Metabolism Biosynthesis Research Articles

Response of human metabolism to ultra-low and high nicotine cigarettes based on urine metabolomics and bioinformatic analysis.

This study aimed to evaluate the metabolomic profiles of urine samples obtained from smokers who smoked cigarettes with low and high nicotine content. Three smokers participated in this study. They were given low-nicotine (LN) cigarettes, and urine was collected at the end of the third day for the LN group. After 1 week of not smoking, they were given high-nicotine (HN) cigarettes, and urine was collected for the HN group. Untargeted metabolomics and bioinformatic analysis methods were used for urine analysis. PCA showed a high degree of similarity between samples within the group and a large distance between samples between groups, indicating a significant difference between the two groups. A total of 1150 significantly differential metabolites were selected between the HN and LN groups, such as cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol-N-glucuronide. Two-way hierarchical clustering analysis also suggested noticeable differences between the two comparison groups Enrichment analysis indicates that the differential metabolites between the two groups were mainly enriched in 19 pathways, such as the protein kinase G (cGMP)-protein kinase G (PKG) signaling pathway, adenosine monophosphate (AMP)-activated protein kinase signaling pathway, mammalian target of rapamycin signaling pathway, and Parkinson's disease. Cigarettes with different nicotine content may alter the metabolism of smokers. A total of 1150 significantly different metabolites were identified between the HN and LN groups, which were mainly enriched in ABC transporters, protein kinase G (cGMP)-protein kinase G (PKG) signaling pathway, caffeine metabolism, and arginine biosynthesis pathways.

Sijunzi San alleviates the negative energy balance in postpartum dairy cows by regulating rumen fermentation capacity

IntroductionPostpartum dairy cows are susceptible to negative energy balance caused by decreased feed intake and the initiation of lactation. Sijunzi San, a famous Chinese traditional herbal formulation, can promote gastrointestinal digestion and absorption and improve disorders of intestinal microbiota. Therefore, we hypothesized that Sijunzi San might alleviate negative energy balance in postpartum dairy cows by modulating the structure of the rumen microbiota and enhancing its fermentation capacity.MethodsLiquid chromatography-mass spectrometry (LC–MS/MS) was utilized in vitro to identify the main active ingredients in the Sijunzi San. Techniques including in vitro ruminal fermentation, gas chromatography, and 16S rRNA high-throughput sequencing were employed to evaluate their effects on the structure of the rumen microbiota. To test their in vivo effects, sixteen postpartum Holstein dairy cows, with similar body condition and parity, were randomly assigned to two groups, with 8 cows per group. The CONT group was fed a basic diet, while the SJZS group received an additional 300 g/d of Sijunzi San along with the basic diet, continuously for 7 days. ELISA and untargeted metabolomics using ultra-high-performance liquid chromatography-tandem mass (UHPLC–MS/MS) were employed to assess the impacts on immunoglobulin levels, fat mobilization, and the blood metabolome in postpartum dairy cows.ResultsDoses of 100 to 500 mg of the Sijunzi San significantly enhanced gas production, microbial protein (MCP), and short-chain fatty acid (SCFA) levels, while notably reducing pH and NH3-N content (p < 0.05), exhibiting a significant dose-dependent relationship. The results revealed that 500 mg of the prescription significantly increased the abundances of the Succiniclasticum and Prevotella genera and notably decreased the abundances of the Christensenellaceae_R-7_group, Muribaculaceae, UCG-005, Comamonas, and F082 genera (p < 0.05). Succiniclasticum and Prevotella showed a significant positive correlation with ruminal SCFAs, whereas UCG-005 exhibited a significant negative correlation with them (p < 0.05). Additionally, Luteolin and Glycitein were significantly positively correlated with Prevotella, while Licochalcone B and Liquoric acid were significantly negatively correlated with Comamonas (p < 0.05). Subsequently, the prescription significantly increased the concentrations of IgA, IgM, and microsomal triglyceride transfer protein (MTTP) in the blood (p < 0.01), while reducing the levels of ketones (KET) (p < 0.05), non-esterified fatty acids (NEFA), and triglycerides (TG) (p < 0.01). Notable alterations were observed in 21 metabolites in the blood metabolome (p < 0.05). Additionally, metabolic pathways associated with linoleic acid metabolism and steroid hormone biosynthesis were significantly affected.DiscussionThe findings suggest that administering Sijunzi San to dairy cows during the postpartum period can ameliorate negative energy balance by stimulating rumen fermentation and modifying the composition and abundance of the rumen microbiota.

Metabolomic analysis reveals an important role of sphingosine 1-phosphate in the development of HFMD due to EV-A71 infection.

Hand, foot, and mouth disease (HFMD) is a serious pediatric infectious disease that causes immeasurable physical and mental health burdens. Currently, there is a lack of information on the mechanisms of HFMD severity and early diagnosis. We performed metabolomic profiling of sera from 84 Enterovirus A71 (EV-A71) infections and 45 control individuals. Targeted metabolomics assays were employed to further validate some of the differential metabolic molecules. We identified significant molecular changes in the sera of HFMD patients compared to healthy controls (HCs). A total of 54, 60, 35, and 62 differential metabolites were screened between mild cases and HCs, severe cases and HCs, severe cases and mild cases, and among the three groups, respectively. These differential metabolites implicated dysregulation of the tricarboxylic acid cycle, alanine, aspartate, and glutamate metabolism, and valine, leucine, and isoleucine biosynthesis. The diagnostic panel based on some overlapped differential metabolites could effectively discriminate severe cases from mild cases with an AUC of 0.912 (95% CI: 0.85-0.97) using the logistic regression model. Next, we found the elevation of serum sphingosine 1-phosphate (S1P) level in EV-A71 infection mice, which was similar to clinical observation. Importantly, after blocking the release of S1P by MK571, the clinical symptoms and survival of mice were significantly improved, involving the reduction of leukocyte infiltration in infected brain tissues. Collectively, our data provided a landscape view of metabolic alterations in EV-A71 infected children and revealed regulating S1P metabolism was an exploitable therapeutic target against EV-A71 infection.

Genetic and biochemical determinants in potentially toxic metals resistance and plant growth promotion in Rhizobium sp LBMP-C04.

The association of bacteria resistant to potentially toxic metals (PTMs) with plants to remove, transfer, or stabilize these elements from the soil is an appropriate tool for phytoremediation processes in metal-contaminated environments. The objective of this study was to evaluate the potential ofRhizobiumsp. LBMP-C04 forphytoremediation processes and plant growth promotion in metal-contaminated soils. Functional annotation allowed us to predict a variety of genes related to PTMs resistance and plant growth promotion in the bacterial genome. Resistance genes are mainly associated with DNA repair, and the import or export of metals in bacterial cells to maintain cell homeostasis. Genes that promote plant growth are related to mechanisms of osmotic stress tolerance, phosphate solubilization, nitrogen metabolism, biological nitrogen fixation, biofilm formation, heat shock responses, indole-3-acetic acid (IAA) biosynthesis, tryptophan, and organic acids metabolism. Biochemical tests indicated thatRhizobiumsp. LBMP-C04 can solubilize calcium phosphate and produce siderophores and IAAin vitroin the presence of the PTMs Cd2+,Cu2+,Cr3+,Cr6+, Zn2+, and Ni2+. Results indicate the possibility of usingRhizobiumsp. LBMP-C04 as a potentially efficient bacterium in phytoremediation processesin environments contaminated by PTMs and simultaneously promote plant growth.

Exploring the mechanism of seed shattering in Psathyrostachys juncea through histological analysis and comparative transcriptomics

BackgroundSeed shattering (SS) negatively impacts seed yield in Psathyrostachys juncea. Understanding and improving the SS trait requires elucidating the regulatory mechanisms of SS and identifying the key genes involved.ResultsThis study presents a comprehensive analysis of the abscission zone (AZ) structures at four developmental stages in two P. juncea genotypes. High-SS P. juncea (H) exhibited a significantly higher SS rate than low-SS P. juncea (L) at all four developmental stages. Anatomical analysis revealed that the degree of lignification in the AZ cell walls is related to the integrity of the abscission structure. The degradation of the AZ in H occurred earlier and was more severe compared to L. At different developmental stages of the AZ, H exhibited higher cellulase and polygalacturonase activities and higher abscisic acid contents compared to L. Conversely, L showed higher lignin, cytokinin, auxin, and gibberellin contents than H. Transcriptomic analysis identified key metabolic pathways related to SS in P. juncea, such as phenylpropanoid biosynthesis, fructose and mannose metabolism, galactose metabolism, and pentose and glucuronate interconversions. The integration of morphological, histological, physiochemical, and metabolic data led to the identification of critical genes, including AUX1, CKX, ABF, GH3, 4CL, CCoAOMT, BGAL, Gal, and PG. The roles of these genes were involved in the regulation of plant hormones and in the synthesis and degradation of cell walls within the AZ.ConclusionsThis study provides an in-depth understanding of the regulatory mechanisms of SS in P. juncea through comparative transcriptomic analysis. The SS in P. juncea may result from the degradation of the cell wall regulated by cell wall hydrolases genes. The genes identified in this study provide a basis for the genetic improvement of SS traits and serve as a reference for research on other grass species.

Exosome-delivered NR2F1-AS1 and NR2F1 drive phenotypic transition from dormancy to proliferation in treatment-resistant prostate cancer via stabilizing hormonal receptors

Cancer cells acquire the ability to reprogram their phenotype in response to targeted therapies, yet the transition from dormancy to proliferation in drug-resistant cancers remains poorly understood. In prostate cancer, we utilized high-plasticity mouse models and enzalutamide-resistant (ENZ-R) cellular models to elucidate NR2F1 as a key factor in lineage transition and ENZ resistance. Depletion of NR2F1 drives ENZ-R cells into a relative dormancy state, characterized by reduced proliferation and heightened drug resistance, while NR2F1 overexpression yields contrasting outcomes. Transcriptional sequencing analysis of NR2F1-silenced prostate cancer cells and tissues from the Cancer Genome Atlas-prostate cancer and SU2C cohorts indicated exosomes as the most enriched cell component, with pathways implicated in steroid hormone biosynthesis and drug metabolism. Moreover, NR2F1-AS1 forms a complex with SRSF1 to upregulate NR2F1 expression, facilitating its binding with ESR1 to sustain hormonal receptor expression and enhance proliferation in ENZ-R cells. Furthermore, HnRNPA2B1 interacts with NR2F1 and NR2F1-AS1, assisting their packaging into exosomes, wherein exosomal NR2F1 and NR2F1-AS1 promote the proliferation of dormant ENZ-R cells. Our works offer novel insights into the reawaking of dormant drug-resistant cancer cells governed by NR2F1 upregulation triggered by exosome-derived NR2F1-AS1 and NR2F1, suggesting therapeutic potential for phenotype reversal.Graphical

β-lactam antibiotics induce metabolic perturbations linked to ROS generation leads to bacterial impairment

Understanding the impact of antibiotics on bacterial metabolism is crucial for elucidating their mechanisms of action and developing more effective therapeutic strategies. β-lactam antibiotics, distinguished by their distinctive β-lactam ring structure, are widely used as antimicrobial agents. This study investigates the global metabolic alterations induced by three β-lactam antibiotics-meropenem (a carbapenem), ampicillin (a penicillin), and ceftazidime (a cephalosporin)-in Escherichia coli. Our comprehensive metabolic profiling revealed significant perturbations in bacterial metabolism, particularly in pathways such as glutathione metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism, and purine metabolism. Antibiotic treatment markedly increased reactive oxygen species levels, with meropenem reaching nearly 200 ± 7%, ampicillin at 174 ± 11%, and ceftazidime at 152 ± 7%. Additionally, β-lactam antibiotics elevated 8-OHdG levels to 4.73 ± 0.56-fold for meropenem, 2.49 ± 0.19-fold for ampicillin, and 3.19 ± 0.34-fold for ceftazidime; 8-OHG levels increased to 5.57 ± 0.72-fold for meropenem, 3.08 ± 0.31-fold for ampicillin, and 4.45 ± 0.66-fold for ceftazidime, indicating that oxidative stress enhances oxidative damage to bacterial DNA and RNA. Notably, we observed a selective upregulation of specific amino acids associated with cellular repair mechanisms, indicating a metabolic adaptation to counteract oxidative damage. These findings illustrate that β-lactam antibiotics induce a complex metabolic perturbations associated with ROS production, potentially compromising critical cellular components. This study enhances our understanding of the intricate relationship between antibiotic action and bacterial metabolism, providing valuable insights for developing effective strategies against antibiotic-resistant pathogens.

Multi-omics analysis reveals genetic architecture and local adaptation of coumarins metabolites in Populus

BackgroundAccumulation of coumarins plays key roles in response to immune and abiotic stress in plants, but the genetic adaptation basis of controlling coumarins in perennial woody plants remain unclear.ResultsWe detected 792 SNPs within 334 genes that were significantly associated with the phenotypic variations of 15 single-metabolic traits and multiple comprehensive index, such as principal components (PCs) of coumarins metabolites. Expression quantitative trait locus mapping uncovered that 337 eQTLs associated with the expression levels of 132 associated genes. Selective sweep revealed 55 candidate genes have potential selective signature among three geographical populations, highlighting that the coumarins biosynthesis have been encountered forceful local adaptation. Furthermore, we constructed a genetic network of seven candidate genes that coordinately regulate coumarins biosynthesis, revealing the multiple regulatory patterns affecting coumarins accumulation in Populus tomentosa. Validation of candidate gene variations in a drought-tolerated population and DUF538 heterologous transformation experiments verified the function of candidate genes and their roles in adapting to the different geographical conditions in poplar.ConclusionsOur study uncovered the genetic regulation of the coumarins metabolic biosynthesis of Populus, and offered potential clues for drought-tolerance evaluation and regional improvement in woody plants.

Response of soybean root exudates and related metabolic pathways to low phosphorus stress.

Phosphorus (P) is an essential elemental nutrient required in high abundance for robust soybean growth and development. Low P stress negatively impacts plant physiological and biochemical processes, such as photosynthesis, respiration, and energy transfer. Soybean roots play key roles in plant adaptive responses to P stress and other soil-related environmental stressors. Study the changes in soybean root exudates and differences in related metabolic pathways under low phosphorus stress, analyzing the response mechanism of soybean roots to phosphorus stress from the perspective of root exudates, which provide a theoretical basis for further analyzing the physiological mechanism of phosphorus stress on soybean. In this study, soybean roots were exposed to three phosphate levels: 1 mg/L (P stress), 11 mg/L (P stress) and 31 mg/L (Normal P) for 10 days and 20 days, then root exudates were analyzed via ultra-high-performance liquid chromatography-mass spectrometry to identify effects of P stress on root metabolite profiles and associated metabolic pathways. Our results revealed that with increasing P stress severity and/or duration, soybean roots produced altered types, quantities, and increased numbers of exudate metabolites (DMs in the P1 group were primarily upregulated, whereas those in the P11 group were predominately downregulated) caused by changes in regulation of activities of numerous metabolic pathways. These pathways had functions related to environmental adaptation, energy metabolism, and scavenging of reactive oxygen species and primarily included amino acid, flavonoid, and nicotinate and nicotinamide metabolic pathways and pathways related to isoquinoline alkaloid biosynthesis, sugar catabolism, and phospholipid metabolism. These metabolites and metabolic pathways lay a foundation to support further investigations of physiological mechanisms underlying the soybean root response to P deficiency.

Combined transcriptome and metabolome analysis revealed the antimicrobial mechanism of Griseorhodin C against Methicillin-resistant Staphylococcus aureus

The global rise of multidrug-resistant pathogens, particularly Methicillin-resistant Staphylococcus aureus (MRSA), has become a critical public health concern, necessitating the urgent discovery of new antimicrobial agents. Griseorhodin C, a hydroxyquinone compound isolated from Streptomyces, has demonstrated significant inhibitory effects against MRSA. In this study, we employed a comprehensive approach combining transcriptome and metabolome analyses to investigate the underlying antimicrobial mechanism of Griseorhodin C. Our findings reveal that Griseorhodin C interferes with multiple bacterial metabolic pathways, including those essential for the biosynthesis and metabolism of amino acids, purine metabolism and energy metabolism, ultimately leading to bacterial growth inhibition and cell death. Notably, Griseorhodin C showed superior inhibitory effects compared to the clinical standard, vancomycin, both in vivo and vitro. These results highlight the potential of Griseorhodin C as a promising candidate for the development of new therapeutic strategies aimed at combating MRSA infections. The study underscores the importance of exploring natural products as sources of novel antibiotics in the ongoing fight against antimicrobial resistance.

Transcriptome Reveals Molecular Mechanisms of Neuroendocrine Regulation of Allometric Growth in the Red Swamp Crayfish Procambarus clarkii.

Allometric growth is a typical characteristic of crustaceans, which mainly occurs among individuals, life stages, tissues, and between sexes. The red swamp crayfish Procambarus clarkii is an economically important crustacean species in the world. To date, the molecular regulatory mechanisms of neuroendocrine system in the allometric growth of P. clarkii remain unclear. In this study, P. clarkii exhibiting significant allometric growth among individuals were sampled from three full-sibling families. The brain, eyestalk, nerve cord, and Y-organ were dissected for transcriptome analysis. Key functional genes were identified by random forest and DESeq2 methods. The gene pathways were enriched utilizing Kyoto Encyclopedia Genes and Genomes (KEGG) analysis. Gene topological analysis was established through weighted gene co-expression network analysis (WGCNA), and hub genes were screened by protein-protein interaction (PPI) networks. Transcriptomic analysis results were validated via qRT-PCR. RNA-Seq identified 31 differentially expressed genes (DEGs) (7 up- and 24 downregulated); 301 DEGs (23 up- and 278 downregulated); 1308 DEGs (474 up- and 834 downregulated); and 64 DEGs (52 up- and 12 downregulated) in the brain, eyestalk, Y-organ, and nerve cord, respectively. Crucial functional genes such as CHIA in the brain and perlucin-like in the eyestalk were notably identified. WGCNA revealed two hub modules, while PPI networks identified neuroendocrine regulators module which hub genes mainly including CP1876-like and cuticle protein AM1199-like, and structural components module which hub genes mainly including CUB& CCP Domain-Containing Protein, ARRDC, and E3 Ubiquitin protein ligase MCYCBP2-like. Correspondingly, the significant gene pathways such as amino sugar and nucleotide sugar metabolism (pcla00520) and insect hormone biosynthesis (pcla00981) were enriched. The results revealed the complex interactions and regulatory relationships of hub genes within hub modules to coordinate molting and growth. The results of RNA-Seq analysis were validated by the consistency of gene expression in qRT-PCR. In present study, key functional genes in the neuroendocrine system regulating allometric growth among individuals were identified, and significant pathways mainly include hormone synthesis were screened, thus constructing a neuroendocrine molecular regulatory network for the allometric growth of P. clarkii. Building on these investigations, a comprehensive mechanism whereby neuroendocrine regulators interact with structural components to coordinate molting and growth was proposed. The result would provide valuable insights into the molecular regulatory mechanisms of allometric growth, highlighting the interplay between the neuroendocrine system and relevant tissues.

Comprehensive Blood Metabolome and Exposome Analysis, Annotation, and Interpretation in E-Waste Workers

Background: Electronic and electrical waste (e-waste) production has emerged to be of global environmental public health concern. E-waste workers, who are frequently exposed to hazardous chemicals through occupational activities, face considerable health risks. Methods: To investigate the metabolic and exposomic changes in these workers, we analyzed whole blood samples from 100 male e-waste workers and 49 controls from the GEOHealth II project (2017–2018 in Accra, Ghana) using LC-MS/MS. A specialized computational workflow was established for exposomics data analysis, incorporating two curated reference libraries for metabolome and exposome profiling. Two feature detection algorithms, asari and centWave, were applied. Results: In comparison to centWave, asari showed better sensitivity in detecting MS features, particularly at trace levels. Principal component analysis demonstrated distinct metabolic profiles between e-waste workers and controls, revealing significant disruptions in key metabolic pathways, including steroid hormone biosynthesis, drug metabolism, bile acid biosynthesis, vitamin metabolism, and prostaglandin biosynthesis. Correlation analyses linked metal exposures to alterations in hundreds to thousands of metabolic features. Functional enrichment analysis highlighted significant perturbations in pathways related to liver function, vitamin metabolism, linoleate metabolism, and dynorphin signaling, with the latter being observed for the first time in e-waste workers. Conclusions: This study provides new insights into the biological impact of prolonged metal exposure in e-waste workers.

Pasteurized Akkermansia muciniphila Ameliorates Preeclampsia in Mice by Enhancing Gut Barrier Integrity, Improving Endothelial Function, and Modulating Gut Metabolic Dysregulation

Preeclampsia (PE) is a serious complication of pregnancy linked to endothelial dysfunction and an imbalance in the gut microbiota. While Akkermansia muciniphila (AKK) has shown promise in alleviating PE symptoms, the use of live bacteria raises safety concerns. This study explored the potential of pasteurized A. muciniphila (pAKK) as a safer alternative for treating PE, focusing on its effects on endothelial function and metabolic regulation. A PE mouse model was induced via the nitric oxide synthase inhibitor L-NAME, followed by treatment with either pAKK or live AKK. Fecal metabolomic profiling was performed via liquid chromatography–tandem mass spectrometry (LC-MS/MS), and in vivo and in vitro experiments were used to assess the effects of pAKK on endothelial function and metabolic pathways. pAKK exhibited therapeutic effects comparable to those of live AKK in improving L-NAME-induced PE-like phenotypes in mice, including enhanced gut barrier function and reduced endotoxemia. pAKK also promoted placental angiogenesis by restoring endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production. The in vitro experiments further confirmed that pAKK alleviated L-NAME-induced NO reduction and endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). Metabolomic analysis revealed that both pAKK and live AKK reversed metabolic disturbances in PE by modulating key metabolites and pathways related to unsaturated fatty acid biosynthesis, folate, and linoleic acid metabolism. As a postbiotic, pAKK may support existing treatments for preeclampsia by improving gut barrier function, restoring endothelial function, and regulating metabolic dysregulation, offering a safer alternative to live bacteria. These findings highlight the potential clinical value of pAKK as an adjunctive therapy in managing PE.

Biochemical composition and transcriptome analysis revealed nutrients consumption and physiological characteristics of Chinese sturgeon larvae during yolk-sac stage

During the yolk stage, the nutrients of larvae consumed are from the yolk sac, which greatly affect the survival and quality of fish. The aim of this study was to investigate the metabolic changes, physiological characteristics and the related molecular mechanism of Chinese sturgeon (Acipenser sinensis) larvae during yolk stage by biochemical analyses in combination with transcriptome analysis of larvae at three developmental stages (vertical, flat and benthic). The results showed that both total amino acid and protein contents showed a trend of first decreasing and then increasing. The lipid content was stable in the early stages, but decreased significantly in the benthic stage (P < 0.05). In terms of amino acid profile, the contents of leucine, isoleucine and lysine were relatively high in essential amino acids (EAAs), and the contents of glutamate, aspartate and serine were relatively high in non-essential amino acid (NEAA). As for fatty acid content, the most abundant fatty acids are C16:0 (palmitic acid), C18:1 (oleic acid), C18:2n-6 (linoleic acid) and C22:6n-3 (docosahexaenoic acid, DHA). The results of transcriptome analysis showed that 4936 genes were up-regulated and 3079 genes were down-regulated from vertical stage to flat stage, and 1703 genes were up-regulated and 837 genes were down-regulated from flat stage to benthic stage, respectively. According to KEGG enrichment analysis on the differentially expressed genes (DEGs), the up-regulated DEGs mGlu3, mGlu5, NMDAR, PepT1, TAT1, EAAT3, CYP51A1 and CYP7A1 were significantly enriched in pathways related to the nervous system, protein digestion and absorption, steroid synthesis, cholesterol metabolism and bile acid biosynthesis in early development of larvae. Down-regulated DEGs Drg1, NHP2, KRE33 and MPP10 were enriched in the ribosome biogenetic pathway. In late development, up-regulated DEGs, cGAS, IRF3, TRAF2, MHC-I, MHC-II and TAR2, were enriched in pathways associated with innate and adaptive immunity. Down-regulated DKK2 and FGFRs, ITGAs were enriched in Wnt signaling pathway and PI3K-AKT pathway, respectively. In summary, this study revealed that the larval fish consumed protein as the main nutrient from the vertical stage to the flat stage, while mainly consumed lipid from the flat stage to the benthic stage, and highlighted the pathways of DEGs involved in the nervous system and immune system, which would provide new ideal to the high quality larvae production in Chinese sturgeon, thus benefit species protection.

Transcriptome and metabolome revealed the effects of hypoxic environment on ovarian development of Tibetan sheep

Many studies on the adaptability of Tibetan sheep to hypoxia have been reported, but little attention has been paid to the reproduction of Tibetan sheep living at an altitude of more than 4000 m. In this study, the ovaries of Alpine Merino sheep (AM) living in middle-high altitude areas (2500 m) and the ovaries of Gangba Tibetan sheep (GB) and Huoba Tibetan sheep (HB) living in ultra-high altitude areas (4400 m or more) were collected. Through morphological, transcriptomics and metabolomics, the effects of ultra-high altitude areas on Tibetan sheep ovarian development and the molecular mechanism of sheep's adaptability to ultra-high altitude environment were explored. The results showed that the number of granulosa cells in AM was significantly higher than that in GB and HB. The transcriptome revealed several genes related to follicular development, such as DAPL1, IGFBP1, C5, GPR12, STRA6, BMPER, etc., which were mainly enriched in related pathways such as cell growth and development. Through metabolomics analysis, it was found that the differential metabolites between the three groups of sheep were mainly lipids and lipid-like small molecules, such as Glycerol 3-Phosphate, PC (16: 0 / 18: 3 (9Z, 12Z, 15Z)), mainly enriched in lipid metabolism and other related pathways. The results of combined analysis showed that Tryptophan metabolism and Steroid hormone biosynthesis may have a significant effect on Tibetan sheep follicular development. Some genes (including HSD17B7, CYP11A1, CYP19, HSD3B1, CYP17, etc.) and some metabolites (including Cortisone, 2-Methoxyestrone, etc.) are enriched in these pathways, regulating ovarian and follicular development by affecting estrogen, progesterone, etc.. The results further revealed the molecular mechanism of Tibetan sheep to adapt to the ultra-high altitude environment and maintain normal ovarian and follicular development through the regulation of genes and metabolites.

Combined transcriptome and metabolome analysis reveals the mechanism of high nitrite tolerance in freshwater mussel Anodonta woodiana

Nitrite contamination and stress on aquatic organisms are increasingly emphasized in freshwater ecosystems. Freshwater bivalves exhibit high tolerance to nitrite; however, the underlying mechanism is unknown. Accordingly, this study investigated the tolerance mechanism of the globally occurring freshwater bivalve Anodonta woodiana. A. woodiana were exposed to nominal concentrations of 0, 250, 500, 1000, 2000, and 4000 mg/L nitrite for 96 h to calculate the 96-h median lethal concentration (96-h LC50). A combined transcriptome and metabolome analysis of the hemolymph (the most vital component of the bivalve immune system) was performed after exposing A. woodiana to 300 mg/L nitrite (approximately half the 96-h LC50) for 96 h. The 96-h LC50 of nitrite in A. woodiana was 618.7 mg/L. Transcriptome analysis identified 5600 differentially expressed genes (DEGs) primarily related to ribosomes, lysosomes, DNA replication, and nucleotide excision repair. Metabolome analysis identified 216 differentially expressed metabolites (DEMs) primarily involved in biosynthesis of amino acids, 2-oxocarboxylic acid metabolism, protein digestion and absorption, aminoacyl-tRNA biosynthesis, nucleotide metabolism, ABC transporters, and valine, leucine and isoleucine degradation. Combined transcriptome and metabolome analysis revealed that DEGs and DEMs were primarily associated with nucleotide (purine and pyrimidine) and amino acid metabolism (including aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, arginine and proline metabolism, and valine, leucine and isoleucine degradation) as well as the immune system (necroptosis and glutathione metabolism). This study is the first to describe the high tolerance of A. woodiana to nitrite and elucidate the molecular mechanisms underlying high nitrite tolerance in mussels.

Integrated inactivation of Microcystis aeruginosa and degradation of microcystin-LR by direct current glow discharge plasma in liquid-phase: Mechanisms and cell deactivation process

The frequent occurrence of blooms of Microcystis aeruginosa (M. aeruginosa) and the subsequent release of microcystin-LR (MC-LR) in eutrophic waters pose a serious threat to aquatic ecosystems. This study investigated the optimal conditions for inactivating M. aeruginosa and the degrading MC-LR using direct current glow discharge plasma in liquid phase (DC-LGDP), analyzed the potential inactivation mechanisms and the cell deactivation process of M. aeruginosa. The results showed that DC-LGDP generated reactive species (i.e., •OH, 1O2, and H2O2), active Cl and electroporation effect collectively contributed to inactivation of M. aeruginosa and degradation of MC-LR. The 97.07% inactivation efficiency of M. aeruginosa and 94.98% degradation rate of MC-LR were achieved with higher energy yield and without generating nitrogen oxides. Meanwhile, DC-LGDP destroyed the cell integrity, eliminated their antioxidant capacity and reduced the content of photosynthetic pigments. The transcriptome analysis indicated that the transcripts of genes related to photosynthesis, ribosome biosynthesis, ABC transporters, and nitrogen metabolism pathway in M. aeruginosa were altered by DC-LGDP. This study provides insights into the inactivation of M. aeruginosa by DC-LGDP, while elucidating the potential inactivation mechanisms and the cell deactivation process involved. It may be important for the eco-friendly inactivation of M. aeruginosa blooms in natural water bodies. Environmental implicationsThe frequent occurrence of blooms of M. aeruginosa and the subsequent release of MC-LR in eutrophic waters are a global issue. Although glow discharge plasma technologies have been applied for the inactivation of M. aeruginosa, limitations such as low energy yield and additional nitrous oxide production remain. This study aims to explore the optimal conditions for inactivating M. aeruginosa and degrading MC-LR using direct current glow discharge plasma in liquid phase (DC-LGDP), as well as to analyze the inactivation mechanisms and the cell deactivation process of M. aeruginosa. Our results show that the 97.07% inactivation efficiency of M. aeruginosa by DC-LGDP is achieved at higher energy yield and without the generation of nitrogen oxides. The inactivation of M. aeruginosa and degradation of MC-LR are involved in the reactive species generated by DC-LGDP and electroporation effect. These factors induce oxidative stress damaging the cell integrity, impairing the photosynthesis and ribosome biosynthesis pathways of M. aeruginosa, ultimately leading to the cell deactivation of M. aeruginosa. Our findings provide insights into the effective inactivation of M. aeruginosa and the degradation of MC-LR by DC-LGDP with lower energy consumption and environmental friendliness. Thus, it may be important for the inactivation of M. aeruginosa blooms in natural water bodies.

High- and low- embryogenic Taxodium hybrid ‘zhongshanshan’ cell lines reveal involvement of redox homeostasis in somatic embryogenesis

Taxodium hybrid ‘zhongshanshan’ is a valuable horticultural ornamental tree species in China. SE (somatic embryogenesis) technology can regenerate numerous plantlets in a short period and thus has great commercial value for this species. However, the SE efficiency of Taxodium hybrid ‘zhongshanshan’ is highly genotype-dependent, and the mechanisms remain largely unclear so far. Here, we investigated morphological disparities, transcriptional profiles and physiological indices between high- and low-embryogenic cell lines. Our findings suggested that high-embryogenic cell line exhibited promising potential for long-term and robust division maintenance. Additionally, high-embryogenic cell line demonstrated a higher efficacy in inducing somatic embryos compared to low-embryogenic cell line. Discernible variations in cellular architecture between the two cell lines were found and RNA-seq analysis identified a total of 1169 DEGs (differentially expressed genes). Accordingly, DEGs were enriched in tyrosine metabolism, brassinosteroid biosynthesis, glutathione metabolism, phenylpropanoid biosynthesis, galactose metabolism and flavonoid biosynthesis. Physiological measurements indicated that cell line with appropriate endogenous H2O2 (hydrogen peroxide) and a stronger antioxidant system may be conducive to somatic embryo development. Additionally, the exogenous addition of 0.1 mg L–1 ETH (ethylene) could effectively promote somatic embryo induction of Taxodium hybrid ‘zhongshanshan’. Taken together, we highlighted the redox homeostasis effects on SE of Taxodium hybrid ‘zhongshanshan’. Our findings provided theoretical references for understanding the mechanism of SE efficiency and served as experimental foundations for the breeding and rapid propagation of Taxodium hybrid ‘zhongshanshan’.

The cross-talk between the metabolome and microbiome in a double-hit neonatal rat model of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD), a chronic lung disease in preterm infants, is associated with inflammation and high oxygen exposure. However, the effects of antenatal inflammation and postnatal extended hyperoxia on the metabolome and microbiome remain unclear. In this study, pregnant rats received lipopolysaccharide or saline injections on gestational day 20 and were exposed to either 21 % or 80 % oxygen for 4 weeks post-birth. Analysis revealed an increase in Firmicutes, Proteobacteria, and Actinobacteria, with a decrease in Bacteroidetes in BPD rats. Metabolomic analysis identified 78 altered metabolites, primarily lipids, enriched in pathways including arginine biosynthesis, sphingolipid metabolism, and primary bile acid biosynthesis in BPD rats. Integration analysis revealed strong correlations between intestinal microbiota and metabolites in BPD rats. These findings underscored the impact of antenatal inflammation and prolonged postnatal hyperoxia on gut microbiota and serum metabolome, suggesting their role in BPD pathogenesis.

Characteristic lipids and their potential functions generated during the aging process of yak ghee

Yak ghee is an important food source for Tibetan herdsmen; however, the lipid composition, functional lipids changed and best consumption period during the aging process of yak ghee have not been determined. In this study, we identified a total of 386 lipids in Zhongdian yak ghee during aging, including glycerolipids (292 species), glycerophospholipids (47 species), sphingolipids (24 species), and fatty acyls (23 species). The lipids in yak ghee dynamically changed during aging, with the final product containing several polyunsaturated fatty acids (including linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid), indicating its high nutritional value. Lipid fingerprints of yak ghee during aging revealed that triglyceride (16:0/16:0/20:5) and triglyceride (18:1/18:3/21:0) etc. were the characteristic lipids in aged yak ghee. The characteristic lipids in yak ghee were mainly enriched in the biosynthesis of unsaturated fatty acids, glycerolipid metabolism, and ether lipid metabolism pathways. This study provides insight into the lipid changes of yak ghee during aging, which offers a theoretical basis for the development of high-value yak ghee products.