PubMed

Food Chem X. 2024 Nov 20;24:102021. doi: 10.1016/j.fochx.2024.102021. eCollection 2024 Dec 30.ABSTRACTAnaerobic fermentation (AF) is critical process for Yunnan De'ang pickled tea production. Therefore, widely targeted metabolomics and metagenomics were integrated to reveal the AF mechanism. Lactic acid bacteria (LAB) (e.g. Lactiplantibacillus plantarum, Lactobacillus vaccinostercus and Lactobacillus paracollinoides) and yeasts like Candida metapsilosis and Cyberlindnera fabianii dominated in the AF. Based on bacterial community succession and metabolites variation, the whole AF processes were divided into two phases, i.e., before and after four months. A total of 327 characteristic metabolites (VIP >1.0, P < 0.05, and FC > 1.50 or < 0.67) were selected from the AF. Besides amino acids increase, LAB and yeasts also promoted non-galloylated catechins, and several simple flavones/flavonols, flavanones/flavanonols and methoxy flavones/flavonols accumulations along with galloylated catechins, flavonol/flavone glycosides and anthocyanins decrease during the AF. This study would improve the understanding about AF mechanism of tea-leaves from the perspectives of flavonoids metabolism and microbial community succession.PMID:39659682 | PMC:PMC11629561 | DOI:10.1016/j.fochx.2024.102021

Bioinform Adv. 2024 Nov 14;4(1):vbae178. doi: 10.1093/bioadv/vbae178. eCollection 2024.ABSTRACTMOTIVATION: The availability of longitudinal omics data is increasing in metabolomics research. Viewing metabolomics data over time provides detailed insight into biological processes and fosters understanding of how systems react over time. However, the analysis of longitudinal metabolomics data poses various challenges, both in terms of statistical evaluation and visualization.RESULTS: To make explorative analysis of longitudinal data readily available to researchers without formal background in computer science and programming, we present MEtabolite Trajectory ExplORer (MeTEor). MeTEor is an R Shiny app providing a comprehensive set of statistical analysis methods. To demonstrate the capabilities of MeTEor, we replicated the analysis of metabolomics data from a previously published study on COVID-19 patients.AVAILABILITY AND IMPLEMENTATION: MeTEor is available as an R package and as a Docker image. Source code and instructions for setting up the app can be found on GitHub (https://github.com/scibiome/meteor). The Docker image is available at Docker Hub (https://hub.docker.com/r/gordomics/meteor). MeTEor has been tested on Microsoft Windows, Unix/Linux, and macOS.PMID:39659589 | PMC:PMC11631383 | DOI:10.1093/bioadv/vbae178

Theranostics. 2024 Nov 4;14(19):7534-7553. doi: 10.7150/thno.101229. eCollection 2024.ABSTRACTRationale: Ischemia-reperfusion-induced acute kidney injury (IR-AKI), characterized by the abrupt decline in renal function, is distinguished by the intricate interplay between oxidative stress and inflammation. In this study, a reactive oxygen species (ROS) scavenger-CF@PDA was developed to effectively target antioxidant and anti-inflammatory pathways to disrupt the oxidative stress-inflammation cycle in IR-AKI. Methods: UV-vis absorption spectra, FTIR spectra, and TEM were employed to determine the successful construction of CF@P. ABTS, TMB, and NBT analyses were performed to detect the antioxidant ability and enzyme-mimicking ability of CF@P. In vitro and in vitro, the antioxidant/anti-inflammatory effect of CF@P was detected by MTT, qPCR, fluorescence, and flow cytometry. Multi-omics revealed the mechanism of CF@P in IR-AKI therapy, and molecular docking was further used to determine the mechanism. MRI and photoacoustic imaging were employed to explore the dual-mode imaging capacity of CF@P in IR-AKI management. Results: CF@P could disrupt the oxidative stress-inflammatory cascade by scavenging ROS, reducing pro-inflammatory cytokines, and modulation of macrophage polarization. Subsequent multi-omics indicated that the renal protective effects may be attributed to the inhibition of pyruvate dehydrogenase kinase 4 (PDK4). Metabolomics demonstrated that CF@P could improve the production of antioxidant compounds and reduce nephrotoxicity. Additionally, CF@P exhibited promising capabilities in T1-MRI and photoacoustic imaging for AKI management. Conclusions: Collectively, CF@P, possessing antioxidant/anti-inflammatory properties by inhibiting PDK4, as well as imaging capabilities and superior biocompatibility, holds promise as a therapeutic strategy for IR-AKI.PMID:39659578 | PMC:PMC11626943 | DOI:10.7150/thno.101229

Theranostics. 2024 Oct 28;14(19):7292-7308. doi: 10.7150/thno.99323. eCollection 2024.ABSTRACTRationale: Metabolic dysfunction is one of the key pathological events after ischemic stroke. Disruption of cerebral blood flow impairs oxygen and energy substrate delivery, leading to mitochondrial oxidative phosphorylation dysfunction and cellular bioenergetic stress. Investigating the effects of circSCMH1, a brain repair-related circular RNA, on metabolism may identify novel therapeutic targets for stroke treatment. Methods: CircSCMH1 was encapsulated into brain-targeting extracellular vesicles (EVs) mediated by rabies virus glycoprotein (RVG). Using a mouse model of photothrombotic (PT) stroke, we employed metabolomics and transcriptomics, combined with western blotting and behavioral experiments, to identify the metabolic targets regulated in RVG-circSCMH1-EV-treated mice. Additionally, immunofluorescence staining, chromatin immunoprecipitation (ChIP), pull-down, and western blotting were utilized to elucidate the underlying mechanisms. Results: The targeted delivery of circSCMH1 via RVG-EVs was found to promote post-stroke brain repair by enhancing mitochondrial fusion and inhibiting mitophagy through suppression of kynurenine 3-monooxygenase (KMO) expression. Mechanistically, circSCMH1 exerted its inhibitory effect on KMO expression by binding to the transcription activator STAT5B, thereby impeding its nuclear translocation. Conclusions: Our study reveals a novel mechanism by which circSCMH1 downregulates KMO expression, thereby enhancing mitochondrial fusion and inhibiting mitophagy, ultimately facilitating post-stroke brain repair. These findings shed new light on the role of circSCMH1 in promoting stroke recovery and underscore its potential as a therapeutic target for the treatment of ischemic stroke.PMID:39659575 | PMC:PMC11626939 | DOI:10.7150/thno.99323

Front Microbiol. 2024 Nov 26;15:1463958. doi: 10.3389/fmicb.2024.1463958. eCollection 2024.ABSTRACTThe gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic-pituitary-adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.PMID:39659426 | PMC:PMC11628546 | DOI:10.3389/fmicb.2024.1463958

Front Plant Sci. 2024 Nov 26;15:1434462. doi: 10.3389/fpls.2024.1434462. eCollection 2024.ABSTRACTINTRODUCTION: It is desirable to rehabilitate desert ecosystems with a selection of native plant species that render ecosystem services and yield natural products for creating a high-value industry, e.g., pharmaceuticals or cosmetics. However, plant growth under arid and hyper-arid conditions, such as in the Arabian Peninsula, is constrained by heat, freshwater scarcity, and alkaline sandy soils with low nutrient and water holding capacity. Therefore, it is imperative to develop nature-based sustainable technologies to improve arid soil conditions, as well as increase irrigation and nutrient-use eficiency.METHODS: Here, we report on a study evaluating the effects of two complementary soil amendment technologies, namely Superhydrophobic sand (SHS) mulch and engineered biochar (EB) on the growth of Moringa oleifera plants. Effects of SHS (1cm-thick), EB (2% w/w), and SHS+EB treatments were tracked in greenhouse plants under normal (N, 100% field capacity) and reduced (R, 50% of N) irrigation scenarios for over 150 days, where EB treatments were pre-loaded with nutrients and remaining treatments received traditional NPK fertilizer.RESULTS: Significant benefits of the SHS, EB, and SHS+EB treatments were found in terms of increased plant height, trunk diameter, leaf area, leaf chlorophyll content index, stomatal conductance, and shoot and root biomass in comparison with the controls. Evaporation water savings due to SHS mulching significantly enhanced transpiration under N and R scenarios. Similarly, EB and SHS+EB treated plants experienced higher transpiration than in the control plants under N and R conditions (p< 0.05). In response to water stress due to excessive evaporation, metabolomics analysis showed a higher accumulation of amino acids in control plants than other treatments under both irrigation regimes. Meanwhile, a higher abundance of sugars (i.e., D-Mannose, D-Fructose, glucose) and organic acid (i.e., malic acid) was observed in SHS and EB-treatments for Variable Importance in Projection (VIP) scores >1.0 (i.e., the scores considered of significance in contributing to the differences between treatment groups).DISCUSSION: The results show the synergistic benefits of SHS and EB technologies for addressing the challenges of water scarcity and nutrient limitation in arid regions, which couldcontribute to the success and sustainability of agriculture and greening efforts in such regions.PMID:39659422 | PMC:PMC11628278 | DOI:10.3389/fpls.2024.1434462

Front Plant Sci. 2024 Nov 26;15:1475416. doi: 10.3389/fpls.2024.1475416. eCollection 2024.ABSTRACTINTRODUCTION: Inducing natural resistance against pathogen infection in postharvest tomatoes is a sustainable strategy for reducing postharvest losses. The action model underlying the resistance enhancement of tomatoes induced by bacterial volatile organic compounds (VOCs) against Botrytis cinerea, however, have not been explored.METHODS: In this study, RNA-seq, metabolomics and physiological analysis were used to evaluate global change of defense response induced by VOCs in tomatoes.RESULTS: The application of VOCs inhibited the damage to tomatoes caused by B. cinerea. VOCs treatment had remarkable beneficial effects on the activities of the main defence-related enzymes, including chitinases, glucanases, peroxidases, ascorbate peroxidases, polyphenol oxidases, and phenylalanine ammonia-lyases. The expression of response genes involved in salicylic acid and jasmonic acid biosynthesis and signalling pathways was enhanced upon VOCs treatment. Metabolomics data demonstrated that VOC treatment triggered the accumulation of phenolic acids, including substrates in phenolic acid biosynthesis pathways, hydroxycinnamic acid, hydroxybenzoic acid, and their derivatives. Transcriptomics analysis and qRT-PCR verification revealed that VOCs treatment significantly upregulates the expression of core genes related to phenolic acid biosynthesis, specifically in shikimate pathway (SlDAHPS, SlSDH, SlCS, and SlADT3) and phenylalanine metabolic pathway (SlPAL, Sl4CL, SlBAHD1, SlCYP98A2 and SlCAP84A1).DISCUSSION: Results confirmed that VOCs enhanced tomatoes postharvest resistance against B. cinerea by regulating defence enzyme activity, SA/JA signalling, and phenolic acid biosynthesis pathway. This study provides new insights into the mechanisms by which VOCs fumigation manages postharvest grey mould in tomatoes.PMID:39659409 | PMC:PMC11628293 | DOI:10.3389/fpls.2024.1475416

J Sci Food Agric. 2024 Dec 11. doi: 10.1002/jsfa.14062. Online ahead of print.ABSTRACTBACKGROUND: Ginsenosides, the primary active ingredients in Panax ginseng, are secondary metabolites. However, their content varies significantly across batches due to differences in environmental conditions and production methods. Ecological stress can increase the levels of reactive oxygen species (ROS) in plants, and ROS can enhance secondary metabolism. Nitric oxide (NO) can promote the production of O2 ·- and H2O2. This study utilized physiological and non-targeted metabolomics to investigate how NO regulates ginseng quality and how P. ginseng adapts to adversity.RESULTS: Sodium nitroprusside (SNP, an NO donor) at 0.5 mmol·L-1 significantly increased ROS levels, with O2 ·- increasing by 64.3% (P < 0.01) and H2O2 by 79.2% (P < 0.01). Nitric oxide influenced P. ginseng metabolism, with 24 metabolites showing significant differences. Rotenone, lactic acid, and gluconic acid, which are involved in ROS metabolism, increased significantly, whereas tyrosine decreased. Metabolites involved in secondary metabolic pathways, including campesterol, ginsenosides Rh1, Rb1, Rc, Rd, Rg3, phenylalanine, and tryptophan, increased markedly, whereas 2,3-oxidosqualene, glucose 1-phosphate, ferulic acid, and pyrogallol decreased. Isocitric acid, succinic acid, and 3-isopropylmalic acid, associated with respiratory metabolism, showed significant increases, but pyruvic acid decreased. Finally, 18:0 Lyso PC and 9-hydroxy-10E,12Z-octadecadienoic acid, linked to cell membrane protection, increased significantly, and mannose and raffinose decreased.CONCLUSION: Sodium nitroprusside enhances the physiological resilience of P. ginseng under stress and improves its quality. © 2024 Society of Chemical Industry.PMID:39659278 | DOI:10.1002/jsfa.14062

Proteomics. 2024 Dec 10:e202400271. doi: 10.1002/pmic.202400271. Online ahead of print.ABSTRACTAdvances in high-throughput omics technologies have enabled system-wide characterization of biological samples across multiple molecular levels, such as the genome, transcriptome, and proteome. However, as sample sizes rapidly increase in large-scale multi-omics studies, sample mix-ups have become a prevalent issue, compromising data integrity and leading to erroneous conclusions. The interconnected nature of multi-omics data presents an opportunity to identify and correct these errors. This review examines the potential sources of sample mix-ups and evaluates the methodologies and tools developed for detecting and correcting these errors, with an emphasis on approaches applicable to proteomics data. We categorize existing tools into three main groups: expression/protein quantitative trait loci-based, genotype concordance-based, and gene/protein expression correlation-based approaches. Notably, only a handful of tools currently utilize the proteogenomics approach for correcting sample mix-ups at the proteomics level. Integrating the strengths of current tools across diverse data types could enable the development of more versatile and comprehensive solutions. In conclusion, verifying sample identity is a critical first step to reduce bias and increase precision in subsequent analyses for large-scale multi-omics studies. By leveraging these tools for identifying and correcting sample mix-ups, researchers can significantly improve the reliability and reproducibility of biomedical research.PMID:39659081 | DOI:10.1002/pmic.202400271

J Agric Food Chem. 2024 Dec 10. doi: 10.1021/acs.jafc.4c06072. Online ahead of print.ABSTRACTIn this study, we investigated the ameliorative effects of selenium-enriched Lactobacillus fermentum FZU3103 (Lf@Se) and its pathway on alcoholic liver injury (ALI) in mice. The results showed that Lf@Se was superior to Lf and inorganic selenium in alleviating ALI. Oral Lf@Se effectively prevented lipid metabolism disorders, improved liver function, promoted alcohol metabolism, and alleviated liver oxidative damage in mice. 16S amplicons sequencing indicated that Lf@Se intervention modulated intestinal flora homeostasis by increasing (decreasing) the abundance of beneficial bacteria (harmful bacteria), which is associated with the improvement of liver function. Besides, Lf@Se intervention altered the liver metabolic profile, and the characteristic biomarkers were mainly involved in tyrosine metabolism, retinol metabolism, galactose metabolism, and primary bile acid biosynthesis. Additionally, Lf@Se intervention regulated liver gene expression for lipid metabolism and oxidative stress. Western blot analysis revealed increased expression levels of intestinal tight junction proteins after Lf@Se intervention, thereby ameliorating alcohol-induced intestinal barrier damage.PMID:39658842 | DOI:10.1021/acs.jafc.4c06072

Adv Sci (Weinh). 2024 Dec 10:e2412222. doi: 10.1002/advs.202412222. Online ahead of print.ABSTRACTMammalian pre-implantation development is a complex process involving sophisticated regulatory dynamics. WD repeat domain 36 (WDR36) is known to play a critical role in mouse early embryonic development, but its regulatory function in human embryogenesis is still elusive due to limited access to human embryos. The human pluripotent stem cell-derived blastocyst-like structure, termed a blastoid, offers an alternative means to study human development in a dish. In this study, after verifying that WDR36 inhibition disrupted polarization in mouse early embryos, it is further demonstrated that WDR36 interference can block human blastoid formation, dominantly hindering the trophectoderm lineage commitment. Both transcriptomics and targeted metabolomics analyses revealed that WDR36 interference downregulated glucose metabolism. WDR36 can interact with glycolytic metabolic protein lactate dehydrogenase A (LDHA), thereby positively regulating glycolysis during the late stage of human blastoid formation. Taken together, the study has established a mechanistic connection between WDR36, glucose metabolism, and cell fate determination during early embryonic lineage commitment, which may provide potential insights into novel therapeutic targets for early adverse pregnancy interventions.PMID:39656902 | DOI:10.1002/advs.202412222

Cardiovasc Res. 2024 Dec 6:cvae250. doi: 10.1093/cvr/cvae250. Online ahead of print.ABSTRACTAIMS: The transcription factor NRF2 is well recognized as a master regulator of antioxidant responses and cytoprotective genes. Previous studies showed that NRF2 enhances resistance of mouse hearts to chronic hemodynamic overload at least in part by reducing oxidative stress. Evidence from other tissues suggests that NRF2 may modulate glucose intermediary metabolism but whether NRF2 has such effects in the heart is unclear. Here, we investigate the role of NRF2 in regulating glucose intermediary metabolism and cardiac function during disease stress.METHODS AND RESULTS: Cardiomyocyte-specific Keap1 knockout (csKeap1KO) mice, deficient in the endogenous inhibitor of NRF2, were used as a novel model of constitutively active NRF2 signaling. Targeted metabolomics and isotopomer analysis were employed in studies with 13C6-glucose in csKeap1KO and wild-type (WT) mice. Pharmacological and genetic approaches were utilized in neonatal rat ventricular cardiomyocytes (NRVM) to explore molecular mechanisms. We found that cardiac-specific activation of NRF2 redirected glucose metabolism towards the pentose phosphate pathway (PPP), a branch pathway of glycolysis, and mitigated pressure overload-induced cardiomyocyte death and cardiac dysfunction. Activation of NRF2 also protected against myocardial infarction-induced DNA damage in remote myocardium and cardiac dysfunction. In vitro, knockdown of Keap1 upregulated PPP enzymes and reduced cell death in NRVM subjected to chronic neurohumoral stimulation. These pro-survival effects were abolished by pharmacological inhibition of the PPP or silencing of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of NRF2 in NRVM increased stress-induced DNA damage which was rescued by supplementing the cells with either NADPH or nucleosides, the two main products of the PPP.CONCLUSIONS: These results indicate that NRF2 regulates cardiac metabolic reprogramming by stimulating the diversion of glucose into the PPP, thereby generating NADPH and providing nucleotides to prevent stress-induced DNA damage and cardiac dysfunction.PMID:39657243 | DOI:10.1093/cvr/cvae250

Eur Heart J. 2024 Dec 4:ehae829. doi: 10.1093/eurheartj/ehae829. Online ahead of print.ABSTRACTCalcific aortic valve disease (CAVD) resulting in aortic stenosis (AS) is the most common form of valvular heart disease, affecting 2% of those over age 65. Those who develop symptomatic severe AS have an average further lifespan of <2 years without valve replacement, and three-quarters of these patients will develop heart failure, undergo valve replacement, or die within 5 years. There are no approved pharmaceutical therapies for AS, due primarily to a limited understanding of the molecular mechanisms that direct CAVD progression in the complex haemodynamic environment. Here, advances in efforts to understand the pathogenesis of CAVD and to identify putative drug targets derived from recent multi-omics studies [including (epi)genomics, transcriptomics, proteomics, and metabolomics] of blood and valvular tissues are reviewed. The recent explosion of single-cell omics-based studies in CAVD and the pathobiological and potential drug discovery insights gained from the application of omics to this disease area are a primary focus. Lastly, the translation of knowledge gained in valvular pathobiology into clinical therapies is addressed, with a particular emphasis on treatment regimens that consider sex-specific, renal, and lipid-mediated contributors to CAVD, and ongoing Phase I/II/III trials aimed at the prevention/treatment of AS are described.PMID:39656785 | DOI:10.1093/eurheartj/ehae829

Int Immunol. 2024 Dec 4:dxae070. doi: 10.1093/intimm/dxae070. Online ahead of print.ABSTRACTIntestinal bacteria play a critical role in the regulation of the host immune system and an imbalance in intestinal bacterial composition induces various host diseases. Therefore, maintaining a balance in the intestinal bacterial composition is crucial for health. Immunoglobulin A (IgA), produced through T cell-dependent and T cell-independent (TI) pathways, is essential for host defense against pathogen invasion and maintaining the balance of intestinal symbiotic bacteria. Interleukin (IL)-5 is constitutively produced by group 2 innate lymphoid cells (ILC2s) and plays a critical role in the survival and proliferation of B cells and eosinophils. Here, we show that the role of IL-5-producing ILC2s in intestinal TI IgA production at steady state using TCRα deficient mice. In this mouse model, ILC2s increased fecal TI IgA levels in a non-inflammatory state in an IL-5-dependent manner. The administration of recombinant IL-33 (rIL-33) increased the amount of TI IgA production, accompanied by an increase in the number of IL-5-producing ILC2s in the large intestine. In addition, rIL-33 treatment increased IL-5-dependent IgA+ cells in isolated lymphoid follicles, the site of TI IgA production. Furthermore, eosinophils recruited by ILC2s were required for the maximal production of IgA in the TI pathway. Moreover, IL-5 increased the frequency of TI IgA-binding intestinal bacteria and was involved in the maintenance of intestinal bacterial composition. These findings indicate that IL-5-producing ILC2s together with eosinophils contribute to TI IgA production. In addition to their role in TI IgA production, IL-5-producing ILC2s may contribute to the homeostasis of intestinal commensal bacteria.PMID:39656643 | DOI:10.1093/intimm/dxae070

J Sep Sci. 2024 Dec;47(23):e70040. doi: 10.1002/jssc.70040.ABSTRACTResearches regarding quality control of ginseng focusing on the lipids are rare. Herein, ultra-high-performance supercritical fluid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPSFC/IM-QTOF-MS) combined with untargeted metabolomic analysis was utilized to holistically characterize and compare the lipidomic difference among 12 Panax-derived herbal medicines. The established UHPSFC/IM-QTOF-MS method, using a Torus 1-AA column with CO2/CH3OH (modifier) as the mobile phase, well resolved the ginseng lipidome within 30 min. The lipid isomers and those easily co-eluted by conventional reversed-phase chromatography got separated, and integrated analyses of the positive-/negative-mode MS data and IM-derived collision cross section (CCS) greatly enhanced lipids identification. By the pattern recognition chemometric analysis of 90 batches of ginseng samples, the root ginseng samples showed significant differences in lipidome composition from those stem/leaf and flower samples. In contrast, red ginseng also contained lipids significantly different from the other root ginseng. Totally 82 potential differential lipids were discovered and identified based on the positive-mode data and 90 ones in the negative mode. Some of these lipid markers might be diagnostic for their authentication. Conclusively, we first report the lipidomic difference among 12 ginseng varieties, and the information obtained can lay foundation for the accurate identification of ginseng from the lipidome level.PMID:39658817 | DOI:10.1002/jssc.70040

J Cheminform. 2024 Dec 10;16(1):140. doi: 10.1186/s13321-024-00935-9.ABSTRACTFlavor is the main factor driving consumers acceptance of food products. However, tracking the biochemistry of flavor is a formidable challenge due to the complexity of food composition. Current methodologies for linking individual molecules to flavor in foods and beverages are expensive and time-consuming. Predictive models based on machine learning (ML) are emerging as an alternative to speed up this process. Nonetheless, the optimal approach to predict flavor features of molecules remains elusive. In this work we present FlavorMiner, an ML-based multilabel flavor predictor. FlavorMiner seamlessly integrates different combinations of algorithms and mathematical representations, augmented with class balance strategies to address the inherent class of the input dataset. Notably, Random Forest and K-Nearest Neighbors combined with Extended Connectivity Fingerprint and RDKit molecular descriptors consistently outperform other combinations in most cases. Resampling strategies surpass weight balance methods in mitigating bias associated with class imbalance. FlavorMiner exhibits remarkable accuracy, with an average ROC AUC score of 0.88. This algorithm was used to analyze cocoa metabolomics data, unveiling its profound potential to help extract valuable insights from intricate food metabolomics data. FlavorMiner can be used for flavor mining in any food product, drawing from a diverse training dataset that spans over 934 distinct food products.Scientific Contribution FlavorMiner is an advanced machine learning (ML)-based tool designed to predict molecular flavor features with high accuracy and efficiency, addressing the complexity of food metabolomics. By leveraging robust algorithmic combinations paired with mathematical representations FlavorMiner achieves high predictive performance. Applied to cocoa metabolomics, FlavorMiner demonstrated its capacity to extract meaningful insights, showcasing its versatility for flavor analysis across diverse food products. This study underscores the transformative potential of ML in accelerating flavor biochemistry research, offering a scalable solution for the food and beverage industry.PMID:39658805 | DOI:10.1186/s13321-024-00935-9

Int J Obes (Lond). 2024 Dec 10. doi: 10.1038/s41366-024-01695-0. Online ahead of print.ABSTRACTBACKGROUND: Human urine is highly favorable for 1H NMR metabolomics analyses of obesity-related diseases, such as non-alcoholic fatty liver, type 2 diabetes, and hyperlipidemia (HL), due to its non-invasiveness and ease of large-scale collection. However, the wide range of intrinsic urine pH (5.5-8.5) results in inevitably chemical shift and signal intensity modulations in the 1H NMR spectra. For patients where acidic urine pH is closely linked to obesity-related disease phenotypes, the pH-dependent modulations complicate the spectral analysis and deteriorate quantifications of urine metabolites.METHODS: We characterized human urine metabolites by NMR at intrinsic urine pH, across urine pH 4.5 to 9.5, to account for pH-dependent modulations. A pH-dependent chemical shift database for quantifiable urine metabolites was generated and integrated into a "pH intelligence" program developed for quantifications of pH-dependent modulations at various pH. The 1H NMR spectra of urines collected from patients with Ob-HL and healthy controls were compared to uncover potential metabolic biomarkers of Ob-HL disease.RESULTS: Three urine metabolites were unveiled by pH-dependent NMR approach, i.e., TMAO, glycine, and pyruvic acid, with VIP score >1.0 and significant q-value < 0.05, that represent as potential biomarkers for discriminating Ob-HL from healthy controls. Further ROC-AUC analyses revealed that TMAO alone achieved the highest diagnostic accuracy (AUC 0.902), surpassed to that obtained by neutralizing pH approach (AUC 0.549) and enabled better recovering potential urine metabolites from the Ob-HL disease phenotypes.CONCLUSIONS: We concluded that 1H NMR-derived urine metabolite profile represents a snapshot that can reveal the physiological condition of humans in either a healthy or diseased state under intrinsic urine pH. We demonstrated a systematic analysis of pH-dependent modulations on the human urine metabolite signals and further developed software for quantification of urine metabolite profiles with high accuracy, enabling the uncovering of potential metabolite biomarkers in clinical diagnosis applications.PMID:39658677 | DOI:10.1038/s41366-024-01695-0

BMJ Open. 2024 Dec 10;14(12):e089038. doi: 10.1136/bmjopen-2024-089038.ABSTRACTINTRODUCTION: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling condition that can affect adolescents during a vulnerable period of development. The underlying biological mechanisms for ME/CFS remain unclear and have rarely been investigated in the adolescent population, despite this period representing an age peak in the overall incidence. The primary objective of this is to provide a foundational set of biological data on adolescent ME/CFS patients. Data generated will be compared with controls and over several time points within each patient to potentially develop a biomarker signature of the disease, identify subsets or clusters of patients, and to unveil the pathomechanisms of the disease.METHODS AND ANALYSIS: This protocol paper outlines a comprehensive, multilevel, longitudinal, observational study in paediatric ME/CFS. ME/CFS patients aged 12-19 years and controls will donate biosamples of urine, blood, and peripheral blood mononuclear cells for an in-depth omics profiling analysis (whole-genome sequencing, metabolomics and quantitative proteomics) while being assessed by gold-standard clinical and neuropsychological measures. ME/CFS patients will then be provided with a take-home kit that enables them to collect urine and blood microsamples during an average day and during days when they are experiencing postexertional malaise. The longitudinal repeated-measures study design is optimal for studying heterogeneous chronic diseases like ME/CFS as it can detect subtle changes, control for individual differences, enhance precision and boost statistical power. The outcomes of this research have the potential to identify biomarker signatures, aid in understanding the underlying mechanisms, and ultimately, improve the lives of children with ME/CFS.ETHICS AND DISSEMINATION: This project was approved by the Royal Children's Hospital's Human Research Ethics Committee (HREC 74175). Findings from this study will be disseminated through peer-reviewed journal publications and presentations at relevant conferences. All participants will be provided with a summary of the study's findings once the project is completed.PMID:39658280 | DOI:10.1136/bmjopen-2024-089038

J Biochem. 2024 Dec 10:mvae084. doi: 10.1093/jb/mvae084. Online ahead of print.ABSTRACTMonogalactosyl diacylglycerol (MGDG) is a major membrane lipid component in plants and is crucial for proper thylakoid functioning. However, MGDG in mammals has not received much attention, partly because of its relative scarcity in mammalian tissues. In addition, the biosynthetic pathway of MGDG in mammals has not been thoroughly analyzed, although some reports have suggested that UGT8, a ceramide galactosyltransferase, has the potential to catalyze MGDG biosynthesis. Here, we successfully captured the endogenous levels of MGDG in HeLa cells using LC-MS/MS-based lipidomics. Cellular MGDG was completely depleted in CRISPR/Cas9-mediated UGT8 knockout HeLa cells. Transient overexpression of UGT8 enhanced MGDG production in HeLa cells, and the corresponding cell lysates displayed MGDG biosynthetic activity in vitro. Site-directed mutagenesis revealed that His358 within the UGT signature sequence was important for its activity. UGT8 was localized in the endoplasmic reticulum and activation of the unfolded protein response by membrane lipid saturation was impaired in UGT8 knockout cells. These results demonstrate that UGT8 is an MGDG synthase in mammals and that UGT8 regulates membrane lipid saturation signals in cells.PMID:39658193 | DOI:10.1093/jb/mvae084

Food Res Int. 2025 Jan;199:115390. doi: 10.1016/j.foodres.2024.115390. Epub 2024 Nov 19.ABSTRACTDietary fiber from coffee peel is rich in bound polyphenols good for human health due to the antioxidant activity. In this study, we evaluated the bound polyphenol release conditions and activities in coffee peel soluble dietary fiber (CPSDF) in the process of in vitro simulation digestion. The CPSDF structure became loose and porous due to simulated digestion but retained the polysaccharide backbone. Widely-targeted metabolomics analysis identified 550 metabolites, with phenolic acids and flavonoids being main differentially expressed metabolites in digested products (82.18% in total). The most significant increase in the 5,7,8,3',4'-pentamethoxyflavanone content and decrease in the 3,5-dihydroxyacetophenone content were observed after digestion (undigested vs S-intestine). Additionally, the changes in antioxidant and enzyme inhibitory activities followed the same pattern as that observed for total phenolic content. The enzyme inhibitory and antioxidant activities of gastric digestion products were greater than those of the oral and small intestinal digestion products. The present work provided the theoretical foundation for developing high-value CPSDF products and reusing coffee peel waste.PMID:39658178 | DOI:10.1016/j.foodres.2024.115390