Significant Differential Metabolites Research Articles

Untargeted Metabolomics Based on Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Orbitrap High-Resolution Mass Spectrometry for Differential Metabolite Analysis of Pinelliae Rhizoma and Its Adulterants.

The present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma.

Association of metabolomics with PD-1 inhibitor plus chemotherapy outcomes in patients with advanced non-small-cell lung cancer

BackgroundCombining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting...

Serum metabolome perturbation in relation to noise exposure: Exploring the potential role of serum metabolites in noise-induced arterial stiffness

Noise pollution has grown to be a major public health issue worldwide. We sought to profile serum metabolite expression changes related to occupational noise exposure by untargeted metabolomics, as well as to evaluate the potential roles of serum metabolites in occupational noise-associated arterial stiffness (AS). Our study involved 30 noise-exposed industrial personnel (Lipo group) and 30 noise-free controls (Blank group). The untargeted metabolomic analysis was performed by employing a UPLC-HRMS. The associations of occupational noise and significant differential metabolites (between Blank/Lipo groups) with AS were evaluated using multivariable-adjusted generalized linear models. We performed the least absolute shrinkage and selection operator regression analysis to further screen for AS's risk metabolites. We explored 177 metabolites across 21 categories significantly differentially expressed between Blank/Lipo groups, and these metabolites were enriched in 20 metabolic pathways. Moreover, 15 metabolites in 4 classes (including food, glycerophosphocholine, sphingomyelin [SM] and triacylglycerols [TAG]) were adversely associated with AS (all P < 0.05). Meanwhile, five metabolites (homostachydrine, phosphatidylcholine (PC) (32:1e), PC (38:6p), SM (d41:2) and TAG (45:1) have been proven to be useful predictors of AS prevalence. However, none of these 15 metabolites were found to have a mediating influence on occupational noise-induced AS. Our study reveals specific metabolic changes caused by occupational noise exposure, and several metabolites may have protective effects on AS. However, the roles of serum metabolites in noise-AS association remain to be validated in future studies.

Brisk walking improves motor function and lower limb muscle strength in Chinese women aged 80years and older.

This study investigates the effects of a 12-week brisk walking exercise regimen on motor function improvements in elderly women. Twenty-six elderly women, aged 84.2 ± 3.2years, participated in a 12-week brisk walking exercise program. Fitness assessments and blood biomarker analyses (including CHO, HDLC, LDLC, TC) were conducted pre- and post-intervention. Additionally, targeted metabolomics was employed to measure short-chain fatty acids, amino acids, and vitamin metabolites. The intervention led to significant enhancements in participants' flexibility (p < 0.05), lower limb muscle strength (p < 0.01), and cardiorespiratory endurance (p < 0.01), while muscle mass showed no significant changes. Fifteen significant differential metabolites were identified (VIP > 1.0, FC > 1.2 or < 0.8, and p < 0.05), with arginine, ornithine, aspartic acid, glutamine, phenylalanine, tyrosine, and pantothenic acid playing key roles across seven metabolic pathways. A 12-week brisk walking exercise program significantly enhanced flexibility, lower limb muscle strength, and cardiorespiratory endurance among elderly women. These improvements did not extend to muscle mass or upper limb muscle strength. The observed enhancement in exercise capacity may be attributed to improved regulation of neurotransmitters.

UPLC-ESI-MS/MS-based widely targeted metabolomics reveals differences in metabolite composition among four Ganoderma species.

The Chinese name "Lingzhi" refers to Ganoderma genus, which are increasingly used in the food and medical industries. Ganoderma species are often used interchangeably since the differences in their composition are not known. To find compositional metabolite differences among Ganoderma species, we conducted a widely targeted metabolomics analysis of four commonly used edible and medicinal Ganoderma species based on ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Through pairwise comparisons, we identified 575-764 significant differential metabolites among the species, most of which exhibited large fold differences. We screened and analyzed the composition and functionality of the advantageous metabolites in each species. Ganoderma lingzhi advantageous metabolites were mostly related to amino acids and derivatives, as well as terpenes, G. sinense to terpenes, and G. leucocontextum and G. tsugae to nucleotides and derivatives, alkaloids, and lipids. Network pharmacological analysis showed that SRC, GAPDH, TNF, and AKT1 were the key targets of high-degree advantage metabolites among the four Ganoderma species. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes demonstrated that the advantage metabolites in the four Ganoderma species may regulate and participate in signaling pathways associated with diverse cancers, Alzheimer's disease, and diabetes. Our findings contribute to more targeted development of Ganoderma products in the food and medical industries.

Integration of cross-correlation analysis and untargeted flavoromics reveals unique flavor formation of lactic acid bacteria co-fermented oat beverage

Lactic acid bacteria (LAB) fermentation has the potential to be an effective way to improve the flavor of foods. In this study, Lactococcus lactis (L. lactis), Lactobacillus plantarum (L. plantarum) and Lactobacillus rhamnosus (L. rhamnosus) co-fermented oat beverage was prepared and both the molecular and biochemical basis for its unique flavor formation were investigated by using cross-correlation analysis combined with untargeted flavoromics. Results showed that via co-fermentation main flavor substances like organic acids, free amino acids (FAAs) and volatile flavor compounds (VFCs) could be regulated dynamically. Interaction network analysis and redundancy analysis (RDA) convinced the crucial roles of three bacteria in shaping the overall flavor profile of co-fermented beverage, especially for the formation of soft sourness, sweetness, and freshness. According to untargeted metabolomics, it could be concluded that co-fermentation regulated significant differential metabolites (56 in total) unique to LAB co-fermented oat beverage such as benzoic acid, DL-arginine, uridine, and citrate. KEGG pathway enrichment analysis further predicted the viable formation pathways of key flavor compounds obtained by RDA such as organic acids (malate, citrate, et al.), FAAs (aspartate, glutamate, et al.) and VFCs (2,3-butanedione, 1-nonanol, et al.). This work demonstrates the positive flavor contribution of LAB co-fermentation, providing valuable reference for subsequent multi-omics studies on fermented oat products.

UHPLC-qTOF-MS-Based Nontargeted Metabolomics to Characterize the Effects of Capsaicin on Plasma and Skin Metabolic Profiles of C57BL/6 Mice-An In vivo Experimental Study.

Capsaicin is the main compound found in chili pepper and has complex pharmacologic effects. This study aimed to elucidate the mechanism of the effect of capsaicin on physiological processes by analyzing changes in metabolites and metabolic pathways. Female C57BL/6 mice were divided into two groups(n = 10/group) and fed with capsaicin-soybean oil solution(group T) or soybean oil(group C) for 6 weeks. Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was undertaken to assess plasma and skin metabolic profile changes and identify differential metabolites through multivariate analysis. According to the OPLS-DA score plots, the plasma and skin metabolic profiles in the group T and group C were significantly separated. In plasma, 38 significant differential metabolites were identified. KEGG pathway enrichment analysis revealed that the most significant plasma metabolic pathways included pyruvate metabolism and ABC transporters. In skin, seven significant differential metabolites were found. Four metabolic pathways with p values < 0.05 were detected, including sphingolipid metabolism, sphingolipid signaling pathway, apoptosis, and necroptosis. These findings will provide metabolomic insights to assess the physiological functions of capsaicin and contribute to a better understanding of the potential effects of a capsaicin-rich diet on health.

Comparison of the quality of suansun product between starter inoculation and natural fermentation

Suansun (fermented bamboo shoots) was prepared by natural fermentation (NF) and inoculation fermentation (IF) with a starter culture containing Lactococcus lactis, Leuconostoc citreum, and Lactiplantibacillus plantarum in this study, to evaluate the effects of inoculation mixed starter culture on physicochemical, flavor and sensory characteristics of suansun. The results showed that IF suansun acidified faster and to a greater extent than NF. Besides, the accelerated acidification process significantly decreased the nitrite content, shortened the fermentation time and improved the food safety of the final suansun product in IF. At the end of fermentation, the lactic acid concentration was significantly higher in IF (6.17 ± 0.25 g/L) than in NF (3.83 ± 0.28 g/L). Twenty-seven volatile compounds were identified as the characteristic flavor compounds in suansun and the relative content of nonanal, hexanal, 1-octen-3-ol and 3-octanone (ROAV >1) was higher in IF than in NF at the late stage of fermentation. In addition, 132 non-volatile compounds were identified as significant differential metabolites, which were mainly small peptides and fatty acids in both NF and IF. Sensory evaluation found that the aroma, taste, texture and overall quality scores of IF suansun were all superior to those of NF suansun. The above results demonstrated that the use of mixed starter cultures of Lac. lactis, Leu. citreum, and L. plantarum contributed to improving the quality of suansun product, and might provide a feasible approach for standardized production of suansun in the future.

Liquid chromatography coupled to mass spectrometry metabolomic analysis of cerebrospinal fluid revealed the metabolic characteristics of moyamoya disease.

Metabolomics has found extensive applications in the field of neurological diseases, significantly contributing to their diagnosis and treatment. However, there has been limited research applying metabolomics to moyamoya disease (MMD). This study aims to investigate and identify differential metabolites associated with MMD. We employed a liquid chromatography coupled with mass spectrometry (LC-MS) approach, complemented by univariate and multivariate analyses, to discern metabolic biomarkers in cerebrospinal fluid samples. We then compared these biomarkers between MMD patients and healthy controls (Ctl). Sixteen patients diagnosed with MMD via cerebral angiography and eight healthy controls were enrolled in this study. Comparative analyses, including univariate and multivariate analyses, correlation studies, heatmaps, Volcano Plots, and KEGG pathway enrichment, were performed between MMD patients and controls. As a result, we identified 129 significant differential metabolites in the cerebrospinal fluid between MMD patients and controls. These metabolic biomarkers are associated with various pathways, with notable involvement in purine and pyrimidine metabolism. Utilizing an LC-MS-based metabolomics approach holds promise for enhancing the clinical diagnosis of MMD. The identified biomarkers offer potential avenues for the development of novel diagnostic methods for MMD and offer fresh insights into the pathogenesis of the disease.

Metabolomic profiling of ocular tissues in rabbit myopia: Uncovering differential metabolites and pathways

To investigate the metabolic difference among tissue layers of the rabbits’ eye during the development of myopia using metabolomic techniques and explore any metabolic links or cascades within the ocular wall. Ultra Performance Liquid Chromatography - Mass Spectrometry (UPLC-MS) was utilized for untargeted metabolite screening (UMS) to identify the significant differential metabolites produced between myopia (MY) and control (CT) (horizontal). Subsequently, we compared those key metabolites among tissues (Sclera, Choroid, Retina) of MY for distribution and variation (longitudinal). A total of 6285 metabolites were detected in the three tissues. The differential metabolites were screened and the metabolic pathways of these metabolites in each myopic tissue were labeled, including tryptophan and its metabolites, pyruvate, taurine, caffeine metabolites, as well as neurotransmitters like glutamate and dopamine. Our study suggests that multiple metabolic pathways or different metabolites under the same pathway, might act on different parts of the eyeball and contribute to the occurrence and development of myopia by affecting the energy supply to the ocular tissues, preventing antioxidant stress, affecting scleral collagen synthesis, and regulating various neurotransmitters mutually.

Utilizing serum metabolomics for assessing postoperative efficacy and monitoring recurrence in gastric cancer patients

Objective(1) This study aims to identify distinct serum metabolites in gastric cancer patients compared to healthy individuals, providing valuable insights into postoperative efficacy evaluation and monitoring of gastric cancer recurrence; (2) Methods: Serum samples were collected from 15 healthy individuals, 16 gastric cancer patients before surgery, 3 months after surgery, 6 months after surgery, and 15 gastric cancer recurrence patients. T-test and analysis of variance (ANOVA) were performed to screen 489 differential metabolites between the preoperative group and the healthy control group. Based on the level of the above metabolites in the recurrence, preoperative, three-month postoperative, and six-month postoperative groups, we further selected 18 significant differential metabolites by ANOVA and partial least squares discriminant analysis (PLS-DA). The result of hierarchical clustering analysis about the above metabolites showed that the samples were regrouped into the tumor-bearing group (comprising the original recurrence and preoperative groups) and the tumor-free group (comprising the original three-month postoperative and six-month postoperative groups). Based on the results of PLS-DA, 7 differential metabolites (VIP > 1.0) were further selected to distinguish the tumor-bearing group and the tumor-free group. Finally, the results of hierarchical clustering analysis showed that these 7 metabolites could well identify gastric cancer recurrence; (3) Results: Lysophosphatidic acids, triglycerides, lysine, and sphingosine-1-phosphate were significantly elevated in the three-month postoperative, six-month postoperative, and healthy control groups, compared to the preoperative and recurrence groups. Conversely, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol were significantly reduced in the three-month postoperative, six-month postoperative, and healthy control groups compared to the preoperative and recurrence groups. However, these substances did not show significant differences between the preoperative and recurrence groups, nor between the three-month postoperative, six-month postoperative, and healthy control groups; (4) Conclusions: Our findings demonstrate the presence of distinct metabolites in the serum of gastric cancer patients compared to healthy individuals. Lysophosphatidic acid, triglycerides, lysine, sphingosine-1-phosphate, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol hold potential as biomarkers for evaluating postoperative efficacy and monitoring recurrence in gastric cancer patients. These metabolites exhibit varying concentrations across different sample categories.

Reprogramming of arachidonic acid metabolism using α-terpineol to alleviate asthma: insights from metabolomics.

Asthma is a chronic inflammatory disorder in airways with typical pathologic features of airway inflammation and mucus hypersecretion. α-Terpineol is a monocyclic terpene found in many natural plants and foods. It has been reported to possess a wide range of pharmacological activities including anti-inflammatory and expectorant effects. However, the role of α-terpineol in asthma and its potential protective mechanism have not been well elucidated. This study is designed to investigate the pharmacological effect and mechanism of α-terpineol on asthmatic mice using the metabolomics platform. A murine model of asthma was established using ovalbumin (OVA) sensitization and then challenged for one week. The leukocyte count and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), lung histopathology, inflammatory infiltrate and mucus secretion were evaluated. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based metabolomics study was performed on lung tissues and serum to explore endogenous small molecule metabolites affected by α-terpineol in asthmatic mice. After α-terpineol treatment, leukocyte count, inflammatory cytokines in the BALF, and peribronchial inflammation infiltration were significantly downregulated. Goblet cell hyperplasia and mucus secretion were attenuated, with the level of Muc5ac in BALF decreased. These results proved the protective effect of α-terpineol against airway inflammation, mucus hypersecretion and Th1/Th2 immune imbalance. To further investigate the underlying mechanisms of α-terpineol in asthma treatment, UPLC-MS/MS-based metabolomics analysis was performed. 26 and 15 identified significant differential metabolites were found in the lung tissues and serum of the control, model and α-terpineol groups, respectively. Based on the above differential metabolites, enrichment analysis showed that arachidonic acid (AA) metabolism was reprogrammed in both mouse lung tissues and serum. 5-Lipoxygenase (5-LOX) and cysteinyl leukotrienes (CysLTs) are the key enzyme and the end product of AA metabolism, respectively. In-depth studies have shown that pretreatment with α-terpineol can alleviate asthma by decreasing the AA level, downregulating the expression of 5-LOX and reducing the accumulation of CysLTs in mouse lung tissues. In summary, this study demonstrates that α-terpineol is a potential agent that can prevent asthma via regulating disordered AA metabolism.

Integrated serum, urine metabolomics and 16S rRNA sequencing to investigate the modulatory effect of Ziziphi Spinosae Folium flavonoid on D-galactose-induced aging of rats

Ziziphi Spinosae Folium, the leaf of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou (LZJS), was widely distributed in northern China. Our previous study showed that LZJS flavonoid (LZJSF) exerted antioxidant activity at chemical and PC12 cell levels, respectively. Here, we further studied the function of LZJSF on aging-related oxidative stress in D-galactose (D-gal)-induced rats and the potential mechanisms were explored. The aging model was established by intraperitoneal injection of D-gal (300 mg·kg−1·day−1) for 36 days, the low-dose of LZJSF (LLZJSF 100 mg·kg−1·day−1) and the high-dose of LZJSF (HLZJSF, 200 mg·kg−1·day−1) were administered daily by oral gavage at the same time, respectively. Their spatial and learning memory abilities were evaluated by the Morris water maze test. HLZJSF was observed to significantly ameliorate cognitive ability and oxidative indexes, such as reduction of MDA and augmentation of SOD, GSH-Px, T-AOC and CAT, and the effect of HLZJSF on these indexes was stronger than that of LLZJSF. A precise and well-defined research strategy was successfully applied to screen serum differential metabolites. Furthermore, integrated serum and urine metabolomics showed that the derivations of nine significant differential metabolites could be regulated by administration of HLZJSF, which suggested that the intervention effect of HLZJSF against aging may involve in the amino acid metabolism including D-Glutamine and D-glutamate, alanine, aspartate and glutamate, arginine and proline metabolism and arginine biosynthesis. 16S rRNA sequencing analysis showed that HLZJSF could descend the relative abundance of Firmicutes and Actinobacteria, as well as the ratio of Firmicutes/Bacteroidetes, and increase the relative abundance of Bacteroidetes and Proteobacteria. Finally, correlation analysis further showed that the beneficial effects of HLZJSF resulted from the regulation of the disturbance of gut microbiota through the “microbiota-gut-brain” axis to affect amino acid metabolism and regulate oxidative stress. This study will provide a foundation for the development and utilization of LZJSF as functional foods and healthy beneficial food products.

Urine metabolomics phenotyping and urinary biomarker exploratory in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease is a prevalent disease with a heavy global burden and is suggested to be a metabolic disease in the brain in recent years. The metabolome is considered to be the most promising phenotype which reflects changes in genetic, transcript, and protein profiles as well as environmental effects. Aiming to obtain a comprehensive understanding and convenient diagnosis of MCI and AD from another perspective, researchers are working on AD metabolomics. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels. We first enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples and conducted an LC-MS/MS analysis. In parallel, clinical data were collected and clinical examinations were performed. After statistical and bioinformatics analyzes, significant risk factors and differential urinary metabolites were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM. Fifty-seven AD patients, 43 MCI patients and 62 CN subjects were enrolled. A total of 2,140 metabolites were identified among which 125 significantly differed between the AD and CN groups, including 46 upregulated ones and 79 downregulated ones. In parallel, there were 93 significant differential metabolites between the MCI and CN groups, including 23 upregulated ones and 70 downregulated ones. AD diagnostic panel (30 metabolites+ age + APOE) achieved an AUC of 0.9575 in the test set while MCI diagnostic panel (45 metabolites+ age + APOE) achieved an AUC of 0.7333 in the test set. Atropine, S-Methyl-L-cysteine-S-oxide, D-Mannose 6-phosphate (M6P), Spiculisporic Acid, N-Acetyl-L-methionine, 13,14-dihydro-15-keto-tetranor Prostaglandin D2, Pyridoxal 5'-Phosphate (PLP) and 17(S)-HpDHA were considered valuable for both AD and MCI diagnosis and defined as hub metabolites. Besides, diagnostic metabolites were weakly correlated with cognitive functions. In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN. Atropine, M6P and PLP were evidence-based hub metabolites in AD.

Widely targeted metabolomics analysis reveals the formation of nonvolatile flavor qualities during oolong tea manufacturing: a case study of Jinguanyin.

The manufacturing processes of oolong tea significantly impact its nonvolatile components, leading to the emergence of distinct flavor attributes. Understanding the dynamic changes in nonvolatile components during the manufacturing stages of the Jinguanyin (JGY) cultivar is crucial for unraveling the potential mechanism behind flavor formation. Comprehensive metabolomics and sensomics analyses were conducted to investigate the dynamic changes in nonvolatile components throughout various phases of oolong tea processing, focusing on the JGY cultivar. A total of 1,005 nonvolatile metabolites were detected, with 562 recognized as significant differential metabolites during various phases of oolong tea processing. Notably, the third turning-over, third setting, and high-temperature treatments exhibited the most significant effects on the nonvolatile metabolites of oolong tea. JGY finished tea demonstrated a characteristic flavor profile, marked by mellowness, sweetness in aftertaste, and a significant Yin rhyme. This flavor profile was collectively promoted by the accumulation of amino acids and organic acids, the decrease in flavonols (3-O-glycosides) and sugar substances, the alteration of phenolic acids, and the stabilization of caffeine. This study contribute to the understanding of the formation of oolong tea flavor qualities. The dynamic changes observed in various types of nonvolatile compounds during oolong tea processing shed light on the intricate interplay of metabolites and their influence on the final flavor characteristics.

Effects of four diets on the metabolism of megalopa metamorphosis of the mud crab, Scylla paramamosain

Dietary intake is an essential source of energy and nutrients, and plays an irreplaceable role in the breeding of S. paramamosain seedlings. In this study, live Artemia nauplii (LA), compound feeds (CF), frozen copepods (FC) and frozen adult Artemia (FA) were utilized as feed during the megalopa stage. To determine the impact that diet has on the metabolism of crablets that underwent metamorphosis from the megalopa stage, analyses of both metabolomics and fatty acid content were conducted. In the LC-MS-based metabolomics analysis, a total of 104, 205 and 83 significantly different metabolites (SDMs) were identified after being fed with FC, FA, and CF, respectively, as compared to the LA group. Furthermore, significant differences in KEGG compounds among the three comparisons exhibited similarity and were mainly associated with categories such as “Lipids”, “Hormones and transmitters”, and “Peptides”. The fatty acid content analysis indicated that the ΣMUFA was significantly higher in the LA and CF groups compared to the other two groups. In contrast, the highest level of ΣPUFA was found in the LA group. In addition, the CF group showed significantly higher expression levels of the fatty acid synthesis genes, FAS and ACC. Conversely, the expression level of the fatty acid decomposition-related gene CPT1 was the highest in the LA group. In comparison with the FA group, the expression level of FABP3 was significantly decreased in the LA and CF groups. In summary, there were significant differences observed in the metabolic profiles of crablets that metamorphosed from the megalopa under different diets. Our experimental results suggested that LA is more advantageous in the cultivation of the S. paramamosain megalopa compared to the other three diets. While it remains a diet that cannot be entirely substituted at present, LA has the potential to improve the culture performance of the S. paramamosain megalopa. The current study could provide valuable data into the development of artificial diets necessary for the future of the mud crab seedling breeding industry.

Transcriptomics and metabolomics study in mouse kidney of the molecular mechanism underlying energy metabolism response to hypoxic stress in highland areas.

Exposure to hypoxia disrupts energy metabolism and induces inflammation. However, the pathways and mechanisms underlying energy metabolism disorders caused by hypoxic conditions remain unclear. In the present study, a hypoxic animal model was created and transcriptomic and non-targeted metabolomics techniques were applied to further investigate the pathways and mechanisms of hypoxia exposure that disrupt energy metabolism. Transcriptome results showed that 3,007 genes were significantly differentially expressed under hypoxic exposure, and Gene Ontology annotation analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis showed that the differentially expressed genes (DEGs) were mainly involved in energy metabolism and were significantly enriched in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) pathway. The DEGs IDH3A, SUCLA2, and MDH2 in the TCA cycle and the DEGs NDUFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1 in the OXPHOS pathway were validated using mRNA and protein expression, and the results showed downregulation. The results of non-targeted metabolomics showed that 365 significant differential metabolites were identified under plateau hypoxia stress. KEGG enrichment analysis showed that the differential metabolites were mainly enriched in metabolic processes, such as energy, nucleotide and amino acid metabolism. Hypoxia exposure disrupted the TCA cycle and reduced the synthesis of amino acids and nucleotides by decreasing the concentration of cis-aconitate, α-ketoglutarate, NADH, NADPH and that of most amino acids, purines, and pyrimidines. Bioinformatics analysis was used to identify inflammatory genes related to hypoxia exposure and some of them were selected for verification. It was shown that the mRNA and protein expression levels of IL1B, IL12B, S100A8 and S100A9 in kidney tissues were upregulated under hypoxic exposure. The results suggest that hypoxia exposure inhibits the TCA cycle and the OXPHOS signalling pathway by inhibiting IDH3A, SUCLA2, MDH2, NDUFFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1, thereby suppressing energy metabolism, inducing amino acid and nucleotide deficiency and promoting inflammation, ultimately leading to kidney damage.

Integrative transcriptomics and metabolomics analysis of body color formation in the common carp

The coloration of aquatic animals influences their adaptability to environment and economic values. The skin color of common carp (Cyprinus carpio) is various between different strains. Hebao red carp is famous for its bright red color, which is different from the brown skin color of wild-type common carp. To reveal the different components and molecular mechanism between skins with red and brown colors, LC-MS and transcript analysis were conducted. 614 significantly different metabolites (SDM) and 392 differentially expressed genes (DEG) were detected between skins of Hebao red carp (HB) and Yellow River carp (YR). There are 35 KEGG pathways shared by DEGs and SDMs, among which microbial metabolism in diverse environments (ko01120), carbon metabolism (ko01200) and metabolic pathways (ko01100) were significantly enriched by DEGs and SDMs. Pathways related to melanin synthesis and retinal metabolism were down-regulated in HB, such as adh8a, adh8b, cyp3a, dhrs3b, mart1, hgd, hpd and maiA, which may induce the disappear of melanocytes and accumulation of carotenoid. The content of lutein in HB skin was significantly higher than in YR. This study shows retinol and carotenoid metabolism is vital in the common carp body color formation, and will help understand the mechanism of color determination in common carp.

Untargeted metabolomics analysis of plasma metabolic characteristics in patients with acne and insulin resistance.

Acne vulgaris is a chronic inflammatory disease with high incidence, diverse clinical manifestations, poor clinical efficacy, and easy recurrence. Recent studies have found that the occurrence of acne is related to metabolic factors such as insulin resistance; however, the specific mechanism of action remains unclear. This study aimed to identify significantly different metabolites and related metabolic pathways in the serum of acne vulgaris patients with or without insulin resistance. LC-MS/MS was used to analyze serum samples from patients about acne with insulin resistance (n = 51) and acne without insulin resistance (n = 69) to identify significant metabolites and metabolic pathways. In this study, 18 significant differential metabolites were screened for the first time. In the positive-ion mode, the upregulated substances were creatine, sarcosine, D-proline, uracil, Phe-Phe, L-pipecolic acid, and DL-phenylalanine; the downregulated substances were tridecanoic acid (tridecylic acid), L-lysine, cyclohexylamine, sphingomyelin (d18:1/18:0), gamma-L-Glu-epsilon-L-Lys, and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine. In the negative-ion mode, the upregulated substance was cholesterol sulfate, and the downregulated substances were D(-)-beta-hydroxybutyric acid, myristic acid, D-galacturonic acid, and dihydrothymine. Cholesterol sulfate showed the most significant expression among all differential metabolites (VIP = 7.3411). Based on the KEGG database, necroptosis and ABC transporters were the most significantly enriched metabolic pathways in this experiment. The differential metabolites and pathways identified in this study may provide new possibilities for the clinical diagnosis and development of targeted drugs for acne patients with insulin resistance.

Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta.

Nucleosides, organic acids, and amino acids separated from Morchella esculenta are well known for their nutritional value and flavor. However, how to increase their content in a better way has been a challenge. In this study, the effect of adding jujube kernel on the active components of M. esculenta was investigated by untargeted metabolomics using UPLC-MS/MS. A total of 1,243 metabolites were identified, of which 262 metabolites (21.078%) were organic acids and derivatives, 245 metabolites (19.71%) were lipids and lipid-like molecules, and 26 metabolites (2.092%) were nucleosides, nucleotides, and analogues. Subsequently, differential metabolites between groups were screened by the orthogonal partial least squares-discriminant analysis model, which showed that 256 metabolites were identified as significantly different for the positive ion model and 149 for the negative ion model. Moreover, significant differential metabolites (VIP > 1, P < 0.05) in annotation of kyoto encyclopedia of genes and genomes pathway were investigated, which showed that ABC transporters were the most commonly observed transporters, followed by pyrimidine metabolism and purine metabolism. The results indicated that the main components of jujube kernel might be conducive to the accumulation of nucleoside organic acids and amino acid metabolites in M. esculenta. These results provide important information for the understanding of more suitable way for cultivation of M. esculenta.