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Enzyme-linked immunosorbent assays for quantification of MMAE-conjugated ADCs and total antibodies in cynomolgus monkey sera

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Journal of Pharmaceutical Analysis 2022年第4期12卷 645-652页

作者： Min Pei Tingting Liu Lu Ouyang Jianhua Sun Xiaojie Deng Xiaomin Sun Wei Wu peng Huang Yi-Li Chen Xiaorong Tan Xiaoyue Liu peng zhu Yongzhen Liu Deheng Wang Junliang Wu Qi Wang Guifeng Wang Likun Gong Qiuping Qin Chunhe Wang Biotherapeutics Discovery Research Center Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China School of Pharmacy University of Chinese Academy of SciencesBeijing100049China Center for Drug Safety Evaluation and Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China Research and Development Center Dartsbio Pharmaceuticals Ltd.ZhongshanGuangdong528400China Zhongshan Institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshanGuangdong528400China School of Pharmacy Shanghai Engineering Research Center of ImmunotherapeuticsFudan UniversityShanghai201203China

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosorbent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were successfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation between serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias%ranged from -12.2% to -5.2%,precision ranged from -12.4% to -1.4%,and the relative standard deviation(RSD)was less than 6.6% and 8.7%,respectively.The total error was less than 20.4%.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

关键词： Monomethyl auristatin E Antibody-drug conjugates Pharmacokinetics Trophoblast cell surface antigen 2

Wide Stopband Substrate Integrated Waveguide Filter Using Bisection and Trisection Coupling in Multilayer

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Chinese Journal of Electronics 2023年

作者： peng CHU Jianguo FENG peng zhu Lei GUO Long ZHANG Leilei LIU Guoqing LUO Ke WU College of Electronic and Optical Engineering Nanjing University of Posts and Telecommunications School of Electronics and Information Hangzhou Dianzi University Guangdong Provincial Key Laboratory of Optoelectronic Information Processing Chips and Systems Sun Yat-sen University National and Local Joint Engineering Laboratory of RF Integration and Micro-Assembly Technology School of Information and Communication Engineering Dalian University of Technology Poly-Grames Research Center Polytechnique Montreal College of Electronics and Information Engineering Shenzhen University

This article presents a highly efficient method for substrate integrated waveguide (SIW) filters to achieve very wide stopbands. By employing the proposed trisection slots in addition to the bisection slots as the inter-coupling structures, all spurious modes below TE505 of a SIW filter working in the fundamental mode TE101 (f0)can be eliminated without requiring additional structure or complex theoretical analysis, without affecting the design of the fundamental passbands, and without degrading the performance of the filters. For verification, two prototype filters are designed, fabricated, and measured with wide stopbands up to 4.15 f0and 4.83 f0, respectively. The proposed technique could facilitate the development of high-performance wide-stopband SIW filters for microwave/wireless circuits and systems.

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Gonadal transcriptomic analysis and differentially expressed genes between the testes and ovaries in Trachinotus ovatus

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Aquaculture and Fisheries 2022年第1期7卷 31-39页

作者： Pingping He peng zhu Pinyuan Wei Xiaofei zhuo Yuan Ma Xiaohan Chen Yong Lin Youhou Xu Hui Luo Jinxia peng Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture Guangxi Academy of Fisheries SciencesNanning530021China Beibu Gulf University Qinzhou535000China College of Animal Science Southwest UniversityChongqing402460China

The Trachinotus ovatus is a popular aquaculture species in China.There are no obvious morphological differences between male and female fish,even during maturity,prompting research studies on sex-related features of this fish.To examine sex determination-and gonadal development-related genes,we conducted transcriptome analysis of the ovaries and testes of T.ovatus.A total of 345,972,132 high-quality clean reads were obtained from 12 libraries.In addition,28,137 gonad-expressed unigenes were obtained by mapping the clean reads to the T.ovatus reference genome.A total of 8,237 differentially expressed genes(DEGs)were identified between stage I ovaries and testes,including 3,235 testicular upregulated and 5,002 ovarian upregulated genes.Furthermore,13,448 DEGs were obtained between stage III ovarian and testicular libraries,including 7,576 testicular upregulated and 5,872 ovarian upregulated genes.The DEGs included some sex-determining genes such as sry,dmrt1,and amh.DEGs between ovarian and testicular libraries were significantly enriched with KEGG pathways that are involved in gonadal development,sex determination,and gonadal function.Then,10 DEGs(seven testicular upregulated and three ovarian upregulated unigenes)were selected for quantitative real-time PCR analysis.Four genes(zinc-binding protein A33-like,pro-opiomelanocortin-like,leucine-rich repeat and transmembrane domain-containing protein 2-like,and forkhead boxC1)showed a specific testicular expression pattern.The gonadally expressed as well as testicular and ovarian DEGs provide useful information for further research on the reproductive biology of T.ovatus.

关键词： Transcriptome Trachinotus ovatus Gonad High-throughput sequencing RT-qPCR

Weakened humoral immune responses of inactivated SARS-CoV-2 vaccines in patients with solid tumors

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Cancer Communications 2023年第2期43卷 280-284页

作者： Zhiwei Chen peng zhu Zuojin Liu Bin zhu Guobing Yin Jia Ming Rui Song Qingbo Pan Tong Li Xingwei Jiang Bing Wang Shuaibin Liu Hongxing Cai Jingjie Wang Yuling Han Zijing Lin Yang Hong Min Chen Mingli peng Lina Hu Dachuan Cai Hong Ren Department of Infectious Diseases Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education)Institute for Viral Hepatitisthe Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010P.R.China Department of Gastrointestinal Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010P.R.China Department of Hepatobiliary Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010P.R.China Department of Thoracic and Cardiovascular Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010P.R.China Department of Breast and Thyroid Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010P.R.China Department of Gynaecology and Obstetrics Reproductive Medicine Centerthe Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010P.R.China

Dear Editor Coronavirus disease 19(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),remains a pandemic.Cancer patients have a higher risk of poor outcomes for SARS-CoV-2 infection than the general population[1].Vaccines were shown to effectively prevent SARS-CoV-2 infection,severe disease progression,and mortality.Inactivated SARS-CoV-2 vaccines(BBIBPCorV and CoronaVac)have been approved and widely used in China,with the former shown to be more effective than the latter[2].Hence,there is an urgent need to investigate the safety and humoral immune responses of inactivated vaccines in cancer patients.

关键词： patients vaccines humoral

One-step quantum dialogue

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Chinese Physics B 2024年第3期33卷 95-104页

作者：朱鹏辉钟伟杜明明李喜云周澜盛宇波 College of Science Nanjing University of Posts and TelecommunicationsNanjing 210023China College of Electronic and Optical Engineering & College of Flexible Electronics (Future Technology) Nanjing University of Posts and TelecommunicationsNanjing 210023China Institute of Quantum Information and Technology Nanjing University of Posts and TelecommunicationsNanjing 210003China

Quantum dialogue(QD)enables two communication parties to directly exchange secret messages simultaneously.In conventional QD protocols,photons need to transmit in the quantum channel for two rounds.In this paper,we propose a one-step QD protocol based on the hyperentanglement.With the help of the non-local hyperentanglement-assisted Bell state measurement(BSM),the photons only need to transmit in the quantum channel once.We prove that our one-step QD protocol is secure in theory and numerically simulate its secret message capacity under practical experimental condition.Compared with previous QD protocols,the one-step QD protocol can effectively simplify the experiment operations and reduce the message loss caused by the photon transmission loss.Meanwhile,the non-local hyperentanglement-assisted BSM has a success probability of 100%and is feasible with linear optical elements.Moreover,combined with the hyperentanglement heralded amplification and purification,our protocol is possible to realize long-distance one-step QD.

关键词： one-step quantum dialogue hyperentanglement hyperentanglement distribution non-local Bell-state measurement

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Analysis of a Streamline-Diffusion Finite Element Method on Bakhvalov-Shishkin Mesh for Singularly Perturbed Problem

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Numerical Mathematics(Theory,Methods and Applications) 2017年第1期10卷 44-64页

作者： Yunhui Yin peng zhu Bin Wang College of Mathematics Physics and Information Engineering Jiaxing UniversityJiaxingZhejiang 314001China College of Mechanical and Electrical Engineering Jiaxing UniversityJiaxingZhejiang 314001China

In this paper,a bilinear Streamline-Diffusion finite element method on Bakhvalov-Shishkin mesh for singularly perturbed convection–diffusion problem is analyzed.The method is shown to be convergent uniformly in the perturbation parameterǫprovided only that ∈≤N^(−1).An O(N^(−2)(lnN)^(1/2))convergent rate in a discrete streamline-diffusion norm is established under certain regularity assump-tions.Finally,through numerical experiments,we verified the theoretical results.

关键词： singularly perturbed problem Streamline-Diffusion finite element method Bakhvalov-Shishkin mesh error estimate

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聚氨酯固化钙质砂物理力学特性

长江科学院院报 2024年第1期41卷 107-113页

作者：王智超彭柱彭峰闫实湘潭大学岩土力学与工程安全湖南重点实验室湖南湘潭411105 湘潭大学土木工程学院湖南湘潭411105 中国建筑第五工程局有限公司长沙410000

聚氨酯加固是一种新型环保快速的土质改良方法。针对南海钙质砂采用聚氨酯快速改良,并通过室内试验验证该处置方法的有效性和适用性。通过对聚氨酯固化钙质砂试样开展无侧限抗压强度试验、静力荷载和循环荷载下的三轴试验以及渗透试验,... 详细信息

聚氨酯加固是一种新型环保快速的土质改良方法。针对南海钙质砂采用聚氨酯快速改良,并通过室内试验验证该处置方法的有效性和适用性。通过对聚氨酯固化钙质砂试样开展无侧限抗压强度试验、静力荷载和循环荷载下的三轴试验以及渗透试验,研究聚氨酯固化钙质砂的最佳凝胶时间,静、动强度特性及渗透特性。试验结果表明:固化试样的最佳凝胶时间为6.5 h;随着掺量的增加,固化钙质砂黏聚力得到显著提高,内摩擦角基本保持不变,在海水环境养护下的聚氨酯钙质砂仍然保持了较高的强度;随着掺量的增加,聚氨酯钙质砂的初始动剪切模量增加,最大阻尼比降低;钙质素砂渗透系数的数量级为10^(-6),掺入2%~10%聚氨酯后数量级降至10^(-8)~10^(-7),聚氨酯补漏效果较好。

关键词：钙质砂聚氨酯凝胶时间力学特性渗透系数

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参与电商能否促进设施蔬菜种植户绿色生产?——基于山东省五市十一县的微观调研

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中国人口·资源与环境 2024年第2期34卷 106-118页

作者：李全海朱鹏郑军山东农业大学经济管理学院山东泰安271018 山东管理学院山东济南250300

引导设施蔬菜种植户实现绿色转型是保障国家“菜篮子”安全的重中之重。然而,中国设施蔬菜生产分散,不易于政府和消费者监管,种植户违规使用化肥农药的现象屡禁不止,仅从生产端发力恐难以实现上述目标。为此,该研究从销售端着手,基于山... 详细信息

引导设施蔬菜种植户实现绿色转型是保障国家“菜篮子”安全的重中之重。然而,中国设施蔬菜生产分散,不易于政府和消费者监管,种植户违规使用化肥农药的现象屡禁不止,仅从生产端发力恐难以实现上述目标。为此,该研究从销售端着手,基于山东省五市十一县的微观调研数据,利用倾向得分匹配和中介模型,考察参与电商对设施蔬菜种植户绿色生产行为的影响。研究发现:①参与电商的设施蔬菜种植户采纳绿色生产行为的概率比非电商户高23.7%,利用工具变量法控制内生性后,该结论依然成立;从参与强度角度讲,高强度参与比低强度参与电商更能提高设施蔬菜种植户的绿色生产水平;从参与模式角度讲,平台电商对设施蔬菜种植户绿色生产行为的提升作用要强于社交电商。②异质性分析发现,作物类别、经营规模和风险偏好会导致影响效应分化,参与电商对根茎类、中等规模、风险偏好型设施蔬菜种植户绿色生产行为的影响效应尤为明显。③机制分析发现,价格预期激励、交易成本节约、信息获取便利、质量信誉评价是参与电商影响设施蔬菜种植户绿色生产行为的中介渠道,中介效应占比依次为20.48%、16.60%、8.28%、10.63%。据此提出:鼓励种植户通过电商渠道售卖设施蔬菜,引导其提高参与电商强度,增加参与模式的多样性;电商推广过程中,要综合考虑作物类别、经营规模、风险偏好等群体异质性特征,制定差异化策略;重点完善绿色设施蔬菜的价格激励机制和交易成本节约机制,拓宽种植户信息获取渠道,密切关注消费者质量评价反馈。

关键词：农村电商绿色生产设施蔬菜倾向得分匹配

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Model of Underground Ant Nest Structure Using Static and Dynamic Finite Element Analysis

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Acta Mechanica Solida Sinica 2018年第6期31卷 717-730页

作者： Wenjun Qu Wei Zhou peng zhu Zhi Zhang Department of Structural Engineering Tongji University Shanghai 200092 China The High School Affiliated with Shanghai University Shanghai 200444 Chinch

This paper focuses on the structural characteristics of ant nests,which are complex structures.Natural underground ant nests generally have good air circulation,pressure resistance, waterproof properties,thermal insulation and a favorable temperature and relative humidity. Additionally,ant nests are often surrounded by trees and other natural barriers.In this study, the natural underground ant nests of Iridomyrmex anceps were gathered from different collection sites.Manual cutting and frozen computer numerical control milling were performed on the ant nests in a laboratory.The internal structure of each nest was measured and recorded,and then, the 2D and 3D numerical structure models of the Iridomyrmex anceps nest were created.The static and dynamic simulation analysis of an underground ant nest structure was performed by using finite element analysis software (ABAQUS),and the mechanical properties of the ant nest were discussed.The underground ant nest structure effectively resisted the additional stress due to external static and live loads,and the ant nest was not completely destroyed.

关键词： Underground ant nest Iridomyrmex anceps Frozen CNC milling Finite element analysis Static simulation Dynamic simulation