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As enveloped virus, SARS-CoV-2 membrane protein (M) mediates viral release from cellular membranes, but the molecular mechanisms of SARS-CoV-2 virions release remain poorly understood. Here, we performed RNAi screening and identified the E3 ligase RNF5 which mediates ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of viral envelope (E) with M. M-E complex ensures the uniform size of viral particles for viral maturation and mediates viral release. Moreover, overexpression of M induces complete autophagy which is dependent on RNF5-mediated ubiquitin modification. M inhibits the activity of lysosome protease, and uses autolysosomes for virion release. Consequently, all these results demonstrate that RNF5 mediates ubiquitin modification of SARS-CoV-2 M to stabilize the M-E complex and induce autophagy for virion release.
RESUMO
Objective To investigate the relationship between the serum levels of retinol-binding protein 4(RBP4),blood lipid level and glycemic control in patients with chronic schizophrenia complicated with type 2 diabetes.Methods The levels of glycated hemoglobin (HbA1c),fasting plasma glucose (FPG),cholesterol (TC),triglycerides (TG),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C),apolipoproteinA1 (Apo A1),apolipoprotein B(Apo B),apolipoprotein E(Apo E),lipoprotein(a)[Lp (a)],free fatty acid(FFA),RBP4,fasting insulin (FINS) were determined in 96 patients with chronic schizo-phrenia complicated with type 2 diabetes (schizophrenia group) and 50 healthy subjects (healthy control group),the insulin resistance index (HOMA IR)was calculated.The patients were divided into HbA1c<7.0% group and HbA1c≥7.0% group according to the results of the HbA1c,and the results were statistically analyzed.Results In the HbA1c<7.0% group,the levels of HbA1c,FPG,TG,Apo B,Apo E,Lp(a),RBP4 were significantly higher than those in the healthy control group,the levels of serum Apo A1 and HDL-C was lower than those in the healthy control group (P<0.05).In the HbA1c≥7.0% group,the levels of HbA1c, Body mass index (BMI),FPG,TG,Apo E,FFA,RBP4,FINS,HOMA-IR were significantly higher than those in the HbA1c<7.0% group and the healthy control group,the levels of TC,Apo B,Lp(a)were significantly higher than the healthy control group and the levels of serum Apo A 1 and HDL-C were lower than those in the healthy control group (P<0.05).Single factor Logistic regression analysis showed that BMI,TG,Apo E, FFA,RBP4,FINS and HOMA-IR were risk factors for poor control of blood glucose in type 2 diabetes pa-tients with chronic schizophrenia.Conclusion The levels of RBP4 and blood lipid in patients with chronic schizophrenia complicated with type 2 diabetes may be related to the poor control of blood sugar level.
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Objective To perform a comparative research on nucleoside drug resistance mutation and genotypes of chronic hepa‐tits B virus in Shanghai and Lanzhou .Methods The serum samples(Shanghai ,194 cases) and (Lanzhou ,325 cases) were collected . The common 7 drug resistant mutation loci ,genotype B and C were detected by using the PCR‐LDR method .The obtained data were analyzed by using the SPSS17 .0 statistical software .Results (1) Genotype C was the main genotype in two areas (Shanghai 79 .3% ,Lanzhou 81 .4% ) .(2) The mutation rate in Shanghai was higher than that in Lanzhou with statistical difference (48 .9%vs .35 .3% ,P0 .05) .(3) The drug resistance mutation had no correlation with genotype .The C genotype mutation rate in Shanghai was higher than that in Lanzhou ,the difference was statistically significant (49 .0% vs .35 .4% ,P<0 .05 ) .(4) 4 kinds of drug re‐sistance rate had no correlation with genotype .Conclusion The genotype distributions are similar in two areas ;Shanghai has a higher drug resistance rate than Lanzhou ;the drug resistance occurrence has no relation with drug resistance type and genotype .
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Clopidogrel combinated with aspirin can significantly improve the prognosis of cardiovascular disease in patients with coronary heart disease undergoing PCI, but at the same time, which can increase the risk of cardiovascular hemorrhage. However, plus TCM can significantly improve the therapeutic effect, reduce symptoms of angina, reduce the adverse drug reaction to alleviate the suffering of the patients, in particular, which can reduce the dosage of medicine to improve the quality of life of patients, reduce the application time of using clopidogrel to reduce the financial burden of patients,then improve patient compliance. This review provided reference to combat PCI postoperative treatment using the combination of Chinese and western medicine methods.
