短串联重复序列(short tandem repeat,STR)已广泛用于法医学亲子鉴定和个体识别中,但STR的突变可能会影响其结果的解释。在大多数类似研究中,由于忽略“隐性”突变现象,STR的突变率被低估。鉴于此,为获得更加准确的STR实际突变率,本研...短串联重复序列(short tandem repeat,STR)已广泛用于法医学亲子鉴定和个体识别中,但STR的突变可能会影响其结果的解释。在大多数类似研究中,由于忽略“隐性”突变现象,STR的突变率被低估。鉴于此,为获得更加准确的STR实际突变率,本研究使用Slooten与Ricciardi提出的有限突变模型和大规模数据,对28,313例(78,739个体)中国北京汉族已确认亲生关系的亲子鉴定案的20个常染色体STR基因座(D3S1358、D1S1656、D13S317、Penta E、D16S539、D18S51、D2S1338、CSF1PO、Penta D、TH01、vWA、D21S11、D6S1043、D7S820、D5S818、TPOX、D8S1179、D12S391、D19S433和FGA;由于有限突变模型中未包含D6S1043的矫正参数,因此本文实际计算其余19个STR基因座的突变率)进行了调查。结果发现,所有基因座均存在突变现象,总计发生1665个突变事件,包括1614个一步突变,34个两步突变,8个三步突变和9个非整步突变。基因座特异性的平均实际突变率在三联体中为0.00007700(TPOX)~0.00459050(FGA),在二联体中为0.00000000(TPOX)~0.00344850(FGA)。此外,本研究还分析了表面和实际突变率、三联体和二联体突变率、父源和母源的突变率之间的关系。研究表明,实际突变率多大于表面突变率,而且μ1^(*)/μ2^(*)(表面突变率)的比值通常也大于μ1/μ2(实际突变率)(μ1^(*),μ1;μ2^(*),μ2分别是一步和两步的突变率),即更多的“隐性”突变被释放出来。而且父源和母源的三联体和二联体的突变率也有存在差异。随后,将这些突变率数据与已发表的中国其他汉族人口的相关研究进行比较,展现出了STR突变率的时间与区域差异。由于样本量大,本研究中还报告了一些少见的突变事件,例如同卵双胞胎突变和“假四步突变”等。综上所述,本研究通过大量数据获得了接近真实的STR突变率的估计值,不仅可为中国法医DNA数据库和群体遗传学数据库提供重要的基础数据,也对开展法医学个体识别、亲权鉴定和遗传学研究具有重要的意义。展开更多
随着新一代信息通信技术(information and communication technologies,ICT)的高速发展以及新基建的部署,移动通信系统的能耗和碳排放出现较快增长的趋势.ICT行业在自身节能减排之外,使能其他行业节能减排,可有效降低其他行业的碳排放,...随着新一代信息通信技术(information and communication technologies,ICT)的高速发展以及新基建的部署,移动通信系统的能耗和碳排放出现较快增长的趋势.ICT行业在自身节能减排之外,使能其他行业节能减排,可有效降低其他行业的碳排放,是未来理论研究行业应用的重要领域.本文基于ICT使能碳减排评估框架,提出两个定量衡量使能效果的指标,使能减碳比(enable carbon reduction ratio,ECRR)和使能低碳系数(enable carbon reduction coefficient,ECRC)以及相应的定量分析方法,用于评估被使能企业的实际碳减排效果.本文研究可保护数据隐私的多方数据共享,基于安全多方计算(secure multi-party computation,SMPC)框架,提出保护各方数据隐私的使能碳减排评估方法.本文通过实际案例,完成数据采集、分析验证,对所提指标和方法论证其有效性和实用性.展开更多
The present study utilized motor imaginary-based brain-computer interface technology combined with rehabilitation training in 20 stroke patients. Results from the Berg Balance Scale and the Holden Walking Classificati...The present study utilized motor imaginary-based brain-computer interface technology combined with rehabilitation training in 20 stroke patients. Results from the Berg Balance Scale and the Holden Walking Classification were significantly greater at 4 weeks after treatment (P 〈 0.01), which suggested that motor imaginary-based brain-computer interface technology improved balance and walking in stroke patients.展开更多
Two-dimensional(2D)metal organic frameworks(MOFs)are emerging as low-cost oxygen evolution reaction(OER)electrocatalysts,however,suffering aggregation and poor operation stability.Herein,ultrafine Fe_(3)O_(4) nanopart...Two-dimensional(2D)metal organic frameworks(MOFs)are emerging as low-cost oxygen evolution reaction(OER)electrocatalysts,however,suffering aggregation and poor operation stability.Herein,ultrafine Fe_(3)O_(4) nanoparticles(diameter:6±2 nm)are homogeneously immobilized on 2D Ni based MOFs(Ni-BDC,thickness:5±1 nm)to improve the OER stability.Electronic structure modulation for enhanced catalytic activity is studied via adjusting the amount of Fe_(3)O_(4) nanoparticles on Ni-BDC.The optimal Fe_(3)O_(4)/Ni-BDC achieves the best OER performance with an overpotential of 295 mV at 10 mA cm^(-2),a Tafel slope of 47.8 mV dec^(-1) and a considerable catalytic durability of more than 40 h(less than 5 h for Ni-BDC alone).DFT calculations confirm that the active sites for Fe_(3)O_(4)/Ni-BDC are mainly contributed by Fe species with a higher oxidation state,and the potential-determining step(PDS)is the formation of the adsorbed O*species,which are facilitated in the composite.展开更多
Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity.However,no reliable method is currently available to assess its impact on delivery performance.In t...Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity.However,no reliable method is currently available to assess its impact on delivery performance.In this study,a biomimetic nasal model based on three-dimensional(3D)reconstruction and three-dimensional printing(3DP)technology was developed for visualizing the deposition of drug powders in the nasal cavity.The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females.The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test.The experimental device produced the most satisfactory results with five spray times.Furthermore,particle sizes and spray angles were found to significantly affect the experimental device’s performance and alter drug distribution,respectively.Additionally,mometasone furoate(MF)nasal spray(NS)distribution patterns were investigated in a goat nasal cavity model and three male goat noses,confirming the in vitro and in vivo correlation.In conclusion,the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.展开更多
Metal-organic frameworks(MOFs),comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous,crystalline materials.Their tunable porosity,chemical composition,size and shape,and e...Metal-organic frameworks(MOFs),comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous,crystalline materials.Their tunable porosity,chemical composition,size and shape,and easy surface functionalization make this large family more and more popular for drug delivery.There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications.This article presents an overall review and perspectives of MOFs-based drug delivery systems(DDSs),starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands.Then,the synthesis and characterization of MOFs for DDSs are developed,followed by the drug loading strategies,applications,biopharmaceutics and quality control.Importantly,a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics,diseases therapy and advanced DDSs.In particular,the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed.Finally,challenges in MOFs development for DDSs are discussed,such as biostability,biosafety,biopharmaceutics and nomenclature.展开更多
Metal antimony(Sb)is a promising anode material of potassium-ion batteries(PIBs)for its high theoretical capacity but limited by its inferior cycle stability due to the serious volume expansion during cycling.Herein,w...Metal antimony(Sb)is a promising anode material of potassium-ion batteries(PIBs)for its high theoretical capacity but limited by its inferior cycle stability due to the serious volume expansion during cycling.Herein,we design and construct a kind of low-crystalline Sb nanoparticles coated with amorphous Sb2O3 and dispersed into three-dimensional porous carbon via a strategy involving NaCl template-assisted insitu pyrolysis and subsequent low-temperature heat-treated in air.Significantly,the crystallinity and ratio of Sb/Sb_(2)O_(3) have been precisely tuned and controlled,and the optimized sample of HTSb@Sb_(2)O_(3)@C-4 displays a high reversible specific capacity of 543.9 m Ah g^(-1) at 0.1 A g^(-1),superior rate capability and excellent cycle stability(~273 m Ah g^(-1) at 2 A g^(-1) after 2000 cycles)as an anode of PIBs.The outstanding potassium-ion storage performance can be ascribed to the appropriate crystallinity and the multiplebuffer-matrix structure comprising an interconnected porous conductive carbon to relieve the volume changes and suppress the aggregation of Sb,a Sb nanoparticle core to shorten the ion transport pathways and decrease the mechanical stress,and a low-crystalline Sb_(2)O_(3) as the shell to consolidate the interface between Sb and carbon as well as facilitate the rapid electron transport.The dynamic analysis shows that the composite is mainly controlled by pseudocapacitance mechanism.This work provides a novel thought to design high-performance composite electrode in energy storage devices.展开更多
Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize...Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3 D structure of enteric coated pellets recovered from the gastrointestinal tract of rats.The structures of pellets in solid state and in vitro compendium media were measured.Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media.Thus,optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media.The sphericity,pellet volume,pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for2 h were recorded 0.47,1.55 × 10^(8)μm^(3),0.44 × 10^(8)μm^(3)and 27.6%,respectively.After adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64 × 10^(8)μm^(3)0.38 × 10^(8)μm^(3)and 23.0%,respectively.Omeprazole magnesium pellets behaved similarly.The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3 D structures to ensure better design,characterization and quality control of advanced OSDF.展开更多
Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanis...Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3 D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography(SR-μCT). In situ formed 3 D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3 D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral“roadways”. Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed3 D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.展开更多
文摘短串联重复序列(short tandem repeat,STR)已广泛用于法医学亲子鉴定和个体识别中,但STR的突变可能会影响其结果的解释。在大多数类似研究中,由于忽略“隐性”突变现象,STR的突变率被低估。鉴于此,为获得更加准确的STR实际突变率,本研究使用Slooten与Ricciardi提出的有限突变模型和大规模数据,对28,313例(78,739个体)中国北京汉族已确认亲生关系的亲子鉴定案的20个常染色体STR基因座(D3S1358、D1S1656、D13S317、Penta E、D16S539、D18S51、D2S1338、CSF1PO、Penta D、TH01、vWA、D21S11、D6S1043、D7S820、D5S818、TPOX、D8S1179、D12S391、D19S433和FGA;由于有限突变模型中未包含D6S1043的矫正参数,因此本文实际计算其余19个STR基因座的突变率)进行了调查。结果发现,所有基因座均存在突变现象,总计发生1665个突变事件,包括1614个一步突变,34个两步突变,8个三步突变和9个非整步突变。基因座特异性的平均实际突变率在三联体中为0.00007700(TPOX)~0.00459050(FGA),在二联体中为0.00000000(TPOX)~0.00344850(FGA)。此外,本研究还分析了表面和实际突变率、三联体和二联体突变率、父源和母源的突变率之间的关系。研究表明,实际突变率多大于表面突变率,而且μ1^(*)/μ2^(*)(表面突变率)的比值通常也大于μ1/μ2(实际突变率)(μ1^(*),μ1;μ2^(*),μ2分别是一步和两步的突变率),即更多的“隐性”突变被释放出来。而且父源和母源的三联体和二联体的突变率也有存在差异。随后,将这些突变率数据与已发表的中国其他汉族人口的相关研究进行比较,展现出了STR突变率的时间与区域差异。由于样本量大,本研究中还报告了一些少见的突变事件,例如同卵双胞胎突变和“假四步突变”等。综上所述,本研究通过大量数据获得了接近真实的STR突变率的估计值,不仅可为中国法医DNA数据库和群体遗传学数据库提供重要的基础数据,也对开展法医学个体识别、亲权鉴定和遗传学研究具有重要的意义。
基金Prevention&Control of COVID-19 Program of Soochow Securities,Grant/Award Number:JJ12700520Postgraduate Research&Practice Innovation Program of Jiangsu Province,Grant/Award Number:KYCX20_2684.
基金the National Natural Science Foundation of China,No.60970062the Shanghai Pujiang Program,No.09PJ1410200
文摘The present study utilized motor imaginary-based brain-computer interface technology combined with rehabilitation training in 20 stroke patients. Results from the Berg Balance Scale and the Holden Walking Classification were significantly greater at 4 weeks after treatment (P 〈 0.01), which suggested that motor imaginary-based brain-computer interface technology improved balance and walking in stroke patients.
基金support from the Chinese Scholarship Council(201706220080)for W.H.the Natural Science Foundation of Hunan Province(2019JJ50526)for C.P.+1 种基金The Danish Council for Independent Research for the YDUN project(DFF 4093-00297)to J.Z.Villum Experiment(grant No.35844)for X.X.
文摘Two-dimensional(2D)metal organic frameworks(MOFs)are emerging as low-cost oxygen evolution reaction(OER)electrocatalysts,however,suffering aggregation and poor operation stability.Herein,ultrafine Fe_(3)O_(4) nanoparticles(diameter:6±2 nm)are homogeneously immobilized on 2D Ni based MOFs(Ni-BDC,thickness:5±1 nm)to improve the OER stability.Electronic structure modulation for enhanced catalytic activity is studied via adjusting the amount of Fe_(3)O_(4) nanoparticles on Ni-BDC.The optimal Fe_(3)O_(4)/Ni-BDC achieves the best OER performance with an overpotential of 295 mV at 10 mA cm^(-2),a Tafel slope of 47.8 mV dec^(-1) and a considerable catalytic durability of more than 40 h(less than 5 h for Ni-BDC alone).DFT calculations confirm that the active sites for Fe_(3)O_(4)/Ni-BDC are mainly contributed by Fe species with a higher oxidation state,and the potential-determining step(PDS)is the formation of the adsorbed O*species,which are facilitated in the composite.
基金This research was funded by the Key Program for International Science and Technology Cooperation Projects of China(No.2020YFE0201700)the Innovation Leading Talents Short-term Program of Jiangxi Province,China(No.1262000102)Shanghai Science and Technology Plan(No.21DZ2260400,China).
文摘Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity.However,no reliable method is currently available to assess its impact on delivery performance.In this study,a biomimetic nasal model based on three-dimensional(3D)reconstruction and three-dimensional printing(3DP)technology was developed for visualizing the deposition of drug powders in the nasal cavity.The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females.The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test.The experimental device produced the most satisfactory results with five spray times.Furthermore,particle sizes and spray angles were found to significantly affect the experimental device’s performance and alter drug distribution,respectively.Additionally,mometasone furoate(MF)nasal spray(NS)distribution patterns were investigated in a goat nasal cavity model and three male goat noses,confirming the in vitro and in vivo correlation.In conclusion,the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.
基金financially supported by the National Key R&D Program of China(No.2020YFE0201700)National Nature Science Foundation of China(No.81773645)a public grant overseen by the French National Research Agency(ANR),France as part of the“Investissements d’Avenir”program(Labex NanoSaclay:ANR-10-LABX-0035,France)
文摘Metal-organic frameworks(MOFs),comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous,crystalline materials.Their tunable porosity,chemical composition,size and shape,and easy surface functionalization make this large family more and more popular for drug delivery.There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications.This article presents an overall review and perspectives of MOFs-based drug delivery systems(DDSs),starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands.Then,the synthesis and characterization of MOFs for DDSs are developed,followed by the drug loading strategies,applications,biopharmaceutics and quality control.Importantly,a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics,diseases therapy and advanced DDSs.In particular,the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed.Finally,challenges in MOFs development for DDSs are discussed,such as biostability,biosafety,biopharmaceutics and nomenclature.
基金financially supported by the National Natural Science Foundation of China(Nos.51871046,51902046,52071073,51771046,51971055)Natural Science Foundation of Hebei Province(No.E2019501097,E2018501091,E2020501004)The Science and Technology Project of Hebei Province(No.15271302D)。
文摘Metal antimony(Sb)is a promising anode material of potassium-ion batteries(PIBs)for its high theoretical capacity but limited by its inferior cycle stability due to the serious volume expansion during cycling.Herein,we design and construct a kind of low-crystalline Sb nanoparticles coated with amorphous Sb2O3 and dispersed into three-dimensional porous carbon via a strategy involving NaCl template-assisted insitu pyrolysis and subsequent low-temperature heat-treated in air.Significantly,the crystallinity and ratio of Sb/Sb_(2)O_(3) have been precisely tuned and controlled,and the optimized sample of HTSb@Sb_(2)O_(3)@C-4 displays a high reversible specific capacity of 543.9 m Ah g^(-1) at 0.1 A g^(-1),superior rate capability and excellent cycle stability(~273 m Ah g^(-1) at 2 A g^(-1) after 2000 cycles)as an anode of PIBs.The outstanding potassium-ion storage performance can be ascribed to the appropriate crystallinity and the multiplebuffer-matrix structure comprising an interconnected porous conductive carbon to relieve the volume changes and suppress the aggregation of Sb,a Sb nanoparticle core to shorten the ion transport pathways and decrease the mechanical stress,and a low-crystalline Sb_(2)O_(3) as the shell to consolidate the interface between Sb and carbon as well as facilitate the rapid electron transport.The dynamic analysis shows that the composite is mainly controlled by pseudocapacitance mechanism.This work provides a novel thought to design high-performance composite electrode in energy storage devices.
基金financial support from National Key R&D Program of China(2020YFE0201700)Major New Drugs Innovation and Development(2017ZX09101001-005,China)+1 种基金the National Natural Science Foundation of China(81803441,81803446 and 81773645)Youth Innovation Promotion Association CAS(2018323,China)。
文摘Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3 D structure of enteric coated pellets recovered from the gastrointestinal tract of rats.The structures of pellets in solid state and in vitro compendium media were measured.Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media.Thus,optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media.The sphericity,pellet volume,pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for2 h were recorded 0.47,1.55 × 10^(8)μm^(3),0.44 × 10^(8)μm^(3)and 27.6%,respectively.After adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64 × 10^(8)μm^(3)0.38 × 10^(8)μm^(3)and 23.0%,respectively.Omeprazole magnesium pellets behaved similarly.The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3 D structures to ensure better design,characterization and quality control of advanced OSDF.
基金the National Nature Science Foundation of China (Nos.81803446,81803441 and 81773645)Key Program for International Science and Technology Cooperation Projects of China (2020YFE0201700)the Youth Innovation Promotion Association of CAS (2018323)。
文摘Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3 D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography(SR-μCT). In situ formed 3 D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3 D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral“roadways”. Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed3 D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.