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Establishment of an indirect immunofluorescence assay for the detection of African swine fever virus antibodies

Journal of Integrative Agriculture 2024年第1期23卷 228-238页

作者： Wan Wang Zhenjiang zhang Weldu Tesfagaber jiwen zhang Fang Li Encheng Sun Lijie Tang Zhigao Bu Yuanmao Zhu Dongming Zhao State Key Laboratory for Animal Disease Control and Prevention National African Swine Fever Para-reference LaboratoryNational High Containment Facilities for Animal Diseases Control and PreventionHarbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150069China

African swine fever(ASF)continues to cause enormous economic loss to the global pig industry.Since there is no safe and effective vaccine,accurate and timely diagnosis of ASF is essential to implement control measures.Indirect immunofluorescence assay(IFA)is a gold standard serological method recommended by the World Organization for Animal Health(WOAH).In this study,we used primary fetal kidney cells to establish a wild boar cell line(BK2258)that supported the efficient replication of ASF virus(ASFV)SD/DY-I/21 and showed visible cytopathic effect(CPE).Moreover,using BK2258,we established a sensitive and specific IFA for ASFV antibody detection.To standardize and evaluate the performance of this assay,we used serum samples from pigs infected with the low virulent genotype I SD/DY-I/21 and genotype II HLJ/HRB1/20,and immunized with the vaccine candidate HLJ/18-7GD,field samples,and negative serum samples.The IFA reacted with the ASFV-positive sera and displayed bright fluorescence foci.There was no non-specific green fluorescence due to cellular senescence or other cell damage-causing factors.Compared to a commercial indirect enzyme-linked immunosorbent assay(iELISA),ASFV antibodies were detected 1–4 days earlier using our IFA.The detection limits of the IFA and iELISA for the same ASFV-antibody positive serum samples were 1:25,600 and 1:6,400,respectively,indicating that the IFA is more sensitive than iELISA.The newly established IFA was highly specific and did not cross-react with sera positive for six other important porcine pathogens(i.e.,Classical swine fever virus(CSFV),Porcine reproductive and respiratory syndrome virus(PRRSV),Porcme circovirus type 2(PCV2),Pseudorabies virus(PRV),Foot-and-Mouth disease virus type O(FMDV/O),and Porcine epidemic diarrhea virus(PEDV)).This study thus provides a sensitive,specific,and reliable detection method that is suitable for the serological diagnosis of ASF.

关键词： African swine fever antibody IFA serological method

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Visualization of nasal powder distribution using biomimetic human nasal cavity model

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Acta Pharmaceutica Sinica B 2024年第1期14卷 392-404页

作者： Jiawen Su Yan Liu Hongyu Sun Abid Naeem Huipeng Xu Yue Qu Caifen Wang Zeru Li Jianhua Lu Lulu Wang Xiaofeng Wang Jie Wu Lixin Sun jiwen zhang Zhigang Wang Rui Yang Li Wu Key Laboratory of Modern Preparation of TCM Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004China Key Laboratory of Molecular Pharmacology and Drug Evaluation School of PharmacyMinistry of EducationYantai UniversityYantai 264005China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201210China Nantong Haimen People’s Hospital Nantong 226199China Yangtze Delta Drug Advanced Research Institute Nantong 226126China Shenyang Pharmaceutical University Shenyang 110016China National Institutes for Food and Drug Control Beijing 100000China Nanjing University of Chinese Medicine Nanjing 210023China

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.

关键词： Nasal drug deposition Nasal drug distribution Nasal drug delivery Biomimetic nasal model Nasal powder Three-dimensional reconstruction Three-dimensional printing Nasal drug distribution

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Constructal design of a rectangular parallel phase change microchannel in a three-dimensional electronic device

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Science China(Technological Sciences) 2024年第5期67卷 1381-1390页

作者： zhang jiwen FENG HuiJun CHEN LinGen GE YanLin Institute of Thermal Science and Power Engineering Wuhan Institute of TechnologyWuhan430205China College of Power Engineering Naval University of EngineeringWuhan430033China Hubei Provincial Engineering Technology Research Center of Green Chemical Equipment Wuhan430205China School of Mechanical&Electrical Engineering Wuhan Institute of TechnologyWuhan430205China

Based on constructal theory,a rectangular parallel phase change microchannel model in a three-dimensional electronic device(TDED)is established with R134a as the cooling fluid.Based on the minimization of a complex function(CF)composed of linear weighting sum of maximum temperature difference and pumping power consumption,constructal design of the TDED is conducted first;and then,maximum temperature difference and pumping power consumption are minimized by non-dominated sorting genetic algorithm-II methods.The results reveal that there exist an optimal mass flow rate(0.0012 kg/s)and a quadratic optimal aspect ratio(AR)(0.39)of the microchannel which lead to quadratic minimum CF(0.817).Compared with the original value,the CF after optimization is reduced by 18.34%.Reducing the inlet temperature of cooling fluid and microchannel number appropriately can help to enhance the overall performance of TDED.By using the artificial neural network and genetic algorithms in the toolboxes of Matlab software,the optimal AR gained in the Pareto solution set is located between 0.2–0.45.The smallest deviation index among three discussed strategies is 0.346,and the corresponding optimal AR is 0.413,which is selected as the optimal design strategy of the microchannel in the TDED under multiple requirements.The findings in this study can serve as theoretical guides for thermal designs of electronic devices.

关键词： constructal theory parallel microchannel evaporation phase change three-dimensional electronic device multi-objective optimization artificial neural network

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ASFV transcription reporter screening system identifies ailanthone as a broad antiviral compound

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Virologica Sinica 2023年第3期38卷 459-469页

作者： Yuhang zhang Zhenjiang zhang Fan zhang jiwen zhang Jun Jiao Min Hou Nianchao Qian Dongming Zhao Xiaofeng Zheng Xu Tan College of Veterinary Medicine Hunan Agricultural UniversityChangsha 410128China State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150009China Beijing Advanced Innovation Center for Structural Biology Beijing Frontier Research Center for Biological StructureMOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical BiologySchool of Pharmaceutical SciencesTsinghua-Peking Center for Life SciencesTsinghua UniversityBeijing 100084China Institute of Health and Medicine Hefei Comprehensive National Science CenterHefei 230601 China

African swine fever(ASF)is an acute,highly contagious and deadly viral disease in swine that jeopardizes the worldwide pig industry.Unfortunately,there are no authoritative vaccine and antiviral drug available for ASF control.African swine fever virus(ASFV)is the etiological agent of ASF.Among the ASFV proteins,p72 is the most abundant component in the virions and thus a potential target for anti-ASFV drug design.Here,we con-structed a luciferase reporter system driven by the promoter of p72,which is transcribed by the co-transfected ASFV RNA polymerase complex.Using this system,we screened over 3200 natural product compounds and obtained three potent candidates against ASFV.We further evaluated the anti-ASFV effects and proved that among the three candidates,ailanthone(AIL)inhibits the replication of ASFV at the nanomolar concentration(IC_(50)=15 nmol/L).Our in vitro experiments indicated that the antiviral effect of AIL is associated with its inhibition of the HSP90-p23 cochaperone.Finally,we showed the antiviral activity of AIL on Zika virus and hepatitis B virus(HBV),which supports that AIL is a potential broad-spectrum antiviral agent.

关键词： African swine fever virus(ASFV) Replication inhibition Broad-spectrum antiviral drugs Ailanthone(AIL)

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基于机器人建模的航空装配测控仿真分析方法

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清华大学学报（自然科学版） 2024年第4期64卷 724-737页

作者：王斌张继文吴丹清华大学机械工程系高端装备界面科学与技术全国重点实验室北京100084

在航空飞机数字化装配过程中,需要对装配环境中的运动调姿机构的运动能力和靶标测量机构的测量能力进行仿真,以确保调姿机构实现给定运动空间的灵活调姿及测量机构实现对目标测量点的无遮挡、高精度测量,从而测控结合完成装配。而航空... 详细信息

在航空飞机数字化装配过程中,需要对装配环境中的运动调姿机构的运动能力和靶标测量机构的测量能力进行仿真,以确保调姿机构实现给定运动空间的灵活调姿及测量机构实现对目标测量点的无遮挡、高精度测量,从而测控结合完成装配。而航空领域常用的仿真平台如DELMIA、CATIA和SA等,目前无法实现结合设备位置规划、运动控制评估和测量场分析的综合仿真。为了在同一体系下实现航空装配数字化测控系统的综合仿真,该文提出一种基于机器人建模的航空装配测控仿真分析方法。将数字化装配环境中的零部件及工装、调姿机构、测量机构、环境干扰物体等关键要素在机器人仿真平台中分别建模为不同的机器人,进而按照装配需求编写控制程序,使系统按照需求控制各个机器人联合运动执行仿真分析,以完成测控算法验证,并可进一步设置动态优化问题对测调参数、测量设备站位等现有仿真平台难仿信息进行优化。以高遮挡环境下的多个激光跟踪仪对大量测量点的联合测量可达性仿真分析和多激光跟踪仪站位仿真规划为例,阐述了测量机构的机器人建模方法、仿真系统的搭建方法、仿真激光测量系统的原理和站位规划的实施方式,验证了所提方法的可行性。该方法简单、高效,当环境改变时可快速重规划。

关键词：航空数字化装配测控仿真方法激光跟踪仪测量可达性站位优化

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Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth via three-dimensional structure mechanism

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2568-2577页

作者： Abi Maharjan Hongyu Sun Zeying Cao Ke Li Jinping Liu Jun Liu Tiqiao Xiao Guanyun Peng Junqiu Ji Peter York Balmukunda Regmi Xianzhen Yin jiwen zhang Li Wu Center for Drug Delivery System Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationYantai UniversityYantai 264005China University of Chinese Academy of Sciences Beijing 100049China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China Shanghai Synchrotron Radiation Facility/zhangjiang Lab Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201204China Hefei Lifeon Medication Group Hefei 230088China Center for MOST and Image Fusion Analysis Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201210China Maharajgung Medical Campus Institute of MedicineTribhuvan UniversityKathmandu 44606Nepal

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.

关键词： Bilayer osmotic pump tablet Synchrotron radiation micro-computed tomography Three-dimensional microstructure Release kinetics Void formation Peripheral“roadways” Push-pull model Subterranean river model

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Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats

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Acta Pharmaceutica Sinica B 2022年第1期12卷 326-338页

作者： Hongyu Sun Siyu He Li Wu Zeying Cao Xian Sun Mingwei Xu Shan Lu Mingdi Xu Baoming Ning Huimin Sun Tiqiao Xiao Peter York Xu Xu Xianzhen Yin jiwen zhang School of Chemical and Environmental Engineering Shanghai Institute of TechnologyShanghai 201418China Center for Drug Delivery System Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201210China University of Chinese Academy of Sciences Beijing 100049China School of Materials Science and Engineering Center for Supramolecular Chemistry and CatalysisDepartment of ChemistryShanghai UniversityShanghai 200444China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China National Institutes for Food and Drug Control Beijing 100050China Shanghai Synchrotron Radiation Facility/zhangjiang Lab Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201204China Center for MOST and Image Fusion Analysis Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201210China

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.

关键词： Internal 3D structure 3D reconstruction Structural parameter Enteric coated pellets Synchrotron radiation X-ray micro computed tomography In vivo and in vitro structure correlation Esomeprazole magnesium Omeprazole magnesium

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Shanghai center project excavation induced ground surface movements and deformations

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Frontiers of Structural and Civil Engineering 2018年第1期12卷 26-43页

作者： Guolin XU jiwen zhang Huang LIU Changqin REN Department of Civil Engineering Southwest Forestry University Kunming 650224 China Department of Civil Engineering University of Kentucky Lexington KY 40506-0281 USA Shanghai Geotechnical Investigations & Design Institute Company Limited Shanghai 200032 China

Empirical data on deep urban excavations can provide designers a significant reference basis for assessing potential deformations of the deep excavations and their impact on adjacent structures. The construction of the Shanghai Center involved excavations in excess of 33-m-deep using the top-down method at a site underlain by thick deposits of marine soft clay. A retaining system was achieved by 50-m-deep diaphragm walls with six levels of struts. During construction, a comprehensive instrumentation program lasting 14 months was conducted to monitor the behaviors of this deep circular excavation. The following main items related to ground surface movements and deformations were collected：（1） walls and circumferential soils lateral movements; （2） peripheral soil deflection in layers and ground settlements; and （3） pit basal heave. The results from the field instrumentation showed that deflections of the site were strictly controlled and had no large movements that might lead to damage to the stability of the foundation pit. The field performance of another 21 cylindrical excavations in top-down method were collected to compare with this case through statistical analysis. In addition, numerical analyses were conducted to compare with the observed data. The extensively monitored data are characterized and analyzed in this paper.

关键词： deep excavation foundation pit soft clay top-down method field observation ground surface movements,ground deformations

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Sodium dodecyl sulfate/β-cyclodextrin vesicles embedded in chitosan gel for insulin delivery with p H-selective release

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Acta Pharmaceutica Sinica B 2016年第4期6卷 344-351页

作者： Zhuo Li Haiyan Li Caifen Wang Jianghui Xu Vikramjeet Singh Dawei Chen jiwen zhang School of Pharmacy Shenyang Pharmaceutical University Center for Drug Delivery System Shanghai Institute of Materia Medica Chinese Academy of Sciences School of Pharmaceutical Sciences Anhui University of Chinese Medicine

In an answer to the challenge of enzymatic instability and low oral bioavailability of proteins/peptides, a new type of drug-delivery vesicle has been developed. The preparation, based on sodium dodecyl sulfate(SDS) and β-cyclodextrin(β-CD) embedded in chitosan gel, was used to successfully deliver the model drug-insulin. The self-assembled SDS/β-CD vesicles were prepared and characterized by particle size, zeta potential, appearance, microscopic morphology and entrapment efficiency. In addition, both the interaction of insulin with vesicles and the stability of insulin loaded in vesicles in the presence of pepsin were investigated.The vesicles were crosslinked into thermo-sensitive chitosan/β-glycerol phosphate solution for an in-situ gel to enhance the dilution stability. The in vitro release characteristics of insulin from gels in media at different p H values were investigated. The insulin loaded vesicles–chitosan hydrogel(IVG) improved the dilution stability of the vesicles and provided p H-selective sustained release compared with insulin solution–chitosan hydrogel(ISG). In vitro, IVG exhibited slow release in acidic solution and relatively quick release in neutral solutions to provide drug efficacy. In simulated digestive fluid, IVG showed better sustained release and insulin protection properties compared with ISG. Thus IVG might improve the stability of insulin during its transport in vivo and contribute to the bioavailability and therapeutic effect of insulin.

关键词： Vesicles β-Cyclodextrin Insulin Self-assembly Gel p H-selective release

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Multi-dimensional visualization for the morphology of lubricant stearic acid particles and their distribution in tablets

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Asian Journal of Pharmaceutical Sciences 2020年第1期15卷 60-68页

作者： Liu zhang Shailendra Shakya Li Wu Jiangtao Wang Guanghui Jin Huimin Sun Xianzhen Yin Lixin Sun jiwen zhang School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Center for Drug Delivery Systems Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Weihai Disu Pharmaceutical Manufacturer Weihai 264200China National Institutes for Food and Drug Control Beijing 100050China

The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid(SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional(3 D) information of SA particles in tablets was detected by a quantitative and non-invasive 3 D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography(SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA(GUT), reprocessed SA(GRT), as well as reference listed drug(RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.

关键词： Stearic acid Morphology Spatial distribution SR-μCT Glipizide tablets

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