Flaviviruses,such as dengue virus(DENV),Zika virus(ZIKV),and Japanese encephalitis virus(JEV),represent a substantial public health challenge as there are currently no approved treatments available.Here,we investigate...Flaviviruses,such as dengue virus(DENV),Zika virus(ZIKV),and Japanese encephalitis virus(JEV),represent a substantial public health challenge as there are currently no approved treatments available.Here,we investigated the antiviral effects of bis-benzylisoquinoline alkaloids(BBAs)on flavivirus infections.We evaluated five specific BBAs—berbamine,tetrandrine,iso-tetrandrine,fangchinoline,and cepharanthine—and found that they effectively inhibited infections by ZIKV,DENV,or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle.Furthermore,we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes,causing lysosomal pH alkalization.Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels,leading to lysosomal dysfunction and reducing the expression of NCAM1,a key receptor for the entry of ZIKV into cells,thereby decreasing cells susceptibility to ZIKV infection.Additionally,BBAs inhibited the fusion of autophagosomes and lysosomes,significantly reducing viral RNA replication.Collectively,our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy,respectively,underscoring the potential of BBAs as therapeutic agents against flavivirus infections.展开更多
Lithium dendrite formation poses a significant safety hazard in lithium-ion batteries(LIBs),severely impeding their widespread adoption and further technological advancements.Here,we present a novel quaternized polybe...Lithium dendrite formation poses a significant safety hazard in lithium-ion batteries(LIBs),severely impeding their widespread adoption and further technological advancements.Here,we present a novel quaternized polybenzimidazolium(q-PBI)to armor polyimide(PI)nanofiber separator(q-PBI@PI),in which the q-PBI containing lithiophilicity and anionphilicity sites serves as the multifunctional nano-layers to suppress the Li dendrite and reinforce the mechanical properties of PI nanofiber separator.Specifically,the q-PBI@PI separator displays an unprecedented mechanical strength of 82.8 MPa,significantly outperforming previously reported PI nanofiber membranes(typically below 50.0 MPa).Besides,we demonstrate that the q-PBI@PI separator simultaneously possesses low nucleation overpotential(59 mV)and exceptional average coulombic efficiency due to the suppression of Li dendrite.Importantly,q-PBI@PI-based Li||Li battery enables a stable Li plating-stripping at 1.0 mA cm^(-2)for 600 h.Attributing to these exceptional merits,the armored PI separator-based LIBs display remarkable specific capability and capacity retention.The density function theory calculations reveal that q-PBI is conducive to the desolvation of Li+and can immobilize Li+and PF6-ions near affinity sites of PI nanofibers for inhibiting the formation of Li dendrites.Our work paves a new avenue for the design of next-generation high-performing separators in LIBs.展开更多
基金supported by the National Key Research and Development Program of China(2022YFD1800100)the National Natural Science Foundation of China(32302843,32070702,and 82161128014)+5 种基金GuangDong Basic and Applied Basic Research Foundation(2023A1515010748)Innovation and Technology Fund of Hong Kong(MRP/064/21,GHP/097/20GD,and MHP/072/21)Hong Kong Research Grant Council(RGC)grant(11103620 and 11104422)research grants from Shenzhen Science and Technology Innovation Committee(SGDX20201103093201010 and JCYJ20210324134007020)Kunshan Shuang Chuang Grant(kssc202302073)the Kunshan Municipal Government research funding。
文摘Flaviviruses,such as dengue virus(DENV),Zika virus(ZIKV),and Japanese encephalitis virus(JEV),represent a substantial public health challenge as there are currently no approved treatments available.Here,we investigated the antiviral effects of bis-benzylisoquinoline alkaloids(BBAs)on flavivirus infections.We evaluated five specific BBAs—berbamine,tetrandrine,iso-tetrandrine,fangchinoline,and cepharanthine—and found that they effectively inhibited infections by ZIKV,DENV,or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle.Furthermore,we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes,causing lysosomal pH alkalization.Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels,leading to lysosomal dysfunction and reducing the expression of NCAM1,a key receptor for the entry of ZIKV into cells,thereby decreasing cells susceptibility to ZIKV infection.Additionally,BBAs inhibited the fusion of autophagosomes and lysosomes,significantly reducing viral RNA replication.Collectively,our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy,respectively,underscoring the potential of BBAs as therapeutic agents against flavivirus infections.
基金supported by the National Natural Science Foundation of China(22109065)the Natural Science Foundation of Hebei Province(E2024208003)+4 种基金the Opening Foundation of State Key Laboratory of Organic-Inorganic Composites,the Beijing University of Chemical Technology(oic-202301008)the S&T Program of Hebei(21314401D,21371201D)the Science and Technology Project of Hebei Education Department(QN2025127)the Fundamental Research Funds for the Central Universities(20720240059)the Startup Support from Xiamen University。
文摘Lithium dendrite formation poses a significant safety hazard in lithium-ion batteries(LIBs),severely impeding their widespread adoption and further technological advancements.Here,we present a novel quaternized polybenzimidazolium(q-PBI)to armor polyimide(PI)nanofiber separator(q-PBI@PI),in which the q-PBI containing lithiophilicity and anionphilicity sites serves as the multifunctional nano-layers to suppress the Li dendrite and reinforce the mechanical properties of PI nanofiber separator.Specifically,the q-PBI@PI separator displays an unprecedented mechanical strength of 82.8 MPa,significantly outperforming previously reported PI nanofiber membranes(typically below 50.0 MPa).Besides,we demonstrate that the q-PBI@PI separator simultaneously possesses low nucleation overpotential(59 mV)and exceptional average coulombic efficiency due to the suppression of Li dendrite.Importantly,q-PBI@PI-based Li||Li battery enables a stable Li plating-stripping at 1.0 mA cm^(-2)for 600 h.Attributing to these exceptional merits,the armored PI separator-based LIBs display remarkable specific capability and capacity retention.The density function theory calculations reveal that q-PBI is conducive to the desolvation of Li+and can immobilize Li+and PF6-ions near affinity sites of PI nanofibers for inhibiting the formation of Li dendrites.Our work paves a new avenue for the design of next-generation high-performing separators in LIBs.
