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Evaluation of the metabolism of PEP06,an endostatin-RGDRGD 30-amino-acid polypeptide and a promising novel drug for targeting tumor cells

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Journal of Pharmaceutical Analysis 2022年第5期12卷 766-773页

作者： Liyun Niu Huiyu Zhou Yueru Lian Ya Gao Yulu Liu Ruolan Gu Zhuona Wu Xiaoxia Zhu Hui Gan zhiyun meng Guifang Dou State Key Laboratory of Drug Metabolism and Pharmacokinetics Department of Pharmaceutical SciencesBeijing Institute of Radiation MedicineBeijing100850China Henan University KaifengHenan475004China

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEP06 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.

关键词： PEP06 HRMS Metabolic stability Metabolites identification

A Survey on Distributed Network Localization from a Graph Laplacian Perspective

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Journal of Systems Science & Complexity 2024年第1期37卷 273-293页

作者： HAN Zhimin LIN zhiyun FU Minyue Artificial Intelligence Institute School of AutomationHangzhou Dianzi UniversityHangzhou 310018China Shenzhen Key Laboratory of Control Theory and Intelligent Systems School of System Design and Intelligent ManufacturingSouthern University of Science and TechnologyShenzhen 518055China Peng Cheng Laboratory Shenzhen 518000China

Network localization serves as a fundamental component for enabling various position based operations in multi-agent systems,facilitating tasks like target searching and formation control by providing accurate position information for all nodes in the network.Network localization focuses on the challenge of determining the positions of nodes within a network,relying on the known positions of anchor nodes and internode relative measurements.Over the past few decades,distributed network localization has garnered significant attention from researchers.This paper aims to provide a review of main results and advancements in the field of distributed network localization,with a particular focus on the perspective of graph Laplacian.Owning to its favorable characteristics,graph Laplacian unifies various network localization,even when dealing with diverse types of internode relative measurements,into a unified protocol framework,which can be constructed by a linear method and ensure the global convergence.

关键词： Distributed network localization graph Laplaian sensor network

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放创复合伤动物模型的研究进展

中国辐射卫生 2024年第2期33卷 209-214页

作者：郝若林窦桂芳孟志云叶彤李南熹朱晓霞顾若兰吴卓娜甘慧军事科学院军事医学研究院辐射医学研究所北京100850

放射损伤合并创伤称为放创复合伤。放创复合伤由于结合放射伤和创伤,具有创口反复溃烂,持久难愈的特点,是难愈性创伤的重点研究对象。动物模型的建立是放创复合伤相关研究的关键环节,合理的动物模型是可靠实验结果的有力保障。本文从辐... 详细信息

放射损伤合并创伤称为放创复合伤。放创复合伤由于结合放射伤和创伤,具有创口反复溃烂,持久难愈的特点,是难愈性创伤的重点研究对象。动物模型的建立是放创复合伤相关研究的关键环节,合理的动物模型是可靠实验结果的有力保障。本文从辐射类型、动物种类、致伤类型、致伤位置等多方面概述和归纳目前各类放创复合伤动物模型的研究进展,为放创复合伤标准化动物模型的建立、伤情机制研究以及防治功效评估提供科学基础。

关键词：放创复合伤动物模型难愈创伤辐射

A phaseⅠtrial of an oral subtype-selective histone deacetylase inhibitor,chidamide,in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer

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Chinese Journal of Cancer Research 2016年第4期28卷 444-451页

作者： Xingsheng Hu Lin Wang Lin Lin Xiaohong Han Guifang Dou zhiyun meng Yuankai Shi Department of Medical Oncology Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsNational Cancer Center/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China Laboratory of Drug Metabolism and Pharmacokinetics Beijing Institute of Transfusion MedicineBeijing 100850China

Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer （NSCLC）. Methods： Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel （175 mg/m2） and carboplatin [area under the curve （AUC） 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacoldnetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results： Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response （PR）. Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions： Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.

关键词： Chidamide HDAC inhibitor phase I paclitaxel and carboplatin non-small cell lung cancer

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放射性核素污染伤口去污膜的研制与表征

中华放射医学与防护杂志 2024年第4期44卷 247-254页

作者：田庄何琪乔璇李林涛胡瑄全晓筱叶彤甘慧吴卓娜顾若兰朱晓霞孙云波刘曙晨窦桂芳孟志云军事科学院军事医学研究院辐射医学研究所北京100850

目的研发一款适用于放射性核素污染的去污膜,对其物理性质、核素清除效果和安全性进行考察。方法以海藻酸钠和壳聚糖为基质膜,负载复方洗消剂配方制备去污膜。通过将去污膜置于生理盐水中,测试其溶胀性能;通过拉力机测试去污膜的断裂应... 详细信息

目的研发一款适用于放射性核素污染的去污膜,对其物理性质、核素清除效果和安全性进行考察。方法以海藻酸钠和壳聚糖为基质膜,负载复方洗消剂配方制备去污膜。通过将去污膜置于生理盐水中,测试其溶胀性能;通过拉力机测试去污膜的断裂应力与应变。以生理盐水、基质膜、1%二乙烯三胺五乙酸五钠(DTPA-5Na)基质膜组作为对照组,在豚鼠完整皮肤与伤口模型上检测去污膜对铀、铯、钴、铈和锶的清除效果。采用噻唑蓝比色法(MTT)测试去污膜的浸提液对小鼠上皮样成纤维细胞(L929)的毒性;将去污膜的浸提液注射到Kunming(KM)小鼠体内,测试其全身急性毒性。将去污膜覆盖于新西兰兔背部测试皮肤刺激性。结果去污膜成膜时间为1.5 min,溶胀率为(134.96±3.49)%,断裂应力为(393.88±53.53)kN/m2,断裂应变为(163.00±35.29)%。在完整皮肤上,去污膜对铀的清除率为(95.38±0.23)%,对铯为(96.57±0.49)%。在伤口模型上,去污膜对铀、铯、锶、钴和铈的清除率分别为(92.16±0.52)%、(90.44±1.16)%、(92.03±0.87)%、(92.79±0.51)%和(92.85±0.82)%,均优于生理盐水、基质膜与1%DTPA-5Na基质膜组(t=3.81~4498.55,P<0.001)。安全性评价试验表明,去污膜符合国家医疗器械生物学评价标准。结论去污膜能够快速成膜且对多种核素均有良好的清除效果,安全性良好,适用放射性核素污染人员的完整皮肤或伤口去污,有望为核污染区域的工作人员提供安全保障。

关键词：洗消剂去污膜放射性污染

Influence of Repetitive Impulse Waveforms on Surface Discharge Characteristics and Insulation Life for Polyimide Film

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CSEE Journal of Power and Energy Systems 2024年第2期10卷 746-755页

作者： zhiyun Han Qingmin Li Yujin Guo Tao Liu Guojing Dong Hanwen Ren State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources North China Electric Power UniversityBeijing 102206China Electric Power Research Institute Beijing 100085China Inner Mongolia Electric Economy and Technology Academy Hohhot 010020China

Accelerated insulation aging problems under high frequency repetitive impulses in power electronic transformers are drawing more and more attention in modern power systems. Partial discharge (PD) characteristics including discharge inception voltage, phase distribution and statistical characteristics on polyimide (PI) surface under different impulse waveforms and the insulation life of PI films are studied in this paper. We carry out experiments based on PD and insulation lifetime test systems, using five different types of repetitive impulses, including three bipolar waves and two unipolar waves. The experimental results show that there is little variation in discharge inception voltage under different waveforms, but great variation in phase distribution and statistical characteristics of PD. In addition, insulation life is approximately the same under different waveforms with the same polarity, and the aging rate under bipolar waveforms is larger than that under unipolar waveforms. We explain the differences between the bipolar and unipolar waveforms on insulation life, which can be concluded that the surface charge under unipolar waveform accumulates more significnatly compared with bipolar waveform and decreases the electric filed strength in discharging the air gap and inhibits surface discharge from occurring.

关键词： Insulation life polyimide film power electronic transformer repetitive impulse surface discharge characteristics

Molecule configurations modulate packing array and charge transfer in cocrystal engineering

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Science China Chemistry 2024年第2期67卷 512-516页

作者： Shenglong An mengyuan Qiao Xin Jin Xuanying Chen Jianhua Su Lifang Guo zhiyun Zhang Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Feringa Nobel Prize Scientist Joint Research CentreFrontiers Science Center for Materiobiology and Dynamic ChemistryEast China University of Science&TechnologyShanghai200237China

Organic cocrystal as an emerging assembly strategy has received increasing attention in constructing multiple functional materials,through continually screening suitable constituent monomers or changing their stoichiometry ratios.However,the role of molecule configuration in the cocrystal field is rarely explored despite the fascinating potential in regulating the packing mode.In this study,the N,N′-diphenyl-5,10-dihydrophenazine derivatives(DPPs) with the flexible scaffold and different methyl substitutions are selected as the donors bearing various molecular configurations.In a simple collaborative way,a series of cocrystals based on DPPs and OFN(octafluoronaphthalene) are fabricated,exhibiting two self-adaptive molecular stacking arrays.X-ray crystallographic analysis and theoretical calculation unveil their different π···π interactions and charge transfer characters,leading to the significant emission redshift up to 125 nm compared with individual DPPs.As a result,controllable molecule stacking structure,tunable emission,and charge transfer properties can be achieved.The study provides a new perspective to reveal the structure-property relationships at the molecular level by controlling the molecule configuration in cocrystal engineering,contributing to the development of cocrystal theoretical physics and organic functional materials.

关键词： cocrystals molecular configuration self-adaptive packing mode charge transfer

Boosting oxygen reduction activity and CO_(2) resistance on bismuth ferrite-based perovskite cathode for low-temperature solid oxide fuel cells below 600℃

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Journal of Energy Chemistry 2024年第3期90卷 600-609,I0013页

作者： Juntao Gao zhiyun Wei mengke Yuan Zhe Wang Zhe Lü Qiang Li Lingling Xu Bo Wei School of Physics Harbin Institute of TechnologyHarbin 150001HeilongjiangChina Key Laboratory of Functional Inorganic Material Chemistry Ministry of EducationSchool of Chemistry and Materials ScienceHeilongjiang UniversityHarbin 150080HeilongjiangChina School of Physics and Electronic Engineering Harbin Normal UniversityHarbin 150025HeilongjiangChina

Developing efficient and stable cathodes for low-temperature solid oxide fuel cells(LT-SOFCs) is of great importance for the practical commercialization.Herein,we propose a series of Sm-modified Bi_(0.7-x)Sm_xSr_(0.3)FeO_(3-δ) perovskites as highly-active catalysts for LT-SOFCs.Sm doping can significantly enhance the electrocata lytic activity and chemical stability of cathode.At 600℃,Bi_(0.675)Sm_(0.025)Sr_(0.3)FeO_(3-δ)(BSSF25) cathode has been found to be the optimum composition with a polarization resistance of 0.098 Ω cm^2,which is only around 22.8% of Bi_(0.7)Sr_(0.3)FeO_(3-δ)(BSF).A full cell utilizing BSSF25 displays an exceptional output density of 790 mW cm^(-2),which can operate continuously over100 h without obvious degradation.The remarkable electrochemical performance observed can be attributed to the improved O_(2) transport kinetics,superior surface oxygen adsorption capacity,as well as O_(2)p band centers in close proximity to the Fermi level.Moreover,larger average bonding energy(ABE) and the presence of highly acidic Bi,Sm,and Fe ions restrict the adsorption of CO_(2) on the cathode surface,resulting in excellent CO_(2) resistivity.This work provides valuable guidance for systematic design of efficient and durable catalysts for LT-SOFCs.

关键词： Low-temperature solid oxide fuel cell Perovskite cathode DFT calculations CO_(2) tolerance

Early-life famine exposure,adulthood obesity patterns,and risk of low-energy fracture

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Frontiers of Medicine 2024年第1期18卷 192-203页

作者： Hongyan Qi Chunyan Hu Jie Zhang Lin Lin Shuangyuan Wang Hong Lin Xiaojing Jia Yuanyue Zhu Yi Zhang Xueyan Wu Mian Li Min Xu Yu Xu Tiange Wang zhiyun Zhao Weiqing Wang Yufang Bi meng Dai Yuhong Chen Jieli Lu Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People’s Republic of ChinaShanghai National Center for Translational MedicineRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown.This study included 5323 community-dwelling subjects aged⩾40 years from China.Early-life famine exposure was identified based on the participants’birth dates.General obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or lower.Compared to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in men.Significant interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

关键词： famine obesity body mass index waist-to-hip ratio low-energy fracture