Glutamate receptors and schizophrenia:Schizophrenia is a chronic mental disorder affecting approximately 1%of the global population,with 70%-80%heritability.It has a multifactorial etiology involving both environmenta...Glutamate receptors and schizophrenia:Schizophrenia is a chronic mental disorder affecting approximately 1%of the global population,with 70%-80%heritability.It has a multifactorial etiology involving both environmental factors and a complex polygenic genetic architecture.Over the last two decades,large-scale genome-wide approaches revealed contributions of common variants with individually small effect sizes and of rare copy number variants with a large effect size.N-methy l-D-a spar tat e receptor(NMDAR)hypofunction has been implicated as a central mechanism in the pathophysiology of schizophrenia(Coyle et al.,2020).展开更多
BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient ...BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.展开更多
BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver fu...BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver function of patients with chronic liver disease(CLD).CASE SUMMARY This study involved data from patients whose chief complaint was reduced quality of life attributable to CLD.The new treatment approach resulted in improvements in the liver function and fatty liver of 30 patients with CLD.Im-provements were observed using abdominal ultrasonography.Unlike traditional methods,this protocol provided more sustainable and meaningful results.Treat-ment with 10 mL of HPE administered intravenously once or twice per week significantly improved liver function.The observed improvements in fatty liver and liver function suggest the utility of this approach for the management of patients with CLD.CONCLUSION This case series highlights the potential of innovative treatments for patients with CLD that could improve the quality of life of the patients.展开更多
Apicomplexan parasites predominantly generate ATP and lactic acid through glycolysis and anaerobic glucose metabolism,incorporating CO_(2) into glycolysis via a stage-dependent phosphoenolpyruvate carboxylase(PEPC)mec...Apicomplexan parasites predominantly generate ATP and lactic acid through glycolysis and anaerobic glucose metabolism,incorporating CO_(2) into glycolysis via a stage-dependent phosphoenolpyruvate carboxylase(PEPC)mechanism.Although the role of PEPC in plant and bacterial carbon fixation is well documented,its function within Babesia remains largely unexplored.This study employs reverse genetics to probe the biological role of PEPC in Babesia gibsoni,noting its conservation across similar protozoa,suggesting a pivotal and conserved biological function.Western blotting and immunofluorescence(IFA)experiments using the BgPEPC-3×Flag strain revealed that the BgPEPC protein has a molecular weight of 105 kDa and localizes predominantly to the cytoplasm.Attempts to knock out the PEPC gene in BgPEPC-3×Flag strains failed under standard media conditions,succeeded only with the addition of 5 mM malate,an upstream metabolite of oxaloacetic acid(OAA).In addition to malate,the downstream metabolite of OAA can also partially compensate for the phenotypic defects caused by PEPC deficiency.This intervention alleviated severe growth deficits,underscoring the critical role of aspartate in the parasite lifecycle.Moreover,metabolic inhibitors such as L-cycloserine and triazamidine,which target aspartate aminotransferase and mitochondrial functions,respectively,demonstrated increased efficacy against BgPEPC knockout strains.The lack of a compensatory response to malic acid supplementation underscores the integral role of BgPEPC in intermediary carbon metabolism and its necessity in providing aspartate as a precursor to pyrimidine synthesis.Collectively,these findings suggest that PEPC could be a potential target for future drug development against B.gibsoni infections.展开更多
[Objective]The study aimed to investigate the effects of the amino acids of aspartate family on the biosynthesis of CoQ10 in Rhodpseudomonas palustris J001.[Method]The impacts of amino acids of this family on the bios...[Objective]The study aimed to investigate the effects of the amino acids of aspartate family on the biosynthesis of CoQ10 in Rhodpseudomonas palustris J001.[Method]The impacts of amino acids of this family on the biosynthesis of CoQ10 in Rhodopseudomnas palustris J001 were investigated by feeding these amino acids at the end of the logarithmic phase during incubation,which aim was for the optimization of the fermentation medium and genetic improvement of the strain for CoQ10 production.[Result]The results showed that feeding proper amount of methione(125 mg/L)could increase CoQ10 production by 20.2%,but feeding of lysine(above 500 mg/L),threonine(above 400 mg/L)and/or isoleucine(above 400 mg/L)repressed the biosynthesis of CoQ10.The results indicated that the aspartate kinase is subject to feedback inhibition or repression by lysine,threonine and isoleucine in the strain,which was unfavorable to the formation of methioine and then caused the decrease of CoQ10 production.[Conclusion]Lysine,threonine and isoleucine auxotrophic mutants with resistance to analogues of lysine,threonine and isoleucine could increase the production of CoQ10.展开更多
文摘Glutamate receptors and schizophrenia:Schizophrenia is a chronic mental disorder affecting approximately 1%of the global population,with 70%-80%heritability.It has a multifactorial etiology involving both environmental factors and a complex polygenic genetic architecture.Over the last two decades,large-scale genome-wide approaches revealed contributions of common variants with individually small effect sizes and of rare copy number variants with a large effect size.N-methy l-D-a spar tat e receptor(NMDAR)hypofunction has been implicated as a central mechanism in the pathophysiology of schizophrenia(Coyle et al.,2020).
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2023-I2M-C&T-B-043National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015+1 种基金CAMS Innovation Fund for Medical Sciences,No.2021-1-12M-002Beijing Municipal Natural Science Foundation,No.M22014.
文摘BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.
文摘BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver function of patients with chronic liver disease(CLD).CASE SUMMARY This study involved data from patients whose chief complaint was reduced quality of life attributable to CLD.The new treatment approach resulted in improvements in the liver function and fatty liver of 30 patients with CLD.Im-provements were observed using abdominal ultrasonography.Unlike traditional methods,this protocol provided more sustainable and meaningful results.Treat-ment with 10 mL of HPE administered intravenously once or twice per week significantly improved liver function.The observed improvements in fatty liver and liver function suggest the utility of this approach for the management of patients with CLD.CONCLUSION This case series highlights the potential of innovative treatments for patients with CLD that could improve the quality of life of the patients.
基金supported by the National Natural Science Foundation of China(32172879)the National Key Research and Development Program of China(2022YFD1801700 and 2022YFD1800200)the Top-notch Young Talent Supporting Program to Lan He.Additionally,funding was obtained from the Fundamental Research Funds for the Central Universities(2662020DKPY016 and 2262022DKYJ001).
文摘Apicomplexan parasites predominantly generate ATP and lactic acid through glycolysis and anaerobic glucose metabolism,incorporating CO_(2) into glycolysis via a stage-dependent phosphoenolpyruvate carboxylase(PEPC)mechanism.Although the role of PEPC in plant and bacterial carbon fixation is well documented,its function within Babesia remains largely unexplored.This study employs reverse genetics to probe the biological role of PEPC in Babesia gibsoni,noting its conservation across similar protozoa,suggesting a pivotal and conserved biological function.Western blotting and immunofluorescence(IFA)experiments using the BgPEPC-3×Flag strain revealed that the BgPEPC protein has a molecular weight of 105 kDa and localizes predominantly to the cytoplasm.Attempts to knock out the PEPC gene in BgPEPC-3×Flag strains failed under standard media conditions,succeeded only with the addition of 5 mM malate,an upstream metabolite of oxaloacetic acid(OAA).In addition to malate,the downstream metabolite of OAA can also partially compensate for the phenotypic defects caused by PEPC deficiency.This intervention alleviated severe growth deficits,underscoring the critical role of aspartate in the parasite lifecycle.Moreover,metabolic inhibitors such as L-cycloserine and triazamidine,which target aspartate aminotransferase and mitochondrial functions,respectively,demonstrated increased efficacy against BgPEPC knockout strains.The lack of a compensatory response to malic acid supplementation underscores the integral role of BgPEPC in intermediary carbon metabolism and its necessity in providing aspartate as a precursor to pyrimidine synthesis.Collectively,these findings suggest that PEPC could be a potential target for future drug development against B.gibsoni infections.
文摘[Objective]The study aimed to investigate the effects of the amino acids of aspartate family on the biosynthesis of CoQ10 in Rhodpseudomonas palustris J001.[Method]The impacts of amino acids of this family on the biosynthesis of CoQ10 in Rhodopseudomnas palustris J001 were investigated by feeding these amino acids at the end of the logarithmic phase during incubation,which aim was for the optimization of the fermentation medium and genetic improvement of the strain for CoQ10 production.[Result]The results showed that feeding proper amount of methione(125 mg/L)could increase CoQ10 production by 20.2%,but feeding of lysine(above 500 mg/L),threonine(above 400 mg/L)and/or isoleucine(above 400 mg/L)repressed the biosynthesis of CoQ10.The results indicated that the aspartate kinase is subject to feedback inhibition or repression by lysine,threonine and isoleucine in the strain,which was unfavorable to the formation of methioine and then caused the decrease of CoQ10 production.[Conclusion]Lysine,threonine and isoleucine auxotrophic mutants with resistance to analogues of lysine,threonine and isoleucine could increase the production of CoQ10.
