Energy-related Metabolic Pathways Research Articles

Integrated analysis of transcriptomics and metabolomics of garden asparagus (Asparagus officinalis L.) under drought stress

BackgroundDrought is a leading environmental factor affecting plant growth. To explore the drought tolerance mechanism of asparagus, this study analyzed the responses of two asparagus varieties, namely, ‘Jilv3’ (drought tolerant) and ‘Pacific Early’ (drought sensitive), to drought stress using metabolomics and transcriptomics.ResultsIn total, 2,567 and 7,187 differentially expressed genes (DEGs) were identified in ‘Pacific Early’ and ‘Jilv3’, respectively, by comparing the transcriptome expression patterns between the normal watering treatment and the drought stress treatment. These DEGs were significantly enriched in the amino acid biosynthesis, carbon metabolism, phenylpropanoid biosynthesis, and plant hormone signal transduction pathways. In ‘Jilv3’, DEGs were also enriched in the following energy metabolism-related pathways: citrate cycle (TCA cycle), glycolysis/gluconeogenesis, and pyruvate metabolism. This study also identified 112 and 254 differentially accumulated metabolites (DAMs) in ‘Pacific Early’ and ‘Jilv3’ under drought stress compared with normal watering, respectively. The amino acid, flavonoid, organic acid, and soluble sugar contents were more significantly enhanced in ‘Jilv3’ than in ‘Pacific Early’. According to the metabolome and transcriptome analysis, in ‘Jilv3’, the energy supply of the TCA cycle was improved, and flavonoid biosynthesis increased. As a result, its adaptability to drought stress improved.ConclusionsThese findings help to better reveal the molecular mechanism underlying how asparagus responds to drought stress and improve researchers’ ability to screen drought-tolerant asparagus varieties as well as breed new varieties.

Comparative proteomic and metabolomic analyses reveal stress responses of hemp to salinity.

Integrated omics analyses outline the cellular and metabolic events of hemp plants in response to salt stress and highlight several photosynthesis and energy metabolism related pathways as key regulatory points. Soil salinity affects many physiological processes of plants and leads to crop yield losses worldwide. For hemp, a crop that is valued for multiple aspects, such as its medical compounds, fibre, and seed, a comprehensive understanding of its salt stress responses is a prerequisite for resistance breeding and tailoring its agronomic performance to suit certain industrial applications. Here, we first observed the phenotype of salt-stressed hemp plants and found that under NaCl treatment, hemp plants displayed pronounced growth defects, as indicated by the significantly reduced average height, number of leaves, and chlorophyll content. Next, we conducted comparative proteomics and metabolomics to dissect the complex salt-stress response mechanisms. A total of 314 proteins and 649 metabolites were identified to be differentially behaving upon NaCl treatment. Functional classification and enrichment analysis unravelled that many differential proteins were proteases associated with photosynthesis. Through metabolic pathway enrichment, several energy-related pathways were found to be altered, such as the biosynthesis and degradation of branched-chain amino acids, and our network analysis showed that many ribosomal proteins were involved in these metabolic adaptations. Taken together, for hemp plants, influences on chloroplast function probably represent a major toxic effect of salinity, and modulating several energy-producing pathways possibly through translational regulation is presumably a key protective mechanism against the negative impacts. Our data and analyses provide insights into our understanding of hemp's stress biology and may lay a foundation for future functional genomics studies.

Human Milk Composition Is Associated with Maternal Body Mass Index in a Cross-Sectional, Untargeted Metabolomics Analysis of Human Milk from Guatemalan Mothers

BackgroundMaternal overweight and obesity has been associated with poor lactation performance including delayed lactogenesis and reduced duration. However, the effect on human milk composition is less well understood. ObjectivesWe evaluated the relationship of maternal BMI on the human milk metabolome among Guatemalan mothers. MethodsWe used data from 75 Guatemalan mothers who participated in the Household Air Pollution Intervention Network trial. Maternal BMI was measured between 9 and <20 weeks of gestation. Milk samples were collected at a single time point using aseptic collection from one breast at 6 mo postpartum and analyzed using high-resolution mass spectrometry. A cross-sectional untargeted high-resolution metabolomics analysis was performed by coupling hydrophilic interaction liquid chromatography (HILIC) and reverse phase C18 chromatography with mass spectrometry. Metabolic features associated with maternal BMI were determined by a metabolome-wide association study (MWAS), adjusting for baseline maternal age, education, and dietary diversity, and perturbations in metabolic pathways were identified by pathway enrichment analysis. ResultsThe mean age of participants at baseline was 23.62 ± 3.81 y, and mean BMI was 24.27 ± 4.22 kg/m2. Of the total metabolic features detected by HILIC column (19,199 features) and by C18 column (11,594 features), BMI was associated with 1026 HILIC and 500 C18 features. Enriched pathways represented amino acid metabolism, galactose metabolism, and xenobiotic metabolic metabolism. However, no significant features were identified after adjusting for multiple comparisons using the Benjamini–Hochberg false discovery rate procedure (FDRBH < 0.2). ConclusionsFindings from this untargeted MWAS indicate that maternal BMI is associated with metabolic perturbations of galactose metabolism, xenobiotic metabolism, and xenobiotic metabolism by cytochrome p450 and biosynthesis of amino acid pathways. Significant metabolic pathway alterations detected in human milk were associated with energy metabolism-related pathways including carbohydrate and amino acid metabolism.This trial was registered at clinicaltrials.gov as NCT02944682.

Plasma metabolite profiling for S. haematobium biomarkers of infection in pre-school aged children in Shamva District, Zimbabwe

BackgroundMetabolomics approaches are indispensable tools in infection biomarker discovery efforts as they shed light on the underlying pathophysiological mechanisms of disease. In this study, we analysed plasma metabolites that can be used as biomarkers of urogenital schistosomiasis in pre-school aged children below the age of five.MethodsA case-control study was conducted involving 82 pre-school aged children that were age- and sex-matched. Urine samples were collected for three consecutive days to detect S. haematobium infection using urine filtration. Blood samples were also collected and processed to obtain plasma. Beckman Coulter AU480 chemistry analyser and commercial metabolite kits were used for profiling biomarkers in plasma samples. Descriptive statistics and MetaboAnalyst tool, were used for metabolite analysis. For the determination of diagnostic efficiency of plasma biomarkers, the area under the curve (AUC) was calculated from receiver operating characteristic curves at 95% CI.ResultsSuccinic acid, glucose-6-phosphate, phosphatidylcholine, alanine and creatinine levels in plasma were significantly associated with urogenital schistosomiasis (p&amp;lt;0.005) at the population level. Significant increase in concentration at 1.5-fold change (FC) threshold was highest for glucose-6-phosphate with FC value of 2.02 followed by creatinine, albumin and phosphatidylcholine. Creatinine was significantly downregulated with a FC value of 1.98. Of the six dysregulated metabolic pathways, glucose and sucrose metabolism were predominantly affected. Glucose-6-phosphate had the highest AUC (0.81), sensitivity (88.85%) and specificity (90.37%). Phosphatidylcholine and succinic acid also had AUC values greater than 0.7.ConclusionUrogenital schistosomiasis affects the energy-related metabolic pathways in pre-school aged children. Glucose-6-phosphate was identified as a potential indicator of infection at the population level. Furthermore, we recommend intensive validation of schistosome metabolite biomarkers.

Transcriptomic investigation unveils the role of energy metabolism under low phosphorus and salt combined stress in soybean (Glycine max).

Soybean (Glycine max) is economically significant, but the mechanisms underlying its adaptation to simultaneous low phosphorus and salt stresses are unclear. We employed the Shennong 94-1-8 soybean germplasm to conduct a comprehensive analysis, integrating both physiochemical and transcriptomic approaches, to unravel the response mechanisms of soybean when subjected to simultaneous low phosphorus and salt stresses. Remarkably, the combined stress exhibited the most pronounced impact on the soybean root system, which led to a substantial reduction in total soluble sugar (TSS) and total soluble protein (TSP) within the plants under this treatment. A total of 20,953 differentially expressed genes were identified through pairwise comparisons. Heatmap analysis of genes related to energy metabolism pathways demonstrated a significant down-regulation in expression under salt and low phosphorus + salt treatments, while low phosphorus treatment did not exhibit similar expression trends. Furthermore, the weighted gene co-expression network analysis (WGCNA) indicated that the blue module had a strong positive correlation with TSS and TSP. Notably, 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 1, FCS-Like Zinc finger 8, auxin response factor 18 isoform X2, and NADP-dependent malic enzyme emerged as hub genes associated with energy metabolism. In summary, our findings indicate that soybean roots are more adversely affected by salt and combined stress than by low phosphorus alone due to reduced activity in energy metabolism-related pathways and hub genes. These results offer novel insights into the adaptive mechanisms of soybeans when facing the combined stress of low phosphorus and salinity.

Attenuated cell cycle and DNA damage response transcriptome signatures and overrepresented cell adhesion processes imply accelerated progression in patients with lower-risk myelodysplastic neoplasms.

Patients with myelodysplastic neoplasms (MDS) are classified according to the risk of acute myeloid leukemia transformation. Some lower-risk MDS patients (LR-MDS) progress rapidly despite expected good prognosis. Using diagnostic samples, we aimed to uncover the mechanisms of this accelerated progression at the transcriptome level. RNAseq was performed on CD34+ ribodepleted RNA samples from 53 LR-MDS patients without accelerated progression (stMDS) and 8 who progressed within 20 months (prMDS); 845 genes were differentially expressed (ІlogFCІ > 1, FDR < 0.01) between these groups. stMDS CD34+ cells exhibited transcriptional signatures of actively cycling, megakaryocyte/erythrocyte lineage-primed progenitors, with upregulation of cell cycle checkpoints and stress pathways, which presumably form a tumor-suppressing barrier. Conversely, cell cycle, DNA damage response (DDR) and energy metabolism-related pathways were downregulated in prMDS samples, whereas cell adhesion processes were upregulated. Also, prMDS samples showed high levels of aberrant splicing and global lncRNA expression that may contribute to the attenuation of DDR pathways. We observed overexpression of multiple oncogenes and diminished differentiation in prMDS; the expression of ZEB1 and NEK3, genes not previously associated with MDS prognosis, might serve as potential biomarkers for LR-MDS progression. Our 19-gene DDR signature showed a significant predictive power for LR-MDS progression. In validation samples (stMDS = 3, prMDS = 4), the key markers and signatures retained their significance. Collectively, accelerated progression of LR-MDS appears to be associated with transcriptome patterns of a quiescent-like cell state, reduced lineage differentiation and suppressed DDR, inherent to CD34+ cells. The attenuation of DDR-related gene-expression signature may refine risk assessment in LR-MDS patients.

Milk fat globule membrane modulates inflammatory pathways in human monocytes: A crossover human intervention study

BackgroundIntake of high-fat foods raises postprandial plasma triglycerides and inflammatory markers, which may depend on the type of fat ingested. Dairy products are commonly consumed, but not much is known about the impact of milk fat and the milk fat globule membrane on postprandial inflammation. Here, we aimed to study the effect of milk fat with and without milk fat globule membrane and vegetable blend fat on post-prandial inflammation, with a focus on blood monocyte gene expression. MethodsWe performed a randomized, double-blind cross-over trial in 37 middle-aged healthy male and female volunteers (BMI 22-27 kg/m2). The participants consumed a meal shake containing 95.5 g of fat consisting of either a vegetable fat blend (VEGE), anhydrous milk fat (AMF, without milk fat globule membrane), or cream (CREAM, containing milk fat globule membrane). Blood monocytes were collected at 0 hours and 6 hours postprandially and used for bulk RNA sequencing and ex vivo stimulation with LPS. ResultsConsumption of all three shakes significantly decreased the percentage of classical monocytes and increased the percentages of intermediate monocytes and non-classical monocytes. No differences in these measures were observed between shakes. Using a threshold of P<0.01, 787 genes were differentially regulated postprandially between the three shakes. 89 genes were differentially regulated postprandially between AMF and VEGE, 373 genes between AMF and CREAM, and 667 genes between VEGE and CREAM, indicating that the effect of CREAM on monocyte gene expression was distinct from AMF and VEGE. Pathway analyses showed that VEGE significantly increased the expression of genes involved in inflammatory pathways, whereas this was less pronounced after AMF and not observed after CREAM. In addition, CREAM significantly down-regulated the expression of genes involved in energy metabolism-related pathways, such as glycolysis, TCA cycle, and oxidative phosphorylation, as well as HIF1 signaling. ConclusionCompared to the consumption of an anhydrous milk fat without milk fat globule membrane and a vegetable fat blend, the consumption of cream with milk fat globule membrane downregulated inflammatory pathways in blood monocytes, thus suggesting a potential inflammation inhibitory effect of milk fat globule membrane.

Identification and validation of autophagy-related genes in primary open-angle glaucoma

BackgroundAs the most common type of glaucoma, the etiology of primary open-angle glaucoma (POAG) has not been unified. Autophagy may affect the occurrence and development of POAG, while the specific mechanism and target need to be further explored.MethodsThe GSE27276 dataset from the Gene Expression Omnibus (GEO) database and the autophagy gene set from the GeneCards database were selected to screen differentially expressed autophagy-related genes (DEARGs) of POAG. Hub DEARGs were selected by constructing protein-protein interaction (PPI) networks and utilizing GSE138125 dataset. Subsequently, immune cell infiltration analysis, genome-wide association study (GWAS) analysis, gene set enrichment analysis (GSEA) and other analyses were performed on the hub genes. Eventually, animal experiments were performed to verify the mRNA levels of the hub genes by quantitative real time polymerase chain reaction (qRT-PCR).ResultsA total of 67 DEARGs and 2 hub DEARGs, HSPA8 and RPL15, were selected. The hub genes were closely related to the level of immune cell infiltration. GWAS analysis confirmed that the causative regions of the 2 hub genes in glaucoma were on chromosome 11 and chromosome 3, respectively. GSEA illustrated that pathways enriched for highly expressed HSPA8 and RPL15 contained immunity, autophagy, gene expression and energy metabolism-related pathways. qRT-PCR confirmed that the expression of Hspa8 and Rpl15 in the rat POAG model was consistent with the results of bioinformatics analysis.ConclusionsThis study indicated that HSPA8 and RPL15 may affect the progression of POAG by regulating autophagy and provided new ideas for the pathogenesis and treatment of POAG.

Nuclear magnetic resonance-based metabolomic study of rat serum after anterior cruciate ligament injury

Anterior cruciate ligament (ACL) injury, a common sports injury, is associated with a high risk of subsequent osteoarthritis (OA), which can cause serious pain and disability. Understanding the detailed mechanism underlying the predisposition of knee with ACL injury to secondary OA at an early stage is key to preventing future degradation and progression to a clinically significant disease. A total of 56 male Sprague Dawley rats (age, 8 weeks; weight, 180–220 g) were randomly divided into three experimental groups: control, ACL transection (ACLT; where surgical procedure was performed with ACLT), and sham (where surgical procedure was performed without ACLT). The ACLT and sham groups were further divided into three subgroups based on when the rats were sacrificed: 4, 8, and 12 weeks after the surgical procedure. The control group and the aforementioned subgroups contained 8 rats each. We used nuclear magnetic resonance (NMR)-based metabolomic analysis to analyze rat serum samples for the metabolic characteristics and the underlying mechanisms. In total, 28 metabolites were identified in the NMR spectra of the rat sera. At 4 and 8 weeks postoperatively, the sham group demonstrated metabolic profiles different from those of the ACLT group. However, this difference was not observed 12 weeks postoperatively. In total, five metabolites (acetate, succinate, sn-glycero-3-phosphocholine, glucose, and phenylalanine) and five metabolic pathways (phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; pyruvate metabolism; starch and sucrose metabolism; and histidine metabolism) demonstrated significant differences between the ACLT and sham groups. ACL injury was noted to considerably affect biochemical homeostasis and metabolism; however, these metabolic changes persisted briefly. Moreover, glucose was a characteristic metabolite, and several energy-related metabolic pathways were significantly disturbed. Therefore, an ACL injury may lead to considerable impairments in energy metabolism. Abnormal glucose levels facilitate chondrocyte function impairment and thereby lead to OA progression. Furthermore, lactate may aid in identifying metabolic changes specific to knee trauma not related to an ACL injury. Overall, the metabolic changes in rat serum after an ACL injury were closely related to disturbances in energy metabolism and amino acid metabolism. The current results may aid in understanding the pathogenesis of posttraumatic osteoarthritis.

Integrative analyses of transcriptomes and metabolomes provide insight into salinity adaption in Bangia (Rhodaphyta)

The salinity of the external environment poses a serious threat to most land plants. Although seaweeds can adapt to this, intertidal species are subject to wide fluctuations in salinity, including hypo- and hyper-saline conditions. The red algal genus Bangiales is a typical example; it is one of the oldest eukaryotes with sexual reproduction and has successfully adapted to both marine and freshwater environments. However, there is a dearth of research focused on elucidating the mechanism by which marine Bangia (Bangia fuscopurpurea) adapts to hypo-salinity, as well as the mechanism by which freshwater Bangia (Bangia atropurpurea) adapts to hyper-salinity. The objective of this study is to employ third-generation full-length transcriptome data and untargeted metabolome data, to provide insights into the salinity adaptation mechanism of as well as the evolutionary relationship between both Bangia species. B. fuscopurpurea and B. atropurpurea exhibited 9112 and 8772 differentially expressed genes (DEGs), respectively, during various periods of hyper-saline condition. These genes were primarily enriched in secondary metabolites and energy-related metabolic pathways. Additionally, B. fuscopurpurea displayed 16,285 DEGs during different periods of hypo-saline condition, which were mainly enriched in metabolic pathways related to ion transport and membrane proteins. In the hyper- and hypo-saline adapt response processes of B. fuscopurpurea, a total of 303 transcription factors were identified, which belonged to 26 families. Among these, 85 and 142 differential transcription factors were identified, respectively, mainly belonging to the C2H2 and MYB family. Similarly, in the response process of B. atropurpurea to hyper-saline condition, a total of 317 transcription factors were identified, mainly belonging to 17 families. Among these, 121 differential transcription factors were identified, mainly belonging to the C2H2 and bZIP family. Furthermore, a correlation analysis was conducted to examine the relationship between the transcriptional and metabolic levels of both species under saline adaptation. The findings demonstrated that Bangia exhibits intricate adaptations to salinity, which involve swift regulation of its photosynthetic processes, alternations in membrane contents, and a robust anti-oxidation system to mitigate the effects of excess redox energy during exposure to varying salinity. Notably, the unsaturated fat and glutathione metabolic pathways were found to be significantly enriched in this context.

Metabolic insights into how multifunctional microbial consortium enhances atrazine removal and phosphorus uptake at low temperature

Agricultural soils in the black soil region of northeast China often face negative stress due to low temperatures, pesticide contamination, and inadequate nutrient supply. In this study, a new cold-tolerant strain of Peribacillus simplex C1 (C1) was selectively isolated from atrazine contaminated soil. The artificially constructed microbial consortium (CPD) [C1, phosphorus-solubilizing bacterium Enterobacter sp. P1, and atrazine-degrading bacterium Acinetobacter lwoffii DNS32] demonstrated the most effective performance in enhancing atrazine degradation and phosphorus-solubilizing capacity when the initial inoculation ratio of 5:1:2 at 15 °C. CPD enhanced energy-related metabolic pathways and increased choline production to regulate bacterial adaptation to temperature decrease. Additionally, the strains could selectively utilize carbon sources (low molecular weight organic acids) or nitrogen sources (some metabolites of atrazine) provided by each other to enhance growth. Furthermore, strain C1 enhanced membrane fluidity through increased expression of the unsaturated fatty acids. Pot experiments demonstrated that CPD assisted soybean seedlings in resisting dual stresses of low temperature and atrazine contamination by inducing the expression of genes related to photosynthesis, membrane permeability, phosphorus response, and cold tolerance.

Expression of expanded GGC repeats within NOTCH2NLC causes cardiac dysfunction in mouse models

BackgroundNeuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by widespread intranuclear inclusions in the nervous system as well as multiple visceral organs. In 2019, expanded GGC repeats within the 5′ untranslated region of the NOTCH2NLC gene was identified as the causative factor. NIID is a heterogeneous disorder with variable clinical manifestations including cognitive impairment, cerebellar ataxia, parkinsonism, paroxysmal symptoms, autonomic dysfunction, and muscle weakness. Although NIID primarily affects the central and peripheral nervous systems, growing evidence suggests potential cardiac abnormalities in NIID. However, the link between expanded GGC repeats within NOTCH2NLC and cardiac dysfunction remains uncertain.ResultsIn this study, we utilized two transgenic mouse models, expressing NOTCH2NLC-(GGC)98 ubiquitously or specifically in cardiomyocytes, and identified p62 (also known as sequestosome 1, SQSTM1)-positive intranuclear NOTCH2NLC-polyG inclusions in cardiomyocytes in two mouse models. We observed that both models exhibited cardiac-related pathological and echocardiographic changes, albeit exhibiting varying degrees of severity. Transcriptomic analysis revealed shared downregulation of genes related to ion channels and mitochondria in both models, with the cardiomyocyte-specific mice showing a more pronounced downregulation of mitochondria and energy metabolism-related pathways. Further investigations revealed decreased expression of mitochondria-related genes and electron transport chain activity. At last, we conducted a retrospective review of cardiac-related examination results from NIID patients at our hospital and also identified some cardiac abnormalities in NIID patients.ConclusionsOur study provided the first in vivo evidence linking GGC repeat expansions within NOTCH2NLC to cardiac abnormalities and highlighted the contribution of mitochondrial dysfunction in the development of cardiac abnormalities.

Adverse effects of thiamethoxam on the behavior, biochemical responses, hepatopancreas health, transcriptome and intestinal flora of juvenile Chinese mitten crab (Eriocheir sinensis)

Frequent detection of thiamethoxam in global surface waters has provoked great concern in environmental safety, as thiamethoxam exhibits high toxicity to aquatic arthropods. However, little systematic investigation has been conducted on the chronic toxicity of thiamethoxam to crustaceans. This study exposed Eriocheir sinensis to thiamethoxam (0, 0.5, 5 and 50 μg/L) in water for 28 days. No significant difference in mortality was observed among all groups. A high concentration of thiamethoxam (50 μg/L) impaired the righting ability of E. sinensis. Thiamethoxam significantly increased antioxidant enzyme activities (superoxide dismutase, total antioxidant capacity and glutathione peroxidase) and malondialdehyde levels. Simultaneously, detoxification enzyme activities (aminopyrine N-demethylase, erythromycin N-demethylase and glutathione-S-transferase) increased under chronic thiamethoxam stress. In addition, thiamethoxam caused immune and hepatopancreas damage. Moreover, thiamethoxam induced intestinal flora dysbiosis by altering the microbiome structure. The reduced complexity of the gut microbiota further illustrated that thiamethoxam could disrupt the stability of the microbiota ecological network. The transcriptomic results revealed that the number of downregulated DEGs increased in a dose-dependent manner, and most downregulated DEGs were enriched in energy metabolism-related pathways. These results indicate that thiamethoxam can adversely affect the crab behavior, biochemistry, intestinal microflora and transcriptomic responses.

Effects of Microhabitat Temperature Variations on the Gut Microbiotas of Free-Living Hibernating Animals.

Variations in ambient temperature (Ta) may significantly influence the gut microbiotas of ectothermic and endothermic animals, affecting fitness. It remains unclear, however, whether temperature fluctuations affect the gut microbial communities of hibernating animals during torpor. To investigate temperature-induced changes in the gut microbiota during hibernation under entirely natural conditions, we took advantage of two adjacent but distinct populations of the least horseshoe bat (Rhinolophus pusillus), which inhabit sites with a similar summer Ta but a different winter Ta. Using 16S rRNA gene high-throughput sequencing, we estimated differences in gut microbial diversity and composition between the hibernating (winter) and active (summer) R. pusillus populations at both sites. During the active period, gut microbiotas did not differ significantly between the two populations, probably due to the similar Tas. However, during hibernation, a higher Ta was associated with decreased α-diversity in the gut microbiome. During hibernation, temperature variation did not significantly affect the relative abundance of Proteobacteria, the dominant phylum at both sites, but marked site-specific differences were detected in the relative abundances of Firmicutes, Actinobacteria, and Tenericutes. In total, 74 amplicon sequence variants (ASVs) were significantly differentially abundant between the hibernating and active bat guts across the two sites; most of these ASVs were associated with the cooler site, and many belonged to pathogenic genera, suggesting that lower ambient temperatures during hibernation may increase the risk of pathogen proliferation in the host gut. Our findings help to clarify the mechanisms underlying the gut microbiota-driven adaptation of hibernating mammals to temperature changes. IMPORTANCE Temperature variations affect gut microbiome diversity and structure in both ectothermic and endothermic animals. Here, we aimed to characterize temperature-induced changes in the gut microbiotas of adjacent natural populations of the least horseshoe bat (Rhinolophus pusillus) which hibernate at different ambient temperatures. We found that the ambient temperature significantly affected the α-diversity, but not the β-diversity, of the gut microbiota. Bats hibernating at cooler temperatures experienced more drastic shifts in gut microbiome structure, with consequent effects on energy-related metabolic pathways. Our results provide novel insights into the effects of ambient temperature on the gut microbiotas of hibernating animals.

Identification of Key Genes Regulating Sorghum Mesocotyl Elongation through Transcriptome Analysis.

Sorghum with longer mesocotyls is beneficialfor improving its deep tolerance, which is important for the seedling rates. Here, we perform transcriptome analysis between four different sorghum lines, with the aim of identifying the key genes regulating sorghum mesocotyl elongation. According to the mesocotyl length (ML) data, we constructed four comparison groups for the transcriptome analysis and detected 2705 common DEGs. GO and KEGG enrichment analysis showed that the most common category of DEGs were involved in cell wall, microtubule, cell cycle, phytohormone, and energy metabolism-related pathways. In the cell wall biological processes, the expression of SbEXPA9-1, SbEXPA9-2, SbXTH25, SbXTH8-1, and SbXTH27 are increased in the sorghum lines with long ML. In the plant hormone signaling pathway, five auxin-responsive genes and eight cytokinin/zeatin/abscisic acid/salicylic acid-related genes showed a higher expression level in the long ML sorghum lines. In addition, five ERF genes showed a higher expression level in the sorghum lines with long ML, whereas two ERF genes showed a lower expression level in these lines. Furthermore, the expression levels of these genes were further analyzed using real-time PCR (RT-qPCR), which showed similar results. This work identified the candidate gene regulating ML, which may provide additional evidence to understand the regulatory molecular mechanisms of sorghum mesocotyl elongation.

Mass spectrometry-based metabolomics reveal Dendrobium huoshanense polysaccharide effects and potential mechanism of N-methyl-N'-nitro-N-nitrosoguanidine -induced damage in GES-1cells.

Dendrobium huoshanense C. Z. Tang et S. J. Cheng is an important edible medicinal plant that thickens the stomach and intestines, and its active ingredient, polysaccharide, can have anti-inflammatory, immunoregulatory, and antitumor effects. However, the gastroprotective effects and potential mechanisms of Dendrobium huoshanense polysaccharides (DHP) remain unclear. An N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced human gastric mucosal epithelial cells (GES-1) damage model was used in this research, aiming to investigate whether DHP has a protective effect on MNNG-induced GES-1cell injury and its underlying mechanism based on the combination of multiple methods. DHP was extracted using water extraction and alcohol precipitation methods, and the proteins were removed using the Sevag method. The morphology was observed using scanning electron microscopy. A MNNG-induced GES-1cell damage model was developed. Cell viability and proliferation of the experimental cells were investigated using a cell counting kit-8 (CCK-8). Cell nuclear morphology was detected using the fluorescent dye Hoechst 33342. Cell scratch wounds and migration were detected using a Transwell chamber. The expression levels of apoptosis proteins (Bcl-2, Bax, Caspase-3) in the experimental cells were detected by Western blotting. Ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was performed to investigate the potential mechanism of action of DHP. The CCK-8 kit analysis showed that DHP increased GES-1cell viability and ameliorated GES-1cell injury by MNNG. In addition, scratch assay and Transwell chambers results suggested that DHP improved the MNNG-induced motility and migration ability of GES-1cells. Likewise, the results of the apoptotic protein assay indicated that DHP had a protective effect against gastric mucosal epithelial cell injury. To further investigate the potential mechanism of action of DHP, we analyzed the metabolite differences between GES-1cells, GES-1cells with MNNG-induced injury, and DHP+MMNG-treated cells using UHPLC-HRMS. The results indicated that DHP upregulated 1-methylnicotinamide, famotidine, N4-acetylsulfamethoxazole, acetyl-L-carnitine, choline and cer (d18:1/19:0) metabolites and significantly down-regulated 6-O-desmethyldonepezil, valet hamate, L-cystine, propoxur, and oleic acid. DHP may protect against gastric mucosal cell injury through nicotinamide and energy metabolism-related pathways. This research may provide a useful reference for further in-depth studies on the treatment of gastric cancer, precancerous lesions, and other gastric diseases.

Transcriptome analysis of Tetrahymena thermophila response to exposure with dihydroartemisinin

Dihydroartemisinin (DHA) is a derivative of artemisinin and is toxic to parasites. We used the Tetrahymena thermophila (T. thermophila) as a model to explore DHA toxicity. Results showed that low concentration of DHA (20 μmol/L) promoted cell proliferation, whereas high concentrations of DHA (40–1280 μmol/L) inhibited that. Appearance of nucleus was pycnosis by laser scanning confocal microscope. DHA significantly elevated activities of SOD and GSH-Px (P < 0.01) and MDA was markedly increased at high level but decreased at low level (P < 0.01). Further results of transcriptome in T. thermophila treated with different concentration DHA group (0, 20, 160 μmol/L) showed that differentially expressed genes (DEGs) were involved in oxidation-reduction and metabolism of exogenous substances indicated oxidative stress stimulation. Kyoto Encyclopedia of Genes and Genomes showed that DEGs were involved in the cytochrome P450-mediated metabolism of exogenous substances, glutathione metabolism and ABC transport. Remarkably, DNA replication was significantly enriched in low concentration DHA, energy metabolism related pathways and necrotic process were considerably enriched in high concentration DHA. The results of RT-qPCR of 13 DEGs were the same as that of transcriptome, in which the expression of GST and GPx family genes were significantly altered after exposed to high-DHA group. DHA induced oxidative stress damage through disturbing with energy. However, detoxification pathways in T. thermophila to resist oxidative damage and cell alleviated low concentration DHA stress by regulating antioxidant enzyme. This study provides good practice on pharmacological mechanism of artemisinin-based drugs in antiparasitic.

Metabolomics for biomarker discovery in schistosomiasis: A systematic scoping review

BackgroundMetabolomic based approaches are essential tools in the discovery of unique biomarkers for infectious diseases via high-throughput global assessment of metabolites and metabolite pathway dysregulation. This in-turn allows the development of diagnostic tools and provision of therapeutics. In this review, we aimed to give an overview of metabolite biomarkers and metabolic pathway alterations during Schistosoma haematobium and Schistosoma mansoni infections.MethodsWe conducted the review by systematically searching electronic databases and grey literature to identify relevant metabolomics studies on schistosomiasis. Arksey and O’Malley methodology for conducting systematic scoping reviews was applied. A narrative summary of results was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping review guidelines.ResultsTwelve articles included in the review identified 127 metabolites, whose concentrations were considerably altered during S. mansoni and S. haematobium infections. The metabolites were assigned to metabolic pathways involved in energy (34.6%), gut microbial (11.0%), amino acid (25.2%), nucleic acids (6.3%), immune proteins (8.7%) hormones (2.4%) and structural proteins/lipids (11.8%). Energy related metabolic pathways were the most affected during schistosome infections with metabolites such as succinate, citrate, aconitate and fumarate of the tricarbocylic acid cycle being significantly altered in organ, serum and plasma samples. Amino acid metabolism was also impacted during schistosome infections as phenylacetylglycine, alanine, taurine, 2-oxoisocaproate and 2-oxoisovalerate emerged as potent biomarkers. Elevated structural proteins such as actin, collagen and keratin concentrations were identified as biomarkers of liver fibrosis, a common pathological feature in chronic schistosomiasis infections. Hippurate was a major metabolite biomarker in the gut microbial related pathway.ConclusionsThe analysis of the literature revealed that energy related metabolic pathways are considerably altered during S. mansoni and S. haematobium infections. Therefore, their metabolites may provide biomarkers for diagnosis and prognosis in addition to providing therapeutics for parasitic infections. This scoping review has identified a need to replicate more schistosomiasis metabolomic studies in humans to complement animal-model based studies.

Comparative pharyngeal cartilage developmental toxicity of bisphenol A, bisphenol S and bisphenol AF to zebrafish (Danio rerio) larvae: A combination of morphometry and global transcriptome analyses

Exposure to BPA is recently shown to affect cartilage development in teleost fishes; whether BPS and BPAF, its two most frequently used phenolic analogues have similar effect, however, remains unclear. Here, we utilize zebrafish (Danio rerio) as an in-vivo larval model for systematic comparison of the pharyngeal arch-derived cartilage developmental toxicity of BPA, BPS and BPAF. Zebrafish are continuously exposed to three bisphenol analogues (3-BPs) at a range of concentrations since the embryonic stage (0.5 hpf), and identified cartilage malformations of the mandibular and hyoid pharyngeal arches at larval stage (120 hpf). BPA and BPAF prolong length and broaden cartilage angles; however, BPS shortens length and narrows the angles of skull cartilages. The results of the comparative transcriptome show that FoxO and MAPK signaling pathways are closely associated with the toxicity of BPA and BPAF, while BPS exposure affects energy metabolism-related pathways. Moreover, exposure to 3-BPs have an impact on the oxidative stress status. Our data collectively indicate that BPS and BPAF may not be safer than BPA regarding the impact on pharyngeal cartilage development in fish model, the mechanisms still need explorations, and that these two analogues should be applied with caution.

Interactions between the gut micro-community and transcriptome of Culex pipiens pallens under low-temperature stress

BackgroundCulex pipiens pallens (Diptera: Culicidae) can survive at low temperature for long periods. Understanding the effects of low-temperature stress on the gut microflora and gene expression levels in Cx. pipiens pallens, as well as their correlation, will contribute to the study of the overwintering mechanism of Cx. pipiens pallens.MethodsThe gut bacteria were removed by antibiotic treatment, and the survival of Cx. pipiens pallens under low-temperature stress was observed and compared with the control group. Then, full-length 16S rRNA sequencing and the Illumina HiSeq X Ten sequencing platform were used to evaluate the gut microflora and gene expression levels in Cx. pipiens pallens under low-temperature stress.ResultsUnder the low-temperature stress of 7 °C, the median survival time of Cx. pipiens pallens in the antibiotic treatment group was significantly shortened by approximately 70% compared to that in the control group. The species diversity index (Shannon, Simpson, Ace, Chao1) of Cx. pipiens pallens decreased under low-temperature stress (7 °C). Non-metric multidimensional scaling (NMDS) analysis divided all the gut samples into two groups: control group and treatment group. Pseudomonas was the dominant taxon identified in the control group, followed by Elizabethkingia and Dyadobacter; in the treatment group, Pseudomonas was the dominant taxon, followed by Aeromonas and Comamonas. Of the 2417 differentially expressed genes (DEGs), 1316 were upregulated, and 1101 were downregulated. Functional GO terms were enriched in 23 biological processes, 20 cellular components and 21 molecular functions. KEGG annotation results showed that most of these genes were related to energy metabolism-related pathways. The results of Pearson’s correlation analysis showed a significant correlation between the gut microcommunity at the genus level and several DEGs.ConclusionsThese results suggest that the mechanism of adaptation of Cx. pipiens pallens to low-temperature stress may be the result of interactions between the gut bacterial community and transcriptome.Graphical