目的研究正常成年人水平特异性CE-Chirp(level specific CE-Chirp,CE-Chirp LS)刺激声与Click刺激声诱发听性脑干反应(auditory brainstem response,ABR)反应阈与纯音听阈的关系及在不同声强下两种刺激声所诱发的ABR波形特点,探讨CE-Chi...目的研究正常成年人水平特异性CE-Chirp(level specific CE-Chirp,CE-Chirp LS)刺激声与Click刺激声诱发听性脑干反应(auditory brainstem response,ABR)反应阈与纯音听阈的关系及在不同声强下两种刺激声所诱发的ABR波形特点,探讨CE-Chirp LS声诱发的ABR在听觉功能客观评估中的应用价值。方法选择正常成年人21例(共42耳)分别在0.5、1.0、2.0、4.0 kHz进行纯音气导听阈测试,获取其双耳各频率的纯音听阈,分别采用CEChirp LS刺激声与Click刺激声诱发ABR,测量2种刺激声在80、60、40 dB nHL的Ⅴ波波幅,获得2种刺激声下受试者的Ⅴ波反应阈,获取其在80 dB nHL刺激强度时Ⅰ、Ⅲ、Ⅴ波潜伏期。按照自身对照的方法对相同刺激强度下2种刺激声诱发的ABR潜伏期及波幅差异性进行统计分析,比较2种刺激声下Ⅴ波反应阈与纯音听阈差值。结果正常成年人80、60、40 dB nHL刺激强度下,CE-Chirp LS刺激声诱发的ABR的Ⅴ波波幅均大于Click刺激声,差异有统计学意义(P<0.001);CE-Chirp LS刺激声诱发的ABR的V波反应阈与纯音平均听阈差值均低于Click刺激声,差异有统计学意义(P<0.05);80 dB nHL声强下CE-Chirp LS刺激声Ⅰ波潜伏期长于Click刺激声,差异有统计学意义(P<0.001),CE-Chirp LS刺激声Ⅲ、Ⅴ波潜伏期与Click刺激声比较,差异无统计学意义(P>0.05)。结论正常成年人CE-Chirp LS刺激声与Click刺激声比较,无论在高强度还是低强度刺激下波幅均明显增大,Ⅴ波反应阈更接近于纯音听阈,更有利于纯音听阈判定,但潜伏期个体差异更大。展开更多
The blockade of cytoprotective autophagy has been demonstrated to effectively enhance the efficacy of sonodynamic therapy(SDT).However,the limited recogni-tion of antiautophagy agents for autophagosomes impedes the cli...The blockade of cytoprotective autophagy has been demonstrated to effectively enhance the efficacy of sonodynamic therapy(SDT).However,the limited recogni-tion of antiautophagy agents for autophagosomes impedes the clinical application of autophagy inhibition.To efficiently deliver hydroxychloroquine(HCQ),an autophagy inhibitor,to autophagosomes,we utilized a strategy based on in situ click chemistry between sulfhydryl(-SH)and maleimide(Mal)groups to trigger autophagosomes tracking and suppress tumor growth synergistically.A cascade nanoreactor was synthesized by encapsulating Mal-modified HCQ(MHCQ)into a manganese porphyrin-based metal-organic framework with sonosensitizer proper-ties,followed by poly(ethylene glycol)ylated liposomal membrane coating.After ultrasound irradiation,SDT-induced apoptotic cells released damaged proteins with free-SH groups,which MHCQ rapidly captured in situ via a Mal-thiol click reaction.When autophagosomes actively wrapped damaged proteins for detoxifi-cation,they simultaneously internalized HCQ anchored on proteins.In this scenario,antiautophagy drugs could actively track intracellular autophagosomes instead of undergoing passive diffusion in the cytosol.The interaction between HCQ and autophagic vesicles was greatly enhanced,which strengthened the blocking effi-ciency of autophagy and resulted in complete cell death.Overall,this study with smart design provides a promising strategy for improving intracellular targeted delivery to autophagosomes,thereby enhancing antitumor therapy.展开更多
Fatty acids(FAs),which were initially recognized as energy sources and essential building blocks of biomembranes,serve as the precursors of important signaling molecules.Tracing FA metabolism is essential to understan...Fatty acids(FAs),which were initially recognized as energy sources and essential building blocks of biomembranes,serve as the precursors of important signaling molecules.Tracing FA metabolism is essential to understanding the biochemical activity and role of FAs in physiological and pathological events.Inspired by the advances in click chemistry for protein enrichment,we herein established a click chemistry-based enrichment(CCBE)strategy for tracing the cellular metabolism of eicosapentaenoic acid(EPA,20:5 n-3)in neural cells.Terminal alkyne-labeled EPA(EPAA)used as a surrogate was incubated with N2a,mouse neuroblastoma cells,and alkyne-labeled metabolites(ALMs)were selectively captured by an azide-modified resin via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction for enrichment.After removing unlabeled metabolites,ALMs containing a triazole moiety were cleaved from solid-phase resins and subjected to liquid chromatography mass spectrometry(LC-MS)analysis.The proposed CCBE strategy is highly selective for capturing and enriching alkyne-labeled metabolites from the complicated matrices.In addition,this method can overcome current detection limits by enhancing MS sensitivity of targets,improving the chromatographic separation of sn-position glycerophospholipid regioisomers,facilitating structural characterization of ALMs by a specific MS/MS fragmentation signature,and providing versatile fluorescence detection of ALMs for cellular distribution.This CCBE strategy might be expanded to trace the metabolism of other FAs,small molecules,or drugs.展开更多
Thiol-ene click reaction is an intriguing strategy for preparing polymer electrolytes due to its high activity,atom economy and less side reaction.However,the explosive reaction rate and the use of non-electrolytic am...Thiol-ene click reaction is an intriguing strategy for preparing polymer electrolytes due to its high activity,atom economy and less side reaction.However,the explosive reaction rate and the use of non-electrolytic amine catalyst hamper its application in in-situ batteries.Herein,a nitrogen-containing eutectic solution is designed as both the catalyst of the thiol-ene reaction and the plasticizer to in-situ synthesize the gel polymer electrolytes,realizing a mild in-situ gelation process and the preparation of high-performance gel electrolytes.The obtained gel polymer electrolytes exhibit a high ionic conductivity of 4×10^(−4)S cm^(−1)and lithium-ion transference number(t_(Li)^(+))of 0.51 at 60°C.The as-assembled Li/LiFePO_(4)(LFP)cell delivers a high initial discharge capacity of 155.9 mAh g^(-1),and a favorable cycling stability with the capacity retention of 82%after 800 cycles at 1 C is also obtained.In addition,this eutectic solution significantly improves the rate performance of the LFP cell with high specific capacity of 141.5 and 126.8 mAh g^(-1)at 5 C and 10 C,respectively,and the cell can steadily work at various charge–discharge rate for 200 cycles.This powerful and efficient strategy may provide a novel way for in-situ preparing gel polymer electrolytes with desirable comprehensive performances.展开更多
建立了由一个制造商和一个分销商组成的基于电子市场的二级供应链模型,讨论了分销商采用Bricks and Clicks模式分销产品,并在电子渠道进行季节后销售的情况,分析了供应链的契约协调问题及供应链成员的利润情况.研究发现改进的回购契约...建立了由一个制造商和一个分销商组成的基于电子市场的二级供应链模型,讨论了分销商采用Bricks and Clicks模式分销产品,并在电子渠道进行季节后销售的情况,分析了供应链的契约协调问题及供应链成员的利润情况.研究发现改进的回购契约可以使Bricks and Clicks分销模式下基于电子市场的二级供应链模型达到协调,使分销商的订货量达到供应链最优,并且使供应链成员的利润达到Pareto改进,达到"双赢".最后,通过算例验证了结论.展开更多
Click是一种模块化的软件路由器体系结构,基于该体系结构用户可以根据自己的需求搭建不同功能的路由器。针对Click软件路由器支持静态路由协议的局限性,引入模块化路由器软件协议栈XORP(eXtensible Open Router Platform),实现了动态路...Click是一种模块化的软件路由器体系结构,基于该体系结构用户可以根据自己的需求搭建不同功能的路由器。针对Click软件路由器支持静态路由协议的局限性,引入模块化路由器软件协议栈XORP(eXtensible Open Router Platform),实现了动态路由协议在Click软件路由器上的扩展。通过搭建实验网络拓扑环境,验证了基于Click转发平台的两种不同的动态路由协议RIP和OSPF,并进行了相关测试和性能分析。实验结果表明,Click软件路由器的转发性能与Linux内核基本一致,但相比较而言,Click软件路由器具有灵活、可扩展、模块化等不可比拟的优势。展开更多
文摘目的研究正常成年人水平特异性CE-Chirp(level specific CE-Chirp,CE-Chirp LS)刺激声与Click刺激声诱发听性脑干反应(auditory brainstem response,ABR)反应阈与纯音听阈的关系及在不同声强下两种刺激声所诱发的ABR波形特点,探讨CE-Chirp LS声诱发的ABR在听觉功能客观评估中的应用价值。方法选择正常成年人21例(共42耳)分别在0.5、1.0、2.0、4.0 kHz进行纯音气导听阈测试,获取其双耳各频率的纯音听阈,分别采用CEChirp LS刺激声与Click刺激声诱发ABR,测量2种刺激声在80、60、40 dB nHL的Ⅴ波波幅,获得2种刺激声下受试者的Ⅴ波反应阈,获取其在80 dB nHL刺激强度时Ⅰ、Ⅲ、Ⅴ波潜伏期。按照自身对照的方法对相同刺激强度下2种刺激声诱发的ABR潜伏期及波幅差异性进行统计分析,比较2种刺激声下Ⅴ波反应阈与纯音听阈差值。结果正常成年人80、60、40 dB nHL刺激强度下,CE-Chirp LS刺激声诱发的ABR的Ⅴ波波幅均大于Click刺激声,差异有统计学意义(P<0.001);CE-Chirp LS刺激声诱发的ABR的V波反应阈与纯音平均听阈差值均低于Click刺激声,差异有统计学意义(P<0.05);80 dB nHL声强下CE-Chirp LS刺激声Ⅰ波潜伏期长于Click刺激声,差异有统计学意义(P<0.001),CE-Chirp LS刺激声Ⅲ、Ⅴ波潜伏期与Click刺激声比较,差异无统计学意义(P>0.05)。结论正常成年人CE-Chirp LS刺激声与Click刺激声比较,无论在高强度还是低强度刺激下波幅均明显增大,Ⅴ波反应阈更接近于纯音听阈,更有利于纯音听阈判定,但潜伏期个体差异更大。
基金China Postdoctoral Science Foundation,Grant/Award Numbers:2022TQ0396,2023MD744153National Natural Science Foundation of China,Grant/Award Numbers:82302218,82171946+2 种基金CQMU Program for Youth Innovation in Future Medicine,Grant/Award Number:W0026Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University,Grant/Award Number:KR2023Y044Chongqing Science and Health Joint Medical Research Project-Young and Middle-Aged High-Level Talent Project,Grant/Award Number:2020GDRC011。
文摘The blockade of cytoprotective autophagy has been demonstrated to effectively enhance the efficacy of sonodynamic therapy(SDT).However,the limited recogni-tion of antiautophagy agents for autophagosomes impedes the clinical application of autophagy inhibition.To efficiently deliver hydroxychloroquine(HCQ),an autophagy inhibitor,to autophagosomes,we utilized a strategy based on in situ click chemistry between sulfhydryl(-SH)and maleimide(Mal)groups to trigger autophagosomes tracking and suppress tumor growth synergistically.A cascade nanoreactor was synthesized by encapsulating Mal-modified HCQ(MHCQ)into a manganese porphyrin-based metal-organic framework with sonosensitizer proper-ties,followed by poly(ethylene glycol)ylated liposomal membrane coating.After ultrasound irradiation,SDT-induced apoptotic cells released damaged proteins with free-SH groups,which MHCQ rapidly captured in situ via a Mal-thiol click reaction.When autophagosomes actively wrapped damaged proteins for detoxifi-cation,they simultaneously internalized HCQ anchored on proteins.In this scenario,antiautophagy drugs could actively track intracellular autophagosomes instead of undergoing passive diffusion in the cytosol.The interaction between HCQ and autophagic vesicles was greatly enhanced,which strengthened the blocking effi-ciency of autophagy and resulted in complete cell death.Overall,this study with smart design provides a promising strategy for improving intracellular targeted delivery to autophagosomes,thereby enhancing antitumor therapy.
基金supported by grants from the Research Committee of the University of Macao,Macao SAR,China(Grant No.:MYRG2022-00020-ICMS)the Science and Technology Development Fund,Macao,China(File Nos.:0074/2021/AFJ and 0052/2022/A1).
文摘Fatty acids(FAs),which were initially recognized as energy sources and essential building blocks of biomembranes,serve as the precursors of important signaling molecules.Tracing FA metabolism is essential to understanding the biochemical activity and role of FAs in physiological and pathological events.Inspired by the advances in click chemistry for protein enrichment,we herein established a click chemistry-based enrichment(CCBE)strategy for tracing the cellular metabolism of eicosapentaenoic acid(EPA,20:5 n-3)in neural cells.Terminal alkyne-labeled EPA(EPAA)used as a surrogate was incubated with N2a,mouse neuroblastoma cells,and alkyne-labeled metabolites(ALMs)were selectively captured by an azide-modified resin via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction for enrichment.After removing unlabeled metabolites,ALMs containing a triazole moiety were cleaved from solid-phase resins and subjected to liquid chromatography mass spectrometry(LC-MS)analysis.The proposed CCBE strategy is highly selective for capturing and enriching alkyne-labeled metabolites from the complicated matrices.In addition,this method can overcome current detection limits by enhancing MS sensitivity of targets,improving the chromatographic separation of sn-position glycerophospholipid regioisomers,facilitating structural characterization of ALMs by a specific MS/MS fragmentation signature,and providing versatile fluorescence detection of ALMs for cellular distribution.This CCBE strategy might be expanded to trace the metabolism of other FAs,small molecules,or drugs.
基金the National Natural Science Foundation of China(Grant no.51973073)the Fel owship of China Postdoctoral Science Foundation(2021M701303)the analytical and testing assistance from the Analysis and Testing Center of HUST for support of this work
文摘Thiol-ene click reaction is an intriguing strategy for preparing polymer electrolytes due to its high activity,atom economy and less side reaction.However,the explosive reaction rate and the use of non-electrolytic amine catalyst hamper its application in in-situ batteries.Herein,a nitrogen-containing eutectic solution is designed as both the catalyst of the thiol-ene reaction and the plasticizer to in-situ synthesize the gel polymer electrolytes,realizing a mild in-situ gelation process and the preparation of high-performance gel electrolytes.The obtained gel polymer electrolytes exhibit a high ionic conductivity of 4×10^(−4)S cm^(−1)and lithium-ion transference number(t_(Li)^(+))of 0.51 at 60°C.The as-assembled Li/LiFePO_(4)(LFP)cell delivers a high initial discharge capacity of 155.9 mAh g^(-1),and a favorable cycling stability with the capacity retention of 82%after 800 cycles at 1 C is also obtained.In addition,this eutectic solution significantly improves the rate performance of the LFP cell with high specific capacity of 141.5 and 126.8 mAh g^(-1)at 5 C and 10 C,respectively,and the cell can steadily work at various charge–discharge rate for 200 cycles.This powerful and efficient strategy may provide a novel way for in-situ preparing gel polymer electrolytes with desirable comprehensive performances.
文摘建立了由一个制造商和一个分销商组成的基于电子市场的二级供应链模型,讨论了分销商采用Bricks and Clicks模式分销产品,并在电子渠道进行季节后销售的情况,分析了供应链的契约协调问题及供应链成员的利润情况.研究发现改进的回购契约可以使Bricks and Clicks分销模式下基于电子市场的二级供应链模型达到协调,使分销商的订货量达到供应链最优,并且使供应链成员的利润达到Pareto改进,达到"双赢".最后,通过算例验证了结论.
文摘Click是一种模块化的软件路由器体系结构,基于该体系结构用户可以根据自己的需求搭建不同功能的路由器。针对Click软件路由器支持静态路由协议的局限性,引入模块化路由器软件协议栈XORP(eXtensible Open Router Platform),实现了动态路由协议在Click软件路由器上的扩展。通过搭建实验网络拓扑环境,验证了基于Click转发平台的两种不同的动态路由协议RIP和OSPF,并进行了相关测试和性能分析。实验结果表明,Click软件路由器的转发性能与Linux内核基本一致,但相比较而言,Click软件路由器具有灵活、可扩展、模块化等不可比拟的优势。
