Over the past two decades,immunotherapies have increasingly been considered as first-line treatments for most cancers.One such treatment is immune checkpoint blockade(ICB),which has demonstrated promising results agai...Over the past two decades,immunotherapies have increasingly been considered as first-line treatments for most cancers.One such treatment is immune checkpoint blockade(ICB),which has demonstrated promising results against various solid tumors in clinical trials.Monoclonal antibodies(mAbs)are currently available as immune checkpoint inhibitors(ICIs).These ICIs target specific immune checkpoints,including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4)and programmed cell death protein 1(PD-1).Clinical trial results strongly support the feasibility of this immunotherapeutic approach.However,a substantial proportion of patients with cancer develop resistance or tolerance to treatment,owing to tumor immune evasion mechanisms that counteract the host immune response.Consequently,substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1,anti-programmed cell death ligand 1(anti-PD-L1),and anti-CTLA-4 treatments.Recently,several immune checkpoint molecular targets have been identified,such as T cell immunoreceptor with Ig and ITIM domains(TIGIT),mucin domain containing-3(TIM-3),lymphocyte activation gene-3(LAG-3),V-domain immunoglobulin suppressor of T cell activation(VISTA),B and T lymphocyte attenuator(BTLA),and signal-regulatory proteinα(SIRPα).Functional m Abs targeting these molecules are under development.CTLA-4,PD-1/PD-L1,and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research.This review discusses these structures,as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.展开更多
Developing nanomaterial-based enzyme mimics for DNA cleavage is an interesting challenge and it has many potential applications.Single-layered graphene oxide(GO)is an excellent platform for DNA adsorption.In addition,...Developing nanomaterial-based enzyme mimics for DNA cleavage is an interesting challenge and it has many potential applications.Single-layered graphene oxide(GO)is an excellent platform for DNA adsorption.In addition,GO has been employed for photosensitized generation of reactive oxygen species(ROS).Herein,we demonstrate that GO sheets could cleave DNA as anuclease mimicking nanozyme in the presence of UV or blue light.For various DNA sequences and lengths,well-defined product bands were observed along with photobleaching of the fluorophore label on the DNA.Different from previously reported GO cleavage of DNA,our method did not require metal ions such as Cu^2+.Fluorescence spectroscopy suggested a high adsorption affinity between GO and DNA.For comparison,although zero-dimensional fluorescent carbon dots(C-dots)had higher photosensitivity ir terms of producing ROS,their cleavage activity was much lower and only smeared cleavage products were observed,indicatingthat the ROS acted on the DNA in solution.Based on the results,GO behaved like a classic heterogeneous catalyst following substrate adsorption,reaction,and product desorption steps.This simple strategy may help in the design of new nanozymes by introducing light.展开更多
Dear Editor,Glutamate is the main excitatory neurotransmitter in the human brain,and it exerts diverse responses through ionotropic glutamate receptors(iGluRs)and metabotropic glutamate receptors(mGluRs)(Nakanishi and...Dear Editor,Glutamate is the main excitatory neurotransmitter in the human brain,and it exerts diverse responses through ionotropic glutamate receptors(iGluRs)and metabotropic glutamate receptors(mGluRs)(Nakanishi and Masu,1994).mGluRs are members of the C family of GPCRs,and are divided into three groups based on G protein coupling,sequence homology,and ligand selectivity(Stansley and Conn,2019).mGlu1 and mGlu5 belong to group I and predominantly couple to Gq/11.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82173087 and 82203533)。
文摘Over the past two decades,immunotherapies have increasingly been considered as first-line treatments for most cancers.One such treatment is immune checkpoint blockade(ICB),which has demonstrated promising results against various solid tumors in clinical trials.Monoclonal antibodies(mAbs)are currently available as immune checkpoint inhibitors(ICIs).These ICIs target specific immune checkpoints,including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4)and programmed cell death protein 1(PD-1).Clinical trial results strongly support the feasibility of this immunotherapeutic approach.However,a substantial proportion of patients with cancer develop resistance or tolerance to treatment,owing to tumor immune evasion mechanisms that counteract the host immune response.Consequently,substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1,anti-programmed cell death ligand 1(anti-PD-L1),and anti-CTLA-4 treatments.Recently,several immune checkpoint molecular targets have been identified,such as T cell immunoreceptor with Ig and ITIM domains(TIGIT),mucin domain containing-3(TIM-3),lymphocyte activation gene-3(LAG-3),V-domain immunoglobulin suppressor of T cell activation(VISTA),B and T lymphocyte attenuator(BTLA),and signal-regulatory proteinα(SIRPα).Functional m Abs targeting these molecules are under development.CTLA-4,PD-1/PD-L1,and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research.This review discusses these structures,as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.
基金supported by the National Natural Science Foundation of China(91953202,31930060,and 31870744)the CAS Strategic Priority Research Program(XDB37030104)+5 种基金the National Science Fund for Distinguished Young Scholars(32022038)the National Key Research and Development Program of China(2018YFA0507000)the Shanghai Rising-Star Program(20QA1406500)the Shanghai Science and Technology Plan(21DZ2260400)the Shanghai Municipal Government and ShanghaiTech University for financial supportsupported by Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University。
基金Funding for this work was from the Natural Sciences and Engineering Research Council of Canada(NSERC)the National Natural Science Foundation of China(No.U19A2005).
文摘Developing nanomaterial-based enzyme mimics for DNA cleavage is an interesting challenge and it has many potential applications.Single-layered graphene oxide(GO)is an excellent platform for DNA adsorption.In addition,GO has been employed for photosensitized generation of reactive oxygen species(ROS).Herein,we demonstrate that GO sheets could cleave DNA as anuclease mimicking nanozyme in the presence of UV or blue light.For various DNA sequences and lengths,well-defined product bands were observed along with photobleaching of the fluorophore label on the DNA.Different from previously reported GO cleavage of DNA,our method did not require metal ions such as Cu^2+.Fluorescence spectroscopy suggested a high adsorption affinity between GO and DNA.For comparison,although zero-dimensional fluorescent carbon dots(C-dots)had higher photosensitivity ir terms of producing ROS,their cleavage activity was much lower and only smeared cleavage products were observed,indicatingthat the ROS acted on the DNA in solution.Based on the results,GO behaved like a classic heterogeneous catalyst following substrate adsorption,reaction,and product desorption steps.This simple strategy may help in the design of new nanozymes by introducing light.
文摘Dear Editor,Glutamate is the main excitatory neurotransmitter in the human brain,and it exerts diverse responses through ionotropic glutamate receptors(iGluRs)and metabotropic glutamate receptors(mGluRs)(Nakanishi and Masu,1994).mGluRs are members of the C family of GPCRs,and are divided into three groups based on G protein coupling,sequence homology,and ligand selectivity(Stansley and Conn,2019).mGlu1 and mGlu5 belong to group I and predominantly couple to Gq/11.
