Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Niobates are promising all-climate Li^(+)-storage anode material due to their fast charge transport,large specific capacities,and resistance to electrolyte reaction.However,their moderate unit-cellvolume expansion(gen...Niobates are promising all-climate Li^(+)-storage anode material due to their fast charge transport,large specific capacities,and resistance to electrolyte reaction.However,their moderate unit-cellvolume expansion(generally 5%–10%)during Li^(+)storage causes unsatisfactory long-term cyclability.Here,“zero-strain”NiNb_(2)O_(6) fibers are explored as a new anode material with comprehensively good electrochemical properties.During Li^(+)storage,the expansion of electrochemical inactive NiO_(6) octahedra almost fully offsets the shrinkage of active NbO_(6) octahedra through reversible O movement.Such superior volume-accommodation capability of the NiO_(6) layers guarantees the“zero-strain”behavior of NiNb_(2)O_(6) in a broad temperature range(0.53%//0.51%//0.74%at 25//−10//60℃),leading to the excellent cyclability of the NiNb_(2)O_(6) fibers(92.8%//99.2%//91.1%capacity retention after 1000//2000//1000 cycles at 10C and 25//−10//60℃).This NiNb_(2)O_(6) material further exhibits a large reversible capacity(300//184//318 mAh g−1 at 0.1C and 25//−10//60℃)and outstanding rate performance(10 to 0.5C capacity percentage of 64.3%//50.0%//65.4%at 25//−10//60℃).Therefore,the NiNb_(2)O_(6) fibers are especially suitable for large-capacity,fast-charging,long-life,and all-climate lithium-ion batteries.展开更多
目的探讨慢性自发性荨麻疹(CSU)患者血清Mas相关G蛋白偶联受体成员X2(MRGPRX2)、白细胞介素-6(IL-6)及IL-24的水平在发病中的意义。方法收集2023年9月—2023年12月就诊于徐州医科大学附属医院的CSU患者75例,作为病例组,并根据病情严重...目的探讨慢性自发性荨麻疹(CSU)患者血清Mas相关G蛋白偶联受体成员X2(MRGPRX2)、白细胞介素-6(IL-6)及IL-24的水平在发病中的意义。方法收集2023年9月—2023年12月就诊于徐州医科大学附属医院的CSU患者75例,作为病例组,并根据病情严重程度分为轻度组、中度组、重度组,完成荨麻疹活动评分(urticaria activity score,UAS7)与慢性荨麻疹生活质量问卷评分(chronic urticaria quality of life questionnaire,CU-Q2oL);另选取60例健康者作为对照组。比较各组血清MRGPRX2、IL-6及IL-24水平,分析其与UAS7、CU-Q2oL得分的相关性。结果病例组血清MRGPRX2、IL-6及IL-24水平均高于对照组(P<0.05),CSU患者血清MRGPRX2、IL-6水平升高与其病情严重程度呈正相关(r=0.531,P<0.05;r=0.462,P<0.05),但IL-24水平升高与CSU患者病情严重程度无显著相关性(r=0.015,P>0.05)。经logistic回归分析显示,血清中MRGPRX2、IL-6、IL-24水平升高均是CSU发生的独立危险因素(P<0.05)。经受试者操作特征(ROC)曲线分析结果显示,血清中MRGPRX2、IL-6、IL-24水平3项指标联合预测的曲线下面积(AUC)高于单独指标(P<0.05)。结论血清MRGPRX2、IL-6及IL-24水平在CSU患者血清中呈高表达,且血清MRGPRX2、IL-6与其病情严重程度相关,三者联合检测CSU发生的效能优于各指标单独检测。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
基金supported by the National Natural Science Foundation of China(51762014,52231007,12327804,T2321003,22088101)in part by the National Key Research Program of China under Grant 2021YFA1200600.
文摘Niobates are promising all-climate Li^(+)-storage anode material due to their fast charge transport,large specific capacities,and resistance to electrolyte reaction.However,their moderate unit-cellvolume expansion(generally 5%–10%)during Li^(+)storage causes unsatisfactory long-term cyclability.Here,“zero-strain”NiNb_(2)O_(6) fibers are explored as a new anode material with comprehensively good electrochemical properties.During Li^(+)storage,the expansion of electrochemical inactive NiO_(6) octahedra almost fully offsets the shrinkage of active NbO_(6) octahedra through reversible O movement.Such superior volume-accommodation capability of the NiO_(6) layers guarantees the“zero-strain”behavior of NiNb_(2)O_(6) in a broad temperature range(0.53%//0.51%//0.74%at 25//−10//60℃),leading to the excellent cyclability of the NiNb_(2)O_(6) fibers(92.8%//99.2%//91.1%capacity retention after 1000//2000//1000 cycles at 10C and 25//−10//60℃).This NiNb_(2)O_(6) material further exhibits a large reversible capacity(300//184//318 mAh g−1 at 0.1C and 25//−10//60℃)and outstanding rate performance(10 to 0.5C capacity percentage of 64.3%//50.0%//65.4%at 25//−10//60℃).Therefore,the NiNb_(2)O_(6) fibers are especially suitable for large-capacity,fast-charging,long-life,and all-climate lithium-ion batteries.
文摘目的探讨慢性自发性荨麻疹(CSU)患者血清Mas相关G蛋白偶联受体成员X2(MRGPRX2)、白细胞介素-6(IL-6)及IL-24的水平在发病中的意义。方法收集2023年9月—2023年12月就诊于徐州医科大学附属医院的CSU患者75例,作为病例组,并根据病情严重程度分为轻度组、中度组、重度组,完成荨麻疹活动评分(urticaria activity score,UAS7)与慢性荨麻疹生活质量问卷评分(chronic urticaria quality of life questionnaire,CU-Q2oL);另选取60例健康者作为对照组。比较各组血清MRGPRX2、IL-6及IL-24水平,分析其与UAS7、CU-Q2oL得分的相关性。结果病例组血清MRGPRX2、IL-6及IL-24水平均高于对照组(P<0.05),CSU患者血清MRGPRX2、IL-6水平升高与其病情严重程度呈正相关(r=0.531,P<0.05;r=0.462,P<0.05),但IL-24水平升高与CSU患者病情严重程度无显著相关性(r=0.015,P>0.05)。经logistic回归分析显示,血清中MRGPRX2、IL-6、IL-24水平升高均是CSU发生的独立危险因素(P<0.05)。经受试者操作特征(ROC)曲线分析结果显示,血清中MRGPRX2、IL-6、IL-24水平3项指标联合预测的曲线下面积(AUC)高于单独指标(P<0.05)。结论血清MRGPRX2、IL-6及IL-24水平在CSU患者血清中呈高表达,且血清MRGPRX2、IL-6与其病情严重程度相关,三者联合检测CSU发生的效能优于各指标单独检测。
