = 3.39 × 10-11) to 0.765 (0.742 to 0.788) in 1000 repetitions of 10-fold cross-validation, while the application of two advanced machine learning algorithms, random forest (RF), and extreme gradient boosting (XGBoost) models produced similar c-statistics, to 0.753 (0.729 to 0.777) and 0.778 (0.733 to 0.824) with increases of 0.074 (0.055 to 0.093; P = 4.11 × 10-14) and 0.073 (0.032 to 0.114; P = 4.00 × 10-4), respectively.CONCLUSIONS: In this study, we identified 22 metabolites associated with longitudinal eGFR change, nine of which were PCs and six were DHA-containing lipids. We screened out a panel of eight metabolites which improved prediction for the development of CKD by 9 % beyond traditional risk factors including baseline eGFR. Our findings highlighted involvement of lipid metabolism in kidney function impairment, and provided novel predictors for CKD risk.PMID:39608488 | DOI:10.1016/j.metabol.2024.156085

Plant Physiol Biochem. 2024 Nov 23;218:109327. doi: 10.1016/j.plaphy.2024.109327. Online ahead of print.ABSTRACTPhotosynthesis is a source of energy for various types of plant life activities and is essential for plant growth and development. Consequently, the study of photosynthetic mechanisms has been a hot spot. Leaf color mutants has always been ideal materials for exploring the mechanisms of chlorophyll metabolism and photosynthesis. In this study, we identified a leaf color mutant of 'Benihoppe' strawberry in the field, which exhibited a darker green leaf color compared with the wild type. The content of total chlorophyll and carotenoid in the mutant leaves was elevated by 7.44-20.23% and 8.9-21.92%, respectively, compared with that of the wild type. Additionally, net photosynthetic rate in the mutant increased by 20.13%. Further transcriptome analysis showed that significant upregulation of genes such as GLK1, PPR, and MORF9 in the mutant leaves, which promoted chloroplast development. The expression levels of UROD, PPOC, PORA, CHLG, and CPOX were significantly upregulated during chlorophyll synthesis, while the expression levels of HCAR and CYP89A9 were significantly downregulated during chlorophyll degradation, thus leading to the accumulation of chlorophyll in mutant leaves. The upregulation of gene expression levels such as PetM, AtpD, PGK, and RPI4 during photosynthesis promoted multiple stages of light and dark reaction, thereby enhancing the photosynthetic capacity of the mutant. And the changes in metabolites such as monogalactosyl monoacylglycerol (MGMG), glucuronosyldiacylglycerol (GlcADG), raffinose, etc. also indicate that the mutant has metabolic differences in chloroplast composition and photosynthesis compared to 'Benihoppe'. The above results not only deepen our understanding of the mechanism behind the dark-green leaf color in strawberry mutants but also provide potential genetic resources for cultivating strawberry varieties with enhanced photosynthetic capacity.PMID:39608287 | DOI:10.1016/j.plaphy.2024.109327

J Reprod Immunol. 2024 Nov 20;167:104398. doi: 10.1016/j.jri.2024.104398. Online ahead of print.ABSTRACTOBJECTIVE: This study aimed to delineate the metabolic differences and identify enriched pathways in the decidual tissue of patients with recurrent spontaneous abortion (RSA) compared to normal pregnant women.METHODS: A cohort of 25 RSA patients and 25 normal pregnant women was recruited for the study. Non-targeted metabolomic analysis of decidual tissue was conducted using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to identify differential metabolites. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to elucidate associated metabolic pathways. Quantitative polymerase chain reaction (qPCR) was utilized to assess the expression levels of key proteins related to these pathways, including acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), and indoleamine 2,3-dioxygenase (IDO).RESULTS: A total of 54 metabolites were identified with significant differences between the decidual tissues of RSA patients and normal controls, corresponding to 29 significantly enriched metabolic pathways (P<0.05). The expression of ACSL4 was markedly upregulated, while the expression of GPX4 and IDO were significantly downregulated in RSA patients (P<0.05).CONCLUSIONS: This study elucidates substantial metabolic disruptions in the decidual tissue of RSA patients, identifying 54 differential metabolites and 29 enriched pathways. The altered expression of ACSL4, GPX4, and IDO underscores their potential involvement in the pathogenesis of RSA. These findings provide critical insights into the metabolic mechanisms underlying RSA and suggest promising targets for diagnostic and therapeutic interventions.PMID:39608278 | DOI:10.1016/j.jri.2024.104398

Int Immunopharmacol. 2024 Nov 27;144:113685. doi: 10.1016/j.intimp.2024.113685. Online ahead of print.ABSTRACTChronic prostatitis and Pelvic Pain syndrome (CP/CPPS) is an autoimmune inflammatory disease characterized by pelvic or perineal pain and infiltration of inflammatory cells in the prostate. C-X-C chemokine receptor type 7 (CXCR7) is an atypical chemokine receptor that has been shown to play a key role in inflammatory processes in prostate cancer. However, the role of CXCR7 in autoimmune prostate and immune regulation in CP/CPPS along with the mechanism of action for CXCR7 remains unclear. In this study, a mouse model of experimental autoimmune prostatitis (EAP) was constructed by subcutaneous injection of antigen, and CXCR7 agonist was administered to investigate the effects of CXCR7 on the proportion of immune cells and fibrosis in CP/CPPS. Western blotting, immunohistochemical staining and immunofluorescence, flow cytometry, and masson's trichrome staining were used to study the regulatory mechanisms of CXCR7 in immune regulation. CXCR7 agonists can significantly reduce pain and prostatic inflammation, and in vivo flow cytometry studies showed that the antagonists restored the imbalance of the Th17/Treg cell ratio. To elucidate the potential mechanisms by which CXCR7 influences the pathogenesis of CP/CPPS, we conducted simultaneous RNA-seq and non-targeted metabolome sequencing. Our findings suggest that CXCR7 agonists alleviate fibrosis in autoimmune prostatitis by inhibiting the TGFβ/SMAD pathway. This study provides the foundation to target the immunological function of CXCR7 as a novel therapy for CP/CPPS.PMID:39608177 | DOI:10.1016/j.intimp.2024.113685

Int Immunopharmacol. 2024 Nov 27;144:113704. doi: 10.1016/j.intimp.2024.113704. Online ahead of print.ABSTRACTBACKGROUND: Clinically, hepatoma patients are more frequently encountered in the intermediate and advanced stages. Consequently, the majority of patients miss out on the chance to undergo liver transplantation or radical surgery. Radiotherapy and chemotherapy often fall short of delivering satisfactory outcomes. The incidence and mortality rates for liver cancer approach nearly 100%. In recent years, both exosomes (Exos) and natural chemical compounds have demonstrated robust anti-cancer properties; however, the synergistic effect of their combination remains unexplored.METHODS: Exos were extracted from human umbilical cord mesenchymal stem cells (hUC-MSCs). The impact of gallic acid (GA), hUC-MSCs-Exos, and their combined administration on the proliferation inhibition rate and apoptosis of SMMC-7721 hepatoma cells was assessed to ascertain the efficacy differences before and after the combined treatment. A combination of cells metabolomics and network pharmacology techniques was employed to investigate the underlying mechanisms of action. The pivotal targets associated with glycolysis, inflammation, and oxidative stress pathways were confirmed through ELISA assays.RESULTS: The findings elucidate that GA profoundly impedes the proliferation of SMMC-7721 hepatoma cells and instigates apoptotic processes therein. While the impact of hUC-MSCs-Exos alone was inconspicuous, a notable augmentation in effect ensued upon their combined application. Concomitantly, a marked reduction was observed in the expressionlevels of key enzymes including HK, PFK, PK, LDH, TNF-α, IL-1β, CAT, SOD and GSH-Px in the malignant hepatocytes, while IL-6 and MDA exhibited heightened expression. Pathway enrichment analysis underscored selenocompound metabolism and cysteine and methionine metabolism as pivotal pathways.CONCLUSION: The potentiated efficacy of GA conjunction with hUC-MSCs-Exos may be attributed to their synergistic modulation of anti-inflammatory, antioxidant, and glycolytic functions, thereby influencing selenocompound metabolism and cysteine and methionine metabolism. This study reveals the efficacy and mechanism of Exos and GA combined therapy for hepatoma, providing new methods and ideas for the clinical treatment of hepatoma.PMID:39608175 | DOI:10.1016/j.intimp.2024.113704

Food Chem. 2024 Nov 26;466:142263. doi: 10.1016/j.foodchem.2024.142263. Online ahead of print.ABSTRACTThis study analyzed human, goat, sheep, and pig milks using metabolomics, lipidomics, and proteomics, specifically untargeted LC-MS/MS metabolomics, untargeted LC-MS/MS lipidomics, and 4D-label-free proteomics. The aim was to determine differences among these milks and identify components with similar functions to human milk, providing a reference for the research and development of infant formulae. In goat milk, expression of lactoperoxidase, inosine, and allantoin were relatively high, while in sheep milk, concentrations of ceruloplasmin and alpha-ketoglutarate were higher. The content of linoleic acid (LA) was relatively high in both goat and sheep milks. A relatively high content of milk fat globule EGF factor 8 protein was found in pig milk.PMID:39608118 | DOI:10.1016/j.foodchem.2024.142263

Food Chem. 2024 Nov 15;466:142078. doi: 10.1016/j.foodchem.2024.142078. Online ahead of print.ABSTRACTLactic acid bacteria (LAB) fermentation can modify the antioxidant capacity of food. This study investigates the impact and mechanisms of various LAB strains (Lactobacillus plantarum NCU116, Lactobacillus acidophilus NCU402, and Lactobacillus casei NCU215) fermentation on the antioxidant properties of mango juice. LAB strains inoculation enhanced the antioxidant activity of mango juice, with metabolomics showing increased in polyphenols and decreased in vitamins and carotenoids, indicating polyphenols as the main contributors. Quantification of polyphenols (free and bound forms) revealed that fermentation decreased bound gallic acid levels while increasing free pyrogallol and 1,2,3,4,6-O-pentagalloylglucose, which mainly contributed to the rise in antioxidant capacity in mango juice. L. acidophilus NCU402 had the highest increase in 1,2,3,4,6-O-pentagalloylglucose (from 918.07 to 1750 μg/10 g), whereas L. casei NCU215 facilitated the greatest release of bound gallic acid (49.29 to 11.77 μg/10 g). Bound polyphenol release may be linked to pectin degradation, with lower galacturonic acid and increased pectinase activity.PMID:39608110 | DOI:10.1016/j.foodchem.2024.142078

ACS Chem Neurosci. 2024 Nov 28. doi: 10.1021/acschemneuro.4c00297. Online ahead of print.ABSTRACTImpulsive and compulsive behaviors are associated with inhibitory control deficits. Diet plays a pivotal role in normal development, impacting both physiology and behavior. However, the specific effects of a high-fat diet (HFD) on inhibitory control have not received adequate attention. This study aimed to explore how exposure to a HFD from postnatal day (PND) 33 to PND77 affects impulsive and compulsive behaviors. The experiment involved 40 Wistar rats subjected to HFD or chow diets. Several tasks were employed to assess behavior, including variable delay to signal (VDS), five choice serial reaction time task (5-CSRTT), delay discounting task (DDT), and rodent gambling task (rGT). Genetic analyses were performed on the frontal cortex, and metabolomics and fatty acid profiles were examined by using stool samples collected on PND298. Our results showed that the HFD group exhibited increased motor impulsive behaviors while not affecting cognitive impulsivity. Surprisingly, reduced impulsive decision-making was shown in the HFD group. Furthermore, abnormal brain plasticity and dopamine gene regulation were shown in the frontal cortex, while metabolomics revealed abnormal fatty acid levels.PMID:39607956 | DOI:10.1021/acschemneuro.4c00297

J Clin Endocrinol Metab. 2024 Nov 28:dgae737. doi: 10.1210/clinem/dgae737. Online ahead of print.ABSTRACTCONTEXT: Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disorder characterized by skeletal and skin abnormalities. Genetic defects in prostaglandin E2 (PGE2) metabolism are known to cause PHO. However, the global impact and clinical significance of eicosanoids and oxylipins beyond PGE2 remain to be elucidated.OBJECTIVE: This study aimed to investigate oxylipin networks in PHO, including the 2 subtypes, PHOAR1 and PHOAR2, and examine their associations with clinical characteristics.METHODS: We conducted a targeted metabolomic study involving 16 patients with PHO and 16 age- and sex-matched healthy controls. Serum samples were collected at the time of diagnosis. Metabolites were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry.RESULTS: Laboratory analyses confirmed elevated levels of PGE2 in patients with PHO, consistent with the established pathogenesis. About 60 oxidized lipid metabolites were identified, with 19 differentially expressed in PHO. Besides the COX/PGE2 pathway, the lipoxygenase-mediated pathway was also involved in PHO. The metabolites 5-OxoETE, 15-OxoETE, 8S,15S-DiHETE, PGE2, 11β-PGE2, PGB2, LTB4, and LTE4 were significantly altered. Correlation analyses revealed associations between oxylipin metabolites and clinical features, including bone microarchitecture. Notably, the study highlighted differences in the oxylipin metabolite profiles between patients with PHOAR1 and patients with PHOAR2, suggesting distinct metabolic signatures for each subtype.CONCLUSION: Our study indicated a significant perturbation in oxylipin metabolism among patients with PHO, with distinct metabolic signatures observed between PHOAR1 and PHOAR2. The disruption extended beyond the metabolism of PGE2. It encompassed a broader alteration across the polyunsaturated fatty acid metabolism spectrum, including various eicosanoids and oxylipins. Our work provided a comprehensive understanding of the pathogenesis of PHO, and underscored the potential for subtype-specific therapeutic interventions.PMID:39607761 | DOI:10.1210/clinem/dgae737

J Gerontol A Biol Sci Med Sci. 2024 Nov 28:glae272. doi: 10.1093/gerona/glae272. Online ahead of print.ABSTRACTSkin autofluorescence (SAF), reflecting advanced glycation end-products' accumulation in tissue, has been proposed as a non-invasive aging biomarker. Yet, SAF has not been compared to well-established blood-based aging biomarkers such as MetaboHealth in association with frailty. Furthermore, no previous study determined the longitudinal association of SAF with frailty. We used 2382 Doetinchem Cohort Study participants' (aged 46.0 to 85.4) cross-sectional data, of whom 1654 had longitudinal SAF measurements. SAF was measured using the AGE reader™. MetaboHealth was calculated on 1H-NMR-metabolomics. Linear regressions were used for the associations of SAF and MetaboHealth on the 36-deficit frailty index and logistic regressions for being pre-frail or frail as determined by the frailty phenotype. Longitudinal associations were determined by an interaction term between age and SAF in a linear mixed model. SAF and MetaboHealth were associated with higher odds of pre-frailty (odd ratios per standard deviation SAF: 1.21(1.10;1.32), MetaboHealth: 1.35(1.24;1.49)) and frailty (SAF: 1.70(1.41;2.06), MetaboHealth: 1.90(1.57;2.32)). When mutually adjusted, both aging biomarkers remained associated with pre-frailty (SAF: 1.16(1.05;1.27), MetaboHealth 1.33(1.21;1.46)) and frailty (SAF: 1.52(1.25;1.85), MetaboHealth: 1.75(1.43;2.14)). Additionally, SAF and MetaboHealth were associated with higher frailty index scores (percentage increase per standard deviation SAF:1.35(1.00;1.70), MetaboHealth: 1.87(1.54;2.20)), also after mutual adjustment (SAF: 1.02(0.68;1.37), MetaboHealth: 1.69(1.35;2.02)). SAF was also longitudinally associated with the frailty index (percentage per unit/year increase 0.12(0.07;0.16)). The mutual independence of SAF and MetaboHealth implies they capture distinct aspects of the aging process. Altogether, these findings emphasize SAF's clinical potential as an age-related decline biomarker, which could be further enhanced when combined with MetaboHealth.PMID:39607723 | DOI:10.1093/gerona/glae272

Metab Brain Dis. 2024 Nov 28;40(1):45. doi: 10.1007/s11011-024-01450-4.ABSTRACTRadix Bupleuri-Radix Paeoniae Alba herb pair (RB-RPA) is the fundamental medication combination of many classic antidepressant prescriptions, and RB-RPA's antidepressant effect is well established. For an extended period, the involvement of intestinal flora in the progression of depression has been widely acknowledged. However, it remains unclear whether RB-RPA could modulate intestinal microbiota disturbances and metabolic abnormalities induced by depression. The research explores the antidepressant mechanism of RB-RPA in chronic unpredictable mild stress (CUMS) rats in terms of intestinal flora and metabolites. We identified critical gut microbial species and metabolites associated with the antidepressant effects of RB-RPA using 16 S rRNA sequencing and Liquid Chromatography-Mass Spectrometry (LC-MS) metabolomics. And then, correlation analysis between critical microbiota and differential metabolites was conducted. The results demonstrate that RB-RPA significantly ameliorated depressive-like behavior in CUMS rats. RB-RPA improved intestinal flora disorders in depressed rats mainly by increasing the abundance of Lactobacillus (especially L. johnsonii), and ameliorated tryptophan synthesis and metabolism disorders in depressed rats and restored the levels of tryptophan and tryptophan microbial metabolites, such as indoleacrylic acid and 4-indoleacetaldehyde. Notably, correlation analysis showed that Lactobacillus had a significant positive correlation with tryptophan, indoleacrylic acid, and 4-indoleacetaldehyde. In conclusion, RB-RPA can improve the disorder of intestinal flora by increasing the abundance of Lactobacillus and improve the metabolic disorder of depressed rats by regulating tryptophan metabolism, thus exerting antidepressant effects.PMID:39607539 | DOI:10.1007/s11011-024-01450-4

Chempluschem. 2024 Nov 28:e202400605. doi: 10.1002/cplu.202400605. Online ahead of print.ABSTRACTZr-monosubstituted polyoxometalates (Zr-POMs) of the Keggin (Bu4N)8[{PW11O39Zr(μ-OH)}2] (Zr-K), Lindqvist (Bu4N)6[{W5O18Zr(μ-OH)}2] (Zr-L), and Wells-Dawson (Bu4N)11H3[{P2W17O61Zr(μ-OH)}2] (Zr-WD) structures are capable of heterolytic activation of the environmentally benign oxidant tert-butyl hydroperoxide (TBHP) and catalyze epoxidation of alkenes and oxidation of alcohols to carbonyl compounds. Catalytic activity of corresponding Ti-POMs is much lower. Among Zr-POMs, Zr-K revealed higher epoxide yields. All Zr-POMs do not catalyze unproductive TBHP degradation, and epoxide yields with both aqueous and anhydrous TBHP are generally higher than with aqueous H2O2. Regioselectivity of the Zr-K-catalyzed limonene epoxidation with TBHP is different from that with H2O2: the more substituted and nucleophilic double bond is preferably epoxidized, pointing to an electrophilic oxygen transfer mechanism. The oxidation rates are first order in catalyst (Zr-K) and substrate (cyclooctene or cyclohexanol) and show a saturation behavior with increasing concentration of TBHP. Studies by HR-ESI-MS, ATR-FT-IR, and 31P NMR spectroscopic techniques implicated the formation of zirconium alkylperoxo species upon interaction of Zr-POMs with TBHP. HR-ESI-MS revealed the existence of monomeric and dimeric alkylperoxo complexes, [{PW11O39Zr}((CH3)3COO)]4- and [{PW11O39Zr((CH3)3COO)}2]8-, with predomination of the former, which is most likely the active species responsible for the selective oxidations.PMID:39606905 | DOI:10.1002/cplu.202400605

J Dev Orig Health Dis. 2024 Nov 28;15:e30. doi: 10.1017/S2040174424000345.ABSTRACTNutrition is the critical nongenetic factor that has a major influence on the health status of an organism. The nutritional status of the mother during gestation and lactation plays a vital role in defining the offspring's health. Undernutrition during these critical periods may induce chronic metabolic disorders like obesity and cardiovascular diseases in mothers as well as in offspring. The present study aims to evaluate the impact of undernutrition during gestational and lactational periods on the plasma metabolic profile of dams. Additionally, we investigated the potential synergistic mitigating effects of astaxanthin and docosahexaenoic acid (DHA) on dysregulated plasma metabolic profiles. Evaluation of plasma lipid profile revealed that undernourishment resulted in elevated levels of total cholesterol, triglycerides, low density and very low-density lipoproteins in dams. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based untargeted metabolomics illustrated that pathways related to lipid metabolism, such as cholesterol metabolism, steroid biosynthesis and metabolism of amine-derived hormones, were dysregulated by undernourishment. Additionally, pathway enrichment analysis predicted that there is a high incidence of development of desmosterolosis, hypercholesterolaemia, lysosomal acid lipase deficiency and Smith-Lemli-Opitz syndrome in the offspring, reflecting predisposition in mothers. However, synergistic supplementation of astaxanthin and DHA ameliorated these adverse effects by regulating a separate set of metabolic pathways associated with lipid metabolism. They included branched chain amino acid degradation such as valine, leucine and isoleucine, metabolism of alpha-linolenic acid, lipoic acid, lysine degradation, biosynthesis, elongation and degradation of fatty acids.PMID:39606856 | DOI:10.1017/S2040174424000345

ArXiv [Preprint]. 2024 Nov 25:arXiv:2411.14464v2.ABSTRACTMOTIVATION: A major challenge in metabolomics is annotation: assigning molecular structures to mass spectral fragmentation patterns. Despite recent advances in molecule-to-spectra and in spectra-to-molecular fingerprint prediction (FP), annotation rates remain low.RESULTS: We introduce in this paper a novel paradigm (JESTR) for annotation. Unlike prior approaches that explicitly construct molecular fingerprints or spectra, JESTR leverages the insight that molecules and their corresponding spectra are views of the same data and effectively embeds their representations in a joint space. Candidate structures are ranked based on cosine similarity between the embeddings of query spectrum and each candidate. We evaluate JESTR against mol-to-spec and spec-to-FP annotation tools on three datasets. On average, for rank@[1-5], JESTR outperforms other tools by 23.6%-71.6%. We further demonstrate the strong value of regularization with candidate molecules during training, boosting rank@1 performance by 11.4% and enhancing the model's ability to discern between target and candidate molecules. Through JESTR, we offer a novel promising avenue towards accurate annotation, therefore unlocking valuable insights into the metabolome.PMID:39606728 | PMC:PMC11601792

Front Vet Sci. 2024 Nov 13;11:1475397. doi: 10.3389/fvets.2024.1475397. eCollection 2024.ABSTRACTMastitis is a disease with frequent incidence in dairy cows, causing huge financial losses to the dairy industry globally. The identification of certain biomarkers is crucial for the early diagnosis and management of mastitis. Metabolomics technology is a useful tool to accurately and efficiently analyze the changes of metabolites in biofluids in response to internal and external stimulations. Milk is the secreted by udder, and milk metabolites can directly reflect whether the udder are in the healthy or diseased state. The milk metabolomics analysis of mastitis can reveal the physiological and pathological changes of mammary gland and screen the related biomarkers, so as to offer useful reference for the prediction, diagnosis, and management of mastitis. Therefore, the aim of the present study was to comprehensively summarize milk metabolic change caused by naturally occurring or experimentally induced mastitis in dairy cows. In addition, comparative analysis and enrichment analysis were conducted to further discover potential biomarkers of mastitis and to identify the relevant pathways differentiating the healthy and mastitic cows. Multiple milk metabolites were identified to be altered during mastitis based on different metabolomics platforms. It was noteworthy that there were 28 metabolites not only identified by at least two different studies, but also showed consistent change tendency among the different studies. By comparison with literature, we further identified 12 milk metabolites, including acetate, arginine, β-hydroxybutyrate, carnitine, citrate, isoleucine, lactate, leucine, phenylalanine, proline, riboflavin, and valine that were linked with the occurrence of mastitis, which suggested that these 12 milk metabolites could be potential biomarkers of mastitis in dairy cows. Several pathways were revealed to explain the mechanisms of the variation of milk metabolites caused by mastitis, such as phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, riboflavin metabolism, and tricarboxylic acid (TCA) cycle. These results offer a further understanding for the alteration of milk metabolites caused by mastitis, which have a potential significance in the development of more reliable biomarkers for mastitic diagnosis in dairy cows.PMID:39606657 | PMC:PMC11598933 | DOI:10.3389/fvets.2024.1475397

Res Sq [Preprint]. 2024 Nov 12:rs.3.rs-5391023. doi: 10.21203/rs.3.rs-5391023/v1.ABSTRACTAntibiotic resistance is one of the most pressing threats to human health, yet recent work highlights how loss of resistance may also drive pathogenesis in some bacteria. In two recent studies, we found that β-lactam antibiotic and nutrient stresses faced during infection selected for the genetic inactivation of the Pseudomonas aeruginosa (Pa) antibiotic efflux pump mexEFoprN. Unexpectedly, efflux pump mutations increased Pa virulence during infection; however, neither the prevalence of efflux pump inactivating mutations in real human infections, nor the mechanisms driving increased virulence of efflux pump mutants are known. We hypothesized that human infection would select for efflux pump mutations that drive increased virulence in Pa clinical isolates. Using genome sequencing of hundreds of Pa clinical isolates, we show that mexEFoprN efflux pump inactivating mutations are enriched in Pa cystic fibrosis isolates relative to Pa intensive care unit clinical isolates. Combining RNA-seq, metabolomics, genetic approaches, and infection models we show that efflux pump mutants have elevated expression of two key Pa virulence factors, elastase and rhamnolipids, which increased Pa virulence and lung damage during both acute and chronic infections. Increased virulence factor production was driven by higher Pseudomonas quinolone signal levels in the efflux pump mutants. Finally, genetic restoration of the efflux pump in a representative ICU clinical isolate and the notorious CF Pa Liverpool epidemic strain reduced their virulence. Together, our findings suggest that mutations inactivating antibiotic resistance mechanisms could lead to greater patient mortality and morbidity.PMID:39606469 | PMC:PMC11601840 | DOI:10.21203/rs.3.rs-5391023/v1

Metabolomics. 2017 May;13(5):50. doi: 10.1007/s11306-017-1188-9. Epub 2017 Mar 6.ABSTRACTINTRODUCTION: The Metabolomics Society Data Quality Task Group (DQTG) developed a questionnaire regarding quality assurance (QA) and quality control (QC) to provide baseline information about current QA and QC practices applied in the international metabolomics community.OBJECTIVES: The DQTG has a long-term goal of promoting robust QA and QC in the metabolomics community through increased awareness via communication, outreach and education, and through the promotion of best working practices. An assessment of current QA and QC practices will serve as a foundation for future activities and development of appropriate guidelines.METHOD: QA was defined as the set of procedures that are performed in advance of analysis of samples and that are used to improve data quality. QC was defined as the set of activities that a laboratory does during or immediately after analysis that are applied to demonstrate the quality of project data. A questionnaire was developed that included 70 questions covering demographic information, QA approaches and QC approaches and allowed all respondents to answer a subset or all of the questions.RESULT: The DQTG questionnaire received 97 individual responses from 84 institutions in all fields of metabolomics covering NMR, LC-MS, GC-MS, and other analytical technologies.CONCLUSION: There was a vast range of responses concerning the use of QA and QC approaches that indicated the limited availability of suitable training, lack of Standard Operating Procedures (SOPs) to review and make decisions on quality, and limited use of standard reference materials (SRMs) as QC materials. The DQTG QA/QC questionnaire has for the first time demonstrated that QA and QC usage is not uniform across metabolomics laboratories. Here we present recommendations on how to address the issues concerning QA and QC measurements and reporting in metabolomics.PMID:39606286 | PMC:PMC11601953 | DOI:10.1007/s11306-017-1188-9