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Selection and characterization of the novel anti-human PD-1 FV78 antibody from a targeted epitope mammalian cell-displayed antibody library

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Cellular & Molecular Immunology 2018年第2期15卷 146-157页

作者： Longlong Luo Shi Wang Xiaoling Lang Tingting Zhou Jing Geng Xinying Li Chunxia qiao Jiannan Feng Beifen Shen Ming Lv yan Li Laboratory of Immunology Institute of Basic Medical SciencesBeijing100850China Laboratory of Cellular and Molecular Immunology Institute of ImmunologyHenan UniversityKaifeng475001China

Currently,display-based methods are well established and widely used in antibody engineering for affinity maturation and structural stability *** obtained a novel anti-human programmed death 1(PD-1)antibody using computer-aided design and a mammalian cell display technology *** used computer-aided modeling and distance geometry methods to predict and assign the key residues that contributed to the binding of human PD-L1 to ***,we analyzed the sequence of nivolumab(an anti-human PD-1 antibody,referred to as MIL75 in the article)to determine the template for antibody design and library *** identified a series of potential substitutions on the obtained template and constructed a virtual epitope-targeted antibody library based on the physicochemical properties and each possible location of the assigned key *** virtual antibody libraries were displayed on the surface of mammalian cells as the antigen-binding fragments of full-length immunoglobulin ***,we used flow cytometry and sequencing approaches to sort and screen the ***,we obtained a novel anti-human PD-1 antibody named ***78 competitively recognized the PD-1 epitopes that interacted with MIL75 and possessed an affinity comparable to *** results implied that FV78 possessed equivalent bioactivity in vitro and in vivo compared with MIL75,which highlighted the probability and prospect of FV78 becoming a new potential antibody therapy.

关键词： antibody computer-guided modeling distance geometry human PD-1 mammalian cell-displayed antibody library

三维斑点追踪成像联合血生化指标对新冠肺炎住院患者死亡风险的预测价值探讨

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湖北医药学院学报 2024年第1期43卷 46-51页

作者：邓鑫淦韩宇琛严定芳张文君湖北医药学院附属太和医院超声科湖北十堰442000 湖北医药学院公共卫生与健康学院湖北十堰442000

目的:探讨三维斑点追踪成像(3D-STI)技术与血生化指标联合预测新型冠状病毒肺炎住院患者死亡的价值。方法:收集2022年11月至2023年2月确诊并住院治疗的165例新冠肺炎患者的入院资料。使用LASSO回归筛选影响新冠肺炎患者死亡的指标。按照... 详细信息

目的:探讨三维斑点追踪成像(3D-STI)技术与血生化指标联合预测新型冠状病毒肺炎住院患者死亡的价值。方法:收集2022年11月至2023年2月确诊并住院治疗的165例新冠肺炎患者的入院资料。使用LASSO回归筛选影响新冠肺炎患者死亡的指标。按照7∶3的比例进行数据拆分,在训练集上使用5次10折交叉验证进行预测模型构建,并绘制列线图以供实际使用。通过ROC曲线下面积、准确度、灵敏度和特异度进行模型评估。在测试集上绘制DCA曲线,以判断模型在临床决策中的实际效益。结果:LASSO回归共筛选出5个关键变量包括主应变、纵向应变、白蛋白、血肌酐及乳酸脱氢酶用于模型构建。训练集包括115例患者,测试集包括50例患者,两组基线资料无差异。在训练集和测试集中,ROC曲线下面积分别为0.909和0.882,准确度为0.835(0.754,0.898)和0.840(0.709,0.928),灵敏度为0.739和0.800,特异度为0.960和0.900。临床决策曲线图显示该模型的潜在临床获益可观。结论:三维斑点追踪成像联合血生化指标构建的列线图模型在预测新冠肺炎住院患者死亡风险方面具有较高的临床应用价值,可指导不良结局的早期干预。

关键词：三维斑点追踪成像血生化指标新冠肺炎死亡预测

Youjing granules ameliorate spermatogenesis in rats through regulating the prolifereation of spermatogonial stem cells

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Chinese Journal of Natural Medicines 2022年第8期20卷 580-588页

作者： JIANG Xu-Ping SUN Yao-Xiang qiao Bin ZHU wen-jiao CHU Yu-Jiao SUN Miao-Miao ANG Ruije MA Tie-Liang ANG Zhi-An Department of Traditional Chinese Medicine the Affiliated Yixing Clinical School of Medical School of Yangzhou UniversityYixing 214200China Central Laboratory the Affiliated Yixing Hospital of Jiangsu UniversityYixing 214200China Department of Rehabilitation the People's Hospital of Daxinganling RegionDaxinganling 165000China School of Medicine School of Integrated Chinese and Western MedicineNanjing University of Chinese MedicineNanjing 210023China

Male infertility has evolved from a common reproductive system disease to a major social *** granule(YG)is a Chinese medicinal material used as a therapy method for tonifying the kidneys and removing dampness due to its pathogenic *** has been shown to regulate sperm quality in clinical trials,but the underlying mechanism is not fully *** present study was aimed to explore the protective effects and mechanism of action of YG on male reproductive system damage caused by methyl methane sulfonate(MMS).We first established an infertility model of rats through oral administration of MMS and then treated with *** determine the effect of YG,spermatogenesis,microvascular density,and secretory function of Leydig cells and Sertoli cells in rats were *** stem cells(SSCs)were co-cultured with mouse embryo fibroblast(MEF)cells as an in vitro cell model before exposure to serum containing ***,the proliferation and apoptosis of SSCs were *** indicated that YG increased the expression of self-renewal and proliferation-related molecules such as glial cell line derived neurotrophic factor(GDNF)and fibroblast growth factor-2(FGF2),and improved the quality of sperm and the proliferation of *** conclusion,YG may protect spermatogenetic function of rats through regulating the proliferation and self-renewal of SSCs.

关键词： Male infertility Youjing granules Spermatogenesis Spermatogonial stem cells

血清FNDC5和CTRP12表达水平与代谢相关脂肪性肝病的临床相关性

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国际消化病杂志 2024年第4期44卷 241-246页

作者：文习兵赵涛黎红霞赵蕾颜悦蓉龙丹洪湖市妇幼保健院外科 433200 华中科技大学同济医学院附属协和医院消化内科湖北武汉430022 湖北文理学院附属襄阳市中心医院消化内科 441021

目的探究血清Ⅲ型纤连蛋白结构域5(FNDC5)和补体C1q/肿瘤坏死因子相关蛋白12(CTRP12)表达水平与代谢相关脂肪性肝病(MAFLD)患者糖脂代谢、肝功能的相关性。方法选择2019年6月至2022年6月在洪湖市妇幼保健院和襄阳市中心医院就诊的100... 详细信息

目的探究血清Ⅲ型纤连蛋白结构域5(FNDC5)和补体C1q/肿瘤坏死因子相关蛋白12(CTRP12)表达水平与代谢相关脂肪性肝病(MAFLD)患者糖脂代谢、肝功能的相关性。方法选择2019年6月至2022年6月在洪湖市妇幼保健院和襄阳市中心医院就诊的100例MAFLD患者作为研究对象(设为MAFLD组),另选择同期洪湖市妇幼保健院体检中心的100名健康体检者作为对照组。采用ELISA法检测血清FNDC5和CTRP12表达水平。采用Pearson相关性分析探讨血清FNDC5、CTRP12与MAFLD患者糖脂代谢、肝功能的关系。采用ROC曲线分析血清FNDC5和CTRP12表达水平对MAFLD的诊断价值。采用logistic回归模型分析影响MAFLD发生的危险因素。结果与对照组相比,MAFLD组的ALT、AST、白蛋白(ALB)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TC)、总胆固醇(TG)、空腹血糖(FBG)、空腹胰岛素(FINS)水平和胰岛素抵抗指数(HOMA-IR)均显著升高,差异均有统计学意义(P均<0.05)。与对照组相比,MAFLD组的血清FNDC5表达水平显著升高,血清CTRP12表达水平显著降低,差异均有统计学意义(P均<0.05)。Pearson相关性分析结果显示,MAFLD组的血清FNDC5表达水平与ALT、FBG、TG、FINS和HOMA-IR均呈显著正相关(r=0.504、0.496、0.474、0.418、0.501,P均<0.001);血清CTRP12表达水平与ALT、FBG、TG、FINS和HOMA-IR均呈显著负相关(r=-0.496、-0.421、-0.403、-0.425、-0.496,P均<0.001)。ROC曲线分析结果显示,血清FNDC5和CTRP12联合检测诊断MAFLD的曲线下面积(AUC)为0.860,分别大于单项检测;此外,联合检测的敏感度、特异度分别均分别高于单项检测。多因素logistic回归模型分析结果显示,TG、HOMA-IR和FNDC5均是MAFLD发生的独立危险因素,而CTRP12是MAFLD发生的保护因素(P均<0.05)。结论 MAFLD患者的血清FNDC5表达上调,血清CTRP12表达下调,且均与糖脂代谢、肝功能密切相关,其可能可以成为诊断MAFLD的生物标志物。

关键词：代谢相关脂肪性肝病 Ⅲ型纤连蛋白结构域5 补体C1q/肿瘤坏死因子相关蛋白12 糖脂代谢肝功能

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A silicon-graphene-silicon transistor with an improved current gain

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Journal of Materials Science & Technology 2022年第9期104卷 127-130页

作者： Chi Liu Xu-Qi yang Wei Ma Xin-Zhe Wang Hai-yan Jiang wen-Cai Ren Dong-Ming Sun Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of Sciences72 Wenhua RoadShenyang 110016China School of Material Science and Engineering University of Science and Technology of China72 Wenhua RoadShenyang 110016China

In history,semiconductor-metal-semiconductor transistor(SMST)was proposed for frequency ***,a general fabrication method is still missing due to the unsolved technological problem of deposition of a general crystalline semiconductor on metal,and a thinner metal base is also difficult to be fabricated with high ***,due to the atomic thickness of graphene,the concept of semiconductor-graphene-semiconductor transistor(SGST)has emerged which leads to the renaissance of SMST,however the experimental study is in its *** this letter,SMST and SGST are fabricated using Si membrane *** is found the common base current gain can be improved from about 0.5%in a Si-Au-Si transistor to about 1%in a Si-Gr-Ge one,and to above 10%in a Si-Gr-Si one,which is attributed to both the ultra-thin thickness and the quantum capacitance effect of graphene.

关键词： Semiconductor metal semiconductor transistor Graphene base transistor Graphene base heterojunction transistor

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波形梁钢护栏旧板翻新方法

兰州石化职业技术大学学报 2024年第1期24卷 32-35页

作者：陈玉贤乔东兴周琪玲王文斌张应龙甘肃路桥新锐交通科技有限责任公司甘肃兰州730100

针对公路改建或扩建时,原公路所用的旧波形护栏被大量报废的问题,研发了一项护栏翻新技术。该技术的工艺流程主要包括翻新准备、旧板挑选、旧板结构整形、旧板除漆除锈、环氧锌基聚酯复合涂层喷涂以及成品包装码垛。技术的关键点在于旧... 详细信息

针对公路改建或扩建时,原公路所用的旧波形护栏被大量报废的问题,研发了一项护栏翻新技术。该技术的工艺流程主要包括翻新准备、旧板挑选、旧板结构整形、旧板除漆除锈、环氧锌基聚酯复合涂层喷涂以及成品包装码垛。技术的关键点在于旧护栏板结构整形、旧板除漆除锈和环氧锌基聚酯复合涂层喷涂三部分,可使旧护栏板满足防撞等级要求、外观要求和使用性能要求,有效解决了旧护栏板的报废处理而带来的资源消耗和浪费问题。通过护栏板翻新技术,使翻新后的护栏板满足使用要求,实现旧护栏板的再利用,从而节约钢铁资源,减少护栏的加工工序,降低了公路的建设成本,具备一定的经济效益和社会效益。

关键词：波形护栏结构整形除漆除锈抛丸表面处理喷涂翻新

Potent anti-angiogenesis and anti-tumor activity of a nove human anti-VEGF antibody, MIL60

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Cellular & Molecular Immunology 2014年第3期11卷 285-293页

作者： Jing yang Qun Wang Chunxia qiao Zhou Lin Xinying Li Yifei Huang Tingting Zhou yan Li Beifen Shen Ming Lv Jiannan Feng Laboratory of Immunology Institute of Basic Medical Sciences Beijing China Department of Pathogens and Immunology Logistics College of Chinese People's Armed Police Forces Tianjin China Department of Ophthalmology General Hospital of People's Liberation Army Beijing China These authors contributed equally to this work

Angiogenesis is crucial for tumor development, growth and metastasis. Vascular endothelial growth factor （VEGF） has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis, and blocking the activity of VEGF can starve tumors. Avastin, which is a humanized anti-VEGF antibody, has been successfully applied in clinics since 2004. However, the price of Avastin is extremely high for Chinese people. Here, we report a novel human anti-VEGF neutralizing antibody, MIL60, which shows an affinity comparable to that of Avastin （the KD value of MIL60 was 44.5 pM, while that of Avastin was 42.7 pM）. MIL60 displays favorable actions in inhibiting VEGF-triggered endothelial cell proliferation （the IC5o value of M IL60 was 31-6.4 ng/ml and that of Avastin was 47--.8.1 ng/ml）, migration （8 pg/ml or 0.8 pg/ml MIL60 versusthe control： P〈O.05） and tube formation （2 I^g/ml or 0.2 lzg/ml MIL60 versusthe control： P〈O.05） viathe VEGFR2 signaling pathway. Moreover, MIL60 was shown to inhibit tumor growth and angiogenesis in vivo in xenograft models of human colon carcinoma and ovarian cancer using immunotherapy and immunohistochemistry analysis （MIL60 versus N.S.： P=0.0007; Avastin versus N.S.： P=0.00046）. These data suggest that MIL60 is a potential therapeutic, anti-angiogenic agent. Our work provides a novel anti-VEGF antibody, which can be considered an anti-tumor antibody candidate and a new option for patients with various cancers.

关键词： angiogenesis anti-VEGF antibody cancer

R-(+)-长叶薄荷酮对腹腔感染耐药菌小鼠的抗炎作用

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中华医院感染学杂志 2024年第16期34卷 2405-2410页

作者：宫海燕杨珊珊王晓娟郑琳川季兴磊熊文娟广东医科大学附属东莞第一医院检验科广东东莞523710 新疆医科大学第五附属医院(第五临床医学院)检验科新疆乌鲁木齐830011

目的明确腹腔感染耐药菌小鼠的半数致死浓度(LC50)和绝对致死浓度(LC100),探讨R-(+)-长叶薄荷酮对腹腔感染耐药菌小鼠的抗炎作用。方法随机将小鼠分为正常对照组(NC组)、耐药菌株感染模型组(Model组)、R-(+)-长叶薄荷酮组(PU组,20 mg/... 详细信息

目的明确腹腔感染耐药菌小鼠的半数致死浓度(LC50)和绝对致死浓度(LC100),探讨R-(+)-长叶薄荷酮对腹腔感染耐药菌小鼠的抗炎作用。方法随机将小鼠分为正常对照组(NC组)、耐药菌株感染模型组(Model组)、R-(+)-长叶薄荷酮组(PU组,20 mg/kg)、头孢克肟组(CFM组,26 mg/kg),每组10只;除NC组外,其他试验组进行干预,连续3 d, 1次/d, Model组按照20 ml/kg经口灌胃食用油,PU组、CFM组分别给予等体积的R-(+)-长叶薄荷酮、头孢克肟,第3天给药后1 h,腹腔注射耐药大肠埃希菌(10 ml/kg),观察24、48 h后收集小鼠眼眶血、腹腔冲洗液、腹膜组织;采用全自动细胞分析仪进行血液、腹腔冲洗液的白细胞计数;瑞氏-吉姆萨染色观察血细胞形态变化;苏木精-伊红(HE)染色法观察腹腔组织病理形态变化。结果腹腔感染耐药菌小鼠的LC50和LC100分别是1.50×10~8 CFU/ml、2.25×10~8 CFU/ml;与NC组相比,Model组小鼠腹腔内存在弥漫性炎症,腹腔充血、水肿;而PU组、CFM组小鼠腹腔内炎症、充血、水肿程度较Model组不明显;眼眶血白细胞计数表明PU组较NC组有所降低,较Model组、CFM组无统计学差异;腹腔冲洗液白细胞计数PU组低于Model组,较NC组增高,较CFM组无统计学差异,表明R-(+)-长叶薄荷酮对腹腔感染耐药菌小鼠具有抗炎作用(P<0.05);HE结果显示,PU组、CFM组腹膜组织结构完整,间皮细胞排列整齐,腹膜组织间质较NC组可见少量淋巴细胞浸润,相对于Model组腹膜组织结构更加完整,淋巴细胞浸润较少,表明R-(+)-长叶薄荷酮对腹腔耐药菌的感染具有显著的抗感染保护作用。结论 R-(+)-长叶薄荷酮对腹腔感染耐药菌小鼠具有一定抗炎作用,为R-(+)-长叶薄荷酮抗感染药理作用机制的探索提供一定的研究基础。

关键词： R-(+)-长叶薄荷酮腹腔感染耐药性大肠埃希菌抗炎作用

Crystal Structure, One-and Two-photon Excited Fluorescence and Bioimaging of a D-π-A Structural Triphenylamine Derivative

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Chinese Journal of Structural Chemistry 2019年第2期38卷 224-232,166页

作者： JIN Feng YE Zhi-Feng LIAO Rong-Bao qiao Ling-yan TAO Dong-Liang LIU Yong College of Chemical and Material Engineering Fuyang Normal University College of Life Science Fuyang Normal University

An electron donor-π-bridge-electron acceptor(D-π-A) optical functional organic compound comprising a triphenylamine moiety as the electron donor and pyridine moiety as the electron acceptor was synthesized. The structure of the compound was solved by single-crystal X-ray diffraction analysis. It crystallizes in monoclinic, space group P21, with a = 9.753(5), b = 8.815(5), c = 25.554(5) ?, β = 96.315(5)°, V = 2184(2) ?~3, Z = 2, D_c = 1.136 g/m^3, F(000) = 792, Μr = 746.92, μ = 0.069 mm^(-1), the final R = 0.0658 and wR = 0.1730 for 6790 observed reflections with I > 2(I). Study of nonlinear optical properties shows that the compound exhibits excellent two-photon excited fluorescence with the two-photon absorption cross-section value of 116 GM. The structure-property relationship was researched in detail through X-ray crystallography and quantum chemical calculation. Result of living cell imaging experiment shows its potential in fluorescence microscopy bioimaging.

关键词： triphenylamine crystal structure two-photon excited fluorescence bioimaging