Monkeypox was declared a global health emergency by the World Health Organization,and as of March 2023,86,000 confirmed cases and 111 deaths across 110 countries have been reported.Its causal agent,monkeypox virus(MPV...Monkeypox was declared a global health emergency by the World Health Organization,and as of March 2023,86,000 confirmed cases and 111 deaths across 110 countries have been reported.Its causal agent,monkeypox virus(MPV)belongs to a large family of double-stranded DNA viruses,Orthopoxviridae,that also includes vaccinia virus(VACV)and others.MPV produces two distinct forms of viral particles during its replication cycles:the enveloped viron(EV)that is released via exocytosis,and the mature viron(MV)that is discharged through lysis of host cells.This study was designed to develop multi-valent m RNA vaccines against monkeypox EV and MV surface proteins,and examine their efficacy and mechanism of action.Four m RNA vaccines were produced with different combinations of surface proteins from EV(A35R and B6R),MV(A29L,E8L,H3L and M1R),or EV and MV,and were administered in Balb/c mice to assess their immunogenicity potentials.A dynamic immune response was observed as soon as seven days after initial immunization,while a strong Ig G response to all immunogens was detected with ELISA after two vaccinations.The higher number of immunogens contributed to a more robust total Ig G response and correlating neutralizing activity against VACV,indicating the additive potential of each immunogen in generating immune response and nullifying VACV infection.Further,the m RNA vaccines elicited an antigen-specific CD4^(+)T cell response that is biased towards Th1.The m RNA vaccines with different combinations of EVand MV surface antigens protected a mouse model from a lethal dose VACV challenge,with the EV and MV antigens-combined vaccine offering the strongest protection.These findings provide insight into the protective mechanism of multi-valent m RNAvaccines against MPV,and also the foundation for further development of effective and safe m RNA vaccines for enhanced protection against monkeypox virus outbreak.展开更多
Lithium(Li)-ion batteries have stimulated the societal transformation to clean energy systems.This carry-on electricity is revolutionizing how society communicates,functions,and evolves efficiently by enabling mobile ...Lithium(Li)-ion batteries have stimulated the societal transformation to clean energy systems.This carry-on electricity is revolutionizing how society communicates,functions,and evolves efficiently by enabling mobile electronics,zero-emission electric vehicles,and stationary energy storage.In preparation for the sustainable energy future,however,there are growing concerns about depleting critical elements used in the Li technology(e.g.,lithium,cobalt,and nickel),especially for large-scale applications that will accelerate the rate of elemental consumption.Various non-Li-based rechargeable batteries composed of earth-abundant elements,such as sodium,potassium,magnesium,and calcium,have been proposed and explored as alternative systems to promote sustainable development of energy storage.In this perspective,we discuss challenges in Li-ion batteries in the sustainability aspect and provide our opinions on the potential applications of non-Li-based batteries.We also highlight the current status,important progress,and remaining challenges of the Li-alternative technologies.展开更多
The rational design of drug delivery systems has led to enhanced targeting,increased efficiency,and a reduction of side effects in chemotherapies and vaccines.As most biological reactions took place at the interface,p...The rational design of drug delivery systems has led to enhanced targeting,increased efficiency,and a reduction of side effects in chemotherapies and vaccines.As most biological reactions took place at the interface,particle-stabilized emulsion(Pickering emulsion),may offer major implications for the advanced drug loading,delivery,and controlled release.In fact,it is the aggregating particles that determined the multi-level structure,multi-valent cellular interactions,and the multi-functional physiochemical properties in drug delivery.A deeper understanding on the tunable aggregating patterns and properties,as well as the underlying mechanisms,may pave the way for the efficient drug delivery,and also aided the progressing of“Aggregology”beyond molecules to particles,emulsions,and the biomedical applications.Here,the recent development of Pickering emulsions and their applications in drug delivery were thoroughly reviewed.Strategies to control over the physiochemical properties were illustrated based on particle properties,energy input,and the choices of continuous and dispersion phases.In particular,enough emphasis was attached on the structure-effect relationship between the tunable physiochemical properties and the delivery process,such as the multi-level structure for effective loading,flexibility and permeability for enhanced delivery,and the stimuli-responsiveness for the controlled release.By channeling the unique interfacial properties and the enhanced drug delivery efficiency,this work may shed light on the rational design of Pickering emulsions for the efficient drug delivery.展开更多
Influenza epidemics frequently and unpredictably break out all over the world,and seriously affect the breeding industry and human activity.Inactivated and live attenuated viruses have been used as protective vaccines...Influenza epidemics frequently and unpredictably break out all over the world,and seriously affect the breeding industry and human activity.Inactivated and live attenuated viruses have been used as protective vaccines but exhibit high risks for biosafety.Subunit vaccines enjoy high biosafety and specificity but have a few weak points compared to inactivated virus or live attenuated virus vaccines,especially in low immunogenicity.In this study,we developed a new subunit vaccine platform for a potent,adjuvant-free,and multivalent vaccination.The ectodomains of hemagglutinins(HAs)of influenza viruses were expressed in plants as trimers(tHAs)to mimic their native forms.tHAs in plant extracts were directly used without purification for binding to inactivated Lactococcus(iLact)to produce iLact-tHAs,an antigen-carrying bacteria-like particle(BLP).tHAs BLP showed strong immune responses in mice and chickens without adjuvants.Moreover,simultaneous injection of two different antigens by two different formulas,t^(HAH5N6+H9N2) BLP or a combination of t^(HAH5N6) BLP and t^(HAH9N2) BLP,led to strong immune responses to both antigens.Based on these results,we propose combinations of plant-based antigen production and BLP-based delivery as a highly potent and cost-effective platform for multivalent vaccination for subunit vaccines.展开更多
基金the National Science and Technology Major Projects(2021YFC2300704)the National Key Research and Development Program of China(2021YFA1301402,2018YFA0903700)+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(XDA24010400)Shanghai Municipal Science and Technology Major Project(ZD2021CY001)the National Natural Science Foundation of China(32270695,31972881)support from Lingang Laboratory(Shanghai,China)。
文摘Monkeypox was declared a global health emergency by the World Health Organization,and as of March 2023,86,000 confirmed cases and 111 deaths across 110 countries have been reported.Its causal agent,monkeypox virus(MPV)belongs to a large family of double-stranded DNA viruses,Orthopoxviridae,that also includes vaccinia virus(VACV)and others.MPV produces two distinct forms of viral particles during its replication cycles:the enveloped viron(EV)that is released via exocytosis,and the mature viron(MV)that is discharged through lysis of host cells.This study was designed to develop multi-valent m RNA vaccines against monkeypox EV and MV surface proteins,and examine their efficacy and mechanism of action.Four m RNA vaccines were produced with different combinations of surface proteins from EV(A35R and B6R),MV(A29L,E8L,H3L and M1R),or EV and MV,and were administered in Balb/c mice to assess their immunogenicity potentials.A dynamic immune response was observed as soon as seven days after initial immunization,while a strong Ig G response to all immunogens was detected with ELISA after two vaccinations.The higher number of immunogens contributed to a more robust total Ig G response and correlating neutralizing activity against VACV,indicating the additive potential of each immunogen in generating immune response and nullifying VACV infection.Further,the m RNA vaccines elicited an antigen-specific CD4^(+)T cell response that is biased towards Th1.The m RNA vaccines with different combinations of EVand MV surface antigens protected a mouse model from a lethal dose VACV challenge,with the EV and MV antigens-combined vaccine offering the strongest protection.These findings provide insight into the protective mechanism of multi-valent m RNAvaccines against MPV,and also the foundation for further development of effective and safe m RNA vaccines for enhanced protection against monkeypox virus outbreak.
基金H.K.acknowledges the support from the Assistant Secretary for Energy Efficiency and Renewable Energy,Vehicle Technologies Office,of the U.S.Department of Energy under Contract No.DE-AC02-05CH11231.J.C.Kacknowledges the Public Service Enterprise Group(PSEG)Foundation's support to advance energy innovation research at Stevens Institute of Technology.
文摘Lithium(Li)-ion batteries have stimulated the societal transformation to clean energy systems.This carry-on electricity is revolutionizing how society communicates,functions,and evolves efficiently by enabling mobile electronics,zero-emission electric vehicles,and stationary energy storage.In preparation for the sustainable energy future,however,there are growing concerns about depleting critical elements used in the Li technology(e.g.,lithium,cobalt,and nickel),especially for large-scale applications that will accelerate the rate of elemental consumption.Various non-Li-based rechargeable batteries composed of earth-abundant elements,such as sodium,potassium,magnesium,and calcium,have been proposed and explored as alternative systems to promote sustainable development of energy storage.In this perspective,we discuss challenges in Li-ion batteries in the sustainability aspect and provide our opinions on the potential applications of non-Li-based batteries.We also highlight the current status,important progress,and remaining challenges of the Li-alternative technologies.
基金Beijing Nova Program of Beijing Municipal Sci-ence&Technology Commission,Grant/Award Number:Z201100006820139CAS Project for Young Scientists in Basic Research,Grant/Award Number:YSBR-010+6 种基金Foundation for Innovative Research Groups of the National Natural Science Foundation of China,Grant/Award Number:21821005Pilot Project of Chinese Academy of Sciences,Grant/Award Number:XDB29040303“From 0 to 1”Original Innovation Project of Basic Frontier Scientific Research Program of Chinese Academy of Sciences,Grant/Award Number:ZDBS-LY-SLH040Youth Project of National Natural Science Foundation of China,Grant/Award Number:21908229Youth Innovation Promotion Association of the Chinese Academy of Sciences,Grant/Award Number:2020000053National Science and Technology Major Project of China,Grant/Award Number:2018ZX10301-103-003Innovation Academy for Green Manufacture,Chinese Academy of Sciences,Grant/Award Number:IAGM2020C30。
文摘The rational design of drug delivery systems has led to enhanced targeting,increased efficiency,and a reduction of side effects in chemotherapies and vaccines.As most biological reactions took place at the interface,particle-stabilized emulsion(Pickering emulsion),may offer major implications for the advanced drug loading,delivery,and controlled release.In fact,it is the aggregating particles that determined the multi-level structure,multi-valent cellular interactions,and the multi-functional physiochemical properties in drug delivery.A deeper understanding on the tunable aggregating patterns and properties,as well as the underlying mechanisms,may pave the way for the efficient drug delivery,and also aided the progressing of“Aggregology”beyond molecules to particles,emulsions,and the biomedical applications.Here,the recent development of Pickering emulsions and their applications in drug delivery were thoroughly reviewed.Strategies to control over the physiochemical properties were illustrated based on particle properties,energy input,and the choices of continuous and dispersion phases.In particular,enough emphasis was attached on the structure-effect relationship between the tunable physiochemical properties and the delivery process,such as the multi-level structure for effective loading,flexibility and permeability for enhanced delivery,and the stimuli-responsiveness for the controlled release.By channeling the unique interfacial properties and the enhanced drug delivery efficiency,this work may shed light on the rational design of Pickering emulsions for the efficient drug delivery.
基金This work was supported by the Ministry of Trade,Industry and Energy(grant number,10063301)by the National Research Foundation grants funded by the Ministry of Science and Information Technology(No.2019R1A2B5B-03099982 and 2019R1A2C1087207),Korea.
文摘Influenza epidemics frequently and unpredictably break out all over the world,and seriously affect the breeding industry and human activity.Inactivated and live attenuated viruses have been used as protective vaccines but exhibit high risks for biosafety.Subunit vaccines enjoy high biosafety and specificity but have a few weak points compared to inactivated virus or live attenuated virus vaccines,especially in low immunogenicity.In this study,we developed a new subunit vaccine platform for a potent,adjuvant-free,and multivalent vaccination.The ectodomains of hemagglutinins(HAs)of influenza viruses were expressed in plants as trimers(tHAs)to mimic their native forms.tHAs in plant extracts were directly used without purification for binding to inactivated Lactococcus(iLact)to produce iLact-tHAs,an antigen-carrying bacteria-like particle(BLP).tHAs BLP showed strong immune responses in mice and chickens without adjuvants.Moreover,simultaneous injection of two different antigens by two different formulas,t^(HAH5N6+H9N2) BLP or a combination of t^(HAH5N6) BLP and t^(HAH9N2) BLP,led to strong immune responses to both antigens.Based on these results,we propose combinations of plant-based antigen production and BLP-based delivery as a highly potent and cost-effective platform for multivalent vaccination for subunit vaccines.
