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Amino acid metabolic remodeling is a hallmark of cancer, driving an increased nutritional demand for amino acids. Amino acids are pivotal for energetic regulation, biosynthetic support, and homeostatic maintenance to stimulate cancer progression. However, the role of phenylalanine in multiple myeloma (MM) remains unknown. Here, we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow (BM) cells. After the treatment, phenylalanine levels increase in plasma and decrease in BM. This suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM progression. The requirement for phenylalanine by MM cells exhibits a similar pattern. Inhibiting phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib (BTZ) treatment in vitro and murine models. Mechanistically, phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3–CHOP–DR5 pathway. Interference with ATF3 significantly affects phenylalanine deprivation therapy. In conclusion, we have identified phenylalanine metabolism as a characteristic feature of MM metabolic remodeling. Phenylalanine is necessary for MM proliferation, and its aberrant demand highlights the importance of low-phenylalanine diets as an adjuvant treatment for MM. Changes in phenylalanine serve as markers for multiple myeloma patients and predict a poor prognosis. Exogenous phenylalanine deprivation inhibits MM progression by perturbing endoplasmic reticulum homeostasis via the ATF3–CHOP–DR5 signaling axis. [Display omitted] [ABSTRACT FROM AUTHOR]

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells. Herein, we constructed a PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) to regulate the metabolism of cancer-associated fibroblasts (CAFs), thus enhancing Epi penetration into both multicellular tumor spheroids (MTSs) and tumor tissues in mouse colon cancer (CT26), mouse breast cancer (4T1) and human breast cancer (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin, α -SMA, and collagen secretion. Besides, thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell (DC) maturation and subsequent immune activation, including elevating the CD4+ T cell population, reducing CD4+ and CD8+ T cell hyperactivation and exhaustion, and amplifying the natural killer (NK) cell proportion and effectively activating them. As a result, this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy. A dendritic polymer-based nanomedicine was constructed to disturb the amino acid metabolism of cancer-associated fibroblasts for enhancing Epi penetration, boosting tumor immune cell infiltration, and elevating its therapeutic effect. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] A substantial proportion of sensitized individuals tolerate suspected foods without developing allergic symptoms; this phenomenon is known as sensitized tolerance. The immunogenic and metabolic features underlying the sensitized-tolerant phenotype remain largely unknown. We aimed to uncover the metabolic signatures associated with clinical milk allergy (MA) and sensitized tolerance using metabolomics. We characterized the serum metabolic and immunologic profiles of children with clinical IgE-mediated MA (n = 30) or milk-sensitized tolerance (n = 20) and healthy controls (n = 21). A comparative analysis was performed to identify dysregulated pathways associated with the clinical manifestations of food allergy. We also analyzed specific biomarkers indicative of different sensitization phenotypes in children with MA. The candidate metabolites were validated in an independent quantification cohort (n = 41). Metabolomic profiling confirmed the presence of a distinct metabolic signature that discriminated children with MA from those with milk-sensitized tolerance. Amino acid metabolites generated via arginine, proline, and glutathione metabolism were uniquely altered in children with sensitized tolerance. Arginine depletion and metabolism through the polyamine pathway to fuel glutamate synthesis were closely associated with suppression of clinical symptoms in the presence of allergen-specific IgE. In children with MA, the polysensitized state was characterized by disturbances in tryptophan metabolism. By combining untargeted metabolomics with targeted validation in an independent quantification cohort, we identified candidate metabolites as phenotypic and diagnostic biomarkers of food allergy. Our results provide insights into the pathologic mechanisms underlying childhood allergy and suggest potential therapeutic targets. [ABSTRACT FROM AUTHOR]

In bacteria, d -amino acids are primarily synthesized from l -amino acids by amino acid racemases, but some bacteria use d -amino acid aminotransferases to synthesize d -amino acids. d -Amino acids are peptidoglycan components in the cell wall involved in several physiological processes, such as bacterial growth, biofilm dispersal, and peptidoglycan metabolism. Therefore, their metabolism and physiological roles have attracted increasing attention. Recently, we identified novel bacterial d -amino acid metabolic pathways, which involve amino acid racemases, with broad substrate specificity, as well as multifunctional enzymes with d -amino acid-metabolizing activity. Here, I review these multifunctional enzymes and their related d - and l -amino acid metabolic pathways in Escherichia coli and the hyperthermophile Thermotoga maritima. [ABSTRACT FROM AUTHOR]

Liquid biopsy is gradually being applied in the clinical diagnosis and treatment of lung cancer. At present, with the development of metabolomics, more and more metabolic biomarkers are considered as potential sensitive markers reflecting the occurrence and development of tumors. This article summarizes the changes in the main metabolic pathways of lung cancer, including glucose metabolism, amino acid metabolism, lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and purine metabolism. Meanwhile, this article reviews the role of metabolic biomarkers in the early diagnosis of lung cancer, predicting disease progression, and evaluating the efficacy of chemotherapy and immunotherapy, aiming to provide effective biomarkers for tumor diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Circulating biomarkers provide potential diagnostic or prognostic information on disease presentation, progression or both. Early detection of circulating risk biomarkers is critical for non-alcoholic fatty liver disease (NAFLD) prevention. We aimed to systematically assess the potential causal relationship of genetically predicted 60 circulatory biomarkers with NAFLD using a two-sample Mendelian randomization (MR) design. We extracted instrumental variables for 60 circulating biomarkers, and obtained genome-wide association data for NAFLD from 3 sources [(including Anstee, FinnGen and UK Biobank (N ranges: 19264–377988)] among individuals of European ancestry. Our primary method was inverse-variance weighted (IVW) MR, with a series of additional and sensitivity analyses to test the hypothesis of MR. MR results showed that genetically predicted higher density lipoprotein-cholesterol (odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.77–0.96) and vitamin D (OR = 0.39, 95% CI: 0.19–0.78) levels decreased the risk of NAFLD, whereas genetically predicted higher alanine (OR = 1.68, 95% CI: 1.21–2.33), histidine (OR = 1.21, 95% CI: 1.00–1.46), lactate (OR = 2.64, 95% CI: 1.09–6.39), triglycerides (OR = 1.16, 95% CI: 1.05–1.13), ferritin (OR = 1.17, 95% CI: 1.01–1.37), serum iron (OR = 1.23, 95% CI: 1.07–1.41) and transferrin saturation (OR = 1.16, 95% CI: 1.05–1.29), component 4 (OR = 1.10, 95% CI: 1.01–1.20), interleukin-1 receptor antagonist (OR = 1.12, 95% CI: 1.04–1.21) and interleukin-6 (OR = 1.62, 95% CI: 1.14–2.30) levels increased the risk of NAFLD. The findings might aid in elucidating the underlying processes of these causal relationships and provide strong evidence for focusing on high-risk populations and the therapeutic management of specific biomarkers. [Display omitted] • The results showed that genetically predicted higher density lipoprotein-cholesterol and vitamin D levels decreased the risk of NAFLD. • Genetically predicted higher alanine, histidine, lactate, triglycerides, ferritin, serum iron and transferrin saturation, complement 4, interleukin-1 receptor antagonist and interleukin-6 levels increased the risk of NAFLD. • The conclusion might aid in elucidating the underlying processes of these causal relationships and provided strong evidence for focusing on high-risk populations and the therapeutic management of specific biomarkers. [ABSTRACT FROM AUTHOR]

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer (CRC). However, the effect of ginsenoside Rk3 (Rk3) on CRC and gut microbiota remains unclear. Therefore, the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation. Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors, repairs intestinal barrier damage, and regulates the gut microbiota imbalance caused by CRC, including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis , and clearance of pathogenic Desulfovibrio. Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids, particularly by upregulating glutamine, which has the potential to regulate the immune response. Furthermore, we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) signaling pathways, which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway. These results indicate that Rk3 modulates gut microbiota, regulates ILC3s immune response, and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors. More importantly, the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota. In summary, these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC. [Display omitted] • Rk3 suppresses colorectal tumorigenesis. • Rk3 modulates dysbiosis of gut microbiota. • Rk3 regulates intestinal ILC3 immune response. • The antitumor effects of Rk3 depend on gut microbiota. • Rk3-modulated gut microbiota inhibits colorectal tumorigenesis. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice. We exposed 6–8-week-old male C57BL/6 mice to 5 mg/(kg·day) and 50 μg/(kg·day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing. Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment. Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates. [ABSTRACT FROM AUTHOR]

Nonhepatic Hyperammonemic encephalopathy (NHAE) following Bariatric Surgery (BS), mainly Roux-en-Y Gastric Bypass (RYGB) and Biliopancreatic Diversion (BPD) is a potentially devastating condition if not diagnosed and managed promptly. A literature review was performed using PRISMA guidelines. Eighteen studies and 3 conference abstracts with a total of 33 patients were included in this review. Majority (28 patients, 84.8 %) had RYGB. Seven patients (21.2 %) had associated metabolic disorders. 60 % of patients presented with neurological symptoms or signs such as confusion, cognitive and/or psychomotor changes, and decreased reflexes. Two patients presented with status epilepticus. In 30 of the 33 patients an elevated serum ammonia levels was reported (90.9 %). The overall mortality was 39.3 %. NHAE is a rare condition following bariatric surgery (in particular bypass procedures), carrying a high mortality rate. The signs and symptoms are predominantly neurological and may be mistaken for Wernicke's encephalopathy or other more common neurological conditions. Serum ammonia levels should be checked in those who present with these symptoms and signs. Prompt treatment might be life saving in patients with NHAE. [ABSTRACT FROM AUTHOR]

Amino-containing compounds, including amino acids, aliphatic amines, aromatic amines, small peptides and catecholamines, are involved in various biological processes and play vital roles in multiple metabolic pathways. Previous studies indicated that some amino-containing metabolites are significant diagnostic and prognostic biomarkers of gastric cancer. However, the discovery of precise biomarkers for the preoperative diagnosis of gastric cancer is still in an urgent need. Herein, we established a polarity-regulated derivatization method coupled with liquid chromatography-mass spectrometry (LC-MS) for amino-containing metabolites profiling in the serum samples of patients with gastric cancer and healthy controls, based on our newly designed and synthesized derivatization reagent (S)-3-(1-(diisopropoxyphosphoryl) pyrrolidine-2-carboxamido)- N -hydroxysuccinimidyl ester (3-DP-NHS). Enhanced separation efficiency and detection sensitivity for amino-containing metabolites were achieved after derivatization. This method exhibited good linearity, recovery, intra- and inter-day precision and accuracy. Only 5 μL serum is needed for untargeted analysis, enabling 202 amino-containing metabolites to be detected. Statistical analysis revealed altered amino acid metabolisms in patients with gastric cancer. Furthermore, ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) analysis quantification revealed increased serum levels of tryptamine and decreased concentrations of arginine and tryptophan in patients with gastric cancer. Receiver operating characteristic (ROC) curves indicated that an increased tryptamine/tryptophan ratio could serve as a potential biomarker for gastric cancer diagnosis. This study demostrated the possibility of using serum amino acid biomarkers for gastric cancer diagnosis, providing new avenues for the treatment of gastric cancer. [Display omitted] • A new derivatization-LC-MS method was used to profile amino-containing metabolites. • 3-DP-NHS derivatization enhanced the separation and detection sensitivity. • Abnormal amino acid metabolisms were disclosed in gastric cancer. • Increased serum TRA/Trp ratio could be served as a biomarker for gastric cancer. [ABSTRACT FROM AUTHOR]

Microorganisms play an important role in cigar fermentation. To further explore the dynamic changes of bacterial community composition, the changes of surface bacterial diversity of cigar filler leaves were investigated in the present study by high-throughput sequencing technology. It was found that the surface bacterial richness was declined after fermentation, and the dominant microorganisms on the surface of cigar filler leaves evolved from Pseudomonas spp. and Sphingomonas spp. before fermentation to Staphylococcus spp. after fermentation. The chemical composition and sensory quality evaluation of cigar filler leaves were closely related to the changes of surface bacterial community. The changes of the dominant surface bacterial community led to the differences of metabolic functions, among which the metabolic pathways such as the synthesis of secondary metabolites, carbon metabolism, and amino acid biosynthesis were significantly different. The results provide a basis for clarifying the roles of bacteria in fermentation of cigar filler leaves. Surface bacterial dynamic changes analysis of cigar filler leaves after fermentation revealed important role of Staphylococcus spp. in aroma improvement. [ABSTRACT FROM AUTHOR]

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Alterations in amino acid metabolism is closely related to the occurrence of clinical diseases. The mechanism of tumorigenesis is complex, involving the complicated relationship between tumor cells and immune cells in local tumor microenvironment. A series of recent studies have shown that metabolic remodeling is intimately related to tumorigenesis. And amino acid metabolic reprogramming is one of the important characteristics of tumor metabolic remodeling, which participates in tumor cells growth, survival as well as the immune cell activation and function in the local tumor microenvironment, thereby affecting tumor immune escape. Recent studies have further shown that controlling the intake of specific amino acids can significantly improve the effect of clinical intervention in tumors, suggesting that amino acid metabolism is gradually becoming one of the new promising targets of clinical intervention in tumors. Therefore, developing new intervention strategies based on amino acid metabolism has broad prospects. In this article, we review the abnormal changes in the metabolism of some typical amino acids, including glutamine, serine, glycine, asparagine and so on in tumor cells and summarize the relationship among amino acid metabolism, tumor microenvironment and the function of T cells. In particular, we discuss the current issues that need to be addressed in the related fields of tumor amino acid metabolism, aiming to provide a theoretical basis for the development of new strategies for clinical interventions in tumors based on amino acid metabolism reprogramming. [ABSTRACT FROM AUTHOR]

The kynurenine pathway is increasingly recognised to play a role in inflammation and disease. We assessed the cross-sectional and longitudinal associations of adiposity measures (body mass index, waist-hip ratio, waist circumference and fat mass ratio) with plasma concentrations of kynurenine pathway metabolites and traditional markers of inflammation. We used data from 970 Melbourne Collaborative Cohort Study participants who had plasma markers measured at baseline (median age 59 years) and follow-up (median age 70 years). Linear regression was used to assess cross-sectional and longitudinal associations between four adiposity measures and concentrations of i) nine kynurenine pathway metabolites; ii) two derived markers; iii) eight traditional inflammatory markers. Cross-sectionally, most kynurenine metabolites were strongly associated with adiposity measures at both time points; associations were generally stronger than for most inflammation markers except CRP (e.g. body mass index at baseline, quinolinic acid (per S.D. β = 0.30, 95%CI: 0.24–0.36, P = 10−21), kynurenine (β = 0.25, 95%CI: 0.19–0.31, P = 10−16) and CRP (β = 0.31, 95%CI: 0.25–0.37, P = 10−24), and remained largely unchanged after adjustment for confounders. Longitudinally, changes in adiposity measures over approximately a decade were positively associated with changes in kynurenine metabolite concentrations (in particular for 3-hydroxyanthranilic acid, kynurenine and quinolinic acid), and more strongly so than for other markers of inflammation, including CRP. In middle-aged and older adults, plasma concentrations of kynurenine metabolites are strongly associated with adiposity, both cross-sectionally and longitudinally. Our study demonstrates that kynurenine metabolites may be valuable markers to monitor the adverse consequences of obesity. [ABSTRACT FROM AUTHOR]

Human milk for very preterm infants need fortification for optimal growth and development but the optimal fortification product remains to be identified. To investigate feasibility, safety and preliminary efficacy on growth and blood biochemistry when using intact bovine colostrum (BC) as a fortifier to human milk in very preterm infants. In an open-label, multicenter, randomized controlled pilot trial (infants 26–31 weeks' gestation), mother's own milk or donor human milk was fortified with powdered BC (n = 115) or a conventional fortifier (CF, bovine-milk-based, n = 117) until 35 weeks' postmenstrual age. Fortifiers and additional micronutrients were added to human milk according to local guidelines to achieve optimal growth (additional protein up to +1.4 g protein/100 mL human milk). Anthropometry was recorded weekly. Clinical morbidities including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) were recorded. Clinical biochemistry included plasma amino acid (AA) levels to assess protein metabolic responses to the new fortifier. A total of 232 infants, gestational age (GA) 28.5 ± 1.4 (weeks + days), fulfilled inclusion criteria. Birthweight, GA and delta Z scores from birth to end of intervention on weight, length or head circumference did not differ between groups, nor between the subgroups of small for gestational age infants. Likewise, incidence of NEC (BC: 3/115 vs. CF: 5/117, p = 0.72, unadjusted values), LOS (BC: 23/113 vs. CF: 14/116, p = 0.08) and other morbidities did not differ. BC infants received more protein than CF infants (+10%, p < 0.05) and showed several elevated AA levels (+10–40%, p < 0.05). Infants fortified with BC showed similar growth but received more protein and showed a moderate increase in plasma AA-levels, compared with CF. Adjustments in protein composition and micronutrients in BC-based fortifiers may be required to fully suit the needs for very preterm infants. [ABSTRACT FROM AUTHOR]

l -theanine has been shown to have a therapeutic effect on depression. However, whether l -theanine has an excellent preventive effect on depression in children and adolescents and what its mechanism is have not been well explained. Given the complexity of the pathogenesis of depression, this study investigated the preventive effect and mechanism of l -theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies. Behavioral tests, hippocampal tissue sections, and serum and hippocampal biochemical indexes were studied, and the results confirmed the preventive effect of l -theanine. Untargeted reversed-phase liquid chromatography-quadrupole-time-of-flight mass spectrometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spectrometry were developed to analyze the metabolism changes in the serum and hippocampus to screen for potential biomarkers related to l -theanine treatment. The results suggested that 28 abnormal metabolites in the serum and hippocampus that were considered as potential biomarkers returned to near-normal levels after l -theanine administration. These biomarkers were involved in various metabolic pathways, mainly including amino acid metabolism and lipid metabolism. The levels of amino acids and neurotransmitters in the phenylalanine, tryptophan, and glutamic acid pathways were significantly reduced after l -theanine administration compared with chronic unpredictable mild stress-induced rats. In summary, l -theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body, such as amino acids, lipids, and inflammation. This research systematically analyzed the mechanism of l -theanine in preventing depression and laid the foundation for applying l -theanine to prevent depression in children and adolescents. [Display omitted] • The mechanism of theanine in prevention of depression based on metabolomics was studied for the first time. • Simultaneous untargeted and targeted metabolomics studies in CUMS-induced rat periphery and central nervous system. • A rapid HILIC-QQQ-MS/MS method was developed and validated for the accurate determination of altered neurotransmitters. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a developmental disorder with symptoms that range from social and communication impairments to restricted interests and repetitive behavior and is the 4th most disabling condition for children aged 5–14. Risk factors of ASD are not fully understood. Environmental risk factors are believed to play a significant role in the ASD epidemic. Research focusing on air pollution exposure as an early-life risk factor of autism is growing, with numerous studies finding associations of traffic and industrial emissions with an increased risk of ASD. One of the possible mechanisms linking autism and air pollution exposure is metabolic dysfunction. However, there were no consensus about the key metabolic pathways and corresponding metabolite signatures in mothers and children that are altered by air pollution exposure and cause the ASD. Therefore, we performed a review of published papers examining the metabolomic signatures and metabolic pathways that are associated with either air pollution exposure or ASD risk in human studies. In conclusion, we found that dysregulated lipid, fatty acid, amino acid, neurotransmitter, and microbiome metabolisms are associated with both short-term and long-term air pollution exposure and the risk of ASD. These dysregulated metabolisms may provide insights into ASD etiology related to air pollution exposure, particularly during the perinatal period in which neurodevelopment is highly susceptible to damage from oxidative stress and inflammation. [Display omitted] • Fatty acid metabolisms such as phospholipids were associated with PM 2.5 exposure. • Amino Acid metabolism including lysine and glutamate were associated with autism. • Lipid and amino acid metabolisms were associated with both air pollution and autism. • Common pathway suggested oxidative stress and inflammation may contribute to autism. [ABSTRACT FROM AUTHOR]

Although immune checkpoint inhibitors (ICIs) have revolutionized immuno-oncology with effective clinical responses, only 30 to 40 % of patients respond to ICIs, highlighting the need for reliable biomarkers to predict and enhance therapeutic outcomes. This study investigated how amino acid, glycolysis, and bile acid metabolism affect ICI efficacy in non-small cell lung cancer (NSCLC) patients. Through targeted metabolomic profiling and machine learning analysis, we identified amino acid metabolism as a key factor, with histidine (His) linked to favorable outcomes and homocysteine (HCys), phenylalanine (Phe), and sarcosine (Sar) linked to poor outcomes. Importantly, the His/HCys+Phe+Sar ratio emerges as a robust biomarker. Furthermore, we emphasize the role of glycolysis-related metabolites, particularly lactate. Elevated lactate levels post-immunotherapy treatment correlate with poorer outcomes, underscoring lactate as a potential indicator of treatment efficacy. Moreover, specific bile acids, glycochenodeoxycholic acid (GCDCA) and taurolithocholic acid (TLCA), are associated with better survival and therapeutic response. Particularly, TLCA enhances T cell activation and anti-tumor immunity, suggesting its utility as a predictive biomarker and therapeutic agent. We also suggest a connection between gut microbiota and TLCA levels, with the Eubacterium genus modulating this relationship. Therefore, modulating specific metabolic pathways—particularly amino acid, glycolysis, and bile acid metabolism—could predict and enhance the efficacy of ICI therapy in NSCLC patients, with potential implications for personalized treatment strategies in immuno-oncology. Our study identifies metabolic biomarkers and pathways that could predict and enhance the outcomes of immune checkpoint inhibitor therapy in NSCLC patients [ABSTRACT FROM AUTHOR]

The increasing exposure to environmental chemicals calls for comprehensive non-targeted analysis to detect unrecognized substances in human samples. We examined human serum samples to classify compounds as endogenous or exogenous using public databases and to explore the relationships between exposure markers and metabolic patterns. Serum samples from 84 pregnant women at 32 weeks gestation were analyzed using LC-QToFMS. Using the PubChemLite for Exposomics database, we annotated and classified 106 compounds (51 endogenous, 55 exogenous). The compound patterns were analyzed using three dimensional reduction methods: Principal Component Analysis (PCA), regularized Generalized Canonical Correlation Analysis (rGCCA), and Uniform Manifold Approximation and Projection (UMAP). OPTICS clustering applied to these methods revealed two distinct clusters, with 89 % of significant compounds overlapping between clusters. The detected exogenous compounds included dietary substances, phthalates, nitrogenous compounds, and parabens. Pathway enrichment analysis showed that chemical exposure was linked to changes in amino acid metabolism, protein and mineral transport, and energy metabolism. While we found associations between exposure and metabolite changes, we could not establish causality. Our approach of analyzing both exogenous and endogenous chemicals from the same dataset using PubChemLite database presents a new method for exposome research, despite limitations in sample size and peak annotation accuracy. These findings contribute to understanding multiple chemical exposures and their metabolic effects in human biomonitoring. [Display omitted] • Classified serum compounds into endogenous and exogenous categories. • Annotated 51 metabolites and 55 potential exposures using PubchemLite and HRMS. • Dimensionality-reduction with clustering find the subgroups with specific exposures. • Explored associations between exposures and metabolic pathways. [ABSTRACT FROM AUTHOR]

Weed infestation is the major biological threat in direct-seeded rice production and can cause significant yield losses. The effective use of herbicides is particularly important in direct-seeded rice production. Anilofos, a pre-emergence herbicide, has been shown to be effective against the weed barnyardgrass. However, its impacts on crop yield and the direct-seeded rice production ecosystem remain underexplored. In this study, we conducted field trials and used untargeted metabolomics to investigate systemic effects of two different treatments (40 g/acre and 60 g/acre) on rice shoot and root as well as the rhizosphere soil during the critical tillering stage. Here, a total of 400 metabolites were determined in the crop and soil, with differential metabolites primarily comprising lipids and lipid-like molecules as well as phenylpropanoids and polyketides. Spearman correlation network analysis and a Zi-Pi plot revealed 7 key differential metabolites with significant topological roles, including succinic acid semialdehyde and riboflavin. KEGG pathway analysis showed that anilofos downregulated the amino acid metabolism while mainly promoted carbohydrate metabolism and secondary metabolites biosynthesis of the crop, which made minimal disruption on soil metabolism. Notably, we found 40 g/acre anilofos application could significantly improve the rice yield, potentially linked to the improved activity of flavonoid biosynthesis and starch and sucrose metabolism. This research provides a comprehensive evaluation of anilofos effects in the direct-seeded rice production system, offering new insights into optimizing herbicide use to improve agricultural sustainability and productivity. [Display omitted] • Anilofos' effects were studied in the whole production system of direct-seed rice. • Metabolomic variation of direct-seed rice during tillering stage was provided. • Anilofos can affect crop metabolism with minimal effects on soil metabolism. • Low-dose application (40 g/acre) is an optimal choice to promote the grain yield. [ABSTRACT FROM AUTHOR]

Pichia kudriavzevii could resist high concentrations of sodium selenite and efficiently biotransform over 80% of the absorbed selenium. However, the specific molecular mechanisms underlying this biotransformation remain unclear. This study aimed to investigate the mechanism of selenium biotransformation focusing on selenium transport, detoxification, reduction, and the formation of organic selenium compounds through a comprehensive approach combining transcriptomic, proteomic, and non-targeted metabolomic analyze. Results showed that the JEN1 gene was responsible for selenium transport, while the upregulation of cysJ , CYSK , TRXB1 and sat genes as well as the involvement of glutathione, are crucial for the accumulation of organic selenium. Furthermore, GSTY2 , TRXB1 and GPX3 were pivotal genes in Se(IV) reduction and their corresponding proteins were key proteins. Additionally, the enhanced expression of genes related to antioxidant enzymes (GSTY2 , TRXB1 , and GPX3), ABC transports, heat shock proteins and antioxidant enzymes proteins (GSTY2, TRXB1, and GPX3) collectively contributed to selenium tolerance, detoxification and protection against oxidative damage. GO and KEGG analysis highlighted alterations in amino acid metabolism, carbohydrate metabolism, and energy metabolism in the selenium biotransformation process. These findings provide novel insight into the mechanisms of selenium biotransformation in P. kudriavzevii and its application in the fields of the food industry. [Display omitted] • The cysJ, CYSK TRXB1 and sat genes played important roles in high content of organic Se. • The high expression of JEN1 involved in the uptake sodium selenite. • TRXB1 and GPX3 were pivotal genes and their corresponding proteins were key proteins in Se (Ⅳ) reduction. • The ABC transports, antioxidant enzymes and HSPs contributed to the Se tolerance. [ABSTRACT FROM AUTHOR]

Maternal food environment can program fecal microbiota in offspring mediated by the imprint of intrauterine conditions. Gut bacteria play a role in host fatty acid and amino acid metabolism. This study aimed to determine the effects of maternal diet on fecal microbiota, and the impact on fatty acid and amino acid metabolism in male offspring rats. Ten male pups from dams fed standard diet (C-C, n = 5) and cafeteria diet (Caf-C, n = 5) were fed standard chow diet for twenty-three weeks. Fresh fecal samples were collected at three and twenty-six weeks of age for fecal microbiota analysis by metagenomic sequencing of the V3-V4 region of the 16S rRNA gene. At the end of the study, serum samples were collected to analyse fatty acids from phospholipid and cholesterol ester fractions by gas chromatography and free amino acids by liquid chromatography. The bacterial abundance from the Actinobacteria and Proteobacteria phyla significantly decreased over time for both groups. Additionally, significant differences were found between C-C and Caf-C groups in these bacterial phyla. In the Caf-C group, Firmicutes and Elusimicrobia phyla increased, while Bacteroidetes decreases in adulthood samples. At the genus level, the abundance of Bacteroides decreased, while Elusimicrobium , Lactobacillus , Turicibacter , Blautia , and Veillonella increased in the Caf-C group. Several metabolites including PL-MCFAs (caprylic acid and capric acid), CE-MUFAs (palmitoleic acid and heptadecenoic acid), and free amino acids aspartate, glutamic acid, and cysteine were significantly higher in Caf-C group. This study underscores the putative programming of offspring fecal microbiota by maternal diet impact. These changes led to alterations fatty acids and amino acids metabolism in adult male offspring rats. [ABSTRACT FROM AUTHOR]

The metabolic activity of microorganisms can influence the characteristics of dry-cured meat. This study aimed to investigate the impact of single or combined inoculation of Staphylococcus vitulinus CICC10850 and Staphylococcus xylosus CICC21445 on the quality of dry-cured duck. The results showed that co-inoculation significantly inhibited the lipid oxidation of dry-cured duck compared to single inoculation S. vitulinus CICC10850 or S. xylosus CICC21445, and the viable cell counts of Staphylococcus were higher (8.3 ± 0.04 log CFU/g, on the 7th day). Co-inoculation significantly increased the activities of neutral lipase (1.68 ± 0.12 U/g) and phospholipase (1.78 ± 0.10 U/g) on the 7th day. The contents of 12 free fatty acids in the dry-cured duck were significantly altered, with notable changes in the levels of C16:0, C18:0, and C18:6n9c. 43 flavor compounds were detected, and the aldehydic flavor compounds were significantly influenced by Staphylococcus inoculation. Compared to the control, co-inoculation led to significant changes in the contents of 333 non-volatile metabolites, 150 of which were lipid-related. KEGG analysis identified 11 differented metabolic pathways, primarily involving amino acid and lipid metabolism. Furthermore, the human-machine interaction evaluation demonstrated that the co-inoculation of S. xylosus CICC21445 and S. vitulinus CICC10850 significantly enhanced the sensory attributes of dry-cured ducks. [Display omitted] • FFA production and lipase activity are affected by S. xylosus and S. vitulinus. • 43 flavor substances were found, of which 12 were differential flavor substances. • Inoculation with Staphylococcus improves the sensory quality of dry-cured ducks. [ABSTRACT FROM AUTHOR]

This study employed metagenomics and metabolomics to evaluate the impact of Tetragenococcus halophilus and Zygosaccharomyces rouxii on microbiota composition and metabolite profiles in secondary fortified fermented soy sauce. The Co-culturing of T. halophilus T10 and Z. rouxii QH-1(T1Z) enriched microbial diversity and promoted the proliferation of functional species, thereby enhancing biomarker species. Annotations matched from EggNOG, KEGG, and CAZy databases underscored the significance of carbohydrate and amino acid metabolism in moromi. Sample T1Z enhanced the metabolism by increasing the abundance and catalytic efficiency of the relevant enzymes, resulting in increases of 3.94%, 2.69%, and 11.14%, respectively, with total nitrogen, amino acid nitrogen, and free amino acids. It introduced 11 volatile compounds and increased the alcohol content by 13.65%, and the aldehyde content by 49.28%, while also suppressing the accumulation of ammonium nitrogen and biogenic amines. Metabolic pathway analysis identified Staphylococcus gallinarum , Mammaliicoccus sciuri , and certain Bacillus species, especially B. parathracis , B. velezensis , and B. subtilis , as principal contributors to carbohydrate and amino acid metabolism. These findings offer insight into microbial strain selection for industrial fermentation and provide a foundation for optimizing the process through co-culture bioaugmentation to enhance and underscore the potential of modern microbial techniques in traditional practices. [Display omitted] • Characterized the metabolites in the secondary fortified fermented moromi. • Revealed contribution of fortifying patterns to metabolic potential by metagenomics. • Enhanced the capacity of carbohydrate and amino acid metabolism, improved taste feature. • The contribution of coculture fortification lay the inoculated strains specificity. [ABSTRACT FROM AUTHOR]

Whey protein hydrolysate (WPH) has been proven to possess anti-fatigue effects, but its regulatory mechanism on muscle metabolism in exercise mice is unclear. In the present study, the effects of WPH on muscle metabolites in mice before and after exercise were explored using metabolomics techniques. Results showed that 34 muscle metabolites were significantly altered by exercise in the WPH group, which was less than 71 in the WP group and 101 in the control group. Specifically, supplementation of WPH significantly increased the levels of amino acid and carbohydrate metabolites (i.e., 1-methylhistamine, guanidoacetic acid, melibiose, and xylulose 5-phosphate) pre-exercise, thereby delaying energy depletion and maintaining metabolic homeostasis during exercise. Furthermore, simulated gastrointestinal digestion (SGID), peptidomics and bioinformatics tools were employed to screen potential peptides in WPH. A total of 37 peptides with 2–5 residues in WPH were resistant to SGID (peak intensity > 105). Among them, YGLF showed favorable potentials in physicochemical property, bioavailability, bioactivity, SwissTargetPrediction, and molecular docking. In addition, the anti-fatigue activity of YGLF was evaluated in vivo. YGLF (100 mg/kg) significantly increased the contents of glucose, glycogens, and amino acids and decreased the levels of lactate and urea nitrogen in mice after exercise. These findings may serve as a reference for the screening of anti-fatigue peptides. [Display omitted] [ABSTRACT FROM AUTHOR]

Fucoidan (ANP) from Ascophyllum nodosum demonstrates significant anti-inflammatory activity. Because lower-molecular-weight polysaccharides usually process even better bioactivities, in the present study, the photocatalytic degradation method with TiO 2 and H 2 O 2 was used to prepare low-molecular-weight derivatives (D-ANP-1.5 and D-ANP-3.5) with molecular weight of 5.0 kDa and 2.3 kDa, respectively. The characteristics of D-ANP-1.5 and D-ANP-3.5 were identified by chemical composition analysis, high-performance gel permeation chromatography, high-performance liquid chromatography photo-diode array mass, and Fourier transform-infrared spectrum, and compared with that of original fucoidan. The sulfate group retention rates of D-ANP-1.5 and D-ANP-3.5 were over 90.0% and the fucose and total sugar contents increased. However, the uronic acid and protein contents were decreased and the functional groups were not changed during degradation. Subsequently, 7 oligosaccharides in D-ANP-3.5 were identified by high-performance liquid chromatography-electrospray ionization detector mass and 6 of them were sulfated. Moreover, D-ANP-3.5 (2.3 kDa) supplement showed stronger inhibition effect of nitric oxide production than D-ANP-1.5 and undegraded ANP in LPS-stimulated RAW 264.7 cells. In addition, metabolic profiles results indicated that arginine biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, the TCA cycle, purine metabolism, and glutathione metabolism, along with influencing metabolic biomarkers such as betaine, arginine, NAD+, ATP, and pyroglutamic acid, were involved in the effects of D-ANP-3.5. The superior regulation effect on metabolomics in LPS-stimulated RAW 264.7 cells of D-ANP-3.5 could be attributed to its relatively low molecular weight and high fucose content. The present study advance understanding of the mechanism for the anti-inflammation of D-ANP-3.5. [Display omitted] • Photocatalytic depolymerize fucoidan (ANP) to obtain D-ANP-3.5 with 2.3 kDa. • Most of oligosaccharide have fucose or its derivative at reducing ends. • Both ANP and D-ANP-3.5 inhibited inflammation by modulating amino acid metabolism. • D-ANP-3.5 with high fucose content and low molecular weight exhibited a stronger effect. [ABSTRACT FROM AUTHOR]

The synergistic mechanisms of ultrasound combined plasma-activated water (US-PAW) against Listeria innocua were investigated with the intention of crayfish disinfection. US and PAW showed a significantly synergistic effect against L. innocua at 7 min. Specifically, no significant change was observed in the CK (sterile water) and US treatment groups as the duration of treatment increased. At 7 min, the reduction of L. innocua achieved by US-PAW treatment was 4.49 Log CFU/mL, which was significantly higher (p < 0.05) than the reduction for PAW treatment (2.46 Log CFU/mL). Furthermore, the Weibull model demonstrated superior efficacy in fitting the kinetic inactivation curves of L. innocua throughout the US, PAW, and US-PAW treatments. In addition, PAW disrupted the morphology of L. innocua and increased the electrical conductivity of the bacterial suspension, accelerated leakage of proteins and nucleic acids from cells and increased the intracellular reactive oxygen species content, which was further promoted by US-PAW. The molecular mechanisms underlying these phenotypic changes were investigated using untargeted metabolomics. The results indicated that US exacerbated the destruction of PAW on the nucleotide, glycerolipid, peptidoglycan and amino acids metabolism, further affecting the metabolism of various substances and energy in cells, ultimately leading to cell death. Besides, US-PAW showed significant antibacterial effects on L. innocua in crayfish with minor effects on the sensory characteristics. These findings provided theoretical support for the application of US-PAW in crayfish disinfection. [Display omitted] • US enhanced the inhibition rates of PAW against L. innocua from 26 % to 47 % at 7 min. • US mainly strengthened the nucleotide metabolic disorder of PAW on L. innocua. • US enhanced PAW disruption of the L. innocua cell membranes and morphology. • US-PAW had a positive impact on the sensory characteristics of crayfish. [ABSTRACT FROM AUTHOR]

Copper (Cu) is recognized as an essential trace elements for the body; However, excessive levels of Cu can lead to toxic effects. We investigated the effects of Cu2+(75 μg/L, 150 μg/L, and 300 μg/L) on the rainbow trout liver. Combination of transcriptome and metabolome analyses, the regulatory mechanisms of the liver under Cu stress were elucidated. The results showed that Cu affected the antioxidant levels, leading to disruptions in the normal tissue structure of the liver. Combined transcriptome and metabolome analyses revealed significant enrichment of the insulin signaling pathway and the adipocytokine signaling pathway. Additionally, Cu2+ stress altered the amino acid metabolism in rainbow trout by reducing serine and arginine levels while increasing proline content. Apoptosis is inhibited and autophagy and lipid metabolism are suppressed; In summary, Cu2+ stress affects energy and lipid metabolism, and the reduction of serine and arginine represents a decrease in the antioxidant capacity, whereas the increase in proline and the promotion of apoptosis potentially serving as crucial strategies for Cu2+ resistance in rainbow trout. These findings provided insights into the regulatory mechanisms of rainbow trout under Cu2+ stress and informed the prevention of heavy metal pollution and the selection of biomarkers under Cu pollution. • Cu affects the antioxidant capacity of rainbow trout. • Cu enhances the glycolytic capacity of the liver. • Cu affects amino acid metabolism and lipid metabolism. • Cu promoted apoptosis and inhibited autophagy. [ABSTRACT FROM AUTHOR]

The impact of emerging stressors, such as pesticides and heavy metals, on the nutritional quality, resistance, and antioxidant systems of crops is the subject of intense monitoring. Due to its low toxicity and biocompatibility, nano-selenium (nano-Se) increases antioxidant capacity more effectively than selenium (Se). However, the protective mechanism of nano-Se in plum trees is still unknown when subjected to long-term abiotic stress. In this study, nano-Se foliar application enhanced the fruit's fresh weight and diameter and plant growth and development by increasing the content of trace elements (Zn and Se) and amino acids (Try, Phe, Pro, and Arg) in leaves and fruits. Compared to the control, nano-Se treatment dramatically improved the plant's antioxidant system, resulting in a substantial increase in SOD (44.3 %), POD (24.3 %), and CAT (95.6 %) levels. It also increased IAA (118.8 %), total flavonoids (23.0 %), total phenols (15.8 %), rutin (37.7 %), quercetin (146.8 %), and caffeic acid (19.8 %) contents by regulating phenylpropane metabolic pathways. Targeted amino acid analysis indicated that nano-Se biofortification greatly enhanced the levels of His (60.7 %), Ser (123.5 %), Thr (105.7 %), Val (202.1 %), Ile (236.2 %), Leu (84.0 %), Tyr (235.0 %), and Phe (164.7 %). The non-target metabolomics results showed that nano-Se treatment stimulated plum growth and nutrition by boosting phenylpropane metabolism and amino acid production. Therefore, nano-Se can improve the quality and resistance of plums by regulating both the primary and secondary metabolic pathways of plants and enhancing the antioxidant capacity. This investigation provides a reference for extrapolating the positive effects of nano-Se on crop quality to other plant species. [Display omitted] • Nano-Se biofortification increases the fruit's fresh weight and diameter. • Up-regulation of amino acids-related metabolites enhances plum's nutrient levels. • Nano-Se increased plum resistance by boosting phenylpropane metabolism. • Nano-Se treatment substantially improved the plant's antioxidant system. [ABSTRACT FROM AUTHOR]

Potatoes (Solanum tuberosum L.) are the third largest food crop globally and are pivotal for global food security. Widespread N fertilizer waste in potato cultivation has caused diverse environmental issues. This study employed microbial metagenomic sequencing to analyze the causes behind the declining N use efficiency (NUE) and escalating greenhouse gas emissions resulting from excessive N fertilizer application. Addressing N fertilizer inefficiency through breeding has emerged as a viable solution for mitigating overuse in potato cultivation. In this study, transcriptome and metabolome analyses were applied to identify N fertilizer-responsive genes. Metagenomic sequencing revealed that excessive N fertilizer application triggered alterations in the population dynamics of 11 major bacterial phyla, consequently affecting soil microbial functions, particularly N metabolism pathways and bacterial secretion systems. Notably, the enzyme levels associated with NO 3 - increased, and those associated with NO and N 2 O increased. Furthermore, excessive N fertilizer application enhanced soil virulence factors and increased potato susceptibility to diseases. Transcriptome and metabolome sequencing revealed significant impacts of excessive N fertilizer use on lipid and amino acid metabolism pathways. Weighted gene co‑expression network analysis (WGCNA) was adopted to identify two genes associated with N fertilizer response: PGSC0003DMG400021157 and PGSC0003DMG400009544. • Excessive Nitrogen (N) fertilizer altered gene abundance in rhizosphere microorganisms. • Rhizosphere microorganism secretion gene abundance increased with N overuse. • N overuse reduced rhizosphere nitrate reductase genes, affecting efficiency. • Genes were found for efficient potato breeding, cutting N use and pollution. [ABSTRACT FROM AUTHOR]

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

The heavy metal lead (Pb) pollution in marine environment has been widely concerned. The liver and intestine are important for the health of fish. In this study, the grouper were exposed to 1 μg/L Pb for 14 days, and the physiological homeostasis changes were explored via gut-liver axis. The results showed that Pb stress caused liver morphological changes, oxidative stress, and the accumulation and peroxidation of the lipids. The liver metabolism were disturbed, especially amino acid metabolism and the synthesis and degradation of ketone bodies. Pb stress also caused intestinal mucosal ablation, tight junction dysfunction and inflammatory response. Additionally, intestinal microbial diversity was decreased, and the community composition was altered especially several bacteria genera (Ruminococcus UCG-005 , Ruminococcus UCG-014 , Oscillibacter , and Streptococcus) were significantly correlated with the physiological indexes and metabolites of the liver. These results reveal that Pb stress negatively affect the physiological homeostasis of the grouper via gut-liver axis. • Lead (Pb) stress can influence the physiological homeostasis of the grouper via the gut-liver axis. • Pb stress causes liver morphological changes, oxidative stress, lipid accumulation and peroxidation. • The liver undergoes metabolic remodeling under stress by mediating amino acids and ketone bodies. • Intestinal health including tight junction, inflammation, and microbial community were affected. • Several intestinal bacteria were correlated with the physiological homeostasis of their host. [ABSTRACT FROM AUTHOR]

The taxonomy of marine plastisphere communities has been extensively studied, demonstrating the ubiquity of hydrocarbonoclastic bacteria of potential biotechnological significance. However, prokaryotic functioning on plastic surfaces has received limited attention, and the question of whether these microorganisms are active and expressing specific molecular mechanisms underpinning plastisphere colonisation remains to be addressed. The aim of this study was to investigate the plastic colonisation process, to identify the active taxa involved in biofilm formation and the mechanisms used to initiate colonisation. To achieve this, a marine plastisphere characterised by active hydrocarbonoclastic genera was used as the inoculum for a short-term microcosm experiment using virgin low-density polyethylene as the sole carbon source. Following incubation for 1 and 2 weeks (representing early and late colonisation, respectively), a taxonomic and comparative metaproteomic approach revealed a significant shift in plastisphere diversity and composition, yet highlighted stability in the predominance of active Proteobacteria spanning 16 genera, including Marinomonas , Pseudomonas , and Pseudoalteromonas. Relative quantification of 1762 proteins shared between the initial plastisphere inoculum, the microcosm plastisphere and the planktonic cells in the surrounding artificial seawater, provided insights into the differential regulation of proteins associated with plastisphere formation. This included the upregulation of proteins mediating cellular attachment in the plastisphere, for example flagellin expressed by Marinomonas , Cobetia , Pseudoalteromonas , and Pseudomonas , and curli expressed by Cobetia. In addition to the differential regulation of energy metabolism in Marinomonas , Psychrobacter , Pseudomonas and Cobetia within the plastisphere relative to the surrounding seawater. Further, we identified the upregulation of amino acid metabolism and transport, including glutamine hydrolysis to glutamate in Marinomonas and unclassified Halomonadaceae, potentially coupled to ammonia availability and oxidative stress experienced within the plastisphere. Our study provides novel insights into the dynamics of plastisphere formation and function, highlighting potential targets for regulating plastisphere growth to enhance plastic bioremediation processes. [Display omitted] • Proteobacteria from 16 genera dominated the active plastisphere taxa. • Physiological, morphological, and metabolic pathways established plastic colonisation. • Energy and glutamine metabolism underpinned plastisphere and planktonic states. • Molecular mechanisms to enhance plastics bio-recycling were identified. [ABSTRACT FROM AUTHOR]

High temperatures and drought present significant abiotic challenges that can limit the survival of many arthropods, including wolf spiders, which are ectothermic and play a crucial role in controlling pest populations. However, the impact of these stress factors on the microbiota of spiders remains poorly understood. In this study, we utilized 16 S rRNA gene sequencing to explore the diversity and composition of bacterial communities within Pardosa pseudoannulata under conditions of high temperature and drought stress. We found that Firmicutes, Bacteroidetes, and Proteobacteria were the predominant bacterial phyla present. Analyses of alpha diversity indicated an increase in bacterial diversity under combined stress conditions, as reflected by various diversity indices such as Ace, Chao1, Shannon, and Simpson. Furthermore, co-occurrence network analysis highlighted intricate interactions among the microbial taxa (e.g., Enterobacter , Chitinophaga , and Eubacterium), revealing the adaptive complexity of the spider's microbiome to environmental stress. Functional prediction analysis suggested that combined stress conditions might enhance key metabolic pathways, particularly those related to oxidative phosphorylation and amino acid metabolism. Using Random Forest analysis, we determined that changes in three heat shock proteins were largely attributed to variations in bacterial communities, with Firmicutes being notably influential. Collectively, this in-depth analysis offers novel insights into the responses of microbial communities within spider microbiomes to combined abiotic stresses, providing valuable information for understanding extreme climate impacts and informing ecological management strategies. • Identified key bacterial communities in spiders facing heat and drought stress. • High temperatures and drought increased bacterial diversity in spiders. • Network analysis revealed complex interactions among microbial taxa. • Heat and drought stress induced activation of heat-responsive proteins. [ABSTRACT FROM AUTHOR]

The co-cultivation of fungi with microalgae facilitates microalgae harvesting and enhances heavy metal adsorption. However, the mechanisms of fungal tolerance to cadmium (Cd) have not yet been studied in detail. In this study, functional groups of fungi were analyzed under Cd stress using Fourier transform infrared spectrometer (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), and transmission electron microscope (TEM) to explore their morphology. Confocal laser scanning microscope (CLSM) was used to characterize the changes in the content of extracellular polysaccharides and proteins, and a decrease in the ratio of glutathione (GSH) to oxidized glutathione (GSSG) was monitored. The GSH and GSSG contents in mycelium were 7.4 and 7.9 times higher than that in the control, respectively. After 72 h of Cd treatment, the fungal extracellular polysaccharide and extracellular protein contents increased by 16 and 11.4 mg/g, respectively, compared to the control. This provided several functional groups for the complexation of Cd ions to enhance fungal Cd tolerance. The metabolomic and transcriptomic results revealed a total of 358 differential metabolites after 20, 48, and 72 h in the positive and negative ion modes, and the number of differential metabolites specific to each group was 104, 14, and 89, respectively. There were 927, 1167, and 1287 up-regulated genes, and 1301, 1480, and 1683 down-regulated genes at 20, 48, and 72 h, respectively. Energy metabolism, amino acid metabolism, and the ABC transport system are the key metabolic pathways for tolerance enhancement and heavy metal detoxification in fungi. The expression of S-cysteinosuccinic acid was significantly up-regulated after Cd stress and associated with enhanced fungal tolerance and resistance to Cd. [Display omitted] • The secretion of EPS is one of the reasons for the increased tolerance of the fungus. • The presence of Cd causes a decrease in the ratio of GSH to GSSG. • Expression of S-Cysteinosuccinic acid correlates with Cd tolerance and resistance in fungi. • The ABC transporter system is a key intracellular detoxification mechanism. [ABSTRACT FROM AUTHOR]

Antimony (Sb) is known for its severe and extensive toxicity, and earthworms are considered important indicator organisms in soil ecosystems. Therefore, the present study investigated the mechanism of toxicity of the Sb at different concentrations (50, 200 mg/kg) on earthworms using biochemical indicators, pathological sections, as well as metabolomics and transcriptomics analyses. The results showed that as the exposure concentration increased, both the antioxidant system of earthworms, extent of intestinal damage, and their metabolomic characteristics were significantly enhanced. In the 50 and 200 mg/kg Sb treatment group, 30 and 177 significant differentially changed metabolites (DCMs) were identified, respectively, with the most DCMs being down- and up-regulated, respectively. Metabolomics analysis showed that the contents of dl-tryptophan, glutamic acid, glycine, isoleucine, l-methionine, involved in the protein digestion and absorption as well as aminoacyl-tRNA biosynthesis were significantly up-regulated under the 200 mg/kg treatment. At the transcriptional level, Sb mainly affected the immune system, nervous system, amino acid metabolism, endocrine system, and carbohydrate metabolism in earthworms. The integration of transcriptomic and metabolomic data indicated that high doses of Sb regulated the metabolites and genes related to the oxidative phosphorylation pathway in earthworms. Overall, these results revealed global responses beyond the scope of conventional toxicity endpoints and facilitated a more in-depth and comprehensive assessment of the toxic effects of Sb. [Display omitted] • The toxicity of Sb(III) on P. guillelmi was evaluated at the molecular level. • T-AOC, GST activity, MT, and MDA content were significantly increased by 200 mg/kg Sb. • Sb affects the earthworm nervous system, immune system, oxidative stress. [ABSTRACT FROM AUTHOR]

The effects of the surrounding environment on the bacterial composition of bioaerosol were well documented for polluted and contaminated sites. However, there is limited data on the impact of plant species, especially those that produce aromas, on bioaerosol composition at agricultural sites. Hence, the aim of this study is to evaluate the variability in bacterial communities present in bioaerosol samples collected from agricultural sites with aroma-producing crops. For this, PM 2.5 , PM 10, and bioaerosol samples were collected from agricultural fields growing Ocimum [two varieties of O. sanctum (CIM-Aayu and CIM-Angana)] and O. kilimandscharicum (Kapoor), nearby traffic junctions and suburban areas. PM 2.5 and PM 10 concentrations at the agricultural site were in between the other two polluted sites. However, bioaerosol concentration was lower at agricultural sites than at other sites. The culturable bacteria Bacillus subtilis , Bacillus tequilensis , and Staphylococcus saprophyticus were more prevalent in agricultural sites than in other areas. However, the composition of non-culturable bacteria varied between sites and differed in three fields where Ocimum was cultivated. The CIM-Aayu cultivated area showed a high bacterial richness, lower Simpson and Shannon indices, and a distinctive metabolic profile. The sites CIM-Angana and CIM-Kapoor had a higher abundance of Aeromonas , while Pantoea and Pseudomonas were present at CIM-Aayu. Acinetobacter, Staphylococcus , and Bacillus were the dominant genera at the other two sites. Metabolic profiling showed that the CIM-Aayu site had a higher prevalence of pathways related to amino acid and carbohydrate metabolism and environmental information processing compared to other sites. The composition of bioaerosol among the three different Ocimum sites could be due to variations in the plant volatile and cross-feeding nature of bacterial isolates, which further needs to be explored. [Display omitted] • The particulate matter and bacterial bioaerosol were analyzed at different sites. • High bioaerosol and particulate matter were observed at traffic junction. • The bacterial genera present in each sample exhibited limited inter-site correlation. • The phyllosphere and rhizopshere contributed to bioaerosol at agricultural site. • Distinct bacterial communities were observed site with different Ocimum varieties. [ABSTRACT FROM AUTHOR]

Silicosis, caused by silica exposure, is the most widespread and deadliest occupational disease. However, effective treatments are lacking. Therefore, it is crucial to elucidate the mechanisms and targets involved in the development of silicosis. We investigated the basic processes of silicosis development and onset at different exposure durations (2 or 4 weeks) using various techniques such as histopathology, immunohistochemistry, Enzyme linked immunosorbent assay(ELISA),16 S rRNA, and untargeted metabolomics.These results indicate that exposure to silica leads to progressive damage to lung tissue with significant deterioration observed over time. Time-dependent cytokines such as the IL-4, IL-13, and IL-6 are detected in lung lavage fluid, the model group consistently exhibited elevated levels of these cytokines, indicating a persistent and worsening inflammatory response in the lungs. Meanwhile, HE and Masson results show that 4-week exposure to silica causes more obvious lung injury and pulmonary fibrosis. Besides, the model group consistently exhibited a distinct lung bacterial population, known as the Lachnospiraceae_NK4A136_group, regardless of exposure duration. However, with increasing exposure duration, specific temporal changes were observed in lung bacterial populations, including Haliangium, Allobaculum, and Sandaracinus (at 4 weeks; p < 0.05). Furthermore, our study revealed a strong correlation between the mechanism of silica-induced lung injury and three factors: oxidative stress, impaired lipid metabolism, and imbalanced amino acid metabolism. We observed a close correlation between cytokine levels, changes in lung microbiota, and metabolic disturbances during various exposure periods. These findings propose that a possible mechanism of silica-induced lung injury involves the interplay of cytokines, lung microbiota, and metabolites. [Display omitted] • Lung microbiota and metabolism provide accurate assessment of silica-induced lung injury. • Silica exposure disrupts lung microbiota, worsening its harmful effects. • Silica-induced lung injury in rats reveals distinct metabolic traits linked to lipid metabolism. • Microorganisms can impact lung lipid metabolism by degrading and processing lipids. • Cytokines, lung microbiota, and metabolites interact in silica-induced lung injury. [ABSTRACT FROM AUTHOR]

Enzymology, the study of enzyme structures and reaction mechanisms can be considered a classical discipline. However, enzymes cannot be freely designed to catalyze desired reactions yet, and enzymology is by no means a complete science. I have long studied the reaction mechanisms of enzymes related to amino acid metabolism, such as aminotransferases and racemases, which depend on pyridoxal 5'-phosphate, a coenzyme form of vitamin B6. During these studies, I have often been reminded that enzymatic reactions are extremely sophisticated processes based on chemical principles and enzyme structures, and have often been amazed at the evolutionary mechanisms that bestowed them with such structures. In this review, I described the reaction mechanism of various pyridoxal enzymes especially related to d -amino acids metabolism, whose roles in mammals have recently attracted attention. I hope to convey some of the significance and interest in enzymology through this review. [ABSTRACT FROM AUTHOR]

Exposure to pesticide could contribute to neurodevelopmental and neurodegenerative disorders. Notably, research suggests that prenatal or early postnatal exposure to paraquat (PQ), an herbicide, might trigger neurodevelopmental toxicity in neural stem cells (NSCs) via oxidative stress. However, the molecular mechanisms of PQ-induced perturbations in NSCs, particularly at the metabolite level, are not fully understood. Using a dose-response metabolomics approach, we examined metabolic changes in murine NSCs exposed to different PQ doses (0, 10, 20, 40 μM) for 24h. At 20 μM, PQ treatment led to significant metabolic alterations, highlighting unique toxic mechanisms. Metabolic perturbations, mainly affecting amino acid metabolism pathways (e.g., phenylalanine, tyrosine, arginine, tryptophan, and pyrimidine metabolism), were associated with oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation. Dose-response models were used to identify potential biomarkers (e.g., Putrescine, L-arginine, ornithine, L-histidine, N-acetyl-L-phenylalanine, thymidine) reflecting early damage from low-dose PQ exposure. These biomarkers could be used as points of departure (PoD) for characterizing PQ exposure hazard in risk assessment. Our study offers insights into mechanisms and risk assessment related to PQ-induced neurotoxicity in NSCs. [Display omitted] • PQ induced broad metabolic perturbations in mNSCs. • Phenylalanine and tyrosine, arginine, and pyrimidine metabolism were altered by PQ. • Putrescine, L-arginine, ornithine, etc. served as potential biomarkers for PQ. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is the most common extracranial solid tumor in the pediatric population with a high degree of heterogeneity in clinical outcomes. Upregulation of the tumor suppressor miR-204 in neuroblastoma is associated with good prognosis. Although miR-204 has been recognized as a potential therapeutic candidate, its delivery is unavailable. We hypothesized that REP-204, the red blood cell-derived extracellular particles (REP) with miR-204 loading, can suppress neuroblastoma cells in vitro. After miR-204 loading by electroporation, REP-204, but not REP carriers, inhibited the viability, migration, and 3D spheroid growth of neuroblastoma cells regardless of MYCN amplification status. SWATH-proteomics revealed that REP-204 treatment may trigger a negative regulation of mRNA splicing by the spliceosome, suppression of amino acid metabolism and protein production, and prevent SLIT/ROBO signaling-mediated cell migration, to halt neuroblastoma tumor growth and metastasis. The therapeutic efficacy of REP-204 should be further investigated in preclinical models and clinical studies. REP-204 is a biocompatible red blood cell-derived nanovesicles loaded with tumor suppressor microRNA mimics, miR-204, that can exhibit anti-neuroblastoma effects in vitro. SWATH-Proteomics revealed REP-204 may interfere with onco-mRNA splicing by spliceosome in neuroblastoma cells to halt tumor growth and suppress SLIT/ROBO-related pathways to mitigate cancer cell migration and metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Hydrogen sulphide (H 2 S) is considered an immunotoxicant, and its presence in the water can influence the mucosal barrier functions of fish. However, there is a significant knowledge gap on how fish mucosa responds to low environmental H 2 S levels. The present study investigated the consequences of prolonged exposure to sub-lethal levels of H 2 S on the mucosal defences of Atlantic salmon (Salmo salar). Fish were continuously exposed to two levels of H 2 S (low: 0.05 µM; and high: 0.12 µM) for 12 days. Unexposed fish served as control. Molecular and histological profiling focused on the changes in the skin, gills and olfactory rosette. In addition, metabolomics and proteomics were performed on the skin and gill mucus. The gene expression profile indicated that the gills and olfactory rosette were more sensitive to H 2 S than the skin. The olfactory rosette showed a dose-dependent response, but not the gills. Genes related to stress responses were triggered at mucosal sites by H 2 S. Moreover, H 2 S elicited strong inflammatory responses, particularly in the gills. All mucosal organs demonstrated the key molecular repertoire for sulphide detoxification, but their temporal and spatial expression was not substantially affected by sub-lethal H 2 S levels. Mucosal barrier integrity was not considerably affected by H 2 S. Mucus metabolomes of the skin and gills were unaffected, but a matrix-dependent response was identified. Comparing the high-concentration group's skin and gills mucus metabolomes identified altered amino acid biosynthesis and metabolism pathways. The skin and gill mucus exhibited distinct proteomic profiles. Enrichment analysis revealed that proteins related to immunity and metabolism were affected in both mucus matrices. The present study expands our knowledge of the defence mechanisms against H 2 S at mucosal sites in Atlantic salmon. The findings offer insights into the health and welfare consequences of sub-lethal H 2 S, which can be incorporated into the risk assessment protocols in salmon land-based farms. [Display omitted] • Gills and olfactory rosette were more sensitive to H 2 S than the skin. • Stress responses were triggered at mucosal sites by H 2 S. • All mucosal organs demonstrated the key molecular repertoire for sulphide detoxification. • Mucosal barrier integrity was not considerably affected by H 2 S. • Immunity and metabolism-relevant molecules were affected in mucus proteomes and metabolomes. [ABSTRACT FROM AUTHOR]

Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV 1 and FVC by 35.26 mL (95 % CI: −60.75, −9.78) and 38.56 mL (95 % CI: −66.60, −10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways. [Display omitted] • The average blood chromium levels in young adults from Shandong, China were 1.83 ng/mL. • Blood chromium levels were associated with reduced lung function in young adults. • Blood chromium exposure could affect multiple metabolic pathways in the body. [ABSTRACT FROM AUTHOR]

Grass carp are highly perishable under the action of spoilage bacteria including Aeromonas rivipollensis , Pseudomonas putida , and Shewanella putrefaciens. However, the metabolic characteristics of the three bacteria in degrading fish proteins and small molecular nutrients are unclear. In this study, we used LC-MS/MS-based peptidomics and metabolomics to detect peptides and small molecular metabolites in grass carp flesh inoculated with the three bacteria. The peptidomic results showed that A. rivipollensis and S. putrefaciens induced an overall increase in the molecular weight of peptides in grass carp flesh. S. putrefaciens tended to hydrolyze peptide bonds composed of at least one hydrophobic amino acid whereas A. rivipollensis and P. putida preferred hydrolyzing Xaa-serine bonds. The metabolomic results showed that amino acid metabolism and nucleotide metabolism are among the most enriched pathways of differential metabolites. P. putida and S. putrefaciens were active in decomposing amino acids and nucleosides, respectively. Besides, lipid metabolism also plays an important role in grass carp spoilage, representing as the degradation from phosphatidylcholine to lysophosphatidylcholine by the three bacteria. To conclude, this study revealed distinct metabolic characteristics of the three bacteria in degrading proteins and small molecular metabolites, and thus contribute to the understanding of fish spoilage mechanisms. [Display omitted] • A.rivipollensis and S. putrefaciens induced overall increases in peptide MW in fish. • Cleavage sites of S. putrefaciens proteases were more diverse than other bacteria. • A.rivipollensis and P. putida preferred to break Xaa-serine bonds in fish proteins. • S.putrefaciens induced rapid degradations from nucleosides to purine bases. • Bacteria degraded phosphatidylcholine in grass carp flesh to lysophosphatidylcholine. [ABSTRACT FROM AUTHOR]

Lacidophilin, which is a bacteriocin produced by food-grade lactic acid bacteria, modulates the gut microbiota structure to enhance gut health. This study investigated the effects and mechanism of lacidophilin in a mouse model of low-grade colitis and NAFLD. After 126 days of feeding and medication intervention, high-dose lacidophilin (1.2 g per kg body weight) mitigated NAFLD-associated changes in biochemical parameters and prevented hyperlipidemia and hepatic lipid accumulation. Additionally, lacidophilin exerted a protective effect by reducing damage to the intestinal barrier (ZO-1/Mucin 2), increasing the relative abundance of Lachnospiraceae and Prevotellaceae , decreasing the relative abundance of Erysipelotrichaceae in low-grade colitis and NAFLD mice. In addition, fecal metabolomics studies showed that lacidophilin could regulate both amino acid and lipid metabolism to protect against NAFLD. Flow cytometry analysis of blood samples showed that lacidophilin could regulate the balance of Th1/Th2 and Th17/Treg. Transcriptomic analysis of the liver suggests that treatment with lacidophilin helped maintain immune homeostasis and facilitate lipid metabolism. In short, lacidophilin extracts alleviated lipid accumulation and inflammation in NAFLD mice. [Display omitted] [ABSTRACT FROM AUTHOR]

Color development in avocado fruits is a complex mechanism influenced by several factors. To understand this process, a comparative analysis was conducted between fruits of 'Fuerte' and 'Hass' avocado cultivars using metabolomic approaches. Pigment content in the exocarp differs between cultivars, accumulating anthocyanins in 'Hass' avocado. Carbohydrate abundance differed at ready-to-eat stage showing that 'Hass' accumulated higher amounts of sucrose, mannoheptulose, and perseitol than 'Fuerte' in both tissues. Higher amounts of fatty acids were observed in both tissues of 'Fuerte'. Polar metabolites indicated differences in amino acid and carbohydrate metabolisms between cultivars. Hormone analysis suggested that abscisic acid is involved in pigment biosynthesis. These findings showed that hormone and primary metabolites cross-talk plays an important role in color development in the exocarp and in the softening in the mesocarp of 'Hass', opening new perspectives about this metabolic interplay and its relation to the development of the exocarp-mesocarp synchronization during ripening. [Display omitted] • 'Hass' avocados accumulated higher amounts of sucrose, mannoheptulose, and perseitol in both tissues. • 'Fuerte' avocados accumulated stearic acid, oleic acid, and linoleic acid in the exocarp. • Cultivars presented differences in amino acid and carbohydrate metabolisms. • 'Hass' avocado exocarp showed higher abscisic acid and salicylic acid content. • Cytokinins, trans -zeatin and dihydrozeatin were found accumulated in 'Fuerte' skins. [ABSTRACT FROM AUTHOR]

Bacillus cereus , a food-borne pathogen, threatens human health and food safety. The quest for biologically active substances from natural sources acting as antimicrobial agents for the replacement of antibiotics and chemical additives has received increasing attention. In this study, the antimicrobial mechanism of morusin against B. cereus was outlined, as well as its function as a food supplement to extend the shelf-life of skimmed milk was assessed. Our findings demonstrated that the minimum inhibitory concentration (MIC) value of morusin against B. cereus was 2.25 μg/mL, inhibiting biofilm formation and reducing intracellular ATP and membrane depolarization by disturbing the permeability of the B. cereus cytoplasmic membrane. Damage or collapse of B. cereus cell membranes produced by morusin was identified using the field gun scanning electron microscope (FEG-SEM). Transcriptomic assessment indicated that the two-component system of B. cereus (narG , narH , narI , phoP , phoR , motA) responded positively to morusin within an adverse environment. Moreover, several genes associated with cell membrane and cell wall generation (murA , murB , ddlB) and amino acid metabolism (argF , argH , BCN_RS02850) were significantly downregulated, potentially accelerating the death of B. cereus. In addition, metabolomic investigation suggested that morusin restricted pyruvate metabolism, cysteine and methionine metabolic pathways, and disturbed the intracellular amino acid metabolism of B. cereus. Ultimately, 4.5 μg/mL of morusin was determined to significantly inhibit the growth of B. cereus within skimmed milk. Overall, morusin can be utilized as a natural antimicrobial agent for regulating B. cereus contamination in skimmed milk. [Display omitted] • Morusin exhibited antibacterial activity against Bacillus cereus. • Morusin destroyed the cell membrane structure of Bacillus cereus. • The addition of 4.5 μg/mL morusin can extend the shelf life of skimmed milk. [ABSTRACT FROM AUTHOR]

The successful use of indigenous strains as starter cultures is dependent not only upon their capacity to complete a fermentation but also on their ability to dominate the fermentation. Chinese strain NX11424 was identified as an indigenous Chinese wine strain with commercial potential. Fermentations to assess the ability of NX11424 to compete with a commercial strain, Montrachet (UCDVEN 522), in pure and co-inoculations were performed with exo- and endo-metabolomic analyses. Metabolome analysis was run at three time points (days 2, 4 and 6). The metabolic profiles of all three treatment were similar at day 2. The endo-metabolome of the co-culture most closely resembles that of Montrachet strain at days 4 and 6, while exo-metabolomic data most closely resembles the NX11424 strain at day 6. The levels of key biomarkers among different fermentations varied at different time points, especially in amino acid metabolism; however glycerolipid, sucrose and starch metabolism were consistently most impactful in driving differences across treatment. Sulfur metabolism was also differential among treatments, with higher levels of associated metabolites in Montrachet strain. This study demonstrated the effects of pure and co-starter fermentations on cellular and wine metabolites, which can be helpful for control of wine fermentation and management of desirable wine flavor. • The metabolic profiles of all three treatments were similar at initial stage of fermentation. • Fermentation kinetics characteristics of multistarter were similar to that of commercial strain. • Amino acid, glycerolipid, sucrose and starch metabolism differentiated among three treatments. [ABSTRACT FROM AUTHOR]

The mechanism by which Angelica essential oil (AEO) can act as an antimicrobial agent at cellular and metabolic levels to inhibit Pseudomonas fluorescens (P. fluorescens), and its effectiveness in beef preservation, were investigated and evaluated in this study. Our results showed that the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of AEO to P. fluorescens were 12.5 μL/mL and 25 μL/mL, respectively, at which AEO could effectively inhibit P. fluorescens reproduction and retard its growth (p < 0.05). Severe morphological damage to the AEO-treated cells of the microorganism, including cell walls and membranes, were observed via scanning electron microscopy (SEM). AEO treatment was also seen to lead to an increase in alkaline phosphatase (AKPase) activity and conductivity, and a significant leakage of intracellular macromolecular components (such as nucleic acids and proteins), providing further evidence of damage to the integrity of cell wall and cell membrane. Metabolomics analysis revealed that the differential metabolites in the AEO hindered nucleic acid synthesis and expression in the P. fluorescens , leading to tricarboxylic acid (TCA) cycle blockage and amino acid restriction, energy metabolism disorders and membrane damage, mainly through nucleotide metabolism, amino acid metabolism, carbohydrate metabolism and membrane transport. Moreover, application testing demonstrated the efficacy of AEO in slowing the increase of beef pH and total volatile basic nitrogen (TVB-N), extending the shelf life of chilled beef by 5.39 d, and effectively maintaining the organoleptic quality of beef. These results lay a foundation for the development of AEO as a natural bacteriostatic agent. [ABSTRACT FROM AUTHOR]