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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]

The aim of this study is to perform proteomic and metabolomic analyses in bilateral renal pelvis urine of patients with unilateral uric acid kidney stones to identify the specific urinary environment associated with uric acid stone formation. Using cystoscopy-guided insertion of ureteral catheters, bilateral renal pelvis urine samples are collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is employed to identify differentially expressed proteins and metabolites in the urine environment. Differentially expressed proteins and metabolites are further analyzed for their biological functions and potential metabolic pathways through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In the urine from the stone-affected side, eight differential proteins were significantly upregulated, and six metabolites were dysregulated. The uric acid stone urinary environment showed an excess of α-ketoisovaleric acid and 3-methyl-2-oxovaleric acid, which may contribute to the acidification of the urine. Functional and pathway analyses indicate that the dysregulated metabolites are mainly associated with insulin resistance and branched chain amino acid metabolism. [ABSTRACT FROM AUTHOR]

ABSTRACT Pear lace bug (Stephanitis nashi) is a significant herbivorous pest, harbouring a diverse microbiome crucial for crabapple (Malus sp.) host adaptation. However, the mutual influence of S. nashi‐ and plant‐associated microbiomes on plant responses to pest damage remains unclear. This study found that S. nashi damage significantly altered bacterial community structure and reduced bacterial evenness in the crabapple phyllosphere. Notably, bacterial diversity within S. nashi was significantly lower than that in the environment, potentially influenced by insect developmental stage, bacterial diffusion stage and endosymbiont species number and abundance. Extensive bacterial correlation and diffusion effect between S. nashi and adjacent plant environments were observed, evident in a gradual decrease in bacterial diversity and an increase in bacterial acquisition ratio from soil to phyllosphere to S. nashi. Correspondingly, S. nashi significantly impacted the metabolic response of crabapple leaves, altering pathways involved in vitamin, amino acid and lipid metabolism and so forth. Furthermore, association analysis linked these metabolic changes to phyllosphere bacterial alterations, emphasizing the important role of diffusive phyllosphere microbiome in regulating S. nashi‐crabapple interactions. This study highlights bacterial diffusion effect between insect and plants and their potential role in regulating insect adaptability and plant defence responses, providing new insights into plant−insect−microbiome interactions. [ABSTRACT FROM AUTHOR]

Background: Recurrent pregnancy loss (RPL) affects women's reproductive health seriously, with immune dysfunction playing a key role in its cause, yet the exact mechanisms remain elusive. We aim to investigate potential mechanisms and identify biomarkers linked to RPL. Methods: Immune cytokine testing and metabolomic profiling were conducted on the serum of 34 RPL patients and 30 healthy individuals. The metabolic pathways of the differential metabolites were analyzed, and specific metabolites were validated through targeted profiling. Potential biomarkers were identified, and the relationships between immune cytokines and differential metabolites were explored. Results: In the RPL group, serum interleukin-6 and interleukin-10 levels were significantly higher, while interleukin-2 and interferon-g were significantly lower. A total of 296 differential metabolites were detected by untargeted metabolomic profiling between the RPL and control groups, with most linked to amino acid metabolism. Targeted metabolomic profiling of amino acid metabolism revealed upregulation of indole-3-acetic acid, tyrosine, glycine, isoleucine, tryptophan, lysine, aspartic acid, arginine, leucine, threonine, glutamic acid, cystine, and phenylpyruvic acid (PPA) in the RPL group. Moreover, PPA and 5-hydroxy-Ltryptophan showed great potential in predicting RPL in a diagnostic model. Cystine and tyrosine were associated with immune cytokines in correlation analysis. Conclusion: The study highlights the role of amino acid metabolism in RPL pathogenesis, suggesting that PPA and 5-HTP may be potential predictive indicators, while cystine and tyrosine may potentially regulate immune responses related to RPL. Further investigation into the molecular mechanisms underlying these findings could potentially result in the creation of novel diagnostic and therapeutic approaches for RPL. [ABSTRACT FROM AUTHOR]

Summary: The gut microbiota plays a crucial role in foodwebs, carbon cycling, and related elements. Exopalaemon annandalei and Exopalaemon carinicauda are two important forage species in the Yangtze River estuary with extremely similar living habits andmorphological characteristics. Exploring the microorganisms in the guts of these two shrimp species can help us understand the survival status of forage species and gut microbiota in the Yangtze River estuary. Therefore, this study analyzed the similarities and differences in the intestinal flora of E. annandalei and E. carinicauda through high-throughput sequencing of 16S rRNA gene amplicons. The results showed that the dominant bacteria in the intestinal flora of E. annandalei and E. carinicauda at the phylum level were Proteobacteria and Firmicutes, respectively. At the genus level, the intestinal flora had higher concentrations of Psychrobacter, Bacillus, Pseudomonas, Acinetobacter, and Macrococcus. In both shrimp species, the contents of Acinetobacter and Macrococcus were higher in spring than in winter. The most important potential functions of the intestinal microbiota were amino acid metabolism and purine metabolism. Additionally, the functions of metabolismand diseases in the intestinal microbiota of E. annandalei were greatly influenced by the season. Furthermore, the experimental results indicated that a lower ratio of Firmicutes to Bacteroidetes was associated with a larger body weight in shrimp. Overall, this study provides a theoretical reference for understanding the intestinal bacterial community of shrimp in estuaries and the healthy cultivation of E. annandalei and E. carinicauda. [ABSTRACT FROM AUTHOR]

Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation. First, we found that CTH is induced in the colon mucosa in mice with dextran sulfate sodium-induced colitis. Expression of CTH was completely absent in the colon of Cth–/– mice. We observed that clinical and histological parameters are ameliorated in Cth-deficient mice compared to wild-type animals. However, Cth deletion had no effect on tumorigenesis and the level of dysplasia in mice treated with azoxymethane-DSS, as a reliable model of colitis-associated carcinogenesis. Mechanistically, we determined that the deletion of the gene Slc7a11 encoding for solute carrier family 7 member 11, the transporter of the anionic form of cysteine, does not affect DSS colitis. Lastly, we found that the richness and diversity of the fecal microbiota were significantly increased in Cth–/– mice compared to both WT and Slc7a11–/– mice. In conclusion, our data suggest that the enzyme CTH represents a target for clinical intervention in patients with inflammatory bowel disease, potentially by beneficially reshaping the composition of the gut microbiota. [ABSTRACT FROM AUTHOR]

Promiscuous enzymes often serve as the starting point for the evolution of novel functions. Yet, the extent to which the promiscuity of an individual enzyme can be harnessed several times independently for different purposes during evolution is poorly reported. Here, we present a case study illustrating how NAD(P)+-dependent succinate semialdehyde dehydrogenase of Escherichia coli (Sad) is independently recruited through various evolutionary mechanisms for distinct metabolic demands, in particular vitamin biosynthesis and central carbon metabolism. Using adaptive laboratory evolution (ALE), we show that Sad can substitute for the roles of erythrose 4-phosphate dehydrogenase in pyridoxal 5'-phosphate (PLP) biosynthesis and glyceraldehyde 3-phosphate dehydrogenase in glycolysis. To recruit Sad for PLP biosynthesis and glycolysis, ALE employs various mechanisms, including active site mutation, copy number amplification, and (de)regulation of gene expression. Our study traces down these different evolutionary trajectories, reports on the surprising active site plasticity of Sad, identifies regulatory links in amino acid metabolism, and highlights the potential of an ordinary enzyme as innovation reservoir for evolution. Enzyme promiscuity seeds evolutionary innovation, but how flexible a single enzyme can be (re-)used during evolution remains unclear. Here, the authors show that various evolutionary trajectories applied to succinate semialdehyde dehydrogenase can compensate for the loss of two different functions in E. coli. [ABSTRACT FROM AUTHOR]

Ferroptosis is a cell death modality in which iron-dependent lipid peroxides accumulate on cell membranes. Cysteine, a limiting substrate for the glutathione system that neutralizes lipid peroxidation and prevents ferroptosis, can be converted by cystine reduction or synthesized from methionine. However, accumulating evidence shows methionine-based cysteine synthesis fails to effectively rescue intracellular cysteine levels upon cystine deprivation and is unable to inhibit ferroptosis. Here, we report that methionine-based cysteine synthesis is tissue-specific. Unexpectedly, we find that rather than inhibiting ferroptosis, methionine in fact plays an essential role during cystine deprivation-induced ferroptosis. Methionine-derived S-adenosylmethionine (SAM) contributes to methylation-dependent ubiquinone synthesis, which leads to lipid peroxides accumulation and subsequent ferroptosis. Moreover, SAM supplementation synergizes with Imidazole Ketone Erastin in a tumor growth suppression mouse model. Inhibiting the enzyme that converts methionine to SAM protects heart tissue from Doxorubicin-induced and ferroptosis-driven cardiomyopathy. This study broadens our understanding about the intersection of amino acid metabolism and ferroptosis regulation, providing insight into the underlying mechanisms and suggesting the methionine-SAM axis is a promising therapeutic strategy to treat ferroptosis-related diseases. Ferroptosis is regulated by amino acid metabolism. Here, authors show that the methionine-SAM-UQ axis is responsible for mtROS generation and ferroptosis induction, suggesting potential therapeutic strategies for diseases associated with ferroptosis. [ABSTRACT FROM AUTHOR]

The risk of developing diabetes and cardiometabolic disorders is associated with increased levels of alpha-aminoadipic acid and disturbances in the metabolism of branched-chain amino acids. The side effects of the widely used antidiabetic drug metformin include impaired degradation of branched-chain amino acids and inhibition of intracellular thiamin transport. These effects may be interconnected, as thiamine deficiency impairs the functioning of thiamine diphosphate (ThDP)-dependent dehydrogenases of 2-oxo acids involved in amino acids degradation, while diabetes is often associated with perturbed thiamine status. In this work, we investigate the action of metformin in rats with impaired thiamine availability. The reduction in the thiamine influx is induced by simultaneous administration of the thiamine transporters inhibitors metformin and amprolium. After 24 days of combined metformin/amprolium administration, no significant changes in the total brain levels of ThDP or activities of ThDP-dependent enzymes of central metabolism are observed, but the affinities of transketolase and 2-oxoglutarate dehydrogenase to ThDP increase. The treatment also significantly elevates the brain levels of free amino acids and ammonia, reduces the antioxidant defense, and alters the sympathetic/parasympathetic regulation, which is evident from changes in the ECG and behavioral parameters. Strong positive correlations between brain ThDP levels and contents of ammonia, glutathione disulfide, alpha-aminoadipate, glycine, citrulline, and ethanolamine are observed in the metformin/amprolium-treated rats, but not in the control animals. Analysis of the obtained data points to a switch in the metabolic impact of ThDP from the antioxidant and nitrogen-sparing in the control rats to the pro-oxidant and hyperammonemic in the metformin/amprolium-treated rats. As a result, metformin administration along with the amprolium-reduced thiamine supply significantly perturb the metabolism of amino acids in the rat brain, altering behavioral and ECG parameters. [ABSTRACT FROM AUTHOR]

The Keap1-Nrf2 pathway is an essential system that maintains redox homeostasis and modulates key metabolic processes, including metabolism of amino acids to promote the synthesis of antioxidant enzymes. Inhibitors of the protein-protein interaction (PPI) between Keap1 and Nrf2 have emerged as a promising strategy for developing novel classes of antioxidant agents that selectively activate this pathway without off-target effects. Carotenoids, a large family of lipophilic isoprenoids synthesized by all photosynthetic organisms, are well-known for their antioxidant activities. However, the ability of carotenoids to inhibit the Keap1-Nrf2 PPI through the involvement of specific amino acid residues has not yet been revealed. We utilized molecular docking, molecular dynamic simulations, and pharmacokinetic prediction techniques to investigate the potential of eight oxygenated carotenoids, known as xanthophylls, to inhibit Keap1. Among the compounds investigated, fucoxanthin and astaxanthin established multiple hydrogen-bonding and hydrophobic interactions within the Kelch domain of Keap1, showing remarkable binding affinities. Furthermore, fucoxanthin and astaxanthin displayed the ability to form a stable complex with Keap1 and fit into the binding pocket of its Kelch domain. These analyses led to the identification of critical amino acid residues in the binding pocket of Keap1 which are involved in the interaction with carotenoid xanthophylls. Our analyses further revealed that fucoxanthin and astaxanthin demonstrate a favorable safety profile and possess pharmacokinetic properties consistent with acceptable drug-like characteristics. These findings lay the preliminary foundation for developing a novel class of Keap1-Nrf2 PPI inhibitors with potential applications against oxidative stress-related diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a global health problem caused by uncontrolled cell growth and changes in how cells get and use energy. This review compares cancer's hidden metabolic changes to dark matter and dark energy in the universe, which are mysterious and often ignored. It looks at how cancer cells alter their energy use, such as through the Warburg effect and changes in fat and protein production, driven by genetic mutations. These changes help cancer grow and survive. The review suggests that targeting these metabolic pathways could be a new way to treat cancer. It calls for more research to better understand these changes and develop new therapies by focusing on the "dark energy" that fuels cancer cells. Background: Cancer remains a global health challenge, characterized not just by uncontrolled cell proliferation but also by the complex metabolic reprogramming that underlies its development and progression. Objectives: This review delves into the intricate relationship between cancer and its metabolic alterations, drawing an innovative comparison with the cosmological concepts of dark matter and dark energy to highlight the pivotal yet often overlooked role of metabolic reprogramming in tumor evolution. Methods: It scrutinizes the Warburg effect and other metabolic adaptations, such as shifts in lipid synthesis, amino acid turnover, and mitochondrial function, driven by mutations in key regulatory genes. Results: This review emphasizes the significance of targeting these metabolic pathways for therapeutic intervention, outlining the potential to disrupt cancer's energy supply and signaling mechanisms. It calls for an interdisciplinary research approach to fully understand and exploit the intricacies of cancer metabolism, pointing toward metabolic reprogramming as a promising frontier for developing more effective cancer treatments. Conclusion: By equating cancer's metabolic complexity with the enigmatic nature of dark matter and energy, this review underscores the critical need for innovative strategies in oncology, highlighting the importance of unveiling and targeting the "dark energy" within cancer cells to revolutionize future therapy and research. [ABSTRACT FROM AUTHOR]

Simple Summary: Under heat stress, the aerobic metabolic activity of the body is significantly accelerated, which easily leads to hypoxia of high-oxygen consumption tissues, such as the mammary gland. In dairy cattle growing in the high-temperature and high-humidity environment in Guangxi, especially those in the peak period of lactation with strong metabolism, the lack of oxygen in the mammary cells is more obvious, and the milk volume and composition are greatly affected, and even lead to metabolic disorders. Nitidine chloride (NC) is a natural alkaloid with antioxidant properties that can remove excess reactive oxygen species (ROS). However, there is limited information on the effect of NC on BMECs hypoxic injury and its molecular mechanism. In this study, molecular biological methods combined with non-targeted metabolomics were used to study the protective effect of NC on BMECs induced by hypoxic stress. Based on the results obtained, we found that NC has a protective effect on hypoxic mitochondria and regulates amino acid metabolism in response to hypoxic stress. Hypoxia in the mammary gland epithelial cells of milk buffalo (BMECs) can affect milk yield and composition, and it can even cause metabolic diseases. Nitidine chloride (NC) is a natural alkaloid with antioxidant properties that can scavenge excessive reactive oxygen species (ROS). However, the effect of NC on the hypoxic injury of BMECs and its molecular mechanisms are still unknown. Here, an immunofluorescence assay, transmission electron microscopy (TEM), and flow cytometry, combined with untargeted metabolomics, were used to investigate the protective effect of NC on hypoxic stress injury in BMECs. It was found that NC can significantly reduce cell activity (p < 0.05) and inhibit cellular oxidative stress (p < 0.05) and cell apoptosis (p < 0.05). A significant decrease in mitophagy mediated by the PINK1-Parkin pathway was observed after NC pretreatment (p < 0.05). In addition, a metabolic pathway enrichment analysis demonstrated that the mechanisms of NC against hypoxic stress may be related to the downregulation of pathways involving aminoacyl tRNA biosynthesis; arginine and proline metabolism; glycine, serine, and threonine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Thus, NC has a protective effect on hypoxic mitochondria, and it can regulate amino acid metabolism in response to hypoxic stress. The present study provides a reference for the application of nitidine chloride to regulate the mammary lactation function of milk buffalo. [ABSTRACT FROM AUTHOR]

Skin barrier impairment is becoming increasingly common due to changes in lifestyle and modern living environments. Oily sensitive skin (OSS) is a condition that is characterized by an impaired skin barrier. Thus, examining the differences between OSS and healthy skin will enable a more objective evaluation of the characteristics of OSS and facilitate investigations of potential treatments. Initially, a self-assessment questionnaire was used to identify patients with OSS. Biophysical measurements and LAST scores were used to determine whether skin barrier function was impaired. Epidermal biophysical properties, including skin hydration, transepidermal water loss (TEWL), sebum content, erythema index (EI), and a* value, were measured with noninvasive instruments. We subsequently devised a noninvasive D-square sampling technique to identify changes in the skin metabolome in conjunction with an untargeted metabolomics analysis with an Orbitrap Q ExactiveTM series mass spectrometer. In the stratum corneum of 47 subjects, 516 skin metabolites were identified. In subjects with OSS, there was an increase in the abundance of 15 metabolites and a decrease in the abundance of 48 metabolites. The participants with OSS were found to have the greatest disruptions in sphingolipid and amino acid metabolism. The results revealed that an impaired skin barrier is present in patients with OSS and offers a molecular target for screening for skin barrier damage. [ABSTRACT FROM AUTHOR]

The large yellow croaker (Larimichthys crocea) is an important economic fish in China. However, intensive farming practices, such as high stocking densities, suboptimal water quality, and imbalanced nutrition, have led to a decline in muscle quality. Muscle elasticity is a key texture property influencing muscle quality. Herein, transcriptomic and metabolomic analyses were performed on four groups: male high muscle elasticity (MEHM), female high muscle elasticity (MEHF), male low muscle elasticity (MELM), and female low muscle elasticity (MELF), to explore the molecular regulation underlying muscle elasticity in the large yellow croaker. Transcriptomics identified 2594 differentially expressed genes (DEGs) across the four groups, while metabolomics revealed 969 differentially expressed metabolites (DEMs). Association analysis indicated that the valine, leucine, and isoleucine biosynthesis pathways were significantly enriched between the MELF and MEHF groups; 2-Oxoisovalerate and L-Valine were DEMs; and the gene encoding L-threonine ammonia-lyase was a DEG. In the MELM and MEHM groups, pathways such as arginine biosynthesis; arginine and proline metabolism; and valine, leucine, and isoleucine degradation were significantly enriched. 4-guanidinobutanoate, L-aspartate, N-acetylornithine, and L-leucine were among the DEMs, while the DEGs included glul, gls, srm, hmgcs, and aacs. These findings provide insights into the molecular mechanisms controlling muscle elasticity, representing a theoretical foundation to breed high-quality large yellow croakers. [ABSTRACT FROM AUTHOR]

Tillandsia recurvata is an epiphytic plant commonly found in tropical regions and colonizes tree trunks, fences, and power wires. This plant plays an important role in interacting with trees, sharing microorganisms, and performing specific functions in the process of tree colonization. The objective of this study was to evaluate and compare the microbiomes of T. recurvata collected from two different locations (trees and fences) and two plant tissues (leaves and roots). The hypothesis of this study was that the microbiome of T. recurvata is composed of microorganisms that would provide nutritional support to compensate for the lack of nutrients in a particular growth support. The results showed significant differences in microbial diversity between trees and fences, with trees exhibiting higher richness and more complex microbial networks. Proteobacteria was the most prevalent bacterial phylum, with Actinobacteria and Sphingomonas also playing key roles in nitrogen fixation and plant growth. Fungal communities were similar across locations, with Ascomycota and Basidiomycota being predominant, but Paraconiothyrium and Nigrospora showed significant differences in abundance between trees and fences. Functional analysis indicated similar metabolic profiles across leaf and root samples, with key functions for T. recurvata including carbohydrate and amino acid metabolism, stress control, and biofertilization. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Soybean reddening during storage and transportation has caused great concern due to the serious economic loss. However, the mechanism of reddening has not been clearly elucidated. In this study, metabolomics was employed to investigate the reasons for soybean reddening during storage.The results of multivariate statistical analysis showed that the metabolite level of red soybean was significantly different from that of normal soybean. The differentially expressed metabolites were mainly enriched by biosynthesis of secondary metabolites and amino acid metabolism. Metabolism analysis showed that the biosynthesis of cyanidin and betalains was enhanced in reddening soybean. In addition, it was found that phenolic and flavonoid compounds decreased, while quinones, furans and 5‐hydroxymethylfurfural increased in reddening soybeans compared to normal soybeans.The upregulation of cyanidin and betalains was the main reason for soybean reddening. Besides, the oxidation of phenols and flavonoids, as well as Maillard reaction, also contributed to the color change. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Monoglycerides have emerged as a promising alternative to conventional practices due to their biological activities, including antimicrobial properties. However, few studies have assessed the efficacy of monoglyceride blend on weaned pigs and their impacts on performance, immune response, and gut health using a disease challenge model. Therefore, this study aimed to investigate the effects of dietary monoglycerides of short- and medium-chain fatty acids on the immunity and gut health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli F18. Results: Pigs supplemented with high-dose zinc oxide (ZNO) had greater (P < 0.05) growth performance than other treatments, but no difference was observed in average daily feed intake between ZNO and monoglycerides groups during the post-challenge period. Pigs in ZNO and antibiotic groups had lower (P < 0.05) severity of diarrhea than control, but the severity of diarrhea was not different between antibiotic and monoglycerides groups. Pigs fed with monoglycerides or ZNO had lower (P < 0.05) serum haptoglobin on d 2 or 5 post-inoculation than control. Pigs in ZNO had greater (P < 0.05) goblet cell numbers per villus, villus area and height, and villus height:crypt depth ratio (VH:CD) in duodenum on d 5 post-inoculation than pigs in other treatments. Pigs supplemented with monoglycerides, ZNO, or antibiotics had reduced (P < 0.05) ileal crypt depth compared with control on d 5 post-inoculation, contributing to the increase (P = 0.06) in VH:CD. Consistently, pigs in ZNO expressed the lowest (P < 0.05) TNFa, IL6, IL10, IL12, IL1A, IL1B, and PTGS2 in ileal mucosa on d 5 post-inoculation, and no difference was observed in the expression of those genes between ZNO and monoglycerides. Supplementation of ZNO and antibiotic had significant impacts on metabolic pathways in the serum compared with control, particularly on carbohydrate and amino acid metabolism, while limited impacts on serum metabolites were observed in monoglycerides group when compared with control. Conclusions: The results suggest that supplementation of monoglyceride blend may enhance disease resistance of weaned pigs by alleviating the severity of diarrhea and mitigating intestinal and systemic inflammation, although the effectiveness may not be comparable to high-dose zinc oxide. [ABSTRACT FROM AUTHOR]

Background: Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce. Methods: The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways. Results: As parameterized in tertiles, titanium showed positive dose–response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk. Conclusions: In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk. [ABSTRACT FROM AUTHOR]

Background: Exercise can be used as a model to understand immunometabolism. Biological data on elite athletes are limited, especially for female athletes, including relevant data on acute-phase proteins and amino acid metabolism. Methods: We analyzed acute-phase proteins and amino acids collected at South American, Pan-American, and Olympic Games for 16 Olympic sports. We compared female and male elite athletes (447 vs. 990 samples) across four states (fasting, pre-exercise, post-exercise, and resting) to understand sex-specific immunometabolic responses in elite athletes. Results: Considering all states and sports, we found that elite female athletes exhibited higher concentrations of C-reactive protein, lipopolysaccharide-binding protein, myeloperoxidase, haptoglobin, and IGF1, with ratios ranging from 1.2 to 2.0 (p < 0.001). Women exhibited lower concentrations of most amino acids, except for glutamate and alanine. Although almost 30% lower in women, branched-chain amino acids (BCAAs) showed a similar pattern in all states (ρ ≥ 0.9; p < 0.001), while aromatic amino acids (AAAs) showed higher consumption during exercise in women. Conclusion: We established sex dimorphism in elite athletes' metabolic and inflammatory responses during training and competition. Our data suggest that female athletes present a lower amino acid response towards central fatigue development than male athletes. Understanding these differences can lead to insights into sex-related immuno-metabolic responses in sports or other inflammatory conditions. [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 a-diversity and b-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 a-diversity and b-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 gutmicrobiota and metabolismon brain function in individuals with schizophrenia. [ABSTRACT FROM AUTHOR]

Oncolytic viral immunotherapy is a cancer treatment that uses native or genetically modified viruses that selectively replicate and destroy tumor cells. In this study, we aimed to construct a virus-based prognostic model for risk assessment and prognosis prediction in patients with hepatocellular carcinoma (HCC) and determine the most appropriate virus as a candidate vector for oncolytic virus immunotherapy. Microbiome and RNA sequencing data and clinical information were obtained from The Cancer Genome Atlas, and viruses with prognostic value were identified (Deltabaculovirus, Sicinivirus, and Cytomegalovirus) to construct the prognostic model. Correlation analyses were performed to evaluate the predictive function of the viral signature. Bioinformatics analyses were conducted to explore the functional enrichment of viral expression in HCC. The risk score generated by this model could distinguish patients with different survival outcomes, have excellent reliability and accuracy, and could be used as an independent prognostic indicator. The high-risk score group showed significantly lower overall survival, and this trend was also observed in subgroups with different clinicopathological features. Furthermore, Deltabaculovirus positively correlated with amino acid metabolism, energy metabolism signaling pathways, peroxisomes, and complement coagulation cascades. In addition, Deltabaculovirus was significantly related to immune cell infiltration; therefore, patients with high Delta-baculovirus expression might respond better to HCC immunotherapy. Our study identified a promising predictive viral signature for assessing clinical prognosis and guiding immunotherapy in HCC. Deltabaculovirus might be a suitable viral vector for oncolytic virus immunotherapy. [ABSTRACT FROM AUTHOR]

Background: In preterm infants, IV administration of fat is less well tolerated compared to intake via the enteral route, often resulting in hypertriglyceridemia. It is therefore recommended that parenteral fat intake should not exceed 3.5 to 4.0 g/kg/d whereas human milk can provide up to 8 g/kg/d. It is unknown whether such hypertriglyceridemic conditions are caused by a uniform increase of all fatty acids or it is linked to an elevation of distinct fatty acids due to an unbalanced intake. Obviously, both scenarios could potentially influence the formulation of novel lipid solutions for preterm infants. Objective of this exploratory study was to compare fatty acid profiles between a) different nutritional sources and corresponding plasma samples, b) plasma of infants fed breast milk versus those receiving lipid emulsion, and c) plasma of infants with normal versus elevated triglyceride levels. Methods: Forty-seven preterm infants < 36 weeks of gestation were included; fatty acid profiles were measured in serum samples and corresponding nutritional sources (breast milk and lipid emulsion) using gas chromatography/mass spectrometry. Results: Compared to breast milk levels, plasma contained significantly lower C8:0, C10:0, C12:0, C14:0, C19:1n9, C18:3n3 (p < 0.0001). In contrast, relative abundance of C16:0, C18:0 and C20:4n6 was higher in plasma than in corresponding breast milk samples (p < 0.001) and lipid emulsion (p < 0.01). Compared to the corresponding lipid emulsion, the abundance of C18:2n6 and C18:3n3 was significantly lower in plasma (p < 0.001). Fatty acid profiles in plasma of infants fed breast milk compared to lipid emulsion were not markedly different. Hypertriglyceridemic samples showed elevated levels for C18:1n9 and C16:0 when compared with normotriglyceridemic samples. Conclusions: Our study reveals that lipid levels in plasma show both depletion and enrichment of distinct fatty acids which do not seem to be closely related to dietary intake. A more detailed understanding of fatty acid flux rates is needed, like the understanding of amino acid metabolism and is supported by the finding that hypertriglyceridemia might be a state of selective fatty acid accumulation. This would allow to develop more balanced diets for intensive care and potentially improve clinical outcomes. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is involved in most biological processes and actively participates in the regulation of reproduction. According to recent research, long non-coding RNAs (lncRNAs) and their m6A modifications are involved in reproductive diseases. In the present study, using m6A-modified RNA immunoprecipitation sequencing (m6A-seq), we established the m6A methylation transcription profiles in patients with recurrent implantation failure (RIF) for the first time. There were 1443 significantly upregulated m6A peaks and 425 significantly downregulated m6A peaks in RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that genes associated with differentially methylated lncRNAs are involved in the p53 signalling pathway and amino acid metabolism. The competing endogenous RNA network revealed a regulatory relationship between lncRNAs, microRNAs and messenger RNAs. We verified the m6A methylation abundances of lncRNAs by using m6A-RNA immunoprecipitation (MeRIP)–real-time polymerase chain reaction. This study lays a foundation for further exploration of the potential role of m6A modification in the pathogenesis of RIF. [ABSTRACT FROM AUTHOR]

Trypanosoma cruzi, the causative agent of Chagas disease, has a complex life cycle that involves triatomine insects as vectors and mammals as hosts. The differentiation of epimastigote forms into metacyclic trypomastigotes within the insect vector is crucial for the parasite's life cycle progression. Factors influencing this process, including temperature, pH, and nutritional stress, along with specific metabolite availability, play a pivotal role. Amino acids like proline, histidine, and glutamine support cell differentiation, while branched-chain amino acids (BCAAs) inhibit it. Interestingly, combining the pro-metacyclogenic amino acid proline with one of the anti-metacyclogenic BCAAs results in viable metacyclics with significantly reduced infectivity. To explore the characteristics of metacyclic parasites differentiated in the presence of BCAAs, proteomics analyses were conducted. Metacyclics obtained in triatomine artificial urine (TAU) supplemented with proline alone and in combination with leucine, isoleucine, or valine were compared. The analyses revealed differential regulation of 40 proteins in TAU-Pro-Leu, 131 in TAU-Pro-Ile, and 179 in TAU-Pro-Val, as compared to metacyclics from TAU-Pro. Among these, 22%, 11%, and 13% of the proteins were associated with metabolic processes, respectively. Notably, enzymes related to glycolysis and the tricarboxylic acid (TCA) cycle were reduced in metacyclics with Pro-BCAAs, while enzymes involved in amino acid and purine metabolic pathways were increased. Furthermore, metacyclics with Pro-Ile and Pro-Val exhibited elevated enzymes linked to lipid and redox metabolism. The results revealed five proteins that were increased and four that were decreased in common in the presence of Pro+BCAAs, indicating their possible participation in key processes related to metacyclogenesis. These findings suggest that the presence of BCAAs can reshape the metabolism of metacyclics, contributing to the observed reduction in infectivity in these parasites. Author summary: Trypanosoma cruzi, the parasite causing Chagas disease, infects 6–7 million people in the Americas. Its life cycle involves the infection of triatomine insects which transmit the infection to humans and other mammals. Inside the insects, the parasite proliferates as non-infective forms, and its transmission to mammals depends on their differentiation into infective forms. Proline is a factor supporting this differentiation, while valine, leucine and isoleucine (known collectively as BCAA for branched-chain amino acids) do not. Combining proline with each BCAA results in a diminished number of viable parasites, with significantly reduced infectivity. To explore the causes of such diminished infectivity, we performed a proteomics analysis to compare parasites obtained with proline, in the presence or absence of BCAA. We observed that BCAA differentially regulated different proteins associated with metabolic processes: BCAA diminished enzymes related to glycolysis and the tricarboxylic acid (TCA) cycle while increased enzymes involved in amino acid and purine metabolism. Furthermore, isoleucine or valine increased enzymes linked to lipid and redox metabolism. These findings suggest that the presence of BCAAs can reshape the metabolism of the parasite, contributing to the observed reduction in infectivity. [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 a-diversity and b-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 a-diversity and b-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]

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]

Sprouts are well known for having a remarkable nutritional profile. Enhancing plant chemical composition and quality of sprouts is essential since these metabolites offer numerous health advantages. To this end, this study aimed to investigate the effects of priming with multiwalled carbon nanotubes (MWCNTs) on the growth and nitrogen (N) metabolism of four horticultural plants, namely, Trigonella foenum-graecum, Linium grandiflorum, Lepidium sativum, and Anethum gravelones. The properties of our synthesized MWCNTs included three characteristic peaks 3434, 1539, and 1068 cm−1 attributable to the stretching vibration of O–H, bending vibration, and C − O, respectively. MWCNT priming increased the sprouting process by inducing biomass and protein accumulation. MWCNT priming improved N metabolism, including amino acid and polyamine metabolism. At the amino acid level, there was an increase in amino acid levels (e.g., glycine, lysine, asparagine, and glutamic acid) as well as their metabolic enzyme activities, including glutamine synthetase (GS), threonine synthetase (TS), and glutamate synthetase (GOGAT). Increased polyamine levels like spermine, putrescine, and spermidine were also associated with boosting their related biosynthetic enzyme activities, i.e., arginine decarboxylase (ADC), ornithine decarboxylase (ODC), spermidine synthase, and spermine synthase (SpmS). This improvement of nitrogen metabolic pathways highlights the potential of MWCNT to boost the chemical composition of horticultural plants. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease featured by chronic synovitis and progressive joint damage. Early treatment before the onset of clinical symptoms (also known as the pre-RA stage) may slow or stop the progression of the disease. We sought to discover the dynamic metabolic changes during the evolution of collagen-induced arthritis (CIA) to better characterize the disease stages. Untargeted metabolomics analysis using gas chromatography–mass spectrometry revealed that the metabolic profiles of CIA mice gradually differed from that of the control group with the progression of the disease. During the induction phase, the CIA group showed some metabolic alterations in galactose metabolism, arginine biosynthesis, tricarboxylic acid cycle (TCA cycle), pyruvate metabolism, and starch/sucrose metabolism. During the early inflammatory phase, no joint swelling was observed in CIA mice, and metabolites changed mainly involving amino acid metabolism (arginine biosynthesis, arginine/proline metabolism, phenylalanine/tyrosine/tryptophan biosynthesis), and glutathione metabolism. During the peak inflammatory phase, severe arthritis symptoms were observed in CIA mice, and there were more extensive metabolic alterations in valine/leucine/isoleucine biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, TCA cycle, galactose metabolism, and arginine biosynthesis. Moreover, the reduction of specific amino acids, such as glycine, serine, and proline, during the early stages may result in an imbalance in macrophage polarization and enhance the inflammatory response in CIA mice. Our study confirmed that specific perturbations in amino acid metabolism have occurred in CIA mice prior to the onset of joint symptoms, which may be related to autoimmune disorders. The findings could provide insights into the metabolic mechanism and the diagnosis of pre-RA. [ABSTRACT FROM AUTHOR]

Gut microbiome of animals is affected by external environmental factors and can assist them in adapting to changing environments effectively. Consequently, elucidating the gut microbes of animals under different environmental conditions can provide a comprehensive understanding of the mechanisms of their adaptations to environmental change, with a particular focus on animals in extreme environments. In this study, we compared the structural and functional differences of the gut microbiome of grazing yaks between the summer and winter seasons through metagenomic sequencing and bioinformatics analysis. The results indicated that the composition and function of microbes changed significantly. The study demonstrated an increase in the relative abundance of Actinobacteria and a higher ratio of Firmicutes to Bacteroidetes (F/B) in winter, this process facilitated the adaptation of yaks to the consumption of low‐nutrient forages in the winter. Furthermore, the network structure exhibited greater complexity in the winter. Forage nutrition exhibited a significant seasonal variation, with a notable impact on the gut microbiota. The metagenomic analysis revealed an increase in the abundance of enzymes related to amino acid metabolism, axillary activity, and mucin degradation in the winter. In conclusion, this study demonstrated that the gut microbiome of grazing yaks exhibits several adaptive characteristics that facilitate better nutrient accessibility and acid the host in acclimating to the harsh winter conditions. Furthermore, our study offers novel insights into the mechanisms of highland animal adaptation to external environments from the perspective of the gut microbiome. [ABSTRACT FROM AUTHOR]

In tumor cells, changes in specific amino acids can have a significant impact on the metabolism of cancer cells and alter the response of immune cells in the tumor microenvironment, affecting the occurrence, development, and therapeutic effects of tumors. This article first introduces the role of amino acids in tumors, exploring the metabolism of essential amino acids in tumors from the intake of exogenous amino acids, amino acid modification, and metabolism of branched chain amino acids, and clarify the role of nonessential amino acids in nonessential amino acid deficient tumors. Secondly, the impact of amino acid metabolism reprogramming on the occurrence and development of hepatocellular carcinoma was elucidated. Essential and nonessential amino acids play an indispensable role in hepatocellular carcinoma development. In liver cancer cells, the abnormally high content of essential amino acids promotes the occurrence and development of liver cancer cells, but the increase of branched chain amino acid content has a dual effect. Nonessential amino acids often act as inhibitory factors in liver cancer cells, but arginine can combine with asparagine to form a positive feedback loop and promote the occurrence and development of liver cancer. Finally, the impact of amino acid metabolism reprogramming on the treatment of hepatocellular carcinoma was elucidated. Glutamate, serine, branched chain amino acids, S-adenosylmethionine, glycine, arginine, etc. can serve as targets for liver cancer. Inhibiting the expression of glutarate dehydrogenase can improve the drug sensitivity of liver cancer patients to sorafenib. The reprogramming of amino acid metabolism in the tumor microenvironment of hepatocellular carcinoma promotes the malignant proliferation and immune escape of liver cancer cells. Studying the specific changes in amino acids is beneficial for developing personalized immunotherapy for patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of Lentilactobacillus plantarum (LP), cellulase (CE), and xylanase (XE) supplementation on the fermentation quality, chemical composition, and bacterial community of Caragana korshinskii Kom. silage. Four groups were designed for the study. No additives were used in the control group (CK), and LP (1 × 106 cfu/g), CE (1 × 104 IU/g) and XE (2 × 105 IU/g) were added to the experimental groups on a fresh matter basis, with three replicates per group. To promote fermentation, 5% molasses was added to all of the groups. On days 15 and 60, fermentation quality, chemical composition and the bacterial community were analysed. The pH of groups CE and XE was lower than that of the CK group at 60 days. During ensiling, the lactic acid (LA) content in the experimental groups and the acetic acid (AA) content in the CK and LP groups increased. At 60 days, the dominant genera in the CK and LP groups was Weissella and the dominant genera in the CE and XE groups was Lentilactobacillus. At different times during silage, nucleotide metabolism was enhanced, whereas the metabolism of carbohydrate, amino acids, energy, cofactors and vitamins was inhibited in the LP group. However, the metabolism of amino acids, energy, cofactors and vitamins in the CE and XE groups was increased, whereas the metabolism of nucleotides was inhibited. In conclusion, LP, CE and XE could exert a positive effect on the fermentation quality of C. korshinskii Kom. silage by shifting the bacterial community composition. [ABSTRACT FROM AUTHOR]

Soil salinization and alkalinization are pervasive environmental issues that severely restrict plant growth and crop yield. Utilizing plant growth-promoting rhizobacteria (PGPR) is an effective strategy to enhance plant tolerance to saline–alkaline stress, though the regulatory mechanisms remain unclear. This study employed biochemical and RNA-Seq methods to uncover the critical growth-promoting effects of Trichoderma spp. on Salix linearistipularis under saline–alkaline stress. The results showed that, during saline–alkaline stress, inoculation with Trichoderma sp. M4 and M5 significantly increased the proline and soluble sugar contents in Salix linearistipularis, enhanced the activities of SOD, POD, CAT, and APX, and reduced lipid peroxidation levels, with M4 exhibiting more pronounced effects than M5. RNA-Seq analysis of revealed that 11,051 genes were upregulated after Trichoderma sp. M4 inoculation under stress conditions, with 3532 genes primarily involved in carbon metabolism, amino acid biosynthesis, and oxidative phosphorylation—processes that alleviate saline–alkaline stress. Additionally, 7519 genes were uniquely upregulated by M4 under stress, mainly enriched in secondary metabolite biosynthesis, amino acid metabolism, cyanamide metabolism, and phenylpropanoid biosynthesis. M4 mitigates saline–alkaline stress-induced damage in Salix linearistipularis seedlings by reducing oxidative damage, enhancing organic acid and amino acid metabolism, and activating phenylpropanoid biosynthesis pathways to eliminate harmful ROS. This enhances the seedlings' tolerance to saline–alkaline stress, providing a basis for studying fungi–plant interactions under such conditions. [ABSTRACT FROM AUTHOR]

Sulfur (S) is an essential nutrient for plant growth, influencing not only crop yields but also the composition and function of soil microbial communities. However, the differential effects of S fertilization on abundant and rare taxa in agricultural soils remain poorly understood. This study investigates the impact of different S fertilizer types on maize yield and the structure and stability of soil microbial communities, with a particular focus on abundant and rare taxa. S fertilization led to significant increases maize yield on two typical soils (black soil and sandy soil) (5.3–24.3%) and altered soil properties, including reducing pH (0.04–0.20) and increasing the available sulfur (AS) content (3.8–8.0 mg kg−1), with ammonium sulfate having a more pronounced effect than elemental sulfur. Microbial analysis revealed distinct impacts on the diversity and community structure of both abundant and rare taxa. Elemental sulfur reduced the alpha diversity of abundant taxa more than ammonium sulfate, while NMDS indicated significant shifts in community structures, particularly among abundant taxa. Network analysis showed that S fertilization decreased the complexity of microbial interactions among rare taxa, with ammonium sulfate leading to simpler networks and elemental sulfur resulting in higher modularity. SEM highlighted that the diversity of rare taxa played a crucial role in influencing maize yield, alongside direct effects from soil properties such as AS and SAR (aryl sulfatase). Functional predictions demonstrated that amino acid metabolism and xenobiotic biodegradation and metabolism pathways were enriched in rare taxa, suggesting significant implications for soil health and crop productivity. This study provides new insights into the roles of abundant and rare bacterial taxa under S fertilization, emphasizing their importance in optimizing fertilization strategies for enhanced crop yield in specific soil types. [ABSTRACT FROM AUTHOR]

Water deficit is a major cause of yield loss for maize (Zea mays), leading to ovary abortion when applied at flowering time. To help understand the mechanisms involved in this phenomenon, the proteome response to water deficit has been analysed in developing ovaries at the silk emergence stage and five days later. Differential analysis, abundance pattern clustering and co-expression networks were performed in order to draw a general picture of the proteome changes all along ovary development and under the effect of water deficit. The results show that even mild water deficit has a major impact on ovary proteome, but this impact is very different from a response to stress. A part of the changes can be related to a slowdown of ovary development, while another part cannot. In particular, ovaries submitted to water deficit show an increase in proteins involved in protein biosynthesis and in vesicle transport together with a decrease in proteins involved in amino acid metabolism and proteolysis. According to the functions of increased proteins, the changes may be linked to auxin, brassinosteroids and jasmonate signalling but not abscisic acid. [ABSTRACT FROM AUTHOR]

Deep-sea sediments harbor abundant microbial communities extending vertically up to ~2.5 km below the seafloor. Despite their prevalence, the reasons for their large community sizes and low energy fluxes remain unclear. Particularly, the reliance of fungi, the predominant eukaryotic group, on amino acids in these energy-limited, anaerobic conditions is poorly understood. We investigated the role of amino acids in the growth and development of the fungus Schizophyllum commune 20R-7-F01, isolated from anaerobic sub-seafloor sediments. The fungus efficiently used all amino acids as carbon sources, and some as nitrogen sources, with specific amino acids influencing sexual reproduction and fruit-body formation. Notably, amino acids with hydrocarbon chains or methyl groups appeared crucial for fruit-body production. The upregulation of genes, metabolites, and pathways related to amino acid metabolism in the fungus under anaerobic conditions underscores the significance of amino acids as energy and nutrient sources in such environments. Amino acids not only served as carbon/nitrogen sources but also contributed to fungal fruit-body formation under low oxygen conditions, vital for long-term fungal survival in the energy-limited deep biosphere. This study sheds light on the crucial role of amino acids in fungal growth and reproduction in energy-limited anaerobic conditions. IMPORTANCE In the depths beneath the ocean floor, where darkness, anaerobic conditions, and energy scarcity prevail, life persists against all odds. This study illuminates the pivotal role of amino acids, the fundamental building blocks of life, as a vital energy for deep subseafloor fungi. Our research uncovers how these fungi not only rely on amino acids for survival but also utilize them to reproduce, forming fruit bodies in environments deprived of oxygen and energy. This revelation not only elucidates the mechanisms enabling fungal survival in extreme conditions but also hints at the essentiality of amino acids as nutrients for other deep-sea microbes. By unraveling these mysteries of the hidden biosphere, our study opens new frontiers in understanding the resilience and adaptation of life in the most inhospitable environments on our planet. [ABSTRACT FROM AUTHOR]

Disruptions in circadian rhythms are associated with an increased risk of developing metabolic diseases. General control nonderepressible 2 (GCN2), a primary sensor of amino acid insufficiency and activator of the integrated stress response (ISR), has emerged as a conserved regulator of the circadian clock in multiple organisms. The objective of this study was to examine diurnal patterns in hepatic ISR activation in the liver and whole body rhythms in metabolism. We hypothesized that GCN2 activation cues hepatic ISR signaling over a natural 24-h feeding-fasting cycle. To address our objective, wild-type (WT) and whole body Gcn2 knockout (GCN2 KO) mice were housed in metabolic cages and provided free access to either a control or leucine-devoid diet (LeuD) for 8 days in total darkness. On the last day, blood and livers were collected at CT3 (CT = circadian time) and CT15. In livers of WT mice, GCN2 phosphorylation followed a diurnal pattern that was guided by intracellular branched-chain amino acid concentrations (r2 = 0.93). Feeding LeuD to WT mice increased hepatic ISR activation at CT15 only. Diurnal oscillations in hepatic ISR signaling, the hepatic transcriptome including lipid metabolic genes, and triglyceride concentrations were substantially reduced or absent in GCN2 KO mice. Furthermore, mice lacking GCN2 were unable to maintain circadian rhythms in whole body energy expenditure, respiratory exchange ratio, and physical activity when fed LeuD. In conclusion, GCN2 activation functions to maintain diurnal ISR activation in the liver and has a vital role in the mechanisms by which nutrient stress affects whole body metabolism. NEW & NOTEWORTHY: This work reveals that the eIF2 kinase GCN2 functions to support diurnal patterns in the hepatic integrated stress response during natural feeding and is necessary to maintain circadian rhythms in energy expenditure, respiratory exchange ratio, and physical activity during amino acid stress. [ABSTRACT FROM AUTHOR]

Domestication has shaped the population structure and agronomic traits of tea plants, yet the complexity of tea population structure and genetic variation that determines these traits remains unclear. We here investigated the resequencing data of 363 diverse tea accessions collected extensively from almost all tea distributions and found that the population structure of tea plants was divided into eight subgroups, which were basically consistent with their geographical distributions. The genetic diversity of tea plants in China decreased from southwest to east as latitude increased. Results also indicated that Camellia sinensis var. assamica (CSA) illustrated divergent selection signatures with Camellia sinensis var. sinensis (CSS). The domesticated genes of CSA were mainly involved in leaf development, flavonoid and alkaloid biosynthesis, while the domesticated genes in CSS mainly participated in amino acid metabolism, aroma compounds biosynthesis, and cold stress. Comparative population genomics further identified ~730 Mb novel sequences, generating 6,058 full‐length protein‐encoding genes, significantly expanding the gene pool of tea plants. We also discovered 217,376 large‐scale structural variations and 56,583 presence and absence variations (PAVs) across diverse tea accessions, some of which were associated with tea quality and stress resistance. Functional experiments demonstrated that two PAV genes (CSS0049975 and CSS0006599) were likely to drive trait diversification in cold tolerance between CSA and CSS tea plants. The overall findings not only revealed the genetic diversity and domestication of tea plants, but also underscored the vital role of structural variations in the diversification of tea plant traits. [ABSTRACT FROM AUTHOR]

Exogenous brassinolide (BR) and strigolactones (SLs) play an important role in alleviating salt stress in maize. We studied the morphological and physiological responses of the salt-sensitive genotype PH4CV and salt-tolerant genotype Zheng58 to BR (1.65 nM), SL (1 µM), and BS (1.65 nM BR + 1 µM SL) under salt stress. Phenotypic analysis showed that salt stress significantly inhibited the growth of maize seedlings and significantly increased the content of Na+ in the roots. Exogenous hormones increased oxidase activity and decreased Na+ content in the roots and mitigated salt stress. Transcriptome analysis showed that the interaction of BR and SL is involved in photosynthesis–antenna proteins, the TCA cycle, and plant hormone signal transduction pathways. This interaction influences the expression of chlorophyll a/b-binding protein and glucose-6-phosphate isomerase 1 chloroplastic, and aconitase genes are affected. Furthermore, the application of exogenous hormones regulates the expression of genes associated with the signaling pathways of cytokinin (CK), gibberellins (GA), auxin (IAA), brassinosteroid (BR), abscisic acid (ABA), and jasmonic acid (JA). Additionally, exogenous hormones inhibit the expression of the AKT2/3 genes, which are responsible for regulating ion transduction and potassium ion influx. Four candidate genes that may regulate the seedling length of maize were screened out through WGCNA. Respective KOG notes concerned inorganic ion transport and metabolism, signal transduction mechanisms, energy production and conversion, and amino acid transport and metabolism. The findings of this study provide a foundation for the proposition that BR and SL can be employed to regulate salt stress alleviation in maize. [ABSTRACT FROM AUTHOR]

Alkaline water is toxic to cultured aquatic animals that frequently live in pH-neutral freshwater. Overfishing and habitat destruction have contributed to the decline in the wild sturgeon population; consequently, the domestic hybrid sturgeon has become an increasingly important commercial species in China. Hybrid sturgeons are widely cultured in alkaline water, but little is known about the effects of alkalinity stress on hybrid sturgeon liver tissues. We exposed hybrid sturgeons to four alkaline concentrations (3.14 ± 0.02 mmol/L, 7.57 ± 0.08 mmol/L, 11.78 ± 0.24 mmol/L and 15.46 ± 0.48 mmol/L). Histopathology, biochemical index assessment, gene expression level detection and metabolomics analysis were used to investigate the negative effects on liver functions following exposure to NaHCO3. Livers exposed to alkaline stress exhibited severe tissue injury and clear apoptotic characteristics. With increased exposure concentrations, the hepatic superoxide dismutase, catalase, glutathione peroxidase and alkaline phosphatase activities significantly decreased in a dose-dependent manner. NaHCO3 exposure up-regulated the transcriptional levels of apoptosis/ferroptosis-related genes in livers. Similarly, the expression trends of interleukin-1β and heat shock protein genes also increased in high-alkalinity environments. However, the expression levels of complement protein 3 significantly decreased (p < 0.05). Hepatic untargeted metabolomics revealed the alteration conditions of various metabolites associated with the antioxidant response, the ferroptosis process and amino acid metabolism (such as beta-alanine metabolism; alanine, aspartate and glutamate metabolism; and glycine, serine and threonine metabolism). These data provided evidence that NaHCO3 impaired immune functions and the integrity of hybrid sturgeon liver tissues by mediating oxidative-stress-mediated apoptosis and ferroptosis. Our results shed light on the breeding welfare of domestic hybrid sturgeons and promote the economic development of fisheries in China. [ABSTRACT FROM AUTHOR]

Leaves are the primary harvest portion in forage crops such as alfalfa (Medicago sativa). Delaying leaf senescence is an effective strategy to improve forage biomass production and quality. In this study, we employed transcriptome sequencing to analyze the transcriptional changes and identify key senescence-associated genes under age-dependent leaf senescence in Medicago truncatula, a legume forage model plant. Through comparing the obtained expression data at different time points, we obtained 1057 differentially expressed genes, with 108 consistently up-regulated genes across leaf growth and senescence. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the 108 SAGs mainly related to protein processing, nitrogen metabolism, amino acid metabolism, RNA degradation and plant hormone signal transduction. Among the 108 SAGs, seven transcription factors were identified in which a novel bZIP transcription factor MtbZIP60 was proved to inhibit leaf senescence. MtbZIP60 encodes a nuclear-localized protein and possesses transactivation activity. Further study demonstrated MtbZIP60 could associate with MtWRKY40, both of which exhibited an up-regulated expression pattern during leaf senescence, indicating their crucial roles in the regulation of leaf senescence. Our findings help elucidate the molecular mechanisms of leaf senescence in M. truncatula and provide candidates for the genetic improvement of forage crops, with a focus on regulating leaf senescence. [ABSTRACT FROM AUTHOR]

Increased plasma concentrations of glucagon (hyperglucagonemia) are reported in patients with type 2 diabetes (T2D) and are considered a diabetogenic risk factor. Emerging evidence suggests that hepatic steatosis in obesity is causing a condition of resistance toward glucagon's effects on amino acid metabolism, resulting in an amino acid-induced hyperglucagonemia. We investigated the presence of hyperglucagonemia in individuals with biopsy-verified metabolic dysfunction-associated steatotic liver disease (MASLD), and whether body mass index (BMI), T2D, hepatic steatosis, and/or fibrosis contribute to this relationship. To dissect potential mechanisms, we also determined hepatic gene expression related to amino acid transport and catabolism. Individuals with MASLD had hyperglucagonemia {controls (n = 74) vs. MASLD (n = 106); median [Q1, Q3]; 4 [3, 7] vs. 8 [6, 13] pM), P < 0.0001} and were glucagon resistant (assessed by the glucagon-alanine index) {1.3 [0.9, 2.1] vs. 3.3 [2.1, 5.3] pM·mM, P < 0.0001}. These changes were associated with hepatic steatosis (P < 0.001, R2 > 0.25) independently of BMI, sex, age, and T2D. Plasma levels of glucagon were similar in individuals with MASLD when stratified on T2D status {MASLD-T2D (n = 52) vs. MASLD + T2D (n = 54); 8 [6, 11] vs. 8 [6, 13] pM, P = 0.34} and hepatic fibrosis {MASLD + F0 (n = 25) vs. MASLD + F1-F3 (n = 67); 8.4 [7.0, 13.3] vs. 7.9 [5.2, 11.6] pM, P = 0.43}. Obesity (BMI = 30 kg/m2) did not alter glucagon levels (P = 0.65) within groups (control/MASLD). The mRNA expression of proteins involved in amino acid transport and catabolism was downregulated in MASLD. Thus, relative hyperglucagonemia is present in individuals with biopsy-verified MASLD, and hepatic steatosis partially drives hyperglucagonemia and glucagon resistance, irrespective of T2D, BMI, and hepatic fibrosis. NEW & NOTEWORTHY: Individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) present with increased plasma levels of glucagon (hyperglucagonemia), irrespective of body mass index (BMI) and type 2 diabetes. Therefore, MASLD and the resultant hyperglucagonemia may act as a diabetogenic risk factor. Notably, hepatic steatosis was a significant contributor to the hyperglucagonemia in MASLD, potentially unveiling a pathway for the hyperglucagonemia in some patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objectives: Recurrent aphthous ulcer (RAU) is a prevalent oral mucosal disease, affecting around 20% of the global population. It can greatly impair the quality of life for affected individuals. However, the exact etiology of RAU remains unknown. Subjects and Methods: 16S rRNA sequencing (16S rRNA‐seq) and non‐targeted liquid chromatography‐mass spectrometry (LC–MS) were employed to investigate the salivary microbiota and metabolic phenotype between RAU patients (N = 61) and healthy controls (HCs) (N = 105). Results: Findings from 16S rRNA ‐seq indicated reduced oral microbial diversity in RAU patients compared to HCs, but increased interactions. Clinical variables did not show any significant association with the overall diversity of oral microbiota in RAU patients. However, significant correlations were observed between specific microorganisms and clinical variables. LC–MS results revealed dysregulation of amino acid, lipid, nucleotide, and caffeine metabolism in RAU patients. Furthermore, correlation analysis of 16S rRNA‐seq and LC–MS data revealed a significant association between salivary microbiota and metabolites in RAU patients. Conclusions: Our study revealed notable differences in salivary microbiota and metabolic profiles between RAU patients and HCs, indicating a strong link between oral microbiota dysbiosis, metabolic disturbances, and the onset and progression of RAU. [ABSTRACT FROM AUTHOR]

The composition and profile of amino acids in Rubus chingii (R. chingii) Hu serve as critical indicators of its nutritional quality. A comprehensive understanding of the amino acid metabolism within R. chingii is instrumental in the formulation and innovation of functional foods derived from this species. Utilizing advanced techniques such as wide-ranging untargeted metabolomics, transcriptome analysis, interaction network mapping, heat map analysis, and quantitative real-time PCR, we conducted a comprehensive assessment of the quality attributes across four distinct developmental stages of R. chingii. Our meticulous analysis uncovered a rich tapestry of 76 distinct amino acids and their derivatives within the developmental stages of R. chingii. The spectrum of essential amino acids was not only broad but also displayed a high degree of variety. Notably, leucine, lysine, and phenylalanine stood out as the most abundant amino acids, underscoring their significant presence throughout the growth cycle of R. chingii. The proportion of essential amino acids relative to the total amino acid content in R. chingii exhibited a notable trajectory of change throughout its developmental stages. It began with 30.92% in the immature green phase, advanced to 31.04% during the transition from green to yellow, peaked at 33.62% in the yellow to red stage, and then moderated to 30.43% in the full red phase. This pattern suggests a strategic modulation of amino acid composition, aligning with the evolving nutritional requirements and metabolic shifts as the fruit matures. Concurrent analysis of interaction networks and heat maps, alongside comprehensive profiling of amino acid metabolism and transcriptomic examination, was conducted to elucidate the intricate dynamics of cellular processes. The results showed that seven differentially expressed genes (DEGs) played important roles in amino acid metabolism, including PFK, BCAT1, TSB, ASA, ACO, TOM2AH3, and BCAT2. The expression patterns of seven DEGs conformed closely to the findings revealed by the preceding RNA-seq analysis. In this investigation, we elucidated the regulatory mechanisms underlying amino acid metabolism across the four distinct developmental stages of R. chingii through comprehensive amino acid profiling and transcriptomic analysis. These insights lay the groundwork for the development of novel functional food applications utilizing R. chingii. [ABSTRACT FROM AUTHOR]

Background: Acute Kidney Injury (AKI), a prevalent complication of Liver Transplantation (LT) that occurs during the perioperative period has been established to profoundly impact the prognosis of transplant recipients. This study aimed to investigate the mechanism of the hepatic IRI-induced AKI and to identify potential therapeutic targets for treating this condition and improving the prognosis of LT patients. Methods: An integrated transcriptomics and proteomics approach was employed to investigate transcriptional and proteomic alterations in hepatic IRI-induced AKI and the hypoxia-reoxygenation (H/R) model using TCMK-1 cells and the hepatic IRI-induced AKI mouse model using male C57BL/6 J mice were employed to elucidate the underlying mechanisms. Hematoxylin–eosin staining, reverse transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot were used to assess the effect of Rosiglitazone (RGZ) on hepatic IRI-induced AKI in vitro and in vivo. Results: According to the results, 322 genes and 128 proteins were differentially expressed between the sham and AKI groups. Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analyses revealed significant enrichment in pathways related to amino acid and lipid metabolism. Additionally, the Protein–Protein Interaction (PPI) network analysis of the kidney tissues obtained from a hepatic IRI-induced AKI mouse model highlighted arachidonic acid metabolism as the most prominent pathway. Animal and cellular analyses further revealed that RGZ, a PPAR-γ agonist, could inhibit the expression of the PPAR-γ/NF-κB signaling pathway-associated proteins in in vitro and in vivo. Conclusions: These findings collectively suggest that RGZ ameliorates hepatic IRI-induced AKI via PPAR-γ/NF-κB signaling pathway modulation, highlighting PPAR-γ as a crucial therapeutic target for AKI prevention post-LT. [ABSTRACT FROM AUTHOR]

Increased plasma levels of glucagon (hyperglucagonemia) promote diabetes development but are also observed in patients with metabolic dysfunction–associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance toward amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated. We evaluated our glucagon sensitivity (GLUSENTIC) test, which consists of 2 study days: a glucagon injection and measurements of plasma amino acids and an infusion of mixed amino acids and subsequent calculation of the GLUSENTIC index (primary outcome measure) from measurements of glucagon and amino acids. To distinguish glucagon-dependent from insulin-dependent actions on amino acid metabolism, we also studied patients with type 1 diabetes (T1D). The δ-decline in total amino acids was 49% lower in MASLD following exogenous glucagon (P = 0.01), and the calculated GLUSENTIC index was 34% lower in MASLD (P < 0.0001) but not T1D (P > 0.99). In contrast, glucagon-induced glucose increments were similar in control participants and participants with MASLD (P = 0.41). The GLUSENTIC test and index may be used to measure glucagon resistance in individuals with obesity and MASLD. Article Highlights: Patients with metabolic dysfunction–associated steatotic liver disease have an increased risk of developing diabetes due to altered insulin and glucagon signaling. While standardized methods exist to assess and identify insulin resistance, this is not the case for glucagon resistance. We aimed to determine the clinical applicability of an experimental test for assessing glucagon sensitivity (GLUSENTIC) and found that glucagon resistance may be captured by the GLUSENTIC test and index. Individuals with obesity and metabolic dysfunction–associated steatotic liver disease have glucagon resistance, as characterized by the impaired effects of glucagon on amino acid metabolism. The GLUSENTIC test may be applied in the clinical evaluation of glucagon resistance. [ABSTRACT FROM AUTHOR]

Insulin is a key regulator of amino acid metabolism. Many plasma amino acids, including lysine and its metabolite, α-aminoadipic acid (α-AA), a predictor for developing diabetes, are elevated in insulin resistance (IR). In 18 overweight women with IR and polycystic ovary syndrome compared with 12 lean control women, high physiological insulin during a euglycemic clamp failed to normalize many elevated amino acid metabolites, including branched-chain and aromatic amino acids, α-aminobutyric acid, and lysine, but normalized α-AA. To understand the underpinnings of differential responses of lysine and its metabolic product α-AA to high physiological insulin in IR compared with control participants, we developed a kinetic model using [α-15N1]-lysine and [13C1]-α-AA as tracers and measured the two tracers simultaneously in α-AA by innovative mass spectrometry. High insulin increased lysine conversion to α-AA in the IR and control groups but failed to normalize plasma lysine concentrations in IR due to a decrease in lysine metabolic clearance rate (MCR). In contrast, despite higher conversion rates of lysine to α-AA by high insulin, α-AA concentration decreased in IR because of the sustained greater MCR of α-AA. The abnormal amino acids and metabolites, even while on high physiological insulin, could potentially explain many functional derangements in IR. Article Highlights: This study aimed to determine whether high physiological insulin normalizes abnormal plasma amino metabolites in individuals with insulin resistance. High insulin levels failed to normalize many amino acids, including lysine, but normalized the lysine metabolite α-aminoadipic acid (α-AA) reported to predict future diabetes. A novel kinetic model was developed using two stable isotope tracers to measure lysine and α-AA kinetics simultaneously in humans during a single protocol using innovative mass spectrometry that can be applied to study other amino acid kinetics. High physiological insulin normalized α-AA in insulin resistance by maintaining its higher metabolic clearance, suggesting that high α-AA resulted from insulin resistance. [ABSTRACT FROM AUTHOR]

An integrated transcriptome and metabolome profiling was used to investigate how exogenous H2O2 affects amino acid metabolism and its underlying regulatory mechanism involved in post-harvest broccoli's yellowing and senescence processes. This approach found 86 differentially expressed genes (DEGs) and 28 differentially accumulated metabolites (DAMs) associated with amino acid metabolism during broccoli storage in the Control, H2O2, and DPI (diphenylene iodonium, an H2O2 inhibitor) treatments on 2 or 4 d. Furthermore, H2O2 treatment promoted the biosynthesis and accumulation of amino acids (e.g., tryptophan, valine, isoleucine, arginine, lysine, histidine, and glutamate) while inhibiting the degradation of seven amino acids (e.g., tyrosine, valine, leucine, isoleucine, β-alanine, glutamate, and proline) into tricarboxylic acid (TCA) cycle precursor (pyruvate) and intermediates (fumarate, acetyl-CoA, and 2-oxoglutarate). This inhibition alleviated metabolic disorders and ammonium-induced toxicity of post-harvest broccoli. Additionally, H2O2 treatment promoted the NH3 conversion into glutamine and the urea cycle, further mitigating ammonium-induced toxicity. H2O2 treatment also down-regulated the expressions of S-adenosylmethionine synthases (SAM), 1-aminocyclopropane-1-carboxylate synthases (ACS), and 1-aminocyclopropane-1-carboxylate oxidases (ACO), which reduced the S-adenosyl-L-methionine content, thereby inhibiting ethylene biosynthesis from methionine. Therefore, this study provides insights into the role and potential underlying regulatory mechanism of H2O2 on amino acid metabolism during broccoli senescence, thus offering a theoretical basis for delaying senescence in post-harvest horticultural products by regulating their amino acid metabolism. [ABSTRACT FROM AUTHOR]