LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)material,as the promising cathode candidate for next-generation highenergy lithium-ion batteries,has gained considerable attention for extremely high theoretical capacity and low...LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)material,as the promising cathode candidate for next-generation highenergy lithium-ion batteries,has gained considerable attention for extremely high theoretical capacity and low cost.Nevertheless,the intrinsic drawbacks of NCM811 such as unstable structure and inevitable interface side reaction result in severe capacity decay and thermal runaway.Herein,a novel polyimide(denoted as PI-Om DT)constructed with the highly polar and micro-branched crosslinking network is reported as a binder material for NCM811 cathode.The micro-branched crosslinking network is achieved by using 1,3,5-Tris(4-aminophenoxy)benzene(TAPOB)as a crosslinker via condensation reaction,which endows excellent mechanical properties and large free volume.Meanwhile,the massive polar carboxyl(-COOH)groups provide strong adhesion sites to active NCM811 particles.These functions of PIOm DT binder collaboratively benefit to forming the mechanically robust and homogeneous coating layer with rapid Li+diffusion on the surface of NCM811,significantly stabilizing the cathode structure,suppressing the detrimental interface side reaction and guaranteeing the shorter ion-diffusion and electron-transfer paths,consequently enhancing electrochemical performance.As compared to the NCM811 with PVDF binder,the NCM811 using PI-Om DT binder delivers a superior high-rate capacity(121.07 vs.145.38 m Ah g^(-1))at 5 C rate and maintains a higher capacity retention(80.38%vs.91.6%)after100 cycles at 2.5–4.3 V.Particularly,at the high-voltage conditions up to 4.5 and 4.7 V,the NCM811 with PI-Om DT binder still maintains the remarkable capacity retention of 88.86%and 72.5%after 100 cycles,respectively,paving the way for addressing the high-voltage operating stability of the NCM811 cathode.Moreover,the full-charged NCM811 cathode with PI-Om DT binder exhibits a significantly enhanced thermal stability,improving the safety performance of batteries.This work opens a new avenue for developing high-energy NCM811 based lithium-ion batteries with long cycle-life and superior safety performance using a novel and effective binder.展开更多
Along with our country urbanization advancement quickening, the scale of construction land expands, but there are many problems in collecting land. These questions have directly restricted the land collection work to ...Along with our country urbanization advancement quickening, the scale of construction land expands, but there are many problems in collecting land. These questions have directly restricted the land collection work to develop smoothly. This paper analyzes the main questions which collection work is up against and puts forward the improved proposal aiming at the peasant losing territory being short of participating in the process of pricing compensation, social security vacancy and so on.展开更多
Among the various families of G protein-couple receptors(GPCR),the adhesion family of GPCRs is specialized by its expansive extracellular region,which facilitates the recruitment of various ligands.Previous hypothesis...Among the various families of G protein-couple receptors(GPCR),the adhesion family of GPCRs is specialized by its expansive extracellular region,which facilitates the recruitment of various ligands.Previous hypothesis proposed that aGPCRs are activated by mechanical force,wherein a Stachel peptide is liberated from the GPCR autoproteolysis-inducing(GAIN)domain and subsequently binds to the transmembrane domain(7TM)upon activation.In this review,we summarize recent advancements in structural studies of aGPCRs,unveiling a conserved structural change of the Stachel peptide from the GAIN domain-embeddedβ-strand conformation to the 7TM-loadedα-helical conformation.Notably,using single-molecule studies,we directly observed the unfolding of GAIN domain and the release of Stachel peptide under physiological level of force,precisely supporting the mechanosensing mechanism for aGPCRs.We observed that the current complex structures of aGPCR adhesion domains with their respective ligands share a common pattern with the C-termini of each binding partner extending in opposite directions,suggesting a similar shearing stretch geometry for these aGPCRs to transmit the mechanical force generated in the circulating environment to the GAIN domain for its unfolding.Outstanding questions,including the relative orientations and interactions between 7TM and its preceding GAIN and adhesion domains of different aGPCRs,may require further structural and mechanical studies at the full-length receptor scale or cell-based level.Our analysis extends the current view of aGPCR structural organization and activation and offers valuable insights for the development of mechanosensor based on aGPCRs or discovery of mechanotherapy against aGPCRs.展开更多
The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy candidates.One of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡcl...The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy candidates.One of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡclinical trial to treat rectal cancer.However,the precise mechanism underlying its dual-antagonistic properties remains elusive.Herein,we report crystal structures of the A_(2A)R complexed with AB928 and a selective A_(2A)R antagonist 2-118.The structures revealed a common binding mode on A_(2A)R,wherein the ligands established extensive interactions with residues from the orthosteric and secondary pockets.In contrast,the cAMP assay and A_(2A)R and A_(2B)R molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A_(2B)R.Detailed analysis of their chemical structures suggested that AB928 readily adapted to the A_(2B)R pocket,while 2-118 did not due to intrinsic differences.This disparity potentially accounted for the difference in inhibitory efficacy between A_(2B)R and A_(2A)R.This study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A_(2A)R/A_(2B)R for cancer therapy.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 Fundamental Research Funds for the Central Universities(XK1802-2)the National Key Basic Research Program of China(973 Program,2014CB643604)+2 种基金the National Natural Science Foundation of China(51673017)National Natural Science Foundation of China(21404005)the Natural Science Foundation of Jiangsu Province(BK20150273)。
文摘LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)material,as the promising cathode candidate for next-generation highenergy lithium-ion batteries,has gained considerable attention for extremely high theoretical capacity and low cost.Nevertheless,the intrinsic drawbacks of NCM811 such as unstable structure and inevitable interface side reaction result in severe capacity decay and thermal runaway.Herein,a novel polyimide(denoted as PI-Om DT)constructed with the highly polar and micro-branched crosslinking network is reported as a binder material for NCM811 cathode.The micro-branched crosslinking network is achieved by using 1,3,5-Tris(4-aminophenoxy)benzene(TAPOB)as a crosslinker via condensation reaction,which endows excellent mechanical properties and large free volume.Meanwhile,the massive polar carboxyl(-COOH)groups provide strong adhesion sites to active NCM811 particles.These functions of PIOm DT binder collaboratively benefit to forming the mechanically robust and homogeneous coating layer with rapid Li+diffusion on the surface of NCM811,significantly stabilizing the cathode structure,suppressing the detrimental interface side reaction and guaranteeing the shorter ion-diffusion and electron-transfer paths,consequently enhancing electrochemical performance.As compared to the NCM811 with PVDF binder,the NCM811 using PI-Om DT binder delivers a superior high-rate capacity(121.07 vs.145.38 m Ah g^(-1))at 5 C rate and maintains a higher capacity retention(80.38%vs.91.6%)after100 cycles at 2.5–4.3 V.Particularly,at the high-voltage conditions up to 4.5 and 4.7 V,the NCM811 with PI-Om DT binder still maintains the remarkable capacity retention of 88.86%and 72.5%after 100 cycles,respectively,paving the way for addressing the high-voltage operating stability of the NCM811 cathode.Moreover,the full-charged NCM811 cathode with PI-Om DT binder exhibits a significantly enhanced thermal stability,improving the safety performance of batteries.This work opens a new avenue for developing high-energy NCM811 based lithium-ion batteries with long cycle-life and superior safety performance using a novel and effective binder.
文摘Along with our country urbanization advancement quickening, the scale of construction land expands, but there are many problems in collecting land. These questions have directly restricted the land collection work to develop smoothly. This paper analyzes the main questions which collection work is up against and puts forward the improved proposal aiming at the peasant losing territory being short of participating in the process of pricing compensation, social security vacancy and so on.
基金supported by the National Natural Science Foundation of China(32171215)Basic Research Program of the Science and Technology Commission of Shanghai Municipality(21JC1402400).
文摘Among the various families of G protein-couple receptors(GPCR),the adhesion family of GPCRs is specialized by its expansive extracellular region,which facilitates the recruitment of various ligands.Previous hypothesis proposed that aGPCRs are activated by mechanical force,wherein a Stachel peptide is liberated from the GPCR autoproteolysis-inducing(GAIN)domain and subsequently binds to the transmembrane domain(7TM)upon activation.In this review,we summarize recent advancements in structural studies of aGPCRs,unveiling a conserved structural change of the Stachel peptide from the GAIN domain-embeddedβ-strand conformation to the 7TM-loadedα-helical conformation.Notably,using single-molecule studies,we directly observed the unfolding of GAIN domain and the release of Stachel peptide under physiological level of force,precisely supporting the mechanosensing mechanism for aGPCRs.We observed that the current complex structures of aGPCR adhesion domains with their respective ligands share a common pattern with the C-termini of each binding partner extending in opposite directions,suggesting a similar shearing stretch geometry for these aGPCRs to transmit the mechanical force generated in the circulating environment to the GAIN domain for its unfolding.Outstanding questions,including the relative orientations and interactions between 7TM and its preceding GAIN and adhesion domains of different aGPCRs,may require further structural and mechanical studies at the full-length receptor scale or cell-based level.Our analysis extends the current view of aGPCR structural organization and activation and offers valuable insights for the development of mechanosensor based on aGPCRs or discovery of mechanotherapy against aGPCRs.
基金supported by the National Key Research and Development Program of China(2018YFA0507001)the Basic Research Program of Science and Technology Commission of Shanghai Municipality(21JC1402400)+1 种基金the National Natural Science Foundation of China(32171215,81972828,82172644,82273857 and 81830083)the National Key Scientific Infrastructure for Translational Medicine(Shanghai)(TMSK-2021-120)。
文摘The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy candidates.One of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡclinical trial to treat rectal cancer.However,the precise mechanism underlying its dual-antagonistic properties remains elusive.Herein,we report crystal structures of the A_(2A)R complexed with AB928 and a selective A_(2A)R antagonist 2-118.The structures revealed a common binding mode on A_(2A)R,wherein the ligands established extensive interactions with residues from the orthosteric and secondary pockets.In contrast,the cAMP assay and A_(2A)R and A_(2B)R molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A_(2B)R.Detailed analysis of their chemical structures suggested that AB928 readily adapted to the A_(2B)R pocket,while 2-118 did not due to intrinsic differences.This disparity potentially accounted for the difference in inhibitory efficacy between A_(2B)R and A_(2A)R.This study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A_(2A)R/A_(2B)R for cancer therapy.
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.
