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Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers

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Cancer Biology & Medicine 2020年第4期17卷 1026-1038页

作者： Ying Cheng Xiaodong Zheng xuefu Wang Yongyan Chen Haiming Wei Rui Sun Zhigang Tian Haoyu Sun Hefei National Laboratory for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Sciences and MedicineInstitute of ImmunologyUniversity of Science and Technology of ChinaHefei 230027China Research Unit of NK Cell Study Chinese Academy of Medical SciencesBeijing 100864China

Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic ***:We constructed a trispecific killer engager(TriKE)consisting of anti-CD16,IL-15,and *** TriKE was designed to attract CD19^(+)tumor cells to CD16^(+)NK cells,whereas IL-15 sustained the proliferation,development,and survival of NK ***:Treatment with 161519 TriKE in the presence of CD19^(+)targets upregulated expression of CD69,CD107 a,TRAIL,IFN-γ,and TNF-α in NK cells,and significantly improved the proliferation and cytotoxicity of NK *** cells"armed"with 161519 TriKE showed stronger cytolysis against CD19+targets compared with that of"unarmed"NK cells.A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE,when compared with that in control mice or mice treated with 1619 *** use of IL-2 was a more effective treatment with 1619 BiKE,when compared with that using 161519 ***:The newly generated 161519 TriKE enhanced the proliferation,activation,cytokine secretion,and cytotoxicity of NK cells in the presence of CD19+tumor *** 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts,and could be used to treat CD19-positive cancers.

关键词： Trispecific antibody trispecific killer engager(TriKE) NK cell B-cell lymphoma tumor immunotherapy

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Cyclic and Linear Thiopeptides from Soil-Derived Streptomyces *** 203702 with Antiviral and Antibacterial Activities

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Chinese Journal of Chemistry 2021年第12期39卷 3277-3284页

作者： Dewu Zhang Yujia Wang Xinxin Hu Xiaoyu Wang Linzi Li Guowei Gu Bingyuan Zhang Shan Cen xuefu You Liyan Yu Division for Medicinal Microorganisms Related Strains CAMS Collection Center of Pathogenic Microorganisms Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China College of Health and Environment Beijing Union UniversityBeijing 100023China School of Pharmacy Yantai UniversityYantaiShangdong 264005China

A new cyclic thiopeptide,berninamycin F(3),three new linear thiopeptides,berninamycins G—I(4-6),and two known berninamycin derivatives,berninamycins C and D(1 and 2)were isolated from Streptomyces *** *** structures were elucidated through HRESIMS and one-and two-dimensional NMR data,and the absolute configurations were assigned using Marfey's *** 4-6 are the first examples of linear berninamycin ***,compound 4 is the first example of linear thiopeptide with a 1-(oxazol-2-yl)ethan-1-one group,compound 6 is the first linear thiopeptide derivative with methylated oxoacetate *** 1-6 exhibited excellent anti-Zika virus activities with IC_(50) values in the range of 4.4-10.5μmol/L,which were superior to that of the positive control ribavirin(IC_(50)=49.2μmol/L).Compounds 1 and 3 showed strong anti-influenza A virus activities with the IC_(50) values of 15.6 and 3.2μmol/L,*** 1 exhibited good antibacterial activities against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus ***.

关键词： Thiopeptide Streptomyces Natural products Structure elucidation Antiviral agents

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全关节镜下可吸收免打结线带重建在距腓前韧带损伤所致慢性踝关节外侧不稳患者中的应用效果

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国际医药卫生导报 2024年第1期30卷 99-103页

作者：刘磊李学福吕树振丁家宁侯昊聊城市第三人民医院骨科聊城252000

目的探讨全关节镜下可吸收免打结线带重建在距腓前韧带损伤所致慢性踝关节外侧不稳患者中的应用效果。方法选取2020年1月至2023年1月聊城市第三人民医院收治的110例距腓前韧带损伤所致慢性踝关节外侧不稳患者进行随机对照试验,采用随机... 详细信息

目的探讨全关节镜下可吸收免打结线带重建在距腓前韧带损伤所致慢性踝关节外侧不稳患者中的应用效果。方法选取2020年1月至2023年1月聊城市第三人民医院收治的110例距腓前韧带损伤所致慢性踝关节外侧不稳患者进行随机对照试验,采用随机数字表法将其分为对照组和观察组,各55例。对照组男30例,女25例,年龄(55.48±3.57)岁。观察组男35例,女20例,年龄(56.38±2.64)岁。对照组采用传统韧带修复手术治疗,观察组采用全关节镜下可吸收免打结线带重建手术治疗。比较两组术前及术后2个月美国足踝外科协会评分(American Orthopedic Foot&Ankle Society Score,AOFAS)、Kofoed踝关节功能评分、Y平衡测试(Y balance test,YBT)及自觉踝关节稳定性量表(Perceived Ankle Instability,PAI)评分和并发症发生率、疼痛视觉模拟量表(Visual Analogue Scale,VAS)评分。采用t检验、χ^(2)检验。结果术后2个月,观察组AOFAS评分、Kofoed踝关节功能评分均高于对照组[(90.13±2.89)分比(79.27±3.28)分、(90.29±2.21)分比(78.44±2.46)分],差异均有统计学意义(t=18.424、26.575,均P<0.05);观察组YBT、PAI评分均优于对照组[(88.28±2.69)分比(78.22±1.66)分、(3.02±1.22)分比(5.34±2.30)分],差异均有统计学意义(t=23.603、6.609,均P<0.05)。观察组术后1、2个月VAS评分均低于对照组[(3.20±1.15)分比(6.89±1.26)分、(1.34±0.54)分比(4.64±1.12)分],差异均有统计学意义(t=16.041、19.683,均P<0.05)。观察组并发症发生率低于对照组[16.36%(9/55)比49.09%(27/55)],差异有统计学意义(χ^(2)=13.378,P<0.05)。结论全关节镜下可吸收免打结线带重建治疗距腓前韧带损伤所致慢性踝关节外侧不稳患者可显著改善他们的踝关节功能,提高自觉踝关节稳定性,减轻术后疼痛,减少术后并发症,具有较高的临床应用价值。

关键词：关节镜可吸收免打结线带重建距腓前韧带慢性踝关节外侧不稳应用效果

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Novel Gas Sensor Based on Nano-zeolite Films for the Nerve agent simulant Dimethylmethylphosphonate detection

Novel Gas Sensor Based on Nano-zeolite Films for the Nerve a...

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2004 7th International Conference on Solid-State and Integrated Circuits Technology（ICSICT 2004）

作者： Haifen Xie~(a,b) Xiao Xiang Sun~a Qiudong Yang~a Jianye Wang~a Yiping Huang~(a*) aASIC and System State Key Lab,Department of Microelectronics,220 Handan road,Shanghai,China,200433 bPhysics department of East China University of Science and Technolegy,Jinshan campuse 1000 xuefu road,Shanghai, China,201512

A novel gas sensor based on nanosized zeolite for the detection of nerve agent simulant gas Dimethylmethylphosphonate(DMMP)is developed in this *** ZSM-5 zeolite films and Ag modified ZSM-5 zeolites films as a novel sensing membrane materials are immobilized on the piezoelectric sensor device QCM(Quartz Crystal Microbalance).A frequency shift with different concentrations of DMMP is *** gas sensor based on nanosized zeolite in resonating mode,whose resonant frequency shifts due to mass loading,has shown high sensitivity for detecting *** minimum detection concentration of DMMP is 1ppm in the N at *** frequency shift is about 60H for lppm *** order to improve the selectivity of the sensor to the DMMP from other organic gases,different pore size zeolite films such as ZSM-5 zeolites and Ag modified ZSM-5 zeolites are studied. The frequency shifts to another two organic gases such as acetone and ethanol at lppm concentration are observed for the sensor selectivity *** relationship between frequency shift and temperature for lppm DMMP has been *** best adsorption temperature is 303K and the desorption temperature is at the DMMP boiling point,*** principle component analysis(PCA);we can easily qualify and quantify the DMMP gas.

关键词： Zeolite QCM DMMP Gas sensor PCA

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SOFTWARE SERVO COURSE(ATTITUDE) SYSTEMS

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Chinese Journal of Aeronautics 1995年第4期8卷 256-262页

作者： Zhang xuefu(Hunan Radio and TV University, Changsha, Hunan, China, 410004)

To cope with the shortcomings of aircraft course (attitude) analogue servosystems: complicate structure, difficulty of matching in a complete set, less reliability,high cost and their accuracy hard to raise, a system mode 'computer plus detector unit'is put forward. The advantage of this project is that the software takes the place of thehardware servo mechanism in a complete set and accomplishes the servo and filteringfunctions. Additionally, it can be used to correct all sorts of errors exactly.

关键词： servocontrol analog simulation filtration detectors

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Validated LC–MS/MS method for determination of YH-8, a novel PKnB inhibitor, in rat plasma and its application to pharmacokinetic study

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Acta Pharmaceutica Sinica B 2015年第5期5卷 467-472页

作者： Qianqian Zhai Jing Pang Guoqing Li Congran Li Xinyi Yang Liyan Yu Yucheng Wang Jian Li xuefu You Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Key Laboratory of Sustainable Development of Marine Fisheries Ministry of Agriculture Yellow Sea Fisheries Research Institute Chinese Academy of Fishery Sciences

(E)-Methyl-4-aryl-4-oxabut-2-enoate(YH-8) is a novel PKn B protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography–tandem mass spectrometric(LC–MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid–liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol–water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring(SRM) mode. Method validation revealed good linearity over the range of1–500 ng/m L for YH-8 with a lower limit of quantification(LLOQ) of 1 ng/m L. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%–6.8%, with accuracy of the method being 100.69%–106.18%.Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to15 days at -70℃, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg.

关键词： YH-8 LC–MS/MS Pharmacokinetics Rat plasma Method validation

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阿戈美拉汀片联合盐酸帕罗西汀对抑郁伴失眠患者SOD、BDNF水平的影响

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宁夏医科大学学报 2024年第7期46卷 680-684页

作者：徐卫国李莎王慧李纪迎周倩胡学福宁夏回族自治区宁安医院银川750021 山东省精神卫生中心济南205514

目的探讨阿戈美拉汀片联合盐酸帕罗西汀对抑郁伴失眠患者超氧化物歧化酶(SOD)、脑源性神经营养因子(BDNF)水平的影响。方法选取宁夏回族自治区宁安医院2021年1—12月诊断为抑郁伴失眠的住院患者120例,分为对照组60例和实验组60例。在使... 详细信息

目的探讨阿戈美拉汀片联合盐酸帕罗西汀对抑郁伴失眠患者超氧化物歧化酶(SOD)、脑源性神经营养因子(BDNF)水平的影响。方法选取宁夏回族自治区宁安医院2021年1—12月诊断为抑郁伴失眠的住院患者120例,分为对照组60例和实验组60例。在使用盐酸帕罗西汀进行常规抗抑郁治疗的基础上,实验组和对照组分别联合阿戈美拉汀、右佐匹克隆进行8周治疗。使用汉密尔顿抑郁量表(HAMD)评定患者抑郁程度;匹兹堡睡眠质量指数(PSQI)评定患者睡眠质量;酶联免疫吸附实验法检测褪黑素、SOD、BDNF水平;电化学发光免疫法检测去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)水平。对比两组治疗后临床症状改善程度及各递质水平变化。结果治疗8周后,相比对照组,实验组HAMD、PSQI评分降低(P均<0.05);褪黑素、SOD、BDNF、NE、DA、5-HT水平升高(P均<0.05)。结论阿戈美拉汀片联合盐酸帕罗西汀治疗抑郁伴失眠患者,可改善患者抑郁程度和睡眠质量,升高褪黑素水平,抑制氧化应激状态,上调BDNF水平,改善患者神经递质水平。

关键词：抑郁伴失眠障碍阿戈美拉汀片超氧化物歧化酶脑源性神经营养因子

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Effects of C-reactive protein on the expression of OX40 ligand in mouse aorta endothelial cells

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Journal of Nanjing Medical University 2009年第4期23卷 247-250页

作者： Fei Wang Shushu Zhu xuefu Han Jindan Xu Jinnan Zhang Di Yang Institute of Cardiovascular Disease the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Objective： To investigate the expression of OX40 ligand（OX40L） on C-reactive protein（CRP）-triggered mouse aorta endothelial cells （MAECs） in vitro. Methods： MAECs from aorta were isolated by digestion with collagenase type II. The cell growth was confirmed by morphological characteristics and the immunological marker, factor Ⅷ（or Willebrand factor, vWF）. The expression of OX40L by MAECs was detected by RT-PCR and western blot after incubating with 100μg/ml CRP for 48 hours. Results： Twenty-day cultures of MAECs formed confluent monolayer of a cobblestone pattern. RT-PCR and western blot assay showed that the level of OX40L expression in MAECs receiving CRP treatment was higher than control. Conclusion： A reliable method is described to isolate and propagate MAECs. CRP upregulates OX40L expression in MAECs.

关键词： endothelial cells C-reactive protein OX40L

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CudA,a novel transcription factor required for Dictyostelium development

CudA,a novel transcription factor required for Dictyostelium...

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2012全国发育生物学大会

作者： Hong-Yu Wang Nanjing Biomedical Research Institute of Nanjing University xuefu road 12,Hi-Tech distract,Nanjing 210061

Social amoebae Dictyostelium aggregate together upon *** aggregating cells form migrating slugs, which contain two types of cells,prespore and prestalk *** a novel transcription factor required for expression of both prespore-specific gene cotCand prestalk tip-organizer geneexpl7 throughdirect binding to their *** CudA DNA-binding site containsa 14 nucleotide dyad *** Dictyostelium,there are five other proteins similar to CudAthat together with CudAform a small gene *** parasite Entamoebahistolytica,a pathogenic microbe closely related to *** are also six CudAhomologues that all share a conserved,putative DNA-binding *** Cud orthologue is found in human,therefore Cud homologues in Entamoebamight be a new drug target for parasite treatmnent.

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汽轮机热力性能计算平台研究与应用

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热力透平 2024年第3期53卷 184-188,194页

作者：吕长虹郭建匡磊林明星张学富张红梅广东大唐国际雷州发电有限责任公司雷州524200 上海汽轮机厂有限公司上海200240

为方便电厂运行人员进行机组性能评估,基于ASME汽轮机性能试验规程和汽轮机热力性能计算原理建立了汽轮机热力计算模型,对机组负荷、主蒸汽温度、再热蒸汽温度等表征工况稳定性的关键运行参数进行了稳态筛选,借助热力仿真平台建立了以... 详细信息

为方便电厂运行人员进行机组性能评估,基于ASME汽轮机性能试验规程和汽轮机热力性能计算原理建立了汽轮机热力计算模型,对机组负荷、主蒸汽温度、再热蒸汽温度等表征工况稳定性的关键运行参数进行了稳态筛选,借助热力仿真平台建立了以凝结水流量为基准的主蒸汽流量计算模型,利用仿真平台中的湿汽透平模块完成了整机热力系统的仿真,进而实现了热力性能指标计算和指标修正计算,并验证了结果的合理性与准确性。在此基础上开发了汽轮机热力性能自动计算平台,利用该平台对某1000 MW超超临界二次再热机组的热耗进行了偏差分析计算,基于偏差计算结果给出了运行调整方向。研究成果可以为机组性能评估与运行优化提供参考。

关键词：汽轮机机组性能计算稳态检测仿真模型软件开发热耗偏差分析

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