Fatty Acid Metabolism Pathways Research Articles

Identification of Potential Biomarkers and Spectral Fingerprinting for Detection of Foodborne Pathogens in Raw Chicken Meat Matrix Using GCMS and FTIR

Foodborne illnesses pose a serious threat to public health, with increasing global incidence rates driven by factors such as rising meat consumption. Rapid detection of foodborne pathogens in meat is critical for preventing outbreaks. This study investigates the potential of gas chromatography-mass spectrometry (GC-MS) and Fourier-transform infrared spectroscopy (FTIR) for identifying biomarkers and spectral fingerprints indicative of foodborne pathogens in raw chicken meat. Raw broiler chicken meat samples were surface-sterilized and inoculated with foodborne pathogens. The samples were challenge inoculated with the specific pathogen and the physical quality parameters like pH, color, texture, drip loss, and water activity were assessed. GC-MS analysis identified 113 metabolites, including potential biomarkers like ureidopropionic acid, 5-sulfosalicylic acid, 11,14-eicosadienoic acid, methyl ester for E. coli O157:H7; 11-bromoundecanoic acid, neocurdione, glafenin, eicosanoic acid for Salmonella; azepan-1-yl-acetic acid, methyl ester, tramadol, cytarabine, dipipanone for Staphylococcus and cyclopentaneundecanoic acid, phosphonofluoridic acid, î-n-formyl-l-lysine for Pseudomonas. Pathway analysis revealed the involvement of fatty acid metabolism and amino acid degradation pathways. FTIR spectral data showed significant variances between control and spiked samples, particularly in the fatty acid spectral region. The identified metabolites and spectral patterns could serve as biomarkers for developing rapid pathogen detection methods, contributing to enhanced food safety protocols.

Genetic Loci Mining and Candidate Gene Analysis for Determining Fatty Acid Composition in Rice

Fatty acid composition and its proportions are critical to the nutritional value and storage quality of rice (Oryza sativa L.) as the third major nutrient component in this staple food. This study involved crossing an indica rice variety, Huazhan (HZ), as the male parent, with a japonica variety, Nekken2, as the female parent, to produce the F1 generation. Subsequently, a population of 120 recombinant inbred lines (RILs) was developed through multiple generations of self-breeding. By utilizing a high-density molecular genetic linkage map and phenotypic data of four fatty acid components, we identified a total of 14 quantitative trait loci (QTLs) related to fatty acid composition across chromosomes 1, 3, 4, 6, 8, and 9. These included two QTLs for C14 content, three for C16:0 content, six for C18:1 content, and three for C18:2 content. Notably, the QTL qCOPT4.2 exhibited a high LOD score of 5.22. Within QTL intervals, genes such as OsACX3 and SLG affecting grain length were identified. The expression of candidate genes within these intervals was assessed and further analyzed by using quantitative real-time PCR. Genes such as LOC_Os01g15000, LOC_Os04g47120, LOC_Os04g49194, LOC_Os06g22080, LOC_Os06g23870, LOC_Os06g24704, LOC_Os06g30780, LOC_Os08g44840, and LOC_Os09g36860 were found to regulate fatty acid synthesis or metabolic pathways, potentially enhancing fatty acid content in rice. These QTLs are indispensable for breeding rice varieties with improved fatty acid profiles, offering new genetic resources for enhancing the nutritional and storage qualities of rice.

The role of micronutrients and serum metabolites in intervertebral disk degeneration: insights from a Mendelian randomization study and mediation analysis

BackgroundIntervertebral disk degeneration (IVDD) is a complex degenerative skeletal condition, potentially influenced by micronutrients and serum metabolites in its etiology. However, the exact causal relationship between these factors and IVDD remains ambiguous.MethodsThe research employed a Two-Sample Mendelian Randomization (2SMR) analysis to thoroughly evaluate the causal relationship between 15 micronutrients (consisting of 7 minerals and 8 vitamins) as exposure variables, 1,091 blood metabolites, and 309 metabolite ratios as intermediary factors, and IVDD as the outcome. Additionally, reverse MR analysis and mediation analysis were carried out to validate the reliability of the results and explore the underlying mechanism by which micronutrients influence the risk of IVDD by regulating metabolites.ResultsAmong the micronutrients examined, vitamin B12 exhibited a noteworthy negative correlation with the incidence of IVDD (OR: 0.752, 95% [CI]: 0.573–0.987, p = 0.040), indicating a potential reduction in IVDD risk with increased vitamin B12 consumption. Of the 1,091 blood metabolites and 309 metabolite ratios analyzed, 52 metabolites displayed significant associations with IVDD, primarily linked to amino acid, fatty acid, nucleotide, and sphingolipid metabolic pathways. Mediation analysis identified 4-acetaminophen sulfate as a potential mediator in the protective effect of vitamin B12 against IVDD.ConclusionThis study has shown that vitamin B12 may reduce the risk of IVDD and has identified 52 serum metabolites that are associated with IVDD. Furthermore, it proposes that 4-acetaminophen sulfate could serve as a potential mechanism by which vitamin B12 exerts its inhibitory effects on IVDD.

Zhi-Kang-Yin formula attenuates high-fat diet-induced metabolic disorders through modulating gut microbiota-bile acids axis in mice

BackgroundMetabolic disorders have become one of the global medical problems. Due to the complexity of its pathogenesis, there is still no effective treatment. Bile acids (BAs) and gut microbiota (GM) have been proved to be closely related to host metabolism, which could be important targets for metabolic disorders. Zhi-Kang-Yin (ZKY) is a traditional Chinese medicine (TCM) formula developed by the research team according to theory of TCM and has been shown to improve metabolism in clinic. However, the underlying mechanisms are unclear.Aim of the studyThis study aimed to investigate the potential mechanisms of the beneficial effect of ZKY on metabolism.MethodsHigh-fat diet (HFD)-fed mice were treated with and without ZKY. The glucose and lipid metabolism-related indexes were measured. BA profile, GM composition and hepatic transcriptome were then investigated to analyze the changes of BAs, GM, and hepatic gene expression. Moreover, the relationship between GM and BAs was identified with functional gene quantification and ex vivo fermentation experiment.ResultsZKY reduced weight gain and lipid levels in both liver and serum, attenuated hepatic steatosis and improved glucose tolerance in HFD-fed mice. BA profile detection showed that ZKY changed the composition of BAs and increased the proportion of unconjugated BAs and non-12-OH BAs. Hepatic transcriptomic analysis revealed fatty acid metabolism and BA biosynthesis related pathways were regulated. In addition, ZKY significantly changed the structure of GM and upregulated the gene copy number of bacterial bile salt hydrolase. Meanwhile, ZKY directly promoted the growth of Bifidobacterium, which is a well-known bile salt hydrolase-producing genus. The ex vivo co-culture experiment with gut microbiota and BAs demonstrated that the changes of BAs profile in ZKY group were mediated by ZKY-shifted GM, which led to increased expression of genes associated with fatty acid degradation in the liver.ConclusionOur study indicated that the effect of ZKY on improving metabolism is associated with the modulation of GM-BAs axis, especially, by upregulating the abundance of bile salt hydrolase-expression bacteria and increasing the levels of unconjugated BAs. This study indicates that GM-BAs axis might be an important pathway for improving metabolic disorders by ZKY.

Genome-Scale Metabolic Modeling of Halomonas elongata 153B Explains Polyhydroxyalkanoate and Ectoine Biosynthesis in Hypersaline Environments.

Halomonas elongata thrives in hypersaline environments producing polyhydroxyalkanoates (PHAs) and osmoprotectants such as ectoine. Despite its biotechnological importance, several aspects of the dynamics of its metabolism remain elusive. Here, we construct and validate a genome-scale metabolic network model for H. elongata 153B. Then, we investigate the flux distribution dynamics during optimal growth, ectoine, and PHA biosynthesis using statistical methods, and a pipeline based on shadow prices. Lastly, we use optimization algorithms to uncover novel engineering targets to increase PHA production. The resulting model (iEB1239) includes 1534 metabolites, 2314 reactions, and 1239 genes. iEB1239 can reproduce growth on several carbon sources and predict growth on previously unreported ones. It also reproduces biochemical phenotypes related to Oad and Ppc gene functions in ectoine biosynthesis. A flux distribution analysis during optimal ectoine and PHA biosynthesis shows decreased energy production through oxidative phosphorylation. Furthermore, our analysis unveils a diverse spectrum of metabolic alterations that extend beyond mere flux changes to encompass heightened precursor production for ectoine and PHA synthesis. Crucially, these findings capture other metabolic changes linked to adaptation in hypersaline environments. Bottlenecks in the glycolysis and fatty acid metabolism pathways are identified, in addition to PhaC, which has been shown to increase PHA production when overexpressed. Overall, our pipeline demonstrates the potential of genome-scale metabolic models in combination with statistical approaches to obtain insights into the metabolism of H. elongata. Our platform can be exploited for researching environmental adaptation, and for designing and optimizing metabolic engineering strategies for bioproduct synthesis.

Detection of H1N1 Influenza Virus in the Bile of a Severe Influenza Mouse Model.

Influenza virus infection may lead to fatal complications including multi-organ failure and sepsis. The influenza virus was detected in various extra-pulmonary organs in autopsy studies during the 2009 pandemic. However, limited research has been conducted on the presence of viral particle or viral components in the peripheral blood. We established a mouse model for severe H1N1 influenza. The bile and blood samples were collected over time and inoculated into embryonated chicken eggs. We detected live influenza virus in bile and blood samples in early infection. Immunofluorescence showed influenza viral components in the liver tissue. No live virus was isolated in the bile in mice intragastrically administered with influenza virus, indicating that the virus was spread from the blood stream. Targeted metabolomics analysis of bile acid and liver tissues showed that a secondary bile acid (3-dehydrocholic acid) was decreased after influenza H1N1 infection. Genes related with fatty acid metabolism and bile secretion pathways were down-regulated in liver after influenza virus infection. Our study indicated that influenza virus viremia is present in severe influenza, and that the liver is a target organ for influenza viral sepsis.

The cytotoxic activities of the major diterpene extracted from Salvia multicaulis (Bardakosh) are mediated by the regulation of heat-shock response and fatty acid metabolism pathways in human leukemia cells

BackgroundLeukemia is one of the most lethal cancers worldwide and represents the sixth-leading cause of cancer deaths. The results of leukemia treatment have not been as positive as desired, and recurrence is common. PurposeThus, there is an urgent requirement for the development of new therapeutic drugs. Salvia multicaulis (Bardakosh) is a widespread species that contains multiple phytochemical components with anti-cancer activities. MethodsWe isolated and characterized the major diterpene candesalvone B methyl ester from S. multicaulis and investigated its action as a cytotoxic agent towards sensitive and drug-resistant leukemia cells by the resazurin reduction assay. Additionally, the targeted genes and the affected molecular mechanisms attributed to the potent cytotoxic activities were discovered by transcriptome-wide mRNA expression profiling. The targets predicted to be regulated by candesalvone B methyl ester in each cell line were confirmed by qRT-PCR, molecular docking, microscale thermophoresis, and western blotting. Moreover, cell cycle distribution and apoptosis were analyzed by flow cytometry. ResultsCandesalvone B methyl ester was cytotoxic with IC50 values of 20.95 ± 0.15 µM against CCRF-CEM cells and 4.13 ± 0.10 µM against multidrug-resistant CEM/ADR5000 leukemia cells. The pathway enrichment analysis disclosed that candesalvone B methyl ester could regulate the heat-shock response signaling pathway via targeting heat shock factor 1 (HSF1) in CCRF-CEM cells and ELOVL fatty acid elongase 5 (ELOVL5) controls the fatty acid metabolism pathway in CEM/ADR5000 cells. Microscale thermophoresis showed the binding of candesalvone B methyl ester with HSF1 and ELOVL5, confirming the results of molecular docking analysis. Down-regulation of both HSF1 and ELOVL5 by candesalvone B methyl ester as detected by both western blotting and RT-qPCR was related to the reversal of drug resistance in the leukemia cells. Furthermore, candesalvone B methyl ester increased the arrest in the sub-G1 phase of the cell cycle in a dose-dependent manner from 1.3 % to 32.3 % with concomitant induction of apoptosis up to 29.0 % in CCRF-CEM leukemic cells upon inhibition of HSF1. ConclusionCandesalvone B methyl ester isolated from S. multicaulis exerted cytotoxicity by affecting apoptosis, cell division, and modulation of expression levels of genes contributing to the heat stress signaling and fatty acid metabolism pathways that could relieve drug resistance of leukemia cells.

Assessing the effects of imidacloprid exposure on the microbiota of Binodoxys communis (Hymenoptera: Braconidae) and gene expression

Imidacloprid is a potent neonicotinoid insecticide that exerts control over cotton aphids. Binodoxys communis is the predominant parasitic threat to cotton aphids, serving as a crucial biological means to control cotton aphids. Imidacloprid has been Sprayed to control cotton aphids, but it also causes toxic effects on the natural enemies of cotton aphids, such as parasitic wasps, Binodoxys communis. However, the sublethal impact of imidacloprid on parasitic antagonists has remained unclear. This study sought to investigate the sublethal effects of imidacloprid on B. communis at the biological phenotype and transcriptional level, as well as the impact of imidacloprid on the microbial composition in the B. communis. Our research indicated that the sublethal dosages of imidacloprid imparted significant biologic adverse impacts on B. communis, including extended larval and pupal stages, as well as reduced parasitism and emergence rates. Following treatment with imidacloprid, transcriptomic analysis identified 1263 significantly differentially expressed genes. These differentially expressed genes were predominantly annotated in metabolic routes, and the annotated genes mainly belong to the fatty acid metabolism pathway, the carbon metabolism pathway, and protein processing in the endoplasmic reticulum pathway. 16S rDNA sequencing results showed significant changes in the composition of the microbial community in B. communis after exposure to imidacloprid. A total of 14 bacteria exhibiting the highest abundance in parasitic wasps were found, and the microbiota abundance of Akkermansia, Bacteroides, Streptomyces, Helicobacter, and Prevotellaceae UCG_001 was noticeably reduced, while Lactobacillus, Escherichia Shigella, Ligilactobacillus, Lachnospiraceae, Rikenellaceae RC9_gut_group, Erysipelatoclostridium, Acinetobacter, Enterococcus, and Aquabacterium were significantly elevated. By evaluating the enrichment pathways of microbial functions, it was found that the microbial functions with significant changes in proportion were mainly annotated to the carbon, fatty acid, and amino acid (aa) metabolic pathways, which was consistent with the transcriptome sequencing results. This finding mirrored transcriptome analysis results. According to transcriptomics analysis and 16S rDNA sequencing data, imidacloprid limits changes in metabolic pathways of B. communis, including fatty acid metabolism, impacting the development and parasitic competence of B. communis. Accordingly, the gene expression linked to detoxification and the cytochrome P450 gene family was significantly elevated at 1 h and significantly declined after three days.

Unveiling responses and mechanisms of spice crop chive exposure to three typical pesticides using metabolomics combined with transcriptomics, physiology and biochemistry

Pesticides are frequently used to control target pests in the production of spice crops such as chives (Allium ascalonicum). However, little information is available on the responses and underlying mechanisms of pesticide exposure in this crop. Our findings revealed that the uptake, transportation, and subcellular distribution of three typical pesticides—the fungicide pyraclostrobin (PAL), insecticide acetamiprid (ATP), and herbicide pendimethalin (PND) in chives, as well as their physiological, biochemical, metabolic, and transcriptomic responses—were dependent on pesticide properties, especially hydrophobicity. The distribution of PAL and PND in chives decreased in the order root > stem > leaf, but the distribution order of ATP was the opposite. The proportion of PAL and PND in the solid phase of the root cells gradually increased, but ATP mainly existed in the cell-soluble component, indicating that the latter had an upward translocation ability and thus mainly accumulated in the leaves. Malondialdehyde levels in chive leaves were not significantly affected by exposure to these pesticides; however, the activities of superoxide dismutase (SOD) and catalase (CAT) in chive leaves increased significantly. Moreover, these pesticides exhibited critical differences in chive responses through the interaction of metabolites and regulation of differentially expressed genes. PAL dramatically influenced five carbohydrate metabolic pathways (34.35 %), disturbing the starch-to-sucrose balance. ATP strongly affected five amino acid (AC) metabolic pathways (33.38 %), enhancing four free amino acid levels. PND notably affected eight fatty acid (FA) metabolic pathways (25.38 %), increasing two unsaturated and decreasing one saturated FA. Simultaneously, PND, ATP, and PND accumulated in the chives could be detoxified through metabolic pathways mediated by cytochrome P450 (P450) and glycosyltransferase (GT)/glutathione S-transferase (GST), producing phase I (7, 4, and 5) and II (11, 13, and 10) metabolites, respectively. This study provides important molecular insights into the responses and underlying mechanisms of spice crop exposure to pesticides.

Analysis of Aroma Characteristics of 'Binzi' and 'Xiangguo' Apple-Ancient Cultivars in China.

'Binzi' (BZ) (Malus domestica subsp. chinensis var. binzi Li Y.N.) and 'Xiangguo' (XG) (Malus domestica subsp. chinensis var. xiangguo Li Y.N.) are the ancient cultivars in China. The BZ fruits have a low-fragrant flavor on harvest day but a high-fragrant flavor after storage at room temperature, while the XG fruits have a stronger flavor when mature. 'Starking' (SK) and 'Golden Delicious' (GD) fruits have a rich flavor and are recognized by all countries in the world. However, information on the differences between ancient Chinese cultivars and Western apple cultivars in aroma compounds remains unknown. The apple fruits were collected for continuous two years. Aroma compounds in the skin and pulp of the fruits were detected at room temperature (20 ± 1 °C) during storage. The dynamics of VOCs in BZ and SK fruits were more similarly reflected in esters, while those of XG and GD fruits were reflected in aldehydes and alcohols. Ethyl 2-methylbutyrate, with an extremely low odor threshold, was the main source of typical apple flavor in SK, BZ, and XG fruits, while hexyl acetate was the source of the banana flavor in GD fruits. 6-methyl-5-hepten-2-one and β-damascenone were the important ketones produced in the later stage of storage, derived from the carotenoid metabolism pathway and providing a citrus and rose flavor to the four apple cultivars. SK had the highest number of characteristic aroma components, which were mainly derived from the amino acid metabolism pathway, providing fruits with a sweet and fruity flavor. Although the characteristic aroma components of GD were derived from the fatty acid metabolic pathway, the number of volatile esters was lower. Ethyl butyrate, derived from the saturated fatty acid metabolism, had the highest content in BZ, providing a pineapple flavor; the flavor of XG was mainly derived from ethyl 2-methylbutyrate, 6-methyl-5-hepten-2-one, and β-damascenone. Therefore, we suggest BZ and XG apples as the aroma-breeding material with which to enrich new cultivars' aroma components, derived from the fatty acid metabolism and carotenoid metabolism pathways, respectively.

A transcriptome-wide analysis provides novel insights into how Metabacillus indicus promotes coral larvae metamorphosis and settlement

BackgroundCoral reefs experience frequent and severe disturbances that can overwhelm their natural resilience. In such cases, ecological restoration is essential for coral reef recovery. Sexual reproduction has been reported to present the simplest and most cost-effective means for coral reef restoration. However, larval settlement and post-settlement survival represent bottlenecks for coral recruitment in sexual reproduction. While bacteria play a significant role in triggering coral metamorphosis and settlement in many coral species, the underlying molecular mechanisms remain largely unknown. In this study, we employed a transcriptome-level analysis to elucidate the intricate interactions between bacteria and coral larvae that are crucial for the settlement process.ResultsHigh Metabacillus indicus strain cB07 inoculation densities resulted in the successful induction of metamorphosis and settlement of coral Pocillopora damicoris larvae. Compared with controls, inoculated coral larvae exhibited a pronounced increase in the abundance of strain cB07 during metamorphosis and settlement, followed by a significant decrease in total lipid contents during the settled stage. The differentially expressed genes (DEGs) during metamorphosis were significantly enriched in amino acid, protein, fatty acid, and glucose related metabolic pathways. In settled coral larvae induced by strain cB07, there was a significant enrichment of DEGs with essential roles in the establishment of a symbiotic relationship between coral larvae and their symbiotic partners. The photosynthetic efficiency of strain cB07 induced primary polyp holobionts was improved compared to those of the negative controls. In addition, coral primary polyps induced by strain cB07 showed significant improvements in energy storage and survival.ConclusionsOur findings revealed that strain cB07 can promote coral larval settlement and enhance post-settlement survival and fitness. Manipulating coral sexual reproduction with strain cB07 can overcome the current recruitment bottleneck. This innovative approach holds promise for future coral reef restoration efforts.

Early-life milk replacer feeding mediates lipid metabolism disorders induced by colonic microbiota and bile acid profiles to reduce body weight in goat model

BackgroundDysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention, especially in the context of alternative feeding strategies. This study aims to elucidate the effects of milk replacer (MR) feeding on growth, lipid metabolism, colonic epithelial gene expression, colonic microbiota composition and systemic metabolism in goat kids compared to breast milk (BM) feeding, addressing a critical knowledge gap in early life nutrition.MethodsTen female goat kids were divided into 2 groups: those fed breast milk (BM group) and those fed a milk replacer (MR group). Over a period of 28 d, body weight was monitored and blood and tissue samples were collected for biochemical, transcriptomic and metabolomic analyses. Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing. Intestinal microbiota transplantation (IMT) experiments in gnotobiotic mice were performed to validate causality.ResultsMR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol (TC) and non-esterified fatty acid (NEFA) concentrations. Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism, concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria. Specifically, genera such as Bifidobacterium and Prevotella were enriched in the MR group, while Clostridium and Faecalibacterium were depleted. Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic pathways. IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats, confirming the role of the microbiota in modulating host lipid metabolism.ConclusionsMilk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics, resulting in reduced growth rates and metabolic alterations. These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants. This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.

Multiomic Insights into Human Health: Gut Microbiomes of Hunter-Gatherer, Agropastoral, and Western Urban Populations.

Societies with exposure to preindustrial diets exhibit improved markers of health. Our study used a comprehensive multi-omic approach to reveal that the gut microbiome of the Ju/'hoansi hunter-gatherers, one of the most remote KhoeSan groups, exhibit a higher diversity and richness, with an abundance of microbial species lost in the western population. The Ju/'hoansi microbiome showed enhanced global transcription and enrichment of complex carbohydrate metabolic and energy generation pathways. The Ju/'hoansi also show high abundance of short-chain fatty acids that are associated with health and optimal immune function. In contrast, these pathways and their respective species were found in low abundance or completely absent in Western populations. Amino acid and fatty acid metabolism pathways were observed prevalent in the Western population, associated with biomarkers of chronic inflammation. Our study provides the first in-depth multi-omic characterization of the Ju/'hoansi microbiome, revealing uncharacterized species and functional pathways that are associated with health.

Identification of candidate genes and genomic prediction of soybean fatty acid components in two soybean populations.

Soybean, a source of plant-derived lipids, contains an array of fatty acids essential for health. A comprehensive understanding of the fatty acid profiles in soybean is crucial for enhancing soybean cultivars and augmenting their qualitative attributes. Here, 180 F10 generation recombinant inbred lines (RILs), derived from the cross-breeding of the cultivated soybean variety 'Jidou 12' and the wild soybean 'Y9,' were used as primary experimental subjects. Using inclusive composite interval mapping (ICIM), this study undertook a quantitative trait locus (QTL) analysis on five distinct fatty acid components in the RIL population from 2019 to 2021. Concurrently, a genome-wide association study (GWAS) was conducted on 290 samples from a genetically diverse natural population to scrutinize the five fatty acid components during the same timeframe, thereby aiming to identify loci closely associated with fatty acid profiles. In addition, haplotype analysis and the Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to predict candidate genes. The QTL analysis elucidated 23 stable QTLs intricately associated with the five fatty acid components, exhibiting phenotypic contribution rates ranging from 2.78% to 25.37%. In addition, GWAS of the natural population unveiled 102 significant loci associated with these fatty acid components. The haplotype analysis of the colocalized loci revealed that Glyma.06G221400 on chromosome 6 exhibited a significant correlation with stearic acid content, with Hap1 showing a markedly elevated stearic acid level compared with Hap2 and Hap3. Similarly, Glyma.12G075100 on chromosome 12 was significantly associated with the contents of oleic, linoleic, and linolenic acids, suggesting its involvement in fatty acid biosynthesis. In the natural population, candidate genes associated with the contents of palmitic and linolenic acids were predominantly from the fatty acid metabolic pathway, indicating their potential role as pivotal genes in the critical steps of fatty acid metabolism. Furthermore, genomic selection (GS) for fatty acid components was conducted using ridge regression best linear unbiased prediction based on both random single nucleotide polymorphisms (SNPs) and SNPs significantly associated with fatty acid components identified by GWAS. GS accuracy was contingent upon the SNP set used. Notably, GS efficiency was enhanced when using SNPs derived from QTL mapping analysis and GWAS compared with random SNPs, and reached a plateau when the number of SNP markers exceeded 3,000. This study thus indicates that Glyma.06G221400 and Glyma.12G075100 are genes integral to the synthesis and regulatory mechanisms of fatty acids. It provides insights into the complex biosynthesis and regulation of fatty acids, with significant implications for the directed improvement of soybean oil quality and the selection of superior soybean varieties. The SNP markers delineated in this study can be instrumental in establishing an efficacious pipeline for marker-assisted selection and GS aimed at improving soybean fatty acid components.

Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model.

Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/- control mice treated with normal saline, those in the ApoE-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg-1 d-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm2vs. (0.032±0.0062) mm2, P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.

Differences in flavor characteristics of rounds of Sauce-based Baijiu based on GC-IMS, GC-MS, and electronic tongue

The volatile flavor and metabolic pathway differences of rounds of Sauce-based Baijiu (RSBs, R-1∼R-7) were analyzed using HS-GC-IMS and HS-SPME-GC-MS. Firstly, 18 (R-1, R-2, R-4, R-6, and R-7), 17 (R-3), and 19 (R-5) characteristic flavor compounds were identified based on GC-IMS by the relative odor activity value (ROAV) analysis. Secondly, a total of 751 metabolites were identified using GC-MS, and the differential metabolites were screened for pathway enrichment analysis by variable importance in projection (VIP) > 1 combined with fold change (FC) ≥ 2 or ≤ 0.5. The results demonstrated that unsaturated fatty acid metabolism, fatty acid metabolism, terpene metabolism, and secondary metabolite biosynthesis pathways were the most significant metabolic pathways influencing the flavor of basic baijiu, which primarily resulted in alterations in the composition and concentration of metabolites, including fatty acids and terpenes. Furthermore, RSBs demonstrated distinctive taste attributes, the addition of R-1 was found to markedly influence the astringency of baijiu (p < 0.05), while no notable impact was observed on the acidity or aftertaste. This study elucidates the flavor characteristics of RSBs, which provides a reference for the flavor quality regulation and blending of baijiu.

Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid (CSF) biomarkers for AD-related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact. We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. AD pathology on biopsy correlates with CSF β-amyloid-42/40, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/β-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data. As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking. AD CSF biomarkers correlate with CNS pathology and transcriptomic changes. Seven proteins correlate with CNS pathology and gene expression changes. Inflammatory and neuronal gene expression changes correlate with YKL-40 and NPTXR, respectively. CSF metabolomic analysis identifies pathways that correlate with biopsy data. Fatty acid metabolic pathways correlate with β-amyloid pathology.

Sulforaphane modulates some stress parameters in TPT-exposed Cyprinus carpio in relation to liver metabolome

This study aimed to investigate the protective effect of sulforaphane (SFN) on liver injury induced by triphenyltin (TPT) in Cyprinus carpio (C. carpio). The fish (average weight of 56.9±0.4 g) were divided into 4 groups with four replicates: the control, TPT, SFN+TPT and SFN groups. Twenty fish were selected from each tank and cultured for 8 weeks. Then, serum and liver samples were collected for physiological, biochemical and metabolomic analyses. In the present study, TPT downregulated the expression of the lysozyme gene, upregulated HSP70 and Hsp90 gene expression, and decreased the activities of serum antioxidant enzymes (SOD, CAT, and GPX). However, dietary SFN alleviated oxidative stress, and prevented changes in immune genes. Metabolomic analysis revealed that TPT exposure changed key metabolites in the main phenylalanine, fatty acid and glycerophosphatide metabolic pathways, which are related to inflammation, oxidative stress and immunity and might also lead to an imbalance of liver energy and lipid metabolism. Dietary SFN promoted amino acid metabolism and increased metabolites related to immunity, anti-inflammation, antioxidation, and protein synthesis in liver of C. carpio. In summary, dietary SFN supplementation reversed TPT-induced decreases in immunity and oxidative stress and regulated amino acid metabolism, lipid metabolism, inflammation and immunity-related metabolic pathways.

Analysis of Serum Exosome Metabolites Identifies Potential Biomarkers for Human Hepatocellular Carcinoma.

Currently, the clinical cure rate for primary liver cancer remains low. Effective screening and early diagnosis of hepatocellular carcinoma (HCC) remain clinical challenges. Exosomes are intimately associated with tumor development and their contents have the potential to serve as highly sensitive tumor-specific markers. A comprehensive untargeted metabolomics study was conducted using exosome samples extracted from the serum of 48 subjects (36 HCC patients and 12 healthy controls) via a commercial kit. An ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) strategy was used to identify the metabolic compounds. A total of 18 differential metabolites were identified using the non-targeted metabolomics approach of UPLC-QTOF-MS/MS. Pathway analysis revealed significant alterations in the arachidonic acid metabolism, linoleic acid metabolism, and unsaturated fatty acid metabolism pathways. ROC analysis indicated that three metabolites with AUC values exceeding 0.900 were selected as potential biomarkers: caprylic acid and linoleic acid were upregulated in the HCC group, whereas pentadecanoic acid was downregulated. Linoleic acid, caprylic acid, and pentadecanoic acid are potential biomarkers for diagnosing HCC. The significant alterations in these three metabolic pathways offer new insights into the mechanisms underlying HCC formation and progression.

Circulating miRNA Signaling for Fatty Acid Metabolism in Response to a Maximum Endurance Test in Elite Long-Distance Runners.

Maximal oxygen uptake (VO2max) is a determining indicator for cardiorespiratory capacity in endurance athletes, and epigenetics is crucial in its levels and variability. This initial study examined a broad plasma miRNA profile of twenty-three trained elite endurance athletes with similar training volumes but different VO2max in response to an acute maximal graded endurance test. Six were clustered as higher/lower levels based on their VO2max (75.4 ± 0.9 and 60.1 ± 5.0 mL.kg-1.min-1). Plasma was obtained from athletes before and after the test and 15 ng of total RNA was extracted and detected using an SYBR-based 1113 miRNA RT-qPCR panel. A total of 51 miRNAs were differentially expressed among group comparisons. Relative amounts of miRNA showed a clustering behavior among groups regarding distinct performance/time points. Significantly expressed miRNAs were used to perform functional bioinformatic analysis (DIANA tools). Fatty acid metabolism pathways were strongly targeted for the significantly different miRNAs in all performance groups and time points (p < 0.001). Although this pathway does not solely determine endurance performance, their significant contribution is certainly achieved through the involvement of miRNAs. A highly genetically dependent gold standard variable for performance evaluation in a homogeneous group of elite athletes allowed genetic/epigenetic aspects related to fatty acid pathways to emerge.