Background Toxoplasma gondii,an intracellular parasitic protozoan,which infects almost all warm-blooded animals,including humans,causes toxoplasmosis.However,we lack effective drugs and vaccines to control toxoplasmos...Background Toxoplasma gondii,an intracellular parasitic protozoan,which infects almost all warm-blooded animals,including humans,causes toxoplasmosis.However,we lack effective drugs and vaccines to control toxoplasmosis,representing a clinical challenge.Therefore,safe and effective vaccines are urgently needed.In this study,a self-replicating mRNA vaccine comprising four T.gondii antigens:ROP18,TGME49_237490,TGME49_268230,and MIC13,named 4x-mRNA-LNP(lipid nanoparticle),was developed,and its protective efficacy was evaluated in mice.Methods The expression of this vaccine in eukaryotic Human embryonic kidney 293 T(HEK-293 T)cells and mouse myoblast(C2C12)cells were analyzed,followed by enzyme-linked immunosorbent assay(ELISA)evaluation of the elicited humoral immune response.Subsequently,the vaccine-triggered immune responses in mice were detected,including antibody titers,T lymphocyte subsets,and cytokine levels.Finally,its immunoprotective effects were evaluated after challenging mice with T.gondii PRU oocysts or tachyzoites of different strains and analyzing the pathological changes,parasite loads,and mouse survival time.Western blotting and ELISA confirmed the successful eukaryotic expression and immunogenicity of 4x-mRNA,respectively.Statistical analyses,including the log-rank(Mantel–Cox)test,Student’s t-test,and one-way ANOVA,were performed using GraphPad Prism software.Results Mice vaccinated with 4x-mRNA-LNP generated higher levels of IgG1 and IgG2a antibodies(P<0.05)and cytokines(IL-2,IL-4,IL-10,IL-12,IFN-γ)(P<0.05)compared with the control group.The high specific IgG titer was maintained for at least 10 weeks after the last vaccination.The proportion of CD3^(+)CD4^(+)T cells and CD3^(+)CD8^(+)T cells also increased significantly(P<0.05),along with increased spleen cell proliferation in 4x-mRNA-LNP-vaccinated mice.Notably,limited pathological changes and<10 fg of parasites/mg were found in the immunized mice tissues post-pathogen challenge.During observation for 30 days,4x-mRNA-LNP-immunized mice survived significantly longer under challenge with lethal doses of RH,ME49,or WH6 tachyzoites(survival rates=60%,80%,and 60%,respectively).Following PRU oocyst challenge,vaccinated mice had notably decreased cyst burdens(72.5%,P<0.05)compared with control mice.Conclusions The 4x-mRNA-LNP vaccine triggered effective long-term antibody levels in mice,thus representing a promising candidate to further develop anti-toxoplasmosis vaccines.展开更多
Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy.Nonetheless,the optimization of the catal...Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy.Nonetheless,the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes.Herein,we reported a self-amplifying fluorescent molecular probe,Bis-HTPICG,for photodynamic therapy(PDT)and subsequent PDT-induced immunoreaction.The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase(MPO),a crucial enzyme secreted by neutrophils at inflammation sites.Upon exposure to laser irradiation,Bis-HTP-ICG showed a high PDT efficacy,inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion.The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis,instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG,neutrophils and MPO.Meanwhile,PDT efficiently incites immunogenic cell death(ICD)in tumor cells,initiating an anti-tumor immune response including dendritic cells(DCs)maturation,T cell proliferation and reprogramming of tumor-associated neutrophils(TANs).This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels,potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.展开更多
The protein,N-myc downstream-regulated gene 2(NDRG2),a tumor suppressor,is significantly decreased or absent in many types of cancer.There is a significant negative correlation between the levels of NDRG2 and the deve...The protein,N-myc downstream-regulated gene 2(NDRG2),a tumor suppressor,is significantly decreased or absent in many types of cancer.There is a significant negative correlation between the levels of NDRG2 and the development and progression of cancer tumor recurrence and tumor invasion,in different cancers.In contrast,the in vitro and in vivo overexpression of the NDRG2 protein decreases the proliferation,growth,adhesion and migration of many types of cancer cells.The in vitro overexpression of NDRG2 increases the efficacy of certain anticancer drugs in specific types of cancer cells.We hypothesize that the delivery of the mRNA of the NDRG2 protein,encapsulated by lipid nanoparticles,could represent a potential treatment of metastatic and drug-resistant cancers.This would be accomplished using a self-amplifying mRNA that encodes the NDRG2 protein and an RNA-dependent-RNA polymerase,obtained from an in vitrotranscribed(IVT)mRNA.The IVT mRNA would be encapsulated in a lipid nanoformulation.The efficacy of the nanoformulation would be determined in cultured cancer cells and if the results are positive,nude mice transplanted with either drug-resistant or metastatic drug-resistant cancer cells,would be treated with the nanoformulation and monitored for efficacy and adverse effects.If the appropriate preclinical studies indicate this formulation is efficacious and safe,it is possible it could be evaluated in clinical trials.展开更多
Nanoparticles induced potent antitumor immunotherapy plays a significant role for enhancing conventional therapeutic effectiveness.However,revealing the pathway of how nanoagents themselves trigger the host immunity o...Nanoparticles induced potent antitumor immunotherapy plays a significant role for enhancing conventional therapeutic effectiveness.However,revealing the pathway of how nanoagents themselves trigger the host immunity or how to maximize the immunotherapy efficacy still needs further exploration.Herein,rose-like MoS2 nanoflowers modified with 2-deoxy-D-glucose(2-DG)and glucose oxidase(GOx)(MPGGFs)have been successfully fabricated via a one-pot hydrothermal reaction and following one-by-one surface modification as a multifunctional nanocatalyst for photothermal therapy enhanced self-amplified chemodynamic immunotherapy(PTT-co-CDT).By introducing GOx,the obtained MPGGFs exhibited self-amplified chemodynamic therapeutic efficacy under hypoxia tumor microenvironment(TME)because of the raised intracellular H2O2 level via enzyme-catalysis of oxygen.Furthermore,combined with the intrinsic excellent photothermal conversion efficiency of MoS2 nanoflowers,PTT-co-CDT performances by MPGGFs could effectively induce the necroptosis of tumor cells both in vitro and in vivo.Then the induced necroptosis via PTT-co-CDT by MPGGFs could directly trigger host immunity by activating the antigen-specific T-cells(CD4^(+) and CD8^(+)).Finally,the excellent in vivo safety of MPGGFs makes us believe that the successful construction of rose-like multifunctional nanocatalyst not only has great potentials for self-amplified chemodynamic immunotherapy,but also provides a paradigm for exploring necroptosis triggered host immunity for cancer treatment.展开更多
Ferroptosis is a recently discovered pathway for regulated cell death pathway.However,its efficacy is affected by limited iron content and intracellular ion homeostasis.Here,we designed a metalorganic framework(MOF)-b...Ferroptosis is a recently discovered pathway for regulated cell death pathway.However,its efficacy is affected by limited iron content and intracellular ion homeostasis.Here,we designed a metalorganic framework(MOF)-based nanoplatform that incorporates calcium peroxide(CaO_(2))and oridonin(ORI).This platform can improve the tumor microenvironment and disrupt intracellular iron homeostasis,thereby enhancing ferroptosis therapy.Fused cell membranes(FM)were used to modify nanoparticles(ORI@CaO_(2)@Fe-TCPP,NPs)to produce FM@ORI@CaO_(2)@Fe-TCPP(FM@NPs).The encapsulated ORI inhibited the HSPB1/PCBP1/IREB2 and FSP1/COQ10 pathways simultaneously,working in tandem with Fe^(3+) to induce ferroptosis.Photodynamic therapy(PDT)guided by porphyrin(TCPP)significantly enhanced ferroptosis through excessive accumulation of reactive oxygen species(ROS).This selfamplifying strategy promoted robust ferroptosis,which could work synergistically with FM-mediated immunotherapy.In vivo experiments showed that FM@NPs inhibited 91.57%of melanoma cells within six days,a rate 5.6 times higher than chemotherapy alone.FM@NPs were biodegraded and directly eliminated in the urine or faeces without substantial toxicity.Thus,this study demonstrated that combining immunotherapy with efficient ferroptosis induction through nanotechnology is a feasible and promising strategy for melanoma treatment.展开更多
Messenger RNA(mRNA)is a type of RNA that carries genetic information from DNA to the ribosome,where it is translated into proteins.mRNA has emerged as a powerful platform for development of new types of medicine,espec...Messenger RNA(mRNA)is a type of RNA that carries genetic information from DNA to the ribosome,where it is translated into proteins.mRNA has emerged as a powerful platform for development of new types of medicine,especially after the clinical approval of COVID-19 mRNA vaccines.Chemical modification and nanoparticle delivery have contributed to this success significantly by improving mRNA stability,reducing its immunogenicity,protecting it from enzymatic degradation,and enhancing cellular uptake and endosomal escape.Recently,substantial progresses have been made in new modification chemistries,sequence design,and structural engineering to generate more stable and efficient next-generation mRNAs.These innovations could further facilitate the clinical translation of mRNA therapies and vaccines.Given that numerous review articles have been published on mRNA nanoparticle delivery and biomedical applications over the last few years,we herein focus on overviewing recent advances in mRNA chemical modification,mRNA sequence optimization,and mRNA engineering(e.g.,circular RNA and multitailed mRNA),with the aim of providing new perspectives on the development of more effective and safer mRNA medicines.展开更多
The X-ray free-electron laser(XFEL),a new X-ray light source,presents numerous opportunities for scientific research.Self-amplified spontaneous emission(SASE)is one generation mode of XFEL in which each pulse is uniqu...The X-ray free-electron laser(XFEL),a new X-ray light source,presents numerous opportunities for scientific research.Self-amplified spontaneous emission(SASE)is one generation mode of XFEL in which each pulse is unique.In this paper,we propose a pinhole diffraction method to accurately determine the XFEL photon energy,pulses'photon energy jitter,and sample-to-detector distance for soft X-ray.This method was verified at Shanghai soft X-ray Free-Electron Laser(SXFEL).The measured average photon energy was 406.5 eV,with a photon energy jitter(root-mean-square)of 1.39 eV,and the sample-to-detector distance was calculated to be 16.61 cm.展开更多
Nucleic acid vaccines have attracted enormous attention for resolving the limitations of conventional vaccines using live attenuated viruses. Because nucleic acid vaccines can be produced rapidly in response to the em...Nucleic acid vaccines have attracted enormous attention for resolving the limitations of conventional vaccines using live attenuated viruses. Because nucleic acid vaccines can be produced rapidly in response to the emergence of new virus strains, they are more appropriate for the control of urgent epidemic and pandemic issues. In particular, messenger RNA （mRNA） vaccines have evolved as a new type of nucleic acid vaccines in accordance with their superior protein expression and a lack of mutagenesis as compared with DNA vaccines. Using mRNA vaccines, large amounts of target proteins can be expressed in immune cells for efficient immunization. For instance, antigen-specific vaccination is a feasible option involving the expression of specific antigens in antigen-presenting cells. Immunological reactions are modulated by expressing several proteins associated with stimulation or maturation of immune cells. In addition, mRNA vaccines can stimulate innate immunity through specific recognition by pattern recognition receptors. On the basis of these remarkable properties, mRNA vaccines have been used for prophylactic and therapeutic applications. This review highlights the role of mRNA vaccines as prophylactic vaccines for prevention of future infections and as therapeutic vaccines for cancer immunotherapy. In addition to the conventional type of mRNA vaccines, RNA replicons （self-amplifying mRNA vaccines） will be described.展开更多
This paper reviews the development of X-ray free-electron lasers ( XFELs) . With the unprecedented characteristics of flexible wavelength tunability ,high brightness ,ultrashort pulse duration ,and fully transverse co...This paper reviews the development of X-ray free-electron lasers ( XFELs) . With the unprecedented characteristics of flexible wavelength tunability ,high brightness ,ultrashort pulse duration ,and fully transverse coherence ,these accelerator-based X-ray light sources will open newfields in physics ,chemistry , material ,and life sciences . Based on the present status of XFELs in the worldwide context ,the future directions are analyzed .A brief summary of the developments of free-electron lasers (FELs) in China is given .展开更多
基金supported by the National Natural Science Foundation of China[Grant Numbers 32370997,81871684]the Provincial Key R&D program of Zhejiang Department of Science and Technology[Grant Number 2022C03109]+3 种基金the Central Leading Local Science and Technology Development Fund Project[Grant Number 2023ZY1019]the Key Projects Jointly Constructed by the Ministry and the Province of Zhejiang Medical and Health Science and Technology Project[Grant Number WKJ-ZJ-2545]the Foundation of GuoTai(Taizhou)Center of Technology Innovation for Veterinary Biologicals[Grant Number GTKF(23)001]the Key Discipline of Zhejiang Province in Public Health and Preventive Medicine(First Class,Category A),Hangzhou Medical College.
文摘Background Toxoplasma gondii,an intracellular parasitic protozoan,which infects almost all warm-blooded animals,including humans,causes toxoplasmosis.However,we lack effective drugs and vaccines to control toxoplasmosis,representing a clinical challenge.Therefore,safe and effective vaccines are urgently needed.In this study,a self-replicating mRNA vaccine comprising four T.gondii antigens:ROP18,TGME49_237490,TGME49_268230,and MIC13,named 4x-mRNA-LNP(lipid nanoparticle),was developed,and its protective efficacy was evaluated in mice.Methods The expression of this vaccine in eukaryotic Human embryonic kidney 293 T(HEK-293 T)cells and mouse myoblast(C2C12)cells were analyzed,followed by enzyme-linked immunosorbent assay(ELISA)evaluation of the elicited humoral immune response.Subsequently,the vaccine-triggered immune responses in mice were detected,including antibody titers,T lymphocyte subsets,and cytokine levels.Finally,its immunoprotective effects were evaluated after challenging mice with T.gondii PRU oocysts or tachyzoites of different strains and analyzing the pathological changes,parasite loads,and mouse survival time.Western blotting and ELISA confirmed the successful eukaryotic expression and immunogenicity of 4x-mRNA,respectively.Statistical analyses,including the log-rank(Mantel–Cox)test,Student’s t-test,and one-way ANOVA,were performed using GraphPad Prism software.Results Mice vaccinated with 4x-mRNA-LNP generated higher levels of IgG1 and IgG2a antibodies(P<0.05)and cytokines(IL-2,IL-4,IL-10,IL-12,IFN-γ)(P<0.05)compared with the control group.The high specific IgG titer was maintained for at least 10 weeks after the last vaccination.The proportion of CD3^(+)CD4^(+)T cells and CD3^(+)CD8^(+)T cells also increased significantly(P<0.05),along with increased spleen cell proliferation in 4x-mRNA-LNP-vaccinated mice.Notably,limited pathological changes and<10 fg of parasites/mg were found in the immunized mice tissues post-pathogen challenge.During observation for 30 days,4x-mRNA-LNP-immunized mice survived significantly longer under challenge with lethal doses of RH,ME49,or WH6 tachyzoites(survival rates=60%,80%,and 60%,respectively).Following PRU oocyst challenge,vaccinated mice had notably decreased cyst burdens(72.5%,P<0.05)compared with control mice.Conclusions The 4x-mRNA-LNP vaccine triggered effective long-term antibody levels in mice,thus representing a promising candidate to further develop anti-toxoplasmosis vaccines.
基金supported by the Key Areas Research and Development Program of Guangzhou(202007020006)the National Natural Science Foundation of China(51933011,31971296,82102194,82302360)+1 种基金the Science and Technology Projects of Guangzhou(2023A03J0215)the Guangdong Basic Research Center of Excellence for Functional Molecular Engineering。
文摘Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy.Nonetheless,the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes.Herein,we reported a self-amplifying fluorescent molecular probe,Bis-HTPICG,for photodynamic therapy(PDT)and subsequent PDT-induced immunoreaction.The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase(MPO),a crucial enzyme secreted by neutrophils at inflammation sites.Upon exposure to laser irradiation,Bis-HTP-ICG showed a high PDT efficacy,inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion.The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis,instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG,neutrophils and MPO.Meanwhile,PDT efficiently incites immunogenic cell death(ICD)in tumor cells,initiating an anti-tumor immune response including dendritic cells(DCs)maturation,T cell proliferation and reprogramming of tumor-associated neutrophils(TANs).This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels,potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.
文摘The protein,N-myc downstream-regulated gene 2(NDRG2),a tumor suppressor,is significantly decreased or absent in many types of cancer.There is a significant negative correlation between the levels of NDRG2 and the development and progression of cancer tumor recurrence and tumor invasion,in different cancers.In contrast,the in vitro and in vivo overexpression of the NDRG2 protein decreases the proliferation,growth,adhesion and migration of many types of cancer cells.The in vitro overexpression of NDRG2 increases the efficacy of certain anticancer drugs in specific types of cancer cells.We hypothesize that the delivery of the mRNA of the NDRG2 protein,encapsulated by lipid nanoparticles,could represent a potential treatment of metastatic and drug-resistant cancers.This would be accomplished using a self-amplifying mRNA that encodes the NDRG2 protein and an RNA-dependent-RNA polymerase,obtained from an in vitrotranscribed(IVT)mRNA.The IVT mRNA would be encapsulated in a lipid nanoformulation.The efficacy of the nanoformulation would be determined in cultured cancer cells and if the results are positive,nude mice transplanted with either drug-resistant or metastatic drug-resistant cancer cells,would be treated with the nanoformulation and monitored for efficacy and adverse effects.If the appropriate preclinical studies indicate this formulation is efficacious and safe,it is possible it could be evaluated in clinical trials.
基金the National Natural Science Foundation of China(Nos.81671829,21788102,and 51971116)Many thanks to Hunan Provincial Innovation Foundation for Postgraduate(No.2020zzts079)。
文摘Nanoparticles induced potent antitumor immunotherapy plays a significant role for enhancing conventional therapeutic effectiveness.However,revealing the pathway of how nanoagents themselves trigger the host immunity or how to maximize the immunotherapy efficacy still needs further exploration.Herein,rose-like MoS2 nanoflowers modified with 2-deoxy-D-glucose(2-DG)and glucose oxidase(GOx)(MPGGFs)have been successfully fabricated via a one-pot hydrothermal reaction and following one-by-one surface modification as a multifunctional nanocatalyst for photothermal therapy enhanced self-amplified chemodynamic immunotherapy(PTT-co-CDT).By introducing GOx,the obtained MPGGFs exhibited self-amplified chemodynamic therapeutic efficacy under hypoxia tumor microenvironment(TME)because of the raised intracellular H2O2 level via enzyme-catalysis of oxygen.Furthermore,combined with the intrinsic excellent photothermal conversion efficiency of MoS2 nanoflowers,PTT-co-CDT performances by MPGGFs could effectively induce the necroptosis of tumor cells both in vitro and in vivo.Then the induced necroptosis via PTT-co-CDT by MPGGFs could directly trigger host immunity by activating the antigen-specific T-cells(CD4^(+) and CD8^(+)).Finally,the excellent in vivo safety of MPGGFs makes us believe that the successful construction of rose-like multifunctional nanocatalyst not only has great potentials for self-amplified chemodynamic immunotherapy,but also provides a paradigm for exploring necroptosis triggered host immunity for cancer treatment.
基金the Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(No.CACM-QNRC2-A03,China)the Beijing Natural Science Foundation(No.7202121,China)the National Natural Science Foundation of China(No.81703715).
文摘Ferroptosis is a recently discovered pathway for regulated cell death pathway.However,its efficacy is affected by limited iron content and intracellular ion homeostasis.Here,we designed a metalorganic framework(MOF)-based nanoplatform that incorporates calcium peroxide(CaO_(2))and oridonin(ORI).This platform can improve the tumor microenvironment and disrupt intracellular iron homeostasis,thereby enhancing ferroptosis therapy.Fused cell membranes(FM)were used to modify nanoparticles(ORI@CaO_(2)@Fe-TCPP,NPs)to produce FM@ORI@CaO_(2)@Fe-TCPP(FM@NPs).The encapsulated ORI inhibited the HSPB1/PCBP1/IREB2 and FSP1/COQ10 pathways simultaneously,working in tandem with Fe^(3+) to induce ferroptosis.Photodynamic therapy(PDT)guided by porphyrin(TCPP)significantly enhanced ferroptosis through excessive accumulation of reactive oxygen species(ROS).This selfamplifying strategy promoted robust ferroptosis,which could work synergistically with FM-mediated immunotherapy.In vivo experiments showed that FM@NPs inhibited 91.57%of melanoma cells within six days,a rate 5.6 times higher than chemotherapy alone.FM@NPs were biodegraded and directly eliminated in the urine or faeces without substantial toxicity.Thus,this study demonstrated that combining immunotherapy with efficient ferroptosis induction through nanotechnology is a feasible and promising strategy for melanoma treatment.
基金the U.S.National Institutes of Health grants(Nos.R01CA200900,R01HL159012,and R33HL168751)the Innovation Discovery Grants award from the Mass General Brigham.
文摘Messenger RNA(mRNA)is a type of RNA that carries genetic information from DNA to the ribosome,where it is translated into proteins.mRNA has emerged as a powerful platform for development of new types of medicine,especially after the clinical approval of COVID-19 mRNA vaccines.Chemical modification and nanoparticle delivery have contributed to this success significantly by improving mRNA stability,reducing its immunogenicity,protecting it from enzymatic degradation,and enhancing cellular uptake and endosomal escape.Recently,substantial progresses have been made in new modification chemistries,sequence design,and structural engineering to generate more stable and efficient next-generation mRNAs.These innovations could further facilitate the clinical translation of mRNA therapies and vaccines.Given that numerous review articles have been published on mRNA nanoparticle delivery and biomedical applications over the last few years,we herein focus on overviewing recent advances in mRNA chemical modification,mRNA sequence optimization,and mRNA engineering(e.g.,circular RNA and multitailed mRNA),with the aim of providing new perspectives on the development of more effective and safer mRNA medicines.
基金supported by the Major State Basic Research Development Program of China(No.2022YFA1603703)the National Natural Science Foundation of China(No.12335020)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB37040303)supported by the Shanghai Soft X-ray Free-Electron Laser Beamline Project。
文摘The X-ray free-electron laser(XFEL),a new X-ray light source,presents numerous opportunities for scientific research.Self-amplified spontaneous emission(SASE)is one generation mode of XFEL in which each pulse is unique.In this paper,we propose a pinhole diffraction method to accurately determine the XFEL photon energy,pulses'photon energy jitter,and sample-to-detector distance for soft X-ray.This method was verified at Shanghai soft X-ray Free-Electron Laser(SXFEL).The measured average photon energy was 406.5 eV,with a photon energy jitter(root-mean-square)of 1.39 eV,and the sample-to-detector distance was calculated to be 16.61 cm.
文摘Nucleic acid vaccines have attracted enormous attention for resolving the limitations of conventional vaccines using live attenuated viruses. Because nucleic acid vaccines can be produced rapidly in response to the emergence of new virus strains, they are more appropriate for the control of urgent epidemic and pandemic issues. In particular, messenger RNA （mRNA） vaccines have evolved as a new type of nucleic acid vaccines in accordance with their superior protein expression and a lack of mutagenesis as compared with DNA vaccines. Using mRNA vaccines, large amounts of target proteins can be expressed in immune cells for efficient immunization. For instance, antigen-specific vaccination is a feasible option involving the expression of specific antigens in antigen-presenting cells. Immunological reactions are modulated by expressing several proteins associated with stimulation or maturation of immune cells. In addition, mRNA vaccines can stimulate innate immunity through specific recognition by pattern recognition receptors. On the basis of these remarkable properties, mRNA vaccines have been used for prophylactic and therapeutic applications. This review highlights the role of mRNA vaccines as prophylactic vaccines for prevention of future infections and as therapeutic vaccines for cancer immunotherapy. In addition to the conventional type of mRNA vaccines, RNA replicons （self-amplifying mRNA vaccines） will be described.
文摘This paper reviews the development of X-ray free-electron lasers ( XFELs) . With the unprecedented characteristics of flexible wavelength tunability ,high brightness ,ultrashort pulse duration ,and fully transverse coherence ,these accelerator-based X-ray light sources will open newfields in physics ,chemistry , material ,and life sciences . Based on the present status of XFELs in the worldwide context ,the future directions are analyzed .A brief summary of the developments of free-electron lasers (FELs) in China is given .
