PubMed

Arch Microbiol. 2023 Aug 1;205(8):299. doi: 10.1007/s00203-023-03628-3.ABSTRACTIndustrial tobacco waste was mainly treated via a reconstituted tobacco process using the paper-making method, which involves aqueous concentrated tobacco waste extract (cTWE) fermentation (aging). The fermentation was done to improve the quality of reconstituted tobacco. However, cTWE is a multi-stress environment that is characterized by low pH (about 4), as well as high sugar (above 150 g/L) and nicotine (above 15 g/L) content. In this study, a specific selection strategy was used to successfully isolate multi-stress-resistant bacterial or fungal strains, that exhibited positive effects on cTWE fermentation, thereby improving the quality of final products. A potential strain Zygosaccharomyces parabailii MC-5K3 was used for the bioaugmentation of cTWE fermentation and it significantly influenced the microbial diversity of the fermented cTWE. Zygosaccharomyces was observed to be the only dominant fungal genus instead of some pathogenic bacterial genera, with an abundance of over 95% after four days, and still more than 80% after a week. Meanwhile, metabolomics profiling showed significant concentration decrease with regard to some flavor-improving relative metabolites, such as 3-hydroxybenzoic acid (log2FC = - 5.25) and sorbitol (log2FC = - 5.54). This finding is extrapolated to be the key influence factor on the quality of the fermented cTWE. The correlation analysis also showed that the alterations in microbial diversity in the fermented cTWE led to some important differential metabolite changes, which finally improved various properties of tobacco products.PMID:37525014 | DOI:10.1007/s00203-023-03628-3

Sci Rep. 2023 Jul 31;13(1):12395. doi: 10.1038/s41598-023-38904-1.ABSTRACTMigraine is a common, polygenic disorder that is characterized by moderate to severe headache attacks. Migraine attacks are commonly treated with triptans, i.e. serotonin receptor agonists. However, triptans are effective in ~ 60% of the population, and the mechanisms of triptans are debated. Here, we aim to expose the mechanisms of triptan using metabolomics and transcriptomics in spontaneous migraine attacks. We collected temporal multi-omics profiles on 24 migraine patients, using samples collected at a migraine attack, 2 h after treatment with a triptan, when headache-free, and after a cold-pressor test. Differential metabolomic analysis was performed to find metabolites associated with treatment. Their effect was further investigated using correlation analysis and a machine learning approach. We found three differential metabolites: cortisol, sumatriptan and glutamine. The change in sumatriptan levels correlated with a change in GNAI1 and VIPR2 gene expression, both known to regulate cAMP levels. Furthermore, we found fatty acid oxidation to be affected, a mechanism known to be involved in migraine but not previously found in relation to triptans. In conclusion, using an integrative approach we find evidence for a role of glutamine, cAMP regulation, and fatty acid oxidation in the molecular mechanisms of migraine and/or the effect of triptans.PMID:37524744 | DOI:10.1038/s41598-023-38904-1

Nat Commun. 2023 Jul 31;14(1):4494. doi: 10.1038/s41467-023-40201-4.ABSTRACTHeart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase A2β (iPLA2β) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage in caspase-independent cell death. Here, we show that lysophosphatidylserine generated by iPLA2β induces necrotic cardiomyocyte death, as well as contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34). Cardiomyocyte-specific iPLA2β-deficient male mice were subjected to pressure overload. While control mice showed left ventricular systolic dysfunction with necrotic cardiomyocyte death, iPLA2β-deficient mice preserved cardiac function. Lipidomic analysis revealed a reduction of 18:0 lysophosphatidylserine in iPLA2β-deficient hearts. Knockdown of Gpr34 attenuated 18:0 lysophosphatidylserine-induced necrosis in neonatal male rat cardiomyocytes, while the ablation of Gpr34 in male mice reduced the development of pressure overload-induced cardiac remodeling. Thus, the iPLA2β-lysophosphatidylserine-GPR34-necrosis signaling axis plays a detrimental role in the heart in response to pressure overload.PMID:37524709 | DOI:10.1038/s41467-023-40201-4

BMJ Open. 2023 Jul 31;13(7):e073658. doi: 10.1136/bmjopen-2023-073658.ABSTRACTINTRODUCTION: Traditional dietary assessment methods such as 24-hour recalls and food frequency questionnaires rely on self-reported data and are prone to error, bias and inaccuracy. Identification of dietary metabolites associated with different dietary patterns can provide objective markers of whole diet patterns that account for metabolism and individual responses to dietary interventions. Additionally, few studies have investigated country-specific healthy and unhealthy dietary patterns using metabolomics. Therefore, the current study aims to identify urinary and plasma metabolites that characterise a 'healthy' (aligned with current national dietary guidelines) and an 'unhealthy' dietary pattern (Typical Australian Diet) in Australian adults.METHODS AND ANALYSIS: The Diet Quality Feeding Study (DQFS) is an 8-week cross-over feeding study that will recruit 40 healthy adults from the Hunter region (NSW, Australia). Data collected includes biospecimens (whole blood, urine, stool) for quantification of dietary metabolite biomarkers; questionnaires (medical history/demographic, physical activity, quality of life); physical measures (anthropometry, body composition, waist circumference, blood pressure, arterial pressure); skin carotenoids and dietary intake (24-hour recalls, food frequency questionnaire). Participants will attend the research facility every 2 weeks (end of the run-in, each diet intervention and washout period) for collection of physical measures. All food will be provided to participants for each dietary intervention period, and participants will return to their usual diet during the run-in and washout periods. Targeted and untargeted metabolomics using liquid chromatography-mass spectrometry and/or proton nuclear magnetic resonance (1H-NMR) spectroscopy will be used to identify metabolites in biospecimens associated with dietary intake.ETHICS AND DISSEMINATION: This study is approved by the Hunter New England Human Research Ethics Committee (HNEHREC; 2022/ETH01649) and the University of Newcastle's Human Research Ethics Committee (HREC; H-2022-0330). Findings will be disseminated to study participants, funding bodies supporting the DQFS, peer-review publications and presented at scientific conferences within the field of research.TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12622001321730).PMID:37524561 | DOI:10.1136/bmjopen-2023-073658

PLoS One. 2023 Jul 31;18(7):e0288871. doi: 10.1371/journal.pone.0288871. eCollection 2023.ABSTRACTPalatine tonsils (PT) are B cell-predominant lymphoid organs that provide primary immune responses to airborne and dietary pathogens. Numerous histopathological and immunological studies have been conducted on PT, yet no investigations have been conducted on its metabolic profile. We performed high-resolution magic angle spinning nuclear magnetic resonance spectroscopy-based metabolic profiling in 35 pediatric and 28 adult human palatine tonsillar tissue samples. A total of 36 metabolites were identified, and the levels of 10 metabolites were significantly different depending on age. Among them, partial correlation analysis shows that glucose levels increased with age, whereas glycine, phosphocholine, phosphoethanolamine, and ascorbate levels decreased with age. We confirmed the decrease in immunometabolic activity in adults through metabolomic analysis, which had been anticipated from previous histological and immunological studies on the PT. These results improve our understanding of metabolic changes in the PT with aging and serve as a basis for future tonsil-related metabolomic studies.PMID:37523386 | DOI:10.1371/journal.pone.0288871

J Am Soc Mass Spectrom. 2023 Jul 31. doi: 10.1021/jasms.3c00181. Online ahead of print.ABSTRACTLipid metabolism is implicated in a variety of diseases, including cancer, cell death, and inflammation, but lipidomics has proven to be challenging due to the vast structural diversity over a narrow range of mass and polarity of lipids. Isotope labeling is often used in metabolomics studies to follow the metabolism of exogenously added labeled compounds because they can be differentiated from endogenous compounds by the mass shift associated with the label. The application of isotope labeling to lipidomics has also been explored as a method to track the metabolism of lipids in various disease states. However, it can be difficult to differentiate a single isotopically labeled lipid from the rest of the lipidome due to the variety of endogenous lipids present over the same mass range. Here we report the development of a dual-isotope deuterium labeling method to track the metabolic fate of exogenous polyunsaturated fatty acids, e.g., arachidonic acid, in the context of ferroptosis using hydrophilic interaction-ion mobility-mass spectrometry (HILIC-IM-MS). Ferroptosis is a type of cell death that is dependent on lipid peroxidation. The use of two isotope labels rather than one enables the identification of labeled species by a signature doublet peak in the resulting mass spectra. A Python-based software, D-Tracer, was developed to efficiently extract metabolites with dual-isotope labels. The labeled species were then identified with LiPydomics based on their retention times, collision cross section, and m/z values. Changes in exogenous AA incorporation in the absence and presence of a ferroptosis inducer were elucidated.PMID:37523294 | DOI:10.1021/jasms.3c00181

J Chem Ecol. 2023 Jul 31. doi: 10.1007/s10886-023-01435-0. Online ahead of print.ABSTRACTEucalyptus species are among the most planted trees in forestry production, an ever-increasing commercial activity worldwide. Forestry expansion demands a continuous search for preventive and sanitary measures against pests and diseases. Massive application of phytosanitary products is incompatible with the forestry sector, so forest health management must be based on other principles. In this context, studies on insect plant relationships mediated by plant metabolites may contribute information relevant to plant resistance and genotype selection. In this study, we analyzed the leaf metabolome of four Eucalyptus species commonly planted in southern South America, to correlate this chemical information with feeding preference of Thaumastocoris peregrinus (Hemiptera: Thaumastocoridae), an important pest of eucalypt plantations. Gas chromatography mass spectrometry analyses were performed on polar and non-polar leaf extracts from Eucalyptus globulus, Eucalyptus grandis, Eucalyptus robusta, and Eucalyptus tereticornis (Myrtaceae). Feeding preferences were assessed in two-choice laboratory bioassays resulting in a preference gradient of the four plant species. Moreover, a performance bioassay where we contrasted survival and development time between the most and least preferred plants, showed a clear correlation with preference both in survival and developmental time of the most susceptible nymph instar. We found that species with high or low feeding preferences differ significantly in several foliar metabolites, which may be acting as feeding stimulants or deterrents for T. peregrinus. These findings may provide useful criteria for choosing Eucalyptus genotypes when planting in bronze bug infested areas.PMID:37523036 | DOI:10.1007/s10886-023-01435-0

Endocr Connect. 2023 Jul 1:EC-23-0079. doi: 10.1530/EC-23-0079. Online ahead of print.ABSTRACTPrevious studies, have shown that elevated levels of circulating BCAAs are associated with the development of insulin resistance and its complications, including obesity, type 2 diabetes, cardiovascular disease, and some cancers. However, animal models that can mimic the metabolic state of chronically elevated BCAAs in humans are rare. Therefore, the aim of this study was to establish the above animal model and analyze the metabolic changes associated with high BCAA levels. Sixteen 8-week-old SD rats were randomly divided into two groups and given either a high fructose diet or a normal diet. BCAA levels as well as blood glucose and lipid levels were measured at different time points of feeding. The mRNA expression levels of two key enzymes of BCAA catabolism, ACAD (acyl-CoA dehydrogenase) and BCKDH (branched-chain α-keto acid dehydrogenase), were measured by qPCR, and the protein expression levels of these two enzymes were analyzed by immunohistochemistry. Finally, the metabolite expression differences between the two groups were analyzed by Q300 metabolomics technology. Our study confirms that defects in the catabolic pathways of BCAAs lead to increased levels of circulating BCAAs, resulting in disorders of glucose and lipid metabolism characterized by insulin resistance by affecting metabolic pathways associated with amino acids and bile acids.PMID:37522853 | DOI:10.1530/EC-23-0079

Microbiol Spectr. 2023 Jul 31:e0057723. doi: 10.1128/spectrum.00577-23. Online ahead of print.ABSTRACTPulmonary tuberculosis (PTB) and diabetes mellitus (DM) are common chronic diseases that threaten human health. Patients with DM are susceptible to PTB, an important factor that aggravates the complications of diabetes. However, the molecular regulatory mechanism underlying the susceptibility of patients with DM to PTB infection remains unknown. In this study, healthy subjects, patients with primary PTB, and patients with primary PTB complicated by DM were recruited according to inclusion and exclusion criteria. Peripheral whole blood was collected, and alteration profiles and potential molecular mechanisms were further analyzed using integrated bioinformatics analysis of metabolomics and transcriptomics. Transcriptional data revealed that lipocalin 2 (LCN2), defensin alpha 1 (DEFA1), peptidoglycan recognition protein 1 (PGLYRP1), and integrin subunit alpha 2b (ITGA2B) were significantly upregulated, while chloride intracellular channel 3 (CLIC3) was significantly downregulated in the group with PTB and DM (PTB_DM) in contrast to the healthy control (HC) group. Additionally, the interleukin 17 (IL-17), phosphatidylinositol 3-kinase (PI3K)-AKT, and peroxisome proliferator-activated receptor (PPAR) signaling pathways are important for PTB infection and regulation of PTB-complicated diabetes. Metabolomic data showed that glycerophospholipid metabolism, carbon metabolism, and fat digestion and absorption processes were enriched in the differential metabolic analysis. Finally, integrated analysis of both metabolomic and transcriptomic data indicated that the NOTCH1/JAK/STAT signaling pathway is important in PTB complicated by DM. In conclusion, PTB infection altered the transcriptional and metabolic profiles of patients with DM. Metabolomic and transcriptomic changes were highly correlated in PTB patients with DM. Peripheral metabolite levels may be used as biomarkers for PTB management in patients with DM. IMPORTANCE The comorbidity of diabetes mellitus (DM) significantly increases the risk of tuberculosis infection and adverse tuberculosis treatment outcomes. Most previous studies have focused on the relationship between the effect of blood glucose control and the outcome of antituberculosis treatment in pulmonary tuberculosis (PTB) with DM (PTB_DM); however, early prediction and the underlying molecular mechanism of susceptibility to PTB infection in patients with DM remain unclear. In this study, transcriptome sequencing and untargeted metabolomics were performed to elucidate the key molecules and signaling pathways involved in PTB infection and the susceptibility of patients with diabetes to PTB. Our findings contribute to the development of vital diagnostic biomarkers for PTB or PTB_DM and provide a comprehensive understanding of molecular regulation during disease progression.PMID:37522815 | DOI:10.1128/spectrum.00577-23

Int J Med Mushrooms. 2023;25(6):1-20. doi: 10.1615/IntJMedMushrooms.2023048295.ABSTRACTPleurotus spp. have been gaining popularity as a source for the creation of functional foods, nutraceuticals and novel pharmaceuticals. Despite Pleurotus is a specious genus including 208 legitimate species, only a few of them such as P. ostreatus are commercially accessible. The genetic and metabolic diversity of Pleurotus both at specific and subspecific level is therefore of main concern for many researchers. In addition to the conventional morphological approach, molecular and biochemical markers have been greatly contributing to investigate these issues. In this study, samples from six Pleurotus species (P. eryngii is represented by three varieties) were molecularly identified and the phylogeny was inferred to assess the relationships between the various taxa. Strains in pure culture obtained from 6 out of 7 species were cultivated as mycelium in vitro to investigate the metabolites by untargeted LC-MS/MS-based metabolomics. The results pointed out species-specific metabolite patterns and highlighted a clear difference between the P. eryngii group and P. ostreatus, although the latter appears more versatile depending on the strain. This is the first study pointing out and comparing different metabolite patterns in Italian samples of Pleurotus species, including P. eryngii varieties.PMID:37522529 | DOI:10.1615/IntJMedMushrooms.2023048295

Plant J. 2023 Jul 31. doi: 10.1111/tpj.16406. Online ahead of print.ABSTRACTDiurnal dark to light transition causes profound physiological changes in plant metabolism. These changes require distinct modes of regulation as a unique feature of photosynthetic lifestyle. The activities of several key metabolic enzymes are regulated by light-dependent post-translational modifications (PTM) and have been studied at depth at the level of individual proteins. In contrast, a global picture of the light-dependent PTMome dynamics is lacking, leaving the response of a large proportion of cellular function undefined. Here, we investigated the light-dependent metabolome and proteome changes in Arabidopsis rosettes in a time resolved manner to dissect their kinetic interplay, focusing on phosphorylation, lysine acetylation, and cysteine-based redox switches. Of over 24 000 PTM sites that were detected, more than 1700 were changed during the transition from dark to light. While the first changes, as measured 5 min after onset of illumination, occurred mainly in the chloroplasts, PTM changes at proteins in other compartments coincided with the full activation of the Calvin-Benson cycle and the synthesis of sugars at later timepoints. Our data reveal connections between metabolism and PTM-based regulation throughout the cell. The comprehensive multiome profiling analysis provides unique insight into the extent by which photosynthesis reprograms global cell function and adds a powerful resource for the dissection of diverse cellular processes in the context of photosynthetic function.PMID:37522418 | DOI:10.1111/tpj.16406

Cardiovasc Res. 2023 Jul 31:cvad124. doi: 10.1093/cvr/cvad124. Online ahead of print.ABSTRACTAIMS: Mitochondria play a vital role in cellular metabolism and energetics and support normal cardiac function. Disrupted mitochondrial function and homeostasis cause a variety of heart diseases. Fam210a (family with sequence similarity 210 member A), a novel mitochondrial gene, is identified as a hub gene in mouse cardiac remodeling by multi-omics studies. Human FAM210A mutations are associated with sarcopenia. However, the physiological role and molecular function of FAM210A remain elusive in the heart. We aim to determine the biological role and molecular mechanism of FAM210A in regulating mitochondrial function and cardiac health in vivo.METHODS AND RESULTS: Tamoxifen-induced αMHCMCM-driven conditional knockout of Fam210a in the mouse cardiomyocytes induced progressive dilated cardiomyopathy and heart failure, ultimately causing mortality. Fam210a deficient cardiomyocytes exhibit severe mitochondrial morphological disruption and functional decline accompanied by myofilament disarray at the late stage of cardiomyopathy. Furthermore, we observed increased mitochondrial reactive oxygen species production, disturbed mitochondrial membrane potential, and reduced respiratory activity in cardiomyocytes at the early stage before contractile dysfunction and heart failure. Multi-omics analyses indicate that FAM210A deficiency persistently activates integrated stress response (ISR), resulting in transcriptomic, translatomic, proteomic, and metabolomic reprogramming, ultimately leading to pathogenic progression of heart failure. Mechanistically, mitochondrial polysome profiling analysis shows that FAM210A loss of function compromises mitochondrial mRNA translation and leads to reduced mitochondrial encoded proteins, followed by disrupted proteostasis. We observed decreased FAM210A protein expression in human ischemic heart failure and mouse myocardial infarction tissue samples. To further corroborate FAM210A function in the heart, AAV9-mediated overexpression of FAM210A promotes mitochondrial-encoded protein expression, improves cardiac mitochondrial function, and partially rescues murine hearts from cardiac remodeling and damage in ischemia-induced heart failure.CONCLUSION: These results suggest that FAM210A is a mitochondrial translation regulator to maintain mitochondrial homeostasis and normal cardiomyocyte contractile function. This study also offers a new therapeutic target for treating ischemic heart disease.PMID:37522353 | DOI:10.1093/cvr/cvad124

Front Public Health. 2023 Jul 13;11:1147403. doi: 10.3389/fpubh.2023.1147403. eCollection 2023.ABSTRACTBACKGROUND: Protecting and improving the personal health of healthcare workers is critical to improving the efficiency and quality of care. To effectively meet the needs of the emergency service system, emergency physicians need to be in a good state of health. However, due to the special characteristics of work in the emergency department, emergency physicians have to face various psychosocial pressures, which may bring them physical and mental distress. Therefore, this study aims to explore the emergency physicians' self-rated health status and its related factors, to provide an empirical study for the improvement of emergency physicians' self-rated health status.METHOD: A cross-sectional survey of emergency physicians was conducted in China between July and August 2018. The questionnaires contained items on demographic characteristics, behavioral lifestyle and job-related factors, as well as self-rated health. The generalized ordinal logistic model was used to identify related factors of emergency physicians' self-rated health status.RESULTS: Only 14.4% of Chinese emergency physicians considered themselves in good health status. Results showed that emergency physicians who never exercised (β = 0.76, p < 0.001) and exercised <2 times per week (β = 0.34, p < 0.001) were more likely to report poor health status. In addition, emergency physicians with good sleep quality (β = -3.84, p < 0.001), fewer night work shifts (β = -0.47, p < 0.001), less frequency of visiting patients (β = -0.33, p < 0.001), never suffered the workplace violence (β = -0.47, p < 0.001) and never perceived effort-reward imbalance (β = -0.68, p < 0.001) were more likely to report good self-rated health.CONCLUSION: Chinese emergency physicians' self-rated health status was not optimistic. Self-rated health is associated with multiple domains of work-related factors and personal lifestyle. Feasible measures should be taken to improve the working environment of emergency physicians, develop acceptable shift schedules for employees, monitor and maintain the health status of emergency department physicians.PMID:37521980 | PMC:PMC10372430 | DOI:10.3389/fpubh.2023.1147403

Front Med (Lausanne). 2023 Jul 13;10:1162808. doi: 10.3389/fmed.2023.1162808. eCollection 2023.ABSTRACTWe independently analyzed two large public domain datasets that contain 1H-NMR spectral data from lung cancer and sex studies. The biobanks were sourced from the Karlsruhe Metabolomics and Nutrition (KarMeN) study and Bayesian Automated Metabolite Analyzer for NMR data (BATMAN) study. Our approach of applying novel artificial intelligence (AI)-based algorithms to NMR is an attempt to globalize metabolomics and demonstrate its clinical applications. The intention of this study was to analyze the resulting spectra in the biobanks via AI application to demonstrate its clinical applications. This technique enables metabolite mapping in areas of localized enrichment as a measure of true activity while also allowing for the accurate categorization of phenotypes.PMID:37521348 | PMC:PMC10373878 | DOI:10.3389/fmed.2023.1162808

Front Immunol. 2023 Jul 14;14:1205616. doi: 10.3389/fimmu.2023.1205616. eCollection 2023.ABSTRACTINTRODUCTION: Assessing labial salivary gland exocrinopathy is a cornerstone in primary Sjögren's syndrome. Currently this relies on the histopathologic diagnosis of focal lymphocytic sialadenitis and computing a focus score by counting lym=phocyte foci. However, those lesions represent advanced stages of primary Sjögren's syndrome, although earlier recognition of primary Sjögren's syndrome and its effective treatment could prevent irreversible damage to labial salivary gland. This study aimed at finding early biomarkers of primary Sjögren's syndrome in labial salivary gland combining metabolomics and machine-learning approaches.METHODS: We used a standardized targeted metabolomic approach involving high performance liquid chromatography coupled with mass spectrometry among newly diagnosed primary Sjögren's syndrome (n=40) and non- primary Sjögren's syndrome sicca (n=40) participants in a prospective cohort. A metabolic signature predictive of primary Sjögren's syndrome status was explored using linear (logistic regression with elastic-net regularization) and non-linear (random forests) machine learning architectures, after splitting the data set into training, validation, and test sets.RESULTS: Among 126 metabolites accurately measured, we identified a discriminant signature composed of six metabolites with robust performances (ROC-AUC = 0.86) for predicting primary Sjögren's syndrome status. This signature included the well-known immune-metabolite kynurenine and five phospholipids (LysoPC C28:0; PCaa C26:0; PCaaC30:2; PCae C30:1, and PCaeC30:2). It was split into two main components: the first including the phospholipids was related to the intensity of lymphocytic infiltrates in salivary glands, while the second represented by kynurenine was independently associated with the presence of anti-SSA antibodies in participant serum.CONCLUSION: Our results reveal an immuno-lipidomic signature in labial salivary gland that accurately distinguishes early primary Sjögren's syndrome from other causes of sicca symptoms.PMID:37520535 | PMC:PMC10375713 | DOI:10.3389/fimmu.2023.1205616

Front Immunol. 2023 Jul 14;14:1168308. doi: 10.3389/fimmu.2023.1168308. eCollection 2023.ABSTRACTINTRODUCTION: To control the COVID-19 pandemic, great efforts have been made to realize herd immunity by vaccination since 2020. Unfortunately, most of the vaccines against COVID-19 were approved in emergency without a full-cycle and comprehensive evaluation process as recommended to the previous vaccines. Metabolome has a close tie with the phenotype and can sensitively reflect the responses to stimuli, rendering metabolomic analysis have the potential to appraise and monitor vaccine effects authentically.METHODS: In this study, a retrospective study was carried out for 330 Chinese volunteers receiving recommended two-dose CoronaVac, a vaccine approved in emergency in 2020. Venous blood was sampled before and after vaccination at 5 separate time points for all the recipients. Routine clinical laboratory analysis, metabolomic and lipidomic analysis data were collected.RESULTS AND DISCUSSION: It was found that the serum antibody-positive rate of this population was around 81.82%. Most of the laboratory parameters were slightly perturbated within the relevant reference intervals after vaccination. The metabolomic and lipidomic analyses showed that the metabolic shift after inoculation was mainly in the glycolysis, tricarboxylic acid cycle, amino acid metabolism, urea cycle, as well as microbe-related metabolism (bile acid metabolism, tryptophan metabolism and phenylalanine metabolism). Time-course metabolome changes were found in parallel with the progress of immunity establishment and peripheral immune cell counting fluctuation, proving metabolomics analysis was an applicable solution to evaluate immune effects complementary to traditional antibody detection. Taurocholic acid, lysophosphatidylcholine 16:0 sn-1, glutamic acid, and phenylalanine were defined as valuable metabolite markers to indicate the establishment of immunity after vaccination. Integrated with the traditional laboratory analysis, this study provided a feasible metabolomics-based solution to relatively comprehensively evaluate vaccines approved under emergency.PMID:37520533 | PMC:PMC10375237 | DOI:10.3389/fimmu.2023.1168308

Front Mol Neurosci. 2023 Jul 13;16:1215637. doi: 10.3389/fnmol.2023.1215637. eCollection 2023.ABSTRACTINTRODUCTION: Vascular dementia (VaD) is one of the most common causes of dementia among the elderly. Despite this, the molecular basis of VaD remains poorly characterized when compared to other age-related dementias. Pervasive cerebral elevations of urea have recently been reported in several dementias; however, a similar analysis was not yet available for VaD.METHODS: Here, we utilized ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to measure urea levels from seven brain regions in post-mortem tissue from cases of VaD (n = 10) and controls (n = 8/9). Brain-urea measurements from our previous investigations of several dementias were also used to generate comparisons with VaD.RESULTS: Elevated urea levels ranging from 2.2- to 2.4-fold-change in VaD cases were identified in six out of the seven regions analysed, which are similar in magnitude to those observed in uremic encephalopathy. Fold-elevation of urea was highest in the basal ganglia and hippocampus (2.4-fold-change), consistent with the observation that these regions are severely affected in VaD.DISCUSSION: Taken together, these data not only describe a multiregional elevation of brain-urea levels in VaD but also imply the existence of a common urea-mediated disease mechanism that is now known to be present in at least four of the main age-related dementias.PMID:37520429 | PMC:PMC10372345 | DOI:10.3389/fnmol.2023.1215637

Front Microbiol. 2023 Jul 13;14:1210288. doi: 10.3389/fmicb.2023.1210288. eCollection 2023.ABSTRACTIn this study, the function of a non-ribosomal peptide synthetase-like (NRPS-like) encoding gene AOL_s00188g306 (g306) was investigated to reveal the association between NRPS and nematocidal activity in the nematode-trapping fungus Arthrobotrys oligospora. Sequence analysis indicated that the encoded product of g306 is an adenylation domain of non-ribosomal peptide synthetases and extended short-chain dehydrogenase/reductase domain-containing proteins, and displays a wide substrate spectrum. The Δg306 mutants were more sensitive to chemical stressors than the wild type. Disruption of g306 impeded the nematocidal efficiency of A. oligospora. Metabolomics analysis showed that secondary metabolite biosynthesis and lipid metabolism were altered in the mutants. The phenotypic changes in the mutants can be attributed to the down-regulation of various metabolites, including fatty acyls, prenol lipids, steroidsand steroid derivative, and amino acid derivatives, identified in the present study. This study investigated the association between the non-ribosomal polypeptide-encoding gene g306 and nematicidal activity in A. oligospora, providing a reference for resolving the predation mechanism of nematode-trapping fungus.PMID:37520361 | PMC:PMC10373296 | DOI:10.3389/fmicb.2023.1210288

Front Microbiol. 2023 Jul 13;14:1218152. doi: 10.3389/fmicb.2023.1218152. eCollection 2023.ABSTRACTINTRODUCTION: The Chinese mitten crab (Eriocheir sinensis) is a highly valued freshwater crustacean in China. While the natural shell color of E. sinensis is greenish brown (GH), we found a variety with a brownish-orange shell color (RH). Although RH is more expensive, it exhibits a lower molting frequency and growth rate compared with GH, which significantly reduces its yield and hinders large-scale farming. The growth and development of animals are closely related to their gut microbiota and gut tissue metabolic profiles.METHODS: In this study, we compared the gut microbiome communities and metabolic profiles of juvenile RH and GH crabs using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS), respectively.RESULTS: Our findings indicated that the intestinal microbial composition and metabolic characteristics of E. sinensis differed significantly between RH and GH. At the operational taxonomic unit (OTU) level, the α-diversity of the gut microbiota did not differ significantly between RH and GH, while the β-diversity of the RH gut microbiota was higher than that of the GH gut microbiota. At the species level, the richness of unclassified_c_Alphaproteobacteria was significantly higher in the GH group, while the RH group had a significantly higher richness of three low-abundance species, Flavobacteria bacterium BAL38, Paraburkholderia ferrariae, and uncultured_bacterium_g__Legionella. In the current study, 598 gut tissue metabolites were identified, and 159 metabolites were significantly different between GH and RH. The metabolite profile of RH was characteristic of a low level of most amino acids and lipid metabolites and a high level of several pigments compared with that of GH. These metabolites were enriched in 102 KEGG pathways. Four pathways, including (1) Central carbon metabolism in cancer, (2) protein digestion and absorption, (3) alanine, aspartate and glutamate metabolism, and (4) aminoacyl-tRNA biosynthesis, were significantly enriched. The correlation analysis between metabolites and microbiotas indicated that most key differential metabolites were positively correlated with the abundance of Shewanella_sp_MR-7.DISCUSSION: This research provided a greater understanding of the physiological conditions of E. sinensis varieties with different shell colors by comparing the gut microbiota and gut tissue metabolome.PMID:37520354 | PMC:PMC10374289 | DOI:10.3389/fmicb.2023.1218152

Front Microbiol. 2023 Jul 14;14:1224096. doi: 10.3389/fmicb.2023.1224096. eCollection 2023.ABSTRACTTranscription factors in phytopathogenic fungi are key players due to their gene expression regulation leading to fungal growth and pathogenicity. The KilA-N family encompasses transcription factors unique to fungi, and the Bqt4 subfamily is included in it and is poorly understood in filamentous fungi. In this study, we evaluated the role in growth and pathogenesis of the homologous of Bqt4, FspTF, in Fusarium sp. isolated from the ambrosia beetle Xylosandrus morigerus through the characterization of a CRISPR/Cas9 edited strain in Fsptf. The phenotypic analysis revealed that TF65-6, the edited strain, modified its mycelia growth and conidia production, exhibited affectation in mycelia and culture pigmentation, and in the response to certain stress conditions. In addition, the plant infection process was compromised. Untargeted metabolomic and transcriptomic analysis, clearly showed that FspTF may regulate secondary metabolism, transmembrane transport, virulence, and diverse metabolic pathways such as lipid metabolism, and signal transduction. These data highlight for the first time the biological relevance of an orthologue of Bqt4 in Fusarium sp. associated with an ambrosia beetle.PMID:37520351 | PMC:PMC10375492 | DOI:10.3389/fmicb.2023.1224096