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ABSTRACT In Pseudomonas donghuensis SVBP6, isolated from an agricultural field, the well‐conserved Gac‐Rsm pathway upregulates biosynthesis of the antifungal compound 7‐hydroxytropolone (7‐HT). However, 7‐HT does not fully explain the strain's Gac‐Rsm‐dependent antimicrobial activity. Here, we combined comparative transcriptomic, proteomic, and metabolomic approaches to identify novel GacS‐dependent biosynthetic gene clusters (BGC) and/or extracellular specialized metabolites. Our data revealed a broad impact of GacS on gene expression and extracellular metabolite profile of SVBP6. At both the mRNA and polypeptide levels, specialized metabolism was the main affected functional category in the gacS mutant. The major extracellular MS/MS spectral families promoted by GacS were fatty acid amides, fatty acids, and alkaloids. GacS was required for the production of the antimicrobial compound pseudoiodinine and to activate expression of the corresponding BGC. We also detected GacS‐dependent production of 2,3,4‐trihydro‐β‐carboline‐1‐one, which may add to the antimicrobial arsenal of SVBP6. Furthermore, transcriptomics and proteomics pinpointed several GacS‐activated BGCs that had escaped in silico genome mining tools. Altogether, comparative multi‐omics analyses of gacS loss‐of‐function mutants in Pseudomonas isolates are a promising strategy to uncover bioactive metabolites and/or their BGCs. Discovery of novel natural products is important for harnessing the potential of microbiota to improve crop plant growth and health. [ABSTRACT FROM AUTHOR]

Cyclocarya paliurus tea, also known as "sweet tea", an herbal tea with Cyclocarya paliurus leaves as raw material, is famous for its unique nutritional benefits and flavor. However, due to the unique "bittersweet" of Cyclocarya paliurus tea, it is still unable to fully satisfy consumers' high-quality taste experience and satisfaction. Therefore, this study aimed to explore metabolites in Cyclocarya paliurus leaves during their growth period, particularly composition and variation of sweet and bitter taste compounds, by combining multi-platform metabolomics analysis with an electronic tongue system and molecular docking simulation technology. The results indicated that there were significant differences in the contents of total phenols, flavonoids, polysaccharides, and saponins in C. paliurus leaves in different growing months. A total of 575 secondary metabolites were identified as potential active metabolites related to sweet/bitter taste using nontargeted metabolomics based on UHPLC-MS/MS analysis. Moreover, molecular docking technology was utilized to study interactions between the candidate metabolites and the sweet receptors T1R2/T1R3 and the bitter receptors T2R4/T2R14. Six key compounds with high sweetness and low bitterness were successfully identified by using computational simulation analysis, including cis-anethole, gluconic acid, beta-D-Sedoheptulose, asparagine, proline, and citrulline, which may serve as candidates for taste modification in Cyclocarya paliurus leaves. These findings provide a new perspective for understanding the sweet and bitter taste characteristics that contribute to the distinctive sensory quality of Cyclocarya paliurus leaves. [ABSTRACT FROM AUTHOR]

Objective To investigate the differences in plasma metabolites between patients with altitude-related hypertension (ARH) and healthy individuals, and analyze the potential pathogenesis of ARH. Methods Convenient sampling was conducted on a unit of male healthy officers and soldiers who resident at altitude of < 500 m and migrated to an altitude of 4 200 m in July 2020. Twenty of them diagnosed with ARH were assigned into the ARH group, and another 30 non-ARH individuals served as the control group. Their blood pressure, body mass index (BMI), blood oxygen saturation, and heart rate were measured and recorded, and fasting venous blood samples were harvested to screen and identify plasma metabolites with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Metabolite fingerprinting was performed using unsupervised Principal Component Analysis (PCA) and supervised Orthogonal Partial Least Squares Discrimination Analysis (OPLS-DA) models in order to assist in biomarker screening. The quality of the OPLS-DA model was assessed and validated to guarantee the stability and reliability of the model. Differential plasma metabolites were screened using independent sample t test and fold change (FC) analysis, and volcano plots were drawn. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis was used to perform functional pathway enrichment and topological analysis on the screened differential metabolites. Results Compared to the control group, the ARH group showed significantly higher systolic and diastolic blood pressure and heart rate, and lower arterial oxygen saturation (P < 0.05). PCA analysis showed that 81.96% of the variance was explained in the positive ion mode and 79.25% in the negative ion mode, indicating significant metabolic differences between the 2 groups. OPLS-DA model analysis indicated that in the positive ion mode, PC1 explained 77.36% of the variance and PC2 explained 12.25% of the variance, with R2Y=0.96 and Q2Y=0.91; in the negative ion mode, PC1 explained 84.15% of the variance and PC2 explained 17.24% of the variance, with R2Y=0.99 and Q2Y=0.86. Inter-group difference exceeded 75%, and intra-group difference was less than 20%. The 7-fold cross-validation and 200 permutation test confirmed that the model was stable and reliable. In the positive ion mode, the Y-axis intercepts of the R2 and Q2 fitted lines were 0.58 and -0.48, respectively; in the negative ion mode, the Y-axis intercepts were 0.93 and -0.41, respectively. A total of 32 significantly different metabolites were screened out, including amino acids, nucleosides, fatty acids, and organic alkaloids. KEGG analysis revealed that among the 10 metabolic pathways, 4 were amino acid metabolic pathways, with the aminoacyl-tRNA biosynthesis pathway having the most enriched metabolites. Conclusion Based on UHPLC-MS/MS technology, untargeted metabolomics analysis identifies 32 significantly different metabolites, which may serve as characteristic biomarkers for ARH, and the aminoacyl-tRNA biosynthesis pathway may be associated with the pathogenesis of ARH.

Moderate traumatic brain injury (mTBI) involves a series of complex pathophysiological processes in not only the area in direct contact with mechanical violence but also in other brain regions far from the injury site, which may be important factors influencing subsequent neurological dysfunction or death. The medulla oblongata (MO) is a key area for the maintenance of basic respiratory and circulatory functions, whereas the pathophysiological processes after mTBI have rarely drawn the attention of researchers. In this study, we established a closed-head cortical contusion injury model, identified 6 different time points that covered the acute, subacute, and chronic phases, and then used nontargeted metabolomics to identify and analyze the changes in differential metabolites (DMs) and metabolic pathways in the MO region. Our results showed that the metabolic profile of the MO region underwent specific changes over time: harmaline, riboflavin, and dephospho-coenzyme A were identified as the key DMs and play important roles in reducing inflammation, enhancing antioxidation, and maintaining homeostasis. Choline and glycerophospholipid metabolism was identified as the key pathway related to the changes in MO metabolism at different phases. In addition, we confirmed increases in the levels of inflammatory factors and the activation of astrocytes and microglia by Western blot and immunofluorescence staining, and these findings were consistent with the nontargeted metabolomic results. These findings suggest that neuroinflammation plays a central role in MO neuropathology after mTBI and provide new insights into the complex pathophysiologic mechanisms involved after mTBI. [ABSTRACT FROM AUTHOR]

In this study, three fermentation treatments of spontaneous fermentation (SF), direct inoculation of CECA (YF), and inoculation with CECA after addition of dimethyl dicarbonate (YDF) were carried out. Multivariate statistical analysis approved that CECA inoculation significantly influenced the composition of 141 metabolites (15 volatile organic compounds (VOCs) and 126 non-VOCs), mainly consisting of 36 acids and derivatives and 25 lipids and lipid-like molecules. YF and YDF wines exhibited similar correlations with aroma types, while there were differences in the kinds and number of VOCs. Moreover, CECA-inoculated fermentation was more favorable to the formation of aftertaste-A, umami, sourness, and richness. The KEGG metabolic pathway analysis indicated that the inoculation strategy significantly affected the amino acid metabolism. The antimicrobial treatment effectively enhanced bitterness, astringency, umami and saltiness while reducing acidity. Further studies are needed to assess the effects of antimicrobial treatment on lipid metabolism.

Abstract Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values

Abstract Taiwanofungus camphoratus has attracted much attention because it can abundantly produce various active substances that exhibit blood-sugar lowering, immunity improving, and antioxidant properties. Currently, T. camphoratus is cultured using four main methods: cutting wood culture, solid-state fermentation, submerged fermentation, and dish culture. T. camphoratus produces different metabolites under different culture methods. In this study, nontargeted metabolomics was used to compare the metabolites of T. camphoratus produced under these four culture methods. Principal component analysis and supervised partial least squares-discriminant analysis were used to analyze the differences in the metabolites. Moreover, in vitro hypoglycemic activity of T. camphoratus extracts produced under four culture methods was compared by assessing their ability to inhibit the activity of α-glucosidase, α-amylase, and sucrase. A total of 186 metabolites were identified. In total, 127 metabolites were common under the four culture methods. Under solid-state fermentation, submerged fermentation, and cutting wood culture, 12, 1, and 4 metabolites were unique, respectively. The differential metabolites produced by T. camphoratus under four culture methods were mainly triterpenoids, phenolic compounds, and fatty acid compounds. α-glucosidase, α-amylase, and sucrase activity inhibition was the best using T. camphoratus extract obtained under cutting wood culture; the inhibition rates were 55.97%, 51.96%, and 78.02%, respectively, which were comparable to those exhibited by 0.001, 3, and 12 mg/mL acarbose (positive control). The metabolites produced by T. camphoratus and α-glucosidase, α-amylase, and sucrase inhibitory activities were different under the four culture methods. Cutting wood culture exhibited the best enzyme inhibitory activity. This study provided a theoretical basis for further use and development of various culture methods for the rational production of active metabolites of T. camphoratus.

Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values < 0.05. Three substances were detected by both methods: hypoxanthine, phytosphingosine, and xanthine. Furthermore, 1-(sn-glycero-3-phospho)-1D-myo-inositol had the largest area under the curve (AUC) value (AUC = 0.842). The purine metabolic pathway is the most important change in metabolic pathways. These findings show that there were differences in plasma metabolites between the depression cohort and the non-depression cohort. These identified differential metabolites may be markers of depression and can be used to study the changes in depression metabolic pathways. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is inseparable from metabolic disorders but lacks assessment of specific metabolite alteration. To explore the sequential metabolic changes in PD progression, we evenly divided 78 C57BL/6 mice (10 weeks) into six groups (one control group and five experimental groups) and collected the hippocampus tissue of mice after treating with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, and probenecid (twice a week) at five periods (1, 2, 3, 4, and 5 weeks) for metabolome analysis. Our study identified 567 differentially abundant metabolites (DAMs) (total 4348 metabolites). Compared with controls, 145, 146, 171, 208, and 213 DAMs were obtained from the five experimental groups, respectively. Notably, 40 shared DAMs were present in five experimental groups, of which 22 shared DAMs formed a new metabolic network based on amino acid metabolism. Compared with group W3, 84 DAMs were identified in group W5, including 12 unique DAMs. DAMs in different stages of PD were significantly enriched in amino acid metabolism pathway, lipid metabolism pathway, and ferroptosis pathway. l‐Glutamine, spermidine, and l‐tryptophan were the key hubs in the whole metabolic process of PD. N‐Formyl‐l‐methionine gradually increased in abundance with PD progression, whereas 5‐methylcytosine gradually decreased. The study emphasized the sequential changes in DAMs in PD progression, stimulating subsequent studies. [ABSTRACT FROM AUTHOR]

Abstract Introduction Duck enteritis virus (DEV) mainly causes infectious diseases characterized by intestinal haemorrhage, inflammation and parenchymal organ degeneration in ducks and other poultry. However, the mechanism by which it causes intestinal damage in ducks is not well understood. Metabolomics can provide an in-depth understanding of the full complexity of the disease. Methods In this study, 24 clinically healthy green-shell ducks (weight 1.5 kg ± 20 g) were randomly divided into 2 groups (experimental group, 18; control group, 6). The experimental group was intramuscularly injected with 0.2 mL of DEV virus in solution (TCID50 3.16 × 108 PFU/mL), and the control group was injected with 0.2 mL of sterile normal saline. Duck duodenum and ileum tissue samples were collected at 66 h, 90 h and 114 h post-injection (12 h of fasting before killing), and metabolomics analysis of duck duodenum and ileum tissues at the three time points (66, 90, 114 h) was performed by liquid chromatography–mass spectrometry (LC–MS) to screen for and analyse the potential differentiated metabolites and related signalling pathways. Results Screening was performed in the positive/negative mode (Pos: Positive ion mode; the ionization of substances at the ion source with positive ions such as H+, NH4 +, Na+ and K+; Neg: Negative ion mode; the ionization of substances at the ion source with negative ions such as Cl−, OAc−), and compound abundance was compared to that in the control group. The total number of differentially abundant compounds in the duodenum at 66 h, 90 h and 114 h of DEV infection gradually increased, and metabolites such as cytidine, 2′-deoxyriboside and 4-guanidinobutyric acid were differentially abundant metabolites common to all three time periods. The metabolic pathways related to inflammatory response and immune response were tryptophan acid metabolism, cysteine-methionine metabolism, histidine metabolism and other amino acid metabolism and fat metabolism. Among them, the metabolic pathways with more differentially abundant metabolites were amino acid biosynthesis, cysteine and methionine metabolism, tryptophan metabolism, unsaturated fatty acid biosynthesis and purine metabolism, and the metabolic pathways with more enrichment factors were the IgA-related intestinal immune network pathway and lysosome pathway. Compared with the control group, there were 16 differentially abundant metabolites in the ileum tissue of DEV-infected ducks at 66 h of infection, 52 at 90 h of infection, and 40 at 14 h of infection with TD114. The metabolic pathways with more enriched differentially abundant metabolites were pyrimidine metabolism, tyrosine metabolism, phenylalanine metabolism and tryptophan biosynthesis. The metabolic pathways with the most enrichment factors were the mTOR signalling pathway, ferroptosis pathway, tryptophan metabolism pathway and caffeine metabolism pathway. Conclusion Comparative analysis showed that the number of differentially abundant metabolites in the duodenum and ileum differed to some extent after DEV infection, with significantly more differentially abundant metabolites in duodenal tissues and fewer in ileal tissues; after DEV infection, the highest number of differentially abundant metabolites was obtained at 114 h of DEV infection, followed by the second highest at 90 h of infection and the lowest at 66 h of infection. The common differentially abundant metabolites in duodenal and ileal tissues were prostaglandins, arachidonic acid, and arachidonic ethanolamine. The main metabolic pathways in the duodenum were the IgA-associated intestinal immune network pathway and the lysosomal pathway, and the metabolic pathways with more enriched factors in the ileum were the mTOR signalling pathway, the ferroptosis pathway, and the tryptophan metabolism pathway.

To investigate the soil-specific metabolites of Codonopsis pilosula under different stubble management practices, this study analyzed differentially abundant metabolites in the rhizosphere soils of rotational (DS) and continuous (LS) cropping systems via liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based metabolomic approaches. The results revealed that 66 metabolites, including amino acids and their derivatives, nucleic acids, alcohols, organic acids, amines, fatty acids, purines, and sugars, were significantly different (p < 0.05) between the DS and LS groups. Under continuous cropping, the levels of amines, fatty acids, organic acids, and sugars in the rhizosphere soil were significantly greater (p < 0.05) than those under rotational cropping, whereas the levels of amino acids and their derivatives, nucleic acids, and purines and pyrimidines were significantly lower (p < 0.05). KEGG pathway enrichment analysis revealed that these differentially abundant metabolites were enriched in metabolic pathways such as amino acid metabolism (e.g., alanine, aspartate, and glutamate metabolism), carbon metabolism, the cAMP signaling pathway, ABC transporter proteins, phenylalanine metabolism, and the biosynthesis of plant secondary metabolites. These metabolic pathways were involved in osmoregulation, energy supply, and resilience in plants. In conclusion, inter-root soil metabolites in rotational and continuous cropping of Codonopsis pilosula were able to influence soil physicochemical properties and microbial populations by participating in various biological processes.

Cyclocarya paliurus tea, also known as “sweet tea”, an herbal tea with Cyclocarya paliurus leaves as raw material, is famous for its unique nutritional benefits and flavor. However, due to the unique “bittersweet” of Cyclocarya paliurus tea, it is still unable to fully satisfy consumers’ high-quality taste experience and satisfaction. Therefore, this study aimed to explore metabolites in Cyclocarya paliurus leaves during their growth period, particularly composition and variation of sweet and bitter taste compounds, by combining multi-platform metabolomics analysis with an electronic tongue system and molecular docking simulation technology. The results indicated that there were significant differences in the contents of total phenols, flavonoids, polysaccharides, and saponins in C. paliurus leaves in different growing months. A total of 575 secondary metabolites were identified as potential active metabolites related to sweet/bitter taste using nontargeted metabolomics based on UHPLC-MS/MS analysis. Moreover, molecular docking technology was utilized to study interactions between the candidate metabolites and the sweet receptors T1R2/T1R3 and the bitter receptors T2R4/T2R14. Six key compounds with high sweetness and low bitterness were successfully identified by using computational simulation analysis, including cis-anethole, gluconic acid, beta-D-Sedoheptulose, asparagine, proline, and citrulline, which may serve as candidates for taste modification in Cyclocarya paliurus leaves. These findings provide a new perspective for understanding the sweet and bitter taste characteristics that contribute to the distinctive sensory quality of Cyclocarya paliurus leaves.

Introduction: Roses are one of the most essential ornamental flowers and are commonly used in perfumery, cosmetics, and food. They are rich in bioactive compounds, which are of interest for therapeutic effects. Objectives: The objective of this study was to understand the kinds of changes that occur between the nocturnal and diurnal metabolism of rose and to suggest hypotheses. Methods: Reversed-phase ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry or triple quadrupole mass spectrometry (TQ MS/MS) was used for nontargeted metabolomics and hormonal profiling respectively. For metabolite annotation, accurate mass spectra were compared with those in databases. Results: The hormonal profile of flowers showed an increase in jasmonate at night, while that of leaves indicated an increase in the salicylic acid pathway. Nontargeted analyses of the flower revealed a switch in the plant's defense mechanisms from glycosylated metabolites during the day to acid metabolites at night. In leaves, a significant decrease in flavonoids was observed at night in favor of acid metabolism to maintain a level of protection. Moreover, it might be possible to place back some of the annotated molecules on the shikimate pathway. Conclusion: The influence of day and night on the metabolome of rose flowers and leaves has been clearly demonstrated. The hormonal modulations occurring during the night and at day are consistent with the plant circadian cycle. A proposed management of the sesquiterpenoid and triterpenoid biosynthetic pathway may explain these changes in the flower. In leaves, the metabolic differences may reflect night-time regulation in favor of the salicylic acid pathway. [ABSTRACT FROM AUTHOR]

Introduction: Duck enteritis virus (DEV) mainly causes infectious diseases characterized by intestinal haemorrhage, inflammation and parenchymal organ degeneration in ducks and other poultry. However, the mechanism by which it causes intestinal damage in ducks is not well understood. Metabolomics can provide an in-depth understanding of the full complexity of the disease. Methods: In this study, 24 clinically healthy green-shell ducks (weight 1.5 kg ± 20 g) were randomly divided into 2 groups (experimental group, 18; control group, 6). The experimental group was intramuscularly injected with 0.2 mL of DEV virus in solution (TCID50 3.16 × 108 PFU/mL), and the control group was injected with 0.2 mL of sterile normal saline. Duck duodenum and ileum tissue samples were collected at 66 h, 90 h and 114 h post-injection (12 h of fasting before killing), and metabolomics analysis of duck duodenum and ileum tissues at the three time points (66, 90, 114 h) was performed by liquid chromatography–mass spectrometry (LC–MS) to screen for and analyse the potential differentiated metabolites and related signalling pathways. Results: Screening was performed in the positive/negative mode (Pos: Positive ion mode; the ionization of substances at the ion source with positive ions such as H+, NH4+, Na+ and K+; Neg: Negative ion mode; the ionization of substances at the ion source with negative ions such as Cl−, OAc−), and compound abundance was compared to that in the control group. The total number of differentially abundant compounds in the duodenum at 66 h, 90 h and 114 h of DEV infection gradually increased, and metabolites such as cytidine, 2′-deoxyriboside and 4-guanidinobutyric acid were differentially abundant metabolites common to all three time periods. The metabolic pathways related to inflammatory response and immune response were tryptophan acid metabolism, cysteine-methionine metabolism, histidine metabolism and other amino acid metabolism and fat metabolism. Among them, the metabolic pathways with more differentially abundant metabolites were amino acid biosynthesis, cysteine and methionine metabolism, tryptophan metabolism, unsaturated fatty acid biosynthesis and purine metabolism, and the metabolic pathways with more enrichment factors were the IgA-related intestinal immune network pathway and lysosome pathway. Compared with the control group, there were 16 differentially abundant metabolites in the ileum tissue of DEV-infected ducks at 66 h of infection, 52 at 90 h of infection, and 40 at 14 h of infection with TD114. The metabolic pathways with more enriched differentially abundant metabolites were pyrimidine metabolism, tyrosine metabolism, phenylalanine metabolism and tryptophan biosynthesis. The metabolic pathways with the most enrichment factors were the mTOR signalling pathway, ferroptosis pathway, tryptophan metabolism pathway and caffeine metabolism pathway. Conclusion: Comparative analysis showed that the number of differentially abundant metabolites in the duodenum and ileum differed to some extent after DEV infection, with significantly more differentially abundant metabolites in duodenal tissues and fewer in ileal tissues; after DEV infection, the highest number of differentially abundant metabolites was obtained at 114 h of DEV infection, followed by the second highest at 90 h of infection and the lowest at 66 h of infection. The common differentially abundant metabolites in duodenal and ileal tissues were prostaglandins, arachidonic acid, and arachidonic ethanolamine. The main metabolic pathways in the duodenum were the IgA-associated intestinal immune network pathway and the lysosomal pathway, and the metabolic pathways with more enriched factors in the ileum were the mTOR signalling pathway, the ferroptosis pathway, and the tryptophan metabolism pathway. [ABSTRACT FROM AUTHOR]

Due to its significant physiological effects, a sulfated polysaccharide has been considered an important nutrient of sea cucumber, but its metabolism in vivo is still unclear. The present study investigated the metabolism of a sea cucumber sulfated polysaccharide (SCSP) in rats and its influence on the metabolite profiles. The quantification by HPLC-MS/MS revealed that the blood level of SCSP achieved a maximum of 54.0 ± 4.8 μg/mL at 2 h after gavage, almost no SCSP was excreted through urine, and 55.4 ± 29.8% of SCSP was eliminated through feces within 24 h. These results prove the utilization of SCSP by gut microbiota, and a further microbiota sequencing analysis indicated that the SCSP utilization in the gut was positively correlated with Muribaculaceae and Clostridia_UCG-014. In addition, the non-targeted metabolomic analysis demonstrated the significant effects of SCSP administration on the metabolite profiles of blood, urine, and feces. It is worth noting that the SCSP supplement decreased palmitic acid, stearic acid, and oleic acid in blood and urine while increasing stearic acid, linoleic acid, and γ-linolenic acid in feces, suggesting the inhibition of fat absorption and the enhancement of fat excretion by SCSP, respectively. The present study shed light on the metabolism in vivo and the influence on the fat metabolism of SCSP. [ABSTRACT FROM AUTHOR]

In this study, comprehensive and systematic nontargeted metabolomics analysis was performed with the metabolites of Zangju peel (Citrus reticulata cv. Manau Gan, CRZP, which has been cultivated for over 400 years in Derong County, China.) at four different mature stages. A total of 1878 metabolites were identified, among which flavonoids were the most abundant (62.04 %), and identified 62 key differential metabolites significantly affected by maturity. Based on biological activity measurements, CRZP showed better antioxidant activity, lipase inhibition ability, inhibition of adipogenic differentiation in 3TT-L1 cells and promotion of lipid metabolism, with the biological activity of CRZP at different maturity stages being associated with key differential metabolite. Thus, CRZP is natural antioxidants and possess anti-obesity potential, and industrial production needs to consider the Maturity stage of its collection.

Saeu-jeot is a widely consumed variety of jeotgal, a South Korean salt-fermented food. However, there is a lack of existing studies conducting nontargeted metabolomic analyses of saeu-jeot during fermentation. To evaluate the changes in saeu-jeot during fermentation, saeu-jeot samples were fermented for 360 days under controlled conditions. Samples collected at different time points were subjected to physicochemical (including nontargeted metabolomic analysis) and microbial analyses. As fermentation progressed, the pH decreased and acidity increased, whereas total nitrogen, amino-nitrogen, and specific amino acid concentrations increased. Nontargeted metabolite analysis supports these results. Metabolite profiling classified changes in saeu-jeot during fermentation into those occurring in the early (15–45 days), middle (60–180 days), and late (270–360 days) stages. Pathogenic bacteria were not detected, and biogenic amine levels were not elevated, suggesting that saeu-jeot is safe to consume. Overall, pH, amino-nitrogen, and pathogenic bacteria, according to the fermentation stage of saeu-jeot, can be useful parameters for evaluating the quality of salted shrimp. [ABSTRACT FROM AUTHOR]

The purpose of this study was to distinguish the effect of age on the meat quality and chemical composition of Yangzhou goose breast meat. Nontargeted metabolomics analysis (UHPLC-MS/MS) was used to distinguish the metabolic composition of goose meat at different ages, and Pearson’s correlations between differential metabolites and key meat parameters were assessed. Compared with goslings, adult geese had lighter, redder and chewier meat (p

The fruits of Rubus chingii Hu have high medicinal and nutritional values. However, the metabolite profiles of R. chingii, especially the alterations during different development stages of fruit, have not been comprehensively analyzed, hindering the effective utilization of the unique species. In this study, we comprehensively analyzed the metabolites of R. chingii fruit at four developmental stages using systematic untargeted and targeted liquid chromatography‐mass spectrometry metabolomics analysis and identified 682 metabolites. Significant changes were observed in metabolite accumulation and composition in fruits during the different developmental stages. The contents of the index components, kaempferol‐3‐O‐rutinoside and ellagic acid, were the highest in immature fruit. The analysis identified 64 differentially expressed flavonoids and 39 differentially expressed phenolic acids; the accumulation of most of these differentially expressed metabolites decreased with the developmental stages of fruit from immaturity to maturity. These results confirmed that the developmental stages of fruit are a critical factor in determining its secondary metabolite compositions. This study elucidated the metabolic profile of R. chingii fruit at different stages of development to understand the dynamic changes in metabolites. [ABSTRACT FROM AUTHOR]

Simple Summary: Overusing synthetic pesticides has resulted in environmental problems and human health risks while contributing to pesticide-resistant pests. Microalgae, being natural producers of highly diverse bioactive compounds, represent a promising alternative to replace synthetic pesticides as a more environmentally friendly and safe alternative. In this study, we screened biomass extracts from 10 green microalgae from the Chlorophyta phylum to identify molecules with potential pesticide activities. All tested strains exhibited herbicidal, nematocidal, or algicidal activities. Metabolomics analysis of six strains showed the presence of fatty acids, isoquinoline alkaloids, and aldehydes, which may be responsible for the observed pesticide activities. Our study highlights the algicidal, herbicidal, and nematocidal activities of biomass extracts derived from green microalgae and the metabolites and metabolic pathways potentially involved in producing the bioactive molecules. Our study supports the potential of microalgae for developing more effective and eco-friendlier biopesticides for sustainable agriculture. The excessive use of synthetic pesticides has caused environmental problems and human health risks and increased the development of resistance in several organisms. Allelochemicals, secondary metabolites produced as part of the defense mechanisms in plants and microorganisms, are an attractive alternative to replace synthetic pesticides to remediate these problems. Microalgae are natural producers of a wide range of allelochemicals. Thus, they provide new opportunities to identify secondary metabolites with pesticide activities and an alternative approach to discover new modes of action and circumvent resistance. We screened 10 green microalgae strains belonging to the Chlorophyta phylum for their potential to inhibit the growth of photosynthetic and nonphotosynthetic organisms. Bioassays were established to assess microalgae extracts' effectiveness in controlling the growth of Chlorella sorokiniana, Arabidopsis thaliana, Amaranthus palmeri, and the model nematode Caenorhabditis elegans. All tested strains exhibited herbicidal, nematocidal, or algicidal activities. Importantly, methanol extracts of a Chlamydomonas strain effectively controlled the germination and growth of a glyphosate-resistant A. palmeri biotype. Likewise, some microalgae extracts effectively killed C. elegans L1 larvae. Comprehensive metabolic profiling using LC-MS of extracts with pesticide activities showed that the metabolite composition of Chlamydomonas, Chlorella, and Chloroidium extracts is diverse. Molecules such as fatty acids, isoquinoline alkaloids, aldehydes, and cinnamic acids were more abundant, suggesting their participation in the pesticide activities. [ABSTRACT FROM AUTHOR]

Saussurea involucrata oral liquid (SIOL) can clinically relieve symptoms, such as joint pain and swelling, and morning stiffness, in patients with rheumatoid arthritis (RA). However, the mechanism of action remains unclear. This study used a combination of gut microbiota and serum metabolomics analysis to investigate the effects and potential mechanisms of SIOL intervention on rats with RA induced by type II bovine collagen and Freund's complete adjuvant. Results showed that SIOL treatment consequently improved the degree of ankle joint swelling, joint histopathological changes, joint pathological score, and expression of serum‐related inflammatory cytokines (interleukin (IL)‐1β, IL‐4, IL‐6, IL‐10, and tumor necrosis factor‐α) in RA model rats. 16 S rRNA sequencing results showed that SIOL increased the relative richness of the Lactobacillus and Bacteroides genus and decreased the relative richness of Romboutsia, Alloprevotella, Blautia, and Helicobacter genus. Serum nontargeted metabolomic results indicated that SIOL could regulate metabolites related to metabolic pathways, such as glycine, serine, threonine, galactose, cysteine, and methionine metabolism. Spearman correlation analysis showed that the regulatory effects of SIOL on the tricarboxylic acid (TCA) cycle, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism pathways were correlated with changes in the richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus in the gut microbiome. In conclusion, this study revealed the ameliorative effects of SIOL on RA and suggested that the therapeutic effects of SIOL on RA may be related to the regulation of the community richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus, thereby improving the TCA cycle; phenylalanine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism‐related pathways. [ABSTRACT FROM AUTHOR]

Purpose: To identify fasting serum metabolites associated with WG intake in a free-living population adjusted for potential confounders. Methods: We selected fasting serum samples at baseline from a subset (n = 364) of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) cohort. The samples were analyzed using nontargeted metabolomics with liquid chromatography coupled with mass spectrometry (LC–MS). Association with WG intake was investigated using both random forest followed by linear regression adjusted for age, BMI, smoking, physical activity, energy and alcohol consumption, and partial Spearman correlation adjusted for the same covariates. Features selected by any of these models were shortlisted for annotation. We then checked if we could replicate the findings in an independent subset from the same cohort (n = 200). Results: Direct associations were observed between WG intake and pipecolic acid betaine, tetradecanedioic acid, four glucuronidated alkylresorcinols (ARs), and an unknown metabolite both in discovery and replication cohorts. The associations remained significant (FDR<0.05) even after adjustment for the confounders in both cohorts. Sinapyl alcohol was positively correlated with WG intake in both cohorts after adjustment for the confounders but not in linear models in the replication cohort. Some microbial metabolites, such as indolepropionic acid, were positively correlated with WG intake in the discovery cohort, but the correlations were not replicated in the replication cohort. Conclusions: The identified associations between WG intake and the seven metabolites after adjusting for confounders in both discovery and replication cohorts suggest the potential of these metabolites as robust biomarkers of WG consumption. [ABSTRACT FROM AUTHOR]

Background This study was performed to identify metabolites associated with incident acute coronary syndrome (ACS) and explore causality of the associations. Methods and Results We performed nontargeted metabolomics in a nested case‐control study in the Dongfeng‐Tongji cohort, including 500 incident ACS cases and 500 age‐ and sex‐matched controls. Three metabolites, including a novel one (aspartylphenylalanine), and 1,5‐anhydro‐d‐glucitol (1,5‐AG) and tetracosanoic acid, were identified as associated with ACS risk, among which aspartylphenylalanine is a degradation product of the gut‐brain peptide cholecystokinin‐8 rather than angiotensin by the angiotensin‐converting enzyme (odds ratio [OR] per SD increase [95% CI], 1.29 [1.13–1.48]; false discovery rate–adjusted P=0.025), 1,5‐AG is a marker of short‐term glycemic excursions (OR per SD increase [95% CI], 0.75 [0.64–to 0.87]; false discovery rate–adjusted P=0.025), and tetracosanoic acid is a very‐long‐chain saturated fatty acid (OR per SD increase [95% CI], 1.26 [1.10–1.45]; false discovery rate–adjusted P=0.091). Similar associations of 1,5‐AG (OR per SD increase [95% CI], 0.77 [0.61–0.97]) and tetracosanoic acid (OR per SD increase [95% CI], 1.32 [1.06–1.67]) with coronary artery disease risk were observed in a subsample from an independent cohort (152 and 96 incident cases, respectively). Associations of aspartylphenylalanine and tetracosanoic acid were independent of traditional cardiovascular risk factors (P‐trend=0.015 and 0.034, respectively). Furthermore, the association of aspartylphenylalanine was mediated by 13.92% from hypertension and 27.39% from dyslipidemia (P

Due to its significant physiological effects, a sulfated polysaccharide has been considered an important nutrient of sea cucumber, but its metabolism in vivo is still unclear. The present study investigated the metabolism of a sea cucumber sulfated polysaccharide (SCSP) in rats and its influence on the metabolite profiles. The quantification by HPLC-MS/MS revealed that the blood level of SCSP achieved a maximum of 54.0 ± 4.8 μg/mL at 2 h after gavage, almost no SCSP was excreted through urine, and 55.4 ± 29.8% of SCSP was eliminated through feces within 24 h. These results prove the utilization of SCSP by gut microbiota, and a further microbiota sequencing analysis indicated that the SCSP utilization in the gut was positively correlated with Muribaculaceae and Clostridia_UCG-014. In addition, the non-targeted metabolomic analysis demonstrated the significant effects of SCSP administration on the metabolite profiles of blood, urine, and feces. It is worth noting that the SCSP supplement decreased palmitic acid, stearic acid, and oleic acid in blood and urine while increasing stearic acid, linoleic acid, and γ-linolenic acid in feces, suggesting the inhibition of fat absorption and the enhancement of fat excretion by SCSP, respectively. The present study shed light on the metabolism in vivo and the influence on the fat metabolism of SCSP.

Ying Ning,&ast; Yanju Gong,&ast; Tianyan Zheng, Ya Xie, Shiqing Yuan, Weijun Ding School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weijun Ding; Shiqing Yuan, Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Road, Chengdu, 611137, People’s Republic of China, Tel + 86-28-61800219, Fax + 86-28-61800225, Email Dingweijun@cdutcm.edu.cn; yuanshiqing@cdutcm.edu.cnBackground: The increasing incidence of obesity and its complications has become a global public health problem. Lingguizhugan decoction (LGZGD) is a representative compound of traditional Chinese medicine (TCM) for metabolic diseases, such as nonalcoholic fatty liver disease, but its role in insulin resistance (IR) treatment is still less known. This study aims to evaluate the therapeutic properties of LGZGD on obesity-induced IR and explore the potential mechanism of LGZGD on gut microbiota and its metabolites in the treatment of IR.Methods: In this study, we induced an IR model in the form of high-fat diet (HFD) rats gavaged with LGZGD (1.64 g/kg BW) for three weeks. The IR status was measured by biochemical assays and oral glucose tolerance tests. The degrees of damage to liver function and the intestinal barrier were observed by hematoxylin and eosin (H&E) staining and immunohistochemistry. Alterations in intestinal microbiota and metabolites were assessed by 16S rRNA and an untargeted metabolomics platform.Results: Our results showed that after LGZGD treatment, the body weight, plasma insulin concentration and blood lipids were significantly decreased, and glucose tolerance and hepatic steatosis were ameliorated. In addition, small intestinal villi were restored, and the expression of Occludin was upregulated. The relative abundance of Akkermansia, Faecalibacterium and Phascolarctobacterium in the HFD-LGZG group was upregulated. Obesity-related metabolic pathways, such as bile secretion, biosynthesis of amino acids, phenylalanine metabolism, serotonergic synapse, protein digestion and absorption, taurine and hypotaurine metabolism, and primary bile acid biosynthesis, were changed. After LGZGD intervention, metabolites developed toward the healthy control group. In addition, the expression of bile acid metabolism related genes was also regulated in IR rats.Conclusion: We showed that LGZGD relieved IR, possibly by regulating the composition of the fecal microbiota and its metabolites. The above studies provide a basis for further study of LGZGD in the treatment of IR and its clinical application.Keywords: insulin resistance, IR, lingguizhugan decoction, LGZGD, intestinal microbiota, nontargeted metabolomics, high-fat diet, HFD

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Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Saeu-jeot is a widely consumed variety of jeotgal, a South Korean salt-fermented food. However, there is a lack of existing studies conducting nontargeted metabolomic analyses of saeu-jeot during fermentation. To evaluate the changes in saeu-jeot during fermentation, saeu-jeot samples were fermented for 360 days under controlled conditions. Samples collected at different time points were subjected to physicochemical (including nontargeted metabolomic analysis) and microbial analyses. As fermentation progressed, the pH decreased and acidity increased, whereas total nitrogen, amino-nitrogen, and specific amino acid concentrations increased. Nontargeted metabolite analysis supports these results. Metabolite profiling classified changes in saeu-jeot during fermentation into those occurring in the early (15–45 days), middle (60–180 days), and late (270–360 days) stages. Pathogenic bacteria were not detected, and biogenic amine levels were not elevated, suggesting that saeu-jeot is safe to consume. Overall, pH, amino-nitrogen, and pathogenic bacteria, according to the fermentation stage of saeu-jeot, can be useful parameters for evaluating the quality of salted shrimp.

Abstract Background Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder diagnosed during adolescence and adulthood. Assessment of the long-term risks of the current drugs for ADHD treatment has been insufficient, and little is known concerning the long-term therapeutic effects of psychostimulants. Commercially available traditional Chinese medicine compound oral preparations [e.g., Dimu Ningshen (DMNS)] have been widely used in the clinical treatment of ADHD, but their influence on the interaction between gut microbes and potential metabolomes remains inconclusive. Methods We used a series of behavioral experiments to evaluate the behavioral effects of DMNS on adolescent and adult ADHD rats and used 16S rDNA sequencing of gut microbes and nontarget metabolomics to evaluate the potential pathogenesis of ADHD and explore the biological mechanism of DMNS in ADHD treatment. Results For the first time, DMNS was shown to reduce the excessive activity of adult and adolescent ADHD rats and improve the attention deficit of adult ADHD rats. DMNS improved the structural composition of the ADHD gut microbiota and reduced the abundance of Ruminococcaceae_NK4A214_group, Ruminococcus_2, and Eubacterium_nodatum_group. Simultaneously, DMNS increased the circulating levels of peripheral monoamine neurotransmitter precursors (e.g., phenylalanine) and reduced the circulating levels of peripheral fatty acid amides (e.g., oleamide). Finally, the changes in the ADHD serum metabolites were strongly correlated with the gut microbiota. Conclusion DMNS has a good effect in treating ADHD, and it may exert this effect by regulating the gut microbiota and affecting metabolites in the peripheral circulation.

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a recurrent and common disease featuring dysbiotic intestinal microbiota, with limited treatments. Si-Jun-Zi Decoction (SJZD), a classic Chinese prescription, has been extensively used for IBS-D. This work aimed to explore the ex vivo interactions of SJZD and IBS-D's intestinal microbiota. Methods: Five samples of intestinal microbiota collected from IBS-D volunteers and five age-matched healthy controls were recruited from the Affiliated Hospital, Chengdu University of Traditional Chinese Medicine (TCM). A representative mixture of intestinal microbiota was composed of an equal proportion of these fecal samples. To simulate the clinical interaction, this microbiota was cocultivated with SJZD at clinical dosage in an anaerobic incubator at 37 ℃ for 35 h. Microbiota and metabolic alterations were assessed by 16S rRNA gene sequencing in the V3/V4 regions and a nontargeted metabolome platform, respectively. Results: After being cocultivated with SJZD, the dysbiotic intestine microbiota from IBS-D subjects was largely restored to those of the healthy controls. A total of 624 differentially expressed metabolites were detected by nontargeted metabolomics, of which 16 biomarkers were identified. These metabolites were then enriched into 11 pathways by KEGG, particularly those involved in neurotransmitter metabolism responses for the major symptom of IBS-D. Correlation analysis of bacterial metabolites demonstrated a synergisticpattern of neurotransmitter metabolism between Streptococcus and E. Shigella. Conclusion: SJZD rescued the dysbiotic intestinal microbiota and ameliorated the dysfunctional neurotransmitter metabolism involved in IBS-D's major symptoms. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5) is an important risk factor affecting human health. Therefore, a quick method for finding metabolic targets in situ in ambient fine particulate matter is crucial. In this study, the impact of PM2.5 on human lung epithelial cells (A549) was investigated by Raman spectroscopy and mass spectrometry (MS)–based nontargeted metabolomics analysis. Raman detection indicated that exposure to PM2.5 reduced the levels of phenylalanine, tyrosine, and nucleotides. Metabolomics results not only demonstrated a significant decrease of the aforementioned metabolites but also added some important metabolite information that could not be detected by Raman spectroscopy. Our study demonstrated that Raman spectroscopy was an in situ, real-time, and rapid detection method for detecting metabolites, especially suitable for the assignment of phenylalanine/tyrosine and nucleotides, which play important roles in cellular growth. Moreover, the metabolic profiling changes observed upon PM2.5 treatment mainly involved phenylalanine, tyrosine metabolism, purine and pyrimidine metabolism, and energy metabolism, clearly demonstrating that PM2.5 can inhibit the synthesis of protein and DNA/RNA and reduce cellular energy supplies, further influencing cellular proliferation and other activities. [ABSTRACT FROM AUTHOR]

Hibiscus mutabilis, commonly known as the cotton rose, is a widely cultivated ornamental and has been acclaimed as the representative flower of the 2024 World Horticultural Exposition. The growth and ornamental characteristics of Hibiscus mutabilis can be affected by drought stress. Therefore, we investigated the physiological and metabolic responses of drought-sensitive Hibiscus mutabilis JRX-1 and drought-tolerant Hibiscus mutabilis CDS-4 under drought stress. The results of the physiological analyses revealed that, compared to JRX-1,CDS-4 maintained good growth and greater water use efficiency through stronger antioxidant defences, osmoregulatory capacity and stomatal regulation. A total of 3277 metabolites were identified in positive and negative ion modes, of which 663 metabolites presented changes in expression under drought conditions, including 306 upregulated metabolites and 357 downregulated metabolites. Secondary metabolites, such as flavonoids and diterpenoids, are crucial in the plant response to drought stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the differentially aboundant metabolites were significantly enriched in the pathways valine, leucine and isoleucine degradation; linoleic acid metabolism; one carbon pool by folate; and folate biosynthesis. The results of this study will not only help to elucidate and apply the physiological and metabolic regulatory strategies of Hibiscus mutabilis to improve its adaptation to water deficit conditions, but will also provide valuable guidance to breeders and molecular biologists in the screening and use of drought resistant genes in ornamental plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The excessive use of synthetic pesticides has caused environmental problems and human health risks and increased the development of resistance in several organisms. Allelochemicals, secondary metabolites produced as part of the defense mechanisms in plants and microorganisms, are an attractive alternative to replace synthetic pesticides to remediate these problems. Microalgae are natural producers of a wide range of allelochemicals. Thus, they provide new opportunities to identify secondary metabolites with pesticide activities and an alternative approach to discover new modes of action and circumvent resistance. We screened 10 green microalgae strains belonging to the Chlorophyta phylum for their potential to inhibit the growth of photosynthetic and nonphotosynthetic organisms. Bioassays were established to assess microalgae extracts’ effectiveness in controlling the growth of Chlorella sorokiniana, Arabidopsis thaliana, Amaranthus palmeri, and the model nematode Caenorhabditis elegans. All tested strains exhibited herbicidal, nematocidal, or algicidal activities. Importantly, methanol extracts of a Chlamydomonas strain effectively controlled the germination and growth of a glyphosate-resistant A. palmeri biotype. Likewise, some microalgae extracts effectively killed C. elegans L1 larvae. Comprehensive metabolic profiling using LC-MS of extracts with pesticide activities showed that the metabolite composition of Chlamydomonas, Chlorella, and Chloroidium extracts is diverse. Molecules such as fatty acids, isoquinoline alkaloids, aldehydes, and cinnamic acids were more abundant, suggesting their participation in the pesticide activities.

This study prepared enzymatic theabrownins (TBs-e), alkaline theabrownins (TBs-a), and Pu-erh tea theabrownins (TBs-f), and investigated whether different preparation processes affected the structures, nonvolatile metabolites, and biofunctional activities of TBs. Structural characterization revealed that TBs were polymeric phenolic compounds rich in hydroxyl and carboxyl groups. Nontargeted metabolomics revealed that amino acids were the primary nonvolatile metabolites in TBs-e and TBs-a, accounting for over 70 % of the total nonvolatile content. TBs-f contained more polyphenols, caffeine, and flavonoids, accounting for 14.2 %, 3.9 %, and 0.8 % of total nonvolatile content, respectively. In vivo, at 560 mg/kg body weight, TBs-f were associated with regulation of blood glucose and lipid concentrations in mice. Moreover, 16S rRNA indicated that at 1120 mg/kg body weight, TBs-a were associated with increased numbers of microbiota linked with hypolipidemic activity. This study explores the impacts of different preparation processes on TBs and provides a theoretical foundation for the understanding of TBs. • Structure characteristics of the three theabrownins differed significantly. • Nonvolatile metabolites of the three theabrownins differed significantly. • TBs-f showed greater hypolipidemic activity than TBs-e and TBs-a. • TBs-a increased the number of microbiota with hypolipidemic activity. [ABSTRACT FROM AUTHOR]

Oxapliplatin-induced peripheral neuropathy (OIPN) is a significant adverse effect encountered in patients with colorectal cancer undergoing oxaliplatin therapy. However, the pathogenesis of OIPN remains unclear. This study aimed to identify potential diagnostic biomarkers for OIPN and discover the metabolic pathways associated with the disease. Serum samples were collected from 218 subjects, including patients with OIPN and control (CONT). The metabolite profiles were analyzed using nontargeted liquid chromatography-mass spectrometry (LC-MS) serum metabolomics method. Subsequently, differentially altered metabolites were identified and evaluated through multivariate statistical analyses. In this study, patients with OIPN and CONT were distinguished by ten significant metabolites. The levels of racemethionine, O-acetylcarnitine, stearolic acid, aminoadipic acid, iminoarginine, galactaric acid, and all-trans-retinoic acid were increased, whereas the levels of 3-methyl-L-tyrosine, 5-aminopentanoic acid, and erythritol compared were found to be diminished in patients with OIPN when compared to the CONT. Through receiver operating characteristic (ROC) curve analysis, racemethionine, stearolic acid, 5-aminopentanoic acid, erythritol, aminoadipic acid, and all-trans-retinoic acid were pinpointed as promising biomarkers for OIPN. Significantly altered pathways included amino acids (arginine biosynthesis, beta-alanine metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, lysine degradation, and phenylalanine, tyrosine and tryptophan biosynthesis), lipid (linoleic acid metabolism and the biosynthesis of unsaturated fatty acids), and energy metabolism. This study, by identifying serum biomarkers and dissecting metabolic pathways, offers a groundbreaking perspective on the susceptibility mechanisms underlying OIPN. It stands as an invaluable resource for the adjunctive diagnosis of OIPN, with the potential to diminish the incidence of adverse reactions and to enhance the objectivity and reliability of clinical diagnoses of OIPN. • Serum metabolomics could distinguish OIPN patients from healthy controls (CONT). • Six metabolites were identified as potential biomarkers in OIPN and CONT. • Significantly altered pathways including amino acid, lipid, and energy metabolism. [ABSTRACT FROM AUTHOR]

Rosa rugosa is extensively cultivated in China for its remarkable fragrance and flavor, however, the metabolic changes in roses during growth and drying remain unclear. Our results revealed significant variations in phenol and flavonoid contents and antioxidant capacity in roses (Rosa rugosa f. plena (Regel) Byhouwer) under different conditions. Phenol contents were positively correlated with antioxidant capacity, with phytochemicals being most prominent in unfolded petals. The highest antioxidant capacity and phenol and flavonoid contents were observed in April. Considering their greater consumption value, whole flowers were more suitable than petals alone. Furthermore, considerable sensory and nutritional differences were observed in dried roses. Different drying methods increased their total phenol content of roses by 4.2–5.4 times and the antioxidant capacity by 2.9 times. Metabolomics revealed the altered contents of flavonoids, anthocyanins, lipids, amino acids, and saccharides. This study provides baseline data for the potential of roses as a natural source of antioxidants in the food and pharmaceutical industries. [Display omitted] • Bioactive chemicals in rose showed the highest level at the preanthesis stage. • Terpenes were the most volatile metabolites in roses during daytime. • Stamens had a much higher flavonoid content than petals and receptacles. • An increase in anthocyanin content maintained the desired appearance of freeze–dried roses. [ABSTRACT FROM AUTHOR]

This study comprehensively evaluated the effects of Lactiplantibacillus plantarum T1 and CSK (ropy and non-ropy phenotypes), on flavour, and nutrient metabolites of fermented milks using gas chromatography-mass spectrometry and non-targeted metabolomics. The microrheological analysis showed that the protein gelation time of CSK fermented milk was earlier (5.2 h) than that of T1 (7.0 h), while the fermented milk by T1 had higher elastic modulus. Fermentation by both strains significantly enhanced the antioxidant activity of the fermented milk, including scavenging capabilities against ABTS, DPPH, and hydroxyl radicals. Meanwhile, fermentation by two strains produced various volatile flavor compounds (hexanoic acid, caprylic acid, capric acid, nonanal, decanal, 2-heptanone and 2-nonanone, etc.), and L. plantarum CSK displayed more stronger acid production capacity. In addition, a total of 397 shared metabolites and 81 unique metabolites were identified by untargeted metabolomics analysis of the two groups of fermented milks, mainly including lipids and lipid-like molecules (66, 27.27%), organic heterocyclic compounds (40, 16.53%), phenylketones and polyketones (23, 9.5%), and organic acids and their derivatives (49, 20.25%). Furthermore, both strains significantly elevated the amino acid nutritional levels in the fermented milk, conferred an abundance of active metabolites such as niacin and nicotinamide. During the fermentation, L. plantarum CSK notably produced antioxidant fumaric acid and exhibited higher fatty acid metabolism compared to L. plantarum T1. Overall, this study provides some practical basis for the development of fermented cow's milk with good antioxidant activity and high nutritional quality using different phenotypes of L. plantarum. [Display omitted] • Two L. plantarum exhibited good cow's milk fermentation viability. • Fermented milk by two L. plantarum showed good antioxidant activity. • L. plantarum fermentation effectively increased the amino acid nutrient levels. • L. plantarum CSK could produce abundant fumaric acid during milk fermentation. • Fermented milk enriched with active metabolites such as niacin and nicotinamide. [ABSTRACT FROM AUTHOR]

[Display omitted] • Using multi-omics approaches revealed aroma formation of GAGT for the first time. • Anaerobic treatment mainly affected lipids and glycoside-derived volatiles. • Five volatiles were screened as target metabolites. • CsERFs might engage in regulating GABA accumulation and target volatile metabolism. • First proposed ethylene might engage in GAGT aroma formation and GABA metabolism. Gabaron green tea (GAGT) has unique flavor and health benefits through the special anaerobic treatment. However, how this composite processing affects the aroma formation of GAGT and the regulatory mechanism was rarely reported. This study used nontargeted metabolomics and molecular sensory science to overlay screen differential metabolites and key aroma contributors. The potential regulatory mechanism of anaerobic treatment on the aroma formation of GAGT was investigated by transcriptomics and correlation analyses. Five volatiles: benzeneacetaldehyde, nonanal, geraniol, linalool, and linalool oxide III, were screened as target metabolites. Through the transcriptional-level differential genes screening and analysis, some CsERF transcription factors in the ethylene signaling pathway were proposed might participate the response to the anaerobic treatment. They might regulate the expression of related genes in the metabolic pathway of the target metabolites thus affecting the GAGT flavor. The findings of this study provide novel information on the flavor and its formation of GAGT. [ABSTRACT FROM AUTHOR]

• Acetamiprid showed low bioconcentration potential in Xenopus laevis tadpoles. • Acetamiprid may have toxic effects on Xenopus laevis tadpoles. • Exposure to acetamiprid induces disorders in the antioxidant defense system. • Exposure to acetamiprid alters transcriptome and metabolome profiles in tadpoles. • Imbalances in purine metabolism and amino acid metabolism are potential molecular mechanisms. Acetamiprid is a neonicotinoid commonly detected in aquatic ecosystems, with residual concentrations of up to 0.41 mg/L in surface water, posing a threat to the health of nontarget aquatic organisms. However, studies on the potential toxicity and underlying mechanisms of action of acetamiprid on nontarget aquatic organisms are limited. This study investigated the acute and short-term toxicity of acetamiprid to Xenopus laevis tadpoles. A 96-h acute toxicity test determined the LC 50 of acetamiprid to be 32.1 mg/L. After 28 days of exposure to 1/10 and 1/100 LC 50 concentrations, tadpole samples were collected for bioconcentration elimination analysis, biochemical analyses, transcriptomics, and metabolomics studies to comprehensively evaluate the toxic effects of acetamiprid and its underlying mechanisms. The results, indicating bioconcentration factors (BCFs) < 1, suggest that acetamiprid has a low bioconcentration in tadpoles. Additionally, oxidative stress was observed in treated Xenopus laevis tadpoles. Transcriptomic and nontargeted metabolomic analyses identified 979 differentially expressed genes (DEGs) and 95 differentially metabolites in the 0.321 mg/L group. The integrated analysis revealed that disruption of purine and amino acid metabolic pathways potentially accounts for acetamiprid-induced toxic effects in tadpoles. The disruptive effects of acetamiprid on valine, leucine and isoleucine biosynthesis; and aminoacyl-tRNA biosynthesis metabolic pathways in tadpoles were validated through targeted metabolomics analysis. These findings are crucial for assessing the risk of acetamiprid to nontarget aquatic organisms. [ABSTRACT FROM AUTHOR]

Background: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder diagnosed during adolescence and adulthood. Assessment of the long-term risks of the current drugs for ADHD treatment has been insufficient, and little is known concerning the long-term therapeutic effects of psychostimulants. Commercially available traditional Chinese medicine compound oral preparations [e.g., Dimu Ningshen (DMNS)] have been widely used in the clinical treatment of ADHD, but their influence on the interaction between gut microbes and potential metabolomes remains inconclusive. Methods: We used a series of behavioral experiments to evaluate the behavioral effects of DMNS on adolescent and adult ADHD rats and used 16S rDNA sequencing of gut microbes and nontarget metabolomics to evaluate the potential pathogenesis of ADHD and explore the biological mechanism of DMNS in ADHD treatment. Results: For the first time, DMNS was shown to reduce the excessive activity of adult and adolescent ADHD rats and improve the attention deficit of adult ADHD rats. DMNS improved the structural composition of the ADHD gut microbiota and reduced the abundance of Ruminococcaceae_NK4A214_group, Ruminococcus_2, and Eubacterium_nodatum_group. Simultaneously, DMNS increased the circulating levels of peripheral monoamine neurotransmitter precursors (e.g., phenylalanine) and reduced the circulating levels of peripheral fatty acid amides (e.g., oleamide). Finally, the changes in the ADHD serum metabolites were strongly correlated with the gut microbiota. Conclusion: DMNS has a good effect in treating ADHD, and it may exert this effect by regulating the gut microbiota and affecting metabolites in the peripheral circulation. [ABSTRACT FROM AUTHOR]

Background: The relationship between metabolic syndrome (MetS) and gastric cancer (GC), which is a common metabolic disease, has attracted much attention. However, the specific metabolic characteristics of MetS in elderly patients with GC remain unclear., Aim: To investigate the differentially abundant metabolites and metabolic pathways between preoperative frailty and MetS in elderly patients with GC based on nontargeted metabolomics techniques., Methods: In this study, 125 patients with nonfrail nonmeal GC were selected as the control group, and 50 patients with GC in the frail group were selected as the frail group. Sixty-five patients with GC combined with MetS alone were included in the MetS group, and 50 patients with GC combined with MetS were included in the MetS group. Nontargeted metabolomics techniques were used to measure plasma metabolite levels by ultrahigh-performance liquid chromatography-mass spectrometry. Multivariate statistical analysis was performed by principal component analysis, orthogonal partial least squares, pattern recognition analysis, cluster analysis, and metabolic pathway annotation., Results: A total of 125 different metabolites, including amino acids, glycerophospholipids, sphingolipids, fatty acids, sugars, nucleosides and nucleotides, and acidic compounds, were identified via nontargeted metabolomics techniques. Compared with those in the control group, there were 41, 32, and 52 different metabolites in the MetS group, the debilitated group, and the combined group, respectively. Lipid metabolites were significantly increased in the MetS group. In the weak group, amino acids and most glycerol phospholipid metabolites decreased significantly, and fatty acids and sphingosine increased significantly. The combined group was characterized by significantly increased levels of nucleotide metabolites and acidic compounds. The alanine, aspartic acid, and glutamate metabolic pathways were obviously enriched in the asthenic group, and the glycerol and phospholipid metabolic pathways were obviously enriched in the combined group., Conclusion: Elderly GC patients with simple frailty, simple combined MetS, and frailty combined with MetS have different metabolic characteristics, among which amino acid and glycerophospholipid metabolite levels are significantly lower in frail elderly GC patients, and comprehensive supplementation of fat and protein should be considered. Many kinds of metabolites, such as amino acids, lipids, nucleotides, and acidic compounds, are abnormally abundant in patients with MetS combined with fthenia, which may be related to tumor-related metabolic disorders., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Inflammatory bowel disease (IBD) is a recurrent inflammatory condition affecting the gastrointestinal tract, and its clinical treatment remains suboptimal. Probiotics have shown effectiveness in alleviating dextran sulfate sodium salt (DSS)-induced colitis, exhibiting strain-specific anti-inflammatory properties. In this study, we compared the therapeutic effects of five strains of Bifidobacterium bifidum isolated from healthy adult feces on DSS-induced colitis in mice. Additionally, we investigated the underlying mechanisms by examining gut microbiota composition and microbial metabolome. Our findings highlighted the superior efficacy of B. bifidum M1-3 compared to other strains. It significantly improved colitis symptoms, mitigated gut barrier disruption, and reduced colonic inflammation in DSS-treated mice. Moreover, gut microbiota composition analysis revealed that B. bifidum M1-3 treatment increased the abundance and diversity of gut microbiota. Specifically, it significantly increased the abundance of Muribaculaceae , Lactobacillus , Bacteroides , and Enterorhabdus , while decreasing the abundance of Escherichia-Shigella . Furthermore, our nontargeted metabolomics analysis illustrated that B. bifidum M1-3 treatment had a regulatory effect on various metabolic pathways, including tyrosine metabolism, lysine degradation, and tryptophan metabolism. Importantly, we confirmed that the therapeutic efficiency of B. bifidum M1-3 was dependent on the gut microbiota. These results are conducive to the development of probiotic products for alleviating colitis.

Liver injury is a clinical disorder caused by toxins, drugs, and alcohol stimulation without effective therapeutic approaches thus far. Scutellarin (SCU), isolated from the edible herb Erigeron breviscapus (Vant.) Hand. -Mazz. showed potential hepatoprotective effects, but the mechanisms remain unknown. In this study, transcriptomics combined with nontargeted metabolomics and 16S rRNA amplicon sequencing were performed to elucidate the functional mechanisms of SCU in carbon tetrachloride (CCl4)–induced liver injury in mice. The results showed that SCU exerted potential hepatoprotective effects against CCl4-induced liver injury by repressing CYP2E1 and IκBα/NF-κB signaling pathways, modulating the gut microbiota (especially enriching Lactobacillus), and regulating the endogenous metabolites involved in lipid metabolism and bile acid homeostasis. SCU originates from a functional food that appears to be a promising agent to guard against liver injury.

Liver injury is a clinical disorder caused by toxins, drugs, and alcohol stimulation without effective therapeutic approaches thus far. Scutellarin (SCU), isolated from the edible herb Erigeron breviscapus (Vant.) Hand. -Mazz. showed potential hepatoprotective effects, but the mechanisms remain unknown. In this study, transcriptomics combined with nontargeted metabolomics and 16S rRNA amplicon sequencing were performed to elucidate the functional mechanisms of SCU in carbon tetrachloride (CCl4)–induced liver injury in mice. The results showed that SCU exerted potential hepatoprotective effects against CCl4-induced liver injury by repressing CYP2E1 and IκBα/NF-κB signaling pathways, modulating the gut microbiota (especially enriching Lactobacillus), and regulating the endogenous metabolites involved in lipid metabolism and bile acid homeostasis. SCU originates from a functional food that appears to be a promising agent to guard against liver injury. [ABSTRACT FROM AUTHOR]

The chemical and biologically active characterization of jujube samples (fruits, cores, and leaves) were carried out by the integrated nontargeted metabolomics and bioassay. Firstly, collision cross-section values of active compounds in jujubes were determined by ultrahigh-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry. Then, a multidimensional statistical analysis that contained principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis was employed to effectively cluster different tissues and types of jujubes, making identification more scientific. Furthermore, angiotensin-converting enzyme (ACE) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the quality of jujubes from a double activity dimension. The analytical results obtained by using ACE and DPPH to evaluate the quality of jujube were different from multivariate statistics, providing a reference for the application of jujube. Therefore, integrating chemical and biological perspectives to evaluate the quality of jujube provided a more comprehensive evaluation and effective reference for clinical needs. [Display omitted] • A novel bioassay assisted nontargeted metabolomics was developed. • Secondary metabolites were identified by UHPLC-IM-Q-TOF/MS. • ACE and DPPH were employed to evaluate the quality of jujubes. • Chemometrics contained PCA, PLS-DA, and HCA were employed. [ABSTRACT FROM AUTHOR]

• Comprehensive metabolites profiles among the petals of Liriodendron. • Different accumulation of chlorogenic acid was found in the petal of the Liriodendron. • The chlorogenic acid synthesis pathway was identified in Liriodendron petals. • CYP98A gene family showed significant expansion in Liriodendron. Petal secondary metabolites can affect pollinator selection and invasion of pathogenic microorganisms to change the adaptability to the environment. Meanwhile, the active components in petal are widely used in many aspects of human society. At present, research into bioactive compounds in Liriodendron have mainly focused on bark, leaf and root tissues, with few studies systematically studying the differences in secondary metabolite content of petals coming from different Liriodendron accessions. By combining untargeted LC–MS metabolome analysis with analysis of the Liriodendron petal transcriptome, the biosynthetic pathway of activity in Liriodendron petals was studied, and the 6097 different accumulated metabolites were identified in different Liriodendron. These differentially accumulated metabolites (DAMs) are synthesized through multiple secondary metabolic pathways, with a strong enrichment for flavonoid and phenylpropanoid biosynthetic compounds, suggesting that these active substances may be potentially valid medicinal components. In this study, the accumulation of chlorogenic acid (CGA) was increased in the petals of L. chinense. In addition, the chlorogenic acid synthesis pathway, which is mainly involved in the regulation of multiple CYP98A enzymes. These results reveal differential accumulation of secondary metabolites and potential medicinal ingredients in Liriodendron petals and thus provide a basis for further effective utilization of petals. [Display omitted] [ABSTRACT FROM AUTHOR]

A key segment in medicinal plant authentication is the establishment of quality markers that embody the intrinsic metabolites difference independent of instruments and experiment conditions. A strategy integrating nontargeted metabolomics and multicriteria decision‐making model for robust quality markers discovery is presented and applied to authenticate Ophiopogon japonicus (L. f.) Ker‐Gawl. First, an ultra‐performance liquid chromatography/quadrupole time‐of‐flight MSE approach was established for global metabolites profiling and identification. Second, multivariate statistical analysis was performed to explore potential quality markers of different origins of ophiopogonis radix. Third, potential quality markers were ordered and filtered by multicriteria decision‐making model to infer robust quality markers and further validated in different instruments and experiment conditions by validation model. Fourth, the validation model using the robust quality markers managed to discriminate the origins of ophiopogonis radix samples procured from the herbal markets. Consequently, two robust quality markers, cixi‐ophiopogon B and ophiopogonin D, were discovered and further validated on different instruments and experiment conditions. This integrated strategy provided a practical solution for reliable and convenient authentication of geo‐authentic herb. [ABSTRACT FROM AUTHOR]