LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'The phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 inhibitor 3PO is a modulator of neutrophil metabolism, ROS production and NET release'.
Answer: Neutrophils are key effector leukocytes of the innate immune system and play a pivotal role in defending the host against microbial infections. Recent studies have identified a crucial link between glycolysis and neutrophil cellular functions. We have investigated in human neutrophils, the intricate relationship between glycolysis, extracellular glucose availability, and the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), in the regulation of reactive oxygen species (ROS) and neutrophil extracellular trap (NET) production. We have identified that the PFKFB3 inhibitor 3PO is a key regulator of neutrophil ROS and NETs, which are both implicated in the pathogenesis of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA). 3PO blocked the production of ROS and NETs in a dose-dependent manner in both RA and HC neutrophils (p<0.01), and RA neutrophils were more sensitive to lower concentrations of 3PO. Bacterial killing was only partially inhibited by 3PO, and the proportion of live neutrophils after 24h incubation was unchanged. Using NMR metabolomics, we identified that 3PO increases the concentration of lactate, phenylalanine and L-glutamine in neutrophils, as well as significantly decreasing intracellular glutathione (adj. p-value<0.05), suggesting 3PO may have molecular targets beyond PFKFB3. We also demonstrated that RA neutrophils produce ROS and NETs in culture conditions which mimic the low glucose environments encountered in the RA synovial joint. By dissecting the intricate interplay between metabolism and neutrophil effector functions, this study advances the understanding of the molecular mechanisms governing pro-inflammatory neutrophil responses and identifies 3PO as a potential therapeutic for conditions characterized by dysregulated neutrophil activation.
Question: Write a study description for the study titled 'Untargeted Metabolite Profiling (LC-MS) of Root Exudates of Grassland Species'.
Answer: Plants exude a diverse cocktail of metabolites into the soil as response to exogenous and endogenous influences. So far, root exudates have only been studied under artificial conditions due to methodological difficulties. In this study, each five perennial grass and forb species were investigated for polar metabolites in exudates under field conditions. Therefore, exudate samples were measured by liquid chromatography coupled to electron spray ionisation quadrupole time of flight mass spectrometry and analysed by untargeted metabolite profiling.Linked study: MTBLS866
Question: Write a study description for the study titled 'MetaboLights--an open-access general-purpose repository for metabolomics studies and associated meta-data.'.
Answer: MetaboLights (http://www.ebi.ac.uk/metabolights) is the first general-purpose, open-access repository for metabolomics studies, their raw experimental data and associated metadata, maintained by one of the major open-access data providers in molecular biology. Metabolomic profiling is an important tool for research into biological functioning and into the systemic perturbations caused by diseases, diet and the environment. The effectiveness of such methods depends on the availability of public open data across a broad range of experimental methods and conditions. The MetaboLights repository, powered by the open source ISA framework, is cross-species and cross-technique. It will cover metabolite structures and their reference spectra as well as their biological roles, locations, concentrations and raw data from metabolic experiments. Studies automatically receive a stable unique accession number that can be used as a publication reference (e.g. MTBLS1). At present, the repository includes 15 submitted studies, encompassing 93 protocols for 714 assays, and span over 8 different species including human, Caenorhabditis elegans, Mus musculus and Arabidopsis thaliana. Eight hundred twenty-seven of the metabolites identified in these studies have been mapped to ChEBI. These studies cover a variety of techniques, including NMR spectroscopy and mass spectrometry.
Question: Write a study description for the study titled 'Microbiome Metabolism of Dietary Phytochemicals Controls the Anticancer Activity of PI3K Inhibitors'.
Answer: Phosphatidylinositol 3-kinase (PI3K) signaling is both the effector pathway of insulin and among the most frequently activated pathways in human cancer. In murine cancer models, the efficacy of PI3K inhibitors is dramatically enhanced by a ketogenic diet, with a proposed mechanism involving dietary suppression of insulin. Here we confirm profound diet-PI3K anticancer synergy but show that it is, surprisingly, unrelated to diet macronutrient composition. Instead, the diet-PI3K interaction involves microbiome metabolism of ingested phytochemicals. Specifically, murine ketogenic diet lacks the complex spectrum of phytochemicals found in standard chow, including the soy phytochemicals soyasaponins. We find that soyasaponins are converted by the microbiome into inducers of the hepatic cytochrome P450 enzyme CYP3A11, and thereby lower PI3K inhibitor blood levels and anticancer activity. A high-carbohydrate, low-phytochemical diet synergizes with PI3K inhibition to treat cancer in mice, as do antibiotics that curtail the gut microbiome. Thus, diet impacts anticancer drug activity through phytochemical-microbiome-liver interactions.
Question: Write a study description for the study titled 'A Pathogen-Responsive Gene Cluster for Highly Modified Fatty Acids in Tomato'.
Answer: In response to biotic stress, plants produce suites of highly modified fatty acids that bear unusual chemical functionalities. Despite their chemical complexity and proposed roles in pathogen defense, little is known about the biosynthesis of decorated fatty acids in plants. Falcarindiol is a prototypical acetylenic lipid present in carrot, tomato, and celery that inhibits growth of fungi and human cancer cell lines. Using a combination of untargeted metabolomics and RNA sequencing, we discovered a biosynthetic gene cluster in tomato (Solanum lycopersicum) required for falcarindiol production. By reconstituting initial biosynthetic steps in a heterologous host and generating transgenic pathway mutants in tomato, we demonstrate a direct role of the cluster in falcarindiol biosynthesis and resistance to fungal and bacterial pathogens in tomato leaves. This work reveals a mechanism by which plants sculpt their lipid pool in response to pathogens and provides critical insight into the complex biochemistry of alkynyl lipid production.
Question: Write a study description for the study titled 'Disorders of gut microbiota and fecal-serum metabolic patterns are associated with pulmonary tuberculosis and pulmonary tuberculosis co-morbid type 2 diabetes mellitus'.
Answer: BACKGROUND: Pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are prevalent chronic diseases with substantial implications for human health. DM patients are more susceptible to PTB, which exacerbates diabetes-related complications. However, the complex molecular mechanisms underlying the enhanced susceptibility of DM patients to PTB infection remain poorly understood. RESULTS: α-and β-diversity of gut microbiota were significantly reduced in PTB patients and PTB-DM patients. In addition, the abundances of families Lachnospiraceae and Ruminococcaceae in Firmicutes phylum were downregulated in PTB patients and further diminished in PTB-DM patients. On the other hand, untargeted metabolomics in frozen serum and stool samples indicated that such as Phenylalanine, tyrosine and tryptophan biosynthesis, Arginine and proline metabolism, Tryptophan metabolism and Histidine metabolism et al were consistently and significantly altered in PTB patients and PTB-DM patients, with the significant upregulation of most metabolites. Amino acids like serine, proline, histidine et al were both remarkably elevated in PTB and PTB-DM patients. The correlation network analysis reveals the relationships between the shared microbial biomarkers and the shared metabolic pathways. CONCLUSIONS: This research contributes to the exploration of pivotal diagnostic biomarkers for both patients with PTB and PTB accompanied by diabetes. Specifically, shared reductions were identified in the genera g-Roseburia, g-Ruminococcaceae_UCG.013, g-Ruminococcaceae_NK4A214, g-Lachnospiraceae_unclassified and g-Firmicutes_unclassified, in addition to notable regulation of amino acids like glycine, serine and histine in patients with PTB and PTB-DM. Our study expands the comprehension of the intricate connections linking gut microbiota, fecal metabolites and serum metabolites in PTB and PTB-DM patients.
Question: Write a study description for the study titled 'Integrated GWAS and metabolomic analyses identified metabolic pathways and candidate genes involved in free asparagine accumulation in durum wheat grain'.
Answer: Free asparagine content is a key factor in acrylamide formation in wheat derivatives after high temperature processing. Therefore, the control of free asparagine levels is of interest in crop and food sciences. Our study aims to explore the natural variation in durum wheat to identify candidate genes controlling this trait. Durum wheat genotypes were selected from an international germplasm collection and sown in an experimental field in Italy for three years. Free asparagine content was measured on whole grain using an enzymatic assay. A genome-wide association study was performed, and six associated quantitative trait nucleotides were identified. Moreover, the whole grain metabolome of the durum wheat genotypes was investigated to identify metabolic pathways associated to free asparagine accumulation. Specific enriched pathways involved in amino acids metabolism were detected and four candidate genes were identified. This study paved the way to characterize the genetic determinants of free asparagine accumulation in wheat grain.
Question: Write a study description for the study titled 'Paeonol Ameliorates Ulcerative Colitis in Mice by Modulating the Gut Microbiota and its Metabolites'.
Answer: BACKGROUND: Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the gastrointestinal tract. Recent studies demonstrate that the phenolic tannin paeonol (Pae) attenuates UC in mouse models by downregulating inflammatory factors; however, molecular mechanisms linking the gut microbiota and microbial metabolism with Pae remain elusive. METHODS: The UC mouse model was induced using 3% dextran sodium sulfate (DSS). Clinical symptoms were assessed, hematoxylin-eosin staining were used to analyze the effect of Pae on pathological changes to mouse colons, and ELISA was used to evaluate inflammatory factor expression in the serum. Transmission electron microscopy and immunohistochemistry were used to examine the structure of the colonic epithelial barrier and its tight junction proteins. Potential mechanisms of Pae were explored by 16S rRNA-based gut microbiota analysis, fecal metabolomics and construction of a multiscale, multifactorial network. RESULTS: Pae treatment significantly reduced the weight loss and disease activity index, colon shortening, tissue damage, and changes in TNF-α, IL-1β, IL-6, and IL-4 cytokine levels. Conversely, Pae restored the integrity of the intestinal epithelial barrier by increasing the expression of Occludin and ZO-1. Pae also partially reverted the DSS-induced disturbance in intestinal flora composition by increasing the proportion of probiotic bacteria and inhibiting UC-associated dysregulation of gut microbiota metabolites such as bile acids (BA) and short chain fatty acids. Network analysis demonstrated that Lactobacillus was associated with increased levels of unbound BAs, which in turn were strongly associated with inflammatory factor levels. The results suggest that Pae influences BA synthesis by regulating hepatic FXR-SHP/LRH-1 and ileum FXR-FGF15 signaling pathways to maintain intestinal integrity in UC mice. CONCLUSION: Pae can alleviate DSS-induced UC in mice by restoring dysregulated intestinal microbiota and BA metabolism, which improves intestinal barrier function and colonic inflammation, thus suggesting a new mechanism for Pae treatment of UC.
Question: Write a study description for the study titled 'Integration of time-series meta-omics data reveals how microbial ecosystems respond to disturbance'.
Answer: The development of reliable, mixed-culture biotechnological processes hinges on understanding how microbial ecosystems respond to disturbances. Here we reveal extensive phenotypic plasticity and niche complementarity in oleaginous microbial populations from a biological wastewater treatment plant. We perform meta-omics analyses (metagenomics, metatranscriptomics, metaproteomics and metabolomics) on in situ samples over 14 months at weekly intervals. Based on 1,364 de novo metagenome-assembled genomes, we uncover four distinct fundamental niche types. Throughout the time-series, we observe a major, transient shift in community structure, coinciding with substrate availability changes. Functional omics data reveals extensive variation in gene expression and substrate usage amongst community members. Ex situ bioreactor experiments confirm that responses occur within five hours of a pulse disturbance, demonstrating rapid adaptation by specific populations. Our results show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity, and set the foundation for future ecological engineering efforts.
Question: Write a study description for the study titled 'NMR-Based Metabolomics of Non-Human Primate Ocular Tissues: A Dataset'.
Answer: Model animals are employed in experiments as substitutes for human tissues and fluids, particularly when accessing particular human samples (such as cerebrospinal fluid, brain, ocular tissues, etc.) poses significant challenges or is ethically constrained. Nonhuman primates are frequently regarded as superior animal models for investigating human ophthalmological diseases. However, despite this recognition, the metabolomic composition of ocular tissues in non-human primates remains predominantly unexplored. In this work, we present a dataset on metabolite concentrations in serum and ocular tissues, including aqueous humor (AH), vitreous humor (VH), and lens, in two Macaque species: crab-eating macaque (Macaca fascicularis) and rhesus macaque (Macaca mulatta). A total of 99 compounds were quantified in 45 samples, shedding light on the previously unknown metabolomic profiles of primate eye tissues.
Question: Write a study description for the study titled 'Genome-scale metabolic modelling of responses to polymyxins in Pseudomonas aeruginosa'.
Answer: Background: Pseudomonas aeruginosa often causes multidrug-resistant infections in immunocompromised patients and polymyxins are often used as the last-line therapy. Alarmingly, resistance to polymyxins has been increasingly reported worldwide recently. To rescue this last-resort class of antibiotics, it is necessary to systematically understand how P. aeruginosa alters its metabolism in response to polymyxin treatment, thereby facilitating the development of effective therapies. To this end, a genome-scale metabolic model (GSMM) was employed to analyse bacterial metabolic changes at the systems level. Findings: A high-quality GSMM iPAO1 was constructed for P. aeruginosa PAO1 for antimicrobial pharmacological research. Model iPAO1 encompasses an additional periplasmic compartment and contains 3,022 metabolites, 4,265 reactions and 1,458 genes in total. Growth prediction on 190 carbon and 95 nitrogen sources achieved an accuracy of 89.1%, outperforming all reported P. aeruginosa models. Notably, prediction of the essential genes for growth achieved a high accuracy of 87.9%. Metabolic simulation showed that lipid A modifications associated with polymyxin resistance exert a limited impact on bacterial growth and metabolism, but remarkably change the physiochemical properties of the outer membrane. Modelling with transcriptomics constraints revealed a broad range of metabolic responses to polymyxin treatment, including reduced biomass synthesis, upregulated amino acids catabolism, induced flux through the tricarboxylic acid cycle, and increased redox turnover. Conclusions: Overall, iPAO1 represents the most comprehensive GSMM constructed to date for Pseudomonas. It provides a powerful systems pharmacology platform for the elucidation of complex killing mechanisms of antibiotics.
Question: Write a study description for the study titled 'Metabolomic responses to long-term salt stress in related Lotus species (B)'.
Answer: The legume genus Lotus includes glycophytic forage crops and other species adapted to extreme environments, such as saline soils. Understanding salt tolerance mechanisms will contribute to the discovery of new traits which may enhance the breeding efforts towards improved performance of legumes in marginal agricultural environments. Here, we used a combination of ionomic and gas chromatography-mass spectrometry (GC-MS)-based metabolite profilings of complete shoots (pooling leaves, petioles and stems) to compare the extremophile Lotus creticus, adapted to highly saline coastal regions, and two cultivated glycophytic grassland forage species, Lotus corniculatus and Lotus tenuis. L. creticus exhibited better survival after exposure to long-term lethal salinity and was more efficient at excluding Cl- from the shoots than the glycophytes. In contrast, Na+ levels were higher in the extremophile under both control and salt stress, a trait often observed in halophytes. Ionomics demonstrated a differential rearrangement of shoot nutrient levels in the extremophile upon salt exposure. Metabolite profiling showed that responses to NaCl in L. creticus shoots were globally similar to those of the glycophytes, providing little evidence for metabolic pre-adaptation to salinity. This study is the first comparing salt acclimation responses between extremophile and non-extremophile legumes, and challenges the generalization of the metabolic salt pre-adaptation hypothesis.
Question: Write a study description for the study titled 'Impact of in vitro hormone treatments on the bibenzyl production of Radula complanata (Untargeted metabolomics)'.
Answer: Bibenzyls are a specialized metabolite class found throughout the plant kingdom. One of the most prolific producers of bibenzyls are liverworts, specifically plants of the Radula genera. These plants possess an incredible diversity of bibenzyls, prenylated bibenzyls and a few (bis)bibenzyls, several of which have medicinal properties, including perrottetinene, an analog of tetrahydrocannabinol from cannabis. To provide insight into the bibenzyls’ biosynthesis in planta, exogenous phytohormones were applied to in vitro grown Radula complanata and bibenzyl metabolite production was monitored with targeted and untargeted metabolomics. The targeted metabolomic analysis of six prenylated bibenzyls revealed that production of these metabolites was largely reduced when plants were treated with abscisic acid (AA), salicylic acid (SA), 1-naphthaleneacetic acid (NAA) or 6-benzylaminopurine (BAP). The reduction of these metabolites in the BAP and NAA treatment suggests that prenylated bibenzyl production is negatively correlated with vegetative plant growth. The reduction of bibenzyls at low AA and SA concentrations and mild increase at higher AA and SA concentrations suggest that their production is regulated by these stress hormones. In addition, six other bibenzyl metabolites were tentatively identified from the untargeted analysis. These results provide insight into the influence of phytohormones on the bioactive bibenzyl content of R. complanata.Untargeted metabolomics is reported in the current study MTBLS3563.Targeted metabolomics is reported in MTBLS4321.
Question: Write a study description for the study titled 'Proteomic and metabolomic profiling of extracellular vesicles produced by human gut archaea'.
Answer: Gastrointestinal bacteria interact with the host and each other through various mechanisms, including the production of extracellular vesicles (EVs). However, the composition and potential roles of EVs released by gut archaea are poorly understood. Here, we study EVs produced by four strains of human gut-derived methanogenic archaea: Methanobrevibacter smithii ALI, M. smithii GRAZ-2, Candidatus Methanobrevibacter intestini and Methanosphaera stadtmanae. The size (~130 nm) and morphology of these EVs are comparable to those of bacterial EVs. Proteomic and metabolomic analyses reveal that the archaeal EVs are enriched in putative adhesins or adhesin-like proteins, free glutamic and aspartic acid, and choline glycerophosphate. The archaeal EVs are taken up by macrophages in vitro and elicit species-specific responses in immune and epithelial cell lines, including production of chemokines such as CXCL9, CXCL11 and CX3CL1. The EVs produced by Ca. M. intestini strongly induce pro-inflammatory cytokine IL-8 in epithelial cells. Future work should examine whether archaeal EVs play roles in the interactions of archaea with other gut microbes and with the host.
Question: Write a study description for the study titled 'Fatal COVID-19 pulmonary disease involves ferroptosis.'.
Answer: SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.