PubMed

Molecules. 2024 Nov 5;29(22):5230. doi: 10.3390/molecules29225230.ABSTRACTThe aim of the present study was to comprehensively analyze and identify the metabolites of different varieties of raw peanut, as well as provide a reference for the utilization of different varieties of peanuts. In this study, three varieties of peanuts, namely ZKH1H, ZKH13H, and CFD, were investigated via ultrahigh-performance liquid chromatography (UPLC) and widely targeted metabolomics methods based on tandem mass spectrometry (MS) and solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS). In total, 417 nonvolatile and 55 volatile substances were detected. The nonvolatile substances were classified into the following 10 categories: organic acids and derivatives (28.9%); organic oxygen compounds (21.9%); lipids and lipid-like molecules (12.6%); organoheterocyclic compounds (9.9%); nucleosides, nucleotides, and analogues (9.4%); benzenoids (7.8%); phenylpropanoids and polyketides (6.1%); organic nitrogen compounds (2.7%); lignans, neolignans, and related compounds (0.5%); and alkaloids and their derivatives (0.3%). The volatile compounds (VOCs) were classified into the following eight categories: organic oxygen compounds (24.1%); organic cyclic compounds (20.4%); organic nitrogen compounds (13%); organic acids and their derivatives (13%); lipids and lipid-like molecules (11.2%); benzenoids (11.1%); hydrocarbons (3.7%); and homogeneous non-metallic compounds (3.7%). Differentially abundant metabolites among the different peanut varieties (ZKH13H vs. CFD, ZKH1H vs. CFD, and ZKH1H vs. ZKH13H) were investigated via multivariate statistical analyses, which identified 213, 204, and 157 nonvolatile differentially abundant metabolites, respectively, and 12, 11, and 10 volatile differentially abundant metabolites, respectively. KEGG metabolic pathway analyses of the differential non-VOCs revealed that the most significant metabolic pathways among ZKH13H vs. CFD, ZKH1H vs. CFD, and ZKH1H vs. ZKH13H were galactose metabolism, purine metabolism, and aminoacyl-tRNA, while the nitrogen metabolism pathway was identified as a significant metabolic pathway for the VOCs. The present findings provide a theoretical foundation for the development and utilization of these three peanut species, as well as for the breeding of new peanut varieties.PMID:39598620 | DOI:10.3390/molecules29225230

Molecules. 2024 Nov 5;29(22):5221. doi: 10.3390/molecules29225221.ABSTRACTDrug and toxin-related deaths are common worldwide, making it essential to detect the postmortem concentration of various toxic substances at different stages of decomposition in a corpse. Indeed, determining the postmortem interval (PMI) and cause of death in an advanced stage of decomposed corpses has been a significant challenge in forensic investigations. Notably, the presence of drugs or toxins can have a significant impact on the microbial profile, potentially altering the succession of microbial communities and subsequent production of volatile organic compounds (VOCs), which, in turn, affect insect colonization patterns. This review aims to highlight the importance of investigating the interactions between drugs or toxins, microbial succession, VOC profiles, and insect behavior, which can provide valuable insights into forensic investigations as well as the ecological consequences of toxins occurring in decomposition. Overall, the detection of drugs and other toxins at different stages of decomposition can yield more precise forensic evidence, thereby enhancing the accuracy of PMI estimation and determination of the cause of death in decomposed remains.PMID:39598612 | DOI:10.3390/molecules29225221

Pharmaceutics. 2024 Oct 28;16(11):1385. doi: 10.3390/pharmaceutics16111385.ABSTRACTThis study investigated the effects of a single dose of desvenlafaxine via oral administration on the pharmacokinetic parameters and clinical and laboratory characteristics in healthy volunteers using a pharmacometabolomics approach. In order to optimize desvenlafaxine's therapeutic use and minimize potential adverse effects, this knowledge is essential. Methods: Thirty-five healthy volunteers were enrolled after a health trial and received a single dose of desvenlafaxine (Pristiq®, 100 mg). First, liquid chromatography coupled to tandem mass spectrometry was used to determine the main pharmacokinetic parameters. Next, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to identify plasma metabolites with different relative abundances in the metabolome at pre-dose and when the desvenlafaxine peak plasma concentration was reached (pre-dose vs. post-dose). Results: Correlations were observed between metabolomic profiles, such as tyrosine, sphingosine 1-phosphate, and pharmacokinetic parameters, as well as acetoacetic acid and uridine diphosphate glucose associated with clinical characteristics. Our findings suggest that desvenlafaxine may have a broader effect than previously thought by acting on the proteins responsible for the transport of various molecules at the cellular level, such as the solute carrier SLC and adenosine triphosphate synthase binding cassette ABC transporters. Both of these molecules have been associated with PK parameters and adverse events in our study. Conclusions: This altered transporter activity may be related to the reported side effects of desvenlafaxine, such as changes in blood pressure and liver function. This finding may be part of the explanation as to why people respond differently to the drug.PMID:39598509 | DOI:10.3390/pharmaceutics16111385

Pharmaceuticals (Basel). 2024 Nov 9;17(11):1509. doi: 10.3390/ph17111509.ABSTRACTObjectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint damage and commonly linked to symptoms such as inflammation, swelling, and pain. Traditional Chinese Medicine offers complementary and integrative approaches in the management of rheumatoid arthritis, potentially providing additional options that may help address treatment challenges and enhance overall patient care. This paper explores the mechanism of action of berberine from the perspective of cellular exosomes by mediating exosomal contents and thus treating RA. Methods: With the help of flow cytometry and confocal laser scanning microscope, it was determined that berberine promotes apoptosis in RA-FLS cells, and then lipid metabolomics technology was applied to screen and characterize the exosomes of RA-FLS cells to identify lipid core biomarkers closely related to RA, which were then projected into various databases for comprehensive analysis. Results: The data analysis showed that berberine could call back 11 lipid core biomarkers closely associated with RA, and interactive visualization of the database revealed that these markers were mainly focused on lipid metabolism aspects such as fatty acid elongation, degradation, and biosynthesis, as well as the biosynthesis of unsaturated fatty acids or PPARA activation of gene expression, PPARα's role in lipid metabolism regulation, glycerophospholipid metabolism, mitochondrial fatty acid oxidation disorders, and organelle biogenesis and maintenance. Conclusions: Berberine exerts its therapeutic effect on RA by mediating exosomal contents and thus regulating multiple lipid-related biological pathways, affecting the PPARγ-NF-κB complex binding rate, CREB and EGR-1 expression, cellular phagocytosis, and other aspects needed to inhibit proliferation and inflammatory responses in RA-FLS. This study offers a research foundation for exploring the mechanism of action of berberine in the treatment of RA.PMID:39598419 | DOI:10.3390/ph17111509

Life (Basel). 2024 Nov 20;14(11):1511. doi: 10.3390/life14111511.ABSTRACTBACKGROUND: Accumulating evidence has proposed phase angle (PhA) as a marker for assessing cellular integrity and nutritional status in ulcerative colitis (UC) patients; the aim of the study was to evaluate the efficacy of PhA in assessing nutritional status in patients with UC, investigating its potential as a biomarker of disease activity.METHODS: We conducted a cross-sectional study in patients with UC and healthy controls. We determined PhA by electrical bioimpedance and categorized participants through bioelectrical impedance analysis. They were classified as normal PhA > 6.1° and low PhA < 6.1° in men and normal PhA > 5.6° and low PhA < 5.6° in women.RESULTS: PhA was significantly lower in UC patients than in controls (5.8 ± 0.8 vs. 6.6 ± 0.7°; p < 0.001). Among UC patients, participants with low PhA showed a decrease in lean, dry mass (LDM) (p < 0.001), total body water (p = 0.008), and intracellular water (p = 0.005), accompanied by an increase in extracellular water (p = 0.001) compared to UC patients with normal PhA.CONCLUSIONS: PhA significantly decreases in UC patients compared to healthy controls and is even more reduced when UC is active. A cut-off point of <6.1 for men and <5.6 for women could be suitable for nutritional diagnosis in patients with UC, but it still needs to be validated.PMID:39598309 | DOI:10.3390/life14111511

Microorganisms. 2024 Nov 6;12(11):2242. doi: 10.3390/microorganisms12112242.ABSTRACTIt is known that the addition of feed rich in bioactive components to animal diets will affect rumen fermentation parameters and flora structure. However, research on the regulatory effects of prickly ash seeds (PASs) during rumen development or on the rumen microbiome and its metabolites in sheep is limited. The current study was designed to explore the effects of PASs on sheep rumen development and growth performance using metagenomics and metabolomics. Eighteen 3-month-old Hu lambs were randomly allotted to three different dietary treatment groups: 0% (basal diet, CK), 3% (CK with 3% PAS, low-dose PAS, LPS), and 6% (CK with 6% PAS, high-dose PAS, HPS) PASs. The lambs were slaughtered to evaluate production performance. Our results showed that dietary PAS addition improved the average daily gain and reduced the F/G ratio of the experimental animals. Additionally, the height and width of the rumen papilla in the treatment groups were significantly higher than those in the CK group. The fermentation parameters showed that the levels of acetate and butyrate were significantly higher in the LPS group than in the CK and HPS groups. The propionate levels in the HPS group were significantly higher than those in the CK and LPS groups. Metagenomics analysis revealed that PAS dietary supplementation improved the abundance of Clostridiales and Bacteroidales and reduced the abundance of Prevotella, Butyrivibrio, and Methanococcus. Metabolomic analyses revealed that increased metabolite levels, such as those of serotonin, L-isoleucine, and L-valine, were closely related to growth-related metabolic pathways. The correlations analyzed showed that papilla height and muscular thickness were positively and negatively correlated with serotonin and L-valine, respectively. Average daily gain (ADG) was positively and negatively correlated with L-valine and several Prevotella, respectively. In addition, muscular thickness was positively correlated with Sodaliphilus pleomorphus, four Prevotella strains, Sarcina_sp_DSM_11001, and Methanobrevibacter_thaueri. Overall, PAS addition improved sheep growth performance by regulating beneficial microorganism and metabolite abundances, facilitating bacterial and viral invasion resistance.PMID:39597631 | DOI:10.3390/microorganisms12112242

Microorganisms. 2024 Oct 29;12(11):2176. doi: 10.3390/microorganisms12112176.ABSTRACTBreed selection alters the coevolution of plant-microbiome associations that have developed over long periods of natural evolution. We investigated the effects of breed selection on the rhizosphere microbiomes and metabolites of hybrid parents (I101 and 84K) and their offspring (Q1-Q5) using metagenomics and untargeted metabolomics. Rhizosphere archaeal, bacterial and fungal community β-diversity significantly differed among hybrid parents and offspring, but only the dominant bacterial phyla and bacterial community α-diversity revealed significant differences. Approximately 5.49%, 14.90% and 7.86% of the archaeal, bacterial and fungal species significantly differed among the poplar hybrid parents and offspring. Rhizosphere microbial functional genes and metabolites were both clustered into the following three groups: I101 and 84K; Q2 and Q4; and Q1, Q3 and Q5. Compared with the hybrid parents, 15 phytochemical compounds were enriched in the hybrid offspring and explained 7.15%, 18.24% and 6.68% of the total variation in the archaeal, bacterial and fungal community compositions, respectively. Rhizosphere metabolites significantly affected the bacterial community, rather than the archaeal and fungal communities. Our observations suggested that poplar breed selection imposed greater selection pressure on the rhizosphere bacterial community, which was mainly driven by metabolites.PMID:39597565 | DOI:10.3390/microorganisms12112176

Microorganisms. 2024 Oct 29;12(11):2174. doi: 10.3390/microorganisms12112174.ABSTRACTWith the reclassification of COVID-19 as an endemic disease and the relaxation of measures, Slovenia needed a complementary system for monitoring SARS-CoV-2 infections. This article provides an overview of the epidemiological situation of SARS-CoV-2 in Slovenia using a wastewater surveillance system, demonstrating its usefulness as a complementary tool in epidemiological surveillance. This study found that estimated SARS-CoV-2 infections in Slovenia peaked in September 2022 and showed a declining trend with subsequent lower peaks in March-April and December 2023, mirroring the trends observed from clinical data. Based on both surveillance systems, the most prevalent variant in 2022 was BA.5. By 2023, BQ.1 and other Omicron variants increased in prevalence. By the end of 2023, XBB sublineages and the BA.2.86 variant had become predominant, demonstrating consistent dynamic shifts in variant distribution across both monitoring methods. This study found that wastewater surveillance at wastewater treatment plants in Slovenia effectively tracked SARS-CoV-2 infection trends, showing a moderate to strong correlation with clinical data and providing early indications of changes in infection trends and variant emergence. Despite limitations during periods of low virus concentration, the system proved significant in providing early warnings of infection trends and variant emergence, thus enhancing public health response capabilities.PMID:39597564 | DOI:10.3390/microorganisms12112174

Microorganisms. 2024 Oct 23;12(11):2124. doi: 10.3390/microorganisms12112124.ABSTRACTCampylobacter spp. are prevalent foodborne bacterial enteric pathogens. Their inclusion in biofilms on abiotic surfaces is considered a strategy that facilitates their extraintestinal survival. Organic acid (OA) treatments could be used in a green approach to decontaminate various surfaces. This work aimed to evaluate the inhibitory and eradicative effects of L(+)-lactic acid (LA), a naturally occurring OA, on a dual-species biofilm formed on two food processing model surfaces (polystyrene and stainless steel) by three selected foodborne Campylobacter spp. isolates (two C. jejuni and one C. coli). The influence of aerobiosis conditions (microaerophilic, aerobic and CO2 enriched) on the resistance of the established biofilms to the acid was also tested. In parallel, the predominant metabolites contained in the planktonic media of biofilm monocultures and mixed-culture biofilm were comparatively analyzed by an untargeted metabolomics approach. Results revealed that LA inhibited mixed-culture biofilm formation by more than 2 logs (>99%) on both surfaces when this was applied at its highest tested concentration (4096 μg/mL; 0.34% v/v). However, all the preformed mixed-culture biofilms (ca. 106-7 CFU/cm2) could not be eradicated even when the acid was used at concentrations exceeding 5% v/v, denoting their extremely high recalcitrance which was still influenced by the abiotic substratum, and the biofilm-forming aerobiosis conditions. The metabolic analysis revealed a strain-specific metabolite production which might also be related to the strain-specific biofilm-forming and resistance behaviors and resulted in the distinct clustering of the different samples. Overall, the current findings provide important information on the effectiveness of LA against biofilm campylobacteria and may assist in mitigating their risk in the food chain.PMID:39597514 | DOI:10.3390/microorganisms12112124

Biology (Basel). 2024 Oct 28;13(11):876. doi: 10.3390/biology13110876.ABSTRACTLacquer trees (Toxicodendron vernicifluum), economically vital, face high-temperature stress in summer. Transcriptomic, proteomic, and metabolomic analyses were employed to investigate the mechanisms by which lacquer trees respond to high temperatures. High-temperature treatment led to notable metabolite changes with 224 upregulated and 69 downregulated. Indole-3-acetic acid remained stable while abscisic acid decreased, with increases in jasmonic acid and jasmonoyl-L-isoleucine indicating complex hormonal responses. JAR1 and ABA 8'-hydroxylase encoding genes were upregulated. The rise in JAs boosted the alkaloid content and activated nitrogen transport. High temperatures also increased specific amino acids and upregulated aminotransferase and protease-encoding genes. Metabolomic analysis showed elevated flavonoid glycosides and the upregulation of glycosyltransferase genes. WPCNA found 35 protein modules involved in secondary metabolite biosynthesis, protein phosphorylation, and signal transduction. Protein-protein interaction analysis revealed MYC6's link with flavonoid biosynthesis, indicating its role in promoting flavonoids.PMID:39596831 | DOI:10.3390/biology13110876

Biology (Basel). 2024 Oct 22;13(11):848. doi: 10.3390/biology13110848.ABSTRACTWith the advent of high-throughput technologies, the field of omics has made significant strides in characterizing biological systems at various levels of complexity. Transcriptomics, proteomics, and metabolomics are the three most widely used omics technologies, each providing unique insights into different layers of a biological system. However, analyzing each omics data set separately may not provide a comprehensive understanding of the subject under study. Therefore, integrating multi-omics data has become increasingly important in bioinformatics research. In this article, we review strategies for integrating transcriptomics, proteomics, and metabolomics data, including co-expression analysis, metabolite-gene networks, constraint-based models, pathway enrichment analysis, and interactome analysis. We discuss combined omics integration approaches, correlation-based strategies, and machine learning techniques that utilize one or more types of omics data. By presenting these methods, we aim to provide researchers with a better understanding of how to integrate omics data to gain a more comprehensive view of a biological system, facilitating the identification of complex patterns and interactions that might be missed by single-omics analyses.PMID:39596803 | DOI:10.3390/biology13110848

Genes (Basel). 2024 Oct 29;15(11):1391. doi: 10.3390/genes15111391.ABSTRACTBACKGROUND: Strawberries are bright in color, sweet and sour in taste, and rich in nutrients and flavonoid compounds such as anthocyanins and proanthocyanidins. The synthesis and accumulation of anthocyanins are the decisive factors that make strawberries appear bright red. From the perspective of plant breeding, a change in flesh color is an important goal.METHODS: In this study, two strawberry plants with different flesh colors were selected, and transcriptome and metabolome analyses were performed during the color change period (S1) and ripening period (S2).RESULTS: RNA-seq revealed a total of 13,341 differentially expressed genes (DEGs) between and within materials, which were clustered into 5 clusters. A total of 695 metabolites were detected via metabolome analysis, and 243 differentially regulated metabolites (DRMs) were identified. The anthocyanin biosynthesis, starch and sucrose metabolism and glycolysis/gluconeogenesis pathways were determined to be important regulatory pathways for changes in strawberry flesh color through a joint analysis of RNA-seq data and the metabolome. The leucoanthocyanidin reductase (LAR) and chalcone synthase (CHS) gene is a key gene related to anthocyanins, cinnamic acid, and phenylalanine. In addition, through joint RNA-seq and metabolome analyses combined with weighted gene co-expression network analysis (WGCNA), we identified 9 candidate genes related to strawberry flesh color.CONCLUSIONS: Our research findings have laid the groundwork for a more comprehensive understanding of the molecular mechanisms governing the color transformation in strawberry flesh. Additionally, we have identified novel genetic resources that can be instrumental in advancing research related to strawberry color change.PMID:39596590 | DOI:10.3390/genes15111391

Int J Mol Sci. 2024 Nov 20;25(22):12446. doi: 10.3390/ijms252212446.ABSTRACTBananas (Musa spp.) are among the most important fruit and staple food crops globally, holding a significant strategic position in food security in tropical and subtropical regions. However, the industry is grappling with a significant threat from Fusarium wilt, a disease incited by Fusarium oxysporum f. sp. cubense (Foc). In this study, we explored the potential of Piriformospora indica (Pi), a mycorrhizal fungus renowned for bolstering plant resilience and nutrient assimilation, to fortify bananas against this devastating disease. Through a meticulous comparative analysis of mRNA and miRNA expression in control, Foc-inoculated, Pi-colonized, and Pi-colonized followed by Foc-inoculated plants via transcriptome and sRNAome, we uncovered a significant enrichment of differentially expressed genes (DEGs) and DE miRNAs in pathways associated with plant growth and development, glutathione metabolism, and stress response. Our findings suggest that P. indica plays a pivotal role in bolstering banana resistance to Foc. We propose that P. indica modulates the expression of key genes, such as glutathione S-transferase (GST), and transcription factors (TFs), including TCP, through miRNAs, thus augmenting the plant's defensive capabilities. This study offers novel perspectives on harnessing P. indica for the management of banana wilt disease.PMID:39596511 | DOI:10.3390/ijms252212446

Int J Mol Sci. 2024 Nov 19;25(22):12410. doi: 10.3390/ijms252212410.ABSTRACTIn neuroscience research, chiral metabolomics is an emerging field, in which D-amino acids play an important role as potential biomarkers for neurological diseases. The targeted chiral analysis of the brain metabolome, employing liquid chromatography (LC) coupled to mass spectrometry (MS), is a pivotal approach for the identification of biomarkers for neurological diseases. This review provides an overview of D-amino acids in neurological diseases and of the state-of-the-art strategies for the enantioselective analysis of chiral amino acids (AAs) in biological samples to investigate their putative role as biomarkers for neurological diseases. Fluctuations in D-amino acids (D-AAs) levels can be related to the pathology of neurological diseases, for example, through their role in the modulation of N-methyl-D-aspartate receptors and neurotransmission. Because of the trace presence of these biomolecules in mammals and the complex nature of biological matrices, highly sensitive and selective analytical methods are essential. Derivatization strategies with chiral reagents are highlighted as critical tools for enhancing detection capabilities. The latest advances in chiral derivatization reactions, coupled to LC-MS/MS analysis, have improved the enantioselective quantification of these AAs and allow the separation of several chiral metabolites in a single analytical run. The enhanced performances of these methods can provide an accurate correlation between specific D-AA profiles and disease states, allowing for a better understanding of neurological diseases and drug effects on the brain.PMID:39596475 | DOI:10.3390/ijms252212410

Int J Mol Sci. 2024 Nov 18;25(22):12375. doi: 10.3390/ijms252212375.ABSTRACTBlood is an important component for maintaining animal lives and synthesizing sugars, lipids, and proteins in organs. Revealing the relationship between genes and metabolite expression and milk somatic cell count (SCC), milk fat percentage, milk protein percentage, and lactose percentage in blood is helpful for understanding the molecular regulation mechanism of milk formation. Therefore, we separated the buffy coat and plasma from the blood of Xinjiang Brown cattle (XJBC) and Chinese Simmental cattle (CSC), which exhibit high and low SCC/milk fat percentage/milk protein percentage/lactose percentages, respectively. The expression of genes in blood and the metabolites in plasma was detected via RNA-Seq and LC-MS/MS, respectively. Based on the weighted gene coexpression network analysis (WGCNA) and functional enrichment analysis of differentially expressed genes (DEGs), we further found that the expression of genes in the blood mainly affected the SCC and milk fat percentage. Immune or inflammatory-response-related pathways were involved in the regulation of SCC, milk fat percentage, milk protein percentage, and lactose percentage. The joint analysis of the metabolome and transcriptome further indicated that, in blood, the metabolism pathways of purine, glutathione, glycerophospholipid, glycine, arginine, and proline are also associated with SCC, while lipid metabolism and amino-acid-related metabolism pathways are associated with milk fat percentage and milk protein percentage, respectively. Finally, related SCC, milk fat percentage, and milk protein percentage DEGs and DEMs were mainly identified in the blood.PMID:39596441 | DOI:10.3390/ijms252212375

Int J Mol Sci. 2024 Nov 16;25(22):12320. doi: 10.3390/ijms252212320.ABSTRACTThe classical function of the mineralocorticoid receptor (MR) is to maintain electrolytic homeostasis and control extracellular volume and blood pressure. The MR is expressed in the central nervous system (CNS) and is involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis as well as sleep physiology, playing a role in the non-rapid eye movement (NREM) phase of sleep. Some patients with psychiatric disorders have very poor sleep quality, and a relationship between MR dysregulation and this disorder has been found in them. In addition, the MR is involved in the regulation of the renal peripheral clock. One of the most common comorbidities observed in patients with chronic kidney disease (CKD) is poor sleep quality. Patients with CKD experience sleep disturbances, including reduced sleep duration, sleep fragmentation, and insomnia. To date, no studies have specifically investigated the relationship between MR activation and CKD-associated sleep disturbances. However, in this review, we analyzed the environment that occurs in CKD and proposed two MR-related mechanisms that may be responsible for these sleep disturbances: the circadian clock disruption and the high levels of MR agonist observed in CKD.PMID:39596384 | DOI:10.3390/ijms252212320

Int J Mol Sci. 2024 Nov 16;25(22):12310. doi: 10.3390/ijms252212310.ABSTRACTThe relationship between circulating metabolites and sarcopenia-related phenotypes remains unclear. We explored the causality between circulating metabolites and sarcopenia-related phenotypes. Instrumental variables for the human metabolome were derived from the recently published GWAS, which included 690 plasma metabolites. Summary statistics for four sarcopenia phenotypes (whole-body lean mass (WBLM), usual walking pace, appendicular lean mass (ALM), and handgrip strength (HGS)) (both sexes, males and females) were obtained from relevant GWASs. We used MR to evaluate the association between circulating metabolites and sarcopenia-related phenotypes. Colocalization analysis was utilized to determine whether two associated signals were consistent with a shared causal variant rather than the confounding effect of linkage disequilibrium. Subsequently, we explored associations between modifiable risk factors and sarcopenia-related metabolites to explore which metabolites may serve as potential intervention targets through lifestyle modification. Genetically predicted plasma levels of 95 known metabolites were associated with sarcopenia-related phenotypes, and 27 metabolites were supported by robust evidence of colocalization, among which 13 metabolites had a cross-sarcopenia effect. These metabolites primarily included acyl carnitines, amino acids and their derivatives, and phospholipids. Specifically, our analyses supported causal relationships between 23, 6, and 15 metabolites and ALM, HGS, and WBLM, respectively. Seven relevant metabolites might be associated with six modifiable factors. We identified 27 metabolite biomarkers with robust causal evidence for sarcopenia-related phenotypes, highlighting 13 metabolites with a cross-sarcopenia effect, and prioritized several metabolites as the potential interventional targets of lifestyle changes. Our study provided new insight into the etiology and prevention of sarcopenia.PMID:39596375 | DOI:10.3390/ijms252212310

Int J Mol Sci. 2024 Nov 16;25(22):12308. doi: 10.3390/ijms252212308.ABSTRACTSpinosad is an efficient and broad-spectrum environmentally friendly biopesticide, but its low yield in wild-type Saccharopolyspora spinosa limits its further application. ARTP/NTG compound mutagenesis was used in this study to improve the spinosad titer of S. spinosa and obtain a high-yield mutant-NT24. Compared with the wild-type strain, the fermentation cycle of NT24 was shortened by 2 days and its maximum titer of spinosad reached 858.3 ± 27.7 mg/L, which is 5.12 times more than for the same-period titer of the wild-type strain. In addition, RT-qPCR, resequencing, and targeted metabolomics showed that the upregulation of the key differential genes accD6, fadD, sdhB, oadA, and gntZ caused increased metabolic flux in the tricarboxylic acid cycle and pentose phosphate pathway, suggesting that the accumulation of pyruvate and short-chain acyl-CoA was the primary cause of spinosad accumulation in NT24. This study demonstrates the effectiveness of ARTP mutagenesis in S. spinosa, and provides new insights for the mechanism of spinosad biosynthesis and metabolic engineering in S. spinosa.PMID:39596372 | DOI:10.3390/ijms252212308

Int J Mol Sci. 2024 Nov 15;25(22):12274. doi: 10.3390/ijms252212274.ABSTRACTAdipocytes derived from 3T3-L1 cells are a gold standard for analyses of adipogenesis processes and the metabolism of fat cells. A widely used histological and immunohistochemical staining and mass spectrometry lipidomics are mainly aimed for examining lipid droplets (LDs). Visualizing other cellular compartments contributing to the cellular machinery requires additional cell culturing for multiple labeling. Here, we present the localization of the intracellular structure of the 3T3-L1-derived adipocytes utilizing vibrational spectromicroscopy, which simultaneously illustrates the cellular compartments and provides chemical composition without extensive sample preparation and in the naïve state. Both vibrational spectra (FTIR-Fourier transform infrared and RS-Raman scattering spectroscopy) extended the gathered chemical information. We proved that both IR and RS spectra provide distinct chemical information about lipid content and their structure. Despite the expected presence of triacylglycerols and cholesteryl esters in lipid droplets, we also estimated the length and unsaturation degree of the fatty acid acyl chains that were congruent with known MS lipidomics of these cells. In addition, the clustering of spectral images revealed that the direct surroundings around LDs attributed to lipid-associated proteins and a high abundance of mitochondria. Finally, by using quantified markers of biomolecules, we showed that the fixative agents, paraformaldehyde and glutaraldehyde, affected the cellular compartment differently. We concluded that PFA preserves LDs better, while GA fixation is better for cytochromes and unsaturated lipid analysis. The proposed analysis of the spectral images constitutes a complementary tool for investigations into the structural and molecular features of fat cells.PMID:39596337 | DOI:10.3390/ijms252212274

Int J Mol Sci. 2024 Nov 15;25(22):12273. doi: 10.3390/ijms252212273.ABSTRACTMaize (Zea mays L.) is highly sensitive to temperature during its growth and development stage. A 1 °C drop in temperature can delay maturity by 10 days, resulting in a yield reduction of over 10%. Low-temperature tolerance in maize is a complex quantitative trait, and different germplasms exhibit significant differences in their responses to low-temperature stress. To explore the differences in gene expression and metabolites between B144 (tolerant) and Q319 (susceptible) during germination under low-temperature stress and to identify key genes and metabolites that respond to this stress, high-throughput transcriptome sequencing was performed on the leaves of B144 and Q319 subjected to low-temperature stress for 24 h and their respective controls using Illumina HiSeqTM 4000 high-throughput sequencing technology. Additionally, high-throughput metabolite sequencing was conducted on the samples using widely targeted metabolome sequencing technology. The results indicated that low-temperature stress triggered the accumulation of stress-related metabolites such as amino acids and their derivatives, lipids, phenolic acids, organic acids, flavonoids, lignin, coumarins, and alkaloids, suggesting their significant roles in the response to low temperature. This stress also promoted gene expression and metabolite accumulation involved in the flavonoid biosynthesis pathway. Notably, there were marked differences in gene expression and metabolites related to the glyoxylate and dicarboxylate metabolism pathways between B144 and Q319. This study, through multi-omics integrated analysis, provides valuable insights into the identification of metabolites, elucidation of metabolic pathways, and the biochemical and genetic basis of plant responses to stress, particularly under low-temperature conditions.PMID:39596336 | DOI:10.3390/ijms252212273