On July 23,2022,the World Health Organization(WHO)declared the monkeypox(mpox)outbreak a“Public Health Emergency of International Concern.”Since 2022,outbreaks of mpox in many countries around the world have primari...On July 23,2022,the World Health Organization(WHO)declared the monkeypox(mpox)outbreak a“Public Health Emergency of International Concern.”Since 2022,outbreaks of mpox in many countries around the world have primarily resulted in fatalities among immunocompromised individuals,such as untreated HIV/AIDS patients.Since the eradication of smallpox was declared by the WHO in 1980,the global vaccination against smallpox has been gradually discontinued.China also stopped routine smallpox vaccination in 1981.The protective effect of the smallpox vaccine has decreased over time due to aging and declining immunity in those who were vaccinated.For individuals,timely vaccination against smallpox is an effective means of protection against mpox.However,due to safety concerns with the smallpox vaccine and the limitations of current mpox vaccines,there is no vaccine that is safe,effective,and has low side effects applied in clinical settings.This article provides a comprehensive review of the development of mpox virus(MPXV)vaccines,their application in special populations,and the current state of vaccine research,considering the etiology,transmission,and prevention of the MPXV.Vaccination,as an effective method of epidemic prevention,can provide long-term immune protection and effectively reduce the severity of infection.However,as there is no licensed specific MPXV vaccine available globally,the vaccines currently used for mpox prevention are mostly smallpox vaccines.These smallpox vaccines can offer some degree of protection against mpox by activating cross-protection in the body.展开更多
The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic.However,the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity in...The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic.However,the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored.In our research,we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV,identifying cross-reactive CD8^(+)T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays.Then,in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes.Lastly,single-cell T cell receptor reservoir was analyzed based on tetramer staining.Here,we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19,and identified SARS-CoV-2 CD8^(+)T cell epitopes spanning the major structural antigens.T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents.Cross-T cell reactivity was also observed within the identified series of CD8^(+)T cell epitopes.For representative immunodominant peptide pairs,although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar,the TCR repertoires recognizing these peptides were distinct.Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.展开更多
Background:Gelatin methacryloyl(GelMA)hydrogels loaded with stem cells have proved to be an effective clinical treatment for wound healing.Advanced glycation end product(AGE),interacting with its particular receptor(A...Background:Gelatin methacryloyl(GelMA)hydrogels loaded with stem cells have proved to be an effective clinical treatment for wound healing.Advanced glycation end product(AGE),interacting with its particular receptor(AGER),gives rise to reactive oxygen species(ROS)and apoptosis.Curcumin(Cur)has excellent antioxidant activity and regulates intracellular ROS production and apoptosis.In this study,we developed a Cur-incorporated 3D-printed GelMA to insert into adiposederived stem cells(ADSCs)and applied it to diabetic wounds.Methods:GelMA hydrogels with Cur were fabricated and their in vitro effects on ADSCs were investigated.We used structural characterization,western blot,ROS and apoptosis assay to evaluate the antioxidant and anti-apoptotic activity,and assessed the wound healing effects to investigate the mechanism underlying regulation of apoptosis by Cur via the AGE/AGER/nuclear factor-κB(NF-κB)p65 pathway.Results:A 10%GelMA scaffold exhibited appropriate mechanical properties and biocompatibility for ADSCs.The circular mesh structure demonstrated printability of 10%GelMA and Cur-GelMA bioinks.The incorporation of Cur into the 10%GelMA hydrogel showed an inhibitory effect on AGEs/AGER/NF-κB p65-induced ROS generation and ADSC apoptosis.Furthermore,Cur-GelMA scaffold promoted cell survival and expedited in vivo diabetic wound healing.Conclusions:The incorporation of Cur improved the antioxidant activity of 3D-printed GelMA hydrogel and mitigated AGE/AGER/p65 axis-induced ROS and apoptosis in ADSCs.The effects of scaffolds on wound healing suggested that Cur/GelMA-ADSC hydrogel could be an effective biological material for accelerating wound healing.展开更多
Dear Editor,The coronavirus infectious disease 2019(COVID-19)outbreak is seriously endangering human health.Most patients with severe COVID-19 are characterized by sustained cytokine production and hyper-inflammation,...Dear Editor,The coronavirus infectious disease 2019(COVID-19)outbreak is seriously endangering human health.Most patients with severe COVID-19 are characterized by sustained cytokine production and hyper-inflammation,which is known as cytokine storm syndrome.1-3 Elaborating the anti-inflammatory response is crucial to these patients,and interieukin-6(IL6)inhibitors and steroids have been recommended in clinical practice.1 However,after the cytokine storm phase,the host immune response to sepsis may develop into a protracted immunosuppressive phase.展开更多
Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal women.Under chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of pro...Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal women.Under chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of proinflammatory cytokines,impaired osteogenic differentiation capabilities of bone marrow mesenchymal stem cells(BMMSCs),and disturbed regulatory T cell(Treg)/Th17 cell balance.However,therapeutic strategies that re-establish immune homeostasis in this disorder have not been well developed.Here,we produced T cell-depleting nanoparticles(TDNs)that ameliorated the osteopenia phenotype and rescued the osteogenic deficiency of BMMSCs in ovariectomized(OVX)mice.TDNs consist of monocyte chemotactic protein-1(MCP-1)-encapsulated mesoporous silica nanoparticles as the core and Fas-ligand(FasL)as the corona.We showed that the delicate design of the TDNs enables rapid release of MCP-1 to recruit activated T cells and then induces their apoptosis through the conjugated FasL both in vitro and in vivo.Apoptotic signals recognized by macrophages help skew the Treg/Th17 cell balance and create an immune tolerant state,further attenuating the osteogenic deficiency of BMMSCs and the osteopenia phenotype.Mechanistically,we found that the therapeutic effects of TDNs were partially mediated by apoptotic T cell-derived extracellular vesicles(ApoEVs),which promoted macrophage transformation towards the M2 phenotype.These findings demonstrate that TDNs may represent a promising strategy for treating osteoporosis and other immune disorders.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused the global outbreak of coronavirus disease 2019(COVID-19).By far,more than 35 million people had been infected by SARS-CoV-2,resulting ...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused the global outbreak of coronavirus disease 2019(COVID-19).By far,more than 35 million people had been infected by SARS-CoV-2,resulting in more than 1 million deaths globally.It is well recognized that SARSCoV-2 preferentially attacks pulmonary epithelial cells,leading to acute respiratory distress syndrome(ARDS).展开更多
The outbreak of coronavirus disease 2019(COVID-19)caused by the new virus SARS-CoV-2 has been announced as a public health emergency of international concern.1–3 The clinical features of patients with COVID-19 range ...The outbreak of coronavirus disease 2019(COVID-19)caused by the new virus SARS-CoV-2 has been announced as a public health emergency of international concern.1–3 The clinical features of patients with COVID-19 range from common fever and cough to other rare symptoms,such as diarrhea and nausea.This disease can progress quickly,and 2–3%of patients die within a short time,which is generally due to multiple organ failure.4–7 Clinically,COVID-19 patients are classified into mild,moderate,severe,and critical cases.5–7 The immune response against SARS-CoV-2 is probably linked to the severity of disease.Recently,Zheng et al.8 showed that elevated levels of T-cell exhaustion and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients;however,a more comprehensive understanding of the pathology of SARS-CoV-2 infection remains to be delineated.Here,we profiled immune cellular components using mass cytometry(CyTOF)to analyze the peripheral blood mononuclear cells(PBMCs)from patients with differences in disease progression by comparing with the PBMCs from healthy donors(HDs).展开更多
The 200-hPa wind perturbation(WP) in the subtropical westerly over East Asia(SWEA) has seldom been examined in previous studies, especially in connection with forecast of the summer rainfall in China. Based on the dai...The 200-hPa wind perturbation(WP) in the subtropical westerly over East Asia(SWEA) has seldom been examined in previous studies, especially in connection with forecast of the summer rainfall in China. Based on the daily NCEP/NCAR reanalysis data and precipitation observations in China from 1 June to 31 August of 1960-2015, this study first systematically analyzes the spatiotemporal distribution features of the 200-hPa WP in the SWEA on different scales, especially during the Meiyu season in the Yangtze-Huaihe region and during the rainy period in North China, by using spectral decomposition and period analysis. It is found that in the 56-yr mean fields, the 200-hPa WP in the SWEA is collocated with the East Asian subtropical jet(EASJ), with the centers of the two systems coincidentally overlapped. The WP filed in the subtropical westerly mainly comprises planetary-and synoptic-scale waves. The quasi-stationary planetary-scale wave seems to determine the shape and intensity of the WP in the SWEA, while the synoptic-scale wave is closely related to the local central intensity of the WP. The daily evolution of the 56-yr mean fields shows that, following the northward(southward) movement of SWEA from 1 June to 31 August, the planetaryscale WP in the SWEA becomes gradually weakened(intensified) whereas the synoptic-scale WP is slightly intensified(weakened).The results also reveal that during the Meiyu season in the Yangtze-Huaihe region, the WP in the SWEA moves northward slowly around 37°-39°N, demonstrating a quasi-biweekly oscillation in its geographic location, which is largely attributed to the strong(weak) planetary-scale(synoptic-scale) component. On the contrast, in the summer rainy season over North China, the WP in the SWEA further strives northward beyond 40°N, showing both quasi-biweekly and weekly oscillations in its position; meanwhile, the planetary-scale wave in the SWEA becomes weakened whereas the synoptic-scale wave is enhanced. These salient variational features of the WP in the SWEA and its scaledependent components may be useful for the medium-range forecast of the rain belt migration in eastern China.展开更多
Chemotherapy is one of the most conventional modalities for cancer therapy.However,the high multidrug resistance of tumor cells still limited the clinical application of current chemotherapy.Considering the ability of...Chemotherapy is one of the most conventional modalities for cancer therapy.However,the high multidrug resistance of tumor cells still limited the clinical application of current chemotherapy.Considering the ability of nitric oxide(NO) to modulate potent P-glycoprotein to inhibit multi-drug resistance,a synergistic methodology combining chemotherapy and sustained NO generation is an ideal way to further promote the chemotherapy.Herein,a multi-functional micelle with tumor-selective chemotherapy driven by redox-triggered doxorubicin(DOX) release and drug resistance inhibition based on intracellular NO generation was fabricated for effective tumor treatment.The micelle consists of DOX as core,arginine/glucose oxidase(Arg/GOx) as shell and redox-responsive disulfide bond as a linker,which is denoted as micelle-DOX-Arg-GOx.The Arg serves as the biological precursor of nitric oxide for inhibition of multi-drug resistance to promote chemotherapy and GOx catalyzes glucose to produce hydrogen peroxide(H_(2) O_(2)) for increasing the generation of NO.Moreover,the glucose supply could be simultaneously blocked by the catalytic process,which further enhanced therapeutic efficiency.This micelle requests a tumor-specific microenvironment(a considerable amount of GSH) to perform synergistic therapeutics including chemotherapy,starvation therapy(catalytic medicine),and gas therapy for tumor treatment,which resulted in significant cytotoxicity to tumor tissue.展开更多
We investigated the decadal changes in the different types of summer mean precipitation over China across the mid-1990 s based on observational datasets.The spatial variations in the observed decadal changes were esti...We investigated the decadal changes in the different types of summer mean precipitation over China across the mid-1990 s based on observational datasets.The spatial variations in the observed decadal changes were estimated by comparing the present day(PD)time period of 1994–2011 with an earlier period of 1964–1981.The summer total precipitation increased in southern China and decreased in northern China from the early period to the PD.The increases of precipitation in southern China were due to increases in the frequency of heavy and moderate rainfall,whereas the decreases over northern China were mainly due to decreases in the frequency of moderate and light rainfall.Based on a set of numerical experiments using an atmospheric general circulation model coupled with a multilevel mixed-layer ocean model,we found that the increase of precipitation frequency forced by greenhouse gases is the main reason of increasing precipitation over southern and northeastern China,while the decrease of frequency caused by anthropogenic aerosol(AA)induces the decreasing precipitation over northern China.The water vapor flux convergence and water vapor flux strengthen in southern China and northeastern China by anthropogenic greenhouse gases.This distribution is also conducive to precipitation in most of southern China and northeastern China.Under the control of weakened southwesterly winds and 850-h Pa divergence,precipitation decreases over northern and southwestern China by AA.展开更多
To the Editor:Since the outbreak in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected>2.4 billion people worldwide,resulting in>4.9 million deaths.To understand the pathogenes...To the Editor:Since the outbreak in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected>2.4 billion people worldwide,resulting in>4.9 million deaths.To understand the pathogenesis of SARS-CoV-2 infection,single-cell RNA-sequencing(scRNA-seq)profiles of peripheral blood mononuclear cells(PBMCs)have been constructed in coronavirus disease-2019(COVID-19)patients at different disease stages.展开更多
文摘On July 23,2022,the World Health Organization(WHO)declared the monkeypox(mpox)outbreak a“Public Health Emergency of International Concern.”Since 2022,outbreaks of mpox in many countries around the world have primarily resulted in fatalities among immunocompromised individuals,such as untreated HIV/AIDS patients.Since the eradication of smallpox was declared by the WHO in 1980,the global vaccination against smallpox has been gradually discontinued.China also stopped routine smallpox vaccination in 1981.The protective effect of the smallpox vaccine has decreased over time due to aging and declining immunity in those who were vaccinated.For individuals,timely vaccination against smallpox is an effective means of protection against mpox.However,due to safety concerns with the smallpox vaccine and the limitations of current mpox vaccines,there is no vaccine that is safe,effective,and has low side effects applied in clinical settings.This article provides a comprehensive review of the development of mpox virus(MPXV)vaccines,their application in special populations,and the current state of vaccine research,considering the etiology,transmission,and prevention of the MPXV.Vaccination,as an effective method of epidemic prevention,can provide long-term immune protection and effectively reduce the severity of infection.However,as there is no licensed specific MPXV vaccine available globally,the vaccines currently used for mpox prevention are mostly smallpox vaccines.These smallpox vaccines can offer some degree of protection against mpox by activating cross-protection in the body.
基金supported by the National Key Research and Development Program of China(2022YFC2604100 to J.L.,and 2023YFC2306003 to X.W.)the National Natural Science Foundation of China(grants 92269203).
文摘The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic.However,the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored.In our research,we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV,identifying cross-reactive CD8^(+)T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays.Then,in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes.Lastly,single-cell T cell receptor reservoir was analyzed based on tetramer staining.Here,we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19,and identified SARS-CoV-2 CD8^(+)T cell epitopes spanning the major structural antigens.T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents.Cross-T cell reactivity was also observed within the identified series of CD8^(+)T cell epitopes.For representative immunodominant peptide pairs,although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar,the TCR repertoires recognizing these peptides were distinct.Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.
基金supported by Grants from Zhejiang Provincial Basic PublicWelfare Research Program(LGF19H150008)the Natural Science Foundation of Zhejiang province(LGF20H150004).
文摘Background:Gelatin methacryloyl(GelMA)hydrogels loaded with stem cells have proved to be an effective clinical treatment for wound healing.Advanced glycation end product(AGE),interacting with its particular receptor(AGER),gives rise to reactive oxygen species(ROS)and apoptosis.Curcumin(Cur)has excellent antioxidant activity and regulates intracellular ROS production and apoptosis.In this study,we developed a Cur-incorporated 3D-printed GelMA to insert into adiposederived stem cells(ADSCs)and applied it to diabetic wounds.Methods:GelMA hydrogels with Cur were fabricated and their in vitro effects on ADSCs were investigated.We used structural characterization,western blot,ROS and apoptosis assay to evaluate the antioxidant and anti-apoptotic activity,and assessed the wound healing effects to investigate the mechanism underlying regulation of apoptosis by Cur via the AGE/AGER/nuclear factor-κB(NF-κB)p65 pathway.Results:A 10%GelMA scaffold exhibited appropriate mechanical properties and biocompatibility for ADSCs.The circular mesh structure demonstrated printability of 10%GelMA and Cur-GelMA bioinks.The incorporation of Cur into the 10%GelMA hydrogel showed an inhibitory effect on AGEs/AGER/NF-κB p65-induced ROS generation and ADSC apoptosis.Furthermore,Cur-GelMA scaffold promoted cell survival and expedited in vivo diabetic wound healing.Conclusions:The incorporation of Cur improved the antioxidant activity of 3D-printed GelMA hydrogel and mitigated AGE/AGER/p65 axis-induced ROS and apoptosis in ADSCs.The effects of scaffolds on wound healing suggested that Cur/GelMA-ADSC hydrogel could be an effective biological material for accelerating wound healing.
基金We thank the Beijing Talents Foundation(2017000021223ZK30)Beijing Lab Foundation+1 种基金Special Funds for COVID-19 Prevention and Control of West China Hospital of Sichuan University(HX-2019-nCoV-049)the National Key Research and Developm ent Program of China(SQ2020YFF0426498).
文摘Dear Editor,The coronavirus infectious disease 2019(COVID-19)outbreak is seriously endangering human health.Most patients with severe COVID-19 are characterized by sustained cytokine production and hyper-inflammation,which is known as cytokine storm syndrome.1-3 Elaborating the anti-inflammatory response is crucial to these patients,and interieukin-6(IL6)inhibitors and steroids have been recommended in clinical practice.1 However,after the cytokine storm phase,the host immune response to sepsis may develop into a protracted immunosuppressive phase.
基金This work was supported by the National Natural Science Foundation of China(81930025,31800817,81670915,and 31870970)Innovative Talent Project of Shaanxi province(2020KJXX-057)Key Research and Development Program of Shaanxi Province(2019SF-073).
文摘Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal women.Under chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of proinflammatory cytokines,impaired osteogenic differentiation capabilities of bone marrow mesenchymal stem cells(BMMSCs),and disturbed regulatory T cell(Treg)/Th17 cell balance.However,therapeutic strategies that re-establish immune homeostasis in this disorder have not been well developed.Here,we produced T cell-depleting nanoparticles(TDNs)that ameliorated the osteopenia phenotype and rescued the osteogenic deficiency of BMMSCs in ovariectomized(OVX)mice.TDNs consist of monocyte chemotactic protein-1(MCP-1)-encapsulated mesoporous silica nanoparticles as the core and Fas-ligand(FasL)as the corona.We showed that the delicate design of the TDNs enables rapid release of MCP-1 to recruit activated T cells and then induces their apoptosis through the conjugated FasL both in vitro and in vivo.Apoptotic signals recognized by macrophages help skew the Treg/Th17 cell balance and create an immune tolerant state,further attenuating the osteogenic deficiency of BMMSCs and the osteopenia phenotype.Mechanistically,we found that the therapeutic effects of TDNs were partially mediated by apoptotic T cell-derived extracellular vesicles(ApoEVs),which promoted macrophage transformation towards the M2 phenotype.These findings demonstrate that TDNs may represent a promising strategy for treating osteoporosis and other immune disorders.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29040201)the National Natural Science Foundation of China(NSFC)(81901680)。
基金supported by the Ministry of Science and Technology of the People’s Republic of China(2020YFC0844900,2020YFC0841700,and 2020YFC0848700)the National Natural Science Foundation of China(81470566,81670765,81772165,and 81974303)+1 种基金the China Primary Health Care Foundation-Youan Medical Development Fund(BJYAYY2020PY-01)the funds from Neoline,Gbio and Quanterix。
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused the global outbreak of coronavirus disease 2019(COVID-19).By far,more than 35 million people had been infected by SARS-CoV-2,resulting in more than 1 million deaths globally.It is well recognized that SARSCoV-2 preferentially attacks pulmonary epithelial cells,leading to acute respiratory distress syndrome(ARDS).
基金supported by the COVID-19 Key Technology Research and Development Funding of Beijing Hospital Authority,the National Natural Science Foundation of China(NSFC,81772165 and 81974303)the National 13th Five-Year Grand Program on Key Infectious Disease Control(2017ZX10202102-005-003)。
文摘The outbreak of coronavirus disease 2019(COVID-19)caused by the new virus SARS-CoV-2 has been announced as a public health emergency of international concern.1–3 The clinical features of patients with COVID-19 range from common fever and cough to other rare symptoms,such as diarrhea and nausea.This disease can progress quickly,and 2–3%of patients die within a short time,which is generally due to multiple organ failure.4–7 Clinically,COVID-19 patients are classified into mild,moderate,severe,and critical cases.5–7 The immune response against SARS-CoV-2 is probably linked to the severity of disease.Recently,Zheng et al.8 showed that elevated levels of T-cell exhaustion and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients;however,a more comprehensive understanding of the pathology of SARS-CoV-2 infection remains to be delineated.Here,we profiled immune cellular components using mass cytometry(CyTOF)to analyze the peripheral blood mononuclear cells(PBMCs)from patients with differences in disease progression by comparing with the PBMCs from healthy donors(HDs).
基金Supported by the National Natural Science Foundation of China(41575066)National Science and Technology Support Program of China(2015BAC03B04)
文摘The 200-hPa wind perturbation(WP) in the subtropical westerly over East Asia(SWEA) has seldom been examined in previous studies, especially in connection with forecast of the summer rainfall in China. Based on the daily NCEP/NCAR reanalysis data and precipitation observations in China from 1 June to 31 August of 1960-2015, this study first systematically analyzes the spatiotemporal distribution features of the 200-hPa WP in the SWEA on different scales, especially during the Meiyu season in the Yangtze-Huaihe region and during the rainy period in North China, by using spectral decomposition and period analysis. It is found that in the 56-yr mean fields, the 200-hPa WP in the SWEA is collocated with the East Asian subtropical jet(EASJ), with the centers of the two systems coincidentally overlapped. The WP filed in the subtropical westerly mainly comprises planetary-and synoptic-scale waves. The quasi-stationary planetary-scale wave seems to determine the shape and intensity of the WP in the SWEA, while the synoptic-scale wave is closely related to the local central intensity of the WP. The daily evolution of the 56-yr mean fields shows that, following the northward(southward) movement of SWEA from 1 June to 31 August, the planetaryscale WP in the SWEA becomes gradually weakened(intensified) whereas the synoptic-scale WP is slightly intensified(weakened).The results also reveal that during the Meiyu season in the Yangtze-Huaihe region, the WP in the SWEA moves northward slowly around 37°-39°N, demonstrating a quasi-biweekly oscillation in its geographic location, which is largely attributed to the strong(weak) planetary-scale(synoptic-scale) component. On the contrast, in the summer rainy season over North China, the WP in the SWEA further strives northward beyond 40°N, showing both quasi-biweekly and weekly oscillations in its position; meanwhile, the planetary-scale wave in the SWEA becomes weakened whereas the synoptic-scale wave is enhanced. These salient variational features of the WP in the SWEA and its scaledependent components may be useful for the medium-range forecast of the rain belt migration in eastern China.
基金supported by the National Natural Science Foundation of China (No.81601606to Xin Chen)the"Young Talent Support Plan"of Xi’an Jiaotong University (Xin Chen)+6 种基金the Technology Foundation for Selected Overseas Chinese Scholar of Shaanxi Province (Xin Chen)the Fundamental Research Funds for the Central Universities (No.2016qngz02 to Xin Chen)the One Hundred Talents Program of Shaanxi Province (Xin Chen)National Natural Science Foundation of Shaanxi Province (No.2017JM5023to Xin Chen)open fund of the State Key Laboratory of Military Stomatology (No.2017KA02 to Xin Chen)the Knowledge Innovation Program of Shenzhen (No.JCYJ20170816100941258to Xin Chen)Beijing Nova Program of Science and Technology (No.Z191100001119096 to Zhongning Liu)。
文摘Chemotherapy is one of the most conventional modalities for cancer therapy.However,the high multidrug resistance of tumor cells still limited the clinical application of current chemotherapy.Considering the ability of nitric oxide(NO) to modulate potent P-glycoprotein to inhibit multi-drug resistance,a synergistic methodology combining chemotherapy and sustained NO generation is an ideal way to further promote the chemotherapy.Herein,a multi-functional micelle with tumor-selective chemotherapy driven by redox-triggered doxorubicin(DOX) release and drug resistance inhibition based on intracellular NO generation was fabricated for effective tumor treatment.The micelle consists of DOX as core,arginine/glucose oxidase(Arg/GOx) as shell and redox-responsive disulfide bond as a linker,which is denoted as micelle-DOX-Arg-GOx.The Arg serves as the biological precursor of nitric oxide for inhibition of multi-drug resistance to promote chemotherapy and GOx catalyzes glucose to produce hydrogen peroxide(H_(2) O_(2)) for increasing the generation of NO.Moreover,the glucose supply could be simultaneously blocked by the catalytic process,which further enhanced therapeutic efficiency.This micelle requests a tumor-specific microenvironment(a considerable amount of GSH) to perform synergistic therapeutics including chemotherapy,starvation therapy(catalytic medicine),and gas therapy for tumor treatment,which resulted in significant cytotoxicity to tumor tissue.
基金Supported by the National Natural Science Foundation of China(41905091)Support Plan of the National Science and Technology(2015BAC03B04)+1 种基金Fund Project of the National Meteorological Center Forecaster(Y201904)Buwen DONG is supported by the UK National Centre for Atmospheric Science-Climate(NCAS-Climate)at the University of Reading。
文摘We investigated the decadal changes in the different types of summer mean precipitation over China across the mid-1990 s based on observational datasets.The spatial variations in the observed decadal changes were estimated by comparing the present day(PD)time period of 1994–2011 with an earlier period of 1964–1981.The summer total precipitation increased in southern China and decreased in northern China from the early period to the PD.The increases of precipitation in southern China were due to increases in the frequency of heavy and moderate rainfall,whereas the decreases over northern China were mainly due to decreases in the frequency of moderate and light rainfall.Based on a set of numerical experiments using an atmospheric general circulation model coupled with a multilevel mixed-layer ocean model,we found that the increase of precipitation frequency forced by greenhouse gases is the main reason of increasing precipitation over southern and northeastern China,while the decrease of frequency caused by anthropogenic aerosol(AA)induces the decreasing precipitation over northern China.The water vapor flux convergence and water vapor flux strengthen in southern China and northeastern China by anthropogenic greenhouse gases.This distribution is also conducive to precipitation in most of southern China and northeastern China.Under the control of weakened southwesterly winds and 850-h Pa divergence,precipitation decreases over northern and southwestern China by AA.
基金Beijing Science Foundation of China(No.Z201100005520062,No.Z201100007920017)National Natural Science Foundation of China(No.81772165)China Primary Health Care Foundation-Youan Medical Development Fund(No.BJYAYY-2020PY-01)。
文摘To the Editor:Since the outbreak in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected>2.4 billion people worldwide,resulting in>4.9 million deaths.To understand the pathogenesis of SARS-CoV-2 infection,single-cell RNA-sequencing(scRNA-seq)profiles of peripheral blood mononuclear cells(PBMCs)have been constructed in coronavirus disease-2019(COVID-19)patients at different disease stages.
