The primary energy demand increases, but a large amount of waste heat resources w</span><span style="font-family:Verdana;">ere </span><span style="font-family:Verdana;">...The primary energy demand increases, but a large amount of waste heat resources w</span><span style="font-family:Verdana;">ere </span><span style="font-family:Verdana;">not effectively used. To explore the influence of particle stacking structure on waste heat recovery process, CFD method was used to simulate. An unsteady heat transfer model of two particles was established, effect of particle stacking angle on heat transfer characteristics of the particles close to the wall under different initial temperature conditions was studied. Results show that: higher initial temperature, resulting in increased heat transfer time, the larger particle stacking angle causes the shortening of heat transfer time. When initial temperature is 1073</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">K, the average wall heat flux shows a trend of rapid decline first and then a slow one. At the same moment, the larger stacking angle causes smaller particle average temperature. The change of particle stacking angle shows a greater impact on the temperature of the particles close to adiabatic wall. The increase in the stacking angle resulting in better heat transfer characteristics between particles.展开更多
Applying the air impact molding method to mold the complicated pattern with wider opening surface and deeper concave, there always exist vaulted phenomenon and lower compactibility of sand mold over the entrance and t...Applying the air impact molding method to mold the complicated pattern with wider opening surface and deeper concave, there always exist vaulted phenomenon and lower compactibility of sand mold over the entrance and the concave regions. Using the air-stream and synchro-formed clamp plate impact molding, however, this problem will be preferably solved. In this paper, the compact mechanism of the new molding method and the effect of some configuration factors, such as the area flowed by compressed air and the highness of the protruding block displacement around the diffluent clamp plate, on the compactibility of sand mold were discussed.展开更多
In order to improve the performance of vehicle radiators, a two-dimensional heat transfer steady-state model of the radiator was set up. The influence of the structural parameters (axial ratio) of the heat exchange tu...In order to improve the performance of vehicle radiators, a two-dimensional heat transfer steady-state model of the radiator was set up. The influence of the structural parameters (axial ratio) of the heat exchange tube on the windward side on the heat transfer performance of the radiator was studied. With the increase of the axial ratio of the heat exchange tube on the windward side, the heat exchange capacity of the heat exchange tube surface slightly decreases. The heat exchange area increases significantly, which increases the total heat exchange of the radiator and improves the heat transfer performance of the radiator. When the axial ratio increases from 1.0 to 2.0, the average surface heat transfer capacity decreases from 5664.16</span><span style="font-family:""> </span><span style="font-family:Verdana;">W/m<sup>2</sup> to 5623.57</span><span style="font-family:""> </span><span style="font-family:Verdana;">W/m<sup>2</sup>.展开更多
The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants.In Chengdu,China,an infection wave was predominantly induced...The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants.In Chengdu,China,an infection wave was predominantly induced by the BA.5 subvariant.It is crucial to determine whether the hybrid anti-SARS-CoV-2 immunity following BA.5 infection.展开更多
Eu3+ions doped Zn(OH)F and ZnO micro-structures with specific morphologies were synthesized by a simple hydrothermal method only through altering the addition amount of NH4F and hexamethylenetetramine(HMT).The phase s...Eu3+ions doped Zn(OH)F and ZnO micro-structures with specific morphologies were synthesized by a simple hydrothermal method only through altering the addition amount of NH4F and hexamethylenetetramine(HMT).The phase structure,morphology and luminescence properties of the as-prepared samples were characterized by X-ray powder diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),photoluminescence(PL)spectra and lifetime.The results indicate that the obtained Zn(OH)F:Eu^3+samples possess net-like and dandelion-like morphologies,which have an identical orthorhombic phase structure.It is found that the addition amount of raw materials such as NH4F and HMT plays a critical role for the formation of Zn(OH)F:Eu^3+.If the addition amounts of NH4F or HMT are reduced by half,the hexagonal ZnO:Eu^3+sample with peanut-like morphology can be obtained.Under the excitation of UV light,both the as-prepared Zn(OH)F:Eu^3+and ZnO:Eu^3+samples exhibit the characteristic emission of the doped Eu^3+.展开更多
Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host defense.Contrary to our expec...Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host defense.Contrary to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model.The histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids.Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein.Moreover,histones enhance cell-cell fusion.Finally,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model.These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.展开更多
The outbreak of coronavirus disease 2019(COVID-19)has posed great threats to global health and economy.Several effective vaccines are available now,but additional booster immunization is required to retain or increase...The outbreak of coronavirus disease 2019(COVID-19)has posed great threats to global health and economy.Several effective vaccines are available now,but additional booster immunization is required to retain or increase the immune responses owing to waning immunity and the emergency of new variant strains.The deficiency of intramuscularly delivered vaccines to induce mucosal immunity urged the development of mucosal vaccines.Here,we developed an adjuvanted intranasal RBD vaccine and monitored its long-term immunogenicity against both wild-type and mutant strains of severe acute respiratory syndrome coronavirus-2(SARSCoV-2),including Omicron variants,in mice.Three-dose intranasal immunization with this vaccine induced and maintained high levels of neutralizing IgG antibodies in the sera for at least 1 year.Strong mucosal immunity was also provoked,including mucosal secretory IgA and lung-resident memory T cells(TRM).We also demonstrated that the long-term persistence of lung TRM cells is a consequence of local T-cell proliferation,rather than T-cell migration from lymph nodes.Our data suggested that the adjuvanted intranasal RBD vaccine is a promising vaccine candidate to establish robust,long-lasting,and broad protective immunity against SARS-CoV-2 both systemically and locally.展开更多
Pseudomonas aeruginosa infection continues to be a major threat to global public health,and new safe and efficacious vaccines are needed for prevention of infections caused by P.aeruginosa.X-ray irradiation has been u...Pseudomonas aeruginosa infection continues to be a major threat to global public health,and new safe and efficacious vaccines are needed for prevention of infections caused by P.aeruginosa.X-ray irradiation has been used to prepare whole-cell inactivated vaccines against P.aeruginosa infection.However,the immunological mechanisms of X-ray-inactivated vaccines are still unclear and require further investigation.Our previous study found that an X-ray-inactivated whole-cell vaccine could provide protection against P.aeruginosa by boosting T cells.The aim of the present study was to further explore the immunological mechanisms of the vaccine.Herein,P.aeruginosa PAO1,a widely used laboratory strain,was utilized to prepare the vaccine,and we found nucleic acids and 8-hydroxyguanosine in the supernatant of X-ray-inactivated PAO1(XPa).By detecting CD86,CD80,and MHCII expression,we found that XPa fostered dentritic cell(DC)maturation by detecting.XPa stimulated the cGAS-STING pathway as well as Toll-like receptors in DCs in vitro,and DC finally underwent apoptosis and pyroptosis after XPa stimulation.In addition,DC stimulated by XPa induced CD8+T-cell proliferation in vitro and generated immunologic memory in vivo.Moreover,XPa vaccination induced both Th1 and Th2 cytokine responses in mice and reduced the level of inflammatory factors during infection.XPa protected mice in pneumonia models from infection with PAO1 or multidrug-resistant clinical isolate W9.Chronic obstructive pulmonary disease(COPD)mice immunized with XPa could resist PAO1 infection.Therefore,a new mechanism of an X-ray-inactivated whole-cell vaccine against P.aeruginosa infection was discovered in this study.展开更多
CePO_(4):Tb^(3+)nanorods were successfully obtained via a simple hydrothermal method and combined with carbon dots(CDs)to obtain CDs@CePO_(4):Tb^(3+)nanorods.Due to the combination of CDs,the emission intensity of CDs...CePO_(4):Tb^(3+)nanorods were successfully obtained via a simple hydrothermal method and combined with carbon dots(CDs)to obtain CDs@CePO_(4):Tb^(3+)nanorods.Due to the combination of CDs,the emission intensity of CDs@CePO_(4):Tb^(3+)nanorods increases about 92 times,compared with that of CePO_(4):Tb^(3+)nanorods.The combination of CDs and CePO_(4):Tb^(3+)nanorods was confirmed by Fourier transform infrared spectroscopy(FTIR),transmission electron microscopy(TEM),X-ray photoelectron spectroscopy(XPS)and so on.The mechanism of luminescence enhancement may be attributed to some aspects:the formation of hexagonal phase results in the increase of crystal field symmetry,and the energy transfer among CDs,Ce^(3+)and Tb^(3+)ions,which causes the Tb^(3+)ions in CDs@CePO_(4):Tb^(3+)nano rods to obtain mo re excited energy and less non-radiative atte nuation co mpared to CePO_(4):Tb^(3+)nano rods.The luminescence enhancement strategy through combination of CDs would provide a simple and effective approach for other rare earth ions doped luminescent materials.展开更多
The current pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection has dramatically influenced various aspects of the world.It is urgent to thorough...The current pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection has dramatically influenced various aspects of the world.It is urgent to thoroughly study pathology and underlying mechanisms for developing effective strategies to prevent and treat this threatening disease.It is universally acknowledged that cell death and cell autophagy are essential and crucial to maintaining host homeostasis and participating in disease pathogenesis.At present,more than twenty different types of cell death have been discovered,some parts of which have been fully understood,whereas some of which need more investigation.Increasing studies have indicated that cell death and cell autophagy caused by coronavirus might play an important role in virus infection and pathogenicity.However,the knowledge of the interactions and related mechanisms of SARS-CoV-2 between cell death and cell autophagy lacks systematic elucidation.Therefore,in this review,we comprehensively delineate how SARS-CoV-2 manipulates diverse cell death(including apoptosis,necroptosis,pyroptosis,ferroptosis,and NETosis)and cell autophagy for itself benefits,which is simultaneously involved in the occurrence and progression of COVID-19,aiming to provide a reasonable basis for the existing interventions and further development of novel therapies.展开更多
SARS-CoV-2 recognizes,via its spike receptor-binding domain(S-RBD),human angiotensin-converting enzyme 2(ACE2)to initiate infection.Ecto-domain protein of ACE2 can therefore function as a decoy.Here we show that mutat...SARS-CoV-2 recognizes,via its spike receptor-binding domain(S-RBD),human angiotensin-converting enzyme 2(ACE2)to initiate infection.Ecto-domain protein of ACE2 can therefore function as a decoy.Here we show that mutations of S19W,T27W,and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding.Y330 could be synergistically combined with either W19 or W27,whereas W19 and W27 are mutually unbeneficial.The structures of SARS-CoV-2S-RBD bound to the ACE2 mutants reveal that the enhan ced binding is mainly con tributed by the van der Waals interactio ns mediated by the aromatic side-chai ns from W19,W27,and Y330.While Y330 and W19/W27 are distantly located and devoid of any steric interference,W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts,explai ning their in compatibility.Finally,using pseudotyped SARS-CoV-2 viruses,we dem on strate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses.Taken together,our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W,T27W,and N330Y mutations in ACE2,paving the way for potential application of these mutants in dinical treatment of COVID-19.展开更多
Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vacci...Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vaccine,targeting receptor binding domain(RBD)of the spike protein(S-RBD)of SARS-CoV-2,which could induce a potent antibody response and protect non-human primates from SARS-CoV-2 challenge.1 The recombinant RBD protein is proved as a potent antigen and a novel adjuvant is in demand for the effective stimulation of adaptive immunity.Therefore,to improve the efficacy of the vaccine and seek a novel adjuvant that can stimulate both humoral and cellular immunity,we investigated the potential of series of cationic nanocarriers as adjuvants of the recombinant S-RBD vaccine for SARS-CoV-2.As the surface charge of a nanocarrier might dramatically affect the immunogenicity of a vaccine and enhance and/or shape antigen-specific immune responses,we also used anionic nanocarriers and neutral nanocarriers as controls(Supplementary Table S1).S-RBD vaccines with adjuvant candidates were administered intranasally or intramuscularly in the present study.展开更多
Recently,a paper published in Science by Hadjadj et al.reported that type I interferon(IFN)deficiency,could be a hallmark of severe coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronav...Recently,a paper published in Science by Hadjadj et al.reported that type I interferon(IFN)deficiency,could be a hallmark of severe coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Severe COVID-19 was also associated with a lymphocytopenia,persistent blood viral load,and an exacerbated inflammatory response(Fig.1).These findings provide insights into the treatment of severe COVID-19 patients with type I IFN.展开更多
Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vacci...Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vaccine,targeting receptor binding domain(RBD)of the spike protein(S-RBD)of SARS-CoV-2,which could induce a potent antibody response and protect non-human primates from SARS-CoV-2 challenge.1 The recombinant RBD protein is proved as a potent antigen and a novel adjuvant is in demand for the effective stimulation of adaptive immunity.展开更多
Recently,a paper published in Cell by Ho et al.describes an interesting finding how a virus can highjack the host machinery and gene sequence to synthesize its own virulence proteins to facilitate invasion,replication...Recently,a paper published in Cell by Ho et al.describes an interesting finding how a virus can highjack the host machinery and gene sequence to synthesize its own virulence proteins to facilitate invasion,replication,and spread.The research reveals that RNA viruses like influenza A virus(IAV)can produce previously unrecognized chimeric proteins containing both viral and human genetic information,which can then affect virulence and modulate T cell responses in hosts(Fig.1).展开更多
文摘The primary energy demand increases, but a large amount of waste heat resources w</span><span style="font-family:Verdana;">ere </span><span style="font-family:Verdana;">not effectively used. To explore the influence of particle stacking structure on waste heat recovery process, CFD method was used to simulate. An unsteady heat transfer model of two particles was established, effect of particle stacking angle on heat transfer characteristics of the particles close to the wall under different initial temperature conditions was studied. Results show that: higher initial temperature, resulting in increased heat transfer time, the larger particle stacking angle causes the shortening of heat transfer time. When initial temperature is 1073</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">K, the average wall heat flux shows a trend of rapid decline first and then a slow one. At the same moment, the larger stacking angle causes smaller particle average temperature. The change of particle stacking angle shows a greater impact on the temperature of the particles close to adiabatic wall. The increase in the stacking angle resulting in better heat transfer characteristics between particles.
文摘Applying the air impact molding method to mold the complicated pattern with wider opening surface and deeper concave, there always exist vaulted phenomenon and lower compactibility of sand mold over the entrance and the concave regions. Using the air-stream and synchro-formed clamp plate impact molding, however, this problem will be preferably solved. In this paper, the compact mechanism of the new molding method and the effect of some configuration factors, such as the area flowed by compressed air and the highness of the protruding block displacement around the diffluent clamp plate, on the compactibility of sand mold were discussed.
文摘In order to improve the performance of vehicle radiators, a two-dimensional heat transfer steady-state model of the radiator was set up. The influence of the structural parameters (axial ratio) of the heat exchange tube on the windward side on the heat transfer performance of the radiator was studied. With the increase of the axial ratio of the heat exchange tube on the windward side, the heat exchange capacity of the heat exchange tube surface slightly decreases. The heat exchange area increases significantly, which increases the total heat exchange of the radiator and improves the heat transfer performance of the radiator. When the axial ratio increases from 1.0 to 2.0, the average surface heat transfer capacity decreases from 5664.16</span><span style="font-family:""> </span><span style="font-family:Verdana;">W/m<sup>2</sup> to 5623.57</span><span style="font-family:""> </span><span style="font-family:Verdana;">W/m<sup>2</sup>.
基金This work was supported by the National Science Foundation for Excellent Young Scholars(32122052)National Natural Science Foundation Regional Innovation and Development(No.U19A2003)National Natural Science Foundation of China(82200018).Figure 1a was created by BioRender.
文摘The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants.In Chengdu,China,an infection wave was predominantly induced by the BA.5 subvariant.It is crucial to determine whether the hybrid anti-SARS-CoV-2 immunity following BA.5 infection.
基金Project supported by the National Natural Science Foundation of China(51572303)
文摘Eu3+ions doped Zn(OH)F and ZnO micro-structures with specific morphologies were synthesized by a simple hydrothermal method only through altering the addition amount of NH4F and hexamethylenetetramine(HMT).The phase structure,morphology and luminescence properties of the as-prepared samples were characterized by X-ray powder diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),photoluminescence(PL)spectra and lifetime.The results indicate that the obtained Zn(OH)F:Eu^3+samples possess net-like and dandelion-like morphologies,which have an identical orthorhombic phase structure.It is found that the addition amount of raw materials such as NH4F and HMT plays a critical role for the formation of Zn(OH)F:Eu^3+.If the addition amounts of NH4F or HMT are reduced by half,the hexagonal ZnO:Eu^3+sample with peanut-like morphology can be obtained.Under the excitation of UV light,both the as-prepared Zn(OH)F:Eu^3+and ZnO:Eu^3+samples exhibit the characteristic emission of the doped Eu^3+.
基金supported by the National Science Foundation for Excellent Young Scholars (32122052)National Natural Science Foundation Regional Innovation and Development (No.U19A2003).
文摘Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host defense.Contrary to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model.The histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids.Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein.Moreover,histones enhance cell-cell fusion.Finally,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model.These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.
基金supported by the National Natural Science Foundation Regional Innovation and Development(No.U19A2003)the National Science Fund for Excellent Young Scholars National Science Fund for Excellent Young Scholars(No.32122052).
文摘The outbreak of coronavirus disease 2019(COVID-19)has posed great threats to global health and economy.Several effective vaccines are available now,but additional booster immunization is required to retain or increase the immune responses owing to waning immunity and the emergency of new variant strains.The deficiency of intramuscularly delivered vaccines to induce mucosal immunity urged the development of mucosal vaccines.Here,we developed an adjuvanted intranasal RBD vaccine and monitored its long-term immunogenicity against both wild-type and mutant strains of severe acute respiratory syndrome coronavirus-2(SARSCoV-2),including Omicron variants,in mice.Three-dose intranasal immunization with this vaccine induced and maintained high levels of neutralizing IgG antibodies in the sera for at least 1 year.Strong mucosal immunity was also provoked,including mucosal secretory IgA and lung-resident memory T cells(TRM).We also demonstrated that the long-term persistence of lung TRM cells is a consequence of local T-cell proliferation,rather than T-cell migration from lymph nodes.Our data suggested that the adjuvanted intranasal RBD vaccine is a promising vaccine candidate to establish robust,long-lasting,and broad protective immunity against SARS-CoV-2 both systemically and locally.
基金This study was supported by the Chinese Major Scientific and Technological Special Project for“Significant New Drugs Creation”,National Key Project(2019ZX09721-001-004-004)Key Technologies and Transformation Platform for Rapid Emergency Vaccine R&D for“the Sichuan Province Key R&D Program”(2020YFS0568).
文摘Pseudomonas aeruginosa infection continues to be a major threat to global public health,and new safe and efficacious vaccines are needed for prevention of infections caused by P.aeruginosa.X-ray irradiation has been used to prepare whole-cell inactivated vaccines against P.aeruginosa infection.However,the immunological mechanisms of X-ray-inactivated vaccines are still unclear and require further investigation.Our previous study found that an X-ray-inactivated whole-cell vaccine could provide protection against P.aeruginosa by boosting T cells.The aim of the present study was to further explore the immunological mechanisms of the vaccine.Herein,P.aeruginosa PAO1,a widely used laboratory strain,was utilized to prepare the vaccine,and we found nucleic acids and 8-hydroxyguanosine in the supernatant of X-ray-inactivated PAO1(XPa).By detecting CD86,CD80,and MHCII expression,we found that XPa fostered dentritic cell(DC)maturation by detecting.XPa stimulated the cGAS-STING pathway as well as Toll-like receptors in DCs in vitro,and DC finally underwent apoptosis and pyroptosis after XPa stimulation.In addition,DC stimulated by XPa induced CD8+T-cell proliferation in vitro and generated immunologic memory in vivo.Moreover,XPa vaccination induced both Th1 and Th2 cytokine responses in mice and reduced the level of inflammatory factors during infection.XPa protected mice in pneumonia models from infection with PAO1 or multidrug-resistant clinical isolate W9.Chronic obstructive pulmonary disease(COPD)mice immunized with XPa could resist PAO1 infection.Therefore,a new mechanism of an X-ray-inactivated whole-cell vaccine against P.aeruginosa infection was discovered in this study.
基金Project supported by the National Natural Science Foundation of China(51572303,52002117)。
文摘CePO_(4):Tb^(3+)nanorods were successfully obtained via a simple hydrothermal method and combined with carbon dots(CDs)to obtain CDs@CePO_(4):Tb^(3+)nanorods.Due to the combination of CDs,the emission intensity of CDs@CePO_(4):Tb^(3+)nanorods increases about 92 times,compared with that of CePO_(4):Tb^(3+)nanorods.The combination of CDs and CePO_(4):Tb^(3+)nanorods was confirmed by Fourier transform infrared spectroscopy(FTIR),transmission electron microscopy(TEM),X-ray photoelectron spectroscopy(XPS)and so on.The mechanism of luminescence enhancement may be attributed to some aspects:the formation of hexagonal phase results in the increase of crystal field symmetry,and the energy transfer among CDs,Ce^(3+)and Tb^(3+)ions,which causes the Tb^(3+)ions in CDs@CePO_(4):Tb^(3+)nano rods to obtain mo re excited energy and less non-radiative atte nuation co mpared to CePO_(4):Tb^(3+)nano rods.The luminescence enhancement strategy through combination of CDs would provide a simple and effective approach for other rare earth ions doped luminescent materials.
基金supported by the National Natural Science Foundation of China(81201788).
文摘The current pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection has dramatically influenced various aspects of the world.It is urgent to thoroughly study pathology and underlying mechanisms for developing effective strategies to prevent and treat this threatening disease.It is universally acknowledged that cell death and cell autophagy are essential and crucial to maintaining host homeostasis and participating in disease pathogenesis.At present,more than twenty different types of cell death have been discovered,some parts of which have been fully understood,whereas some of which need more investigation.Increasing studies have indicated that cell death and cell autophagy caused by coronavirus might play an important role in virus infection and pathogenicity.However,the knowledge of the interactions and related mechanisms of SARS-CoV-2 between cell death and cell autophagy lacks systematic elucidation.Therefore,in this review,we comprehensively delineate how SARS-CoV-2 manipulates diverse cell death(including apoptosis,necroptosis,pyroptosis,ferroptosis,and NETosis)and cell autophagy for itself benefits,which is simultaneously involved in the occurrence and progression of COVID-19,aiming to provide a reasonable basis for the existing interventions and further development of novel therapies.
基金supported by the special research fund on COVID-19 of Sichuan Province(Grant no.2020YFS0010)the special research fund on COVID-19 of West China Hospital Sichuan University(Grant no.HX-2019-nCoV-004)the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(Grant no.ZYYC20008).
文摘SARS-CoV-2 recognizes,via its spike receptor-binding domain(S-RBD),human angiotensin-converting enzyme 2(ACE2)to initiate infection.Ecto-domain protein of ACE2 can therefore function as a decoy.Here we show that mutations of S19W,T27W,and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding.Y330 could be synergistically combined with either W19 or W27,whereas W19 and W27 are mutually unbeneficial.The structures of SARS-CoV-2S-RBD bound to the ACE2 mutants reveal that the enhan ced binding is mainly con tributed by the van der Waals interactio ns mediated by the aromatic side-chai ns from W19,W27,and Y330.While Y330 and W19/W27 are distantly located and devoid of any steric interference,W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts,explai ning their in compatibility.Finally,using pseudotyped SARS-CoV-2 viruses,we dem on strate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses.Taken together,our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W,T27W,and N330Y mutations in ACE2,paving the way for potential application of these mutants in dinical treatment of COVID-19.
基金supported by the National Key Research and Development Program of China(No.2016YFA0201402)National Natural Science Foundation Regional Innovation and Development(U19A2003)The National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09733001).
文摘Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vaccine,targeting receptor binding domain(RBD)of the spike protein(S-RBD)of SARS-CoV-2,which could induce a potent antibody response and protect non-human primates from SARS-CoV-2 challenge.1 The recombinant RBD protein is proved as a potent antigen and a novel adjuvant is in demand for the effective stimulation of adaptive immunity.Therefore,to improve the efficacy of the vaccine and seek a novel adjuvant that can stimulate both humoral and cellular immunity,we investigated the potential of series of cationic nanocarriers as adjuvants of the recombinant S-RBD vaccine for SARS-CoV-2.As the surface charge of a nanocarrier might dramatically affect the immunogenicity of a vaccine and enhance and/or shape antigen-specific immune responses,we also used anionic nanocarriers and neutral nanocarriers as controls(Supplementary Table S1).S-RBD vaccines with adjuvant candidates were administered intranasally or intramuscularly in the present study.
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(2019ZX09721001-004-004).
文摘Recently,a paper published in Science by Hadjadj et al.reported that type I interferon(IFN)deficiency,could be a hallmark of severe coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Severe COVID-19 was also associated with a lymphocytopenia,persistent blood viral load,and an exacerbated inflammatory response(Fig.1).These findings provide insights into the treatment of severe COVID-19 patients with type I IFN.
基金This work was supported by the National Key Research and Development Program of China(No.2016YFA0201402)National Natural Science Foundation Regional Innovation and Development(U19A2003)The National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09733001).
文摘Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vaccine,targeting receptor binding domain(RBD)of the spike protein(S-RBD)of SARS-CoV-2,which could induce a potent antibody response and protect non-human primates from SARS-CoV-2 challenge.1 The recombinant RBD protein is proved as a potent antigen and a novel adjuvant is in demand for the effective stimulation of adaptive immunity.
基金supported by National Major Scientific and Technological Special Project for“Significant New Drugs Development”(2019ZX09721001-004-004)supported by the National Institutes of Health for Grants R01 AI138203 and R01 AI109317.
文摘Recently,a paper published in Cell by Ho et al.describes an interesting finding how a virus can highjack the host machinery and gene sequence to synthesize its own virulence proteins to facilitate invasion,replication,and spread.The research reveals that RNA viruses like influenza A virus(IAV)can produce previously unrecognized chimeric proteins containing both viral and human genetic information,which can then affect virulence and modulate T cell responses in hosts(Fig.1).