In this study, a three dimensional(3D) numerical model of six-degrees-of-freedom(6DOF) is applied to simulate the water entries of twin spheres side-by-side at different lateral distances and time intervals.The turbul...In this study, a three dimensional(3D) numerical model of six-degrees-of-freedom(6DOF) is applied to simulate the water entries of twin spheres side-by-side at different lateral distances and time intervals.The turbulence structure is described using the shear-stress transport k-ω(SST k-ω) model, and the volume of fluid(VOF) method is used to track the complex air-liquid interface. The motion of spheres during water entry is simulated using an independent overset grid. The numerical model is verified by comparing the cavity evolution results from simulations and experiments. Numerical results reveal that the time interval between the twin water entries evidently affects cavity expansion and contraction behaviors in the radial direction. However, this influence is significantly weakened by increasing the lateral distance between the two spheres. In synchronous water entries, pressure is reduced on the midline of two cavities during surface closure, which is directly related to the cavity volume. The evolution of vortexes inside the two cavities is analyzed using a velocity vector field, which is affected by the lateral distance and time interval of water entries.展开更多
New solid backfill mining technology provides unique technical advantages for ‘‘three-under'' coal mining which refers to coal resources trapped under buildings, railways, and water bodies. This technology h...New solid backfill mining technology provides unique technical advantages for ‘‘three-under'' coal mining which refers to coal resources trapped under buildings, railways, and water bodies. This technology has a much higher recovery rate and can effectively control the surface subsidence. However, successful application of this technology depends heavily on geological conditions. To avoid the disadvantages associated with downward mining and overhead backfilling with this new technology, a new advanced solid backfill mining design with two pre-driving entries is proposed here to ensure the backfill effect. Taking Huayuan coal mine as an example, this paper tests the double gob-side entries retaining with no pillar left scheme and optimizes an integrated technology setup for backfill mining and gob-side entry retaining. Field applications show that the recovery rate increased from 40% for strip mining to 85% for backfill mining. Moreover, the new backfill technology allowed for better control over the surrounding rock deformation caused by the gob-side entry retaining effect and better control of ground subsidence as compared to strip mining.展开更多
This contribution describes development and application of a user-friendly finite element program,UT3PC, to address three important problems in underground coal mine design:(1) safety of main entries,(2) barrier pilla...This contribution describes development and application of a user-friendly finite element program,UT3PC, to address three important problems in underground coal mine design:(1) safety of main entries,(2) barrier pillar size needed for entry protection, and(3) safety of bleeder entries during the advance of an adjacent longwall panel.While the finite element method is by far the most popular engineering design tool of the digital age, widespread use by the mining community has been impeded by the relatively high cost of and the need for lengthy specialized training in numerical methods.Implementation of UT3PC overcomes these impediments in three easy steps.First, a material properties file is prepared for the considered site.Next, mesh generation is automatic through an interactive process.A third and last step is simply execution of the program.Examples using data from several western coal mines illustrate the ease of using the application for analysis of main entries, barrier pillars, and bleeder entry safety.展开更多
Based on a large amount of field investigation and observations, the paper analyzes and summarizes the mining depths and depth distribution of coal mines in China, discusses the characteristics of undrground pressure ...Based on a large amount of field investigation and observations, the paper analyzes and summarizes the mining depths and depth distribution of coal mines in China, discusses the characteristics of undrground pressure appearance in the entries of deep mining, points out some characteristics of surtounding rocks when rHo> =0.5, such as obvious rheologital deformation,and puts forward the main principles of supporting the entries in deep mining展开更多
Evaluation for blast resistances of rice entries of 20th to 23rd International Rice Blast Nursery (IRBN) was conducted at CNRRI during 1990-1993. The resistance to seedling blast (SB) was evaluated in a greenhouse at ...Evaluation for blast resistances of rice entries of 20th to 23rd International Rice Blast Nursery (IRBN) was conducted at CNRRI during 1990-1993. The resistance to seedling blast (SB) was evaluated in a greenhouse at 3-4 leaf stage with artificial inoculation while resistance to leaf blast (LB) and neck blast (NB) were evaluated in the natural field as instructed by the International Network of Genetic Evaluation for Rice (INGER). Materials with high level of blast resistance and good agronomic traits were selected and展开更多
Let(g_(n))_(n≥1) be a sequence of independent and identically distributed positive random d×d matrices and consider the matrix product G_(n)=g_(n)…g_1.Under suitable conditions,we establish the Berry-Esseen bou...Let(g_(n))_(n≥1) be a sequence of independent and identically distributed positive random d×d matrices and consider the matrix product G_(n)=g_(n)…g_1.Under suitable conditions,we establish the Berry-Esseen bounds on the rate of convergence in the central limit theorem and Cramer-type moderate deviation expansions,for any matrix norm ‖G_(n)‖ of G_(n),its entries G_(n)^(i,j) and its spectral radius ρ(G_(n)).Extended versions of their joint law with the direction of the random walk G_(n)x are also established,where x is a starting point in the unit sphere of R~d.展开更多
Inspired by Phil Benson's study on the relations between ethnocentrism and the China-related entries in the OED2, this paper attempts to further examine how the image of China, a so--called "peripheral object of Wes...Inspired by Phil Benson's study on the relations between ethnocentrism and the China-related entries in the OED2, this paper attempts to further examine how the image of China, a so--called "peripheral object of Western knowledge," has been (ntis-) constructed in the dictionary, particularly its latest 2009 CD-ROM version, into which many laudable updates, including corrections and supplements, have been meticulously incorporated. It argues that ( 1 ) although British imperialism was a closed chapter, its vestiges can still be spotted in the dictionary text, not only in the quotations, which preserve historical information rather than reflect the editors' opinions, but also in the definitions and notes, which betray primarily the thoughts of these editors, ( 2 ) to an average user, the OED, with its legendary philological authority, is very likely to project " historical objectivity" into some problematic contents and thus misleads an innocent and uninformed mind, and (3) if ethnocentrism is an unavoidable component in the OED1 and OED2, then the editorial team of the OED3 in the making would do well to introduce into their work an element of" " entholocalism," by which is meant the ideological neutrality as well as the technical accuracy of encyclopedic information about such important peripheral objects as China, the most populous country and a fast growing economy, in the world in which the English language against the backdrop of globalization has firmly established itself as the international lingua fianca without rival. So long as it is intended to remain a historical dictionary true to its name, the OED ought to push forward, in the form of new editions, with the times.展开更多
This paper explores the deformation mechanism and control technology of roof pre-splitting for gob-side entries in hard roof full-mechanized longwall caving panel(LTCC).The investigation utilizes a comprehensive appro...This paper explores the deformation mechanism and control technology of roof pre-splitting for gob-side entries in hard roof full-mechanized longwall caving panel(LTCC).The investigation utilizes a comprehensive approach that integrates field monitoring,theoretical analysis,and numerical simulation.Theoretical analysis has illuminated the influence of the length of the lateral cantilever beam of the main roof(LCBM)above the roadway on the stability of the gob-side entry behind the panel.Numerical simulations have further revealed that the longer LCBM results in heightened vertical stress within the coal pillar,developed cracks around the roadway,and more pronounced damage to the roadway.Moreover,numerical simulations also demonstrate the potential of roof pre-splitting technology in optimizing the fracture position of the hard roof.This technology significantly reduces the length of the LCBM,thereby alleviating stress concentration in the coal pillars and integrated coal rib while minimizing the destruction of the gob-side entry.Therefore,this manuscript first proposes the use of roof pre-splitting technology to control roadway deformation,and automatically retain the entry within a hard roof LTCC panel.Field implementation has demonstrated that the proposed automatically retained entry by roof pre-splitting technology effectively reduces gob-side entry deformation and achieves automatically retained entry.展开更多
This study is the result of long-term efforts of the authors’team to assess ground response of gob-side entry by roof cutting(GSERC)with hard main roof,aiming at scientific control for GSERC deformation.A comprehensi...This study is the result of long-term efforts of the authors’team to assess ground response of gob-side entry by roof cutting(GSERC)with hard main roof,aiming at scientific control for GSERC deformation.A comprehensive field measurement program was conducted to determine entry deformation,roof fracture zone,and anchor bolt(cable)loading.The results indicate that GSERC deformation presents asymmetric characteristics.The maximum convergence near roof cutting side is 458 mm during the primary use process and 1120 mm during the secondary reuse process.The entry deformation is closely associated with the primary development stage,primary use stage,and secondary reuse stage.The key block movement of roof cutting structure,a complex stress environment,and a mismatch in the supporting design scheme are the failure mechanism of GSERC.A controlling ideology for mining states,including regional and stage divisions,was proposed.Both dynamic and permanent support schemes have been implemented in the field.Engineering practice results indicate that the new support scheme can efficiently ensure long-term entry safety and could be a reliable approach for other engineering practices.展开更多
The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1...The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.展开更多
Objectives To identify the 5'untranslated region of Zika virus(ZIKV 5'UTR)RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site(IRES)located...Objectives To identify the 5'untranslated region of Zika virus(ZIKV 5'UTR)RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site(IRES)located in ZIKV 5'UTR and virus production.Methods Interacting proteins in U251 cells were captured using tRSA-tagged ZIKV 5'UTR RNA and tRSA-ZIKV 5'UTR RNA-binding proteins were visualized by SDS-PAGE silver staining,Subsequently,liquid chromatographytandem mass spectrometry(LC-MS/MS),bioinformatics analysis,and Western blot were used to identify the candidate proteins binding to ZIKV 5'UTR.Dicistronic expression assay and plaque forming assay were performed to analyze the effect of the binding protein on ZIKV IRES activity and ZIKV production,respecitvely.Results tRSA RNA pull-down assay,LC-MS/MS,and Western blot analysis showed that polypyrimidine tractbinding protein(PTB)bound to the ZIKV 5'UTR.Furthermore,dual luciferase reporter assay revealed that overexpression of PTB significantly enhanced the IRES activity of ZIKV(t=10.220,P<0.001),while PTB knockdown had the opposite effect(t=4.897,P<0.01).Additionally,virus plaque forming assay demonstrated that up-regulation of PTB expression significantly enhanced viral titer(t=6.400,P<0.01),whereas reducing PTB expression level weakened virus infectivity(t=5.055,P<0.01).Conclusion PTB positively interacts with the ZIKV 5'UTR and enhances IRES activity and virus production.展开更多
Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United States.It is associated with significant morbidity and mortality due to cirrhosis,live...Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United States.It is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver cancer.Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver complications.However,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver events.Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBV DNA.Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.展开更多
Using the adoption and expansion of wired telegraph in China during the late 19^(th) century,this paper investigates the effect of cost reductions for knowledge exchange on China’s industrial growth before the outbre...Using the adoption and expansion of wired telegraph in China during the late 19^(th) century,this paper investigates the effect of cost reductions for knowledge exchange on China’s industrial growth before the outbreak of the War of Resistance Against Japanese Aggression(1931-1945),thus testing Baldwin’s theory of“the Great Convergence”in which developing countries are empowered by information and communication technologies.Based on panel data of 1858-1937,we found that wired telegraph access had a significantly positive effect,as well as a long-term growth effect,on the entry of industrial enterprises.Our mechanism analysis indicates that wired telegraph access accelerated early-stage industrialization in localities by encouraging market integration,human capital accumulation,and auxiliary commercial organizations.Only a few countries firmly asserted their telegraph sovereignty and set up their own workforce educational system during telegraph adoption.This explains why the Great Convergence arising from technology importation only occurred in a small number of countries.Our findings contribute to understanding the source of China’s modern industrial progress,as well as why global inequities remain.展开更多
The CALPHAD thermodynamic databases are very useful to analyze the complex chemical reactions happening in high temperature material process.The FactSage thermodynamic database can be used to calculate complex phase d...The CALPHAD thermodynamic databases are very useful to analyze the complex chemical reactions happening in high temperature material process.The FactSage thermodynamic database can be used to calculate complex phase diagrams and equilibrium phases involving refractories in industrial process.In this study,the FactSage thermodynamic database relevant to ZrO_(2)-based refractories was reviewed and the application of the database to understanding the corrosion of continuous casting nozzle refractories in steelmaking was presented.展开更多
With the significant increase of the number of entry mails in China, mail inspection has become more and more challenge. Australia and New Zealand are the two countries recognized as the ones with the most stringent i...With the significant increase of the number of entry mails in China, mail inspection has become more and more challenge. Australia and New Zealand are the two countries recognized as the ones with the most stringent inspection and quarantine measures in the world. The mail inspection work in China, Australia and New Zealand was compared on the aspects of mail quarantine system, inspection, quarantine treatment and punishment, based on which something worth learning and referring could be found and some suggestions were put forward, with the aim to provide theoretical basis for the animal and plant quarantine of entry mails.展开更多
In order to analyze and explain the mechanism of the two small inhibitors (ADS-JI and ADS-J2) binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these c...In order to analyze and explain the mechanism of the two small inhibitors (ADS-JI and ADS-J2) binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The binding interactions of gp41-molecule and free energies of binding are obtained through molecular dynamics simulation and molecular mechanic/Poisson- Boitzmann surface area ( MM/PBSA ) calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point tbr further refinement of small molecular gp41 inhibitors.展开更多
基金China Academy of Launch Vehicle Technology(Grant No.CALT-2022-03)Science and Technology on Underwater Information and Control Laboratory(Grant No.2021-JCJQ-LB-030-05).
文摘In this study, a three dimensional(3D) numerical model of six-degrees-of-freedom(6DOF) is applied to simulate the water entries of twin spheres side-by-side at different lateral distances and time intervals.The turbulence structure is described using the shear-stress transport k-ω(SST k-ω) model, and the volume of fluid(VOF) method is used to track the complex air-liquid interface. The motion of spheres during water entry is simulated using an independent overset grid. The numerical model is verified by comparing the cavity evolution results from simulations and experiments. Numerical results reveal that the time interval between the twin water entries evidently affects cavity expansion and contraction behaviors in the radial direction. However, this influence is significantly weakened by increasing the lateral distance between the two spheres. In synchronous water entries, pressure is reduced on the midline of two cavities during surface closure, which is directly related to the cavity volume. The evolution of vortexes inside the two cavities is analyzed using a velocity vector field, which is affected by the lateral distance and time interval of water entries.
基金supported by the Fundamental Research Funds program for the Central Universities (No. 2014RC02)the Research Innovation Program for College Graduates of Jiangsu Province (No. CXLX13_951)Qing Lan Project
文摘New solid backfill mining technology provides unique technical advantages for ‘‘three-under'' coal mining which refers to coal resources trapped under buildings, railways, and water bodies. This technology has a much higher recovery rate and can effectively control the surface subsidence. However, successful application of this technology depends heavily on geological conditions. To avoid the disadvantages associated with downward mining and overhead backfilling with this new technology, a new advanced solid backfill mining design with two pre-driving entries is proposed here to ensure the backfill effect. Taking Huayuan coal mine as an example, this paper tests the double gob-side entries retaining with no pillar left scheme and optimizes an integrated technology setup for backfill mining and gob-side entry retaining. Field applications show that the recovery rate increased from 40% for strip mining to 85% for backfill mining. Moreover, the new backfill technology allowed for better control over the surrounding rock deformation caused by the gob-side entry retaining effect and better control of ground subsidence as compared to strip mining.
文摘This contribution describes development and application of a user-friendly finite element program,UT3PC, to address three important problems in underground coal mine design:(1) safety of main entries,(2) barrier pillar size needed for entry protection, and(3) safety of bleeder entries during the advance of an adjacent longwall panel.While the finite element method is by far the most popular engineering design tool of the digital age, widespread use by the mining community has been impeded by the relatively high cost of and the need for lengthy specialized training in numerical methods.Implementation of UT3PC overcomes these impediments in three easy steps.First, a material properties file is prepared for the considered site.Next, mesh generation is automatic through an interactive process.A third and last step is simply execution of the program.Examples using data from several western coal mines illustrate the ease of using the application for analysis of main entries, barrier pillars, and bleeder entry safety.
文摘Based on a large amount of field investigation and observations, the paper analyzes and summarizes the mining depths and depth distribution of coal mines in China, discusses the characteristics of undrground pressure appearance in the entries of deep mining, points out some characteristics of surtounding rocks when rHo> =0.5, such as obvious rheologital deformation,and puts forward the main principles of supporting the entries in deep mining
文摘Evaluation for blast resistances of rice entries of 20th to 23rd International Rice Blast Nursery (IRBN) was conducted at CNRRI during 1990-1993. The resistance to seedling blast (SB) was evaluated in a greenhouse at 3-4 leaf stage with artificial inoculation while resistance to leaf blast (LB) and neck blast (NB) were evaluated in the natural field as instructed by the International Network of Genetic Evaluation for Rice (INGER). Materials with high level of blast resistance and good agronomic traits were selected and
基金supported by Deutsche Forschungsgemeinschaft (DFG) (Grant No. ME 4473/2-1)the Centre Henri Lebesgue (CHL) (Grant No. ANR-11-LABX-0020-01)National Natural Science Foundation of China (Grants Nos. 11971063, 11731012, 12271062 and 12288201)。
文摘Let(g_(n))_(n≥1) be a sequence of independent and identically distributed positive random d×d matrices and consider the matrix product G_(n)=g_(n)…g_1.Under suitable conditions,we establish the Berry-Esseen bounds on the rate of convergence in the central limit theorem and Cramer-type moderate deviation expansions,for any matrix norm ‖G_(n)‖ of G_(n),its entries G_(n)^(i,j) and its spectral radius ρ(G_(n)).Extended versions of their joint law with the direction of the random walk G_(n)x are also established,where x is a starting point in the unit sphere of R~d.
文摘Inspired by Phil Benson's study on the relations between ethnocentrism and the China-related entries in the OED2, this paper attempts to further examine how the image of China, a so--called "peripheral object of Western knowledge," has been (ntis-) constructed in the dictionary, particularly its latest 2009 CD-ROM version, into which many laudable updates, including corrections and supplements, have been meticulously incorporated. It argues that ( 1 ) although British imperialism was a closed chapter, its vestiges can still be spotted in the dictionary text, not only in the quotations, which preserve historical information rather than reflect the editors' opinions, but also in the definitions and notes, which betray primarily the thoughts of these editors, ( 2 ) to an average user, the OED, with its legendary philological authority, is very likely to project " historical objectivity" into some problematic contents and thus misleads an innocent and uninformed mind, and (3) if ethnocentrism is an unavoidable component in the OED1 and OED2, then the editorial team of the OED3 in the making would do well to introduce into their work an element of" " entholocalism," by which is meant the ideological neutrality as well as the technical accuracy of encyclopedic information about such important peripheral objects as China, the most populous country and a fast growing economy, in the world in which the English language against the backdrop of globalization has firmly established itself as the international lingua fianca without rival. So long as it is intended to remain a historical dictionary true to its name, the OED ought to push forward, in the form of new editions, with the times.
基金Project(52104139)supported by the National Natural Science Foundation of China Youth Science FoundationProject(SKLGDUEK2132)supported by the State Key Laboratory for Geomechanics and Deep Underground Engineering,China University of Mining and Technology/China University of Mining and Technology-BeijingProjects([2020]2Y030,[2020]2Y019,[2020j3007,[2020]3008,and[2022j0il]supported by the Guizhou Province Science and Technology Planning,China Project(2022B01051)supported by the Key Research and Development Special Tasks of Xinjiang,China。
文摘This paper explores the deformation mechanism and control technology of roof pre-splitting for gob-side entries in hard roof full-mechanized longwall caving panel(LTCC).The investigation utilizes a comprehensive approach that integrates field monitoring,theoretical analysis,and numerical simulation.Theoretical analysis has illuminated the influence of the length of the lateral cantilever beam of the main roof(LCBM)above the roadway on the stability of the gob-side entry behind the panel.Numerical simulations have further revealed that the longer LCBM results in heightened vertical stress within the coal pillar,developed cracks around the roadway,and more pronounced damage to the roadway.Moreover,numerical simulations also demonstrate the potential of roof pre-splitting technology in optimizing the fracture position of the hard roof.This technology significantly reduces the length of the LCBM,thereby alleviating stress concentration in the coal pillars and integrated coal rib while minimizing the destruction of the gob-side entry.Therefore,this manuscript first proposes the use of roof pre-splitting technology to control roadway deformation,and automatically retain the entry within a hard roof LTCC panel.Field implementation has demonstrated that the proposed automatically retained entry by roof pre-splitting technology effectively reduces gob-side entry deformation and achieves automatically retained entry.
基金Project(WPUKFJJ2019-19)supported by the Open Fund of State Key Laboratory of Water Resource Protection and Utilization in Coal Mining,ChinaProject(51974317)supported by the National Natural Science Foundation of China。
文摘This study is the result of long-term efforts of the authors’team to assess ground response of gob-side entry by roof cutting(GSERC)with hard main roof,aiming at scientific control for GSERC deformation.A comprehensive field measurement program was conducted to determine entry deformation,roof fracture zone,and anchor bolt(cable)loading.The results indicate that GSERC deformation presents asymmetric characteristics.The maximum convergence near roof cutting side is 458 mm during the primary use process and 1120 mm during the secondary reuse process.The entry deformation is closely associated with the primary development stage,primary use stage,and secondary reuse stage.The key block movement of roof cutting structure,a complex stress environment,and a mismatch in the supporting design scheme are the failure mechanism of GSERC.A controlling ideology for mining states,including regional and stage divisions,was proposed.Both dynamic and permanent support schemes have been implemented in the field.Engineering practice results indicate that the new support scheme can efficiently ensure long-term entry safety and could be a reliable approach for other engineering practices.
基金National Institutes of Health(NIH)(grants R01 A/130092 and Al161085).
文摘The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.
文摘Objectives To identify the 5'untranslated region of Zika virus(ZIKV 5'UTR)RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site(IRES)located in ZIKV 5'UTR and virus production.Methods Interacting proteins in U251 cells were captured using tRSA-tagged ZIKV 5'UTR RNA and tRSA-ZIKV 5'UTR RNA-binding proteins were visualized by SDS-PAGE silver staining,Subsequently,liquid chromatographytandem mass spectrometry(LC-MS/MS),bioinformatics analysis,and Western blot were used to identify the candidate proteins binding to ZIKV 5'UTR.Dicistronic expression assay and plaque forming assay were performed to analyze the effect of the binding protein on ZIKV IRES activity and ZIKV production,respecitvely.Results tRSA RNA pull-down assay,LC-MS/MS,and Western blot analysis showed that polypyrimidine tractbinding protein(PTB)bound to the ZIKV 5'UTR.Furthermore,dual luciferase reporter assay revealed that overexpression of PTB significantly enhanced the IRES activity of ZIKV(t=10.220,P<0.001),while PTB knockdown had the opposite effect(t=4.897,P<0.01).Additionally,virus plaque forming assay demonstrated that up-regulation of PTB expression significantly enhanced viral titer(t=6.400,P<0.01),whereas reducing PTB expression level weakened virus infectivity(t=5.055,P<0.01).Conclusion PTB positively interacts with the ZIKV 5'UTR and enhances IRES activity and virus production.
文摘Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United States.It is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver cancer.Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver complications.However,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver events.Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBV DNA.Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.
基金supported by the General Project of the National Social Science Fund of China(Grant No.NSSFC)“Research on the Changes of Modern East Asian Order”(Grant No.18BSS028).
文摘Using the adoption and expansion of wired telegraph in China during the late 19^(th) century,this paper investigates the effect of cost reductions for knowledge exchange on China’s industrial growth before the outbreak of the War of Resistance Against Japanese Aggression(1931-1945),thus testing Baldwin’s theory of“the Great Convergence”in which developing countries are empowered by information and communication technologies.Based on panel data of 1858-1937,we found that wired telegraph access had a significantly positive effect,as well as a long-term growth effect,on the entry of industrial enterprises.Our mechanism analysis indicates that wired telegraph access accelerated early-stage industrialization in localities by encouraging market integration,human capital accumulation,and auxiliary commercial organizations.Only a few countries firmly asserted their telegraph sovereignty and set up their own workforce educational system during telegraph adoption.This explains why the Great Convergence arising from technology importation only occurred in a small number of countries.Our findings contribute to understanding the source of China’s modern industrial progress,as well as why global inequities remain.
基金Tata Steel Netherlands,Posco,Hyundai Steel,Nucor Steel,RioTinto,Nippon Steel Corp.,JFE Steel,Voestalpine,RHi-Magnesita,Doosan Enerbility,Seah Besteel,Umicore,Vesuvius and Schott AG are gratefully acknowledged.
文摘The CALPHAD thermodynamic databases are very useful to analyze the complex chemical reactions happening in high temperature material process.The FactSage thermodynamic database can be used to calculate complex phase diagrams and equilibrium phases involving refractories in industrial process.In this study,the FactSage thermodynamic database relevant to ZrO_(2)-based refractories was reviewed and the application of the database to understanding the corrosion of continuous casting nozzle refractories in steelmaking was presented.
文摘With the significant increase of the number of entry mails in China, mail inspection has become more and more challenge. Australia and New Zealand are the two countries recognized as the ones with the most stringent inspection and quarantine measures in the world. The mail inspection work in China, Australia and New Zealand was compared on the aspects of mail quarantine system, inspection, quarantine treatment and punishment, based on which something worth learning and referring could be found and some suggestions were put forward, with the aim to provide theoretical basis for the animal and plant quarantine of entry mails.
基金The National Basic Research Program of China (973 Program) (No. 2007CB936300)
文摘In order to analyze and explain the mechanism of the two small inhibitors (ADS-JI and ADS-J2) binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The binding interactions of gp41-molecule and free energies of binding are obtained through molecular dynamics simulation and molecular mechanic/Poisson- Boitzmann surface area ( MM/PBSA ) calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point tbr further refinement of small molecular gp41 inhibitors.