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A comprehensive recent study by Trommelen et al. demonstrated that muscle tissue exhibits a greater capacity to incorporate exogenous exogenous protein-derived amino acids into bound muscle protein than was previously appreciated, at least when measured in "anabolically sensitive," recreationally active (but not resistance-trained), young men following resistance exercise. Moreover, this study demonstrated that the duration of the postprandial period is modulated by the dose of ingested protein contained within a meal, that is, the postexercise muscle protein synthesis response to protein ingestion was more prolonged in 100PRO than 25PRO. Both observations represent important scientific advances in the field of protein metabolism. However, we respectfully caution that the practical implications of these findings may have been misinterpreted, at least in terms of dismissing the concept of protein meal distribution as an important factor in optimizing muscle tissue anabolism and/or metabolic health. Moreover, based on emerging evidence, this idea that the anabolic response to protein ingestion has no upper limit does not appear to translate to resistance-trained young women. [ABSTRACT FROM AUTHOR]

UNLABELLED: There is growing interest in engineering Pseudomonas putida KT2440 as a microbial chassis for the conversion of renewable and waste-based feedstocks, and metabolic engineering of P. putida relies on the understanding of the functional relationships between genes. In this work, independent component analysis (ICA) was applied to a compendium of existing fitness data from randomly barcoded transposon insertion sequencing (RB-TnSeq) of P. putida KT2440 grown in 179 unique experimental conditions. ICA identified 84 independent groups of genes, which we call fModules (functional modules), where gene members displayed shared functional influence in a specific cellular process. This machine learning-based approach both successfully recapitulated previously characterized functional relationships and established hitherto unknown associations between genes. Selected gene members from fModules for hydroxycinnamate metabolism and stress resistance, acetyl coenzyme A assimilation, and nitrogen metabolism were validated with engineered mutants of P. putida. Additionally, functional gene clusters from ICA of RB-TnSeq data sets were compared with regulatory gene clusters from prior ICA of RNAseq data sets to draw connections between gene regulation and function. Because ICA profiles the functional role of several distinct gene networks simultaneously, it can reduce the time required to annotate gene function relative to manual curation of RB-TnSeq data sets. IMPORTANCE: This study demonstrates a rapid, automated approach for elucidating functional modules within complex genetic networks. While Pseudomonas putida randomly barcoded transposon insertion sequencing data were used as a proof of concept, this approach is applicable to any organism with existing functional genomics data sets and may serve as a useful tool for many valuable applications, such as guiding metabolic engineering efforts in other microbes or understanding functional relationships between virulence-associated genes in pathogenic microbes. Furthermore, this work demonstrates that comparison of data obtained from independent component analysis of transcriptomics and gene fitness datasets can elucidate regulatory-functional relationships between genes, which may have utility in a variety of applications, such as metabolic modeling, strain engineering, or identification of antimicrobial drug targets.

A diverse array of plant aromatic compounds contributes to the tremendous chemical diversity in the plant kingdom that cannot be seen in microbes or animals. Such chemodiversity of aromatic natural products has emerged, occasionally in a lineage-specific manner, to adopt to challenging environmental niches, as various aromatic specialized metabolites play indispensable roles in plant development and stress responses (e.g. lignin, phytohormones, pigments and defence compounds). These aromatic natural products are synthesized from aromatic amino acids (AAAs), l-tyrosine, l-phenylalanine and l-tryptophan. While amino acid metabolism is generally assumed to be conserved between animals, microbes and plants, recent phylogenomic, biochemical and metabolomic studies have revealed the diversity of the AAA metabolism that supports efficient carbon allocation to downstream biosynthetic pathways of AAA-derived metabolites in plants. This review showcases the intra- and inter-kingdom diversification and origin of committed enzymes involved in plant AAA biosynthesis and catabolism and their potential application as genetic tools for plant metabolic engineering. I also discuss evolutionary trends in the diversification of plant AAA metabolism that expands the chemical diversity of AAA-derived aromatic natural products in plants. This article is part of the theme issue 'The evolution of plant metabolism'. [ABSTRACT FROM AUTHOR]

AbstractAlterations in amino acid metabolism have emerged as a critical component in cancer biology, influencing various aspects of tumor initiation, progression, and metastasis. This review explores how amino acids, beyond their role as protein building blocks, are essential for redox balance, cell proliferation, metastasis, signaling/epigenetic regulation, and tumor microenvironment modulation in cancer. We particularly focus on the intricate relationship between amino acid metabolism and nuclear factor erythroid 2-related factor 2 (NRF2) signaling, a master regulator of oxidative stress response that frequently hyperactivated in cancer. Increasing evidence indicates that NRF2 is a key player in amino acid metabolism, orchestrating metabolism of cysteine, glutamine, and serine/glycine to promote cancer cell survival and growth. This comprehensive analysis provides insights into potential therapeutic strategies targeting the NRF2-amino acid metabolism axis, offering new avenues for cancer treatment that address multiple aspects of tumor biology. [ABSTRACT FROM AUTHOR]

The article pays tribute to the late Professor Peter J. Lea, a renowned scientist and Emeritus Professor at Lancaster University. Professor Lea's research focused on nitrogen assimilation in plants, contributing significantly to crop improvement and nitrogen metabolism. He was also involved in various activities, such as serving as President of the Association of Applied Biologists and mentoring students and scientists. His impactful work and collaborations have left a lasting legacy in the field of plant science. [Extracted from the article]

Pyroglutamic acid [(5-oxoproline (5-oxp)], a non-protein amino acid, can be converted to glutamate to regulate amino acid metabolism in plants. Its roles in plant adaptation to abiotic stresses, including heat stress, are not well understood. The objectives of this study were to determine whether exogenous application of 5-oxp could promote heat tolerance in cool-season perennial grass species and identify the major metabolic pathways that could be activated or responsive to 5-oxp for enhancing heat tolerance. Perennial ryegrass (Lolium perenne L.) plants were foliar-sprayed with 5-oxp or water (untreated control) prior to and during the exposure to heat stress (35/33 ℃, day/night temperature) or ambient temperature (25/22 ℃, day/night temperature, non-stress control) in controlled-environment growth chambers. Application of 5-oxp improved the heat tolerance of perennial ryegrass, as manifested by the chlorophyll content, photochemical efficiency, cell membrane stability, and antioxidant enzyme activities increasing by 31.2%, 25.7%, 37.2%, and 57.1-258.3%, as well as the reduction in hydrogen peroxide production by 36.8%. Metabolic profiling identified metabolites up-regulated by 5-oxp that are involved in the metabolic pathways of carbon assimilation in photosynthesis, glycolysis and the tricarboxylic acid cycle of respiration, proteinogenic amino acid metabolism, glutathione metabolism, and nucleotide metabolism for DNA or RNA synthesis and ATP generation. The up-regulation or activation of those metabolic processes could contribute to 5-oxp-mediated enhancement in the heat tolerance of perennial ryegrass. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSC) are considered an aberrant population of immature myeloid cells that have attracted considerable attention in recent years due to their potent immunosuppressive activity. These cells are typically absent or present in very low numbers in healthy individuals but become abundant under pathological conditions such as chronic infection, chronic inflammation and cancer. The immunosuppressive activity of MDSC helps to control excessive immune responses that might otherwise lead to tissue damage. This same immunosuppressive activity can be detrimental, particularly in cancer and chronic infection. In the cancer setting, tumors can secrete factors that promote the expansion and recruitment of MDSC, thereby creating a local environment that favors tumor progression by inhibiting the effective immune responses against cancer cells. This has made MDSC a target of interest in cancer therapy, with researchers exploring strategies to inhibit their function or reduce their numbers to improve the efficacy of cancer immunotherapies. In the context of chronic infections, MDSC can lead to persistent infections by suppressing protective immune responses thereby preventing the clearance of pathogens. Therefore, targeting MDSC may provide a novel approach to improve pathogen clearance during chronic infections. Ongoing research on MDSC aims to elucidate the exact processes behind their expansion, recruitment, activation and suppressive mechanisms. In this context, it is becoming increasingly clear that the metabolism of MDSC is closely linked to their immunosuppressive function. For example, MDSC exhibit high rates of glycolysis, which not only provides energy but also generates metabolites that facilitate their immunosuppressive activity. In addition, fatty acid metabolic pathways, such as fatty acid oxidation (FAO), have been implicated in the regulation of MDSC suppressive activity. Furthermore, amino acid metabolism, particularly arginine metabolism mediated by enzymes such as arginase-1, plays a critical role in MDSC-mediated immunosuppression. In this review, we discuss the metabolic signature of MDSC and highlight the therapeutic implications of targeting MDSC metabolism as a novel approach to modulate their immunosuppressive functions. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a persistent incurable mental disorder and is characterized by the manifestation of negative emotions and behaviors with anxiety and depression, fear and insecurity, self-harm and social withdrawal. The intricate molecular mechanisms underlying this phenomenon remain largely elusive. Accumulating evidence points towards the gut microbiota exerting an influence on brain function via the gut-brain axis, potentially contributing to the development of schizophrenia. Therefore, the objective of this study is to delineate the gut microbial composition and metabolic profile of fecal samples from individuals with schizophrenia. Methods: Liquid chromatography-mass spectrometry (LC-MS) and 16S ribosomal RNA (16S rRNA) gene sequencing were employed to analyze fecal metabolites and gut microbiota profiles in a cohort of 29 patients diagnosed with schizophrenia and 30 normal controls. The microbial composition of fecal samples was determined through the 16S rRNA gene sequencing, and microbial α-diversity and β-diversity indices were calculated. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to analyze the distribution of samples. The metabolites and gut microbiota exhibiting differential expression were identified through the application of biological variance criteria. Co-occurrence analysis of bacteria and metabolites was conducted using the spearman's rank correlation coefficient and visualized in a circular layout with the Cytoscape software. Results: The findings of the study indicated a lack of substantial evidence supporting significant disparities in α-diversity and β-diversity between individuals with schizophrenia and normal controls. In terms of metabolomics, a discernible pattern in sample distribution between the two groups was observed. Our analysis has revealed 30 bacterial species and 45 fecal metabolites that exhibited notable differences in abundance between individuals diagnosed with schizophrenia and normal controls. These alterations in multilevel omics have led to the development of a co-expression network associated with schizophrenia. The perturbed microbial genes and fecal metabolites consistently demonstrated associations with amino acid and lipid metabolism, which play essential roles in regulating the central nervous system. Conclusion: Our results offered profound insights into the impact of imbalanced gut microbiota and metabolism on brain function in individuals with schizophrenia. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore whether and how Bacillus subtilis KC1 can enhance the growth performance of Mycoplasma gallisepticum (MG)-infected broilers. Broilers were randomly divided into 4 groups: the control group (basal diet), the MG group (basal diet + MG challenge), the KC group (basal diet + B. subtilis KC1 supplementation), the KC + MG group (basal diet + B. subtilis KC1 supplementation + MG challenge). The results showed that, compared to the control group, MG group exhibited significantly reduced body weight and average daily gain, and increased feed conversion ratio of broilers. However, compared to the MG group, the B. subtilis KC1 + MG group exhibited significantly improved above indicators of growth performance. In addition, compared to the MG group, B. subtilis KC1 + MG group exhibited increased superoxide dismutase levels and reduced levels of malondialdehyde, interleukin-1β, and tumor necrosis factor- α of broilers. Furthermore, metabolomics and transcriptomics analyses indicated that MG infection disrupted amino acid metabolism in broilers, whereas B. subtilis KC1 supplementation alleviated the abnormal amino acid metabolism caused by MG. These results suggested that B. subtilis KC1 may alleviate the poor growth performance caused by MG infection in broilers by improving amino acid metabolism. [ABSTRACT FROM AUTHOR]

Microplastic is globally regarded as an important factor impacting biogeochemical cycles, yet our understanding of such influences is limited by the uncertainties of intricate microbial processes. By multiomics analysis, coupled with soil chemodiversity characterization and microbial carbon use efficiency (CUE), we investigated how microbial responses to microplastics impacted soil carbon cycling in a long-term field experiment. We showed that biodegradable microplastics promoted soil organic carbon accrual by an average of 2.47%, while nondegradable microplastics inhibited it by 17.4%, as a consequence of the virus-bacteria coadaptations to the microplastics disturbance. In the relevant functional pathways, nondegradable microplastics significantly (P < 0.05) enhanced the abundance and transcriptional activity related to complex carbohydrate metabolism, whereas biodegradable microplastics significantly (P < 0.05) promoted functions involved in amino acid metabolism and glycolysis. Accordingly, viral lysis enhanced in nondegradable microplastics treatments to introduce more complex organic compounds to soil dissolved organic matters, thus benefiting the oligotrophs with high carbon metabolic capabilities in exploitation competition. In contrast, biodegradable microplastics enriched viral auxiliary metabolic genes of carbon metabolism through "piggyback-the-winner" strategy, conferring to dominant copiotrophs, enhanced substrate utilization capabilities. These virus-host interactions were also demonstrated in the corresponding soil plastisphere, which would alter microbial resource allocation and metabolism via CUE, affecting carbon storage consequently. Overall, our results underscore the importance of viral-host interactions in understanding the microplastics-dependent carbon storage in the soil ecosystem. [ABSTRACT FROM AUTHOR]

Introduction: Cutibacterium acnes (C. acnes) resides in various organs such as the skin, prostate, eye, nose, stomach, and intestine, indicating the possibility of extensive crosstalk between this bacterium and the human body. C. acnes strains are classified into three subspecies based on phylogenetics and distinguishable phenotypes. Among them, C. acnes subsp. defendens strains are characterized by anti-inflammatory features, raising expectations for their potential as future microbiome therapeutics. However, the heterogeneity of C. acnes subsp. defendens and its corresponding immunological functions have not been clearly addressed. Methods: The genetic diversity of the strains was assessed using single- and multi-locus sequence typing. Their immune-modulatory functions were evaluated in vitro using 2D and 3D assays with immune and epithelial cells. The anti-inflammatory effects were further confirmed in vivo using a rosacea-like mouse model. Comparative genomic and transcriptomic analyses were conducted to uncover mechanisms underlying the immunosuppressive activity of the strains. Results: We demonstrated that the newly isolated C. acnes subsp. defendens strains, exhibiting phenotypic heterogeneity, are distinctly clustered using single- and multi-locus sequence typing methods. These strains showed strong immune-regulatory functions in immune and epithelial cell-based 2D and 3D in vitro assays. Furthermore, their anti-inflammatory role was functionally confirmed in vivo using a rosacea-like mouse model, where they alleviated skin lesions characterized by hyperplasia and dermal inflammation. Comparative transcriptomics revealed that these strains may exert their immunosuppressive effects through the enhanced expression of acnecins and transcriptional variation in envelope stress regulators (specifically the two-component systems, CesSR homologs). Additionally, we propose that these C. acnes type II strains produce anti-inflammatory metabolites or peptides smaller than 3 kDa, which are associated with elevated pyrimidine and reduced L-arginine biosynthesis. Discussion: The newly isolated C. acnes subsp. defendens strains demonstrate significant anti-inflammatory properties both in vitro and in vivo , suggesting their potential as microbiome-based therapeutics. Their unique genomic and transcriptomic profiles, including the production of small bioactive compounds and specific transcriptomic patterns, underpin their immunosuppressive capabilities. These findings provide a foundation for developing novel treatments for inflammatory skin conditions, such as rosacea. [ABSTRACT FROM AUTHOR]

CD8 + T cells have critical roles in tumor control, but a range of factors in their microenvironment such as low pH can suppress their function. Here, we demonstrate that acidity restricts T-cell expansion mainly through impairing IL-2 responsiveness, lowers cytokine secretion upon re-activation, and reduces the cytolytic capacity of CD8 + T cells expressing low-affinity TCR. We further find decreased mTORC1 signaling activity and c-Myc levels at low pH. Mechanistically, nuclear/cytoplasmic acidification is linked to mTORC1 suppression in a Rheb-, Akt/TSC2/PRAS40-, GATOR1- and Lkb1/AMPK-independent manner, while c-Myc levels drop due to both decreased transcription and higher levels of proteasome-mediated degradation. In addition, lower intracellular levels of glutamine, glutamate, and aspartate, as well as elevated proline levels are observed with no apparent impact on mTORC1 signaling or c-Myc levels. Overall, we suggest that, due to the broad impact of acidity on CD8 + T cells, multiple interventions will be required to restore T-cell function unless intracellular pH is effectively controlled. Synopsis: Extracellular acidity is a common immunosuppressive feature of tumors. This study reveals that low pH suppresses T-cell functions and alters IL-2/IL-2R, mTORC1, and c-Myc signaling, as well as amino acid metabolism. Acidity increases the activation threshold in CD8 + T cells and lowers their cytotoxic potential, cytokine secretion, and cell proliferation upon re-activation. Acidity decreases IL-2/IL-2R binding, IL-2R levels, and IL-2 intracellular signaling, to lower the proliferative capacity of CD8 + T cells. Acidic conditions (pH 6.6) suppress mTORC1 signaling independently of impaired IL-2R signaling and of Rheb, Akt, TSC, PRAS40, GATOR1 and Lkb1/AMPK. Low pH decreases c-Myc levels via proteasomal degradation and lower transcription. Low pH reduces glutamine import and enhances intracellular glutamine-to-proline conversion to modulate cellular amino acid ratios. Tumor-associated acidic microenvironments cause reduced CD8 + T cell proliferation, expansion, and cytolytic potential by broadly interfering with intracellular signaling. [ABSTRACT FROM AUTHOR]

Background: Continuous cropping of the same crop leads to land degradation. This is also called the continuous-cropping obstacle. Currently, intercropping tobacco with other crops can serve as an effective strategy to alleviate continuous cropping obstacles. Results: In this study, tobacco K326 and insectary floral plants were used as materials, and seven treatments of tobacco monoculture (CK), tobacco intercropped with Tagetes erecta, Vicia villosa, Fagopyrum esculentum, Lobularia maritima, Trifolium repens, and Argyranthemum frutescens respectively, were set up to study their effects on rhizosphere soil chemical properties and composition and structure of rhizosphere soil microbial community of tobacco. The 16 S rRNA gene and ITS amplicons were sequenced using Illumina high-throughput sequencing. tobacco/insectary floral plants intercropping can influence rhizosphere soil chemical properties, which also change rhizosphere microbial communities. The CK and treatment groups tobacco rhizosphere soil microorganisms had significantly different genera, such as tobacco intercropping with T. repens and A. frutescens significantly increased the number of Fusarium and intercropping T. erecta, V. villosa, L. maritima, T. repens, and A. frutescens significantly increased the number of Sphingomonas and unknown Gemmatimonadaceae. Additionally, intercropping T. erecta, V. villosa and L. maritima changed the rhizosphere fungal and bacteria community and composition of tobacco and the positive correlation between tobacco rhizosphere the genera of fungi and bacterial were greater than CK. The pathway of the carbohydrate metabolism, amino acid metabolism, and energy metabolism in rhizosphere bacteria were significantly decreased after continuous cropping. Fungal symbiotic trophic and saprophytic trophic were significantly increased after intercropping V. villosa, L. maritima and plant pathogen and animal pathogen were increased after intercropping T. repens and A. frutescens. Additionally, bacterial and fungal communities significantly correlated with soil chemical properties, respectively. Conclusion: This study reveals that intercropping tobacco with insectary floral plants, particularly T. erecta, V. villosa, L. maritima and A. frutescens significantly affects soil chemical properties and alters rhizosphere microbial communities, increasing the abundance of certain microbial genera. Additionally, intercropping enhances pathways related to carbohydrate, amino acid, and energy metabolism in rhizosphere bacteria. These findings suggest that intercropping could provide a promising strategy to overcome challenges associated with continuous tobacco cropping by regulating the rhizosphere environment. [ABSTRACT FROM AUTHOR]

Background: Streptococcus canis is a commensal bacterium in companion animals. This microorganism can infect humans who have been in deep contact with or bitten by pet dogs, suggesting that the skin/soft tissue is one of infection entry sites. To understand pathological process in human cells, we aimed to determine S. canis transcriptomic changes in invasive environments of human keratinocytes. Methods: We selected one isolate from candidates with whole-genome sequences, based on re-obtained cell invasion ability (CIA) data into human keratinocytes along with bacterial cytotoxicity. RNA-sequencing was conducted for the samples at baselines and 2 h/5 hr post-inoculation using NovaSeq 6000. Global/differential gene expression analyses [principal component analysis (PCA)/k-means clustering analysis/differentially expressed gene (DEG) analyses] were performed. We classified DEGs into their functional categories. To validate transcriptomic results, we did quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Results: FU1 isolate was selected from seven candidates, based on re-obtained CIA data with less cytotoxicity. Total read bases of 6.17–9.02 Gbp were obtained by RNA-sequencing. PCA and k-means clustering analysis indicated clustering according to their inoculation times. Volcano plots and Venn diagrams revealed that S. canis invasion into keratinocytes produced altered distributions of many genes. Gene ontology enrichment analysis showed most of the gene expressions were downregulated. DEG functional analysis showed the downregulated DEGs belonging to energy production and conversion/carbohydrate transport and metabolism/amino acid transport and metabolism/nucleotide transport and metabolism, with the upregulated DEGs belonging to transcription. qRT-PCR assays for downregulated/upregulated expressions of four genes (pgk–slo/opuAA–kdpB) validated transcriptomic results. Conclusion: Our observations suggest that S. canis can downregulate its metabolism-associated gene expressions in human keratinocyte environments. The observed gene expression changes can imply the latent infection in human cells. Further investigation is needed to elucidate the underlying mechanisms for the latent infection. [ABSTRACT FROM AUTHOR]

Introduction: Long-term use of chemical fertilizers (CFs) can cause soil compaction and acidification. In recent years, bio-organic fertilizers (BOFs) have begun to replace CFs in some vegetables and cash crops, but the application of CFs or BOFs has resulted in crop quality and disease occurrence. Methods: This study aimed to analyze the microbial mechanism of differences between CFs and BOFs in root disease, quality, and yield of tuber Chinese herbal medicine. We studied the effects of CFs, organic fertilizers, commercial BOFs, biocontrol bacteria BOFs, and biocontrol fungi BOFs on rhizosphere microbial community structure and function, root rot, quality, and yield of Codonopsis pilosula at different periods after application and analyzed the correlation. Results and discussion: Compared to CFs, the emergence rate and yield in BOF treatments were increased by 21.12 and 33.65%, respectively, and the ash content, water content, and disease index in the BOF treatments were decreased by 17.87, 8.19, and 76.60%, respectively. The structural equation model showed that CFs promoted the quality and yield of C. pilosula by influencing soil environmental factors, while BOFs directly drove soil bacterial community to reduce disease index and improve the quality and yield of C. pilosula. There was a stronger interaction and stability of soil microbial networks after BOF treatments. Microlunatus , Rubrobacter , Luteitalea , Nakamurella , and Pedomicrobium were identified as effector bacteria, which were related to disease prevention and yield and quality increase of C. pilosula. Microbial functional analysis indicated that the signal transduction and amino acid metabolism of soil bacteria might play a major role in improving the quality and yield of C. pilosula in the early and middle growth stages. In conclusion, compared to CFs, BOFs obtained a lower disease index of root rot and a higher quality and yield of C. pilosula by changing the structure and function of the rhizosphere bacterial community. [ABSTRACT FROM AUTHOR]

Introduction: Hyperlipidemia is a condition characterized by abnormal levels of lipids and lipoproteins in the plasma, posing significant health risks. Ferulic acid (FA) is an organic acid with therapeutic properties for diabetes and hyperlipidemia. Methods: To explore biomarkers for FA treatment of hyperlipidemia and elucidate the mechanisms of lipid-lowering-related changes in metabolic pathways by metabolomics and network pharmacology. Initially, a hyperlipidemic mouse model induced by triton WR-1339 was established to evaluate the therapeutic effects of FA. Subsequently, serum metabolomics was utilized to identify differential metabolites, and metabolic pathway analysis was performed using MetaboAnalyst 6.0. Thirdly, network pharmacology was employed to identify potential targets of FA for hyperlipidemia. Finally, the compound-target-metabolite (C-T-M) network obtained core targets and validated them with molecular docking. Results: Biochemical analysis and histological examination showed that FA had lipid-lowering effects on hyperlipidemic mice. It identified 31 potential biomarkers for FA against hyperlipidemia by metabolomics involving lipid and amino acid metabolism. Lipid and atherosclerosis signaling pathways were identified as the key signaling pathways of FA against hyperlipidemia by KEGG analysis. Conjoint analysis showed that FA against hyperlipidemia was associated with 18 core targets and six biomarkers. Molecular docking results showed that FA has a high binding affinity to these core targets. Discussion: Through the synergy of network pharmacology and metabolomics, this study provides insights into how FA regulates endogenous metabolites, underscoring its promise as a treatment for hyperlipidemia. [ABSTRACT FROM AUTHOR]

Amino acids are essential building blocks for proteins, crucial energy sources for cell survival, and key signaling molecules supporting the resistant growth of tumor cells. In tumor cells, amino acid metabolic reprogramming is characterized by the enhanced uptake of amino acids as well as their aberrant synthesis, breakdown, and transport, leading to immune evasion and malignant progression of tumor cells. This article reviews the altered amino acid metabolism in tumor cells and its impact on tumor microenvironment, and also provides an overview of the current clinical applications of amino acid metabolism. Innovative drugs targeting amino acid metabolism hold great promise for precision and personalized cancer therapy. [ABSTRACT FROM AUTHOR]

Mutations in the SLC1A4 transporter lead to neurodevelopmental impairments, spastic tetraplegia, thin corpus callosum and microcephaly in children. SLC1A4 catalyses obligatory amino acid exchange between neutral amino acids, but the physiopathology of SLC1A4 disease mutations and progressive microcephaly remain unclear. Here, we examined the phenotype and metabolic profile of three Slc1a4 mouse models: a constitutive Slc1a4-knockout mouse; a knock-in mouse with the major human Slc1a4 mutation (Slc1a4-K256E); and a selective knockout of Slc1a4 in brain endothelial cells (Slc1a4tie2-cre). We show that Slc1a4 is a bona fide L- serine transporter at the blood–brain barrier (BBB) and that acute inhibition or deletion of Slc1a4 leads to a decrease in serine influx into the brain. This results in microcephaly associated with decreased L- serine content in the brain, accumulation of atypical and cytotoxic 1-deoxysphingolipids, neurodegeneration, synaptic and mitochondrial abnormalities and behavioural impairments. Prenatal and early postnatal oral administration of L- serine at levels that replenish the serine pool in the brain rescued the observed biochemical and behavioural changes. Administration of L- serine until the second postnatal week also normalized brain weight in Slc1a4-E256K mice. Our observations suggest that the transport of 'non-essential' amino acids from the blood through the BBB is at least as important as that of essential amino acids for brain metabolism and development. We propose that SLC1A4 mutations cause a BBB aminoacidopathy with deficits in serine import across the BBB, required for optimal brain growth, leading to a metabolic microcephaly, which may be amenable to treatment with L- serine. [ABSTRACT FROM AUTHOR]

The cytochrome P450s enzyme family metabolizes ∼80% of small molecule drugs. Variants in cytochrome P450s can substantially alter drug metabolism, leading to improper dosing and severe adverse drug reactions. Due to low sequence conservation, predicting variant effects across cytochrome P450s is challenging. Even closely related cytochrome P450s like CYP2C9 and CYP2C19, which share 92% amino acid sequence identity, display distinct phenotypic properties. Using variant abundance by massively parallel sequencing, we measured the steady-state protein abundance of 7,660 single amino acid variants in CYP2C19 expressed in cultured human cells. Our findings confirmed critical positions and structural features essential for cytochrome P450 function, and revealed how variants at conserved positions influence abundance. We jointly analyzed 4,670 variants whose abundance was measured in both CYP2C19 and CYP2C9, finding that the homologs have different variant abundances in substrate recognition sites within the hydrophobic core. We also measured the abundance of all single and some multiple wild type amino acid exchanges between CYP2C19 and CYP2C9. While most exchanges had no effect, substitutions in substrate recognition site 4 reduced abundance in CYP2C19. Double and triple mutants showed distinct interactions, highlighting a region that points to differing thermodynamic properties between the 2 homologs. These positions are known contributors to substrate specificity, suggesting an evolutionary tradeoff between stability and enzymatic function. Finally, we analyzed 368 previously unannotated human variants, finding that 43% had decreased abundance. By comparing variant effects between these homologs, we uncovered regions underlying their functional differences, advancing our understanding of this versatile family of enzymes. [ABSTRACT FROM AUTHOR]

In this study, "Longjia (LJ)" and "Yangpao (YP)"exhibited higher contents of major nutrients compared to "Niangqing (NQ)" walnuts. The combination of transcriptome and proteome by RNA sequencing and isotope labeling for relative and absolute quantification techniques provides new insights into the molecular mechanisms underlying the nutritional quality of the three walnut species. A total of 4146 genes and 139 proteins showed differential expression levels in the three comparison groups. Combined transcriptome and proteome analyses revealed that these genes and proteins were mainly enriched in signaling pathways such as fatty acid biosynthesis, protein processing in endoplasmic reticulum, and amino acid metabolism, revealing their relationship with the nutritional quality of walnut kernels. This study identified key genes and proteins associated with nutrient metabolism and accumulation in walnut kernels, provided transcriptomic and proteomic information on the molecular mechanisms of nutrient differences in walnut kernels, and contributed to the elucidation of the mechanisms of nutrient differences and the selection and breeding of high-quality walnut seedlings. [ABSTRACT FROM AUTHOR]

Intracellular AA regulate milk protein synthesis within the mammary gland by modifying mammary plasma flow (MPF) and AA transporter activity. Amino acid transporters catalyze translocation using Na+ gradient, substrate gradient (uniporters), and exchange mechanisms; further, they exhibit specificity for individual AA or groups of AA with similar side-chain properties within each transport system. Nonessential AA are actively transported through Na+-dependent transporters and, thus, are often used as intracellular currencies for EAA transport through exchange transporters. Therefore, it was hypothesized that individual EAA supplementation would compete with other EAA for shared transporters, and supplementation with Ala, Gln, and Gly would stimulate EAA transport through exchange transporters. Ten primiparous lactating dairy cows were divided into 2 groups based on milk production and were randomly assigned to treatment sequences within 2 balanced 5 × 5 Latin squares by group. Period length was 14 d. Treatments were 9-d jugular infusions of (1) saline; (2) 34.5 g of Val per day; (3) a ratio of 32.7 g of Ala to 40 g of Gln to 26.7 g of Gly per day (AQG); (4) 43 g of Lys per day; or (5) 33.5 g of Ile per day. All cows were fed a common base diet formulated to contain 15.0% CP. Infusions of Ile, Lys, or AQG did not affect milk protein or milk production; however, Val infusion decreased both. The effects of Val infusion on milk protein production appeared to be partially driven by decreased DMI. The decline in milk protein percentage indicated that milk lactose production was also affected. Additionally, Val infusion increased MPF efficiency (MPF/milk; L/L) by approximately 44%. Infusion of Val tended to decrease or decreased mammary net uptakes of Lys, Leu, Met, and total AA. Infusion of Ile tended to increase its mammary net uptakes but did not affect any other AA. Infusions of Lys and AQG did not affect any mammary net uptakes. Infusion of Val tended to decrease Phe and total NEAA mammary clearance rates. Infusion with AQG stimulated Tyr clearance rates and tended to decline system N mammary clearance rates. Ratios of branched-chain AA mammary uptake to milk protein output (U:O) did not differ from 1 for Val-infused cows, which indicated that little intramammary catabolism was occurring. Additionally, the average NEAA U:O in response to all treatments except Val was 0.70, but Val-infused cows had NEAA U:O that averaged 0.09, indicating increased synthesis within the glands. The effects of Val on mammary net clearance rates of multiple EAA support the incorporation of AA limitations in ration optimizers to prevent AA imbalances. It is possible that oversupplementation of EAA other than Val may also decrease DMI and mammary activity. Identifying efficiency apexes for each of the EAA will allow more precise diet formulation and supplementation, leading to improved production efficiency. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Purpose: To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or 18F-FDG positron-emission-tomography (PET)-CT]. Methods: 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with 18F-fluciclovine and 68Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and 18F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of 18F-fluciclovine and 68Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test. Results: The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. 68Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. 18F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for 18F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between 68Ga-PSMA-11 and standard-of care imaging. 18F-fluciclovine cDR was also significantly higher than 68Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with 18F-fluciclovine (n = 18) was significantly greater than for 68Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021]. Conclusion: In this exploratory trial, 18F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to 68Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with 18F-fluciclovine than for 68Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study. Clinical trial registration: Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280). [ABSTRACT FROM AUTHOR]

• Nitric oxide (NO) induce tolerance to cadmium stress. • Nitric oxide induces antioxidant defense system and osmolytes accumulation. • Nitric oxide alleviate cadmium stress by regulating genes related to signal transduction, carbohydrate transport and metabolism, amino acid biosynthesis and phenylpropane biosynthesis. Cadmium (Cd) is harmful to the environment, as it is a non-essential biological element. It leads to the normal dysfunction and degradation of soil quality, and is toxic to plants. Many studies reported that the application of nitric oxide (NO) can effectively reduce the toxicity of Cd in plants. However, the underlying molecular mechanism of the positive effects of exogenous NO on plant Cd tolerance has not been well documented. In the present study, comparative transcriptome analysis was performed on Kentucky bluegrass seedlings treated with Cd (Cd alone) and Cd + NO (Cd and NO simultaneously).Comparative transcriptional regulation analysis showed that Differential expressed genes (DEGs) was mainly involved in mitogen-activated protein kinase (MAPK) signal transduction, plant hormone signal transduction, phenylpropanoid biosynthesis, amino acid transport and metabolism, fatty acid metabolism and biosynthesis related pathways. These results suggest that exogenous NO may alleviate cadmium stress by regulating genes related to signal transduction, carbohydrate transport and metabolism, amino acid biosynthesis and phenylpropane biosynthesis. Additionally, the DEGs and metabolic pathways between Cd and Cd + NO treatment groups were analyzed in this study, and a series of key genes mediated by NO signal in response to cadmium stress were screened out, and they were listed as candidate genes related to NO alleviating cadmium stress in Kentucky bluegrass. This study helps to understand the transcriptional regulation and complex internal network of exogenous NO alleviating Cd -tolerance in Kentucky bluegrass. [ABSTRACT FROM AUTHOR]

Background: Necrotic enteritis (NE) is an economically important disease of broiler chickens caused by Clostridium perfringens (CP). The pathogenesis, or disease process, of NE is still not clear. This study aimed to identify the alterations of metabolites and metabolic pathways associated with subclinical or clinical NE in CP infected birds and to investigate the possible variations in the metabolic profile of birds infected with different isolates of CP. Methodology: Using a well-established NE model, the protein content of feed was changed abruptly before exposing birds to CP isolates with different toxin genes combinations (cpa, cpb2, netB, tpeL; cpa, cpb2, netB; or cpa, cpb2). Metabolomics analysis of jejunal contents was performed by a targeted, fully quantitative LC-MS/MS based assay. Results: This study detected statistically significant differential expression of 34 metabolites including organic acids, amino acids, fatty acids, and biogenic amines, including elevation of butyric acid at onset of NE in broiler chickens. Subsequent analysis of broilers infected with CP isolates with different toxin gene combinations confirmed an elevation of butyric acid consistently among 21 differentially expressed metabolites including organic acids, amino acids, and biogenic amines, underscoring its potential role during the development of NE. Furthermore, protein-metabolite network analysis revealed significant alterations in butyric acid and arginine-proline metabolisms. Conclusion: This study indicates a significant metabolic difference between CP-infected and non-infected broiler chickens. Among all the metabolites, butyric acid increased significantly in CP-infected birds compared to non-infected healthy broilers. Logistic regression analysis revealed a positive association between butyric acid (coefficient: 1.23, P < 0.01) and CP infection, while showing a negative association with amino acid metabolism. These findings suggest that butyric acid could be a crucial metabolite linked to the occurrence of NE in broiler chickens and may serve as an early indicator of the disease at the farm level. Further metabolomic experiments using different NE animal models and field studies are needed to determine the specificity and to validate metabolites associated with NE, regardless of predisposing factors. [ABSTRACT FROM AUTHOR]

Objective: Nicotinamide (NAM) is easily degraded in the rumen, but the rumen-protected NAM (RPN) supplementation might enable the use of NAM in ruminants. This study aimed to elucidate the effects of RPN supplementation on growth performance, rumen fermentation, antioxidant status and amino acid (AA) metabolism in growing lambs. Methods: A total of 128 healthy and similar lambs (21.3±0.28 kg, 70±6.3 days of age) were allotted to 1 of 4 groups. The treatments were 0, 0.5, 1, and 2 g/d RPN supplementation. The RPN products (50% bioavailability) were fed at 0700 h every day for 12 weeks. All lambs were fed the same pelleted total mixed rations to allow ad libitum consumption and had free access to water. Results: The RPN tended to increase the average daily gain and feed efficiency. The tendencies of RPNxday interaction were found for dry matter intake during the entire study (p = 0.078 and 0.073, respectively). The proportions of acetic acid, isobutyric acid and isovaleric acid were decreased, whereas the proportions of propionic acid and valeric acid were increased (p<0.05). The ratio of acetic acid to propionic acid was decreased (p<0.05). Moreover, the antioxidative status was enhanced and the glucose concentration was increased by RPN (p<0.05). In addition, 17 AAs were detected in plasma, of which 11 AAs were increased by RPN (p<0.05). Plasma metabolomics analysis identified 1,395 compounds belonging to 15 classes, among which 7 peptides were significantly changed after RPN supplementation. Conclusion: Overall, the results suggested that RPN supplementation favoured the rumen fermentation pattern to propionic acid-type with benefited glucose metabolism, enhanced antioxidant capacity, and changed the AA and small peptide metabolism. This study provides a new perspective for studying the relationship between vitamin and AA metabolism. [ABSTRACT FROM AUTHOR]

Although evidence has documented the associations of ambient air pollution with chronic respiratory diseases (CRDs) and lung function, the underlying metabolic mechanisms remain largely unclear. How does the metabolomic signature for air pollution relate to CRD risk, respiratory symptoms, and lung function? We retrieved 171,132 participants free of COPD and asthma at baseline from the UK Biobank, who had data on air pollution and metabolomics. Exposures to air pollutants (particulate matter with diameter ≤ 2.5 μm [PM 2.5 ], particulate matter with a diameter ≤ 10 μm, nitrogen oxide [NO X ], and NO 2) were assessed for 4 years before baseline considering residential address histories. We used 10-fold cross-validation elastic net regression to identify air pollution-associated metabolites. Multivariable Cox models were used to assess the associations between metabolomic signatures and CRD risk. Mediation and pathway analysis were conducted to explore the metabolic mechanism underlying the associations. During a median follow-up of 12.51 years, 8,951 and 5,980 incident COPD and asthma cases were recorded. In multivariable Cox regressions, air pollution was positively associated with CRD risk (eg, hazard ratio per interquartile range increment in PM 2.5 , 1.09; 95% CI, 1.06-1.13). We identified 103, 86, 85, and 90 metabolites in response to PM 2.5 , particulate matter with a diameter ≤ 10 μm, NO X , and NO 2 exposure, respectively. The metabolomic signatures showed significant associations with CRD risk (hazard ratio per SD increment in PM 2.5 metabolomic signature, 1.11; 95% CI, 1.09-1.14). Mediation analysis showed that peripheral inflammatory and erythrocyte-related markers mediated the effects of metabolomic signatures on CRD risk. We identified 14 and 12 perturbed metabolic pathways (energy metabolism and amino acid metabolism pathways, etc) for PM 2.5 and NO X metabolomic signatures. Our study identifies metabolomic signatures for air pollution exposure. The metabolomic signatures showed significant associations with CRD risk, and inflammatory- and erythrocyte-related markers partly mediated the metabolomic signatures-CRD links. [ABSTRACT FROM AUTHOR]

Transthyretin (TTR), a homotetrameric protein found in plasma, cerebrospinal fluid, and the eye, plays a pivotal role in the onset of several amyloid diseases with high morbidity and mortality. Protein aggregation and fibril formation by wild-type TTR and its natural more amyloidogenic variants are hallmarks of ATTRwt and ATTRv amyloidosis, respectively. The formation of soluble amyloid aggregates and the accumulation of insoluble amyloid fibrils and deposits in multiple tissues can lead to organ dysfunction and cell death. The most frequent manifestations of ATTR are polyneuropathies and cardiomyopathies. However, clinical manifestations such as carpal tunnel syndrome, leptomeningeal, and ocular amyloidosis, among several others may also occur. This review provides an up-to-date listing of all single amino-acid mutations in TTR known to date. Of approximately 220 single-point mutations, 93% are considered pathogenic. Aspartic acid is the residue mutated with the highest frequency, whereas tryptophan is highly conserved. "Hot spot" mutation regions are mainly assigned to β-strands B, C, and D. This manuscript also reviews the protein aggregation models that have been proposed for TTR amyloid fibril formation and the transient conformational states that convert native TTR into aggregation-prone molecular species. Finally, it compiles the various in vitro TTR aggregation protocols currently in use for research and drug development purposes. In short, this article reviews and discusses TTR mutagenesis and amyloidogenesis, and their implications in disease onset. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor-Natural Killer-92 (CAR-NK-92) cell therapy has broad prospects as an effective cellular immunotherapy. Efficient CAR-NK-92 cell expansion ex vivo is crucial for its development and wide use. Unlike NK-92 cells, CAR-NK-92 cells need to maintain the stability of CAR expression during culture, besides keeping cell function. This work compared the growth and metabolism between NK-92 cells and CAR-NK-92 cells and found that the expansion efficiency of CAR-NK-92 cells was significantly lower than that of NK-92 cells. Meanwhile, the amino acid metabolism related to reducing agent production in CAR-NK-92 cells was weaker than in NK-92 cells, resulting in higher intracellular oxidation levels. The antioxidant N-acetylcysteine (NAC) was used to regulate the intracellular redox status of CAR-NK-92 cells. Under 1 mM NAC, the intracellular reactive oxygen species (ROS) level of CAR-NK-92 cells was down-regulated, and the cell expansion ability was improved. Furthermore, the addition of NAC has increased the levels of GSH and NADPH in CAR-NK-92 cells, elevated GSH/GSSG ratio and NADPH/NADP+ ratio, enhanced the antioxidant capacity and mitochondrial function of cells, and promoted cell expansion. This study aims to promote CAR-NK-92 cell expansion ex vivo by regulating intracellular redox levels to facilitate its clinical application. [Display omitted] • The proliferation and redox-related amino acids metabolism of CAR-NK-92 cells were significantly weaker than NK-92 cells. • N-acetylcysteine regulates the intracellular redox state by reducing the level of ROS in CAR-NK-92 cells. • 1 mM NAC can promote CAR-NK-92 cell expansion ex vivo. [ABSTRACT FROM AUTHOR]

BACKGROUND: Alicyclobacillus acidoterrestris is a common microorganism in fruit juice. It can produce off‐odor metabolites and has been considered to be an important factor in juice contamination. Thus, the development of new strategy for the control of A. acidoterrestris has important practical significance. The primary objective of this work was to assess the antibacterial performance of ε‐polylysine‐functionalized magnetic composites (Fe3O4@MoS2@PAA‐EPL) in apple juice and its effect on juice quality. Moreover, the molecular mechanism of Fe3O4@MoS2@PAA‐EPL against A. acidoterrestris was explored by RNA sequencing (RNA‐Seq). RESULTS: Experimental results indicated that the synthesized composites possessed the ability to inhibit the viability of A. acidoterrestris vegetative cells and spores. Besides, investigation on the quality of apple juice incubated with Fe3O4@MoS2@PAA‐EPL implied that the fabricated composites displayed negligible adverse effects on juice quality. In addition, the results of RNA‐Seq demonstrated that 833 differentially expressed genes (DEGs) were identified in Fe3O4@MoS2@PAA‐EPL‐treated A. acidoterrestris, which were associated with translation, energy metabolism, amino acid metabolism, membrane transport and cell integrity. CONCLUSION: These results suggested that the treatment of Fe3O4@MoS2@PAA‐EPL disrupted energy metabolism, repressed cell wall synthesis and caused membrane transport disorder of bacterial cells. This work provides novel insights into the molecular antibacterial mechanism for ε‐polylysine‐functionalized magnetic composites against A. acidoterrestris. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Reprogramming of amino acid metabolism is relevant for initiating and fueling tumor formation and growth. Therefore, there has been growing interest in anticancer therapies targeting amino acid metabolism. While developing personalized therapeutic approaches to glioma, in vivo proton magnetic resonance spectroscopy (MRS) is a valuable tool for non-invasive monitoring of tumor metabolism. Here, we evaluated MRS-detected brain amino acids and myo-inositol as potential diagnostic and prognostic biomarkers in glioma. Method: We measured alanine, glycine, glutamate, glutamine, and myo-inositol in 38 patients with MRI-suspected glioma using short and long echo-time single-voxel PRESS MRS sequences. The detectability of alanine, glycine, and myo-inositol and the (glutamate + glutamine)/total creatine ratio were evaluated against the patients' IDH mutation status, CNS WHO grade, and overall survival. Results: While the detection of alanine and non-detection of myo-inositol significantly correlated with IDH wildtype (p = 0.0008, p = 0.007, respectively) and WHO grade 4 (p = 0.01, p = 0.04, respectively), glycine detection was not significantly associated with either. The ratio of (glutamate + glutamine)/total creatine was significantly higher in WHO grade 4 than in 2 and 3. We found that the overall survival was significantly shorter in glioma patients with alanine detection (p = 0.00002). Conclusion: Focusing on amino acids in MRS can improve its diagnostic and prognostic value in glioma. Alanine, which is visible at long TE even in the presence of lipids, could be a relevant indicator for overall survival. [ABSTRACT FROM AUTHOR]

Astaxanthin is an important aquatic feed additive that enhances the antioxidant capacity, and immune function of rainbow trout (Oncorhynchus mykiss); however, very limited information is available on its underlying molecular mechanisms. Haematococcus pluvialis powder, Phaffia rhodozyma powder, and synthetic astaxanthin were added to the commercial feed (no astaxanthin, NA) to prepare three experimental feeds, referred to as the HPA, PRA, and SA groups, respectively, and their actual astaxanthin contents were 31.25, 32.96, and 31.50 mg.kg-1, respectively. A 16-week feeding trial was conducted on the O. mykiss with an initial body weight of 669.88 ± 36.22 g. Serum and head kidney samples from commercial-sized O. mykiss were collected for metabolomics and transcriptomics analysis, respectively. Metabolomics analysis of the serum revealed a total of 85 differential metabolites between the astaxanthinsupplemented group and the control group. These metabolites were involved in more than 30 metabolic pathways, such as glycerophospholipid metabolism, fatty acid biosynthesis, linoleic acid metabolism, and arginine and proline metabolism. It is speculated that different sources of dietary astaxanthin may regulate antioxidant capacity and immunity mainly by affecting lipid metabolism and amino acid metabolism. Transcriptomic analysis of the head kidney revealed that the differentially expressed genes between the astaxanthin-supplemented group and the control group, such as integrin beta-1 (ITGB1), alpha-2-macroglobulin (A2M), diamine acetyltransferase 1 (SAT1), CCAAT/enhancer-binding protein beta (CEBPB) and DNA damage-inducible protein 45 alpha (GADD45A), which are involved in cell adhesion molecules, the FoxO signaling pathway, phagosomes, and arginine and proline metabolism and play regulatory roles in different stages of the antioxidant and immune response of O. mykiss. [ABSTRACT FROM AUTHOR]

Context Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate, and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers. Objective To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors. Methods Liquid chromatography tandem mass spectrometry–based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26 to 28 weeks' pregnancy, and 3 months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. Results Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared with preconception and postpartum. Renal clearance of carnitine increased with an increase in prepregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration than mothers with normal glucose metabolism at preconception. Conclusion This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Aging is a complex process that involves all tissues in an organism and shows sex dimorphism. While transcriptional changes in aging have been well characterized, the majority of studies have focused on a single sex and sex differences in gene expression in aging are poorly understood. In this study, we explore sex dimorphism in gene expression in aging mice across three tissues. Methods: We collected gastrocnemius muscle, liver and white adipose tissue from young (6 months, n = 14) and old (24 months, n = 14) female and male C57BL/6NIA mice and performed RNA-seq. To investigate sex dimorphism in aging, we considered two levels of comparisons: (a) differentially expressed genes between females and males in the old age group and (b) comparisons between females and males across the aging process. We utilized differential expression analysis and gene feature selection to investigate candidate genes. Gene set enrichment analysis was performed to identify candidate molecular pathways. Furthermore, we performed a co-expression network analysis and chose the gene module(s) associated with aging independent of sex or tissue-type. Results: We identified both tissue-specific and tissue-independent genes associated with sex dimorphism in aged mice. Unique differentially expressed genes between old males and females across tissues were mainly enriched for pathways related to specific tissue function. We found similar results when exploring sex differences in the aging process, with the exception that in the liver genes enriched for lipid metabolism and digestive system were identified in both females and males. Combining enriched pathways across analyses, we identified amino acid metabolism, digestive system, and lipid metabolism as the core mechanisms of sex dimorphism in aging. Although the vast majority of age-related genes were sex and tissue specific, we identified 127 hub genes contributing to aging independent of sex and tissue that were enriched for the immune system and signal transduction. Conclusions: There are clear sex differences in gene expression in aging across liver, muscle and white adipose. Core pathways, including amino acid metabolism, digestive system and lipid metabolism, contribute to sex differences in aging. Plain Language Summary: Aging is a complex process that occurs differently across tissues, and in men compared to women. However, the mechanisms that cause sex differences are not well understood. Using naturally aging mouse models we compared how specific genes were differently expressed in muscle, liver and fat of old and young female and male mice. We found that the vast majority of genes that were changed with age were only changed in one sex and specific tissues. Overall, sex differences in aging across tissues were related to genes involved in amino acid metabolism, digestive system and lipid metabolism. Notably, lipid metabolism is important in aging females across all tissues. We also identified a set of genes associated with aging independent of sex and tissue-type involved in immune pathways and signaling. These results enhance our understanding of sex differences in aging. Highlights: We performed RNA-seq in three tissues from young (6 months) and old (24 months) mice of both sexes, and applied differential expression analysis and machine learning approaches to identify candidate genes to decipher sex dimorphism in aging. We demonstrated that the vast majority of age-related genes were sex and tissue specific, with liver showing greater changes than muscle or white adipose tissue. Enriched pathways underpinning sex differences for each tissue aligned with the function of the tissues. In addition to tissue-specific findings, we also observed pathways in amino acid metabolism, digestive system and lipid metabolism contributing to tissue-wide sex dimorphism. We applied an unsupervised machine learning approach to select key genes involved in aging regardless of sex and tissue, and these genes were related to the immune system and signaling transduction. [ABSTRACT FROM AUTHOR]

Silkworm, Bombyx mori, an economically significant insect, plays a crucial role in silk production. However, silkworm breeding is highly susceptible to various pathogens, particularly the Bombyx mori nucleopolyhedrovirus (BmNPV), which poses a serious threat. Recent metabonomic studies have provided insights into the metabolic changes associated with BmNPV infection. BmNPV infection has obvious temporal characteristics. However, few studies have investigated the silkworms infected in different periods. This study employed gas chromatography–mass spectrometry (GC–MS) to perform a comprehensive analysis of haemolymph metabolites in silkworms at 48, 72, 96 and 120 h post‐infection (h.p.i.). Through the integration of time‐course analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, the study revealed distinct four‐stage metabolic characteristics in the silkworm's response to BmNPV infection. At Stage 1 (48 h.p.i.), silkworms activate antioxidant defence mechanisms, with significant enrichment in metabolic pathways involving key antioxidants such as glutathione, to mitigate oxidative stress induced by viral invasion. By Stage 2 (72 h.p.i.), pathways related to amino acid metabolism and protein synthesis become active, indicating an increase in protein synthesis. In Stage 3 (96 h.p.i.), energy metabolism and substance transport pathways are significantly upregulated to support the rapid viral replication and the enhanced locomotor behaviour of silkworm. Finally, at Stage 4 (120 h.p.i.), there is a further enhancement of pathways related to energy metabolism, nucleic acid synthesis, and substance transport, which align with peak viral assembly and release. These findings contribute to an in‐depth understanding of the biochemical basis of silkworm resistance to NPV. [ABSTRACT FROM AUTHOR]

Understanding the colonization and change patterns of gut microbiota is pivotal for comprehending host health. As a newly cultured breed, the studies on the gut microbiota of Tianfu goats remain limited. This study aimed to address this gap by analyzing the microbial composition and colonization patterns of fecal samples collected from goat kids from birth to weaning. Fecal samples were collected on days 0, 7, 14, 21, 28, 35, 42, 49, 53, 55, 57, and 64, and the changes and colonization patterns of microorganisms were analyzed through high-throughput 16S rRNA sequencing. The results showed that the abundance of fecal microbiota in goat kids gradually increased over time, followed by a decrease after weaning and stabilization, with reduced individual differences. The colonization of fecal microorganisms mainly presented three different stages: days 0–14, days 21–49, and days 53–64. During the suckling period, the relative abundance of Proteobacteria (72.34%) was the highest, followed by Firmicutes (21.66%). From 21  days old, the microbiota in goat kids gradually to be diverse, with Lachnospiraceae and Ruminococcaceae being dominant. During post-weaning, Ruminococcaceae (30.98–33.34%) was becoming prominence which helpful for cellulose decomposition. LEfSe analyzed three important time points (d0 vs. d7, d7 vs. d14, d49 vs. d53, LDA score  >  4 and p  <  0.05), 53 microbial communities with stage differences were identified. Functional prediction using PICRUSt revealed that differential microbial communities are mainly related to carbohydrate and amino acid metabolism pathways. Overall, this study addresses the intricate relationship between ages, diets, and microbiota compositions in Tianfu goat kids, and also offering insights into microorganisms-host interactions. [ABSTRACT FROM AUTHOR]

Plant growth, crop yield, and pest and disease control are enhanced by PGPR (Plant growth promoting rhizobacteria), which are beneficial microorganisms found in a close symbiosis with plant roots. Phytohormones are secreted, nutrient uptake is improved, and soil properties along with the microbiological environment are regulated by these microorganisms, making them a significant focus in agricultural research. In this study, the efficient PGPR strain T1 was isolated and screened from tobacco inter-root soil, and identified and confirmed by ITS sequencing technology. Tobacco growth indicators and soil property changes were observed and recorded through potting experiments. The activities of key enzymes (e.g., sucrase, catalase, urease) in soil were further determined. High-throughput sequencing technology was utilized to sequence the soil microbial community, and combined with macro-genomics analysis, the effects of T1 strain on soil microbial diversity and metabolic pathways were explored. Following the application of T1, significant improvements were observed in the height, leaf length, and width of tobacco plants. Furthermore, the physical and chemical properties of the soil were notably enhanced, including a 26.26% increase in phosphorus availability. Additionally, the activities of key soil enzymes such as sucrase, catalase, and urease were significantly increased, indicating improved soil health and fertility. Comprehensive joint microbiomics and macrogenomics analyses revealed a substantial rise in the populations of beneficial soil microorganisms and an enhancement in metabolic pathways, including amino acid metabolism, synthesis, and production of secondary metabolites. These increase in beneficial microorganisms and the enhancement of their metabolic functions are crucial for plant growth and soil fertility. This study provides valuable references for the development of innovative microbial fertilizers and offers programs for the sustainable development of modern agriculture. [ABSTRACT FROM AUTHOR]

Maintaining metabolic homeostasis is crucial for cellular and organismal health throughout their lifespans. The intricate link between metabolism and inflammation through immunometabolism is pivotal in maintaining overall health and disease progression. The multifactorial nature of metabolic and inflammatory processes makes study of the relationship between them challenging. Homologs of Saccharomyces cerevisiae silent information regulator 2 protein, known as Sirtuins (SIRTs), have been demonstrated to promote longevity in various organisms. As nicotinamide adenine dinucleotide-dependent deacetylases, members of the Sirtuin family (SIRT1–7) regulate energy metabolism and inflammation. In this review, we provide an extensive analysis of SIRTs involved in regulating key metabolic pathways, including glucose, lipid, and amino acid metabolism. Furthermore, we systematically describe how the SIRTs influence inflammatory responses by modulating metabolic pathways, as well as inflammatory cells, mediators, and pathways. Current research findings on the preferential roles of different SIRTs in metabolic disorders and inflammation underscore the potential of SIRTs as viable pharmacological and therapeutic targets. Future research should focus on the development of promising compounds that target SIRTs, with the aim of enhancing their anti-inflammatory activity by influencing metabolic pathways within inflammatory cells. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Hepatocellular carcinoma (HCC) emerges as a formidable malignancy marked by elevated morbidity and mortality rates, coupled with a dismal prognosis. The revelation of gene–protein associations has presented an avenue for the exploration of novel therapeutic targets.Pooling plasma proteomic data (seven published GWAS) and HCC data (DeCODE cohort), we applied MR to identify potential drug targets, which were further validated in the FinnGen cohort and UK Biobank. Subsequent colocalization and summary‐data‐based Mendelian randomization analyses were performed for potential associations of this set of proteins. In addition, enrichment information pathways were investigated in depth by KEGG pathway analysis, single‐cell sequencing, PPI and DGIdb, ChEMBL, and DrugBank database analyses, specific cell types enriched for expression were identified, interacting proteins were identified, and finally, druggability was assessed.In summary, the levels of 10 proteins are linked to HCC risk. Elevated levels of TFPI2 as well as decreased levels of ALDH1A1, KRT18, ADAMTS13, TIMD4, SCLY, HRSP12, TNFAIP6, FTCD, and DDC are associated with increased HCC risk. Notably, HRSP12 show the strongest evidence. These genes are primarily expressed in specific cell types within the HCC TME. Moreover, intricate protein–protein interactions, involving key players like ALDH1A1 and RIDA, ALDH1A1 and DDC, and ALDH1A1 and KRT18, contribute significantly to the amino acid metabolism and dopaminergic neurogenesis pathway. Proteins such as ALDH1A1, KRT18, TFPI2, and DDC are promising targets for HCC therapy and broader cancer drug development. Targeting these proteins offers substantial potential in advancing HCC treatment strategies.This research delineates 10 protein biomarkers linked to HCC risk and offers novel perspectives on its etiology, as well as promising avenues for the screening of HCC protein markers and therapeutic agents. [ABSTRACT FROM AUTHOR]

ABSTRACT Cold resistance in fruit trees has a direct impact on food production and scientific studies. ‘Donghe No.1’ is an excellent cold‐tolerant peach variety. Metabolomic changes under freezing stress were examined to understand the mechanisms of cold adaptation. The UPLC–MS/MS system was used to identify differentially expressed metabolites (DEMs) in branches of ‘Donghe No.1’ under freezing stress for 12 h at −5°C, −20°C, −25°C, or −30°C. In total, 1096 metabolites and 196 DEMs were obtained at −5°C vs −20°C, −25°C, and − 30°C, while 179 DEMs and eight shared DEMs obtained at −5°C vs −20°C, −20°C vs −25°C, and −25°C vs −30°C. KEGG enrichment identified 196 DEMs associated with amino acid metabolism, linoleic acid metabolism, alpha‐linolenic acid metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis under freezing stress. A metabolic network in 1‐year‐old peach branches under freezing stress is proposed. Moreover, these results enhance understanding of metabolite responses and mechanisms to freezing stress in peach and will help in future breeding of freezing‐tolerant varieties and investigating tolerance mechanisms. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown. Principal findings: This study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated. Conclusions: The recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica. Author summary: Schistosomiasis, which seriously threatens human health, is the world's second largest tropical disease caused by schistosome infection. Praziquantel has many problems such as side effects and drug resistance, so it is urgent to develop new prevention strategies. Bacillus amyloliquefaciens has been reported to alleviate the pathological damage of intestinal diseases, which can be used as a potential strategy to alleviate granuloma and fibrosis induced by schistosomiasis japonica in intestine and liver. However, the mechanism of B. amyloliquefaciens regulating schistosomiasis japonica through the mediation of intestinal microbiome is still unclear. In this study, we conducted joint analysis of the gut microbiome and host serum metabolites through mouse models and multi-omics sequencing technology, and found that the intragastric administration of B. amyloliquefaciens could regulate the restoration of intestinal microbiome and the secretion of metabolites derived from intestinal microbiome in mice, improve lipid metabolism disorder and hormone secretion in mice, and ultimately reduce the pathological response of mice infected with Schistosoma japonicum. This study highlights the crosstalk between intestinal microbiome and the host, providing an important reference for the precise treatment based on targeted microbiota, and also providing a new strategy for the prevention and adjuvant treatment of schistosomiasis japonica. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming is a pivotal biological process in which cellular metabolic patterns change to meet the energy demands of increased cell growth and proliferation. In this review, we explore metabolic reprogramming and its impact on fibrotic diseases, providing a detailed overview of the key processes involved in the metabolic reprogramming of renal fibrosis, including fatty acid decomposition and synthesis, glycolysis, and amino acid catabolism. In addition, we report that Chinese medicine ameliorates renal inflammation, oxidative stress, and apoptosis in chronic kidney disease by regulating metabolic processes, thereby inhibiting renal fibrosis. Furthermore, we reveal that multiple targets and signaling pathways contribute to the metabolic regulatory effects of Chinese medicine. In summary, this review aims to elucidate the mechanisms by which Chinese medicine inhibits renal fibrosis through the remodeling of renal cell metabolic processes, with the goal of discovering new therapeutic drugs for treating renal fibrosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions Exposure to environmental contaminants is globally universal. However, communities vary in the specific combination of contaminants to which they are exposed, potentially contributing to variation in human health and creating “locally situated biologies.” We investigated how environmental exposures differ across environments by comparing exposure profiles between two contexts that differ markedly across political, economic, and sociocultural factors—Namqom, Formosa, Argentina, and New Haven, Connecticut, United States.We collected infant urine, maternal urine, and human milk samples from mother–infant dyads in Formosa (n = 13) and New Haven (n = 21). We used untargeted liquid chromatography with high‐resolution mass spectrometry (LC‐HRMS) to annotate environmental contaminants and endogenous metabolites in these samples, and we analyzed the data using exposome‐wide association studies (EWAS) followed by pathway enrichment.We found statistically significant differences between the chemical exposure profiles of the Argentinian and US mothers, mostly involving pesticides; however, we observed similarities in the infant urine and human milk environmental contaminant profiles, suggesting that the maternal body may buffer infant exposure through human milk. We also found that infants and mothers were exposed to contaminants that were associated with alterations in amino acid and carbohydrate metabolism. Infants additionally showed alterations in vitamin metabolism, including vitamins B1, B3, and B6.Differences in chemical exposure profiles may be related to structural factors. Despite variation in the composition of exposure profiles between the two study sites, environmental contaminant exposure was associated with similar patterns in human physiology when we considered contaminants comprehensively rather than individually, with implications for metabolic and cardiovascular disease risk as well as infant cognitive development. [ABSTRACT FROM AUTHOR]

In nature, germination of orchid seeds and early plant development rely on a symbiotic association with orchid mycorrhizal (ORM) fungi. These fungi provide the host with the necessary nutrients and facilitate the transition from embryos to protocorms. Despite recent advances in omics technologies, our understanding of this symbiosis remains limited, particularly during the initial stages of the interaction. To address this gap, we employed transcriptomics and metabolomics to investigate the early responses occurring in the mycorrhizal fungus Tulasnella sp. isolate SV6 when co-cultivated with orchid seeds of Serapias vomeracea. The integration of data from gene expression and metabolite profiling revealed the activation of some fungal signalling pathways before the establishment of the symbiosis. Prior to seed contact, an indole-related metabolite was produced by the fungus, and significant changes in the fungal lipid profile occurred throughout the symbiotic process. Additionally, the expression of plant cell wall-degrading enzymes (PCWDEs) was observed during the pre-symbiotic stage, as the fungus approached the seeds, along with changes in amino acid metabolism. Thus, the dual-omics approach employed in this study yielded novel insights into the symbiotic relationship between orchids and ORM fungi and suggest that the ORM fungus responds to the presence of the orchid seeds prior to contact. [ABSTRACT FROM AUTHOR]

Polypharmacy (use of ≥5 concurrent medications) is highly prevalent among older adults to manage chronic diseases and is linked to adverse geriatric outcomes, including physical and cognitive functional impairments, falls, frailty, hospitalization, and mortality. Deprescribing (withdrawal) is a potential strategy to manage polypharmacy. The broad molecular changes by which polypharmacy causes harm and deprescribing may be beneficial are unknown and unfeasible to study rigorously in tissue from geriatric patients. Therefore, in a randomized controlled trial, we administered therapeutic doses of commonly used chronic medications (oxycodone, oxybutynin, citalopram, simvastatin, or metoprolol) as monotherapy or concurrently (polypharmacy) from middle‐age (12 months) to old‐age (26 months) to male C57BL/6J (B6) mice and deprescribed (gradually withdrew) treatments in a subset from age 21 months. We compared drug‐related hepatic effects by applying proteomics along with transcriptomics and histology. We found that monotherapy effects on hepatic proteomics were limited but significant changes were seen with polypharmacy (93% unique to polypharmacy). Polypharmacy altered the hepatic expression of proteins involved in immunity, and in drug, cholesterol, and amino acid metabolism, accompanied by higher serum drug levels than monotherapies. Deprescribing not only reversed some effects but also caused irreversible and novel changes in the hepatic proteome. Furthermore, our study identified several hepatic protein co‐expressed modules that are associated with clinically relevant adverse geriatric outcomes, such as mobility, frailty, and activities of daily living. This study highlights the complex molecular changes following aging, chronic polypharmacy, and deprescribing. Further exploration of these mechanistic pathways may inform management of polypharmacy and deprescribing in older adults. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of mortality worldwide. Myocardial injury resulting from ischemia can be fatal because of the limited regenerative capacity of adult myocardium. Mammalian cardiomyocytes rapidly lose their proliferative capacities, with only a small fraction of adult myocardium remaining proliferative, which is insufficient to support post‐injury recovery. Recent investigations have revealed that this decline in myocardial proliferative capacity is closely linked to perinatal metabolic shifts. Predominantly glycolytic fetal myocardial metabolism transitions towards mitochondrial fatty acid oxidation postnatally, which not only enables efficient production of ATP but also causes a dramatic reduction in cardiomyocyte proliferative capacity. Extensive research has elucidated the mechanisms behind this metabolic shift, as well as methods to modulate these metabolic pathways. Some of these methods have been successfully applied to enhance metabolic reprogramming and myocardial regeneration. This review discusses recently acquired insights into the interplay between metabolism and myocardial proliferation, emphasizing postnatal metabolic transitions. [ABSTRACT FROM AUTHOR]

Summary Branched‐chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential for maintaining physiological functions and metabolic homeostasis. However, chronic elevation of BCAAs causes metabolic diseases such as obesity, type 2 diabetes (T2D), and metabolic‐associated fatty liver disease (MAFLD). Adipose tissue, skeletal muscle, and the liver are the three major metabolic tissues not only responsible for controlling glucose, lipid, and energy balance but also for maintaining BCAA homeostasis. Under obese and diabetic conditions, different pathogenic factors like pro‐inflammatory cytokines, lipotoxicity, and reduction of adiponectin and peroxisome proliferator‐activated receptors γ (PPARγ) disrupt BCAA metabolism, leading to excessive accumulation of BCAAs and their downstream metabolites in metabolic tissues and circulation. Mechanistically, BCAAs and/or their downstream metabolites, such as branched‐chain ketoacids (BCKAs) and 3‐hydroxyisobutyrate (3‐HIB), impair insulin signaling, inhibit adipogenesis, induce inflammatory responses, and cause lipotoxicity in the metabolic tissues, resulting in multiple metabolic disorders. In this review, we summarize the latest studies on the metabolic regulation of BCAA homeostasis by the three major metabolic tissues—adipose tissue, skeletal muscle, and liver—and how dysregulated BCAA metabolism affects glucose, lipid, and energy balance in these active metabolic tissues. We also summarize therapeutic approaches to restore normal BCAA metabolism as a treatment for metabolic diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Priority effects, where the order and timing of species arrival influence the assembly of ecological communities, have been observed in a variety of taxa and habitats. However, the genetic and molecular basis of priority effects remains unclear, hindering a better understanding of when priority effects will be strong. We sought to gain such an understanding for the nectar yeast Metschnikowia reukaufii commonly found in the nectar of our study plant, the hummingbird‐pollinated Diplacus (Mimulus) aurantiacus. In this plant, M. reukaufii can experience strong priority effects when it reaches flowers after other nectar yeasts, such as M. rancensis. After inoculation into two contrasting types of synthetic nectar simulating early arrival of M. rancensis, we conducted whole‐transcriptome sequencing of 108 strains of M. reukaufii. We found that several genes were differentially expressed in M. reukaufii strains when the nectar had been conditioned by growth of M. rancensis. Many of these genes were associated with amino acid metabolism, suggesting that M. reukaufii strains responded molecularly to the reduction in amino acid availability caused by M. rancensis. Furthermore, investigation of expression quantitative trait loci (eQTLs) revealed that genes involved in amino acid transport and resistance to antifungal compounds were enriched in some genetic variants of M. reukaufii. We also found that gene expression was associated with population growth rate, particularly when amino acids were limited. These results suggest that intraspecific genetic variation in the ability of nectar yeasts to respond to nutrient limitation and direct fungal competition underpins priority effects in this microbial system. [ABSTRACT FROM AUTHOR]

Introduction: This study investigated the combined effects of molybdenum (Mo) and nitrogen (N) fertilization on N metabolism and amino acid content in the leaves of flue-cured tobacco (Nicotiana tabacum L.) during its mature stage through a pot experiment. Methods: Different application levels of Mo (0, 0.15, 0.30 mg/kg soil) and N (0.06, 0.24, 0.42 g/kg soil) were set to observe and analyze changes in leaf quality, N, and amino acid content in the tobacco plants. Results: The results revealed that the N fertilizer application level exhibited a primary effect on regulating the total nitrogen, nitrate nitrogen, soluble protein, and amino acid nitrogen concentrations within tobacco leaves, while the effectiveness of Mo fertilization was influenced by the level of N applied. Specifically, under the conditions of 0.24 g/kg soil N and 0.30 mg/kg soil Mo application, the N content, N accumulation, and dry matter mass of the tobacco plants increased significantly by 110%, 204%, and 48%, respectively. Concurrently, nitrate reductase activity increased by 107-fold, and the nitrate nitrogen content was relatively low, contributing to enhanced tobacco yield and safety. Moreover, this treatment led to a notable (170%) increase in free amino acid nitrogen content, with minimal impact on total amino acids and soluble proteins. Notably, it effectively increased the content of free amino acids beneficial to the sensory quality of tobacco (such as histidine, arginine, aspartic acid, isoleucine, and glutamic acid) without reducing the total amino acid content, while simultaneously reducing other amino acids that might affect quality. Therefore, the combined application of 0.30 mg/kg soil Mo and 0.24 g/kg soil N specifically optimized the amino acid composition in tobacco leaves, positively impacting overall quality and market competitiveness. Discussion: This study provides a theoretical basis for the rational application of Mo fertilizer in Mo-deficient areas to improve the yield and quality of fluecured tobacco. [ABSTRACT FROM AUTHOR]

This study aimed to highlight the molecular and biochemical changes induced by methylglyoxal (MGO) exposure in SH-SY5Y human neuroblastoma cells, and to explore how these changes contribute to its neurotoxicity, utilizing an integrated proteomics and metabolomics approach. Using label-free quantitative nanoLC-MS/MS proteomics and targeted LC-TQ-MS/MS-based metabolomics, the results revealed that MGO exposure, particularly at cytotoxic levels, significantly altered the proteome and metabolome of SH-SY5Y cells. Analysis of proteomics data showed significant alterations in cellular functions including protein synthesis, cellular structural integrity, mitochondrial function, and oxidative stress responses. Analysis of metabolomics and integration of metabolomics and proteomics data highlighted significant changes in key metabolic pathways including arginine biosynthesis, glutathione metabolism, cysteine and methionine metabolism, and the tricarboxylic acid cycle. These results suggest that MGO exposure induced both toxic effects and adaptive responses in cells. MGO exposure led to increased endoplasmic reticulum stress, disruptions in cellular adhesion and extracellular matrix integrity, mitochondrial dysfunction, and amino acid metabolism disruption, contributing to cellular toxicity. Conversely, cells exhibited adaptive responses by upregulating protein synthesis, activating the Nrf2 pathway, and reprogramming metabolism to counteract dicarbonyl stress and maintain energy levels. Furthermore, a set of key proteins and metabolites associated with these changes were shown to exhibit a significant concentration-dependent decrease or increase in their expression levels with increasing MGO concentrations, suggesting their potential as biomarkers for MGO exposure. Taken together, these findings provide insight into the molecular mechanisms underlying MGO-induced neurotoxicity and potential targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]