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•We evaluated the genes involved in catechins biosynthesis in C. sinensis.•In total,47,717 unigenes were obtained from two cultivars of C. sinensis.•KEGG database analysis identified ...13 key enzymes involved in catechins biosynthesis.•The structures of LAR and ANR were spatially modeled.•Our findings established a basis for further studies of catechins biosynthesis.
Camellia sinensis (L.) O. Kuntze is used to produce tea, a beverage consumed worldwide. Catechins are major medically active components of C. sinensis and can be used clinically to treat hyperglycaemia, hypertension, and cancer. In this study, we aimed to identify the genes involved in catechins biosynthesis. To this end, we analysed transcriptome data from two different cultivars of C. sinensis using DNBSEQ technology. In total,47,717 unigenes were obtained from two cultivars of C. sinensis, of which 9429 were predicted as new unigenes. In our analyses of the Kyoto Encyclopedia of Genes and Genomes database, 212 unigenes encoding 13 key enzymes involved in catechins biosynthesis were identified; the structures of leucoanthocyanidin reductase and anthocyanidin reductase were spatially modelled. Some of these key enzymes were verified by real-time quantitative polymerase chain reaction, and multiple genes encoding plant resistance proteins or transcription factors were identified and analysed. Furthermore, two microRNAs involved in the regulation of catechins biosynthesis were explored. Differentially expressed genes involved in the flavonoid biosynthesis pathway were identified from pairwise comparisons of genes from different cultivars of tea plants. Overall, our findings expanded the number of publicly available transcript datasets for this valuable plant species and identified candidate genes related to the biosynthesis of C. sinensis catechins, thereby establishing a foundation for further in-depth studies of catechins biosynthesis in varieties or cultivars of C. sinensis.
Paliurus favonii Unger is recognized and described based on fruits from the Oligocene Ningming flora of Guangxi, South China. Characteristics of the present specimens include circular winged fruits ...that are 10.0-11.5 mm in diameter with a central endocarp at 3.0 to 4.0 mm in diameter. The specimens fall into the morphological range of the fossil species P. favonii, which has been observed in other Cenozoic sites in the Northern Hemisphere. The present discovery represents the lowest latitude distribution of P. favonii in the world, and we are presenting the first P. favonii fossil described with detailed cuticular characteristics from China. Further, this finding demonstrates that the genus existed in the Oligocene Ningming region, South China, and provides new information for understanding the fossil history. The dispersal mode for winged fossils demonstrates that wind dispersal is well-represented in the Oligocene Ningming flora.
Herbivores gastrointestinal microbiota is of tremendous interest for mining novel lignocellulosic enzymes for bioprocessing. We previously reported a set of potential carbohydrate-active enzymes from ...the metatranscriptome of the Hu sheep rumen microbiome. In this study, we isolated and heterologously expressed two novel glucanase genes, Cel5A-h38 and Cel5A-h49, finding that both recombinant enzymes showed the optimum temperatures of 50 °C. Substrate-specificity determination revealed that Cel5A-h38 was exclusively active in the presence of mixed-linked glucans, such as barley β-glucan and Icelandic moss lichenan, whereas Cel5A-h49 (EC 3.2.1.4) exhibited a wider substrate spectrum. Surprisingly, Cel5A-h38 initially released only cellotriose from lichenan and further converted it into an equivalent amount of glucose and cellobiose, suggesting a dual-function as both endo-β-1,3-1,4-glucanase (EC 3.2.1.73) and exo-cellobiohydrolase (EC 3.2.1.91). Additionally, we performed enzymatic hydrolysis of sheepgrass (Leymus chinensis) and rice (Orysa sativa) straw using Cel5A-h38, revealing liberation of 1.91 ± 0.30 mmol/mL and 2.03 ± 0.09 mmol/mL reducing sugars, respectively, including high concentrations of glucose and cellobiose. These results provided new insights into glucanase activity and lay a foundation for bioconversion of lignocellulosic biomass.
•We isolated and characterized two novel glucanases, Cel5A-h38 and Cel5A-h49, from rumen uncultured bacterium.•Cel5A-h38 exclusively generated glucose and cellobiose as end products from glucan.•Cel5A-h38 is a novel bifunctional enzyme with both endo-β-1,3-1,4-glucanase and exo-cellobiohydrolase activities.•Cel5A-h38 was highly effective at releasing glucose and cellobiose from natural lignocellulosic feedstocks.
Background. Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in adults, causing high morbidity and mortality worldwide. In recent years, the prevalence of T2DM has been ...increasing significantly, and genome-wide association studies (GWAS) have shown that KCNQ1 significantly increases the risk of T2DM. Objective. To find large-scale evidence on whether the KCNQ1rs2237892C⟶T gene polymorphism is associated with T2DM susceptibility. Methods. A comprehensive review of the Chinese and English literature on the association of T2DM with KCNQ1rs2237892 is published by PubMed and Baidu Academic. The included literature was part or all of the studied loci which were evaluated for association with T2DM. Forest plots were made of the included literature to analyze the association of KCNQ1 with polymorphisms of the studied loci, and funnel plots and Egger’s test were used to evaluate the publication bias of the selected included literature. Results. Ten case-control studies including a total of 7027 cases and 8208 controls met our inclusion criteria. Allele (C allele frequency distribution) (OR: 1.19; 95% CI: 0.87,1.62; P<0.00001), recessive (OR: 0.73; 95% CI: 0.45,1.18; P<0.00001) genetic model under the full population was observed between KCNQ1rs2237892C⟶T gene polymorphism and T2DM without a significant relationship. In a stratified analysis by race, a meaningful association was found in non-Asian populations under the allelic genetic model, but no association was found in Asian populations. Conclusion. This meta-analysis showed no significant association between the rs2237892 polymorphism of the KCNQ1 gene and the risk of T2DM.
The disruption of the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in bone marrow contributes to the adipocytes accumulation and bone loss, which leads ...to the development of osteoporosis (OP). The circular RNA (circRNA), circRBM23, was generated from the RNA binding motif protein 23 (RBM23) gene. It was reported that circRBM23 was down-regulated in OP patients, but it remains unknown whether its down-regulation is involved in the lineage switch of MSCs.
We aimed to explore the role and mechanism of circRBM23 in regulating the switch between osteogenic and adipogenic differentiation of MSCs.
The expression and function of circRBM23 in vitro were detected by qRT-PCR, alizarin red staining, and oil Red O staining. The interactions between circRBM23 and microRNA-338-3p (miR-338-3p) were analyzed by RNA pull-down assay, FISH, and dual-luciferase reporter assay. MSCs treated with lentivirus overexpression of circRBM23 was applied for both in vitro and in vivo experiments.
CircRBM23 was expressed at lower levels in OP patients. Besides, circRBM23 was up-regulated during osteogenesis and down-regulated during adipogenesis of MSCs. CircRBM23 could promote the osteogenic differentiation but inhibit the adipogenic differentiation of MSCs. Mechanistically, circRBM23 acted as a sponge for microRNA-338-3p (miR-338-3p) to enhance the expression of RUNX family transcription factor 2 (RUNX2).
Our research indicates that circRBM23 could promote the switch from adipogenic to osteogenic differentiation of MSCs via sponging miR-338-3p. It might improve the understanding of the lineage switch of MSCs and provide a potential target for diagnosing and treating OP.
Long microchannels with thin walls, small width, and nanoholes or irregular shaped microgaps, which are similar to capillaries or cancerous vessels, are urgently needed to simulate the physiological ...activities in human body. However, the fabrication of such channels remains challenging. Here, microchannels with designable holes are manufactured by combining laser printing with line‐contact capillary‐force assembly. Two microwalls are first printed by femtosecond laser direct‐writing, and subsequently driven to collapse into a channel by the capillary force that arises in the evaporation of developer. The channel can remain stable in solvent due to the enhanced Van der Waals' force caused by the line‐contact of microwalls. Microchannels with controllable nanoholes and almost arbitrary patterns can be fabricated without any bonding or multistep processes. As‐prepared microchannels, with wall thicknesses less than 1 µm, widths less than 3 µm, lengths more than 1 mm, are comparable with human capillaries. In addition, the prepared channels also exhibit the ability to steer the flow of liquid without any external pump.
A strategy to fabricate microchannels with capillary‐force‐driven self‐assembly has been introduced. Microchannels with controllable nanoholes and almost arbitrary patterns can be prepared without any bonding or multistep processes. As‐prepared microchannels, with wall thicknesses less than 1 µm, widths less than 10 µm, lengths more than 1 mm, are comparable with human capillaries.
Purpose: To evaluate the blood glucose and renal function, determine the prevalence of hyperglycemia/diabetes mellitus (DM) and renal disease (nephropathy), and investigate the association between ...hyperglycemia/DM and renal disease in patients with viral hepatitis (VH). Patients and Methods: A total of 491 subjects were included in the study. Patients with VH were further divided into the hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and HBV-HCV co-infection subgroups. Fasting blood glucose, glycated hemoglobin (HbA.sub.1c), glycated albumin (GA), glutamic oxaloacetic transaminase (GOT), creatinine (Cr), and cystatin C (Cys C) levels were measured. Urine microalbumin levels were also assessed. Formulas for estimated average glucose calculated using glycated albumin (eAG(GA)), estimated average glucose calculated using HbA.sub.1c (eAG(HbA.sub.1c)), and estimated glomerular filtration rate calculated using cystatin C (eGFRcys) were used to evaluate the average glucose and renal function. Results: The prevalence of hyperglycemia/DM and renal disease was significantly higher in the VH group, especially in the HCV subgroup. The prevalence of renal disease was significantly higher in patients with VH with eAG(GA) >200 mg/dL. Conclusion: Our study used multiple parameters to evaluate blood glucose and renal function in patients with VH and found that hyperglycemia/DM and renal disease are closely associated with VH, especially in subjects with HCV infection. Patients with VH, especially those with HCV infection and hyperglycemia/DM, were particularly vulnerable to renal disease. Keywords: viral hepatitis, hyperglycemia, diabetes mellitus, renal disease, nephropathy
Immunotherapies for cancers may cause severe and life-threatening cardiotoxicities. The underlying mechanisms are complex and largely elusive. Currently, there are several ongoing clinical trials ...based on the use of activated invariant natural killer T (iNKT) cells. The potential cardiotoxicity commonly associated with this particular immunotherapy has yet been carefully evaluated. The present study aims to determine the effect of activated iNKT cells on normal and β-adrenergic agonist (isoproterenol, ISO)-stimulated hearts. Mice were treated with iNKT stimulants, α-galactosylceramide (αGC) or its analog OCH, respectively, to determine their effect on ISO-induced cardiac injury. We showed that administration of αGC (activating both T helper type 1 (Th1)- and T helper type 2 (Th2)-liked iNKT cells) significantly accelerated the progressive cardiac injury, leading to enhanced cardiac hypertrophy and cardiac fibrosis with prominent increases in collagen deposition and TGF-β1, IL-6, and alpha smooth muscle actin expression. In contrast to αGC, OCH (mainly activating Th2-liked iNKT cells) significantly attenuated the progression of cardiac injury and cardiac inflammation induced by repeated infusion of ISO. Flow cytometry analysis revealed that αGC promoted inflammatory macrophage infiltration in the heart, while OCH was able to restrain the infiltration. In vitro coculture of αGC- or OCH-pretreated primary peritoneal macrophages with primary cardiac fibroblasts confirmed the profibrotic effect of αGC and the antifibrotic effect of OCH. Our results demonstrate that activating both Th1- and Th2-liked iNKT cells is cardiotoxic, while activating Th2-liked iNKT cells is likely cardiac protective, which has implied key differences among subpopulations of iNKT cells in their response to cardiac pathological stimulation.
Gastrin-releasing peptide (GRP) binds to its receptor (GRP receptor GRPR) to regulate multiple biological processes, but the function of GRP/GRPR axis in acute kidney injury (AKI) remains unknown. In ...the present study, GRPR is highly expressed by tubular epithelial cells (TECs) in patients or mice with AKI, while histone deacetylase 8 may lead to the transcriptional activation of GRPR. Functionally, we uncovered that GRPR was pathogenic in AKI, as genetic deletion of GRPR was able to protect mice from cisplatin- and ischemia-induced AKI. This was further confirmed by specifically deleting the GRPR gene from TECs in GRPRFlox/Flox//KspCre mice. Mechanistically, we uncovered that GRPR was able to interact with Toll-like receptor 4 to activate STAT1 that bound the promoter of MLKL and CCL2 to induce TEC necroptosis, necroinflammation, and macrophages recruitment. This was further confirmed by overexpressing STAT1 to restore renal injury in GRPRFlox/Flox/KspCre mice. Concurrently, STAT1 induced GRP synthesis to enforce the GRP/GRPR/STAT1 positive feedback loop. Importantly, targeting GRPR by lentivirus-packaged small hairpin RNA or by treatment with a novel GRPR antagonist RH-1402 was able to inhibit cisplatin-induced AKI. In conclusion, GRPR is pathogenic in AKI and mediates AKI via the STAT1-dependent mechanism. Thus, targeting GRPR may be a novel therapeutic strategy for AKI.
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Meng et al. first revealed the important mechanism of GRPR mediating AKI through inflammation and necroptosis, suggested that targeting GRPR may be a novel therapeutic strategy for AKI.
Background/Aims: Elevated serum uric acid (UA) was intimately correlated with vascular stiffness and abnormal ankle brachial index (ABI) in various populations. These correlations lost significance ...after adjustment for estimated glomerular filtration rate (eGFR), indicating that the association of UA and brachial-ankle pulse wave velocity (baPWV) or ABI might be driven by kidney function. UA is predominantly eliminated through the kidneys, and metabolic disorders can influence the clearance of UA. In this study, we aimed to explore the putative correlation between FEUA and baPWV or ABI to determine to what extent the associations with UA were affected by renal function. Methods: This cross-sectional study enrolled 2351 participants, who underwent general health screening in Hanzhong people’s hospital from March to June of 2017. BaPWV and ABI were measured using a volume-plethysmographic apparatus (BP-203RPEII; Nihon Colin, Tokyo, Japan). FEUA was divided into quartiles: Q1:FEUA≤3.07; Q2: 3.07<FEUA≤5.32; Q3: 5.32<FEUA≤9.19; and Q4: FEUA> 9.19. Results: Lower FEUA predicted a higher prevalence of high baPWV and low ABI (p for trend <0.001). The respective ORs for high baPWV from the first to the third quartiles of FEUA were 1.777(1.323, 2.387); 1.561(1.158, 2.104); and 1.680 (1.250, 2.259). The prevalence of low ABI was greatly elevated with the decrement of FEUA ORs for the first to third FEUA quartiles were 6.977(2.062, 23.610); 5.123(1.475, 17.790); and 2.685(0.709, 10.171), respectively. The association of FEUA and ABI was independent of related confounding factors. However, the association between FEUA and baPWV was greatly influenced by corresponding confounders, especially gender. The efficacy of FEUA in the prediction of low ABI was stronger than that of serum UA. However, serum UA was more powerful in the prediction of high baPWV. Conclusion: Kidney function exerted a profound influence on the relationship between UA and baPWV or ABI, revealing complex interactions among cardiovascular risk factors.
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