BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture...BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture or detailed guidance for clinical practice.This study is to investigate the optimal application of SDM to guide life-sustaining treatment(LST)in emergencies.METHODS:This study was a prospective two-round Delphi consensus-seeking survey among multiple stakeholders at the China Consortium of Elite Teaching Hospitals for Residency Education.Participants were identified based on their expertise in medicine,law,administration,medical education,or patient advocacy.All individual items and questions in the questionnaire were scored using a 5-point Likert scale,with responses ranging from"very unimportant"(a score of 1)to"extremely important"(a score of 5).The percentages of the responses that had scores of 4-5on the 5-point Likert scale were calculated.A Kendall’s W coefficient was calculated to evaluate the consensus of experts.RESULTS:A two-level framework consisting of 4 domains and 22 items as well as a ready-touse checklist for the informed consent process for LST was established.An acceptable Kendall’s W coefficient was achieved.CONCLUSION:A consensus-based framework supporting SDM during LST in an emergency department can inform the implementation of guidelines for clinical interventions,research studies,medical education,and policy initiatives.展开更多
Background:Efficient and selective utilization of metabolic substrates is one of the key strategies in high-altitude animals to cope with hypoxia and hypothermia.Previous findings have shown that the energy substrate ...Background:Efficient and selective utilization of metabolic substrates is one of the key strategies in high-altitude animals to cope with hypoxia and hypothermia.Previous findings have shown that the energy substrate utilization of highland animals varies with evolutionary history and phylogeny.The heart is a proxy for the cardiopulmonary system,and the metabolic substrate utilization in the myocardium is also under the strong selective pressure of chronically hypoxic and hypothermic environments.However,little information is available on the physiological adjustments in relation to metabolic substrate utilization in the myocardium for coping with high-altitude environments.Methods:We compared the metabolic enzyme activities,including hexokinase(HK),phosphofructokinase(PFK),pyruvate kinase(PK),citrate synthase(CS),carnitine palmitoyl transferase 1(CPT-1),lactic dehydrogenase(LDH),and creatine kinase(CK),and metabolic substrate contents including glucose(Glu),triglyceride(TG),and free fatty acid(FFA)in the myocardium of a typical human commensal species,Eurasian Tree Sparrows(Passer montanus)between the Qinghai-Tibet Plateau(the QTP,3230 m)and low altitude population(Shijiazhuang,80 m),and between sexes.Results:Among the seven metabolic enzymes and three substrates investigated,we identified no significant differences in PK,CPT-1,HK,CS,LDH,and CK activities and TG content of the myocardium between high and low altitude populations.However,the QTP sparrows had significantly lower Glu content and PFK activities but higher FFA content relative to their lowland counterparts.In addition,male sparrows had higher myocardial HK and CS activities relative to females,independent of altitude.Conclusions:Our results showed that the QTP sparrows elevated fatty acid utilization rather than glucose preference in the myocardium relative to lowland counterpart,which contributes to uncovering both the physiological adjustments for adapting to the extreme conditions of the QTP,intraspecifically.展开更多
Background: In temperate-breeding birds, individuals must adjust their physiological states from one life-history stage to another in response to changing conditions to maximize ecological fitness. Previous evidences ...Background: In temperate-breeding birds, individuals must adjust their physiological states from one life-history stage to another in response to changing conditions to maximize ecological fitness. Previous evidences have shown that body mass, size-corrected mass(SCM), and hematocrit(Hct) could be used as estimates of the energetic state of individuals to illustrate life-history trade-offs and individual quality in field physiology. Plasma alkaline phosphatase(ALP) plays critical roles in regulating the metabolism of energy but very limited information is known on its link with body mass or Hct.Methods: We determined the changes of plasma ALP levels in both early breeding and wintering stages of male Eurasian Tree Sparrows(Passer montanus), and examined the relationships between ALP and body mass, SCM, and Hct of the birds.Results: Our study showed that(1) in male Eurasian Tree Sparrows, body mass did not vary with life-history stage but plasma ALP activity significantly increased in the wintering stage compared to the breeding stage;(2) ALP activity was not correlated with individual body mass but was positively correlated with individual SCM and Hct. Such positive correlations, however, only occurred in the wintering but not in the breeding stages.Conclusions: Our results suggest that plasma ALP activities in free-living birds can be used as one of the indicators o body condition or nutritional status for analyzing individual variation in the wintering but not in the breeding stages. The life-history dependent relationships between plasma ALP activity and body condition may contribute to our better understanding of the trade-off between individual survival and reproduction in free-living animals.展开更多
Nonlinear time-domain simulations are often used to predict the structural response at the design stage to ensure the acceptable operation and/or survival of floating structures under extreme conditions.An environment...Nonlinear time-domain simulations are often used to predict the structural response at the design stage to ensure the acceptable operation and/or survival of floating structures under extreme conditions.An environmental contour(EC)is commonly employed to identify critical sea states that serve as the input for numerical simulations to assess the safety and performance of marine structures.In many studies,marginal and conditional distributions are defined to construct bivariate joint probability distributions for variables,such as significant wave height and zero-crossing period.Then,ECs can be constructed using the inverse first-order reliability method(IFORM).This study adopts alternative models to describe the generalized dependence structure between environmental variables using copulas and discusses the Nataf transformation as a special case.ECs are constructed using measured wave data from moored buoys.Derived design loads are applied on a semisubmersible platform to assess possible differences.In addition,a linear interpolation scheme is utilized to establish a parametric model using short-term extreme tension distribution parameters and wave data,and the long-term tension response is estimated using Monte Carlo simulation.A 3D IFORM-based approach,in which the short-term extreme response that is ignored in the EC approach is used as the third variable,is proposed to help establish accurate design loads with increased accuracy.Results offer a clear illustration of the extreme responses of floating structures based on different models.展开更多
Epidemiological studies have demonstrated that chronic exposure to polluted concentration of fine ambient particulate matter(PM2.5)can induce markedly harmful effects on human health,however,an enormous research effor...Epidemiological studies have demonstrated that chronic exposure to polluted concentration of fine ambient particulate matter(PM2.5)can induce markedly harmful effects on human health,however,an enormous research effort is still need to the comprehensive understanding of PM2.5 induction of new negative health outcomes.Recently,Maher and colleges[1]from Environmental Magnetism and Paleomagnetism at Lancaster University展开更多
SiC_(f)/SiBCZr composites were prepared by polymer precursor impregnation and pyrolysis process with near stoichiometric ratio SiC fiber preform as reinforcement phase and SiBCZr multiphase ceramic precursor as impreg...SiC_(f)/SiBCZr composites were prepared by polymer precursor impregnation and pyrolysis process with near stoichiometric ratio SiC fiber preform as reinforcement phase and SiBCZr multiphase ceramic precursor as impregnating reagent.The results highlighted that the SiC_(f)/SiBCZr composites exhibited excellent ablative properties after ablative tests at 1200℃/3600 s and 1400℃/3600 s,and the strength retention rates of the composites reached 90%and 85%,respectively.This was mainly due to the liquid sealing effect of the ablative products represented by B2O_(3) and SiO_(2)∙B_(2)O_(3),which inhibited the ablative reaction by reducing the diffusion rate of the oxidation medium,and the solid pinning effect of the substances represented by SiO_(2),ZrO_(2),and ZrSiO_(4),which could play high viscosity and high strength characteristics to improve anti-erosion ability.The above-mentioned SiC_(f)/SiBCZr composites with corrosion resistance,oxidation resistance,and ablative resistance provided a solid material foundation and technical support for the development of reusable spacecraft hot-end components.展开更多
Dear editor,Vaccines are the most efficient and effective means to prevent infectious diseases,but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development.1 The wanin...Dear editor,Vaccines are the most efficient and effective means to prevent infectious diseases,but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development.1 The waning immunity varies depending on the diversification of the pathogen and the number of booster doses.1 Strategies to overcome this warrant is using adjuvants that amplify the immune response,and drive the production of memory B and T cells or long-lived plasma cells that recognize the pathogen for durable protection.2–4 Although existing adjuvants have achieved promising results,research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of global pandemics such as coronavirus disease 2019(COVID-19).The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigenpresenting cell(APCs)uptake,achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses.5 Previously,we reported a manganese nanoadjuvant(MnARK)and receptor-binding domain(RBD)monomer antigen formulated nanovaccine.6 MnARK transported antigens to lymph nodes,activated the STING pathway,elicited strong neutralizing abilities and increased immune memory T cell percentage against the infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).6 Regarding the long-term protection potential of MnARK for subunit vaccine development,we further explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 RBD dimer antigen,which has been used in an approved COVID-19 subunit vaccine ZF2001 with aluminum adjuvant(alum).7,8 TEM result revealed that RBD dimer could interact with BSA on MnARK surface and epitope can be well preserved(Supplementary Fig.1a).The size and zeta potential of MnARK-RBD dimer nanovaccine was~58 nm and-14 mV,respectively(Supplementary Fig.1b,c).展开更多
A multiscale methodology using scanning and transmission electron microscope,synchrotron X-ray nano-tomography and micro-tomography,small angle neutron scattering,and in situ synchrotron X-ray diffrac-tion has been us...A multiscale methodology using scanning and transmission electron microscope,synchrotron X-ray nano-tomography and micro-tomography,small angle neutron scattering,and in situ synchrotron X-ray diffrac-tion has been used,to reveal the effect of Fe-rich phases and precipitates on the mechanical behaviour of an Al-Cu-Mn-Fe-Sc-Zr alloy.Theα-Al grains size is reduced from 185.1μm(0 MPa)and 114.3μm(75 MPa)by applied pressure.Moreover,it has been demonstrated that suitable heat treatments modify the 3D morphology of Fe-rich phases from interconnected to a disaggregated structure that improves the mechanical properties of the alloy.The size and morphology evolution of fine precipitates under differ-ent ageing temperature and time are revealed.At ageing temperature of 160℃,the precipitates change from GP zones toθ’(around 75 nm in length)with ageing time increasing from 1 h to 24 h;the Vick-ers hardness increases from 72.0 HV to 110.7HV.The high ductility of the Sc,Zr modified Al-Cu alloy is related to the complex shape and the loss of interconnectivity of the Fe-rich particles due to the heat treatment.The evolution of the crystal lattice strains inα-Al,andβ-Fe calculated during tensile test us-ing in-situ synchrotron X-ray diffraction corroborates the influence of the microstructure in the ductility of the modified alloy.展开更多
Development of simple methods for controlled integration of DNA molecules with metal-organic frameworks(MOFs)is important for various biomedical applications,yet remains a challenge.Herein,a simple and general approac...Development of simple methods for controlled integration of DNA molecules with metal-organic frameworks(MOFs)is important for various biomedical applications,yet remains a challenge.Herein,a simple and general approach to load DNA on the surface of MOFs is developed via one-pot self-assembly of DNA and FeII ions on nanoscale MOFs,resulting in hierarchical core-shell nanostructures of metal-organic@metal-DNA coordination polymers.The strategy enables assembly of DNA molecules on MOFs with ultra-high contents and precise controllability.By incorporation of a chemotherapeutic drug into the Fe-DNA shell,the systems allow to integrate chemotherapy and gene therapy with photodynamic therapy for combinational tumor treatment.Moreover,the hybrid nanostructures enable light-triggered production of cytotoxic singlet oxygen,which further boosts the endosomal escape of the system for an enhanced gene silencing efficacy and thus improved therapeutic outcome.This work highlights a robust approach for the construction of coordination-based drug delivery systems to combat tumor.展开更多
Vaccines that are reliable and efficacious are essential in the fight against the COVID-19 pandemic.In this study,we designed a dual-adjuvant system with two pathogen-associated molecular patterns(PAMPs),MnOx and CpG....Vaccines that are reliable and efficacious are essential in the fight against the COVID-19 pandemic.In this study,we designed a dual-adjuvant system with two pathogen-associated molecular patterns(PAMPs),MnOx and CpG.This system can improve the retention of antigens at the injection site,facilitate pro-inflammatory cytokines secretion,further recruit and activate dendritic cells(DCs).As a result,antigens can be delivered to lymph nodes specifically,and adaptive immunity was strengthened.The immunized group showed an enhanced and broadened humoral and cellular immune response in systemic immunity and lung protection when combined with a tandem repeat-linked dimeric antigen version of the SARS-CoV-2 receptor binding domain(RBDdimer).Remarkably,even with a significant reduction in antigen dosage(three times lower)and a decrease in injection frequencies,our nanovaccine was able to produce the highest neutralizing antibody titers against various mutants.These titers were four-fold higher for the wild-type strain and two-fold higher for both the Beta and Omicron variants in comparison with those elicited by the Alum adjuvant group.In conclusion,our dual-adjuvant formulation presents a promising protein subunit-based candidate vaccine against SARS-CoV-2.展开更多
Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development.Empowered by the recent progresses of nanobiotechnology,a new generation of multifunctional nanotherapeutics and ima...Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development.Empowered by the recent progresses of nanobiotechnology,a new generation of multifunctional nanotherapeutics and imaging platforms has remarkably improved our capability to cope with the highly heterogeneous and complicated na-ture of cancer.With rationally designed multifunctionality and programmable assembly of functional subunits,the in vivo behaviors of intelligent nanosystems have become increasingly tunable,making them more efficient in performing sophisticated actions in physiological and path-ological microenvironments.In recent years,intelligent nanomaterial-based theranostic platforms have showed great potential in tumor-targeted delivery,biological barrier circumvention,multi-responsive tumor sensing and drug release,as well as convergence with precise medication approaches such as personalized tumor vaccines.On the other hand,the increasing system complexity of anti-cancer nanomedicines also pose significant challenges in charac-terization,monitoring and clinical use,requesting a more comprehensive and dynamic understanding of nano-bio interactions.This review aims to briefly summarize the recent progresses achieved by intelligent nanomaterials in tumor-targeted drug delivery,tumor immunotherapy and temporospatially specific tumor imaging,as well as impor-tant advances of our knowledge on their interaction with biological systems.In the perspective of clinical translation,we have further discussed the major possibilities provided by disease-oriented development of anti-cancer nano-materials,highlighting the critical importance clinically-oriented system design.展开更多
National Center for Nanoscience and Technology(NCNST),China,established in December 2003,is co-founded by the Chinese Academy of Sciences(CAS)and the Ministry of Education as an institution dedicated to fundamental an...National Center for Nanoscience and Technology(NCNST),China,established in December 2003,is co-founded by the Chinese Academy of Sciences(CAS)and the Ministry of Education as an institution dedicated to fundamental and applied researches in the field of nanoscience and technology,especially those with important potential applications.NCNST is operated under the supervision of the Governing Board and aims to become a world-class research center,as well as public technological platform and young talents training center in the field,and to act as an important bridge for international academic exchange and collaboration.The NCNST currently has three CAS Key Laboratories:the CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety,the CAS Key Laboratory for Standardization and Measurement for Nanotechnology and the CAS Key Laboratory for Nanosystem and Hierarchical Fabrication.In 2020,the CAS Key Laboratory of Nanophotonic Materials and Devices started construction.Besides,there are Division of Nanotechnology Development,Nanofabrication Laboratory,Intelligent Nanosensing Laboratory and Theoretical Laboratory.展开更多
Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the...Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.展开更多
Biomarker discovery for early detection and therapy of diseases has been blooming for the past two decades.Following the identification of new biomarkers,research and development of sensing platforms has started to be...Biomarker discovery for early detection and therapy of diseases has been blooming for the past two decades.Following the identification of new biomarkers,research and development of sensing platforms has started to become more urgently needed recently,in both laboratory and clinical settings.展开更多
基金supported by the China Medical BoardOpen Competition Program(20-378)Peking University Third Hospital Fund for Returned Scholars(BYSYLXHG2020004)+1 种基金JX was supported by the Peking Union Medical College Fund for Informatization of Postgraduate Courses(2021YXX001)YLZ was supported by the Sichuan University Graduate Education Reform Project(GSSCU2021046)。
文摘BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture or detailed guidance for clinical practice.This study is to investigate the optimal application of SDM to guide life-sustaining treatment(LST)in emergencies.METHODS:This study was a prospective two-round Delphi consensus-seeking survey among multiple stakeholders at the China Consortium of Elite Teaching Hospitals for Residency Education.Participants were identified based on their expertise in medicine,law,administration,medical education,or patient advocacy.All individual items and questions in the questionnaire were scored using a 5-point Likert scale,with responses ranging from"very unimportant"(a score of 1)to"extremely important"(a score of 5).The percentages of the responses that had scores of 4-5on the 5-point Likert scale were calculated.A Kendall’s W coefficient was calculated to evaluate the consensus of experts.RESULTS:A two-level framework consisting of 4 domains and 22 items as well as a ready-touse checklist for the informed consent process for LST was established.An acceptable Kendall’s W coefficient was achieved.CONCLUSION:A consensus-based framework supporting SDM during LST in an emergency department can inform the implementation of guidelines for clinical interventions,research studies,medical education,and policy initiatives.
基金supported by the National Natural Science Foundation of China(NSFC,No.31971413)to DL and NSFC(No.31770445)to YWthe Second Tibetan Plateau Scientific Expedition and Research Program(STEP,2019QZKK0501)+2 种基金the Natural Science Foundation of Hebei Province(NSFHB,C2020205038)to DLthe Foundation of Hebei Normal University(L2019B26)to CJthe Post-doctoral Research Programm to PD。
文摘Background:Efficient and selective utilization of metabolic substrates is one of the key strategies in high-altitude animals to cope with hypoxia and hypothermia.Previous findings have shown that the energy substrate utilization of highland animals varies with evolutionary history and phylogeny.The heart is a proxy for the cardiopulmonary system,and the metabolic substrate utilization in the myocardium is also under the strong selective pressure of chronically hypoxic and hypothermic environments.However,little information is available on the physiological adjustments in relation to metabolic substrate utilization in the myocardium for coping with high-altitude environments.Methods:We compared the metabolic enzyme activities,including hexokinase(HK),phosphofructokinase(PFK),pyruvate kinase(PK),citrate synthase(CS),carnitine palmitoyl transferase 1(CPT-1),lactic dehydrogenase(LDH),and creatine kinase(CK),and metabolic substrate contents including glucose(Glu),triglyceride(TG),and free fatty acid(FFA)in the myocardium of a typical human commensal species,Eurasian Tree Sparrows(Passer montanus)between the Qinghai-Tibet Plateau(the QTP,3230 m)and low altitude population(Shijiazhuang,80 m),and between sexes.Results:Among the seven metabolic enzymes and three substrates investigated,we identified no significant differences in PK,CPT-1,HK,CS,LDH,and CK activities and TG content of the myocardium between high and low altitude populations.However,the QTP sparrows had significantly lower Glu content and PFK activities but higher FFA content relative to their lowland counterparts.In addition,male sparrows had higher myocardial HK and CS activities relative to females,independent of altitude.Conclusions:Our results showed that the QTP sparrows elevated fatty acid utilization rather than glucose preference in the myocardium relative to lowland counterpart,which contributes to uncovering both the physiological adjustments for adapting to the extreme conditions of the QTP,intraspecifically.
基金supported by the National Natural Science Foundation of China (Grant Nos. 31672292, 31372201)the Natural Science Foundation of Hebei Province (C2017205059)
文摘Background: In temperate-breeding birds, individuals must adjust their physiological states from one life-history stage to another in response to changing conditions to maximize ecological fitness. Previous evidences have shown that body mass, size-corrected mass(SCM), and hematocrit(Hct) could be used as estimates of the energetic state of individuals to illustrate life-history trade-offs and individual quality in field physiology. Plasma alkaline phosphatase(ALP) plays critical roles in regulating the metabolism of energy but very limited information is known on its link with body mass or Hct.Methods: We determined the changes of plasma ALP levels in both early breeding and wintering stages of male Eurasian Tree Sparrows(Passer montanus), and examined the relationships between ALP and body mass, SCM, and Hct of the birds.Results: Our study showed that(1) in male Eurasian Tree Sparrows, body mass did not vary with life-history stage but plasma ALP activity significantly increased in the wintering stage compared to the breeding stage;(2) ALP activity was not correlated with individual body mass but was positively correlated with individual SCM and Hct. Such positive correlations, however, only occurred in the wintering but not in the breeding stages.Conclusions: Our results suggest that plasma ALP activities in free-living birds can be used as one of the indicators o body condition or nutritional status for analyzing individual variation in the wintering but not in the breeding stages. The life-history dependent relationships between plasma ALP activity and body condition may contribute to our better understanding of the trade-off between individual survival and reproduction in free-living animals.
基金Supported by the National Natural Science Foundation of China under Grant No.52171284.
文摘Nonlinear time-domain simulations are often used to predict the structural response at the design stage to ensure the acceptable operation and/or survival of floating structures under extreme conditions.An environmental contour(EC)is commonly employed to identify critical sea states that serve as the input for numerical simulations to assess the safety and performance of marine structures.In many studies,marginal and conditional distributions are defined to construct bivariate joint probability distributions for variables,such as significant wave height and zero-crossing period.Then,ECs can be constructed using the inverse first-order reliability method(IFORM).This study adopts alternative models to describe the generalized dependence structure between environmental variables using copulas and discusses the Nataf transformation as a special case.ECs are constructed using measured wave data from moored buoys.Derived design loads are applied on a semisubmersible platform to assess possible differences.In addition,a linear interpolation scheme is utilized to establish a parametric model using short-term extreme tension distribution parameters and wave data,and the long-term tension response is estimated using Monte Carlo simulation.A 3D IFORM-based approach,in which the short-term extreme response that is ignored in the EC approach is used as the third variable,is proposed to help establish accurate design loads with increased accuracy.Results offer a clear illustration of the extreme responses of floating structures based on different models.
文摘Epidemiological studies have demonstrated that chronic exposure to polluted concentration of fine ambient particulate matter(PM2.5)can induce markedly harmful effects on human health,however,an enormous research effort is still need to the comprehensive understanding of PM2.5 induction of new negative health outcomes.Recently,Maher and colleges[1]from Environmental Magnetism and Paleomagnetism at Lancaster University
文摘SiC_(f)/SiBCZr composites were prepared by polymer precursor impregnation and pyrolysis process with near stoichiometric ratio SiC fiber preform as reinforcement phase and SiBCZr multiphase ceramic precursor as impregnating reagent.The results highlighted that the SiC_(f)/SiBCZr composites exhibited excellent ablative properties after ablative tests at 1200℃/3600 s and 1400℃/3600 s,and the strength retention rates of the composites reached 90%and 85%,respectively.This was mainly due to the liquid sealing effect of the ablative products represented by B2O_(3) and SiO_(2)∙B_(2)O_(3),which inhibited the ablative reaction by reducing the diffusion rate of the oxidation medium,and the solid pinning effect of the substances represented by SiO_(2),ZrO_(2),and ZrSiO_(4),which could play high viscosity and high strength characteristics to improve anti-erosion ability.The above-mentioned SiC_(f)/SiBCZr composites with corrosion resistance,oxidation resistance,and ablative resistance provided a solid material foundation and technical support for the development of reusable spacecraft hot-end components.
基金supported by the National Basic Research Program of China(2022YFA1603701 and 2021YFA1200900)the National Natural Science Foundation of China(82341044,22027810)+2 种基金the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Science(CIFMS 2019-I2M-5-018)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB36000000)the China Postdoctoral Science Foundation(2021TQ0085,2022M720932)。
文摘Dear editor,Vaccines are the most efficient and effective means to prevent infectious diseases,but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development.1 The waning immunity varies depending on the diversification of the pathogen and the number of booster doses.1 Strategies to overcome this warrant is using adjuvants that amplify the immune response,and drive the production of memory B and T cells or long-lived plasma cells that recognize the pathogen for durable protection.2–4 Although existing adjuvants have achieved promising results,research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of global pandemics such as coronavirus disease 2019(COVID-19).The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigenpresenting cell(APCs)uptake,achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses.5 Previously,we reported a manganese nanoadjuvant(MnARK)and receptor-binding domain(RBD)monomer antigen formulated nanovaccine.6 MnARK transported antigens to lymph nodes,activated the STING pathway,elicited strong neutralizing abilities and increased immune memory T cell percentage against the infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).6 Regarding the long-term protection potential of MnARK for subunit vaccine development,we further explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 RBD dimer antigen,which has been used in an approved COVID-19 subunit vaccine ZF2001 with aluminum adjuvant(alum).7,8 TEM result revealed that RBD dimer could interact with BSA on MnARK surface and epitope can be well preserved(Supplementary Fig.1a).The size and zeta potential of MnARK-RBD dimer nanovaccine was~58 nm and-14 mV,respectively(Supplementary Fig.1b,c).
基金financially supported by the Natural Science Foundation of China(Nos.52104373 and 51901042)the Ba-sic and Applied Basic Foundation of Guangdong Province,China(Nos.2020B1515120065 and 2021B1515140028)the Guangdong Province Office of Education,China(No.2018KQNCX256).
文摘A multiscale methodology using scanning and transmission electron microscope,synchrotron X-ray nano-tomography and micro-tomography,small angle neutron scattering,and in situ synchrotron X-ray diffrac-tion has been used,to reveal the effect of Fe-rich phases and precipitates on the mechanical behaviour of an Al-Cu-Mn-Fe-Sc-Zr alloy.Theα-Al grains size is reduced from 185.1μm(0 MPa)and 114.3μm(75 MPa)by applied pressure.Moreover,it has been demonstrated that suitable heat treatments modify the 3D morphology of Fe-rich phases from interconnected to a disaggregated structure that improves the mechanical properties of the alloy.The size and morphology evolution of fine precipitates under differ-ent ageing temperature and time are revealed.At ageing temperature of 160℃,the precipitates change from GP zones toθ’(around 75 nm in length)with ageing time increasing from 1 h to 24 h;the Vick-ers hardness increases from 72.0 HV to 110.7HV.The high ductility of the Sc,Zr modified Al-Cu alloy is related to the complex shape and the loss of interconnectivity of the Fe-rich particles due to the heat treatment.The evolution of the crystal lattice strains inα-Al,andβ-Fe calculated during tensile test us-ing in-situ synchrotron X-ray diffraction corroborates the influence of the microstructure in the ductility of the modified alloy.
基金supported by the National Natural Science Foundation of China(No.32271462)the Young Innovation Promotion Association CAS,National Key R&D Program of China(No.2022YFA1206000)the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB36000000).
文摘Development of simple methods for controlled integration of DNA molecules with metal-organic frameworks(MOFs)is important for various biomedical applications,yet remains a challenge.Herein,a simple and general approach to load DNA on the surface of MOFs is developed via one-pot self-assembly of DNA and FeII ions on nanoscale MOFs,resulting in hierarchical core-shell nanostructures of metal-organic@metal-DNA coordination polymers.The strategy enables assembly of DNA molecules on MOFs with ultra-high contents and precise controllability.By incorporation of a chemotherapeutic drug into the Fe-DNA shell,the systems allow to integrate chemotherapy and gene therapy with photodynamic therapy for combinational tumor treatment.Moreover,the hybrid nanostructures enable light-triggered production of cytotoxic singlet oxygen,which further boosts the endosomal escape of the system for an enhanced gene silencing efficacy and thus improved therapeutic outcome.This work highlights a robust approach for the construction of coordination-based drug delivery systems to combat tumor.
基金supported by the National Basic Research Program of China(Nos.2022YFA1603701 and 2021YFA1200900)Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB36000000)+1 种基金the National Natural Science Foundation of China(Nos.82341044 and 22027810)CAMS Innovation Fund for Medical Sciences(No.CIFMS 2019-I2M-5-018).
文摘Vaccines that are reliable and efficacious are essential in the fight against the COVID-19 pandemic.In this study,we designed a dual-adjuvant system with two pathogen-associated molecular patterns(PAMPs),MnOx and CpG.This system can improve the retention of antigens at the injection site,facilitate pro-inflammatory cytokines secretion,further recruit and activate dendritic cells(DCs).As a result,antigens can be delivered to lymph nodes specifically,and adaptive immunity was strengthened.The immunized group showed an enhanced and broadened humoral and cellular immune response in systemic immunity and lung protection when combined with a tandem repeat-linked dimeric antigen version of the SARS-CoV-2 receptor binding domain(RBDdimer).Remarkably,even with a significant reduction in antigen dosage(three times lower)and a decrease in injection frequencies,our nanovaccine was able to produce the highest neutralizing antibody titers against various mutants.These titers were four-fold higher for the wild-type strain and two-fold higher for both the Beta and Omicron variants in comparison with those elicited by the Alum adjuvant group.In conclusion,our dual-adjuvant formulation presents a promising protein subunit-based candidate vaccine against SARS-CoV-2.
基金supported by the National Basic Research Plan of China(2018YFE0205300)the National Basic Science Center Project(T2288102)the Key Area Research and Development Program of Guangdong Province(2020B0101020004).
文摘Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development.Empowered by the recent progresses of nanobiotechnology,a new generation of multifunctional nanotherapeutics and imaging platforms has remarkably improved our capability to cope with the highly heterogeneous and complicated na-ture of cancer.With rationally designed multifunctionality and programmable assembly of functional subunits,the in vivo behaviors of intelligent nanosystems have become increasingly tunable,making them more efficient in performing sophisticated actions in physiological and path-ological microenvironments.In recent years,intelligent nanomaterial-based theranostic platforms have showed great potential in tumor-targeted delivery,biological barrier circumvention,multi-responsive tumor sensing and drug release,as well as convergence with precise medication approaches such as personalized tumor vaccines.On the other hand,the increasing system complexity of anti-cancer nanomedicines also pose significant challenges in charac-terization,monitoring and clinical use,requesting a more comprehensive and dynamic understanding of nano-bio interactions.This review aims to briefly summarize the recent progresses achieved by intelligent nanomaterials in tumor-targeted drug delivery,tumor immunotherapy and temporospatially specific tumor imaging,as well as impor-tant advances of our knowledge on their interaction with biological systems.In the perspective of clinical translation,we have further discussed the major possibilities provided by disease-oriented development of anti-cancer nano-materials,highlighting the critical importance clinically-oriented system design.
文摘National Center for Nanoscience and Technology(NCNST),China,established in December 2003,is co-founded by the Chinese Academy of Sciences(CAS)and the Ministry of Education as an institution dedicated to fundamental and applied researches in the field of nanoscience and technology,especially those with important potential applications.NCNST is operated under the supervision of the Governing Board and aims to become a world-class research center,as well as public technological platform and young talents training center in the field,and to act as an important bridge for international academic exchange and collaboration.The NCNST currently has three CAS Key Laboratories:the CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety,the CAS Key Laboratory for Standardization and Measurement for Nanotechnology and the CAS Key Laboratory for Nanosystem and Hierarchical Fabrication.In 2020,the CAS Key Laboratory of Nanophotonic Materials and Devices started construction.Besides,there are Division of Nanotechnology Development,Nanofabrication Laboratory,Intelligent Nanosensing Laboratory and Theoretical Laboratory.
基金supported by the National Natural Science Foundation of China (11621505, 11435002, 31671016)
文摘Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.
基金Acknowledgments This work was supported by the National Basic Research Program of China (2012CB934004), the National Funds for Distinguished Young Scientists (31325010), the Key Research Program of the Chinese Academy of Sciences (KGZD-EW-T06) and the National Natural Science Foundation of China (31300822).
文摘Biomarker discovery for early detection and therapy of diseases has been blooming for the past two decades.Following the identification of new biomarkers,research and development of sensing platforms has started to become more urgently needed recently,in both laboratory and clinical settings.