Two erbium(Ⅲ)complexes[ErCl(OAr^(Ad))_(3)][Na(THF)_(6)](1)and Er(OAr^(Ad))_(3)(2)are successfully prepared by using one variety of"hard"base ligand with large steric hindrance.The coordination geometry arou...Two erbium(Ⅲ)complexes[ErCl(OAr^(Ad))_(3)][Na(THF)_(6)](1)and Er(OAr^(Ad))_(3)(2)are successfully prepared by using one variety of"hard"base ligand with large steric hindrance.The coordination geometry around the Er(Ⅲ)site changes from distorted tetrahedral to flat trigonal pyramid geometry in different solvent environment due to the removal of the coordinated chloride.Such an alternation significantly enhances the single-molecule magnet(SMM)behavior and makes the field-induced effective energy barrier(Ueff)arrive at 43(1)cm-1for the latter.Together with theoretical calculations,this study shows that strong equatorial ligand field and high local symmetry are critical to suppress the quantum tunneling of the magnetization(QTM)and achieve high-performance erbium(Ⅲ)based SMMs.展开更多
A disintegrin and metalloprotease 17(ADAM17)is a membrane-bound enzyme that cleaves cell-surface proteins.Here,we discovered that neuronal ADAM17-mediated signaling supports the reduction of inhibitory presynaptic inp...A disintegrin and metalloprotease 17(ADAM17)is a membrane-bound enzyme that cleaves cell-surface proteins.Here,we discovered that neuronal ADAM17-mediated signaling supports the reduction of inhibitory presynaptic inputs to the pre-sympathetic glutamatergic neural hub,located in the paraventricular nucleus of the hypothalamus(PVN),upon stimulation by angiotensin II(Ang-II).For Ang-II-induced disinhibition,targeting microglial migration had an effect similar to ADAM17 knockout in glutamatergic neurons.Ang-II promoted neuron-mediated chemotaxis of microglia via neuronal CX3CL1 and ADAM17.Inhibiting microglial chemotaxis by targeting CX3CR1 abolished the Ang-II-induced microglial displacement of GABAergic presynaptic terminals and significantly blunted Ang-II’s pressor response.Using conditional and targeted knockout models of ADAM17,an increase in the contact between pre-sympathetic neurons and reactive microglia in the PVN was demonstrated to be neuronal ADAM17-dependent during the developmental stage of salt-sensitive hypertension.Collectively,this study provides evidence that neuronal ADAM17-mediated microglial chemotaxis facilitates the disinhibition of pre-sympathetic glutamatergic tone upon hormonal stimulation.展开更多
OBJECTIVES:Anti-citrullinated protein antibodies(ACPAs)are a group of autoantibodies targeted against citrullinated proteins/peptides and are informative rheumatoid arthritis(RA)biomarkers.ACPAs also play a crucial ro...OBJECTIVES:Anti-citrullinated protein antibodies(ACPAs)are a group of autoantibodies targeted against citrullinated proteins/peptides and are informative rheumatoid arthritis(RA)biomarkers.ACPAs also play a crucial role in RA pathogenesis,and their underlying mechanism merits investigation.METHODS:Immunohistochemical(IHC)assays were carried out to determine IL-1βlevels in ACPA+and ACPA−RA patients.PBMCderived monocytes were differentiated into macrophages before stimulation with ACPAs purified from RA patients.The localization and interaction of molecules were analyzed by confocal microscopy,co-IP,and surface plasmon resonance.RESULTS:In our study,we found that IL-1βlevels were elevated in ACPA+RA patients and that ACPAs promoted IL-1βproduction by PBMC-derived macrophages.ACPAs interacted with CD147 to enhance the interaction between CD147 and integrinβ1 and,in turn,activate the Akt/NF-κB signaling pathway.The nuclear localization of p65 promoted the expression of NLRP3 and pro-IL-1β,resulting in priming.Moreover,ACPA stimulation activated pannexin channels,leading to ATP release.The accumulated ATP bound to the P2X7 receptor,leading to NLRP3 inflammasome activation.CONCLUSIONS:Our study suggests a new hypothesis regarding IL-1βproduction in RA involving ACPAs,which may be a potential therapeutic target in RA treatment.展开更多
基金supported by National Natural Science Foundation of China(Nos.21971203,82073271 and 81803026)Key Scientific and Technological Innovation Team of Shaanxi Province(No.2020TD-001)the Fundamental Research Funds for Central Universities。
文摘Two erbium(Ⅲ)complexes[ErCl(OAr^(Ad))_(3)][Na(THF)_(6)](1)and Er(OAr^(Ad))_(3)(2)are successfully prepared by using one variety of"hard"base ligand with large steric hindrance.The coordination geometry around the Er(Ⅲ)site changes from distorted tetrahedral to flat trigonal pyramid geometry in different solvent environment due to the removal of the coordinated chloride.Such an alternation significantly enhances the single-molecule magnet(SMM)behavior and makes the field-induced effective energy barrier(Ueff)arrive at 43(1)cm-1for the latter.Together with theoretical calculations,this study shows that strong equatorial ligand field and high local symmetry are critical to suppress the quantum tunneling of the magnetization(QTM)and achieve high-performance erbium(Ⅲ)based SMMs.
基金supported by the National Natural Science Foundation of China(82100454,32271016,82101586,and 81872563)the National Heart,Lung,Blood,and Sleep Institute(HL163588).
文摘A disintegrin and metalloprotease 17(ADAM17)is a membrane-bound enzyme that cleaves cell-surface proteins.Here,we discovered that neuronal ADAM17-mediated signaling supports the reduction of inhibitory presynaptic inputs to the pre-sympathetic glutamatergic neural hub,located in the paraventricular nucleus of the hypothalamus(PVN),upon stimulation by angiotensin II(Ang-II).For Ang-II-induced disinhibition,targeting microglial migration had an effect similar to ADAM17 knockout in glutamatergic neurons.Ang-II promoted neuron-mediated chemotaxis of microglia via neuronal CX3CL1 and ADAM17.Inhibiting microglial chemotaxis by targeting CX3CR1 abolished the Ang-II-induced microglial displacement of GABAergic presynaptic terminals and significantly blunted Ang-II’s pressor response.Using conditional and targeted knockout models of ADAM17,an increase in the contact between pre-sympathetic neurons and reactive microglia in the PVN was demonstrated to be neuronal ADAM17-dependent during the developmental stage of salt-sensitive hypertension.Collectively,this study provides evidence that neuronal ADAM17-mediated microglial chemotaxis facilitates the disinhibition of pre-sympathetic glutamatergic tone upon hormonal stimulation.
基金This work was supported by the National Basic Research Program“973 Grants”(2015CB553704)the National Basic Research Program of China grant(2014ZX09508002-002)+1 种基金the National Key Research and Development Program of China grant(2017YFC0909000)We would also like to express our gratitude to Professor Zhinan Chen,who helped us design the experiments and provided us with essential experimental equipment.
文摘OBJECTIVES:Anti-citrullinated protein antibodies(ACPAs)are a group of autoantibodies targeted against citrullinated proteins/peptides and are informative rheumatoid arthritis(RA)biomarkers.ACPAs also play a crucial role in RA pathogenesis,and their underlying mechanism merits investigation.METHODS:Immunohistochemical(IHC)assays were carried out to determine IL-1βlevels in ACPA+and ACPA−RA patients.PBMCderived monocytes were differentiated into macrophages before stimulation with ACPAs purified from RA patients.The localization and interaction of molecules were analyzed by confocal microscopy,co-IP,and surface plasmon resonance.RESULTS:In our study,we found that IL-1βlevels were elevated in ACPA+RA patients and that ACPAs promoted IL-1βproduction by PBMC-derived macrophages.ACPAs interacted with CD147 to enhance the interaction between CD147 and integrinβ1 and,in turn,activate the Akt/NF-κB signaling pathway.The nuclear localization of p65 promoted the expression of NLRP3 and pro-IL-1β,resulting in priming.Moreover,ACPA stimulation activated pannexin channels,leading to ATP release.The accumulated ATP bound to the P2X7 receptor,leading to NLRP3 inflammasome activation.CONCLUSIONS:Our study suggests a new hypothesis regarding IL-1βproduction in RA involving ACPAs,which may be a potential therapeutic target in RA treatment.
