In this study,circular dichroism(CD)and molecular dynamics(MD)simulation were used to investigate the thermal unfolding pathway of staphylococcal enterotoxin B(SEB)at temperatures of 298–371 and 298–500 K,and the re...In this study,circular dichroism(CD)and molecular dynamics(MD)simulation were used to investigate the thermal unfolding pathway of staphylococcal enterotoxin B(SEB)at temperatures of 298–371 and 298–500 K,and the relationship between the experimental and simulation results were explored.Our computational findings on the secondary structure of SEB showed that at room temperature,the CD spectroscopic results were highly consistent with the MD results.Moreover,under heating conditions,the changing trends of helix,sheet and random coil obtained by CD spectral fitting were highly consistent with those obtained by MD.In order to gain a deeper understanding of the thermal stability mechanism of SEB,the MD trajectories were analyzed in terms of root mean square deviation(RMSD),secondary structure assignment(SSA),radius of gyration(R_(g)),free energy surfaces(FES),solvent-accessible surface area(SASA),hydrogen bonds and salt bridges.The results showed that at low heating temperature,domain Ⅰ without loops(omitting the mobile loop region)mainly relied on hydrophobic interaction to maintain its thermal stability,whereas the thermal stability of domain Ⅱ was mainly controlled by salt bridges and hydrogen bonds.Under high heating temperature conditions,the hydrophobic interactions in domain Ⅰ without loops were destroyed and the secondary structure was almost completely lost,while domain Ⅱ could still rely on salt bridges as molecular staples to barely maintain the stability of the secondary structure.These results help us to understand the thermodynamic and kinetic mechanisms that maintain the thermal stability of SEB at the molecular level,and provide a direction for establishing safer and more effective food sterilization processes.展开更多
AIM: To explore the change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis (NASH) in rats. METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into control group a...AIM: To explore the change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis (NASH) in rats. METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into control group and model group. Rats in the control group were given normal diet, and rats in the model group were given fat-rich diet. Eight rats in each group were killed at end of the 8th and 12th wk, respectively. The levels of endotoxin, D-xylose, TG, TC, ALT and AST, intestinal tissue SOD and MDA as well as intestinal mucus secretory IgA (sIgA) were measured. The pathology of liver was observed by HE staining. RESULTS: At end of the 8th wk, there was no marked difference in the levels of endotoxin, D-xylose and sIgA between the two groups. At end of the 12th wk, rats in the model group developed steatohepatitis and had a higher serum level of endotoxin (P = 0.01) and D-xylose (P = 0.00) and a lower serum level of sIgA (P = 0.007). CONCLUSION: Intestinal mucosa barrier malfunction may exist in NASH rats and may be an important promoter of NASH in rats.展开更多
It is now widely recognized that chronic hepatitis C (CHC)is associated with insulin resistance(IR)and type 2 diabetes,so can be considered a metabolic disease.IR is most strongly associated with hepatitis C virus(HCV...It is now widely recognized that chronic hepatitis C (CHC)is associated with insulin resistance(IR)and type 2 diabetes,so can be considered a metabolic disease.IR is most strongly associated with hepatitis C virus(HCV)genotype 1,in contrast to hepatic steatosis, which is associated with genotype 3 infection.Apart from the well-described complications of diabetes,IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma.More recently,it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined.This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.展开更多
Background:The proportion of recurrences after discharge among patients with coronavirus disease 2019(COVID-19)was reported to be between 9.1%and 31.0%.Little is known about this issue,however,so we performed a meta-a...Background:The proportion of recurrences after discharge among patients with coronavirus disease 2019(COVID-19)was reported to be between 9.1%and 31.0%.Little is known about this issue,however,so we performed a meta-analysis to summarize the demographical,clinical,and laboratorial characteristics of non-recurrence and recurrence groups.Methods:Comprehensive searches were conducted using eight electronic databases.Data re-garding the demographic,clinical,and laboratorial characteristics of both recurrence and non-recurrence groups were extracted,and quantitative and qualitative analyses were conducted.Results:Ten studies involving 2071 COVID-19 cases were included in this analysis.The proportion of recurrence cases involving patients with COVID-19 was 17.65%(between 12.38%and 25.16%)while older patients were more likely to experience recurrence(weighted mean difference(WMD)=1.67,range between 0.08 and 3.26).The time from discharge to recurrence was 13.38 d(between 12.08 and 14.69 d).Patients were categorized as having moderate severity(odds ratio(OR)=2.69,range between 1.30 and 5.58),while those with clinical symptoms including cough(OR=5.52,range between 3.18 and 9.60),sputum production(OR=5.10,range between 2.60 and 9.97),headache(OR=3.57,range between 1.36 and 9.35),and diz-ziness(OR=3.17,range between 1.12 and 8.96)were more likely to be associated with recurrence.Patients pre-senting with bilateral pulmonary infiltration and decreased leucocyte,platelet,and CD4+T counts were at risk of COVID-19 recurrence(OR=1.71,range between 1.07 and 2.75;WMD=?1.06,range between?1.55 and?0.57,WMD=?40.39,range between?80.20 and?0.48,and WMD=?55.26,range between?105.92 and?4.60,respectively).Conclusions:The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after hospital discharge were older age,moderate severity,bilateral pulmonary infiltration,laboratory findings including decreased leucocytes,platelets,and CD4+T counts,and clinical symptoms including cough,sputum production,headache,and dizziness.These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.展开更多
文摘In this study,circular dichroism(CD)and molecular dynamics(MD)simulation were used to investigate the thermal unfolding pathway of staphylococcal enterotoxin B(SEB)at temperatures of 298–371 and 298–500 K,and the relationship between the experimental and simulation results were explored.Our computational findings on the secondary structure of SEB showed that at room temperature,the CD spectroscopic results were highly consistent with the MD results.Moreover,under heating conditions,the changing trends of helix,sheet and random coil obtained by CD spectral fitting were highly consistent with those obtained by MD.In order to gain a deeper understanding of the thermal stability mechanism of SEB,the MD trajectories were analyzed in terms of root mean square deviation(RMSD),secondary structure assignment(SSA),radius of gyration(R_(g)),free energy surfaces(FES),solvent-accessible surface area(SASA),hydrogen bonds and salt bridges.The results showed that at low heating temperature,domain Ⅰ without loops(omitting the mobile loop region)mainly relied on hydrophobic interaction to maintain its thermal stability,whereas the thermal stability of domain Ⅱ was mainly controlled by salt bridges and hydrogen bonds.Under high heating temperature conditions,the hydrophobic interactions in domain Ⅰ without loops were destroyed and the secondary structure was almost completely lost,while domain Ⅱ could still rely on salt bridges as molecular staples to barely maintain the stability of the secondary structure.These results help us to understand the thermodynamic and kinetic mechanisms that maintain the thermal stability of SEB at the molecular level,and provide a direction for establishing safer and more effective food sterilization processes.
文摘AIM: To explore the change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis (NASH) in rats. METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into control group and model group. Rats in the control group were given normal diet, and rats in the model group were given fat-rich diet. Eight rats in each group were killed at end of the 8th and 12th wk, respectively. The levels of endotoxin, D-xylose, TG, TC, ALT and AST, intestinal tissue SOD and MDA as well as intestinal mucus secretory IgA (sIgA) were measured. The pathology of liver was observed by HE staining. RESULTS: At end of the 8th wk, there was no marked difference in the levels of endotoxin, D-xylose and sIgA between the two groups. At end of the 12th wk, rats in the model group developed steatohepatitis and had a higher serum level of endotoxin (P = 0.01) and D-xylose (P = 0.00) and a lower serum level of sIgA (P = 0.007). CONCLUSION: Intestinal mucosa barrier malfunction may exist in NASH rats and may be an important promoter of NASH in rats.
基金Supported by Australian National Health and Medical Research Council and the Robert W Storr Bequest to the University of Sydney
文摘It is now widely recognized that chronic hepatitis C (CHC)is associated with insulin resistance(IR)and type 2 diabetes,so can be considered a metabolic disease.IR is most strongly associated with hepatitis C virus(HCV)genotype 1,in contrast to hepatic steatosis, which is associated with genotype 3 infection.Apart from the well-described complications of diabetes,IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma.More recently,it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined.This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.
基金Project supported by the National Science and Technology Major Project of China(Nos.2018ZX10302206 , 2017ZX10202203)the Zhejiang University Academic Award for Outstanding Doctoral Candidates(No.2020052),China。
文摘Background:The proportion of recurrences after discharge among patients with coronavirus disease 2019(COVID-19)was reported to be between 9.1%and 31.0%.Little is known about this issue,however,so we performed a meta-analysis to summarize the demographical,clinical,and laboratorial characteristics of non-recurrence and recurrence groups.Methods:Comprehensive searches were conducted using eight electronic databases.Data re-garding the demographic,clinical,and laboratorial characteristics of both recurrence and non-recurrence groups were extracted,and quantitative and qualitative analyses were conducted.Results:Ten studies involving 2071 COVID-19 cases were included in this analysis.The proportion of recurrence cases involving patients with COVID-19 was 17.65%(between 12.38%and 25.16%)while older patients were more likely to experience recurrence(weighted mean difference(WMD)=1.67,range between 0.08 and 3.26).The time from discharge to recurrence was 13.38 d(between 12.08 and 14.69 d).Patients were categorized as having moderate severity(odds ratio(OR)=2.69,range between 1.30 and 5.58),while those with clinical symptoms including cough(OR=5.52,range between 3.18 and 9.60),sputum production(OR=5.10,range between 2.60 and 9.97),headache(OR=3.57,range between 1.36 and 9.35),and diz-ziness(OR=3.17,range between 1.12 and 8.96)were more likely to be associated with recurrence.Patients pre-senting with bilateral pulmonary infiltration and decreased leucocyte,platelet,and CD4+T counts were at risk of COVID-19 recurrence(OR=1.71,range between 1.07 and 2.75;WMD=?1.06,range between?1.55 and?0.57,WMD=?40.39,range between?80.20 and?0.48,and WMD=?55.26,range between?105.92 and?4.60,respectively).Conclusions:The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after hospital discharge were older age,moderate severity,bilateral pulmonary infiltration,laboratory findings including decreased leucocytes,platelets,and CD4+T counts,and clinical symptoms including cough,sputum production,headache,and dizziness.These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.
