ABSTRACT
BACKGROUND AND OBJECTIVE: Recently, vonoprazan-amoxicillin (VA) dual therapy has been reported as a promising approach for Helicobacter pylori (H. pylori) eradication. However, the effects of VA therapy versus bismuth-containing quadruple therapy (BQT) on H. pylori eradication remains unclear. The objective of this meta-analysis was to compare the effects of VA dual therapy with BQT for H. pylori eradication. METHODS: A comprehensive search of the literature was conducted from the beginning to September 2023, utilizing PubMed, Embase, the Cochrane Library and Web of Science database. A random-effects model was used to perform a meta-analysis to determine the pooled relative risk (RR) with 95% confidence intervals (CIs). Moreover, trial sequential analysis (TSA) was conducted to evaluate the conclusiveness of the H. pylori eradication rate. RESULTS: Six randomized controlled trials (RCTs) with 1233 patients were included. The VA therapy has similar eradication rate (ITT analysis: 87% vs. 85.7%, RR = 1.01, 95% CI: 0.93-1.09, p = 0.84; PP analysis: 92.5% vs. 93.2%, RR = 1.00, 95% CI: 0.94-1.06, p = 0.97) and compliance (RR = 1.01, 95% CI: 0.99-1.03, p = 0.32) compared to BQT. The VA therapy group had a significantly lower incidence of total adverse events than the BQT group (16.3% vs. 40.0%, RR = 0.45, 95% CI: 0.37-0.55, p < 0.00001). The TSA result showed that the effect was conclusive. CONCLUSIONS: Current evidence indicated that VA therapy is just as successful as BQT in eliminating H. pylori, yet it has fewer adverse events and similar compliance.
Subject(s)
Amoxicillin , Anti-Bacterial Agents , Bismuth , Helicobacter Infections , Helicobacter pylori , Sulfonamides , Humans , Amoxicillin/adverse effects , Amoxicillin/pharmacology , Amoxicillin/therapeutic use , Anti-Bacterial Agents/pharmacology , Bismuth/adverse effects , Bismuth/pharmacology , Bismuth/therapeutic use , Drug Therapy, Combination , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/pharmacology , Randomized Controlled Trials as Topic , Treatment Outcome , Sulfonamides/adverse effects , Sulfonamides/pharmacology , Sulfonamides/therapeutic useABSTRACT
Background: The Chinese pharmacopeia records Terminalia chebula as effective in treating prolonged diarrhea and dysentery, blood in the stool, and prolapse. Modern pharmacological research proves it has multiple pharmacological benefits, including antioxidant, anti-inflammatory, analgesic, hepatoprotective, neuroprotective, and other properties. Objectives: This study aims to clarify the role of Terminalia chebula's ethyl acetate extract (TCEA) on ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) in mice, as well as explore the potential mechanism of action. Materials and methods: The variation of different extracts of T. chebula was detected using the HPLC technique, and the main components in TCEA were identified. DSS was used to establish a mouse model to mimic the physiological state of UC in humans; the alleviating effect of TCEA and positive control 5-ASA on UC mice were evaluated by gavage treatment. Disease progression was assessed by monitoring the mouse's weight change and disease activity index (DAI). The changes in colon tissue were estimated by measuring colon length, HE, and AB-PAS staining and detecting oxidative stress parameters. The results draw from Western blot and real-time PCR showed the TLR4/MyD88/NF-κB pathway may involve in the anti-inflammatory activity of TCEA. Furthermore, the gut flora sequencing technique was employed to monitor the differentiation of intestinal microbiota of mice induced by DSS and TCEA treatment. Results: TCEA significantly lowered DAI scores and inhibited the weight loss and colonic shortening induced by DSS. The colon histomorphology and oxidative stress levels were enhanced after TCEA treatment compared with DSS induced UC group. TCEA attenuated the inflammatory response by regulating TLR4/MyD88/NF-κB pathway activation. Intestinal flora sequencing showed that DSS and TCEA greatly impacted mice's composition and diversity of intestinal microorganisms. But TCEA increased the abundance of Bacteroidetes and decreased the abundance of Firmicutes and Proteobacteria compared with the DSS group, which contributed a lot to returning the intestinal flora to a balanced state. Conclusion: This study confirms the alleviating effect of TCEA on UC and provides new ideas for developing TCEA into a new drug to treat UC.
ABSTRACT
Ferroptosis suppressor protein 1 (FSP1, also known as AIMF2, AMID or PRG3) is a recently identified glutathione-independent ferroptosis suppressor1-3, but its underlying structural mechanism remains unknown. Here we report the crystal structures of Gallus gallus FSP1 in its substrate-free and ubiquinone-bound forms. The structures reveal a FAD-binding domain and a NAD(P)H-binding domain, both of which are shared with AIF and NADH oxidoreductases4-9, and a characteristic carboxy-terminal domain as well. We demonstrate that the carboxy-terminal domain is crucial for the catalytic activity and ferroptosis inhibition of FSP1 by mediating the functional dimerization of FSP1, and the formation of two active sites located on two sides of FAD, which are responsible for ubiquinone reduction and a unique FAD hydroxylation respectively. We also identify that FSP1 can catalyze the production of H2O2 and the conversion of FAD to 6-hydroxy-FAD in the presence of oxygen and NAD(P)H in vitro, and 6-hydroxy-FAD directly inhibits ferroptosis in cells. Together, these findings further our understanding on the catalytic and ferroptosis suppression mechanisms of FSP1 and establish 6-hydroxy-FAD as an active cofactor in FSP1 and a potent radical-trapping antioxidant in ferroptosis inhibition.
Subject(s)
Ferroptosis , Hydrogen Peroxide , NAD , Ubiquinone , CatalysisABSTRACT
Ulcerative colitis (UC) is a chronic inflammatory disease significantly impacting patients' lives. This study aimed to elucidate the alleviating effect of ethyl acetate extract (TBEA) from Terminalia bellirica fruit on UC and to explore its mechanism. TBEA was the fraction with the best anti-inflammatory activity screened using in vitro anti-inflammatory assays, and HPLC initially characterized its composition. The mice model of ulcerative colitis was established after free drinking of 2.5% dextran sulfate sodium for six days, and the experimental group was treated with 50 mg/kg and 100 mg/kg TBEA for seven days. We found that TBEA significantly alleviated symptoms in UC mice, including a physiologically significant reduction in disease activity index and pathological damage to colonic tissue. TBEA dramatically slowed down oxidative stress and inflammatory process in UC mice, as evidenced by decreasing myeloperoxidase and malondialdehyde activities and increasing glutathione and catalase levels by reducing the concentrations of IL-6, IL-1ß, TNF-α, and NO in UC mice, as well as by regulating key proteins in the IL-6/JAK2/STAT3 pathway. Meanwhile, TBEA maintained intestinal homeostasis by regulating intestinal flora structure. Our study provides new ideas for developing TBEA into a new drug to treat UC.
Subject(s)
Colitis, Ulcerative , Colitis , Gastrointestinal Microbiome , Terminalia , Animals , Mice , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Cytokines/metabolism , Terminalia/metabolism , Inflammation Mediators/metabolism , Interleukin-6/metabolism , Fruit/metabolism , Colon/metabolism , Anti-Inflammatory Agents/therapeutic use , Dextran Sulfate/adverse effects , Mice, Inbred C57BL , Disease Models, Animal , Colitis/drug therapyABSTRACT
This meta-analysis evaluated the role of evidence-based nursing interventions in preventing pressure ulcers in patients with stroke. Computer systems were used to retrieve randomised controlled trials (RCTs) on evidence-based nursing interventions for patients with stroke and comorbid pressure ulcers from PubMed, EMBASE, Scopus, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang Data from database inception until April 2023. Two researchers independently screened the literature, extracted the data and evaluated the quality of the included studies according to the inclusion and exclusion criteria. RevMan 5.4 software was used for the meta-analysis. A total of 23 articles with results on 2035 patients were included, with 1015 patients in the evidence-based nursing group and 1020 patients in the routine nursing group. The meta-analysis results showed that evidence-based nursing interventions significantly reduced the incidence of pressure ulcers in patients with stroke (5.22% vs. 22.84%, odds ratio [OR]: 0.18, 95% confidence interval [CI]: 0.13-0.24, p < 0.001), delayed the onset of pressure ulcers (standardised mean difference [SMD]: 3.41, 95% CI: 1.40-5.42, p < 0.001) and improved patient quality of life (SMD: 2.95, 95% CI: 2.35-3.56, p < 0.001). Evidence-based nursing interventions are effective at preventing pressure ulcers in patients with stroke, delaying the onset of pressure ulcers and improving their quality of life. Evidence-based nursing should be promoted for patients with stroke. However, owing to differences in sample size between studies and the methodological inadequacies of some studies, these results should be verified by large, high-quality RCTs.
Subject(s)
Pressure Ulcer , Stroke , Humans , Pressure Ulcer/prevention & control , Evidence-Based Nursing , Stroke/complications , ChinaABSTRACT
Background and objective: Recently, a large number of trials on proton pump inhibitor-amoxicillin-containing high-dose dual therapy (HDDT) versus bismuth-containing quadruple therapy (BQT) for Helicobacter pylori (H. pylori) eradication have been published with controversial and inconsistent conclusions. The aim of this meta-analysis was to determine the effects of HDDT for H. pylori eradication compared to BQT. Design: A systematic review and meta-analysis was conducted. Methods: PubMed, Embase, and the Cochrane library database were searched to collect all randomized controlled trials (RCTs) assessing the effects of HDDT versus BQT to H. pylori eradication from inception to September 2022. Meta-analysis was conducted to estimate the pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effects model. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis (TSA) was performed to determine the reliability and conclusiveness. Results: A total of 14 RCTs with 5121 patients were included. The results of meta-analysis showed that there was no statistical significance in the eradication rate between HDDT and BQT (intention-to-treat analysis: 86.7% versus 85.1%, RR = 1.01, 95% CI: 0.98-1.04; per-protocol analysis: 89.9% versus 89.4%, RR = 1.01, 95% CI: 0.98-1.03; moderate-quality evidence). The incidence of total adverse effects in HDDT group was significantly lower than in BQT group (5.9% versus 34.1%, RR = 0.42, 95% CI: 0.34-0.50; low-quality evidence). No statistical significance was observed in compliance between HDDT and BQT (RR = 1.01, 95% CI, 1.00-1.03, p = 0.07; low-quality evidence). The TSA result for H. pylori eradication rate indicated that the effect was conclusive. Conclusions: Evidence from our updated meta-analysis suggests that HDDT is as effective as BQT in eradicating H. pylori, with fewer adverse effects and similar compliance. Registration: Open Science Framework registries (No: osf.io/th4vd).
ABSTRACT
Exobasidium rhododendri is a parasite of Rhododendron and also infects apples. A chromosome-level genome of E. rhododendri was assembled using the PacBio and Illumina datasets. The complete genome length is 17.6 Mb, with N50 of 5.45 Mb, and its GC content is 50.08%. The assembly obtained contains four scaffolds, including three nuclear chromosomes and one mitochondrion. There are a total of 6,982 predicted protein-encoding genes containing 406 fungal secretion proteins and 249 candidate effectors in the E. rhododendri genome. This high-quality genome will help understand the pathogenic mechanism of this fungus.
Subject(s)
Basidiomycota , Rhododendron , Plant Diseases/microbiology , Basidiomycota/genetics , Fungal Proteins/genetics , Rhododendron/genetics , PhylogenyABSTRACT
Acetyl-keto-b-boswellic acid (AKBA) functions in combating human malignant tumors, including lung cancer. However, the function of AKBA in regulating the radioresistance of lung cancer and its underlying mechanism still need to be elucidated. Radiation-resistant lung cancer cells (RA549) were established. Quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot were employed to examine the messenger RNA (mRNA) and protein expressions. After being treated with AKBA and different doses of X-ray, cell proliferation and survival were examined using colony formation assay and cell-counting kit-8 (CCK-8) assay. The cellular localization of Forkhead box 1 (FOXO1) was measured by immunofluorescence (IF). Flow cytometry was employed to analyze cell cycle and apoptosis. In addition, in vivo experiment was performed to determine the effect of AKBA on the sensitivity of tumors to radiation. Herein, we found that AKBA could enhance the radiosensitivity in RA549, suppress cell proliferation, induce cell apoptosis and arrest cell cycle. It was observed that maspin was lowly expressed and hypermethylated in RA549 cells compared to that in A549 cells, while these changes were all eliminated by AKBA treatment. Maspin knockdown could reverse the regulatory effects of AKBA on radioresistance and cellular behaviors of RA549 cells. In addition, we found that AKBA treatment could repress the phosphorylation of Serine/Threonine Kinase (AKT), and FOXO1, increase the translocation of FOXO1 and p21 level in RA549 cells, which was abolished by maspin knockdown. Moreover, results of tumor xenograft displayed that AKBA could enhance the sensitivity of tumor to radiation through the maspin/AKT/FOXO1/p21 axis. We discovered that AKBA enhanced the radiosensitivity of radiation-resistant lung cancer cells by regulating maspin-mediated AKT/FOXO1/p21 axis.
Subject(s)
Lung Neoplasms , Proto-Oncogene Proteins c-akt , Triterpenes , Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Forkhead Box Protein O1/metabolism , Forkhead Box Protein O1/pharmacology , Lung Neoplasms/radiotherapy , Methylation , Proto-Oncogene Proteins c-akt/metabolism , Triterpenes/pharmacologyABSTRACT
Physical attributes of Chinese herbal extracts are determined by their chemical components, and the physical and chemical attributes jointly affect the preparation process performance and the final product quality. Therefore, in order to improve the quality control of Chinese herbal extracts, we should comprehensively study the batch-to-batch consistency of physical and chemical attributes as well as the correlations between them. This paper first explored the physical attributes affecting the preparation process performance of the compound Danshen extract and developed a method for characterizing the texture attributes. With such main chemical components as water, phenolic acids, saponins, and saccharides and texture, rheology, and other physical attributes taken into consideration, the batch-to-batch quality fluctuation of products from different production lines and time was analyzed by principal components analysis(PCA). Finally, the correlation and partial least squares(PLS) analysis was conducted, and the regression equation was established. The fitting result of the PLS model for dynamic viscosity was satisfying(R~2Y=0.857, Q~2=0.793), suggesting that the chemical components could be adjusted by the component transfer rate in the extraction process, the impurity removal rate in the alcohol precipitation process, and the water retention rate of the concentration process to meet the control of the extract dynamic viscosity. This study clarified the correlations between physical and chemical attributes of the compound Danshen extract and established a method for controlling its physical attributes based on process regulation, which would provide reference for improving the quality control of Chinese herbal extracts.
Subject(s)
Drugs, Chinese Herbal , Salvia miltiorrhiza , Drugs, Chinese Herbal/chemistry , Quality Control , Salvia miltiorrhiza/chemistry , WaterABSTRACT
In recent years, considerable research efforts have been devoted to the development of wearable multi-functional sensing technology to fulfill the requirements of healthcare smart detection, and much progress has been achieved. Due to the appealing characteristics of flexibility, stretchability and long-term stability, the sensors have been used in a wide range of applications, such as respiration monitoring, pulse wave detection, gait pattern analysis, etc. Wearable sensors based on single mechanisms are usually capable of sensing only one physiological or motion signal. In order to measure, record and analyze comprehensive physical conditions, it is indispensable to explore the wearable sensors based on hybrid mechanisms and realize the integration of multiple smart functions. Herein, we have summarized various working mechanisms (resistive, capacitive, triboelectric, piezoelectric, thermo-electric, pyroelectric) and hybrid mechanisms that are incorporated into wearable sensors. More importantly, to make wearable sensors work persistently, it is meaningful to combine flexible power units and wearable sensors and form a self-powered system. This article also emphasizes the utility of self-powered wearable sensors from the perspective of mechanisms, and gives applications. Furthermore, we discuss the emerging materials and structures that are applied to achieve high sensitivity. In the end, we present perspectives on the outlooks of wearable multi-functional sensing technology.
ABSTRACT
OBJECTIVES: The aim of this study was to investigate a possible association between changes in low parathyroid hormone (PTH) levels and cardiac function decline in maintenance hemodialysis (MHD) patients. METHODS: A total of 150 MHD patients were included and followed for 24 months. The enrolled patients were divided into 3 groups based on their PTH status at baseline and 24 months. Factors potentially involved in changes in the PTH level and cardiac function were compared using multivariate logistic regression analysis. RESULTS: At 24 months, the presence of low PTH levels increased by 26.7%. The main independent factors for low PTH levels were a low BMI, hemoglobin, and serum albumin and high serum calcium (p < 0.05). A persistently low PTH level at 24 months was associated with a decrease in the left ventricular ejection fraction (LVEF) and increase in valvular calcification (p < 0.05). Additionally, a decrease in PTH levels from normal or high to low values was associated with a decrease in LVEF and cardiac output (CO) and an increase in valvular calcification (p < 0.05). Furthermore, compared with those of the persistently low PTH level group, LVEF values were lower at 24 months in the group with a decrease from high/normal to low PTH level (p < 0.05). CONCLUSION: Persistently low PTH levels and changes in the PTH level from high/normal to low were associated with cardiac function decline in MHD patients. Moreover, a PTH level change from high/normal to low showed a stronger correlation with cardiac function decline.
Subject(s)
Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Parathyroid Hormone/blood , Renal Dialysis/adverse effects , Ventricular Function, Left/physiology , Aged , Female , Humans , Hypoparathyroidism , Male , Middle Aged , Stroke VolumeABSTRACT
The mixing process is one of the key operation units for solid preparation of traditional Chinese medicine. The physical properties such as particle size, density and viscosity of the mixture are key factors that need to be controlled, which will directly affect the performance of the preparation molding process and product quality. Subsequent dripping process performance and appearance qua-lity of dripping pills will be affected by dynamic viscosity of materials in the mixing process. Based on this, with mixing process of compound Danshen dripping pills as the object, a feedforward control method for the dripping pill mixing process was established based on the concept of quality by design(QbD). Firstly, critical quality attribute(CQA)-dynamic viscosity, critical material attributes(CMAs)-the moisture content of compound Danshen extract, average molecular weight of polyethylene glycol 6000 and critical process parameter(CPP)-mixing temperature were identified through the analysis of properties for multiple batches of the raw materials and excipients as well as technological mechanism. Then the Box-Behnken experimental design was used to establish the regression model among CMA, CPP and CMA(Râ =0.972 0, RMSE =16.24) to obtain the design space. Finally, through the verification of three batches within the design space, the mixing process temperature was adjusted according to the properties of the raw materials and exci-pients to achieve accurate control of the dynamic viscosity attribute. The relative deviation between the actual dynamic viscosity value and the target value was less than 3.0 %. The feedforward control of the mixing process of compound Danshen dripping pills was rea-lized in this study, which can contribute to improving quality consistency of the mixing process intermediates, simultaneously provide a reference for the research on the process quality control of other Chinese medicine dripping pills.
Subject(s)
Drugs, Chinese Herbal , Research Design , Camphanes , Medicine, Chinese Traditional , Panax notoginseng , Quality Control , Salvia miltiorrhizaABSTRACT
Anxious major depressive disorder is a common subtype of major depressive disorder; however, its unique neural mechanism is not well-understood currently. Using multimodal MRI data, this study examined common and specific alterations of amygdala subregions between patients with and without anxiety. No alterations were observed in the gray matter volume or intra-region functional integration in either patient group. Compared with the controls, both patient groups showed decreased functional connectivity between the left superficial amygdala and the left putamen, and between the right superficial amygdala and the bilateral anterior cingulate cortex and medial orbitofrontal cortex, while only patients with anxiety exhibited decreased activity in the bilateral laterobasal and superficial amygdala. Moreover, the decreased activity correlated negatively with the Hamilton depression scale scores in the patients with anxiety. These findings provided insights into the pathophysiologic processes of anxious major depressive disorder and may help to develop new and effective treatment programs.
ABSTRACT
Two hundred and forty-four ustilaginomycetous yeast or yeast-like strains were isolated from the soil, skin of animals or humans and plant materials during the past 20 years. Among them, 203 strains represent 39 known species, whereas 41 strains represent several novel species based on the sequence analyses of the rDNA genes [18S rDNA, Internal Transcribed Spacer (ITS) regions, 26S rDNA D1/D2 domain] and three protein genes (RPB1, RPB2, and TEF1). In this study, one new order, one new family, four new genera, twenty new species, and two new combinations were proposed. They are Franziozymales ord. nov., Franziozymaceae fam. nov., Baueromyces gen. nov., Franziozyma gen. nov., Guomyces gen. nov., Yunzhangomyces gen. nov., Baueromyces planticola sp. nov., Franziozyma bambusicola sp. nov., Gjaerumia cyclobalanopsidis sp. nov., Gjaerumia pseudominor sp. nov., Jamesdicksonia aceris sp. nov., Jaminaea lantanae sp. nov., Kalmanozyma hebeiensis sp. nov., Langdonia ligulariae sp. nov., Meira hainanensis sp. nov., Meira pileae sp. nov., Meira plantarum sp. nov., Phragmotaenium parafulvescens sp. nov., Sporisorium cylindricum sp. nov., Sympodiomycopsis europaea sp. nov., Tilletiopsis lunata sp. nov., Tilletiopsis pinicola sp. nov., Yunzhangomyces clavatus sp. nov., Yunzhangomyces cylindricus sp. nov., Yunzhangomyces qinlingensis sp. nov., Yunzhangomyces orchidis sp. nov., Guomyces nicotianae comb. nov., and Yunzhangomces scirpi comb. nov.
ABSTRACT
Cyclic di-AMP is a bacterial nucleotide second messenger and evaluated as a potential vaccine adjuvant candidate. Here, we report a practical and economical enzymatic method for gram-scale preparation of c-di-AMP using an immobilized Vibrio cholerae dinucleotide cyclase DncV. The method mainly includes four steps: preparation of DncV-immobilized resin, enzymatic synthesis of c-di-AMP, purification using macroporous absorption resin SP207, and desiccation using rotary evaporation and lyophilization. Enzymatic synthesis is the most critical step, and almost all substrate ATP was converted to c-di-AMP under an optimum condition in which 300 mL of 300 mM NH4Ac/NH3 pH 9.5 buffer supplemented with 20 mM MnCl2, 10 mM ATP and 4 mL of DncV-immobilized resin containing â¼19 mg DncV were incubated at 30 °C overnight. After purification, up to 1 g of the diammonium salt of c-di-AMP with weight purity of ≥98% was obtained as white powder, which corresponds to an overall yield of â¼80% based on the ATP input into the reaction. The method is easily performed in laboratory to prepare c-di-AMP on a gram scale and could be used in industry on a large scale.
Subject(s)
Vibrio cholerae , Bacterial Proteins , Dinucleoside PhosphatesABSTRACT
Polycyclic tetramate macrolactams (PoTeMs) are a group of hybrid PK-NRP natural products having a variable set of carbocyclic rings, a conserved assembly pathway, and diverse bioactivities. We report here the identification of seven new PoTeMs, clifednamides D-J (3-9), along with the known clifednamides A (1) and B (2) through rational pathway refactoring and heterologous expression. Remarkably, clifednamides D (3), G (6), and H (7) feature an unprecedented 27,28-seco skeleton. The cytotoxic activities of compounds 1-9 indicated that the hydroxy group of C-25, the methyl group of C-30, the inner five-membered ring, and the intact macrocycle are all critical for the activities. Meanwhile, the cytochrome P450 enzyme CftS023A and the hydroxylase CftS023E involved in oxidative tailoring of clifednamides were found to decorate the fused 5-6 bicyclic intermediates. Accordingly, the biosynthetic pathway for clifednamides was proposed.
Subject(s)
Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/chemistry , Streptomyces/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Biosynthetic Pathways , Cell Line, Tumor , Cytochrome P-450 Enzyme System/metabolism , Drug Screening Assays, Antitumor , Humans , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Mixed Function Oxygenases/metabolism , Molecular Structure , Oxidation-Reduction , Soil Microbiology , Streptomyces/metabolismABSTRACT
Glycosylation of natural products can influence their pharmacological properties, and efficient glycosyltransferases (GTs) are critical for this purpose. The polyketide epothilones are potent anti-tumour compounds, and YjiC is the only reported GT for the glycosylation of epothilone. In this study, we phylogenetically analysed 8261 GTs deposited in CAZy database and revealed that YjiC locates in a subbranch of the Macrolide I group, forming the YjiC-subbranch with 160 GT sequences. We demonstrated that the YjiC-subbranch GTs are normally efficient in epothilone glycosylation, but some showed low glycosylation activities. Sequence alignment of YjiC-subbranch showed that the 66th and 77th amino acid residues, which were close to the catalytic cavity in molecular docking model, were conserved in five high-active GTs (Q66 and P77) but changed in two low-efficient GTs. Site-directed residues swapping at the two positions in the two low-active GTs (BssGT and BamGT) and the high-active GT BsGT-1 demonstrated that the two amino acid residues played an important role in the catalytic efficiency of epothilone glycosylation. This study highlights that the potent GTs for appointed compounds are phylogenetically grouped with conserved residues for the catalytic efficiency.
Subject(s)
Epothilones/metabolism , Glycosyltransferases/metabolism , Tubulin Modulators/metabolism , Biotransformation , Catalytic Domain , Conserved Sequence , Glycosylation , Glycosyltransferases/classification , Glycosyltransferases/genetics , Kinetics , Molecular Docking Simulation , Phylogeny , Sequence AlignmentABSTRACT
Yimeng wool rabbit is a national breed of geographical indication in China. The complete mitochondrial genome sequence of Yimeng wool rabbit was first determined in this study (Accession number MN296708). The mitogenome (16,740 bp) consists of 22 tRNA genes, 2 ribosomal RNA genes, 13 protein-coding genes, and 1 control region (D-loop region). The complete mitochondrial genome sequence of the Yimeng wool rabbit enriches data resource for further study in genetic mechanism and classification.
ABSTRACT
Neural physiological functions and synaptic changes underlying the pathogenesis of depression have obtained great achievements. However, neuronal morphological changes under a depressive state have not been well understood yet. Here a depressive-like YFP-H transgenic mouse model was produced by light deprivation (LD), and morphological changes of retinal ganglion cells (RGCs) and primary visual and auditory cortical layer 5 pyramidal cells (L5PCs) were investigated. Three distinct RGC subtypes were identified based on soma- and dendritic field (DF) size. RGA cells were highlighted by large soma and medium-sized to large DF. RGB cells were characterized by small- to medium-sized soma and small- to medium-sized DF. RGC cells were typical of small- to medium-sized soma and large DF. LD showed cell-type-specific morphological orchestrations on RGCs and predominantly promoted the dendritic growth of RGA cells, leaving no significant effect on RGB and RGC cells. LD produced a consistently suppressed effect on the morphology of primary visual and auditory cortical L5PCs. LD enhanced the dendritic spine density of primary visual cortical L5PCs, implying a compensation mechanism underlying morphological changes in individual cortical L5PCs. The increased morphological complexity of RGA cells and the simplified morphology of cortical L5PCs suggest a broad range of neuronal morphological "cross-modal plasticity" among different brain areas. Our observations in morphological changes of RGCs and cortical L5PCs under a depressive-like state will provide some insights into the pathogenesis of depression at a single neuronal morphological level.