Layered composite oxide materials with O3/P2 biphasic crystallographic structure typically demonstrate a combination of high capacities of the O3 phase and high operation voltages of the P2 phase.However,their practic...Layered composite oxide materials with O3/P2 biphasic crystallographic structure typically demonstrate a combination of high capacities of the O3 phase and high operation voltages of the P2 phase.However,their practical applications are seriously obstructed by difficulties in thermodynamic phase regulation,complicated electrochemical phase transition,and unsatisfactory cycling life.Herein,we propose an efficient structural evolution strategy from biphase to monophase of Na_(0.766+x)Li_(x)Ni_(0.33-x)Mn_(0.5)Fe_(0.1)Ti_(0.07)O_(2) through Li+substitution.The role of Li+substitution not only simplifies the unfavorable phase transition by altering the local coordination of transition metal(TM)cations but also stabilizes the cathode–electrolyte interphase to prevent the degradation of TM cations during battery cycling.As a result,the thermodynamically robust O_(3)-Na_(0.826)Li_(0.06)Ni_(0.27)Mn_(0.5)Fe_(0.1)Ti_(0.07)O_(2) cathode delivers a high capacity of 139.4 mAh g^(-1) at 0.1 C and shows prolonged cycling life at high rates,with capacity retention of 81.6%at 5 C over 500 cycles.This work establishes a solid relationship between the thermodynamic structure evolution and electrochemistry of layered cathode materials,contributing to the development of long-life sodium-ion batteries.展开更多
The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases(CDKs)is a hallmark of cancer.The inhibition of CDKs is a highly promising and attractive strat...The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases(CDKs)is a hallmark of cancer.The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs.In particular,third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition,exhibiting a perfect balance between anticancer efficacy and general toxicity.To date,three selective CDK4/6 inhibitors have received approval from the U.S.Food and Drug Administration(FDA),and 15 CDK4/6 inhibitors are in clinical trials for the treatment of cancers.In this perspective,we discuss the crucial roles of CDK4/6 in regulating the cell cycle and cancer cells,analyze the rationale for selectively inhibiting CDK4/6 for cancer treatment,review the latest advances in highly selective CDK4/6 inhibitors with different chemical scaffolds,explain the mechanisms associated with CDK4/6inhibitor resistance and describe solutions to overcome this issue,and briefly introduce proteolysis targeting chimera(PROTAC),a new and revolutionary technique used to degrade CDK4/6.展开更多
Sodium-ion intercalation oxides generally possess high compositional diversity according to their different stacking sequences.The sodium diffusion pathway in layered P-type materials used in sodium-ion batteries is o...Sodium-ion intercalation oxides generally possess high compositional diversity according to their different stacking sequences.The sodium diffusion pathway in layered P-type materials used in sodium-ion batteries is open,which can increase their rate capability by directly transmitting Na+between adjacent triangular prismatic channels,rather than passing through an intermediate tetrahedral site in O-type structure.However,how the structure chemistry of the P-type oxides determines their electrochemical properties has not been fully understood yet.Herein,by comparing the crystalline structures,electrochemical behaviors,ion/electron transport dynamics of a couple of P-type intercalation cathodes,P2-Na_(2/3)Ni1/3Mn_(2/3)O_(2)and P3-Na_(2/3)Ni_(1/3)Mn_(2/3)O_(2)with the same compositions,we demonstrate experimentally and computationally that the P2 phase delivers better cycling stability and rate capability than the P3 counterpart due to the predominant contribution of the faster intrinsic Na diffusion kinetics in the P2 bulk.We also point out that it is the electronic conductivity that captures the key electrochemistry of layered P3-type materials and makes them possible to enhance the sodium storage performance.The results reveal that the correlation between stacking structure and functional properties in two typical layered P-type cathodes,providing new guidelines for preparing and designing alkali-metal layered oxide materials with improved battery performance.展开更多
Aims Drought and salinity are severe abiotic stress factors,which limit plant growth and productivity,particularly in desert regions.In this study,we employed two desert poplars,Populus euphratica Oliver and Populus p...Aims Drought and salinity are severe abiotic stress factors,which limit plant growth and productivity,particularly in desert regions.In this study,we employed two desert poplars,Populus euphratica Oliver and Populus pruinosa Schrenk seedlings,to compare their tolerance to drought,salinity and combined stress.Methods We investigated species-specific responses of P.euphratica and P.pruinosa in growth,photosynthetic capacity and pigment contents,nonstructural carbohydrate concentrations,Cl−allocation,osmotic regulation and the accumulation of reactive oxygen species(ROS)under drought,salinity and the combined stress.Important Findings Populus pruinosa exhibited greater growth inhibitory effects,photosynthesis decline,stomatal closure and ROS accumulation,and lower antioxidant enzyme activities and osmotic regulation compared with P.euphratica under drought,salinity and especially under their combined stress.On the other hand,salt-stressed P.euphratica plants restricted salt transportation from roots to leaves,and allocated more Cl−to coarse roots and less to leaves,whereas salt-stressed P.pruinosa allocated more Cl−to leaves.It was shown that there is species-specific variation in these two desert poplars,and P.pruinosa suffers greater negative effects compared with P.euphratica under drought,salinity and especially under the combined stress.Therefore,in ecological restoration and afforestation efforts,species-specific responses and tolerances of these two poplar species to drought and salinity should be considered under climate change with increasing drought and soil salinity developing.展开更多
Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy.Despite the inherent advantages of small-molecule inhibit...Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy.Despite the inherent advantages of small-molecule inhibitors over antibodies,the discovery of small-molecule inhibitors has fallen behind that of antibody drugs.Based on docking studies between small molecule inhibitor and PD-L1 protein,changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein,which was not reported before.A series of novel phthalimide derivatives from structure-based rational design was synthesized.P39 was identified as the best inhibitor with promising activity,which not only inhibited PD-1/PD-L1 interaction(IC_(50)=8.9 nmol/L),but also enhanced killing efficacy of immune cells on cancer cells.Co-crystal data demonstrated that P39 induced the dimerization of PD-L1 proteins,thereby blocking the binding of PD-1/PD-L1.Moreover,P39 exhibited a favorable safety profile with a LD_(50)>5000 mg/kg and showed significant in vivo antitumor activity through promoting CD8^(+)T cell activation.All these data suggest that P39 acts as a promising small chemical inhibitor against the PD-1/PD-L1 axis and has the potential to improve the immunotherapy efficacy of T-cells.展开更多
基金This work was supported by the National Natural Science Foundation of China(52102302,51807146,and 22179021)the Young Talent Support Plan of Xi'an Jiaotong University(Grant No.DQ6J011)+2 种基金Natural Science Foundation of Shaanxi Province(2023-JC-QN-0115)State Key Laboratory of Electrical Insulation and Power Equipment(EIPE23313)the Fundamental Research Funds for the Central Universities(xyz012023165).
文摘Layered composite oxide materials with O3/P2 biphasic crystallographic structure typically demonstrate a combination of high capacities of the O3 phase and high operation voltages of the P2 phase.However,their practical applications are seriously obstructed by difficulties in thermodynamic phase regulation,complicated electrochemical phase transition,and unsatisfactory cycling life.Herein,we propose an efficient structural evolution strategy from biphase to monophase of Na_(0.766+x)Li_(x)Ni_(0.33-x)Mn_(0.5)Fe_(0.1)Ti_(0.07)O_(2) through Li+substitution.The role of Li+substitution not only simplifies the unfavorable phase transition by altering the local coordination of transition metal(TM)cations but also stabilizes the cathode–electrolyte interphase to prevent the degradation of TM cations during battery cycling.As a result,the thermodynamically robust O_(3)-Na_(0.826)Li_(0.06)Ni_(0.27)Mn_(0.5)Fe_(0.1)Ti_(0.07)O_(2) cathode delivers a high capacity of 139.4 mAh g^(-1) at 0.1 C and shows prolonged cycling life at high rates,with capacity retention of 81.6%at 5 C over 500 cycles.This work establishes a solid relationship between the thermodynamic structure evolution and electrochemistry of layered cathode materials,contributing to the development of long-life sodium-ion batteries.
基金supported by the Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZRC07,China)111 Project(B16046,China)+2 种基金“Double First-Class”University Project(CPU2018GF04,China)Jiangsu Key Laboratory of Drug Design and Optimization(DDORC201801,China)65th China Postdoctoral Science Foundation(2019M652030)
文摘The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases(CDKs)is a hallmark of cancer.The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs.In particular,third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition,exhibiting a perfect balance between anticancer efficacy and general toxicity.To date,three selective CDK4/6 inhibitors have received approval from the U.S.Food and Drug Administration(FDA),and 15 CDK4/6 inhibitors are in clinical trials for the treatment of cancers.In this perspective,we discuss the crucial roles of CDK4/6 in regulating the cell cycle and cancer cells,analyze the rationale for selectively inhibiting CDK4/6 for cancer treatment,review the latest advances in highly selective CDK4/6 inhibitors with different chemical scaffolds,explain the mechanisms associated with CDK4/6inhibitor resistance and describe solutions to overcome this issue,and briefly introduce proteolysis targeting chimera(PROTAC),a new and revolutionary technique used to degrade CDK4/6.
基金supported by the National Natural Science Foundation of China (U1607128,52102302 and 21521005)Natural Science Foundation of Beijing (2222020)+1 种基金the Young Talent Support Plan and Siyuan Scholar of Xi’an Jiaotong University (DQ6J011 and DQ1J009)State Key Laboratory of Electrical Insulation and Power Equipment (EIPE23313)
文摘Sodium-ion intercalation oxides generally possess high compositional diversity according to their different stacking sequences.The sodium diffusion pathway in layered P-type materials used in sodium-ion batteries is open,which can increase their rate capability by directly transmitting Na+between adjacent triangular prismatic channels,rather than passing through an intermediate tetrahedral site in O-type structure.However,how the structure chemistry of the P-type oxides determines their electrochemical properties has not been fully understood yet.Herein,by comparing the crystalline structures,electrochemical behaviors,ion/electron transport dynamics of a couple of P-type intercalation cathodes,P2-Na_(2/3)Ni1/3Mn_(2/3)O_(2)and P3-Na_(2/3)Ni_(1/3)Mn_(2/3)O_(2)with the same compositions,we demonstrate experimentally and computationally that the P2 phase delivers better cycling stability and rate capability than the P3 counterpart due to the predominant contribution of the faster intrinsic Na diffusion kinetics in the P2 bulk.We also point out that it is the electronic conductivity that captures the key electrochemistry of layered P3-type materials and makes them possible to enhance the sodium storage performance.The results reveal that the correlation between stacking structure and functional properties in two typical layered P-type cathodes,providing new guidelines for preparing and designing alkali-metal layered oxide materials with improved battery performance.
基金supported by the Natural Science Foundation of China(U1803231)and the Talent Program of the Hangzhou Normal University(2016QDL020).
文摘Aims Drought and salinity are severe abiotic stress factors,which limit plant growth and productivity,particularly in desert regions.In this study,we employed two desert poplars,Populus euphratica Oliver and Populus pruinosa Schrenk seedlings,to compare their tolerance to drought,salinity and combined stress.Methods We investigated species-specific responses of P.euphratica and P.pruinosa in growth,photosynthetic capacity and pigment contents,nonstructural carbohydrate concentrations,Cl−allocation,osmotic regulation and the accumulation of reactive oxygen species(ROS)under drought,salinity and the combined stress.Important Findings Populus pruinosa exhibited greater growth inhibitory effects,photosynthesis decline,stomatal closure and ROS accumulation,and lower antioxidant enzyme activities and osmotic regulation compared with P.euphratica under drought,salinity and especially under their combined stress.On the other hand,salt-stressed P.euphratica plants restricted salt transportation from roots to leaves,and allocated more Cl−to coarse roots and less to leaves,whereas salt-stressed P.pruinosa allocated more Cl−to leaves.It was shown that there is species-specific variation in these two desert poplars,and P.pruinosa suffers greater negative effects compared with P.euphratica under drought,salinity and especially under the combined stress.Therefore,in ecological restoration and afforestation efforts,species-specific responses and tolerances of these two poplar species to drought and salinity should be considered under climate change with increasing drought and soil salinity developing.
基金This study was supported by the National Natural Science Foundation of China(82073701,31900687,81973366)Natural Science Foundation of Jiangsu Province(BK2019040713,China)+3 种基金the Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZ202013,China)This study was also supported by Jiangsu Key Laboratory of Drug Design and Optimization,China Pharmaceutical University(No.2020KFKT-5,China)the“Double First-Class”University Project(CPU2018GF04,China),and CAMS Innovation Fund for Medical Sciences(2021-I2M-1-070)The X-ray data were collected at the Shanghai Synchrotron Radiation Facility(SSRF,China)BL19U beamline.
文摘Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy.Despite the inherent advantages of small-molecule inhibitors over antibodies,the discovery of small-molecule inhibitors has fallen behind that of antibody drugs.Based on docking studies between small molecule inhibitor and PD-L1 protein,changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein,which was not reported before.A series of novel phthalimide derivatives from structure-based rational design was synthesized.P39 was identified as the best inhibitor with promising activity,which not only inhibited PD-1/PD-L1 interaction(IC_(50)=8.9 nmol/L),but also enhanced killing efficacy of immune cells on cancer cells.Co-crystal data demonstrated that P39 induced the dimerization of PD-L1 proteins,thereby blocking the binding of PD-1/PD-L1.Moreover,P39 exhibited a favorable safety profile with a LD_(50)>5000 mg/kg and showed significant in vivo antitumor activity through promoting CD8^(+)T cell activation.All these data suggest that P39 acts as a promising small chemical inhibitor against the PD-1/PD-L1 axis and has the potential to improve the immunotherapy efficacy of T-cells.
