PubMed

Plant J. 2024 Oct 14. doi: 10.1111/tpj.17074. Online ahead of print.ABSTRACTPolyamines act as protective compounds directly protecting plants from stress-related damage, while also acting as signaling molecules to participate in serious abiotic stresses. However, the molecular mechanisms underlying these effects are poorly understood. Here, we utilized metabolome genome-wide association study to investigate the polyamine content of wild and cultivated tomato accessions, and we discovered a new gene cluster that drove polyamine content during tomato domestication. The gene cluster contains two polyphenol oxidases (SlPPOE and SlPPOF), two BAHD acyltransferases (SlAT4 and SlAT5), a coumaroyl-CoA ligase (Sl4CL6), and a polyamine uptake transporter (SlPUT3). SlPUT3 mediates polyamine uptake and transport, while the five other genes are involved in polyamine modification. Further salt tolerance assays demonstrated that SlPPOE, SlPPOF, and SlAT5 overexpression lines showed greater phenolamide accumulation and salt tolerance as compared with wild-type (WT). Meanwhile, the exogenous application of Spm to SlPUT3-OE lines displayed salt tolerance compared with WT, while having the opposite effect in slput3 lines, confirms that the polyamine and phenolamide can play a protective role by alleviating cell damage. SlPUT3 interacted with SlPIP2;4, a H2O2 transport protein, to maintain H2O2 homeostasis. Polyamine-derived H2O2 linked Spm to stress responses, suggesting that Spm signaling activates stress response pathways. Collectively, our finding reveals that the H2O2-polyamine-phenolamide module coordinately enhanced tomato salt stress tolerance and provide a foundation for tomato stress-resistance breeding.PMID:39401077 | DOI:10.1111/tpj.17074

Plant Cell Environ. 2024 Oct 13. doi: 10.1111/pce.15198. Online ahead of print.ABSTRACTAfter an initial evolution in a reducing environment, life got successively challenged by reactive oxygen species (ROS), especially during the great oxidation event (GOE) that followed the development of photosynthesis. Therefore, ROS are deeply intertwined into the physiological, morphological and transcriptional responses of most present-day organisms. Copper-zinc superoxide dismutases (CuZnSODs) evolved during the GOE and are present in charophytes and extant land plants, but nearly absent from chlorophytes. The chemical inhibitor of CuZnSOD, lung cancer screen 1 (LCS-1), could greatly facilitate the study of SODs in diverse plants. Here, we determined the impact of chemical inhibition of plant CuZnSOD activity, on plant growth, transcription and metabolism. We followed a comparative approach by using different plant species, including Marchantia Polymorpha and Physcomitrium patens, representing bryophytes, the sister lineage to vascular plants, and Arabidopsis thaliana. We show that LCS-1 causes oxidative stress in plants and that the inhibition of CuZnSODs provoked a similar core response that mainly impacted glutathione homoeostasis in all plant species analysed. That said, Physcomitrium and Arabidopsis, which contain multiple CuZnSOD isoforms showed a more complex and exacerbated response. In addition, an untargeted metabolomics approach revealed a specific metabolic signature for each plant species. Our comparative analysis exposes a conserved core response at the physiological and transcriptional level towards LCS-1, while the metabolic response largely varies. These differences correlate with the number and localization of the CuZnSOD isoforms present in each species.PMID:39400938 | DOI:10.1111/pce.15198

Curr Microbiol. 2024 Oct 14;81(12):405. doi: 10.1007/s00284-024-03890-8.ABSTRACTArabian Sea is a highly productive Ocean owing to deep upwelling with reports on phosphorus cycling in ocean sediments. In this study, microbes from sea mounts of the Arabian Sea at varying depths (400 m, 900 m) were screened to isolate and characterize phosphate-solubilizing bacteria (PSB) with plant growth-promoting properties. Out of the seven morphologically different PSBs, two bacterial strains with maximum phosphate solubilization index were identified as Priestia megaterium (H1) and Bacillus velezensis (H2) based on biochemical and molecular characteristics. Different factors influencing phosphatase production were optimized, which showed maximum solubilization at temperature of 30 °C (97.5 μg/mL), glucose as best carbon source (70 µg/mL), 1-M NaCl (114.1 µg/mL), and pH 8 (134.3 µg/mL) indicating their halophilic and alkaliphilic characteristics. Alkaline phosphatase enzyme was extracted and partially purified from both PSBs wherein H2 strains showed greater specific activity (24.83 U/mg). Metabolomics studies through HPLC revealed maximum production of gluconic acid (483.75 mg/L) in addition to lactic, oxalic, acetic, and succinic acid during solubilization. Biopriming effect of PSBs on tomato seed germination showed high germination index (80%) in consortia of both isolates which was also validated through root colonization by SEM analysis. Further studies using pot assay experiments also showed comparable results in marine PSB consortia with positive control (Phosphobacteria) for plant growth attributes including root height and weight. These findings suggest that the halophilic PSB strains from marine sediments could be used as potential bio-inoculants to enhance plant growth and combat saline stress for sustainable Agriculture.PMID:39400719 | DOI:10.1007/s00284-024-03890-8

Med Oncol. 2024 Oct 14;41(11):276. doi: 10.1007/s12032-024-02502-6.ABSTRACTWe have read with keen interest the original article by Kettana et al., which investigates the potential cardioprotective effects of rosuvastatin in HER2-positive breast cancer patients undergoing chemotherapy. We appreciate the study's meticulous methodology and its contribution to medicine oncology. However, we suggest a cautious interpretation of the results due to unmeasured confounding variables that could influence cardiotoxicity development and treatment efficacy. The study's fixed dosing approach to rosuvastatin precludes the assessment of dose-dependent effects, prompting a recommendation for future dose-response analyses. We also highlight the need to incorporate patient-reported outcomes for a more holistic treatment efficacy evaluation. Furthermore, we propose metabolomic analysis to uncover the drug's mechanisms of action and computational methods like molecular docking to predict its potential targets, which could refine drug design and inform personalized treatment strategies. Our commentary aims to refine the study's conclusions and encourage research that maximizes the understanding and clinical management of chemotherapy-induced cardiotoxicity.PMID:39400620 | DOI:10.1007/s12032-024-02502-6

Eur J Clin Invest. 2024 Oct 14:e14334. doi: 10.1111/eci.14334. Online ahead of print.ABSTRACTBACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a widely used drug for the treatment of type 2 diabetes that offers significant cardiovascular benefits.RESULTS: This review systematically examines the proteomic and metabolomic indicators associated with the cardiovascular effects of semaglutide. A comprehensive literature search was conducted to identify relevant studies. The review utilizes advanced analytical technologies such as mass spectrometry and nuclear magnetic resonance (NMR) to investigate the molecular mechanisms underlying the effects of semaglutide on insulin secretion, weight control, anti-inflammatory activities and lipid metabolism. These "omics" approaches offer critical insights into metabolic changes associated with cardiovascular health. However, challenges remain such as individual variability in expression, the need for comprehensive validation and the integration of these data with clinical parameters. These issues need to be addressed through further research to refine these indicators and increase their clinical utility.CONCLUSION: Future integration of proteomic and metabolomic data with artificial intelligence (AI) promises to improve prediction and monitoring of cardiovascular outcomes and may enable more accurate and effective management of cardiovascular health in patients with type 2 diabetes. This review highlights the transformative potential of integrating proteomics, metabolomics and AI to advance cardiovascular medicine and improve patient outcomes.PMID:39400314 | DOI:10.1111/eci.14334

Mol Omics. 2024 Oct 14. doi: 10.1039/d4mo00124a. Online ahead of print.ABSTRACTForensic science, an interdisciplinary field encompassing the collection, examination, and presentation of evidence in legal proceedings, has recently embraced lipidomics as a valuable tool. Lipidomics, a subfield of metabolomics, specializes in the analysis of lipid structures and functions, offering insights into biological processes that can aid forensic investigations. While not a substitute for DNA analysis in personal identification, lipidomics complements this technique by focusing on small biological molecules, with distinct sample requirements. This review comprehensively explores the current applications of lipidomics in forensic science. The review commences with an introduction to the concept and historical background of lipidomics, subsequently delving into its utilization in diverse areas such as drug analysis, ethyl alcohol and substitute assessment, latent fingermark detection, fire debris analysis, and seafood authentication. By showcasing the various biological materials and methods employed, this review underscores the potential of lipidomics as a powerful adjunct in forensic investigations.PMID:39400253 | DOI:10.1039/d4mo00124a

Int J Phytoremediation. 2024 Oct 14:1-11. doi: 10.1080/15226514.2024.2414911. Online ahead of print.ABSTRACTThe efficacy of phytoextraction for remediating heavy-metal contaminated soil depends on the bioavailability of the heavy metals and plant growth. In this study, we employed a synergistic system comprising water-soluble chitosan and the novel Cd mobilization bacteria, Serratia sp. K6 (hereafter K6), to enhance cadmium (Cd) extraction by Lolium perenne L. (ryegrass). The application of chitosan and K6 resulted in an increase in the biomass of ryegrass by 11.81% and Cd accumulation by 73.99% and effective-state Cd by 43.69% and pH decreased by 4.67%, compared to the control group. Microbiome and metabolomics analyses revealed significant alterations in the inter-root microbial ommunity, with rhizobacteria such as Sphingomonas, Nocardioides, and Bacillus likely contributing to enhanced plant growth and Cd accumulation in response to chitosan and K6 addition. Additionally, the contents of various organic acids, amino acids, lipids, and other metabolites exhibited significant changes under different additive treatments, suggesting that ryegrass can regulate its own metabolites to resist Cd stress. This study provides valuable insights into the effects of additives on phytoextraction efficiency and the soil bacterial community, offering a promising approach for phytoremediation of Cd-contaminated soils.PMID:39400042 | DOI:10.1080/15226514.2024.2414911

Food Chem (Oxf). 2024 Aug 30;9:100221. doi: 10.1016/j.fochms.2024.100221. eCollection 2024 Dec 30.ABSTRACTCarotenoids, a family of lipid-soluble pigments, have garnered growing interest for their health-promoting benefits and are widely utilized in the food, feed, pharmaceutical, and cosmetic industries. Rhodosporidiobolus odoratus, a representative oleaginous red yeast, is considered a promising alternative for producing high-value carotenoids including β-carotene, torulene, and torularhodin. Here, the impact of varying concentrations of NaCl treatments on carotenoid contents in R. odoratus XQR after 120 h of incubation was examined. The results indicated that, as compared to the control (59.37 μg/gdw), the synthesis of total carotenoids was significantly increased and entirely suppressed under low-to-moderate (0.25 mol/L: 68.06 μg/gdw, 0.5 mol/L: 67.62 μg/gdw, and 0.75 mol/L: 146.47 μg/gdw) and high (1.0, 1.25, and 1.5 mol/L: 0 μg/gdw) concentrations of NaCl treatments, respectively. Moreover, the maximum production of β-carotene (117.62 μg/gdw), torulene (21.81 μg/gdw), and torularhodin (7.04 μg/gdw) was achieved with a moderate concentration (0.75 mol/L) of NaCl treatment. Transcriptomic and metabolomic analyses suggested that the increase in β-carotene, torulene, and torularhodin production might be primarily attributed to the up-regulation of some key protein-coding genes involved in the terpenoid backbone biosynthesis (atoB, HMGCS, and mvaD), carotenoid biosynthesis (crtYB and crtI), and TCA cycle (pckA, DLAT, pyc, MDH1, gltA, acnA, IDH1/2, IDH3, sucA, sucB, sucD, LSC1, SDHA, and fumA/fumB). The present study not only demonstrates a viable method to concurrently increase the production of β-carotene, torulene, torularhodin, and total carotenoids in R. odoratus XQR, but it also establishes a molecular foundation for further enhancing their production through genetic engineering.PMID:39399738 | PMC:PMC11470240 | DOI:10.1016/j.fochms.2024.100221

Food Chem (Oxf). 2024 Sep 22;9:100223. doi: 10.1016/j.fochms.2024.100223. eCollection 2024 Dec 30.ABSTRACTThis study explored the functional effects of cultivated and wild Phyllanthus emblica Linn juice (PEJ) in HD11 poultry macrophage lines, with the aim of potentially developing cultivated PE and its fruit residue as poultry feed additives. RNA-Seq was used to evaluate the functional differences between cultivated and wild PEJ induced HD11 cells. Both cultivated and wild PEJ could regulate cell replication by histone H1/H2 family genes and host immune response by Toll-like receptor 7 regulation. Wild PEJ inhibited M1-type polarization of host macrophages, while cultivated PEJ promoted M2-type polarization. Metabolites of cultivated and wild PE were identified by widely targeted metabolomics based on liquid chromatography-tandem mass spectrometry. Of the 911 metabolites, 238 differed functionally between cultivated and wild PE. The data provide a theoretical basis for the subsequent development of PE as a functional feed additive in poultry.PMID:39399737 | PMC:PMC11470471 | DOI:10.1016/j.fochms.2024.100223

Synth Biol (Oxf). 2024 Sep 20;9(1):ysae013. doi: 10.1093/synbio/ysae013. eCollection 2024.ABSTRACTIn vitro metabolic systems allow the reconstitution of natural and new-to-nature pathways outside of their cellular context and are of increasing interest in bottom-up synthetic biology, cell-free manufacturing, and metabolic engineering. Yet, the analysis of the activity of such in vitro networks is very often restricted by time- and cost-intensive methods. To overcome these limitations, we sought to develop an in vitro transcription (IVT)-based biosensing workflow that is compatible with the complex conditions of in vitro metabolism, such as the crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA (CETCH) cycle, a 27-component in vitro metabolic system that converts CO2 into glycolate. As proof of concept, we constructed a novel glycolate sensor module that is based on the transcriptional repressor GlcR from Paracoccus denitrificans and established an IVT biosensing workflow that allows us to quantify glycolate from CETCH samples in the micromolar to millimolar range. We investigate the influence of 13 (shared) cofactors between the two in vitro systems to show that Mg2+, adenosine triphosphate , and other phosphorylated metabolites are critical for robust signal output. Our optimized IVT biosensor correlates well with liquid chromatography-mass spectrometry-based glycolate quantification of CETCH samples, with one or multiple components varying (linear correlation 0.94-0.98), but notably at ∼10-fold lowered cost and ∼10 times faster turnover time. Our results demonstrate the potential and challenges of IVT-based systems to quantify and prototype the activity of complex reaction cascades and in vitro metabolic networks.PMID:39399720 | PMC:PMC11470758 | DOI:10.1093/synbio/ysae013

Front Immunol. 2024 Sep 27;15:1469500. doi: 10.3389/fimmu.2024.1469500. eCollection 2024.ABSTRACTINTRODUCTION: Kidney transplantation is the optimal treatment for end-stage kidney disease; however, premature allograft loss remains a serious issue. While many high-throughput omics studies have analyzed patient allograft biospecimens, integration of these datasets is challenging, which represents a considerable barrier to advancing our understanding of the mechanisms of allograft loss.METHODS: To facilitate integration, we have created a curated database containing all open-access high-throughput datasets from human kidney transplant studies, termed NephroDIP (Nephrology Data Integration Portal). PubMed was searched for high-throughput transcriptomic, proteomic, single nucleotide variant, metabolomic, and epigenomic studies in kidney transplantation, which yielded 9,964 studies.RESULTS: From these, 134 studies with available data detailing 260 comparisons and 83,262 molecules were included in NephroDIP v1.0. To illustrate the capabilities of NephroDIP, we have used the database to identify common gene, protein, and microRNA networks that are disrupted in patients with chronic antibody-mediated rejection, the most important cause of late allograft loss. We have also explored the role of an immunomodulatory protein galectin-1 (LGALS1), along with its interactors and transcriptional regulators, in kidney allograft injury. We highlight the pathways enriched among LGALS1 interactors and transcriptional regulators in kidney fibrosis and during immunosuppression.DISCUSSION: NephroDIP is an open access data portal that facilitates data visualization and will help provide new insights into existing kidney transplant data through integration of distinct studies and modules (https://ophid.utoronto.ca/NephroDIP).PMID:39399491 | PMC:PMC11466753 | DOI:10.3389/fimmu.2024.1469500

FASEB Bioadv. 2024 Aug 19;6(9):337-350. doi: 10.1096/fba.2024-00060. eCollection 2024 Sep.ABSTRACTStimulation of mammalian cells with inflammatory inducers such as lipopolysaccharide (LPS) leads to alterations in activity of central cellular metabolic pathways. Interestingly, these metabolic changes seem to be important for subsequent release of pro-inflammatory cytokines. This has become particularly clear for enzymes of tricarboxylic acid (TCA) cycle such as succinate dehydrogenase (SDH). LPS leads to inhibition of SDH activity and accumulation of succinate to enhance the LPS-induced formation of IL-1β. If enzymes involved in beta-oxidation of fatty acids are important for sufficient responses to LPS is currently not clear. Using cells from various patients with inborn long-chain fatty acid oxidation disorders (lcFAOD), we report that disease-causing deleterious variants of Electron Transfer Flavoprotein Dehydrogenase (ETFDH) and of Very Long Chain Acyl-CoA Dehydrogenase (ACADVL), both cause insufficient inflammatory responses to stimulation with LPS. The insufficiencies included reduced TLR4 expression levels, impaired TLR4 signaling, and reduced or absent induction of pro-inflammatory cytokines such as IL-6. The insufficient responses to LPS were reproduced in cells from healthy controls by targeted loss-of-function of either ETFDH or ACADVL, supporting that the deleterious ETFDH and ACADVL variants cause the attenuated responses to LPS. ETFDH and ACADVL encode two distinct enzymes both involved in fatty acid beta-oxidation, and patients with these deficiencies cannot sufficiently metabolize long-chain fatty acids. We report that genes important for beta-oxidation of long-chain fatty acids are also important for inflammatory responses to an acute immunogen trigger like LPS, which may have important implications for understanding infection and other metabolic stress induced disease pathology in lcFAODs.PMID:39399475 | PMC:PMC11467727 | DOI:10.1096/fba.2024-00060

PeerJ. 2024 Oct 8;12:e18194. doi: 10.7717/peerj.18194. eCollection 2024.ABSTRACTBACKGROUND: Polycystic ovary syndrome (PCOS) is the most common metabolic disorder and reproductive endocrine disease, posing an elevated risk to women of reproductive age. Although metabolism differences in serum, amniotic fluid and urine have been documented in PCOS, there remains a paucity of evidence for vaginal fluid. This study aimed to identify the metabolic characteristics and potential biomarkers of PCOS in Chinese women of reproductive age.METHODS: We involved ten newly diagnosed PCOS women who attended gynecology at Zhongda Hospital and matched them with ten healthy controls who conducted health check-up programs at Gulou Maternal and Child Health Center in Nanjing, China from January 1st, 2019 to July 31st, 2020. Non-targeted metabolomics based on ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was applied to differentially screen vaginal metabolites between PCOS group and healthy controls. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA) and enrichment analysis were used to observe differences, search for potential biomarkers and enrich related pathways.RESULTS: Among the 20 participants, a total of 195 different metabolites were detected between PCOS group and healthy control group. PCOS and control groups were effectively separated by vaginal fluid. Lipids and lipid-like molecules constituted the majority of differential metabolites. Notably, dopamine exhibited an increased trend in PCOS group and emerged as the most significant differential metabolite, suggesting its potential as a biomarker for identifying PCOS. The application of UHPLC-MS/MS based vaginal metabolomics methods showed significant differences between PCOS and non-PCOS healthy control groups, especially linoleic acid metabolism disorder. Most differential metabolites were enriched in pathways associated with linoleic acid metabolism, phenylalanine metabolism, tyrosine metabolism, nicotinate and nicotinamide metabolism or arachidonic acid metabolism.CONCLUSIONS: In this pilot investigation, significant metabolomics differences could be obtained between PCOS and healthy control groups. For PCOS women of reproductive age, vaginal metabolism is a more economical, convenient and harmless alternative to provide careful personalized health diagnosis and potential targets for therapeutic intervention.PMID:39399434 | PMC:PMC11468964 | DOI:10.7717/peerj.18194

One Health. 2024 Sep 24;19:100902. doi: 10.1016/j.onehlt.2024.100902. eCollection 2024 Dec.ABSTRACTTo provide some glimpses on the possibility of shaping the human gut microbiome (GM) through probiotic exchange with natural ecosystems, here we explored the impact of 15 days of daily interaction with horses on the GM of 10 urban-living Italian children. Specifically, the children were in close contact with the horses in an "educational farm", where they spent almost 10 h/day interacting with the animals. The children's GM was assessed before and after the horse interaction using metabarcoding sequencing and shotgun metagenomics, along with the horses' skin, oral and fecal microbiomes. Targeted metabolomic analysis for GM-produced beneficial metabolites (i.e., short-chain fatty acids) in the children's feces was also performed. Interaction with horses facilitated the acquisition of health-related traits in the children's GM, such as increased diversity, enhanced butyrate production and an increase in several health-promoting species considered to be next-generation probiotics. Among these, the butyrate producers Facecalibacterium prausnitzii and F. duncaniae and a species belonging to the order Christensenellales. Interaction with horses was also associated with increased proportions of Eggerthella lenta, Gordonibacter pamelae and G. urolithinfaciens, GM components known to play a role in the bioconversion of dietary plant polyphenols into beneficial metabolites. Notably, no increase in potentially harmful traits, including toxin genes, was observed. Overall, our pilot study provides some insights on the existence of possible health-promoting exchanges between children and horses microbiomes. It lays the groundwork for an implemented and more systematic enrollment effort to explore the full complexity of human GM rewilding through exchange with natural ecosystems, aligning with the One Health approach.PMID:39399231 | PMC:PMC11470462 | DOI:10.1016/j.onehlt.2024.100902

Drug Des Devel Ther. 2024 Oct 9;18:4527-4528. doi: 10.2147/DDDT.S497570. eCollection 2024.NO ABSTRACTPMID:39399127 | PMC:PMC11471113 | DOI:10.2147/DDDT.S497570

medRxiv [Preprint]. 2024 Sep 24:2024.09.24.24313672. doi: 10.1101/2024.09.24.24313672.ABSTRACTInflammation is a critical component of chronic diseases, aging progression, and lifespan. Omics signatures may characterize inflammation status beyond blood biomarkers. We leveraged genetics (Polygenic-Risk-Score; PRS), metabolomics (Metabolomic-Risk-Score; MRS), and epigenetics (Epigenetic-Risk-Score; ERS) to build multi-omics-multi-marker risk scores for inflammation status represented by the level of circulating C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor alpha (TNFa). We found that multi-omics risk-scores generally outperformed single-omics risk scores in prediction of all-cause mortality in the Canadian Longitudinal Study on Aging. Compared with circulating inflammation biomarkers, some multi-omics risk scores had a higher HR for all cause-mortality when including both score and circulating IL6 in the same model (1-SD IL6 MRS-ERS: HR=1.77 [1.15-2.72] vs. 1-SD circulating IL6 HR=1.11 [0.75,1.66]; 1-SD IL6 PRS-MRS: HR=1.32 [1.21,1.45] vs. 1-SD circulating IL6 HR=1.31 [1.12, 1.53]; 1-SD PRS-MRS-ERS: HR=1.62 [1.04, 2.53] vs. 1-SD circulating IL6: HR=1.16 [0.77, 1.74]). In the Nurses' Health Study (NHS), NHS II, and Health Professional Follow-up Study with available omics, 1-SD of IL6 PRS and 1-SD IL6 PRS-MRS had HR=1.13 [1.00,1.27] and HR=1.13 [1.01,1.27], among individuals >65years without mutual adjustment of the score and circulating IL6. Our study demonstrated that some multi-omics scores for inflammation markers may characterize important inflammation burden for an individual beyond those represented by blood biomarkers and improve our prediction capability for aging process and lifespan.PMID:39399025 | PMC:PMC11469340 | DOI:10.1101/2024.09.24.24313672

Food Chem X. 2024 Sep 21;24:101851. doi: 10.1016/j.fochx.2024.101851. eCollection 2024 Dec 30.ABSTRACTShengmuxiang (SMX), an important aroma in Jiang-flavor base baijiu, significantly influences the quality of the product. This study employed untargeted metabolomics combined with sensomics to explore the key compounds responsible for SMX. Results indicated that SMX samples had higher intensities of green and woody-like odors compare to control samples. A total of 87 aroma compounds were identified by headspace solid phase microextraction combined with gas chromatography-mass spectrometry technology. Based on the variable projection importance, PCA and OPLS-DA were employed to identify 22 potential marker compounds. Quantitative results combined with hierarchical cluster and OAV analysis revealed that 9 aroma compounds (OAV > 1) had high concentrations in SMX samples. Aroma recombination and omission experiments further indicated that acetaldehyde and acetal were the key compounds responsible for the characteristic aroma of SMX in Jiang-flavor base baijiu. These findings provide valuable insights into the distinct aroma profile of SMX and offer a basis for quality control of Jiang-flavor base baijiu.PMID:39398868 | PMC:PMC11470176 | DOI:10.1016/j.fochx.2024.101851

Phenomics. 2024 Mar 10;4(3):227-233. doi: 10.1007/s43657-023-00123-z. eCollection 2024 Jun.ABSTRACTThis research was to reveal the key factors in the progression of osteoarthritis (OA) using non-targeted metabolomics and to find targeted therapies for patients with OA. Twenty-two patients with knee OA scheduled for total knee arthroplasty were divided into two groups: Kellgren-Lawrence (KL) grade 3 (n = 16) and grade 4 (n = 6), according to plain X-rays of the knee. After the operation, the cartilages of femur samples were analyzed using non-targeted metabolomics. When compared with grade 3 patients, the levels of choline, 2-propylpiperidine, rhamnose, and monomethyl glutaric acid were higher; while 1-methylhistamine, sphingomyelin (SM) (d18:1/14:0), zeranol, 3- (4-hydroxyphenyl)-1-propanol, 5-aminopentanamide, dihydrouracil, 2-hydroxypyridine, and 3-amino-2-piperidone were lower in grade 4 patients. Furthermore, some metabolic pathways were found to be significantly different in two groups such as the pantothenate and coenzyme A (CoA) biosynthesis pathway, the glycerophospholipid metabolism pathway, histidine metabolism pathway, lysine degradation pathway, glycine, serine and threonine metabolism pathway, fructose and mannose metabolism pathway, the pyrimidine metabolism pathway, and beta-alanine metabolism pathway. This work used non-targeted metabolomics and screened out differential metabolites and metabolic pathways, providing a reliable theoretical basis for further study of specific markers and their specific pathways in the progression of OA.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-023-00123-z.PMID:39398425 | PMC:PMC11466919 | DOI:10.1007/s43657-023-00123-z

Anal Chem. 2024 Oct 14. doi: 10.1021/acs.analchem.4c03724. Online ahead of print.ABSTRACTA pivotal challenge in metabolite research is the structural annotation of metabolites from tandem mass spectrometry (MS/MS) data. The integration of artificial intelligence (AI) has revolutionized the interpretation of MS data, facilitating the identification of elusive metabolites within the metabolomics landscape. Innovative methodologies are primarily focusing on transforming MS/MS spectra or molecular structures into a unified modality to enable similarity-based comparison and interpretation. In this work, we present CMSSP, a novel Contrastive Mass Spectra-Structure Pretraining framework designed for metabolite annotation. The primary objective of CMSSP is to establish a representation space that facilitates a direct comparison between MS/MS spectra and molecular structures, transcending the limitations of distinct modalities. The evaluation on two benchmark test sets demonstrates the efficacy of the approach. CMSSP achieved a remarkable enhancement in annotation accuracy, outperforming the state-of-the-art methods by a significant margin. Specifically, it improved the top-1 accuracy by 30% on the CASMI 2017 data set and realized a 16% increase in top-10 accuracy on an independent test set. Moreover, the model displayed superior identification accuracy across all seven chemical categories, showcasing its robustness and versatility. Finally, the MS/MS data of 30 metabolites from Glycyrrhiza glabra were analyzed, achieving top-1 and top-3 accuracies of 86.7 and 100%, respectively. The CMSSP model serves as a potent tool for the dissection and interpretation of intricate MS/MS data, propelling the field toward more accurate and efficient metabolite annotation. This not only augments the analytical capabilities of metabolomics but also paves the way for future discoveries in understanding of complex biological systems.PMID:39397774 | DOI:10.1021/acs.analchem.4c03724

Gut Microbes. 2024 Jan-Dec;16(1):2412669. doi: 10.1080/19490976.2024.2412669. Epub 2024 Oct 14.ABSTRACTGut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).PMID:39397690 | DOI:10.1080/19490976.2024.2412669