Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its ...Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its impact on cancer prognosis remains unclear.Methods:We conducted a comprehensive analysis utilizing data from The Cancer Genome Atlas(TCGA)and other databases to assess the prognostic value and functional implications across various tumors.Silence of SLC22A1 RNA in glioma U251 cells was performed to access the impact of SLC22A1 on lowergrade glioma(LGG)progression.Results:Our findings demonstrated a significant correlation between SLC22A1 expression and the survival time of patients with various cancers(p<0.05).Importantly,we found the potential involvement of SLC22A1 in occurrence and progress of certain cancers,with a pronounced impact on LGG.Further examination of the SLC22A1-LGG relationship revealed its status as an independent risk factor for LGG,suggesting its potential involvement in regulating diverse immune pathways and metabolic activities.Chinese Glioma Genome Atlas(CGGA)data supported the reliability of the risk score as a prognostic and recurrence indicator,emphasizing the accuracy of the nomograph(1,3,and 5-year-AUC>0.8).Cell proliferation and clone formation experiment proved that decreased expression of SLC22A1 in glioma U251 cells inhibited glioma cell growth.Conclusion:Our findings suggest SLC22A1 has huge prospects as a promising biomarker and therapeutic target for LGG prognosis.SLC22A1 has only been proved to support cellular function previously.Our findings demonstrated a robust connection between the tumor microenvironment and functional proteins that maintain basal cell metabolism,which gifts unique tumor immune characteristics of gliomas.Additionally,we provide a highly practical prediction model for estimating the survival rate of LGG patients.展开更多
Physicochemical properties of arsenic sulfide sludge(ASS) from copper smelter(ASS-I) and lead-zinc smelter(ASS-II) were examined by XRD, Raman spectroscopy, SEM-EDS, TG-DTA, XPS and chemical phase analysis method. The...Physicochemical properties of arsenic sulfide sludge(ASS) from copper smelter(ASS-I) and lead-zinc smelter(ASS-II) were examined by XRD, Raman spectroscopy, SEM-EDS, TG-DTA, XPS and chemical phase analysis method. The toxicity characteristic leaching procedure(TCLP), Chinese standard leaching tests(CSLT), three-stage sequential extraction procedure(BCR) and batch leaching experiments(BLE) were used to investigate the environmental stability. The ASSs from different smelters had obviously different physicochemical and environmental properties. The phase composition and micrograph analysis indicate that ASS-I mainly consists of super refined flocculent particles including amorphous arsenic sulfide adhered with amorphous sulfur and that ASS-II mainly consists of amorphous arsenic sulfide. The valence state of arsenic in both sludges is trivalent, but the valence composition of sulfur is quite different. The ASSs have thermal instability properties. The results of TCLP and CSLT indicate that the concentrations of As and Pd in the leaching solution exceed the standard limits. More than 5% and 90% of arsenic are in the form of acid soluble and oxidizable fractions, respectively, which explains the high arsenic leaching toxicity and environmental activity of ASS. This research provides comprehensive information for the disposal of ASS from copper and lead-zinc smelter.展开更多
A new hydrometallurgical route for separation and recovery of Cu from Cu-As-bearing copper electrorefining black slime was developed. The proposed process comprised oxidation acid leaching of Cu-As-bearing slime and s...A new hydrometallurgical route for separation and recovery of Cu from Cu-As-bearing copper electrorefining black slime was developed. The proposed process comprised oxidation acid leaching of Cu-As-bearing slime and selective sulfide precipitation of Cu from the leachate. The effects of various process parameters on the leaching and precipitation of Cu and As were investigated. At the first stage, Cu extraction of 95.2% and As extraction of 97.6% were obtained at 80 ℃ after 4 h with initial H2 SO4 concentration of 1.0 mol/L and liquid-to-solid ratio of 10 mL/g. In addition, the leaching kinetics of Cu and As was successfully reproduced by the Avrami model, and the apparent activation energies were found to be 33.6 and 35.1 kJ/mol for the Cu and As leaching reaction, respectively, suggesting a combination of chemical reaction and diffusion control. During the selective sulfide precipitation, about 99.4% Cu was recovered as CuS, while only 0.1% As was precipitated under the optimal conditions using sulfide-to-copper ratio of 2.4:1, time of 1.5 h and temperature of 25 ℃.展开更多
High ionic conductivity,good electrochemical stability,and satisfactory mechanical property are the crucial factors for polymer solid state electrolytes.Herein,fast ion conductor LiAlSiO_4(LASO) is incorporated into p...High ionic conductivity,good electrochemical stability,and satisfactory mechanical property are the crucial factors for polymer solid state electrolytes.Herein,fast ion conductor LiAlSiO_4(LASO) is incorporated into polyethylene oxide(PEO)-based solid-state electrolytes(SSEs).The SSEs containing LASO exhibit enhanced mechanical properties performance compared to pristine PEO-LiTFSI electrolyte.A reduced melting transition temperature of 40.57℃ is enabled by introducing LASO in to PEO-based SSE,which is beneficial to the motion of PEO chain and makes it possible for working at a moderate environment.Coupling with the enhanced motion of PEO,dissociation of the lithium salt,and conducting channel of LASO,the optimized composite polymer SSE exhibits a high ionic conductivity of 4.68×10^(-4),3.16×10^(-4) and 1.62×10^(-4) S cm^(-1) at 60,50 and 40℃,respectively.The corresponding LiFePO_4//Li solid-state battery exhibits high specific capacities of 166,160 and 139 mAh g^(-1) at 0.2 C under 60,40 and 25℃.In addition,it remains 130 mAh g^(-1) at 4.0 C,and maintains 91.74% after 500 cycles at 1.0 C under 60℃.This study provides a simple approach for developing ionic conductor-filled polymer electrolytes in solid-state lithium battery application.展开更多
FeS2/Fe composites were mechanochemically prepared with iron powder and pyrite for the stabilization of ferrite arsenate sludge(FAS).The effects of preparation parameters on stabilization performance were investigated...FeS2/Fe composites were mechanochemically prepared with iron powder and pyrite for the stabilization of ferrite arsenate sludge(FAS).The effects of preparation parameters on stabilization performance were investigated.The results show that the optimum conditions are FeS2/Fe molar ratio of 5:5,milling time of 2 h,ball-to-material mass ratio of 15:1 and milling with stainless steel ball.Then,the composites were characterized by XRD,SEM,FTIR,etc.The physicochemical properties of FeS2/Fe mixture change dramatically,which is responsible for its excellent performance.Finally,the stabilization process of FAS was optimized.When the FAS is mixed with composites at mass ratio of 4:1 and milled for 30 min,the As leaching concentration of FAS can be reduced from 639.15 to 4.74 mg/L with the stabilization ratio of 99.2%.展开更多
An optimized hydrothermal treatment was employed to stabilize the arsenic sulfide sludge(ASS). Under the optimal conditions(160 ℃, 2 h, liquid-to-solid(L/S) ratio of 1:1, and initial pH of 2), the leaching concentrat...An optimized hydrothermal treatment was employed to stabilize the arsenic sulfide sludge(ASS). Under the optimal conditions(160 ℃, 2 h, liquid-to-solid(L/S) ratio of 1:1, and initial pH of 2), the leaching concentrations of As and Cd decreased from 504.0 and 12.0 mg/L to 1.23 and 0.03 mg/L of the treated ASS, respectively. The results indicate that the stabilization of the ASS was achieved through structure transformation from the particles into a bulk and the speciation transformation of As and Cd. Besides, sulfur in the ASS could significantly improve the stabilization property due to its melting and polymerization.展开更多
Lift cycle assessment(LCA)methodology was applied to evaluating and comparing two waste acid disposal processes in zinc smelting.The results indicate that environmental impacts of gas−liquid vulcanization technologies...Lift cycle assessment(LCA)methodology was applied to evaluating and comparing two waste acid disposal processes in zinc smelting.The results indicate that environmental impacts of gas−liquid vulcanization technologies are human toxicity,abiotic depletion potential,and global warming risk,which are mainly caused in neutralizing−evaporating−crystallization unit and electrodialysis unit.As for traditional lime neutralization method,vulcanization unit is the main factor.In this regard,the total environmental impact of traditional lime neutralization method is much higher than that of gas−liquid vulcanization technologies.Furthermore,the sensitive analysis shows that electricity and sodium sulfide(60%)are sensitive factors in two waste acid disposal technologies.In addition,the total cost of disposing a functional unit waste acid in traditional lime neutralization process is nearly 27 times that of the gas−liquid vulcanization waste acid disposal technologies.展开更多
The microstructure and magnetic properties of iron arsenide(FeAs) with coarse-grain and nanocrystalline structure were investigated. Coarse-grain FeAs was synthesized through high-energy ball milling and heat treatmen...The microstructure and magnetic properties of iron arsenide(FeAs) with coarse-grain and nanocrystalline structure were investigated. Coarse-grain FeAs was synthesized through high-energy ball milling and heat treatment. Nanocrystalline FeAs was obtained by ball milling of coarse-grain FeAs. The results suggest that the reduced grain size of FeAs(from >100 to 32.4 nm) is accompanied by the introduction of internal strains up to 0.568% with ball milling time from 0 to 32 h. The magnetic properties of FeAs show that the coercivity is reduced from 29.2 to 15.6 kA/m and the magnetization is increased over time of milling. The low coercivity is mainly due to the small grain size stemmed from ball milling, while the increase of magnetization is primarily caused by the change of lattice parameters of FeAs and the emergence of superparamagnetic phase at the same time.展开更多
COVID-19 is caused by coronavirus SARS-CoV-2.Current systemic vaccines generally pro-vide limited protection against viral replication and shedding within the airway.Recombinant VSV(rVSV)is an effective vector which i...COVID-19 is caused by coronavirus SARS-CoV-2.Current systemic vaccines generally pro-vide limited protection against viral replication and shedding within the airway.Recombinant VSV(rVSV)is an effective vector which inducing potent and comprehensive immunities.Currently,there are two clinical trials investigating COVID-19vaccines based on VSV vectors.These vaccines were developed with spike protein of WA1 which administrated intramuscularly.Although intranasal route is ideal for activating mucosal immunity with VSV vector,safety is of concern.Thus,a highly attenuated rVSV with three amino acids mutations in matrix protein(VSV_(MT))was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern.It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently.VSV_(MT) indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein.With a single-dosed intranasal inoculation of rVSV_(ΔGMT)-S_(Δ21),potent SARS-CoV-2specific neutraliza-tion antibodies could be stimulated in animals,particularly in term of mucosal and cellular immunity.Strikingly,the chimeric VSV encoding S_(Δ21) of Delta-variant can induce more potent immune responses compared with those encoding S_(Δ21) of Omicron-or WA1-strain.VSV_(MT) is a promising platform to develop a mucosal vaccine for countering COVID-19.展开更多
With the proliferation of energy storage and power applications, electric vehicles particularly, solid-state batteries are considered as one of the most promising strategies to address the ever-increasing safety conce...With the proliferation of energy storage and power applications, electric vehicles particularly, solid-state batteries are considered as one of the most promising strategies to address the ever-increasing safety concern and high energy demand of power devices. Here, we demonstrate the Al4B2O9 nanorods-modified poly(ethylene oxide) (PEO)-based solid polymer electrolyte (ASPE) with high ionic conductivity, wide electrochemical window, decent mechanical property and nonflammable performance. Specifically, because of the longer-range ordered Li+ transfer channels conducted by the interaction between Al4B2O9 nanorods and PEO, the optimal ASPE (ASPE-1) shows excellent ionic conductivity of 4.35×10^−1 and 3.1×10^−1 S cm^−1 at 30 and 60℃, respectively. It also has good electrochemical stability at 60℃ with a decomposition voltage of 5.1 V. Besides, the assembled LiFePO4//Li cells show good cycling performance, delivering 155 mA h g−1 after 300 cycles at 1 C under 60℃, and present excellent low temperature adaptability, retaining over 125 mA h g^−1 after 90 cycles at 0.2 C under 30℃. These results verify that the addition of Al4B2O9 nanorods can effectively promote the integrated performance of solid polymer electrolyte.展开更多
New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) appear rapidly every few months.They have showed powerful adaptive ability to circumvent the immune system. To further understand SARS-CoV-2...New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) appear rapidly every few months.They have showed powerful adaptive ability to circumvent the immune system. To further understand SARS-CoV-2’s adaptability so as to seek for strategies to mitigate the emergence of new variants, herein we investigated the viral adaptation in the presence of broadly neutralizing antibodies and their combinations. First, we selected four broadly neutralizing antibodies, including pan-sarbecovirus and pan-betacoronavirus neutralizing antibodies that recognize distinct conserved regions on receptor-binding domain(RBD) or conserved stem-helix region on S2 subunit.Through binding competition analysis, we demonstrated that they were capable of simultaneously binding.Thereafter, a replication-competent vesicular stomatitis virus pseudotyped with SARS-CoV-2 spike protein was employed to study the viral adaptation. Twenty consecutive passages of the virus under the selective pressure of individual antibodies or their combinations were performed. It was found that it was not hard for the virus to adapt to broadly neutralizing antibodies, even for pan-sarbecovirus and pan-betacoronavirus antibodies. The virus was more and more difficult to escape the combinations of two/three/four antibodies. In addition, mutations in the viral population revealed by high-throughput sequencing showed that under the selective pressure of three/four combinational antibodies, viral mutations were not prone to present in the highly conserved region across betacoronaviruses(stem-helix region), while this was not true under the selective pressure of single/two antibodies.Importantly, combining neutralizing antibodies targeting RBD conserved regions and stem helix synergistically prevented the emergence of escape mutations. These studies will guide future vaccine and therapeutic development efforts and provide a rationale for the design of RBD-stem helix tandem vaccine, which may help to impede the generation of novel variants.展开更多
基金supported by National Natural Science Foundation of China(82160639)the Guizhou Provincial Science&Technology Program(QKHJC[2021]571)+2 种基金the Science&Technology Plan of Zunyi(ZSKHHZ[2020]87)the Xin Miao Foundation of Zunyi Medical University(QKPTRC[2019]-026)the PhD Start-Up Foundation of Zunyi Medical University(F-948).
文摘Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its impact on cancer prognosis remains unclear.Methods:We conducted a comprehensive analysis utilizing data from The Cancer Genome Atlas(TCGA)and other databases to assess the prognostic value and functional implications across various tumors.Silence of SLC22A1 RNA in glioma U251 cells was performed to access the impact of SLC22A1 on lowergrade glioma(LGG)progression.Results:Our findings demonstrated a significant correlation between SLC22A1 expression and the survival time of patients with various cancers(p<0.05).Importantly,we found the potential involvement of SLC22A1 in occurrence and progress of certain cancers,with a pronounced impact on LGG.Further examination of the SLC22A1-LGG relationship revealed its status as an independent risk factor for LGG,suggesting its potential involvement in regulating diverse immune pathways and metabolic activities.Chinese Glioma Genome Atlas(CGGA)data supported the reliability of the risk score as a prognostic and recurrence indicator,emphasizing the accuracy of the nomograph(1,3,and 5-year-AUC>0.8).Cell proliferation and clone formation experiment proved that decreased expression of SLC22A1 in glioma U251 cells inhibited glioma cell growth.Conclusion:Our findings suggest SLC22A1 has huge prospects as a promising biomarker and therapeutic target for LGG prognosis.SLC22A1 has only been proved to support cellular function previously.Our findings demonstrated a robust connection between the tumor microenvironment and functional proteins that maintain basal cell metabolism,which gifts unique tumor immune characteristics of gliomas.Additionally,we provide a highly practical prediction model for estimating the survival rate of LGG patients.
基金Projects(51904354,51634010)supported by the National Natural Science Foundation of ChinaProject(51825403)supported by the National Science Fund for Distinguished Young Scholars,ChinaProjects(2018YFC1903301,2018YFC1900301)supported by the National Key R&D Program of China。
文摘Physicochemical properties of arsenic sulfide sludge(ASS) from copper smelter(ASS-I) and lead-zinc smelter(ASS-II) were examined by XRD, Raman spectroscopy, SEM-EDS, TG-DTA, XPS and chemical phase analysis method. The toxicity characteristic leaching procedure(TCLP), Chinese standard leaching tests(CSLT), three-stage sequential extraction procedure(BCR) and batch leaching experiments(BLE) were used to investigate the environmental stability. The ASSs from different smelters had obviously different physicochemical and environmental properties. The phase composition and micrograph analysis indicate that ASS-I mainly consists of super refined flocculent particles including amorphous arsenic sulfide adhered with amorphous sulfur and that ASS-II mainly consists of amorphous arsenic sulfide. The valence state of arsenic in both sludges is trivalent, but the valence composition of sulfur is quite different. The ASSs have thermal instability properties. The results of TCLP and CSLT indicate that the concentrations of As and Pd in the leaching solution exceed the standard limits. More than 5% and 90% of arsenic are in the form of acid soluble and oxidizable fractions, respectively, which explains the high arsenic leaching toxicity and environmental activity of ASS. This research provides comprehensive information for the disposal of ASS from copper and lead-zinc smelter.
基金financial supports from the National Natural Science Foundation of China (51634010,51904354)the National Science Fund for Distinguished Young Scholars of China (51825403)+1 种基金the National Key R&D Program of China (2018YFC1900306,2019YFC1907405)Key Research and Development Program of Hunan Province,China (2019SK2291)。
文摘A new hydrometallurgical route for separation and recovery of Cu from Cu-As-bearing copper electrorefining black slime was developed. The proposed process comprised oxidation acid leaching of Cu-As-bearing slime and selective sulfide precipitation of Cu from the leachate. The effects of various process parameters on the leaching and precipitation of Cu and As were investigated. At the first stage, Cu extraction of 95.2% and As extraction of 97.6% were obtained at 80 ℃ after 4 h with initial H2 SO4 concentration of 1.0 mol/L and liquid-to-solid ratio of 10 mL/g. In addition, the leaching kinetics of Cu and As was successfully reproduced by the Avrami model, and the apparent activation energies were found to be 33.6 and 35.1 kJ/mol for the Cu and As leaching reaction, respectively, suggesting a combination of chemical reaction and diffusion control. During the selective sulfide precipitation, about 99.4% Cu was recovered as CuS, while only 0.1% As was precipitated under the optimal conditions using sulfide-to-copper ratio of 2.4:1, time of 1.5 h and temperature of 25 ℃.
基金financially supported by the National Natural Science Foundation of China (51804344)the Huxiang Youth Talent Support Program (Grant No. 2019RS2002)+2 种基金the Innovation and Entrepreneurship Project of Hunan Province, China (Grant No. 2018GK5026)the Innovation-Driven Project of Central South University (2020CX027)the Guangdong YangFan Plan for Postdoctor Program。
文摘High ionic conductivity,good electrochemical stability,and satisfactory mechanical property are the crucial factors for polymer solid state electrolytes.Herein,fast ion conductor LiAlSiO_4(LASO) is incorporated into polyethylene oxide(PEO)-based solid-state electrolytes(SSEs).The SSEs containing LASO exhibit enhanced mechanical properties performance compared to pristine PEO-LiTFSI electrolyte.A reduced melting transition temperature of 40.57℃ is enabled by introducing LASO in to PEO-based SSE,which is beneficial to the motion of PEO chain and makes it possible for working at a moderate environment.Coupling with the enhanced motion of PEO,dissociation of the lithium salt,and conducting channel of LASO,the optimized composite polymer SSE exhibits a high ionic conductivity of 4.68×10^(-4),3.16×10^(-4) and 1.62×10^(-4) S cm^(-1) at 60,50 and 40℃,respectively.The corresponding LiFePO_4//Li solid-state battery exhibits high specific capacities of 166,160 and 139 mAh g^(-1) at 0.2 C under 60,40 and 25℃.In addition,it remains 130 mAh g^(-1) at 4.0 C,and maintains 91.74% after 500 cycles at 1.0 C under 60℃.This study provides a simple approach for developing ionic conductor-filled polymer electrolytes in solid-state lithium battery application.
基金Projects(2018YFC1900305,2018YFC1903301)supported by the National Key R&D Program of ChinaProject(51825403)supported by the National Natural Science Foundation for Distinguished Young Scholars of China+1 种基金Project(51634010)supported by the National Natural Science Foundation of ChinaProject(2017RS3010)supported by the Science and Technology Program of Hunan Province,China
文摘FeS2/Fe composites were mechanochemically prepared with iron powder and pyrite for the stabilization of ferrite arsenate sludge(FAS).The effects of preparation parameters on stabilization performance were investigated.The results show that the optimum conditions are FeS2/Fe molar ratio of 5:5,milling time of 2 h,ball-to-material mass ratio of 15:1 and milling with stainless steel ball.Then,the composites were characterized by XRD,SEM,FTIR,etc.The physicochemical properties of FeS2/Fe mixture change dramatically,which is responsible for its excellent performance.Finally,the stabilization process of FAS was optimized.When the FAS is mixed with composites at mass ratio of 4:1 and milled for 30 min,the As leaching concentration of FAS can be reduced from 639.15 to 4.74 mg/L with the stabilization ratio of 99.2%.
基金supported by the National Natural Science Foundation of China for Distinguished Young Scholars (No. 51825403)the National Key R&D Program of China (Nos. 2018YFC1903301, 2018YFC1900301)the National Natural Science Foundation of China (Nos. 51634010, 51904354)。
文摘An optimized hydrothermal treatment was employed to stabilize the arsenic sulfide sludge(ASS). Under the optimal conditions(160 ℃, 2 h, liquid-to-solid(L/S) ratio of 1:1, and initial pH of 2), the leaching concentrations of As and Cd decreased from 504.0 and 12.0 mg/L to 1.23 and 0.03 mg/L of the treated ASS, respectively. The results indicate that the stabilization of the ASS was achieved through structure transformation from the particles into a bulk and the speciation transformation of As and Cd. Besides, sulfur in the ASS could significantly improve the stabilization property due to its melting and polymerization.
基金the National Key R&D Program of China(Nos.2018YFC1903304,2019YFC1907405)National Natural Science Foundation of China(No.51904354).
文摘Lift cycle assessment(LCA)methodology was applied to evaluating and comparing two waste acid disposal processes in zinc smelting.The results indicate that environmental impacts of gas−liquid vulcanization technologies are human toxicity,abiotic depletion potential,and global warming risk,which are mainly caused in neutralizing−evaporating−crystallization unit and electrodialysis unit.As for traditional lime neutralization method,vulcanization unit is the main factor.In this regard,the total environmental impact of traditional lime neutralization method is much higher than that of gas−liquid vulcanization technologies.Furthermore,the sensitive analysis shows that electricity and sodium sulfide(60%)are sensitive factors in two waste acid disposal technologies.In addition,the total cost of disposing a functional unit waste acid in traditional lime neutralization process is nearly 27 times that of the gas−liquid vulcanization waste acid disposal technologies.
基金the financial support from National Key Technologies R&D Program of China (No. 2018YFC1900302)。
文摘The microstructure and magnetic properties of iron arsenide(FeAs) with coarse-grain and nanocrystalline structure were investigated. Coarse-grain FeAs was synthesized through high-energy ball milling and heat treatment. Nanocrystalline FeAs was obtained by ball milling of coarse-grain FeAs. The results suggest that the reduced grain size of FeAs(from >100 to 32.4 nm) is accompanied by the introduction of internal strains up to 0.568% with ball milling time from 0 to 32 h. The magnetic properties of FeAs show that the coercivity is reduced from 29.2 to 15.6 kA/m and the magnetization is increased over time of milling. The low coercivity is mainly due to the small grain size stemmed from ball milling, while the increase of magnetization is primarily caused by the change of lattice parameters of FeAs and the emergence of superparamagnetic phase at the same time.
基金supported by Biomedicine and Technology Supporting Project of Shanghai Science and Technology Innovation Plan(Grant Nos.22S11902200 and 20S11904900,China)Open grant of Engineering Research Center of Cell&Therapeutic Antibody,Ministry of Education,Shanghai Jiao Tong University(Grant No.19X110020009-003,China).
文摘COVID-19 is caused by coronavirus SARS-CoV-2.Current systemic vaccines generally pro-vide limited protection against viral replication and shedding within the airway.Recombinant VSV(rVSV)is an effective vector which inducing potent and comprehensive immunities.Currently,there are two clinical trials investigating COVID-19vaccines based on VSV vectors.These vaccines were developed with spike protein of WA1 which administrated intramuscularly.Although intranasal route is ideal for activating mucosal immunity with VSV vector,safety is of concern.Thus,a highly attenuated rVSV with three amino acids mutations in matrix protein(VSV_(MT))was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern.It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently.VSV_(MT) indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein.With a single-dosed intranasal inoculation of rVSV_(ΔGMT)-S_(Δ21),potent SARS-CoV-2specific neutraliza-tion antibodies could be stimulated in animals,particularly in term of mucosal and cellular immunity.Strikingly,the chimeric VSV encoding S_(Δ21) of Delta-variant can induce more potent immune responses compared with those encoding S_(Δ21) of Omicron-or WA1-strain.VSV_(MT) is a promising platform to develop a mucosal vaccine for countering COVID-19.
基金financially supported by the National Natural Science Foundation of China (51804344)the Huxiang Youth Talent Support Program (2019RS2002)+2 种基金the Innovation and Entrepreneurship Project of Hunan Province,China (2018GK5026)the Innovation-Driven Project of Central South University (2020CX027)Guangdong Yang Fan Plan for Postdoctor Program
文摘With the proliferation of energy storage and power applications, electric vehicles particularly, solid-state batteries are considered as one of the most promising strategies to address the ever-increasing safety concern and high energy demand of power devices. Here, we demonstrate the Al4B2O9 nanorods-modified poly(ethylene oxide) (PEO)-based solid polymer electrolyte (ASPE) with high ionic conductivity, wide electrochemical window, decent mechanical property and nonflammable performance. Specifically, because of the longer-range ordered Li+ transfer channels conducted by the interaction between Al4B2O9 nanorods and PEO, the optimal ASPE (ASPE-1) shows excellent ionic conductivity of 4.35×10^−1 and 3.1×10^−1 S cm^−1 at 30 and 60℃, respectively. It also has good electrochemical stability at 60℃ with a decomposition voltage of 5.1 V. Besides, the assembled LiFePO4//Li cells show good cycling performance, delivering 155 mA h g−1 after 300 cycles at 1 C under 60℃, and present excellent low temperature adaptability, retaining over 125 mA h g^−1 after 90 cycles at 0.2 C under 30℃. These results verify that the addition of Al4B2O9 nanorods can effectively promote the integrated performance of solid polymer electrolyte.
基金funded by the National Natural Science Foundation of China(81773621,82073751 to J.Z.)the National Science and Technology Major Project“Key New Drug Creation and Manufacturing Program”of China(No.2019ZX09732001-019 to J.Z.)+1 种基金the Key R&D Supporting Program(Special Support for Developing Medicine for Infectious Diseases)from the Administration of Chinese and Singapore Tianjin Eco-city to Jecho Biopharmaceuticals Ltd.Co.the Shanghai Jiao Tong University“Crossing Medical and Engineering”grant(20X190020003 to J.Z.)
文摘New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) appear rapidly every few months.They have showed powerful adaptive ability to circumvent the immune system. To further understand SARS-CoV-2’s adaptability so as to seek for strategies to mitigate the emergence of new variants, herein we investigated the viral adaptation in the presence of broadly neutralizing antibodies and their combinations. First, we selected four broadly neutralizing antibodies, including pan-sarbecovirus and pan-betacoronavirus neutralizing antibodies that recognize distinct conserved regions on receptor-binding domain(RBD) or conserved stem-helix region on S2 subunit.Through binding competition analysis, we demonstrated that they were capable of simultaneously binding.Thereafter, a replication-competent vesicular stomatitis virus pseudotyped with SARS-CoV-2 spike protein was employed to study the viral adaptation. Twenty consecutive passages of the virus under the selective pressure of individual antibodies or their combinations were performed. It was found that it was not hard for the virus to adapt to broadly neutralizing antibodies, even for pan-sarbecovirus and pan-betacoronavirus antibodies. The virus was more and more difficult to escape the combinations of two/three/four antibodies. In addition, mutations in the viral population revealed by high-throughput sequencing showed that under the selective pressure of three/four combinational antibodies, viral mutations were not prone to present in the highly conserved region across betacoronaviruses(stem-helix region), while this was not true under the selective pressure of single/two antibodies.Importantly, combining neutralizing antibodies targeting RBD conserved regions and stem helix synergistically prevented the emergence of escape mutations. These studies will guide future vaccine and therapeutic development efforts and provide a rationale for the design of RBD-stem helix tandem vaccine, which may help to impede the generation of novel variants.