Perovskite oxides are popular as cathode materials of solid oxide electrolysis cells, because of their good redox stability and high resistance to coke formation.Unexpectedly, a negative effect of Ni doping is found o...Perovskite oxides are popular as cathode materials of solid oxide electrolysis cells, because of their good redox stability and high resistance to coke formation.Unexpectedly, a negative effect of Ni doping is found on Sr2Fe(1.5-x)NixMo(0.5)O(x = 0, 0.05, 0.1, 0.2) cathode for pure CO2 electroreduction at 800 ℃, although Ni is highly active for CO2 electroreduction.The CO2 electroreduction performance degrades with the increase of Ni doping amount.Various characterization techniques are used to disclose the negative effect.Ni doping decreases the perovskite stability under electroreduction conditions, Fe and Ni cations in the B-site are reduced to metal nanoparticles and SrCO3 forms on the surface of the perovskite.The phase instability results from the weaker Ni–O bond.Although the Fe-Ni nanoparticles are in favor of the CO2 electroreduction, too much SrCO3 and carbon deposition block the charge transfer and diffusion of oxygenous species on the cathode surface.展开更多
CO_(2)electroreduction reaction(CO_(2)RR),combined with solid oxide electrolysis cells(SOECs),is a feasible technology for the storage of renewable electric energy,while its development is limited by the catalytic act...CO_(2)electroreduction reaction(CO_(2)RR),combined with solid oxide electrolysis cells(SOECs),is a feasible technology for the storage of renewable electric energy,while its development is limited by the catalytic activity and stability on cathodes.Here,a novel garnet oxide(Gd_(3)Fe_(5)O_(12))cathode is designed,where the garnet oxide is converted to perovskite oxide and iron via in situ electrochemical phase transition during CO_(2)electroreduction,resulting in high activity with Faradaic efficiency close to 100%and great stability over 1000 h galvanostatic test.A variety of experimental characterizations and density functional theory calculations indicate that in situ exsolved Fe clusters can effectively enhance the adsorption energies of intermediates and lowering the CO_(2)dissociation barriers.Microkinetic modelling confirms that CO_(2)RR goes through a dissociative adsorption mechanism and the electronic transfer for CO_(2)dissociation is the rate-determining step.展开更多
To the Editor:In the last decade,neoadjuvant chemotherapy(NAC)has become a well-accepted treatment option for breast cancer,although few detailed description of NAC in China has yet been reported.[1]A previous study f...To the Editor:In the last decade,neoadjuvant chemotherapy(NAC)has become a well-accepted treatment option for breast cancer,although few detailed description of NAC in China has yet been reported.[1]A previous study found that among patients with clinically node-negative(cN0)breast cancer,97.7%(432/442)with breast pathologic complete response(bpCR)had ypN0(absence of metastases in the axillary lymph nodes);and 71.6%(882/1232)without bpCR achieved ypN0(P<0.001).As for human epidermal growth factor receptor 2(HER2)positive or triple-negative breast cancer(TNBC)that achieved bpCR.展开更多
Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum...Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.展开更多
In mammals,the livers regenerate after chemical injury or resection of hepatic lobe by hepatectomy.How liver regeneration is initiated after mass loss remains to be defined.Here we report that following liver injury,a...In mammals,the livers regenerate after chemical injury or resection of hepatic lobe by hepatectomy.How liver regeneration is initiated after mass loss remains to be defined.Here we report that following liver injury,activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7+liver sinusoidal endothelial cell(LSEC)and VEGFR1^(+)myeloid cell,orchestrating hepatic regeneration.After carbon tetrachloride injection or hepatectomy,platelets and CD11b+VEGFR1^(+)myeloid cells were recruited to LSECs,and liver regeneration in both models was impaired in thrombopoietin-deficient(Thpo^(−/−))mice repressing production of circulating platelets.This impeded regeneration phenotype was recapitulated in mice with either conditional ablation of Cxcr7 in LSEC(Cxcr7iΔ/iΔ)or Vegfr1 in myeloid cell(Vegfr1^(lysM/lysM)).Both Vegfr1lysM/lysM and Cxcr7i^(Δ/iΔ)mice exhibited suppressed expression of hepatocyte growth factor and Wnt2,two crucial trophogenic angiocrine factors instigating hepatocyte propagation.Of note,administration of recombinant thrombopoietin restored the prohibited liver regeneration in the tested genetic models.As such,our data suggest that platelets and myeloid cells jointly activate the vascular niche to produce pro-regenerative endothelial paracrine/angiocrine factors.Modulating this‘hematopoietic–vascular niche’might help to develop regenerative therapy strategy for hepatic disorders.展开更多
Doublecortin-like kinase 1(DCLK1)is upregulated in many tumors and is a marker for tumor stem cells.Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy.However,the regulation of...Doublecortin-like kinase 1(DCLK1)is upregulated in many tumors and is a marker for tumor stem cells.Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy.However,the regulation of DCLK1 kinase activity is poorly understood,particularly the function of its autoinhibitory domain(AID),and,moreover,no physiological activators of DCLK1 have presently been reported.Here we determined the first DCLK1 kinase structure in the autoinhibited state and identified the neuronal calcium sensor HPCAL1 as an activator of DCLK1.The C-terminal AID functions to block the ATP-binding site and is competitive with ATP.HPCAL1 binds directly to the AID in a Ca^(2+)-dependent manner,which releases the autoinhibition.We also analyzed cancer-associated mutations occurring in the AID and elucidate how these mutations disrupt DCLK1 autoinhibition to elicit kinase activity upregulation.Our results present a molecular mechanism for autoinhibition and activation of DCLK1 kinase activity and provide insights into DCLK1-associated tumorigenesis.展开更多
This study aims to demonstrate that blocking the receptor-interacting protein2(Rip2)expression can decrease inflammatory cytokine production by macrophage and protect mice from endotoxin lethality.Murine Rip2 small in...This study aims to demonstrate that blocking the receptor-interacting protein2(Rip2)expression can decrease inflammatory cytokine production by macrophage and protect mice from endotoxin lethality.Murine Rip2 small interfering RNA(siRNA)plasmids were constructed and transfected into macrophage and Rip2 expression was detected with reverse transcription-polymerase chain reaction(RT-PCR)and western blot.Cell proliferation was assayed withMTT.TNF-a concentration was assayed with ELISA and high-mobility group box 1 protein(HMGB1)level with semi-quantitative western blot after lipopolysaccharide(LPS)stimulation.LPS challenge was given after the plasmids were injected into mice and the survival rate was calculated.Rip2 siRNA plasmid could block the mRNA and protein expression of Rip2 and promote cell proliferation.Blocking Rip2 could attenuate LPS-induced TNF-a and HMGB1 production.The HMGB1 expression in the liver decreased to(40.21±11.03)pg/g,and serum TNF-a level decreased to(300.43±59.26)ng/L(P<0.05).The survival rate of mice from endotoxemia was also improved(P<0.05).The results demonstrate that Rip2 siRNA plasmid can block the expression of Rip2,decrease the production of TNF-a and HMGB1 and protect mice from fatal endotoxemia.展开更多
Hydrogen separation through oxygen transport membranes(OTMs)has attracted much attention.Asymmetric membranes with thin dense layers provide low bulk diffusion resistances and high overall hydrogen separation performa...Hydrogen separation through oxygen transport membranes(OTMs)has attracted much attention.Asymmetric membranes with thin dense layers provide low bulk diffusion resistances and high overall hydrogen separation performances.However,the resistance in the porous support layer(PSL)limits the overall separation performance significantly.Engineering the structure of the PSL is an appropriate way to enable fast gas transport and increase the separation performance.There is no relevant research on studying the influence of the PSL on hydrogen separation performance so far.Herein,we prepared Ce0.85Sm0.15O1.925–Sm0.6Sr0.4Cr0.3Fe0.7O3-δ(SDC-SSCF)asymmetric membranes with straight grooves in PSL by tape-casting and laser grooving.A~30%improvement in the hydrogen separation rate was achieved by grooving in the PSLs.It indicates that the grooves may reduce the concentration polarization resistance in PSL for the hydrogen separation process.This work provides a straight evidence on optimizing the structures of PSL for improving the hydrogen separation performance of the membrane reactors.展开更多
基金the financial support from the National Natural Science Foundation of China (91545202, U1508203)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No.XDB17000000)+2 种基金Dalian National Laboratory for Clean Energy (DNL)CAS (DICP&QIBEBT UN201708)Dalian Youth Science and Technology Fund (2017RQ064)
文摘Perovskite oxides are popular as cathode materials of solid oxide electrolysis cells, because of their good redox stability and high resistance to coke formation.Unexpectedly, a negative effect of Ni doping is found on Sr2Fe(1.5-x)NixMo(0.5)O(x = 0, 0.05, 0.1, 0.2) cathode for pure CO2 electroreduction at 800 ℃, although Ni is highly active for CO2 electroreduction.The CO2 electroreduction performance degrades with the increase of Ni doping amount.Various characterization techniques are used to disclose the negative effect.Ni doping decreases the perovskite stability under electroreduction conditions, Fe and Ni cations in the B-site are reduced to metal nanoparticles and SrCO3 forms on the surface of the perovskite.The phase instability results from the weaker Ni–O bond.Although the Fe-Ni nanoparticles are in favor of the CO2 electroreduction, too much SrCO3 and carbon deposition block the charge transfer and diffusion of oxygenous species on the cathode surface.
基金financially supported by the National Natural Science Foundation of China(91545202,91945302)the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS,XDB17000000,XDB36030200)+4 种基金the Ministry of Science and Technology of China(2018YFA0704503)the Liao Ning Revitalization Talents Program(XLYC1807066,XLYC1907099)the Youth Innovation Promotion Association of CAS(Y201829)the State Key Laboratory of Catalysis in DICP(No.N-19-13)the DNL Cooperation Fund,CAS(DNL202003)。
文摘CO_(2)electroreduction reaction(CO_(2)RR),combined with solid oxide electrolysis cells(SOECs),is a feasible technology for the storage of renewable electric energy,while its development is limited by the catalytic activity and stability on cathodes.Here,a novel garnet oxide(Gd_(3)Fe_(5)O_(12))cathode is designed,where the garnet oxide is converted to perovskite oxide and iron via in situ electrochemical phase transition during CO_(2)electroreduction,resulting in high activity with Faradaic efficiency close to 100%and great stability over 1000 h galvanostatic test.A variety of experimental characterizations and density functional theory calculations indicate that in situ exsolved Fe clusters can effectively enhance the adsorption energies of intermediates and lowering the CO_(2)dissociation barriers.Microkinetic modelling confirms that CO_(2)RR goes through a dissociative adsorption mechanism and the electronic transfer for CO_(2)dissociation is the rate-determining step.
基金Beijing Medical Reward Foundation(No.YXJL-2016-0040-0012)
文摘To the Editor:In the last decade,neoadjuvant chemotherapy(NAC)has become a well-accepted treatment option for breast cancer,although few detailed description of NAC in China has yet been reported.[1]A previous study found that among patients with clinically node-negative(cN0)breast cancer,97.7%(432/442)with breast pathologic complete response(bpCR)had ypN0(absence of metastases in the axillary lymph nodes);and 71.6%(882/1232)without bpCR achieved ypN0(P<0.001).As for human epidermal growth factor receptor 2(HER2)positive or triple-negative breast cancer(TNBC)that achieved bpCR.
基金supported by the National Natural Science Foundation of China(31730036,31871380,31871382,31930055,31930058,32000500,32022034,32030033,32070730,32130046,3217050247,32150005,32200595,32222024,81730019,81730022,81830014,81921006,81925005,81970426,81971301,81971312,82030041,82061160495,82070805,82071595,82090020,82100841,82120108009,82122024,82125002,82125011,82125012,82130045,82171284,82173061,82173398,82225007,82225015,82225017,82225018,82230047,82230088,82271600,91949106,91949201,92049116,92049302,92049304,92149303,92149306,92157202,92168201,92169102,92249301,92268201)the National Key Research and Development Program of China(2018YFA0800700,2018YFC2000100,2018YFC2000102,2018YFC2002003,2019YFA0110900,2019YFA0801703,2019YFA0801903,2019YFA0802202,2019YFA0904800,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002900,2020YFC2008000,2020YFE0202200,2021YFA0804900,2021YFA1100103,2021YFA1100900,2021YFE0114200,2021ZD0202400,2022YFA0806001,2022YFA0806002,2022YFA0806600,2022YFA1103200,2022YFA1103601,2022YFA1103701,2022YFA1103800,2022YFA1103801,2022YFA1104100,2022YFA1104904,2022YFA1303000,2022YFC2009900,2022YFC2502401,2022YFC3602400,2022YFE0118000,2022ZD0213200)+14 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302,XDB39000000,XDB39030600)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2020085,2021080)CAS Project for Young Scientists in Basic Research(YSBR-076)the Program of the Beijing Natural Science Foundation(JQ20031)Clinical Research Operating Fund of Central High level hospitals(2022-PUMCHE-001)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M1-004)Talent Program of the Chinese Academy of Medical Science(2022RC310-10)Research Funds from Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region,Guangdong Basic and Applied Basic Research Foundation(2020B1515020044)Guangzhou Planned Project of Science and Technology(202002020039)the Major Technology Innovation of Hubei Province(2019ACA141)the Science and Technology Major Project of Hunan Provincial Science and Technology Department(2021SK1010)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Natural Science Foundation of Sichuan Province(2023NSFSC0003)Yunnan Fundamental Research Project(202201AS070080)the State Key Laboratory of Membrane Biology。
文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.
基金supported by the Ansary Stem Cell Institute,the starr foundation TRI-Institution stem cell core projecthe Empire State Stem Cell Board and New York State Department of Health grants(C026878,C028117,C029156,C030160)+3 种基金by grants from the National Institute of Health(NIH)R01(HL119872,HL128158)ZC was supported by Druckenmiller Fellowship from the New York Stem Cell Foundation and U54 CA163167 from NIHThis work was also supported by a National Scientist Development Grant from the American Heart Association(12SDG1213004)R01HL130826 from NIH.SR is supported by the Ansary Stem Cell Institute and grant from the NIH R01(DK095039).
文摘In mammals,the livers regenerate after chemical injury or resection of hepatic lobe by hepatectomy.How liver regeneration is initiated after mass loss remains to be defined.Here we report that following liver injury,activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7+liver sinusoidal endothelial cell(LSEC)and VEGFR1^(+)myeloid cell,orchestrating hepatic regeneration.After carbon tetrachloride injection or hepatectomy,platelets and CD11b+VEGFR1^(+)myeloid cells were recruited to LSECs,and liver regeneration in both models was impaired in thrombopoietin-deficient(Thpo^(−/−))mice repressing production of circulating platelets.This impeded regeneration phenotype was recapitulated in mice with either conditional ablation of Cxcr7 in LSEC(Cxcr7iΔ/iΔ)or Vegfr1 in myeloid cell(Vegfr1^(lysM/lysM)).Both Vegfr1lysM/lysM and Cxcr7i^(Δ/iΔ)mice exhibited suppressed expression of hepatocyte growth factor and Wnt2,two crucial trophogenic angiocrine factors instigating hepatocyte propagation.Of note,administration of recombinant thrombopoietin restored the prohibited liver regeneration in the tested genetic models.As such,our data suggest that platelets and myeloid cells jointly activate the vascular niche to produce pro-regenerative endothelial paracrine/angiocrine factors.Modulating this‘hematopoietic–vascular niche’might help to develop regenerative therapy strategy for hepatic disorders.
基金Financial support for this work was provided by the National Natural Science Foundation of China(31741027,82103226,81672722,and 81501368)Natural Science Foundation of Henan Province(212300410243).
文摘Doublecortin-like kinase 1(DCLK1)is upregulated in many tumors and is a marker for tumor stem cells.Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy.However,the regulation of DCLK1 kinase activity is poorly understood,particularly the function of its autoinhibitory domain(AID),and,moreover,no physiological activators of DCLK1 have presently been reported.Here we determined the first DCLK1 kinase structure in the autoinhibited state and identified the neuronal calcium sensor HPCAL1 as an activator of DCLK1.The C-terminal AID functions to block the ATP-binding site and is competitive with ATP.HPCAL1 binds directly to the AID in a Ca^(2+)-dependent manner,which releases the autoinhibition.We also analyzed cancer-associated mutations occurring in the AID and elucidate how these mutations disrupt DCLK1 autoinhibition to elicit kinase activity upregulation.Our results present a molecular mechanism for autoinhibition and activation of DCLK1 kinase activity and provide insights into DCLK1-associated tumorigenesis.
文摘This study aims to demonstrate that blocking the receptor-interacting protein2(Rip2)expression can decrease inflammatory cytokine production by macrophage and protect mice from endotoxin lethality.Murine Rip2 small interfering RNA(siRNA)plasmids were constructed and transfected into macrophage and Rip2 expression was detected with reverse transcription-polymerase chain reaction(RT-PCR)and western blot.Cell proliferation was assayed withMTT.TNF-a concentration was assayed with ELISA and high-mobility group box 1 protein(HMGB1)level with semi-quantitative western blot after lipopolysaccharide(LPS)stimulation.LPS challenge was given after the plasmids were injected into mice and the survival rate was calculated.Rip2 siRNA plasmid could block the mRNA and protein expression of Rip2 and promote cell proliferation.Blocking Rip2 could attenuate LPS-induced TNF-a and HMGB1 production.The HMGB1 expression in the liver decreased to(40.21±11.03)pg/g,and serum TNF-a level decreased to(300.43±59.26)ng/L(P<0.05).The survival rate of mice from endotoxemia was also improved(P<0.05).The results demonstrate that Rip2 siRNA plasmid can block the expression of Rip2,decrease the production of TNF-a and HMGB1 and protect mice from fatal endotoxemia.
基金the National Natural Science Foundation of China(22008231 and 21776267)grants of Dalian National Laboratory for Clean Energy(DNL)(DNL180203)+1 种基金the LiaoNing Revitalization Talents Program(XLYC1801004)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Y201829).
文摘Hydrogen separation through oxygen transport membranes(OTMs)has attracted much attention.Asymmetric membranes with thin dense layers provide low bulk diffusion resistances and high overall hydrogen separation performances.However,the resistance in the porous support layer(PSL)limits the overall separation performance significantly.Engineering the structure of the PSL is an appropriate way to enable fast gas transport and increase the separation performance.There is no relevant research on studying the influence of the PSL on hydrogen separation performance so far.Herein,we prepared Ce0.85Sm0.15O1.925–Sm0.6Sr0.4Cr0.3Fe0.7O3-δ(SDC-SSCF)asymmetric membranes with straight grooves in PSL by tape-casting and laser grooving.A~30%improvement in the hydrogen separation rate was achieved by grooving in the PSLs.It indicates that the grooves may reduce the concentration polarization resistance in PSL for the hydrogen separation process.This work provides a straight evidence on optimizing the structures of PSL for improving the hydrogen separation performance of the membrane reactors.
