Monoclinic SrAl_(2)Si_(2)O_(8) ceramics for Sr immobilization were prepared by a liquid-phase sintering method.The sintering temperature,mineral phase composition,microstructure,flexural strength,bulk density,and Sr i...Monoclinic SrAl_(2)Si_(2)O_(8) ceramics for Sr immobilization were prepared by a liquid-phase sintering method.The sintering temperature,mineral phase composition,microstructure,flexural strength,bulk density,and Sr ion leaching characteristics of the SrAl_(2)Si_(2)O_(8) ceramics were investigated.A crystalline monoclinic SrAl_(2)Si_(2)O_(8) phase formed through liquid-phase sintering at 1223 K.The introduction of four flux agents(B_(2)O_(3),CaO·2B_(2)O_(3),SrO·2B_(2)O_(3),and BaO·2B_(2)O_(3))to the SrAl_(2)Si_(2)O_(8) ceramics not only reduced the densification temperature and decreased the volatilization of Sr during high-temperature sintering but also impacted the mechanical properties of the ceramics.Product consistency tests showed that the leaching concentration of Sr ions in the sample with flux agent B_(2)O_(3) was the lowest,whereas that of Sr ions in the sample with flux agent BaO·2B_(2)O_(3) was the highest.These results show that the leaching concentration of Sr ions depends largely on the amorphous phase in the ceramics.Meanwhile,the formation of mineral analog ceramics containing Sr is an important factor to improve Sr immobilization.展开更多
Understanding hydrogen diffusion in amorphous SiO2(a-SiO2),especially under strain,is of prominent importance for improving the reliability of semiconducting devices,such as metal-oxide-semiconductor field effect tran...Understanding hydrogen diffusion in amorphous SiO2(a-SiO2),especially under strain,is of prominent importance for improving the reliability of semiconducting devices,such as metal-oxide-semiconductor field effect transistors.In this work,the diffusion of hydrogen atom in a-SiO2 under strain is simulated by using molecular dynamics(MD)with the ReaxFF force field.A defect-free a-SiO2 atomic model,of which the local structure parameters accord well with the experimental results,is established.Strain is applied by using the uniaxial tensile method,and the values of maximum strain,ultimate strength,and Young's modulus of the a-SiO2 model under different tensile rates are calculated.The diffusion of hydrogen atom is simulated by MD with the ReaxFF,and its pathway is identified to be a series of hops among local energy minima.Moreover,the calculated diffusivity and activation energy show their dependence on strain.The diffusivity is substantially enhanced by the tensile strain at a low temperature(below 500 K),but reduced at a high temperature(above 500 K).The activation energy decreases as strain increases.Our research shows that the tensile strain can have an influence on hydrogen transportation in a-SiO2,which may be utilized to improve the reliability of semiconducting devices.展开更多
The effects of uniaxial tensile strain on the structural and electronic properties of positively charged oxygen vacancy defects in amorphous silica(a-SiO2)are systematically investigated using ab-initio calculation ba...The effects of uniaxial tensile strain on the structural and electronic properties of positively charged oxygen vacancy defects in amorphous silica(a-SiO2)are systematically investigated using ab-initio calculation based on density functional theory.Four types of positively charged oxygen vacancy defects,namely the dimer,unpuckered,and puckered four-fold(4×),and puckered five-fold(5×)configurations have been investigated.It is shown by the calculations that applying uniaxial tensile strain can lead to irreversible transitions of defect structures,which can be identified from the fluctuations of the curves of relative total energy versus strain.Driven by strain,a positively charged dimer configuration may relax into a puckered 5×configuration,and an unpuckered configuration may relax into either a puckered 4×configuration or a forward-oriented configuration.Accordingly,the Fermi contacts of the defects remarkably increase and the defect levels shift under strain.The Fermi contacts of the puckered configurations also increase under strain to the values close to that of Eα′center in a-SiO2.In addition,it is shown by the calculations that the relaxation channels of the puckered configurations after electron recombination are sensitive to strain,that is,those configurations are more likely to relax into a two-fold coordinated Si structure or to hold a puckered structure under strain,both of which may raise up the thermodynamic charge-state transition levels of the defects into Si band gap.As strain induces more puckered configurations with the transition levels in Si band gap,it may facilitate directly the development of oxide charge accumulation and indirectly that of interface charge accumulation by promoting proton generation under ionization radiation.This work sheds a light on understanding the strain effect on ionization damage at an atomic scale.展开更多
Background: The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China.Both HIV and HBV can be treated with tenofovir disoproxil fumara...Background: The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China.Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV.Methods: One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen ofTDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.Results: Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%).Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1· 1.73 m-2) to week 12 (104 ml·min-1· 1.73 m-2) but was almost back to baseline at week 48 (1 1 1 ml·min-1· 1.73 m-2).Conclusion: This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.Trial Registration: ClinicalTrials.gov, NCT01751555;https://clinicaltrials.gov/ct2/show/NCT01751555.展开更多
Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-riton...Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.展开更多
Potent combination antiretroviral therapy(cART)has significantly improved the life expectancy of people living with human immunodeficiency virus(HIV),but it has many side effects such as lipodystrophy(LD),hepatic steato...Potent combination antiretroviral therapy(cART)has significantly improved the life expectancy of people living with human immunodeficiency virus(HIV),but it has many side effects such as lipodystrophy(LD),hepatic steatosis,and lactic acidosis.Nucleoside reverse transcriptase inhibitors(NRTIs)could damage the mito-chondria by inhibiting the human DNA polymerase gamma,leading to mtDNA deletion.However,it remains uncertain whether NRTIs could induce the hypervariable region(HV)mutations of the D loop of mitochondria in Chinese HIV/AIDS patients,and whether that effect is different between individuals with and without LD.Hereby,30 Chinese AIDS patients who were receiving antiretroviral drugs were recruited,among which 16 had symptomatic LD and 14 did not.Blood samples were collected prior to and after 96 weeks of treatment.Total DNA was extracted from peripheral blood mononuclear cells(PBMCs).Fragments of 728 bp in length containing HV 2 were amplified by standard polymerase chain reaction(PCR).Direct DNA-sequencing analysis techni-ques were used to detect mitochondrial sequence variants between paired longitudinal samples.Alterations were compared with the revised Cambridge Reference Sequence(rCRS)to determine mutation or polymorphism.Results showed that two years after ART,totally seven cases exhibited sequence variations,five individuals showed 73 A!G revised variation(two with and three without LD),while two cases of LD were found to have other nucleotide alterations.There was no new alteration in individuals without LD.In conclusion,NRTIs could induce mutation of mtDNA HV 2,which might contribute to the development of LD.展开更多
Introduction Although the global human immunodeficiency virus(HIV)epidemic has been effectively curbed,preventing and managing HIV infection in high-risk populations remains challenging.[1]In China,HIV is primarily tr...Introduction Although the global human immunodeficiency virus(HIV)epidemic has been effectively curbed,preventing and managing HIV infection in high-risk populations remains challenging.[1]In China,HIV is primarily transmitted through sexual contact.[1,2]Pre-exposure prophylaxis(PrEP)is a new and effective method for preventing HIV infection using antiretroviral drugs[3];data from multiple clinical trials worldwide have shown that using antiretroviral drugs for PrEP can limit HIV transmission.[4,5,6,7]The World Health Organization(WHO)issued guidelines in 2015 recommending PrEP in populations with an HIV incidence above 3/100 person-years(PY)and in individuals engaging in high-risk behaviors.[3]According to existing studies,the HIV incidence among key populations in China was 5.6/100 PY for men who have sex with men(MSM),[8]1.6/100 PY for intravenous drug users(IDUs),[9]and 1.4/100 PY for female sex workers.[10,11]As of July 2020,54 countries and regions have issued PrEP guidelines for adults to prevent HIV infection,and 36 of these have also published guidelines for children and adolescents.However,there are no PrEP guidelines or related consensus statement in China.As such,there is a strong need for standardized guidance on the implementation of PrEP pertaining to medical selection criteria,PrEP timing,drug safety,and consultation and testing programs.Here we present the consensus statement on the implementation of PrEP in China based on the opinions and suggestions of health policy-makers,scientists,clinical experts,community-based organizations of key populations,and the latest reports in PrEP researches.展开更多
基金This work was financially supported by the National Natural Science Foundation of China(No.11605116).
文摘Monoclinic SrAl_(2)Si_(2)O_(8) ceramics for Sr immobilization were prepared by a liquid-phase sintering method.The sintering temperature,mineral phase composition,microstructure,flexural strength,bulk density,and Sr ion leaching characteristics of the SrAl_(2)Si_(2)O_(8) ceramics were investigated.A crystalline monoclinic SrAl_(2)Si_(2)O_(8) phase formed through liquid-phase sintering at 1223 K.The introduction of four flux agents(B_(2)O_(3),CaO·2B_(2)O_(3),SrO·2B_(2)O_(3),and BaO·2B_(2)O_(3))to the SrAl_(2)Si_(2)O_(8) ceramics not only reduced the densification temperature and decreased the volatilization of Sr during high-temperature sintering but also impacted the mechanical properties of the ceramics.Product consistency tests showed that the leaching concentration of Sr ions in the sample with flux agent B_(2)O_(3) was the lowest,whereas that of Sr ions in the sample with flux agent BaO·2B_(2)O_(3) was the highest.These results show that the leaching concentration of Sr ions depends largely on the amorphous phase in the ceramics.Meanwhile,the formation of mineral analog ceramics containing Sr is an important factor to improve Sr immobilization.
基金Project supported by the Science Challenge Project,China(Grant No.TZ2016003-1-105)the CAEP Microsystem and THz Science and Technology Foundation,China(Grant No.CAEPMT201501).
文摘Understanding hydrogen diffusion in amorphous SiO2(a-SiO2),especially under strain,is of prominent importance for improving the reliability of semiconducting devices,such as metal-oxide-semiconductor field effect transistors.In this work,the diffusion of hydrogen atom in a-SiO2 under strain is simulated by using molecular dynamics(MD)with the ReaxFF force field.A defect-free a-SiO2 atomic model,of which the local structure parameters accord well with the experimental results,is established.Strain is applied by using the uniaxial tensile method,and the values of maximum strain,ultimate strength,and Young's modulus of the a-SiO2 model under different tensile rates are calculated.The diffusion of hydrogen atom is simulated by MD with the ReaxFF,and its pathway is identified to be a series of hops among local energy minima.Moreover,the calculated diffusivity and activation energy show their dependence on strain.The diffusivity is substantially enhanced by the tensile strain at a low temperature(below 500 K),but reduced at a high temperature(above 500 K).The activation energy decreases as strain increases.Our research shows that the tensile strain can have an influence on hydrogen transportation in a-SiO2,which may be utilized to improve the reliability of semiconducting devices.
基金Project supported by the Science Challenge Project,China(Grant No.TZ2016003-1-105)the CAEP Microsystem and THz Science and Technology Foundation(Grant No.CAT201501)。
文摘The effects of uniaxial tensile strain on the structural and electronic properties of positively charged oxygen vacancy defects in amorphous silica(a-SiO2)are systematically investigated using ab-initio calculation based on density functional theory.Four types of positively charged oxygen vacancy defects,namely the dimer,unpuckered,and puckered four-fold(4×),and puckered five-fold(5×)configurations have been investigated.It is shown by the calculations that applying uniaxial tensile strain can lead to irreversible transitions of defect structures,which can be identified from the fluctuations of the curves of relative total energy versus strain.Driven by strain,a positively charged dimer configuration may relax into a puckered 5×configuration,and an unpuckered configuration may relax into either a puckered 4×configuration or a forward-oriented configuration.Accordingly,the Fermi contacts of the defects remarkably increase and the defect levels shift under strain.The Fermi contacts of the puckered configurations also increase under strain to the values close to that of Eα′center in a-SiO2.In addition,it is shown by the calculations that the relaxation channels of the puckered configurations after electron recombination are sensitive to strain,that is,those configurations are more likely to relax into a two-fold coordinated Si structure or to hold a puckered structure under strain,both of which may raise up the thermodynamic charge-state transition levels of the defects into Si band gap.As strain induces more puckered configurations with the transition levels in Si band gap,it may facilitate directly the development of oxide charge accumulation and indirectly that of interface charge accumulation by promoting proton generation under ionization radiation.This work sheds a light on understanding the strain effect on ionization damage at an atomic scale.
文摘Background: The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China.Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV.Methods: One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen ofTDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.Results: Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%).Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1· 1.73 m-2) to week 12 (104 ml·min-1· 1.73 m-2) but was almost back to baseline at week 48 (1 1 1 ml·min-1· 1.73 m-2).Conclusion: This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.Trial Registration: ClinicalTrials.gov, NCT01751555;https://clinicaltrials.gov/ct2/show/NCT01751555.
基金Frontier Biotechnologies Inc.,Ministry of Science and Technology of China(Nos.2013ZX09101001 and 2017ZX09201007)the Beijing Municipal of Science and Technology Major Project(Nos.D141100000314005,D141100000314002,and D161100000416003)+1 种基金the National Natural Science Foundation of China(Nos.81772165,81974303,and 81571973)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089)。
文摘Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.
基金supported by grants from the National 11.5 Major Research Plan of China(No.2008ZX10001-007).
文摘Potent combination antiretroviral therapy(cART)has significantly improved the life expectancy of people living with human immunodeficiency virus(HIV),but it has many side effects such as lipodystrophy(LD),hepatic steatosis,and lactic acidosis.Nucleoside reverse transcriptase inhibitors(NRTIs)could damage the mito-chondria by inhibiting the human DNA polymerase gamma,leading to mtDNA deletion.However,it remains uncertain whether NRTIs could induce the hypervariable region(HV)mutations of the D loop of mitochondria in Chinese HIV/AIDS patients,and whether that effect is different between individuals with and without LD.Hereby,30 Chinese AIDS patients who were receiving antiretroviral drugs were recruited,among which 16 had symptomatic LD and 14 did not.Blood samples were collected prior to and after 96 weeks of treatment.Total DNA was extracted from peripheral blood mononuclear cells(PBMCs).Fragments of 728 bp in length containing HV 2 were amplified by standard polymerase chain reaction(PCR).Direct DNA-sequencing analysis techni-ques were used to detect mitochondrial sequence variants between paired longitudinal samples.Alterations were compared with the revised Cambridge Reference Sequence(rCRS)to determine mutation or polymorphism.Results showed that two years after ART,totally seven cases exhibited sequence variations,five individuals showed 73 A!G revised variation(two with and three without LD),while two cases of LD were found to have other nucleotide alterations.There was no new alteration in individuals without LD.In conclusion,NRTIs could induce mutation of mtDNA HV 2,which might contribute to the development of LD.
基金This work was supported by a grant from the Mega-projects of National Science Research for the 13th Five-Year Plan(No.2017ZX10201101)。
文摘Introduction Although the global human immunodeficiency virus(HIV)epidemic has been effectively curbed,preventing and managing HIV infection in high-risk populations remains challenging.[1]In China,HIV is primarily transmitted through sexual contact.[1,2]Pre-exposure prophylaxis(PrEP)is a new and effective method for preventing HIV infection using antiretroviral drugs[3];data from multiple clinical trials worldwide have shown that using antiretroviral drugs for PrEP can limit HIV transmission.[4,5,6,7]The World Health Organization(WHO)issued guidelines in 2015 recommending PrEP in populations with an HIV incidence above 3/100 person-years(PY)and in individuals engaging in high-risk behaviors.[3]According to existing studies,the HIV incidence among key populations in China was 5.6/100 PY for men who have sex with men(MSM),[8]1.6/100 PY for intravenous drug users(IDUs),[9]and 1.4/100 PY for female sex workers.[10,11]As of July 2020,54 countries and regions have issued PrEP guidelines for adults to prevent HIV infection,and 36 of these have also published guidelines for children and adolescents.However,there are no PrEP guidelines or related consensus statement in China.As such,there is a strong need for standardized guidance on the implementation of PrEP pertaining to medical selection criteria,PrEP timing,drug safety,and consultation and testing programs.Here we present the consensus statement on the implementation of PrEP in China based on the opinions and suggestions of health policy-makers,scientists,clinical experts,community-based organizations of key populations,and the latest reports in PrEP researches.