This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophil...This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant （LA） was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C （PC）, protein S （PS）, antithrombin （AT） and thrombomodulin （TM） was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant （c.112A〉G） APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrornbin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.展开更多
Objective Patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection frequently develop central nervous system damage,yet the mechanisms driving this pathology remain unclear.This study investi...Objective Patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection frequently develop central nervous system damage,yet the mechanisms driving this pathology remain unclear.This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant(lineage B.1.351).Methods K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant.Viral replication,pathological phenotypes,and brain transcriptomes were analyzed.Gene Ontology(GO)analysis was performed to identify altered pathways.Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot.Results Pathological alterations were observed in the lungs of both mouse strains.However,only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection,accompanied by neuropathological injury and weight loss.GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses,including type I interferons,pro-inflammatory cytokines,Toll-like receptor signaling components,and interferon-stimulated genes.Neuroinflammation was evident,alongside activation of apoptotic and pyroptotic pathways.Furthermore,altered neural cell marker expression suggested viral-induced neuroglial activation,resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks.Conclusion These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.展开更多
Sulfur dioxide(SO_(2))frequently coexist with volatile organic compounds(VOCs)in exhaust gas.The competitive adsorption of SO_(2) and VOCs can adversely affect the efficiency of catalytic combustion,leading to catalys...Sulfur dioxide(SO_(2))frequently coexist with volatile organic compounds(VOCs)in exhaust gas.The competitive adsorption of SO_(2) and VOCs can adversely affect the efficiency of catalytic combustion,leading to catalyst poisoning and irreversible loss of activity.To investigate the impact of sulfur poisoning on the catalysts,we prepared the MnO_(2)/Beta zeolite,and a corresponding series of sulfur-poisoned catalysts through in-situ thermal decomposition of(NH_(4))_(2)SO_(4).The decrease in toluene catalytic activity of poisoned MnO_(2)/Beta zeolite primarily results from the conversion of the active species MnO_(2) to MnSO_(4).However,the crystal structure and the porous structure of MnO_(2)/Beta zeolite were stable,and original structure was still maintained when 1.6%(mass)sulfur species were introduced.Furthermore,the extra-framework Al of Beta zeolite could capture sulfur species to generate Al2(SO_(4))_(3),thereby reducing sulfur species from reacting with Mn^(4+) active sites.The combination of sulfur and Beta zeolite was found to directly produce new strong-acid sites,thus effectively compensating for the effect of reduced Mn4+active species on the catalytic activity.展开更多
目的:分析格列吡嗪与二甲双胍联用治疗新发初诊2型糖尿病患者的应用价值。方法:研究对象选取2024年4月至2025年4月在本院收治的102例初诊2型糖尿病患者,以信封法随机分为联合组和二甲双胍组,两组均51例,二甲双胍组予以二甲双胍治疗,联...目的:分析格列吡嗪与二甲双胍联用治疗新发初诊2型糖尿病患者的应用价值。方法:研究对象选取2024年4月至2025年4月在本院收治的102例初诊2型糖尿病患者,以信封法随机分为联合组和二甲双胍组,两组均51例,二甲双胍组予以二甲双胍治疗,联合组予以格列吡嗪联合二甲双胍治疗,两组患者均干预3 m。比较两组血糖水平、空腹C肽、餐后2 h C肽、胰岛β细胞功能指数(Homeostasis model assessment-β,HOMA-β)、胰岛抵抗指数(Homeostasis model assessment-IR,HOMA-IR),统计不良反应。结果:治疗后,联合组在降低糖化血红蛋白、空腹血糖、餐后2 h血糖方面均优于二甲双胍组(P<0.05),两组空腹及餐后2 h C肽均较治疗前有显著升高(P<0.05),且联合组空腹及餐后2 h C肽均高于二甲双胍组(P<0.05),联合组HOMA-β高于二甲双胍组(P<0.05),HOMA-IR低于二甲双胍组(P<0.05),两组不良反应比较无明显差异(P>0.05)。结论:格列吡嗪与二甲双胍联合治疗新发2型糖尿病具有协同降糖效果,能有效改善胰岛β细胞功能,安全性良好。展开更多
文摘This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant （LA） was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C （PC）, protein S （PS）, antithrombin （AT） and thrombomodulin （TM） was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant （c.112A〉G） APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrornbin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.
基金supported by the National Key Research and Development Program of China(2023YFC3041500).
文摘Objective Patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection frequently develop central nervous system damage,yet the mechanisms driving this pathology remain unclear.This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant(lineage B.1.351).Methods K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant.Viral replication,pathological phenotypes,and brain transcriptomes were analyzed.Gene Ontology(GO)analysis was performed to identify altered pathways.Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot.Results Pathological alterations were observed in the lungs of both mouse strains.However,only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection,accompanied by neuropathological injury and weight loss.GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses,including type I interferons,pro-inflammatory cytokines,Toll-like receptor signaling components,and interferon-stimulated genes.Neuroinflammation was evident,alongside activation of apoptotic and pyroptotic pathways.Furthermore,altered neural cell marker expression suggested viral-induced neuroglial activation,resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks.Conclusion These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
基金supported by the National Natural Science Foundation of China(21577094)the Zhejiang Public Welfare Technology Research Project(LGG19B070003).
文摘Sulfur dioxide(SO_(2))frequently coexist with volatile organic compounds(VOCs)in exhaust gas.The competitive adsorption of SO_(2) and VOCs can adversely affect the efficiency of catalytic combustion,leading to catalyst poisoning and irreversible loss of activity.To investigate the impact of sulfur poisoning on the catalysts,we prepared the MnO_(2)/Beta zeolite,and a corresponding series of sulfur-poisoned catalysts through in-situ thermal decomposition of(NH_(4))_(2)SO_(4).The decrease in toluene catalytic activity of poisoned MnO_(2)/Beta zeolite primarily results from the conversion of the active species MnO_(2) to MnSO_(4).However,the crystal structure and the porous structure of MnO_(2)/Beta zeolite were stable,and original structure was still maintained when 1.6%(mass)sulfur species were introduced.Furthermore,the extra-framework Al of Beta zeolite could capture sulfur species to generate Al2(SO_(4))_(3),thereby reducing sulfur species from reacting with Mn^(4+) active sites.The combination of sulfur and Beta zeolite was found to directly produce new strong-acid sites,thus effectively compensating for the effect of reduced Mn4+active species on the catalytic activity.
文摘目的:分析格列吡嗪与二甲双胍联用治疗新发初诊2型糖尿病患者的应用价值。方法:研究对象选取2024年4月至2025年4月在本院收治的102例初诊2型糖尿病患者,以信封法随机分为联合组和二甲双胍组,两组均51例,二甲双胍组予以二甲双胍治疗,联合组予以格列吡嗪联合二甲双胍治疗,两组患者均干预3 m。比较两组血糖水平、空腹C肽、餐后2 h C肽、胰岛β细胞功能指数(Homeostasis model assessment-β,HOMA-β)、胰岛抵抗指数(Homeostasis model assessment-IR,HOMA-IR),统计不良反应。结果:治疗后,联合组在降低糖化血红蛋白、空腹血糖、餐后2 h血糖方面均优于二甲双胍组(P<0.05),两组空腹及餐后2 h C肽均较治疗前有显著升高(P<0.05),且联合组空腹及餐后2 h C肽均高于二甲双胍组(P<0.05),联合组HOMA-β高于二甲双胍组(P<0.05),HOMA-IR低于二甲双胍组(P<0.05),两组不良反应比较无明显差异(P>0.05)。结论:格列吡嗪与二甲双胍联合治疗新发2型糖尿病具有协同降糖效果,能有效改善胰岛β细胞功能,安全性良好。
基金Supported by the National Natural Science Foundation of China(No.51572232,No.51561135015)Key Technology Research and Development Program of Ningbo(No.2011B1001)
