PubMed

Talanta. 2024 Oct 28;283:127109. doi: 10.1016/j.talanta.2024.127109. Online ahead of print.ABSTRACTDeveloping efficient and comprehensive analysis methods for metabolomics and lipidomics in the biological tissues and body fluids is essential for understanding the disease mechanisms. Although various two-dimensional liquid chromatography-mass spectrometry (2D-LC-MS) methods have been proposed to expand metabolite coverage, achieving higher efficiency in integrated metabolomics and lipidomics studies remains a technical challenge. In this work, a novel 4in1 online analysis system with excellent reproducibility and mass accuracy was constructed for metabolomics and lipidomics study in various biological samples from atherosclerotic mice. This system enabled the simultaneous detection in both positive and negative ion modes with extensive polarity separation in a single analytical run. Using the 4in1 online analysis system, we identified distinct but complementary metabolic signatures associated with atherosclerosis in different biological samples. Specifically, a total of 230 and 170 differential metabolites or lipids were detected in mice plasma samples and aortic tissue samples, respectively, including glycerophospholipids, sphingolipids, fatty acyls, glycerolipids, carboxylic acids, and pyrimidine nucleosides. Additionally, atherosclerosis-related metabolic pathways involved in biosynthesis of unsaturated fatty acids, sphingolipid metabolism, cholesterol metabolism, glycerophospholipid metabolism, and choline metabolism further revealed. These findings demonstrate that the novel 4in1 online analysis system is a faithful, stable and powerful tool for comprehensive metabolomics and lipidomics studies in complex biological matrices.PMID:39481347 | DOI:10.1016/j.talanta.2024.127109

Plant Physiol Biochem. 2024 Oct 24;217:109236. doi: 10.1016/j.plaphy.2024.109236. Online ahead of print.ABSTRACTDrought stress is a common hazard faced by sugarcane growth, and utilizing microorganisms to enhance plant tolerance to abiotic stress has become an important method for sustainable agricultural development. Several studies have demonstrated that Streptomyces chartreuses WZS021 improves sugarcane tolerance to drought stress. However, the molecular mechanisms underlying tolerance at the transcriptional and metabolomic levels remain unclear. We comprehensively evaluated the physiological and molecular mechanisms by which WZS021 enhances drought tolerance in sugarcane, by performing transcriptome sequencing and non-targeted metabolomics; and examining rhizosphere soil properties and plant tissue antioxidant capacity. WZS021 inoculation improved the rhizosphere nutritional environment (AP, ammonia, OM) of sugarcane and enhanced the antioxidant capacity of plant roots, stems, and leaves (POD, SOD, CAT). Comprehensive analyses of the transcriptome and metabolome revealed that WZS021 mainly affects plant drought tolerance through phenylalanine metabolism, plant hormone signal transduction, and flavonoid biosynthesis pathways. The drought tolerance signaling molecules mediated by WZS021 include petunidin, salicylic acid, α-Linoleic acid, auxin, geranylgeraniol and phenylalanine, as well as key genes related to plant hormone signaling transduction (YUCCA, amiE, AUX, CYPs, PAL, etc.). Interestingly, inoculation with WZS021 during regular watering induces a transcriptome-level response to biological stress in sugarcane plants. This study further elucidates a WZS021-dependent rhizosphere-mediated regulatory mechanism for improving sugarcane drought tolerance, providing a theoretical basis for increasing sugarcane production capacity.PMID:39481196 | DOI:10.1016/j.plaphy.2024.109236

Chem Biodivers. 2024 Oct 31:e202401747. doi: 10.1002/cbdv.202401747. Online ahead of print.ABSTRACTFusarium verticillioides is a prevalent plant pathogenic fungus known to produce harmful mycotoxins, including fumonisins and emerging toxins. This study aimed to investigate the influence of substrate on the temporal patterns of mycotoxin biosynthesis by F. verticillioides, employing a combined OSMAC (One Strain-Many Compounds) strategy and metabolomics approach. The fungus was cultured under various media conditions, and samples were collected over time. LC-MS/MS analyses and a dereplicative workflow were used to profile the secondary metabolite production, focusing on mycotoxins. The results demonstrated that modifying the culture conditions led to significant variations in fungal growth and the nature and relative concentrations of mycotoxins produced. Corn meal agar (CMA) medium was favorable for fumonisins A1 and B1, while malt extract agar (MEA) favored fumonisins A2 and B2. The study also identified the production of other mycotoxins related compounds as fusarins, bikaverin derivatives and fumonisins analogs, under different growth conditions. This study highlights the potential of combining OSMAC and metabolomics to unravel the substrate-dependent and time-dependent variations in mycotoxin biosynthesis by F. verticillioides. The insights gained provide a better understanding of the ecophysiology of this fungus and the occurrence of its mycotoxins, which can inform targeted mitigation strategies to ensure food and feed safety.PMID:39481006 | DOI:10.1002/cbdv.202401747

J Diabetes Investig. 2024 Oct 31. doi: 10.1111/jdi.14334. Online ahead of print.ABSTRACTAIMS/INTRODUCTION: The aim of this study was to identify a metabolic signature of MIDD as compared to healthy controls and other types of diabetes.METHODS: We performed a comprehensive serum metabolomic analysis using gas chromatography-time of flight mass spectrometry (GC-TOFMS) in participants diagnosed with MIDD (n = 14), latent autoimmune diabetes in adults (LADA) (n = 14), type 2 diabetes mellitus (n = 14), and healthy controls (n = 14). Each group was matched for gender and age.RESULTS: There were significant metabolic differences among MIDD and other diabetic and control groups. Compared with control, MIDD patients had high levels of carbohydrates (glucose, galactose, mannose, sorbose, and maltose), fatty acids (2-Hydroxybutyric acid, eicosapentaenoic acid, and octadecanoic acid), and other metabolites (alanine, threonic acid, cholesterol, lactic acid, and gluconic acid), but low level of threonine. Compared with LADA, MIDD patients had high levels of threonic acid and some amino acids (alanine, tryptophan, histidine, proline, glutamine, and creatine) but low levels of serine. Compared with type 2 diabetes mellitus, MIDD patients had high levels of citrulline, creatine, 3-Amino-2-piperidone, but low levels of ornithine, fatty acids (arachidonic acid and octadecanoic acid), and intermediates of the tricarboxylic acid cycle (malic acid and succinic acid).CONCLUSIONS: Our study identified a specific metabolic profile related to glycolysis and the tricarboxylic acid cycle in MIDD that differs from healthy controls and other types of diabetes. This unique metabolic signature provides new perspectives for understanding the pathophysiology and underlying mechanisms of MIDD.PMID:39480690 | DOI:10.1111/jdi.14334

Plast Reconstr Surg. 2024 Nov 1;154(5):895e-905e. doi: 10.1097/PRS.0000000000011335. Epub 2024 Feb 14.ABSTRACTBACKGROUND: Microfat and nanofat are commonly used in various surgical procedures, from skin rejuvenation to scar correction, to contribute to tissue regeneration. Microfat contains mainly adipocytes and is well suited for tissue augmentation, and nanofat is rich in lipids, adipose-derived stem cells, microvascular fragments, and growth factors, making it attractive for aesthetic use. The authors have previously demonstrated that the mechanical processing of microfat into nanofat significantly changes its proteomic profile. Considering that mechanical fractionation leads to adipocyte disruption and lipid release, they aimed to analyze their lipidomic profiles for their regenerative properties.METHODS: Microfat and nanofat samples were isolated from 14 healthy patients. Lipidomic profiling was performed by liquid chromatography tandem mass spectrometry. The resulting data were compared against the Human Metabolome and LIPID MAPS Structure Database. MetaboAnalyst was used to analyze metabolic pathways and lipids of interest.RESULTS: From 2388 mass-to-charge ratio features, metabolic pathway enrichment analysis of microfat and nanofat samples revealed 109 pathways that were significantly enriched. Microfat samples revealed higher-intensity levels of sphingosines, different eicosanoids, and fat-soluble vitamins. Increased levels of coumaric acids and prostacyclin were found in nanofat.CONCLUSIONS: This is the first study to analyze the lipidomic profiles of microfat and nanofat, providing evidence that mechanical emulsification of microfat into nanofat leads to changes in their lipid profiles. From 109 biological pathways, antiinflammatory, antifibrotic, and antimelanogenic lipid mediators were particularly enriched in nanofat samples when compared with microfat. Although further studies are necessary for a deeper understanding of the composition of these specific lipid mediators in nanofat samples, the authors propose that they might contribute to its regenerative effects on tissue.CLINICAL RELEVANCE STATEMENT: Profiling the unique lipid mediators in nanofat and microfat enhances our understanding of their different therapeutic effects and allows us to link these specific mediators to antiinflammatory, pro-regenerative, or healing properties. Ultimately, this insight can advance personalized therapeutic strategies, where a specific type of fat is selected based on its optimal therapeutic effect.PMID:39480647 | DOI:10.1097/PRS.0000000000011335

J Proteome Res. 2024 Oct 31. doi: 10.1021/acs.jproteome.4c00578. Online ahead of print.ABSTRACTThe disruption of gut microbiota caused by antibiotics favors the intestinal colonization of Clostridioides difficile - a Gram-positive, spore-forming anaerobic bacterium that causes potentially fatal gastrointestinal infections. In an endeavor to elucidate the complexities of the gut-brain axis in the context of Clostridium difficile infection (CDI), a murine model has been used to investigate the potential effects of antibiotic administration and subsequent colonization by C. difficile, as well as the impact of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the cecal metabolome for the first time. This follows our previous research which highlighted the metabolic effect of CDI and these treatments in the brain and employs the same four different metabolomics-based methods (targeted GC-MS/MS, targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS and untargeted GC-MS). A total of 286 unique metabolites have been identified in the mouse cecal profiles and statistical analysis revealed that CDI, as well as the subsequent treatments, significantly alters cecal metabolites and lipids implicated in various biochemical pathways centered around amino acid metabolism, glycerophospholipid metabolism, and central carbon metabolism. To our knowledge, this study represents the first exploration of the effects of C. difficile-induced colitis and potential treatments on the cecal tissue metabolome.PMID:39480487 | DOI:10.1021/acs.jproteome.4c00578

J Agric Food Chem. 2024 Oct 31. doi: 10.1021/acs.jafc.4c04316. Online ahead of print.ABSTRACTA nonthermal pretreatment using dielectric barrier discharge cold plasma (DBD-CP) was developed to improve the stress resistance of paddy rice during postharvest storage. The physicochemical properties, bioactive characteristics, and secondary metabolites of paddy rice were assessed after applying an optimized DBD-CP procedure, with enzyme activities and gene expression monitored over a 60 day storage period at 35 °C. A 17.06% reduction in the total color change index was noted in the DBD-CP group. Bioactive compounds, particularly gallic acid, were significantly increased, enhancing the defense mechanisms against high-temperature stress. Nontargeted metabolomics analysis indicated an upregulation of phenylpropanoid metabolism in DBD-CP-treated rice compared to controls, with notable increases in secondary metabolites such as coumaric acid, caffeic acid, and sinapic acid, suggesting potential biomarkers for stress resistance. Further verification showed significant enhancements in key enzymes of phenylpropanoid metabolism, including phenylalanine ammonia lyase (PAL), cinnamic acid-4-hydroxylase (C4H), plant coumaric acid-3-hydroxylase (C3H), and cinnamyl alcohol dehydrogenase (CAD), with increases ranging from 1.71 to 2.28 times. Gene expression levels of OsPAL7, OsC4H4, and OsCAD2 aligned with these enzymatic changes post-DBD-CP treatment. In conclusion, DBD-CP treatment can modulate phenylpropanoid metabolism in paddy rice, thereby enhancing bioactive compound levels to reduce stress damage during high-temperature storage.PMID:39480226 | DOI:10.1021/acs.jafc.4c04316

J Proteome Res. 2024 Oct 31. doi: 10.1021/acs.jproteome.4c00586. Online ahead of print.ABSTRACTRecent improvements in proteomics technologies have fundamentally altered our capacities to characterize human biology. There is an ever-growing interest in using these novel methods for studying the circulating proteome, as blood offers an accessible window into human health. However, every methodological innovation and analytical progress calls for reassessing our existing approaches and routines to ensure that the new data will add value to the greater biomedical research community and avoid previous errors. As representatives of HUPO's Human Plasma Proteome Project (HPPP), we present our 2024 survey of the current progress in our community, including the latest build of the Human Plasma Proteome PeptideAtlas that now comprises 4608 proteins detected in 113 data sets. We then discuss the updates of established proteomics methods, emerging technologies, and investigations of proteoforms, protein networks, extracellualr vesicles, circulating antibodies and microsamples. Finally, we provide a prospective view of using the current and emerging proteomics tools in studies of circulating proteins.PMID:39479990 | DOI:10.1021/acs.jproteome.4c00586

Food Funct. 2024 Oct 31. doi: 10.1039/d4fo03826f. Online ahead of print.ABSTRACTThis study revealed for the first time the anti-obesity effect of summer-autumn tea aqueous extract (SATE) and its underlying mechanism. High-fat diet (HFD)-fed C57BL/6J mice were treated with or without 400 mg kg-1 SATE for 12 weeks, and administration of SATE significantly ameliorated glucolipid metabolism disorder and induced beige-fat development and brown adipose tissue (BAT)-derived non-shivering thermogenesis via the AMPK-PGC-1α-UCP1 signal axis in HFD-fed mice. 16S rDNA-based microbiota and targeted metabolomics analyses indicated that SATE improved intestinal microbiota dysbiosis and microbial metabolism abnormality caused by HFD, reflected by a dramatic increase in the relative abundance of Muribaculaceae, Bifidobacterium and Odoribacter and production of short-chain fatty acids (SCFAs). Interestingly, SATE-induced thermogenesis was highly correlated with the reconstruction of the gut microbiome and the formation of SCFAs. These findings suggest that SATE has the potential to alleviate obesity by activating adipose browning and thermogenesis in association with the reconstruction of the gut microbiota and its metabolites, providing a theoretical foundation for summer-autumn tea as a functional tea to prevent obesity.PMID:39479981 | DOI:10.1039/d4fo03826f

Anal Chem. 2024 Oct 31. doi: 10.1021/acs.analchem.4c01778. Online ahead of print.ABSTRACTBees produce honey through the collection and transformation of nectar, whose botanical origin impacts the taste, nutritional value, and, therefore, the market price of the resulting honey. This phenomenon has led some to mislabel their honey so that it can be sold at a higher price. Metabolomics has been gaining popularity in food authentication, but rapid data mining algorithms are needed to facilitate the discovery of new authenticity markers. A nontargeted high-resolution liquid chromatography-mass spectrometry (HR/LC-MS) analysis of 262 monofloral honey samples, of which 50 were blueberry honey, was performed. Data mining methods were demonstrated for the discovery of binary single-markers (compound was only detected in blueberry honey), threshold single-markers (compound had the highest concentration in blueberry honey), and interval ratio-markers (the ratio of two compounds was within a unique interval in blueberry honey). A novel convolutional algorithm was developed for the discovery of interval ratio-markers, which trained 14× faster and achieved a 0.2 Matthews correlation coefficient (MCC) units higher classification score than existing open-source implementations. The convolutional algorithm also had classification performance similar to that of a brute-force search but trained 1521× faster. A pipeline for shortlisting candidate authenticity markers from the LC-MS spectra that may be suitable for chemical structure identification was also demonstrated and led to the identification of niacin as a blueberry honey threshold single-marker. This work demonstrates an end-to-end approach to mine the honey metabolome for novel authenticity markers and can readily be applied to other types of food and analytical chemistry instruments.PMID:39479961 | DOI:10.1021/acs.analchem.4c01778

Cancer Sci. 2024 Oct 31. doi: 10.1111/cas.16347. Online ahead of print.ABSTRACTCancer cells rely on mitochondrial oxidative phosphorylation (OXPHOS) and the noncanonical tricarboxylic acid (TCA) cycle. In this paper, we shed light on the vital role played by the noncanonical TCA cycle in a host-side concession to mitochondria, especially in highly energy-demanding malignant tumor cells. Inhibition of ATP-citrate lyase (ACLY), a key enzyme in the noncanonical TCA cycle, induced apoptosis by increasing reactive oxygen species levels and DNA damage while reducing mitochondrial membrane potential. The mitochondrial membrane citrate transporter inhibitor, CTPI2, synergistically enhanced these effects. ACLY inhibition reduced cytosolic citrate levels and CTPI2 lowered ACLY activity, suggesting that the noncanonical TCA cycle is sustained by a positive feedback mechanism. These inhibitions impaired ATP production, particularly through OXPHOS. Metabolomic analysis of mitochondrial and cytosolic fractions revealed reduced levels of glutathione pathway-related and TCA cycle-related metabolite, except fumarate, in mitochondria following noncanonical TCA cycle inhibition. Despite the efficient energy supply to the cell by mitochondria, this symbiosis poses challenges related to reactive oxygen species and mitochondrial maintenance. In conclusion, the noncanonical TCA cycle is indispensable for the canonical TCA cycle and mitochondrial integrity, contributing to mitochondrial domestication.PMID:39479926 | DOI:10.1111/cas.16347

Food Sci Nutr. 2024 Aug 7;12(10):7719-7736. doi: 10.1002/fsn3.4397. eCollection 2024 Oct.ABSTRACTAs a plant classified under the "medicine food homology" concept, garlic offers various health benefits and comes in many different varieties. In this study, the metabolite composition of different garlic varieties were analyzed using LC-MS/MS quadrupole-Orbitrap mass spectrometry and ICP-MS. A total of 30 chemical elements and 1256 metabolites were identified. Significant differences in chemical elements and metabolomics profiles were observed among the five garlic groups (VIP > 1.5). Compared to WG, PG contained 5 unique compounds, HG had 15 unique compounds, SCG had 18 unique compounds, and SBG had 26 unique compounds. Furthermore, the results showed that WG had smaller differences with PG and HG, but significant differences with SBG and SCG. KEGG analysis revealed metabolic pathways associated with the formation of differential metabolites. These findings uncover the differences and mechanisms in the composition of various garlic varieties, providing a theoretical foundation for distinguishing the nutritional components of different garlic types.PMID:39479693 | PMC:PMC11521672 | DOI:10.1002/fsn3.4397

Food Sci Nutr. 2024 Jul 16;12(10):7186-7201. doi: 10.1002/fsn3.4307. eCollection 2024 Oct.ABSTRACTThe determination of optimal levels of green tea amount and brewing time would have a crucial role in the accumulation of desired aromatic volatile compounds to meet worldwide market demand. Aroma is the most important factor influencing tea consumers' choices along with taste, price, and brand. This study aims to determine how the brewing time and amount of green tea affect the aroma profile of green tea infusion. The effect of the amount of Turkish green tea (5-10 g) and brewing time (5-60 min) on aromatic volatile compounds was evaluated using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) technique. The SPME/GC-MS analysis identified 57 components in the aroma profile of green tea infusions including 13 esters, 12 alkanes, 7 unknowns, 6 ketones, 3 alcohols, 2 terpenes, 2 terpenoids, 1 alkaloid, 1 phenolic compound, 1 lactone, 1 pyrazine, and 1 norisoprenoid. The green tea amount and brewing time had significant effects on the number of chemical compounds. A total of 42, 47, and 36 aromatic volatile compounds were determined by brewing 5, 7.5, and 10 g of green tea. The most abundant constituents in green tea infusions were phytone, 2-decenal, lauric acid, unknown 1, methoxy-1-methylethyl pyrazine, α-ionone, β-ionone, and diethyl phthalate (DEP). With this study, the aroma structures of green tea infusion have been revealed for the first time depending on the brewing time and quantity.PMID:39479672 | PMC:PMC11521698 | DOI:10.1002/fsn3.4307

Front Plant Sci. 2024 Oct 16;15:1408141. doi: 10.3389/fpls.2024.1408141. eCollection 2024.ABSTRACTINTRODUCTION: Nitrogen (N) and iron (Fe) are involved in several biochemical processes in living organisms, and their limited bioavailability is a strong constraint for plant growth and yield. This work investigated the interplay between Fe and N nutritional pathways in tomato plants kept under N and Fe deficiency and then resupplied with Fe and N (as nitrate, ammonium, or urea) through a physiological, metabolomics and gene expression study.RESULTS: After 24 hours of Fe resupply, the Fe concentration in Fe-deficient roots was dependent on the applied N form (following the pattern: nitrate > urea > ammonium > Fe-deficient control), and whereas in leaves of urea treated plants the Fe concentration was lower in comparison to the other N forms. Untargeted metabolomics pointed out distinctive modulations of plant metabolism in a treatment-dependent manner. Overall, N-containing metabolites were affected by the treatments in both leaves and roots, while N form significantly shaped the phytohormone profile. Moreover, the simultaneous application of Fe with N to Fe-deficient plants elicited secondary metabolites' accumulation, such as phenylpropanoids, depending on the applied N form (mainly by urea, followed by nitrate and ammonium). After 4 hours of treatment, ammonium- and urea-treated roots showed a reduction of enzymatic activity of Fe(III)-chelate reductase (FCR), compared to nitrate or N-depleted plants (maintained in Fe deficiency, where FCR was maintained at high levels). The response of nitrate-treated plants leads to the improvement of Fe concentration in tomato roots and the increase of Fe(II) transporter (IRT1) gene expression in tomato roots.CONCLUSIONS: Our results strengthen and improve the understanding about the interaction between N and Fe nutritional pathways, thinning the current knowledge gap.PMID:39479546 | PMC:PMC11521840 | DOI:10.3389/fpls.2024.1408141

R Soc Open Sci. 2024 Oct 30;11(10):240930. doi: 10.1098/rsos.240930. eCollection 2024 Oct.ABSTRACTLack of maternal milk commonly leads to Asian elephant calves' death in captivity. Currently, available supplements seem inefficient. Hence, we aimed at characterizing the composition of Asian elephant milk to provide information on calves' nutritional needs. Seventy milk samples from 22 Asian elephants living in semi-captivity in their natural environment in Myanmar were collected. Samples were analysed through various techniques including liquid chromatography tandem mass spectrometry, gas chromatography-flame ionization detector, and bicinchoninic acid assay to determine total protein content and various metabolites. Associations with lactation stage (months postpartum) were investigated through repeated measure mixed models. We identified 160 compounds: 22 amino acids, 12 organic acids of the tricarboxylic acid cycle, 27 fatty acids, 15 acyl-carnitines and 84 phospholipids. The milk contained substantial amounts of free glutamate (median: 1727.9, interquartile range (IQR): 1278.4 µmol l-1) and free glycine (2541.7, IQR: 1704.1 µmol l-1). The fatty acid profile was mostly constituted by saturated fatty acids, particularly capric acid (40.1, IQR: 67.3 g l-1). Milk samples also contained high amounts of carnitines, phospholipids and organic acids. The wide array of metabolites identified and quantified, some of which present high concentrations in the milk from this species as opposed to other species, suggests underpinning physiological functions that might be crucial for the survival of Asian elephant calves.PMID:39479244 | PMC:PMC11522882 | DOI:10.1098/rsos.240930

Front Chem. 2024 Oct 16;12:1504501. doi: 10.3389/fchem.2024.1504501. eCollection 2024.NO ABSTRACTPMID:39478992 | PMC:PMC11521952 | DOI:10.3389/fchem.2024.1504501

Gut Pathog. 2024 Oct 30;16(1):64. doi: 10.1186/s13099-024-00652-6.ABSTRACTSpecific intestinal metabolites are closely associated with the classification, severity, and necrosis of acute pancreatitis (AP) and provide novel insights for in-depth clinical investigations. In this study, the gut microbiota and metabolites of 49 AP patients at different treatment stages and severities were analysed via 16S rDNA sequencing and untargeted metabolomics to investigate the trends in gut microbiota composition and metabolome profiles observed in patients with severe AP. These findings revealed an imbalance in intestinal flora homeostasis among AP patients characterized by a decrease in probiotics and an increase in opportunistic pathogens, which leads to damage to the intestinal mucosal barrier through reduced short-chain fatty acid (SCFA) secretion and disruption of the intestinal epithelium. This dysbiosis influences energy metabolism, anti-inflammatory responses, and immune regulation, and these results highlight significant differences in energy metabolism pathways. These findings suggest that the differential composition of intestinal flora, along with alterations in intestinal metabolites and metabolic pathways, contribute to the compromised integrity of the intestinal mucosal barrier and disturbances in energy metabolism in patients with severe AP.PMID:39478598 | DOI:10.1186/s13099-024-00652-6

Microbiome. 2024 Oct 30;12(1):223. doi: 10.1186/s40168-024-01944-4.ABSTRACTBACKGROUND: Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important. Numerous studies have implicated the gut microbiome in pigs' fat deposition, but research into its suppression remains scarce. The Lulai black pig (LL) is a hybrid breed derived from the Laiwu pig (LW) and the Yorkshire pig, with lower levels of SCF compared to the LW. In this study, we focused on these breeds to identify microbiota that regulate fat deposition. The key questions were: Which microbial populations reduce fat in LL pigs compared to LW pigs, and what is the underlying regulatory mechanism?RESULTS: In this study, we identified four different microbial strains, Eubacterium siraeum, Treponema bryantii, Clostridium sp. CAG:413, and Jeotgalibaca dankookensis, prevalent in both LW and LL pigs. Blood metabolome analysis revealed 49 differential metabolites, including tanshinone IIA and royal jelly acid, known for their anti-adipogenic properties. E. siraeum was strongly correlated with these metabolites, and its genes and metabolites were enriched in pathways linked to fatty acid degradation, glycerophospholipid, and glycerolipid metabolism. In vivo mouse experiments confirmed that E. siraeum metabolites curb weight gain, reduce SCF adipocyte size, increase the number of brown adipocytes, and regulate leptin, IL-6, and insulin secretion. Finally, we found that one important pathway through which E. siraeum inhibits fat deposition is by suppressing the phosphorylation of key proteins in the PI3K/AKT signaling pathway through the reduction of tyrosine.CONCLUSIONS: We compared LW and LL pigs using fecal metagenomics, metabolomics, and blood metabolomics, identifying E. siraeum as a strain linked to fat deposition. Oral administration experiments in mice demonstrated that E. siraeum effectively inhibits fat accumulation, primarily through the suppression of the PI3K/AKT signaling pathway, a critical regulator of lipid metabolism. These findings provide a valuable theoretical basis for improving pork quality and offer insights relevant to the study of human obesity and related chronic metabolic diseases. Video Abstract.PMID:39478562 | DOI:10.1186/s40168-024-01944-4

BMC Neurol. 2024 Oct 31;24(1):423. doi: 10.1186/s12883-024-03926-3.ABSTRACTMultiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj < 0.05). However, they were negatively correlated with the amounts of other metabolites such as L-tyrosine and sphingosine 1-phosphate, as well as the concentrations of IL-8 and MIP-1α. This study outlined the underlying multi-omics integrated mechanisms that might regulate peripheral immunoinflammatory responses and MS progression. These findings are potentially helpful for developing new assisting diagnostic biomarker and therapeutic strategies for MS.PMID:39478468 | DOI:10.1186/s12883-024-03926-3

J Exp Bot. 2024 Oct 30:erae443. doi: 10.1093/jxb/erae443. Online ahead of print.ABSTRACTLeaves evolve shape diversity ranging from simple leaves with smooth margin to complicated shape with toothed/serrated, lobed and dissected leaves with leaflets. In the model plant Arabidopsis thaliana with simple leaves producing serrated margin, boundary regulatory factors CUP SHAPED COTYLEDON 2 (CUC2) and CUC3 play important roles in promoting leaf serration initiation and maintenance. Stem cell related WUSCHEL-RELATED HOMEOBOX1 (WOX1) and PRESSED FLOWER/WOX3 are also essential for leaf margin morphogenesis, but the role of WOX1 and PRS as well as the relationships between CUCs and WOXs on tooth development was unclear. In this study, we found that WOX1, but not PRS, prevents overproduction of tooth number and excessive tooth size by limiting CUC3 expression to a moderate level in a temporally regulated manner. We also revealed that BRASSINAZOLE RESISTANT 1 (BZR1), a known regulator for plant development including boundary regions, is involved in WOX1 negative regulation of tooth development by repressing CUC3 expression during the initiation/early stage of tooth development. WOX1 parallelly limits BZR1 and CUC3 expression from the late stage of the first 2 teeth, while restricts CUC3 activity in a BZR1 dependent manner from the initiation/early stage of subsequently developed teeth. This study uncovers a new mechanism for WOX1 in fine-tuning the leaf margin geometry.PMID:39478336 | DOI:10.1093/jxb/erae443