Tyrosine Metabolic Pathway Research Articles

Bergamot polysaccharides relieve DSS-induced ulcerative colitis via regulating the gut microbiota and metabolites

This study aimed to explore the efficacy of polysaccharides from bergamot (BP) in alleviating DSS-induced colitis. Results showed that BP was primarily composed of two components, BP-1 and BP-2, with similar monosaccharide compositions to BP (mainly glucose and xylose) and molecular weights (Mw) of 4.50 × 105 and 2.35 × 105 Da. This study found BP relieved disease symptoms such as weight loss and colon shortening in mice with colitis. Gut microbiota and metabolomics analysis revealed that the BP could also promote the proliferation of beneficial bacteria such as Bifidobacteria, Butyrivibrio, and Blautia, resulting in increased levels of SCFAs and L-phenylalanine, which were associated with phenylalanine, tyrosine, and tryptophan metabolism pathways. Further analysis validated the inflammatory activity of L-phenylalanine. Hence, BP may relieve colitis symptoms by regulating the gut microbiota and metabolism, which reduced inflammation and enhanced the expression of tight junctional proteins (TJ proteins) and mucin in the intestine.

Urinary Metabolic Distinction of Niemann-Pick Class 1 Disease through the Use of Subgroup Discovery.

In this investigation, we outline the applications of a data mining technique known as Subgroup Discovery (SD) to the analysis of a sample size-limited metabolomics-based dataset. The SD technique utilized a supervised learning strategy, which lies midway between classificational and descriptive criteria, in which given the descriptive property of a dataset (i.e., the response target variable of interest), the primary objective was to discover subgroups with behaviours that are distinguishable from those of the complete set (albeit with a differential statistical distribution). These approaches have, for the first time, been successfully employed for the analysis of aromatic metabolite patterns within an NMR-based urinary dataset collected from a small cohort of patients with the lysosomal storage disorder Niemann-Pick class 1 (NPC1) disease (n = 12) and utilized to distinguish these from a larger number of heterozygous (parental) control participants. These subgroup discovery strategies discovered two different NPC1 disease-specific metabolically sequential rules which permitted the reliable identification of NPC1 patients; the first of these involved 'normal' (intermediate) urinary concentrations of xanthurenate, 4-aminobenzoate, hippurate and quinaldate, and disease-downregulated levels of nicotinate and trigonelline, whereas the second comprised 'normal' 4-aminobenzoate, indoxyl sulphate, hippurate, 3-methylhistidine and quinaldate concentrations, and again downregulated nicotinate and trigonelline levels. Correspondingly, a series of five subgroup rules were generated for the heterozygous carrier control group, and 'biomarkers' featured in these included low histidine, 1-methylnicotinamide and 4-aminobenzoate concentrations, together with 'normal' levels of hippurate, hypoxanthine, quinolinate and hypoxanthine. These significant disease group-specific rules were consistent with imbalances in the combined tryptophan-nicotinamide, tryptophan, kynurenine and tyrosine metabolic pathways, along with dysregulations in those featuring histidine, 3-methylhistidine and 4-hydroxybenzoate. In principle, the novel subgroup discovery approach employed here should also be readily applicable to solving metabolomics-type problems of this nature which feature rare disease classification groupings with only limited patient participant and sample sizes available.

Genetic insights into fiber quality, coat color and adaptation in Changthangi and Muzzafarnagri sheep: A comparative skin transcriptome analysis

Changthangi sheep, which inhabit the high-altitude regions of Ladakh, are known for their fine fiber production and are characterized by grey skin and either black or white coats. In contrast, Muzzafarnagri sheep from the plains of Uttar Pradesh produce coarse wool and have white skin and coats. We conducted comparative global gene expression profiling on four biological replicates of skin from each breed. Notably, our analysis identified 149 up-regulated genes and 2,139 down-regulated genes in Changthangi sheep compared to Muzzafarnagri sheep, with a p-adjusted value (padj) of ≤0.05 and a Log2 fold change of ≥1.5. Gene Ontology analysis of the up-regulated genes revealed an enrichment of terms related to melanin biosynthesis and developmental pigmentation. Additionally, enriched KEGG pathways included tyrosine metabolism and metabolic pathways. Among the melanogenesis-related genes that exhibited higher expression in Changthangi sheep were TYR, TYRP1, DCT, SLC45A2, PMEL, MLANA, and OCA2. These findings confirm melanin's role in both the animals' black coat color and UV protection at high-altitude. Furthermore, we observed more pronounced expression of genes related to fiber quality, namely KRTAP6, KRTAP7, KRTAP13, and KRTAP2, in the fine wool-producing sheep from Ladakh. The results of the RNA sequencing were validated using real-time PCR on 10 genes governing fiber quality and coat color, with ACTB and PPIB serving as reference genes. In conclusion, our comparative skin transcriptome analysis of Changthangi and Muzzafarnagri sheep sheds light on the genetic differences associated with distinct phenotypic traits and environmental adaptability, offering valuable insights into the underlying mechanisms.

New insights into the regulation mechanism of Pacific white shrimp (Litopenaeus vannamei) hepatopancreas under 4-nonylphenol exposure using transcriptome analysis

4-Nonylphenol (4-NP) is one of the common endocrine-disrupting chemicals (EDCs) in estuaries and coastal zones, which can exert detrimental effects on the physiological function of aquatic organisms. However, the molecular response triggered by 4-NP remains largely unknown in Pacific white shrimp (Litopenaeus vannamei). In this study, transcriptomic analysis was performed to investigate the underlying mechanisms of 4-NP toxicity in the hepatopancreas of L. vannamei. Nine RNA-Seq libraries were generated from L. vannamei at 0 h, 24 h, and 48 h following exposure to 4-NP. Compared with 0 h vs 24 h, 962 up- and 463 down-regulated differentially expressed genes (DEGs) were identified, indicating that many genes in L. vannamei were induced to resist adverse circumstances by 4-NP exposure. In contrast, 902 up- and 1027 down-regulated DEGs were revealed in the comparison of 0 h vs 48 h, demonstrating that prolonged exposure to the stress from 4-NP resulted in more inhibited genes. To validate the accuracy of the transcriptome data, eight DEGs were selected for quantitative real-time polymerase chain reaction (qRT-PCR), which were consistent with the RNA-Seq results. Through KEGG pathway enrichment analysis, three specific pathways related to hormonal effects and endocrine function of L. vannamei were enriched significantly, including tyrosine metabolism, insect hormone biosynthesis, and melanogenesis. After 4-NP stress, genes involved in tyrosine metabolism (Tyr) and melanogenesis pathway (AC, CBP, Wnt, Frizzled, Tcf, and Ras) were induced to promote melanin pigment to help shrimp resist adverse environments. In the insect hormone biosynthesis, ALDH, CYP15A1, CYP15A1/C1, and JHE genes were activated to synthesize juvenile hormone (JH), while Spook, Phm, Sad, and CYP18A1 were induced to generate molting hormone. There is an enhanced interaction between the molting hormone and JH, with JH playing a dominant role and maintaining its “classic status quo action”. Our study demonstrated that 4-NP exposure led to impairments of biological functions in L. vannamei hepatopancreas. The genes and pathways identified provide novel insights into the molecular mechanisms underlying 4-NP toxicity effects in prawns and enrich the information on the toxicity mechanism of crustaceans in response to EDCs exposure.

Insight into the mechanisms of neuroendocrine toxicity induced by 6:2FTCA via thyroid hormone disruption

6:2 fluorotonic carboxylic acid (6:2 FTCA), a novel substitute for perfluorooctanoic acid (PFOA), is being used gradually in industrial production such as coatings or processing aids, and its detection rate in the aqueous environment is increasing year by year, posing a potential safety risk to aquatic systems and public health. However, limited information is available on the effects and mechanism of 6:2 FTCA. Therefore, this study was conducted to understand better the neuroendocrine effects of early exposure to 6:2 FTCA and the underlying mechanisms on zebrafish. In this study, zebrafish embryos were treated to varied doses of 6:2 FTCA (0, 0.08 μg/mL, 0.8 μg/mL and 8 μg/mL) at 4 h post-fertilization (hpf) for a duration of six days, which exhibited a pronounced inhibition of early growth and induced a disorganized swim pattern characterized by reduced total swim distance and average swim speed. Simultaneously, the thyroid development of zebrafish larvae was partially hindered, accompanied by decreased T3 levels, altered genes associated with the expression of thyroid hormone synthesis, transformation and transportation and neurotransmitters associated with tryptophan and tyrosine metabolic pathways. Molecular docking results showed that 6:2 FTCA has a robust binding energy with the thyroid hormone receptor (TRβ). Moreover, exogenous T3 supplementation can partially restore the adverse outcomes. Our findings indicated that 6:2 FTCA acts as a thyroid endocrine disruptor and can induce neuroendocrine toxic effects. Furthermore, our results show that targeting TRβ may be a potentially therapeutic strategy for 6:2 FTCA-induced neuroendocrine disrupting effects.

Weighted correlation network analysis of the genes in the eyes of juvenile Plectropomus leopardus provide novel insights into the molecular mechanisms of the adaptation to the background color

Plectropomus leopardus is a valuable marine fish whose skin color is strongly affected by the background color. However, the influence of the visual sense on the skin color variation of P. leopardus remains unknown. In the present study, transcriptome analysis was used to examine the visual response mechanism under different background colors. Paraffin sections of the eyes showed that the background color caused morphological changes in the pigment cells (PCs) and outer nuclear layer (ONL) and the darkening of the iris color. The transcriptome analysis results indicated that the gene expressions in the eyes of P. leopardus were significantly different for different background colors. We identified 4845, 3069, 5874, and 6309 differentially expressed genes (DEGs) in the pairwise comparisons of white vs. initial, blue vs. initial, red vs. initial, and black vs. initial groups, respectively. Some hub genes and key pathways regulating the adaptive mechanism of P. leopardus's eyes to the background color were identified, i.e., the JAK-STAT, mTOR, and Ras signaling pathways, and the ndufb7, slc6a13, and novel.3553 gene. This adaptation was achieved through the synthesis of stress proteins and energy balance supply mediated by hub genes and key pathways. In addition, the phenylalanine metabolism, tyrosine metabolism, and actin cytoskeleton-related processes or pathways and genes were responsible for iris and skin color adaptation. In summary, we inferred that stress protein synthesis, phenylalanine metabolism, and energy homeostasis were critical stress pathways for P. leopardus to adapt its skin color to the environment. These new findings indicate that the P. leopardus skin color variation may have been caused by the environmental adaption of the eyes. The results provide new insights into the molecular mechanisms underlying the skin color adaptation of P. leopardus.

Effects of SLC45A2 and GPNMB on Melanin Deposition Based on Transcriptome Sequencing in Chicken Feather Follicles.

As an essential genetic and economic trait, chicken feather color has long been an important research topic. To further understand the mechanism of melanin deposition associated with coloration in chicken feathers, we selected feather follicle tissues from the neck and wings of chickens with differently colored feathers (yellow, sub-Columbian, and silver) for transcriptome analysis. We focused on genes that were expressed in both the wings and neck and were expressed with the same trends in breeds with two different plumage colors, specifically, SLC45A2, GPNMB, MLPH, TYR, KIT, WNT11, and FZD1. GO and KEGG enrichment analyses showed the DEGs were enriched in melanin-related pathways, such as tyrosine metabolic pathway and melanogenesis, and PPI analysis highlighted the genes SLC45A2 and GPNMB as associated with melanin deposition. Verification experiments in chicken melanocytes demonstrated that these two genes promote melanocyte melanin deposition. These data enrich our knowledge of the mechanisms that regulate chicken feather color.

Early Identification of Serum Biomarkers and Pathways of Sepsis Through GC-MS-Based Metabolomics Analysis.

Early identification of sepsis improves the survival rate; however, it is one of the most challenging tasks for physicians, especially since symptoms are easily confused with those of systemic inflammatory response syndrome (SIRS). Our aim was to explore biomarkers for early identification of sepsis that would aid in its differential diagnosis. Eight patients with SIRS, eight with sepsis, and eight healthy controls were included in this study. Metabolites were screened using gas chromatography-mass spectrometry (GC-MS). Metabolism profiles were analyzed using the untargeted database of GC-MS from Lumingbio (LUG) database, and metabolic pathways were enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The S-plot was used to screen the potential biomarkers distinguishing between patients with SIRS, sepsis, and healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate potential biomarkers between SIRS and sepsis patients. Correlation analysis was used to measure the degree of correlation between differential metabolites. Correlation analysis between 2-deoxy-d-erythro-pentofuranose-5-phosphate and clinical indicators was performed. There were 51 metabolites that were distributed in the SIRS group, and they were enriched with 18 metabolic pathways compared with healthy controls. Moreover, 63 metabolites in the sepsis group were significantly distinguishable compared to the healthy controls, and were associated with 21 metabolic pathways. Methyl 3-o-acetyl-d-galactopyranoside and N-acetylputrescine were found to be candidate biomarkers for distinguishing between SIRS, sepsis, and healthy controls using the S-plot model. Only four differential metabolites, including 2-deoxy-d-erythro-pentofuranose-5-phosphate, terbutaline, allantoic acid, and homovanillic acid (HVA), were enriched in the dopaminergic synapse and tyrosine metabolism pathways when sepsis patients were compared with SIRS patients. The Area Under Curve (AUC) of 2-deoxy-d-erythro-pentofuranose-5-phosphate was 0.9297, indicating a strong diagnostic ability for sepsis. A significant negative correlation was identified between 2-deoxy-d-erythro-pentofuranose-5-phosphate and lactate (r = -0.8756, p = 0.0044). Methyl 3-o-acetyl-d-galactopyranoside and N-acetylputrescine may be used as candidate biomarkers to distinguish SIRS and sepsis patients from healthy controls using GC-MS. 2-deoxy-d-erythro-pentofuranose-5-phosphate may be the candidate biomarker to distinguish sepsis from SIRS. Our study explored candidate biomarkers for the early identification of sepsis, which is vital for improving its prognosis.

Unraveling the differential perturbations of species-level functional profiling of gut microbiota among phases of methamphetamine-induced conditioned place preference

The gut microbiome plays a significant role in methamphetamine addiction. Previous studies using short-read amplicon sequencing have described alterations in microbiota at the genus level and predicted function, in which taxonomic resolution is insufficient for accurate functional measurements. To address this limitation, we employed metagenome sequencing to intuitively associate species to functions of gut microbiota in methamphetamine-induced conditioned place preference. We observed differential perturbations of species-level functional profiling of the gut microbiota across phases of METH-induced CPP, with alterations in SCFA metabolism and bacterial motility at the acquisition phase and substance dependence-alcoholism pathway and amino acid metabolism at the extinction phase. Our findings suggest that reduced beneficial bacteria, i.e., Lactobacillus reuteri, contributed to the alteration of SCFA metabolism, while the increased abundance of Akkermansia muciniphila during the extinction phase may be associated with altered phenylalanine, tyrosine, and tryptophan metabolism and substance dependence pathway. Our study further supports the association between specific microbial taxa and METH-induced rewarding.

Microbial phenolic metabolites 3-(3′,4′-dihydroxyphenyl)propanoic acid and 3′,4′-dihydroxyphenylacetic acid prevent obesity in mice fed with high-fat diet

Obesity is associated with numerous metabolic disorders, and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity. However, the effect of 3-(3′,4′-dihydroxyphenyl)propanoic acid (DHPA) and 3′,4′-dihydroxyphenylacetic acid (DHAA), two main metabolites of dietary polyphenols, on obesity remains poorly understood. In this study, DHPA and DHAA were found to alleviate obesity, as well as regulate insulin resistance, lipid metabolism, and oxidative stress response in high-fat diet (HFD) mice. Surprisingly, the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome, but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion, tyrosine metabolism, pentose phosphate and tricarboxylic acid (TCA) cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Correlation analysis revealed that the differential metabolites are strongly associated with body weight, blood glucose, insulin level, and superoxide dismutase (SOD) enzyme activity. Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose, lipid and tyrosine metabolism pathways.

Defining the toxicological profile of 4-hydroxyphenylpyruvate dioxygenase-directed herbicides to Aedes aegypti and Amblyomma americanum

Inhibitors targeting the 4-hydroxyphenyl pyruvate dioxygenase (HPPD) enzyme are well established herbicides and HPPD is also a primary enzyme within the tyrosine metabolism pathway in hematophagous arthropods, which is an essential metaboilic pathway post-blood feeding to prevent tyrosine-mediated toxicity. The objective of this study was to characterize the toxicity of triketone, pyrazole, pyrazolone, isoxazole, and triazole herbicides that inhibit HPPD to blood-fed mosquitoes and ticks. Topical exposure of nitisinone to blood-fed Aedes aegypti yielded high toxicity with an LD50 of 3.81 ng/insect (95% CI: 3.09 to 4.67 ng; Hillslope: 0.97, r2: 0.99), yet was non-toxic to non-blood fed (NBF) mosquitoes. The rank order of toxicity was nitisinone > tembotrione > pyrazoxyfen > tebuconazole > mesotrione against blood-fed Ae. Aegypti, but nitisinone was approximately 30-fold more toxic than other chemicals tested. We also assessed the toxicity of HPPD-inhibiting herbicides to the lone star tick, Amblyomma americanum and similarly, nitisinone was toxic to Am. americanum with a lethal time to kill 50% of subjects (LT50) of 23 h at 10 μM. Knockdown of the gene encoding the HPPD enzyme was performed through RNA-interference led to significant mortality after blood feeding in both, Ae. aegypti and Am. americanum. Lastly, a fluorescence assay was developed to determine relative quantities of L-tyrosine in Ae. aegypti and Am. americanum treated with HPPD inhibitors. L-tyrosine levels correlated with toxicity with nitisinone exposure leading to increased tyrosine concentrations post-blood feeding. Taken together, these data support previous work suggesting HPPD-inhibitors represent a novel mode of toxicity to mosquitoes and ticks and may represent base scaffolds for development of novel insecticides specific for hematophagous arthropods.

Understanding key genetic make-up of different coat colour in Bayinbuluke sheep through a comparative transcriptome profiling analysis

Coat color is a distinctive feature of mammals, especially in distinguishing animal breeds, and the diversity of animal coat color provides an important model phenotype for exploring gene roles and studying gene mutations. Selective breeding programs can be used to enhance or modify certain physical traits in Bayinbuluke sheep, including their coat color. To elaborately understand the differential expression of coat tissue of Bayinbuluke sheep with respect to coat colour and genetic make ups, the molecular mechanism of the difference in coat color phenotype of the sheep's head and neck was explored through RT-PCR assay based transcriptomic analysis. In this study, sixteen samples of coat tissues of 8 individuals Bayinbuluke sheep with different hair colors were collected for transcriptome sequencing analysis, and the differential expression genes of MEwhite module in BL vs BR group and WGCNA were analyzed by gene ontology and Kyoto Gene Encyclopedia enrichment, and the results were significantly enriched in G protein-coupled receptor, transmembrane signaling receptor activity, tyrosine metabolism, melanin production and other metabolic pathways. The identified DCT, ASIP, GPR143, PMEL, TYRP1 and MC1R genes Bayinbuluke sheep coat have all been linked with important roles in the regulation of melanin synthesis as immune stability. Therefore, understanding the genetic and molecular basis of these pathways can help in developing novel approaches in sheep coat colour as well as improved sheep immunity.

Widely Targeted HPLC-MS/MS Metabolomics Analysis Reveals Natural Metabolic Insights in Insects.

Insect metabolites play vital roles in regulating the physiology, behavior, and numerous adaptations of insects, which has contributed to them becoming the largest class of Animalia. However, systematic metabolomics within the insects is still unclear. The present study performed a widely targeted metabolomics analysis based on the HPLC-MS/MS technology to construct a novel integrated metabolic database presenting comprehensive multimetabolite profiles from nine insect species across three metamorphosis types. A total of 1442 metabolites were identified, including amino acids and their metabolites, organic acids and their derivatives, fatty acids (FAs), glycerophospholipids (GPs), nucleotides and their metabolites, and benzene and its substituted derivatives. Among them, 622 metabolites were used to generate a 0 and 1 matrix based on their presence or absence, and these metabolites were enriched in arachidonic acid metabolism, tyrosine metabolism, phenylalanine metabolism, and insect hormone biosynthesis pathways. Our study revealed that there is a high coincidence between the evolutionary relationships of the species and the hierarchical cluster based on the types of metabolites, while the quantities of the metabolites show a high diversity among species. The metabolome of the nine representative insects provides an important platform for implementing the analysis of insect systemic metabolites and biological events at the metabolic level.

Reduction in gefitinib resistance mediated by Yi-Fei San-Jie pill in non-small cell lung cancer through regulation of tyrosine metabolism, cell cycle, and the MET/EGFR signaling pathway

Ethnopharmacological relevanceThe Chinese herbal prescription Yi-Fei San-Jie pill (YFSJ) has been used for adjuvant treatment in patients with lung cancer for a long time. Aim of the studyReports have indicated that the combination of gefitinib (Gef) with YFSJ inhibits the proliferation of EGFR-TKI-resistant cell lines by enhancing cellular apoptosis and autophagy in non-small cell lung cancer (NSCLC). However, the molecular mechanisms underlying the effect of YFSJ on EGFR-TKI resistance and related metabolic pathways remain to be explored. Materials and methodsIn our report, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), metabolomics, network pharmacology, bioinformatics, and biological analysis methods were used to investigate the mechanism. ResultsThe UPLC-MS/MS data identified 42 active compounds of YFSJ extracts. YFSJ extracts can enhance the antitumor efficacy of Gef without hepatic and renal toxicity in vivo. The analysis of the metabolomics pathway enrichment revealed that YFSJ mainly affected the tyrosine metabolism pathway in rat models. Moreover, YFSJ has been shown to reverse Gef resistance and improve the effects of Gef on the cellular viability, migration capacity, and cell cycle arrest of NSCLC cell lines with EGFR mutations. The results of network pharmacology and molecular docking analyses revealed that tyrosine metabolism-related active compounds of YFSJ affect EGFR-TKIs resistance in NSCLC by targeting cell cycle and the MET/EGFR signaling pathway; these findings were validated by western blotting and immunohistochemistry. ConclusionsYFSJ inhibits NSCLC by inducing cell cycle arrest in the G1/S phase to suppress tumor growth, cell viability, and cell migration through synergistic effects with Gef via the tyrosine metabolic pathway and the EGFR/MET signaling pathway. To summarize, the findings of the current study indicate that YFSJ is a prospective complementary treatment for Gef-resistant NSCLC.

Screening and Identification of Interacting Proteins of Mitfa in Red Tilapia

Skin color variation and differentiation are bottlenecks in the aquaculture industry of red tilapia. The mitfa gene primarily regulates melanocyte survival and proliferation in fish skin pigmentation. In this study, a recombinant expression vector for Mitfa expression was successfully constructed. After induction and purification, nearly 600 μg of Mitfa protein was purified from the fermentation supernatant. His pull-down assay, followed by LC-MS/MS analysis, revealed 10 proteins that interact with the Mitfa protein. Five of these proteins were annotated in the melanogenesis and tyrosine metabolism pathways, including Krt, Tpm, Myh, Tyr and Dct. The purified Mitfa recombinant protein was injected into red tilapia, and its activity and function were examined. The expression levels of the mitfa, tyr, tyrp1, and dct genes increased greatly in the dorsal skin after injection (p < 0.05); meanwhile, the melanin content and tyrosinase activity increased significantly (p < 0.05). These findings provide a theoretical basis for comprehending the function and regulatory mechanism of the red tilapia mitfa gene.

A cross-sectional study identifying disparities in serum metabolic profiles among hypertensive patients with ISH, IDH and SDH subtypes.

It has been well acknowledged that disordered intestinal microflora and their fermented products play crucial role during the development of hypertension (HTN). Aberrant profiles of fecal bacteria have been documented in subjects with isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) previously. Nevertheless, evidence regarding the association of metabolic products in the bloodstream with ISH, IDH and combined systolic and diastolic HTN (SDH) remains scarce. We performed a cross-sectional study and conducted untargeted liquid chromatography-mass spectrometry (LC/MS) analysis on serum samples of 119 participants, including 13 subjects with normotension (SBP < 120/DBP < 80 mm Hg), 11 individuals with ISH (SBP ≥ 130/DBP < 80 mm Hg), 27 patients with IDH (SBP < 130/DBP ≥ 80 mm Hg), and 68 SDH patients (SBP ≥ 130, DBP ≥ 80 mm Hg). Here, the results showed clearly separated clusters in PLS-DA and OPLS-DA score plots for patients suffering from ISH, IDH and SDH when compared with normotension controls. The ISH group was characterized by elevated levels of 3,5-tetradecadien carnitine and notable reduction of maleic acid. While IDH patients were enriched with metabolites in L-lactic acid and depleted in citric acid. Stearoylcarnitine was identified to be specifically enriched in SDH group. The differentially abundant metabolites between ISH and controls were involved in tyrosine metabolism pathways, and in biosynthesis of phenylalanine for those between SDH and controls. Potential linkages between the gut microbial and serum metabolic signatures were detected within ISH, IDH and SDH groups. Furthermore, we found the association of discriminatory metabolites with the characteristics of patients. Our findings demonstrate disparate blood metabolomics signatures across ISH, IDH and SDH, with differentially enriched metabolites and potential functional pathways identified, reveal the underlying microbiome and metabolome network in HTN subtypes, and provide potential targets for disease classification and therapeutic strategy in clinical practice.

Transcriptomic profiling identifies differentially expressed genes and related pathways associated with wound healing and cuproptosis-related genes in Ganxi goats.

Wound healing is very important for the maintenance of immune barrier integrity, which has attracted wide attention in past 10 years. However, no studies on the regulation of cuproptosis in wound healing have been reported. In this study, the skin injury model was constructed in Gnxi goats, and the function, regulatory network and hub genes of the skin before and after the injury were comprehensively analyzed by transcriptomics. The results showed that there were 1,438 differentially expressed genes (DEGs), genes up-regulated by 545 and genes down-regulated by 893, which were detected by comparing day 0 and day 5 posttraumatic skin. Based on GO-KEGG analysis, DEGs that were up-regulated tended to be enriched in lysosome, phagosome, and leukocyte transendothelial migration pathways, while down-regulated DEGs were significantly enriched in adrenergic signaling in cardiomyocytes and calcium signaling pathway. There were 166 overlapped genes (DE-CUGs) between DEGs and cuproptosis-related genes, with 72 up-regulated DE-CUGs and 94 down-regulated DE-CUGs. GOKEGG analysis showed that up-regulated DE-CUGs were significantly enriched in ferroptosis, leukocyte transendothelial migration and lysosome pathways, while down-regulated DE-CUGs were significantly enriched in Apelin signaling pathway and tyrosine metabolism pathways. By constructing and analyzing of protein-protein interaction (PPI) networks of DEGs and DE-CUGs, 10 hub DEGs (ENSCHIG00000020079, PLK1, AURKA, ASPM, CENPE, KIF20A, CCNB2, KIF2C, PRC1 and KIF4A) and 10 hub DE-CUGs (MMP2, TIMP1, MMP9, MMP14, TIMP3, MMP1, EDN1, GCAT, SARDH, and DCT) were obtained, respectively. This study revealed the hub genes and important wound healing pathways in Ganxi goats, and identified the correlation between wound healing and cuproptosis for the first time, and found that MMP2, TIMP1, MMP9, and EDN1 were the core genes associated. This study enriched the transcriptome data of wound healing in Ganxi goats and expanded the research direction of cuproptosis.

Feeding an unsalable carrot total-mixed ration altered bacterial amino acid degradation in the rumen of lambs

The objective of this study was to determine the influence of a total-mixed ration including unsalable carrots at 45% DM on the rumen microbiome; and the plasma, rumen and liver metabolomes. Carrots discarded at processing were investigated as an energy-dense substitute for barley grain in a conventional feedlot diet, and improved feed conversion efficiency by 25%. Here, rumen fluid was collected from 34 Merino lambs at slaughter (n = 16 control; n = 18 carrot) after a feeding period of 11-weeks. The V4 region of the 16S rRNA gene was sequenced to profile archaeal and bacterial microbe communities. Further, a comprehensive, targeted profile of known metabolites was constructed for blood plasma, rumen fluid and biopsied liver metabolites using a gas chromatography mass spectrometry (GC–MS) metabolomics approach. An in vitro batch culture was used to characterise ruminal fermentation including gas and methane (CH4) production. In vivo rumen microbial community structure of carrot fed lambs was dissimilar (P < 0.01; PERMANOVA), and all measures of alpha diversity were greater (P < 0.01), compared to those fed the control diet. Unclassified genera in Bacteroidales (15.9 ± 6.74% relative abundance; RA) were more abundant (P < 0.01) in the rumen fluid of carrot-fed lambs, while unclassified taxa in the Succinivibrionaceae family (11.1 ± 3.85% RA) were greater (P < 0.01) in the control. The carrot diet improved in vitro ruminal fermentation evidenced as an 8% increase (P < 0.01) in DM digestibility and a 13.8% reduction (P = 0.01) in CH4 on a mg/ g DM basis, while the control diet increased (P = 0.04) percentage of propionate within total VFA by 20%. Fourteen rumen fluid metabolites and 27 liver metabolites were influenced (P ≤ 0.05) by diet, while no effect (P ≥ 0.05) was observed in plasma metabolites. The carrot diet enriched (impact value = 0.13; P = 0.01) the tyrosine metabolism pathway (acetoacetic acid, dopamine and pyruvate), while the control diet enriched (impact value = 0.42; P ≤ 0.02) starch and sucrose metabolism (trehalose and glucose) in rumen fluid. This study demonstrated that feeding 45% DM unsalable carrots diversified bacterial communities in the rumen. These dietary changes influenced pathways of tyrosine degradation, such that previous improvements in feed conversion efficiency in lambs could be explained.

Transcriptomic analyses reveal robust changes in the defense response of apples induced by Hannaella sinensis

Research on yeast antagonists has recently demonstrated their safety and efficacy in effectively preventing apple postharvest infections. Our previous study has revealed that the antagonistic yeast Hannaella sinensis has shown control activity against blue mold decay in apples caused by Penicillium expansum. However, the molecular networks underlying H. sinensis-treated apple's disease control mechanisms are not explored. Hence, we aimed to uncover the molecular changes of apples treated with H. sinensis based on transcriptomic analysis. Differentially expressed genes of apples treated with H. sinensis were identified through RNA-seq (152 up-regulated and 1480 down-regulated DEGs) and bioinformatic analysis. Among the DEGs, significant numbers were annotated into apple defense-related pathways, such as plant-pathogen interaction, plant hormone signal transduction, phenylpropanoid biosynthesis, tyrosine metabolism, glycerolipid metabolism, and alpha-linoleic acid pathways related to resistance regulation. Our results indicated that H. sinensis could induce disease resistance in apples, which leads to increased protection against postharvest pathogens. The current study paves the way for further understanding the biocontrol mechanism of antagonistic yeast against postharvest infections by enhancing host defense.

Integrative analysis uncovers the mechanism underlying the environmental adaptation of an indigenous crucian carp (Carassius auratus gibelio) in Dong's Rice Fish Duck System

The golden-back crucian carp (Carassius auratus gibelio), an indigenous fish with significant ecological, economic and cultural value, is found in Dong's Rice Fish Duck System, one of the Globally Important Agricultural Heritage Systems in the world. Its pigment cells undergo a complicated series of physiological and biochemical changes, which is mainly related to the specific local altitudinal, temperature and aquaculture methods. To obtain new insights into the underlying molecular mechanisms, a parallel analysis of morphological, physiological, biochemical, transcriptomic and proteomic of C. gibelio scales and skins with various colors were conducted. The greenish grey scales (Ggsc) and skins (Ggsk) were dominated by dendritic melanocytes, the golden scales (Gsc) and skins (Gsk) were dominated by xanthophores, and no iridophores were found. The activities of SOD and MDA were significantly high in Ggsc, while tyrosinase activity and melanin content were highest in Ggsk. Only two carotenoid components, xanthophyll and β-carotene were detected, and both abundant in Gsc and Gsk. These findings may be related to the irregular distribution of pigment cells. Furthermore, 1308 transcripts and 801 proteins were recognized with significant differential abundances in pairwise comparisons. Using KEGG pathway and protein-protein interaction network analysis, key candidate genes (e.g., tyr, tyrp1, dct, etc.) and proteins (e.g., ASP1, GOT1, HSPB1, etc.) involved in pigment cell differentiation and pigmentation in the melanogenesis, tyrosine metabolism, MAPK and wnt signaling pathway were identified. Noteworthily, we discovered that genes and proteins corresponding to the cardio adrenergic signaling system and cellular dynamics, such as plcb2, mctp2, MYH2 and TPM1, might influence formation and mobility of melanin granules and be the primary causes of golden skin. Finally, qRT-PCR validation indicated that sequencing results were reliable. With this exploratory multi-omics dataset, our results provide theoretical support to explain the relationship between metabolic regulation and phenotype formation in C. gibelio under special aquaculture conditions.