Climate change and air pollution are primarily caused by the combustion and utilization of fossil fuels.Both climate change and air pollution cause health problems.Based on the development of China,it is extremely imp...Climate change and air pollution are primarily caused by the combustion and utilization of fossil fuels.Both climate change and air pollution cause health problems.Based on the development of China,it is extremely important to explore the synergies of the energy transition,CO_(2) reduction,air pollution control,and health improvement under the target of carbon peaking before 2030 and carbon neutrality before 2060.This study introduces the policy evolution and research progress related to energy,climate change,and the environment in China and proposes a complete energy-climate-air-health mechanism framework.Based on the MESSAGE-GLOBIOM integrated assessment model,emission inventory and chemical transport model,and exposure-response function,a comprehensive assessment method of energy-climate-air-health synergies was established and applied to quantify the impacts of Chinese Energy Interconnection Carbon Neutrality(CEICN)scenario.The results demonstrate that,by 2060,the SO_(2),NO_(x) and PM_(2.5) emissions are estimated to be reduced by 91%,85%,and 90%respectively compared to the business-as-usual(BAU)scenario.The direct health impacts brought by achieving the goal of carbon neutrality will drive the proactive implementation of more emission reduction measures and bring greater benefits to human health.展开更多
We demonstrate two ultra-stable laser systems at 1064 nm by independently stabilizing two 10-cm-long Fabry–Pérot cavities.The reference cavities are on a cubic spacer,which is rigidly mounted for both low sensit...We demonstrate two ultra-stable laser systems at 1064 nm by independently stabilizing two 10-cm-long Fabry–Pérot cavities.The reference cavities are on a cubic spacer,which is rigidly mounted for both low sensitivity to environmental vibration and ability for transportation.By comparing against an independent ultra-stable laser at 578 nm via an optical frequency comb,the 1064 nm lasers are measured to have frequency instabilities of 6×10^-16 at 1 s averaging time.展开更多
Optical clocks with an unprecedented accuracy of 10-18 promise innovations in precision spectroscopy and measurement. To harness the full power of optical clocks, we need optical frequency synthesizers(OFSs) to accura...Optical clocks with an unprecedented accuracy of 10-18 promise innovations in precision spectroscopy and measurement. To harness the full power of optical clocks, we need optical frequency synthesizers(OFSs) to accurately convert the stabilities and accuracies of optical clocks to other desired frequencies. This work demonstrates such an OFS referenced to an ytterbium optical clock. The OFS is based on an optical frequency comb phase-locked to a commercial rubidium microwave clock;in this way most combs can operate robustly. Despite comb frequency instability at 10^(-11), the synthesis noise and uncertainty reach 6 × 10^(-18)(1 s) and 5 × 10^(-21), respectively, facilitating frequency synthesis of the best optical clocks. In the OFS, the coherence of the OFS internal oscillator at 1064 nm is accurately transferred to a 578 nm laser for resolving the hertz-level-linewidth ytterbium clock transition(unaffected by megahertz-linewidth comb lines) and faithfully referencing the OFS to an ytterbium optical clock.展开更多
Nanocarriers have emerged as a promising cancer drug delivery strategy.Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemothe...Nanocarriers have emerged as a promising cancer drug delivery strategy.Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemotherapy.Vitamin E derivatives have many essential functions for drug delivery applications,such as biological components that are hydrophobic,stable,water-soluble enhancing compounds,and anticancer activity.In addition,vitamin E derivatives are also effective mitocan which can overcome multi-drug resistance by binding to P glycoproteins.Here,we developed a carboxymethyl chitosan/vitamin E succinate nano-micellar system(O-CMCTS-VES).The synthesized polymers were characterized by Fourier Transform IR,and 1H NMR spectra.The mean sizes of O-CMCTS-VES and DOX-loaded nanoparticles were around 177 nm and 208 nm.The drug loading contents were 6.1%,13.0%and 10.6%with the weight ratio of DOX to O-CMCTS-VES corresponding 1:10,2:10 and 3:10,and the corresponding EEs were 64.3%,74.5%and 39.7%.Cytotoxicity test,hemolysis test and histocompatibility test showed that it had good biocompatibility in vitro and in vivo.Drug release experiments implied good pH sensitivity and sustained-release effect.The DOX/O-CMCTS-VES nanoparticles can be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate is up to 62.57%.In the in vivo study by using H22 cells implanted Balb/C mice,DOX/O-CMCTS-VES reduced the tumor volume and weight efficiently with a TIR of 35.58%.The newly developed polymeric micelles could successfully be utilized as a nanocarrier system for hydrophobic chemotherapeutic agents for the treatment of solid tumors.展开更多
Particle coating is an important method that can be used to expand particle-technology applications. Coated-particle design and preparation for nuclear fuel-element trajectory tracing were focused on in this paper. Pa...Particle coating is an important method that can be used to expand particle-technology applications. Coated-particle design and preparation for nuclear fuel-element trajectory tracing were focused on in this paper. Particles that contain elemental cobalt were selected because of the characteristic gamma ray spectra of 60Co. A novel particle-structure design was proposed by coating particles that contain elemental cobalt with a high-density silicon-carbide (SiC) layer. During the coating process with the high-density SiC layer, cobalt metal was formed and diffused towards the coating, so an inner SiC–CoxSi layer was designed and obtained by fluidized-bed chemical vapor deposition coupled with in-situ chemical reaction. The coating layers were studied by X-ray diffractometry, scanning electron microscopy, and energy dispersive X-ray spectroscopy techniques. The chemical composition was also determined by inductively coupled plasma optical emission spectrometry. The novel particle design can reduce the formation of metallic cobalt and prevent cobalt diffusion in the coating process, which can maintain safety in a nuclear reactor for an extended period. The experimental results also validated that coated particles maintain their structural integrity at extremely high temperatures (~1950 °C), which meets the requirements of next-generation nuclear reactors.展开更多
t OX40 is a costimulatory receptor that is expressed primarily on activated CD4+,CD8+,and regulatory T cells.The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion,differentiation,and activation an...t OX40 is a costimulatory receptor that is expressed primarily on activated CD4+,CD8+,and regulatory T cells.The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion,differentiation,and activation and also promotes dendritic cells to mature to enhance their cytokine production.Therefore,the use of agonistic anti-Ox40 antibodies for cancer immunotherapy has gained great interest.However,most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy.Here,we discovered that BGB-A445,a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation,induced optimal T cell activation without impairing dendritic cell function.In addition,BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity.In the MC38 syngeneic model established in humanized OX40 knock-in mice,BGB-A445 demonstrated robust and dose-dependent antitumor efficacy,whereas the ligand-competitive anti-Ox40 antibody showed antitumor efficacy characterized by a hook effect.Furthermore,BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody.Taken together,our findings show that BGB-A445,which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies,shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.展开更多
In the last decade,the number of transcatheter heart valve replacement for severe heart valve disease has increased exponentially.Although the bioprosthetic artificial heart valve(BHV)has similar fluid dynamics perfor...In the last decade,the number of transcatheter heart valve replacement for severe heart valve disease has increased exponentially.Although the bioprosthetic artificial heart valve(BHV)has similar fluid dynamics performance to the original heart valve compared with mechanical heart valve so that there is no need to take long-term anticoagulant drugs to prevent thromboembolism,transcatheter BHV replacement are still at risk for thrombosis during the first few months according to the clinical data.However,the use of antithrombotic drugs can also increase the risk of bleeding.Therefore,it is particularly important to improve the anticoagulant properties for the BHV itself.In this work,a kind of non-glutaraldehyde cross-linked BHV material with excellent antithrombotic ability has been prepared from carboxylated oxazolidine treated porcine pericardium(consisting of collagen,elastin and glycoprotein)with the further graft of the anticoagulant heparin sodium via hydrophilic modified chitosan.Along with the similar mechanical properties and collagen stability comparable to the glutaraldehyde cross-linked porcine pericardium(PP),these functional non-glutaraldehyde cross-linked PPs exhibit better biocompatibility,promoted endothelial proliferation and superior anti-calcification ability.More importantly,excellent anticoagulant activity can be observed in the hematological experiments in vivo and in vitro.In summary,these excellent performances make these functional non-glutaraldehyde cross-linked PPs great potentialities in the BHV applications.展开更多
基金supported by the GEIGC Science and Technology Project in the framework of“Research on Comprehensive Path Evaluation Methods and Practical Models for the Synergetic Development of Global Energy,Atmospheric Environment and Human Health”(grant No.20210302007).
文摘Climate change and air pollution are primarily caused by the combustion and utilization of fossil fuels.Both climate change and air pollution cause health problems.Based on the development of China,it is extremely important to explore the synergies of the energy transition,CO_(2) reduction,air pollution control,and health improvement under the target of carbon peaking before 2030 and carbon neutrality before 2060.This study introduces the policy evolution and research progress related to energy,climate change,and the environment in China and proposes a complete energy-climate-air-health mechanism framework.Based on the MESSAGE-GLOBIOM integrated assessment model,emission inventory and chemical transport model,and exposure-response function,a comprehensive assessment method of energy-climate-air-health synergies was established and applied to quantify the impacts of Chinese Energy Interconnection Carbon Neutrality(CEICN)scenario.The results demonstrate that,by 2060,the SO_(2),NO_(x) and PM_(2.5) emissions are estimated to be reduced by 91%,85%,and 90%respectively compared to the business-as-usual(BAU)scenario.The direct health impacts brought by achieving the goal of carbon neutrality will drive the proactive implementation of more emission reduction measures and bring greater benefits to human health.
基金supported by the National Natural Science Foundation of China(Nos.11654004,11822402,91636214,and 11804094)the National Key R&D Program of China(No.2017YFA0304403)。
文摘We demonstrate two ultra-stable laser systems at 1064 nm by independently stabilizing two 10-cm-long Fabry–Pérot cavities.The reference cavities are on a cubic spacer,which is rigidly mounted for both low sensitivity to environmental vibration and ability for transportation.By comparing against an independent ultra-stable laser at 578 nm via an optical frequency comb,the 1064 nm lasers are measured to have frequency instabilities of 6×10^-16 at 1 s averaging time.
基金National Natural Science Foundation of China(11927810,11822402,91636214,11654004,11804094)National Key Research and Development Program of China(2017YFA0304403)。
文摘Optical clocks with an unprecedented accuracy of 10-18 promise innovations in precision spectroscopy and measurement. To harness the full power of optical clocks, we need optical frequency synthesizers(OFSs) to accurately convert the stabilities and accuracies of optical clocks to other desired frequencies. This work demonstrates such an OFS referenced to an ytterbium optical clock. The OFS is based on an optical frequency comb phase-locked to a commercial rubidium microwave clock;in this way most combs can operate robustly. Despite comb frequency instability at 10^(-11), the synthesis noise and uncertainty reach 6 × 10^(-18)(1 s) and 5 × 10^(-21), respectively, facilitating frequency synthesis of the best optical clocks. In the OFS, the coherence of the OFS internal oscillator at 1064 nm is accurately transferred to a 578 nm laser for resolving the hertz-level-linewidth ytterbium clock transition(unaffected by megahertz-linewidth comb lines) and faithfully referencing the OFS to an ytterbium optical clock.
基金The authors wish to thank National Natural Science Foundation of China(No.51773188)Key Project of Natural Science Foundation of Shandong Province(No.ZR2020KE016)The National Key Research and Development Program of China(No.2018YFC1105602,2018YFD0900601).
文摘Nanocarriers have emerged as a promising cancer drug delivery strategy.Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemotherapy.Vitamin E derivatives have many essential functions for drug delivery applications,such as biological components that are hydrophobic,stable,water-soluble enhancing compounds,and anticancer activity.In addition,vitamin E derivatives are also effective mitocan which can overcome multi-drug resistance by binding to P glycoproteins.Here,we developed a carboxymethyl chitosan/vitamin E succinate nano-micellar system(O-CMCTS-VES).The synthesized polymers were characterized by Fourier Transform IR,and 1H NMR spectra.The mean sizes of O-CMCTS-VES and DOX-loaded nanoparticles were around 177 nm and 208 nm.The drug loading contents were 6.1%,13.0%and 10.6%with the weight ratio of DOX to O-CMCTS-VES corresponding 1:10,2:10 and 3:10,and the corresponding EEs were 64.3%,74.5%and 39.7%.Cytotoxicity test,hemolysis test and histocompatibility test showed that it had good biocompatibility in vitro and in vivo.Drug release experiments implied good pH sensitivity and sustained-release effect.The DOX/O-CMCTS-VES nanoparticles can be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate is up to 62.57%.In the in vivo study by using H22 cells implanted Balb/C mice,DOX/O-CMCTS-VES reduced the tumor volume and weight efficiently with a TIR of 35.58%.The newly developed polymeric micelles could successfully be utilized as a nanocarrier system for hydrophobic chemotherapeutic agents for the treatment of solid tumors.
基金This work was supported by the Natural Science Foundation of China (Grant Nos. S1302148, 21306097), the Research Fund for Independent Research Projects of Tsinghua University (Grant Nos. 20131089217, 20121088038), the Specialized Research Fund for the Doctoral Program of Higher Education (Grant No. 20110002120023), and the Higher Education Young Elite Teacher Project of Beijing (Grant No. YETP0155).
文摘Particle coating is an important method that can be used to expand particle-technology applications. Coated-particle design and preparation for nuclear fuel-element trajectory tracing were focused on in this paper. Particles that contain elemental cobalt were selected because of the characteristic gamma ray spectra of 60Co. A novel particle-structure design was proposed by coating particles that contain elemental cobalt with a high-density silicon-carbide (SiC) layer. During the coating process with the high-density SiC layer, cobalt metal was formed and diffused towards the coating, so an inner SiC–CoxSi layer was designed and obtained by fluidized-bed chemical vapor deposition coupled with in-situ chemical reaction. The coating layers were studied by X-ray diffractometry, scanning electron microscopy, and energy dispersive X-ray spectroscopy techniques. The chemical composition was also determined by inductively coupled plasma optical emission spectrometry. The novel particle design can reduce the formation of metallic cobalt and prevent cobalt diffusion in the coating process, which can maintain safety in a nuclear reactor for an extended period. The experimental results also validated that coated particles maintain their structural integrity at extremely high temperatures (~1950 °C), which meets the requirements of next-generation nuclear reactors.
文摘t OX40 is a costimulatory receptor that is expressed primarily on activated CD4+,CD8+,and regulatory T cells.The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion,differentiation,and activation and also promotes dendritic cells to mature to enhance their cytokine production.Therefore,the use of agonistic anti-Ox40 antibodies for cancer immunotherapy has gained great interest.However,most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy.Here,we discovered that BGB-A445,a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation,induced optimal T cell activation without impairing dendritic cell function.In addition,BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity.In the MC38 syngeneic model established in humanized OX40 knock-in mice,BGB-A445 demonstrated robust and dose-dependent antitumor efficacy,whereas the ligand-competitive anti-Ox40 antibody showed antitumor efficacy characterized by a hook effect.Furthermore,BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody.Taken together,our findings show that BGB-A445,which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies,shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
基金National Key Research and Development Programs(2020YFC1107802)the National Natural Science Foundation of China(32071357)the Sichuan Science and Technology Program(2021YFH0011),Sichuan Province Major Science and Technology Special Projects(2018SZDZX0011),the National 111 project of Introducing Talents of Discipline to Universities(No.B16033).We would be grateful to the help of VENUS Medtech Inc.(Hangzhou,China)for providing the fresh porcine pericardium.
文摘In the last decade,the number of transcatheter heart valve replacement for severe heart valve disease has increased exponentially.Although the bioprosthetic artificial heart valve(BHV)has similar fluid dynamics performance to the original heart valve compared with mechanical heart valve so that there is no need to take long-term anticoagulant drugs to prevent thromboembolism,transcatheter BHV replacement are still at risk for thrombosis during the first few months according to the clinical data.However,the use of antithrombotic drugs can also increase the risk of bleeding.Therefore,it is particularly important to improve the anticoagulant properties for the BHV itself.In this work,a kind of non-glutaraldehyde cross-linked BHV material with excellent antithrombotic ability has been prepared from carboxylated oxazolidine treated porcine pericardium(consisting of collagen,elastin and glycoprotein)with the further graft of the anticoagulant heparin sodium via hydrophilic modified chitosan.Along with the similar mechanical properties and collagen stability comparable to the glutaraldehyde cross-linked porcine pericardium(PP),these functional non-glutaraldehyde cross-linked PPs exhibit better biocompatibility,promoted endothelial proliferation and superior anti-calcification ability.More importantly,excellent anticoagulant activity can be observed in the hematological experiments in vivo and in vitro.In summary,these excellent performances make these functional non-glutaraldehyde cross-linked PPs great potentialities in the BHV applications.