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一种通过计算机辅助抗体设计技术获得的靶向人表皮生长因子受体2的新型全人抗体HF Article

乔春霞, 吕明, 李新颖, 郞小玲, 吕守芹, 龙勉, 黎燕, 耿树生, 林周, 沈倍奋, 冯健男

《工程（英文）》 2021年 第7卷 第11期   页码 1566-1576 doi: 10.1016/j.eng.2020.10.024

摘要： 目前研究的处于临床试验阶段的大多数抗体药物都是人源化或全人抗体。全人抗体多通过噬菌体展示技术（体外）或转基因小鼠（体内）产生；其他方法包括B淋巴细胞永生化、人-人杂交瘤、单细胞聚合酶链反应等。由于靶向人表皮生长因子受体2（HER2）的注射用曲妥珠单抗（赫赛汀）的结构复杂，我们首先针对赫赛汀识别HER2 的潜在表位设计了6 条短肽。随后，将这些肽作为抗体互补决定区，并采用适合的免疫球蛋白框架，获得名为“HF”的新型抗HER2 抗体。HF比赫赛汀具有更高的亲和力和更有效的抗肿瘤活性。

关键词： 人表皮生长因子受体2（HER2/erb-B2）     全人抗体     计算机辅助设计（CAD）    

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resistance to endocrine therapy in hormone receptor-positive human epidermal growth factor receptor 2-

Wenjie Zhu, Binghe Xu

《医学前沿（英文）》 2021年 第15卷 第2期   页码 208-220 doi: 10.1007/s11684-020-0795-4

摘要： New targeted therapies have been developed to overcome resistance to endocrine therapy (ET) and improve the outcome of HR /HER2 advanced breast cancer (ABC). We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR /HER2 ABC. PUBMED and EMBASE databases were searched for eligible trials. Hazard ratios (HRs) for progression-free survival (PFS), odds ratios (ORs) for objective response rate (ORR), clinical benefit rate (CBR), and toxicity were meta-analyzed. Twenty-six studies with data on 10 347 patients were included and pooled. The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS (pooled HR= 0.547, <0.001), overall survival (pooled HR= 0.755, <0.001), and tumor response rates (ORR, pooled OR= 1.478, <0.001; CBR, pooled OR= 1.201, <0.001) with manageable toxicities (pooled OR= 3.280, <0.001). The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant patients. Moderate improvement in PFS (pooled HR= 0.686, <0.001) yet pronounced toxicities (pooled OR= 2.154, <0.001) were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with fulvestrant. Future studies are warranted to optimize the population and the dosing sequence of these available options.

关键词： endocrine-resistant     HR+/HER2- advanced breast cancer     randomized clinical trials     meta-analysis     targeted therapy    

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星突江鲽胰岛素样生长因子I的体外重组表达及生物活性分析

徐永江,臧 坤,柳学周,史 宝,陈圣毅

《中国工程科学》 2015年 第17卷 第1期   页码 67-73

摘要：

为了在蛋白水平认识星突江鲽（Platichthys stellatus）胰岛素样生长因子I（IGF-I）的生长调控作用及机制，采用RT-PCR方法扩增了其成熟肽片段，利用原核表达载体pET-28a包涵体经6 mol/L盐酸胍变性、Ni2+离子亲和柱纯化和尿素梯度复性后，可获得高纯度的IGF-I重组蛋白。细胞增殖试验结果显示0.6 μg/mL 的星突江鲽IGF-I重组蛋白能显著促进人胚胎肾细胞HEK293T的增殖而大于1.8 μg/mL时则表现出抑制作用。本研究成功构建了星突江鲽IGF-I体外高效表达系统，并获得具有细胞水平生物活性的星突江鲽IGF-I重组蛋白，结果可为深入探究IGF-I在星突江鲽生长发育中的作用机制及研制高效绿色的促生长制剂提供基础资料

关键词： 星突江鲽；胰岛素样生长因子I；原核表达；生物活性    

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左炔诺孕酮宫内释放系统对胰岛素样生长因子-1的影响与预防盆腔炎的相关性研究

吴晓杰,刘霞,陶跃平,王洁

《中国工程科学》 2015年 第17卷 第6期   页码 4-7

摘要：

目的：研究左炔诺孕酮宫内释放系统对子宫内膜组织胰岛素样生长因子-1（IGF-1）的影响及预防盆腔炎疗效分析。分别对术前及术后6个月子宫内膜组织IGF-1的表达情况进行对比，且随访2年，了解患者盆腔炎发生情况。随访2年对照组224例患者中39例发生盆腔炎，复发率为10.89 %，而研究组184例发生盆腔炎12例，差异有显著性；研究组子宫内膜厚度术后明显小于术前，差异有显著性，对照组子宫内膜厚度术后与术前变化无差异性

关键词： 左炔诺孕酮宫内系统；胰岛素样生长因子；盆腔炎    

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延长腺相关病毒递送药物的半衰期提高治疗效果 Article

吴会芳, 胡丹, 李泉晓, 王春雨, 朱晓艺, 李威, 陈宾凡, 季萍, 黄可可, 黄爱玲, 黄竞荷, Dimiter S. Dimitrov, 吴艳玲, 应天雷

《工程（英文）》 2023年 第21卷 第2期   页码 203-213 doi: 10.1016/j.eng.2022.02.009

摘要： 研究表明，延长AAV递送的小分子双功能蛋白和成纤维细胞生长因子21（fibroblast growth factor 21, FGF21）的半衰期显著增加了它们在血液循环中的浓度。此外，AAV递送FGF21 延长其半衰期使2 型糖尿病动物模型中肝损伤和血糖显著降低，并改善了葡萄糖耐量和胰岛素敏感性。这些结果证明了延长药物半衰期的基因治疗在应对人类疾病中的治疗潜力。

关键词： 基因治疗     腺相关病毒     半衰期     成纤维细胞生长因子21     2型糖尿病    

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Fenton oxidation of 2,4- and 2,6-dinitrotoluene and acetone inhibition

HE Yiliang, ZHAO Bin, HUGHES Joseph B., HAN Sung Soo

《环境科学与工程前沿（英文）》 2008年 第2卷 第3期   页码 326-332 doi: 10.1007/s11783-008-0038-4

摘要： The performances and kinetic parameters of Fenton oxidation of 2,4- and 2,6-dinitrotoluene (DNT) in water-acetone mixtures and explosive contaminated soil washing-out solutions were investigated at a laboratory scale. The experimental results show that acetone can be a significant hydroxyl radical scavenger and result in serious inhibition of Fenton oxidation of 2,4- and 2,6-DNT. Although no serious inhibition was found in contaminated soil washing-out solutions, longer reaction time was needed to remove 2,4- and 2,6-DNT completely, mainly due to the competition of hydroxyl radicals. Fenton oxidation of 2,4- and 2,6-DNT fit well with the first-order kinetics and the presence of acetone also reduced DNT’s degradation kinetics. Based on the comparison and matching of retention time and ultraviolet (UV) spectra between high performance liquid chromatography (HPLC) and standards, the following reaction pathway for 2,4-DNT primary degradation was proposed: 2,4-DNT → 2,4-dinitro-benzaldehyde → 2,4-dinitrobenzoic acid → 1,3-dinitrobenzene → 3-nitrophenol.

关键词： presence     2     4-DNT     competition     laboratory     scavenger    

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金属网栅透明导电膜光电性能综合评价因子 Research Articles

张怡蕾1,2,曹瑾璇1,2,陆振刚1,2,王赫岩1,2,谭久彬1,2

《信息与电子工程前沿（英文）》 2021年 第22卷 第11期   页码 1532-1540 doi: 10.1631/FITEE.2000690

摘要： 本文提出一种基于金属网栅光电性能的形式简单的综合评价因子Q，可简便有效地用于不同结构参数的金属网栅光电性能评估。评价因子Q值与TOPSIS的评估结果变化趋势一致，验证了评价因子Q的有效性。评价因子Q还可以对不同图案的金属网栅光电性能进行评估，使其在金属网栅的设计和应用中具有十分广泛的应用前景。

关键词： 金属网栅；TOPSIS法；熵权法；综合评价因子；透明导电膜    

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Anti-β glycoprotein I antibodies in complex with β2 glycoprotein I induce platelet activation via tworeceptors: apolipoprotein E receptor 2' and glycoprotein I bα

null

《医学前沿（英文）》 2016年 第10卷 第1期   页码 76-84 doi: 10.1007/s11684-015-0426-7

摘要：

Anti-β2 glycoprotein I (anti-β2GP I ) antibodies are important contributors to thrombosis, especially in patients with antiphospholipid syndrome (APS). However, the mechanism by which anti-β2GP I antibodies are involved in the pathogenesis of thrombosis is not fully understood. In this report, we investigated the role of anti-β2GP I antibodies in complexes with β2GP I as mediators of platelet activation, which can serve as a potential source contributing to thrombosis. We examined the involvement of the apolipoprotein E receptor 2' (apoER2') and glycoprotein I ba (GP I bα) in platelet activation induced by the anti-β2GP I /β2GP I complex. The interaction between the anti-β2GP I /β2GP I complex and platelets was examined using in vitro methods, in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by measuring GP II b/ III a activation and P-selectin expression and thromboxane B2 production as well as p38 mitogen-activated protein kinase phosphorylation. Our results revealed that the anti-β2GP I /β2GP I complex was able to activate platelets, and this activation was inhibited by either the anti-GP I bα antibody or the apoER2' inhibitor. Results showed that the anti-β2GP I /β2GP I complex induced platelet activation via GP I bα and apoER2', which may then contribute to the prothrombotic tendency in APS patients.

关键词： anti-β2GP I /β2GP I complex     platelet     GP I bα     apoER2'     thrombosis    

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Detection of maternal serum thromboxane B2 in different durations of pregnancy and prediction of preeclampsia

Geqing XIA MD, Zehua WANG MD, Li ZOU MD, Chaoying WU MS, Yu HU MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 235-240 doi: 10.1007/s11684-010-0002-0

摘要： This study was aimed to detect maternal serum levels of thromboxane B2 (TXB2) in different durations of pregnancy and explore the predictive value of TXB2 for preeclampsia. By employing a prospective and double-blind study method, 180 pregnant women with previously normal blood pressures during their progestation were included in the study. Peripheral venous blood samples were obtained during 10–14 (period I), 20–24 (period II) and 30–34 (period III) weeks of gestation. Maternal serum levels of TXB2 were measured by enzyme-linked immunoassay. The pathogenetic condition and pregnancy outcomes of these cases were observed. (1) Among the 180 previously normotensive women, ten developed preeclampsia (case group; four severe and six mild preeclampsia). One hundred and seventy remained normal till the end of pregnancy (control group). (2) With development of pregnancy, the levels of maternal serum TXB2 in the 180 cases gradually ascended as seen through the Wilcoxon Signed Ranks Test. There was a statistical significance in maternal TXB2 levels between two different gestational stages (<0.01). (3) The levels of maternal serum TXB2 were slightly higher in the case group than in the control group during period I of gestation, but the difference was not statistically significant (>0.05); the levels of TXB2 were significantly higher in the case group than in the control group during periods II and III of gestation (both <0.05). (3) The best cutoff points of maternal TXB2 were 3750 and 4400ng/mL during periods II and III of gestation by receiver operator characteristic (ROC) curve; and the sensitivity, specificity, positive predictive value, negative predictive value and odds radio of TXB2 in predicting preeclampsia were 80%, 69.5%, 13.3%, 98.33%, 9.11 and 90%, 68.82%, 13.84%, 99.13, 19.86, respectively. Higher levels of maternal serum TXB2 were detected a long time before clinical symptoms appeared. The maternal serum TXB2 after 20 weeks of gestation had predictive value, and the index after 30 weeks was superior to that prior to 30 weeks .

关键词： thromboxane B2     preeclampsia    

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第三届环境、工业和能源工程国际会议(EI2E 2019)

会议日期： 2019年09月19日

会议地点： 宁夏银川

主办单位： APISE

>In situ growth of phosphorized ZIF-67-derived amorphous CoP/Cu2O@CF electrocatalyst

《化学科学与工程前沿（英文）》 2023年 第17卷 第10期   页码 1430-1439 doi: 10.1007/s11705-023-2320-1

摘要： Transition metal phosphides have been extensively studied for catalytic applications in water splitting. Herein, we report an in situ phosphorization of zeolitic imidazole frameworks (ZIF-67) to generate amorphous cobalt phosphide/ZIF-67 heterojunction on a self-supporting copper foam (CF) substrate with excellent performance for hydrogen evolution reaction (HER). The needle-leaf like copper hydroxide was anchored on CF surface, which acted as implantation to grow ZIF-67. The intermediate product was phosphorized to obtain final electrocatalyst (CoP/Cu2O@CF) with uniform particle size, exhibiting a rhombic dodecahedron structure with wrinkles on the surface. The electrochemical measurement proved that CoP/Cu2O@CF catalyst exhibited excellent HER activity and long-term stability in 1.0 mol·L–1 KOH solution. The overpotential was only 62 mV with the Tafel slope of 83 mV·dec–1 at a current density of 10 mA·cm–2, with a large electrochemical active surface area. It also showed competitive performance at large current which indicated the potential application to industrial water electrolysis to produce hydrogen. First-principle calculations illustrated that benefit from the construction of CoP/ZIF-67 heterojunction, the d-band center of CoP downshifted after bonding with ZIF-67 and the Gibbs free energy (ΔGH*) changed from –0.18 to –0.11 eV, confirming both decrease in overpotential and excellent HER activity. This work illustrates the efficient HER activity of CoP/Cu2O@CF catalyst, which will act as a potential candidate for precious metal electrocatalysts.

关键词： CoP/Cu2O@CF     electrocatalyst     phosphorization     HER     DFT    

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Study of recombinant human IFN-α-2b bacilli Calmette–Guerin activated killer cells and against bladder

FAN Xiaodong, HAN Ruifa

《医学前沿（英文）》 2007年 第1卷 第4期   页码 377-380 doi: 10.1007/s11684-007-0073-8

摘要： Presently, one of the most potent immunotherapies is the application of bacillus Calmette Guerin (BCG) to prevent recurrences of the superficial bladder cancer. Despite its successful use, nonresponders and certain side effects remain a major obstacle. Therefore, current studies aim at developing recombinant BCG (rBCG) strains secreting Th1-like cytokines to improve the effectiveness of the therapy. In this study, a new type of rBCG strain constructed by Tianjin institute of Urology was tested for its immunostimulatory capacity . Peripheral blood monocytes (PBMC) were stimulated by recombinant BCG and transformed into bacilli Calmette–Guerin activated killer (BAK) cells, and the effect of anticancer BAK cells was studied. Recombinant IFN--2b-BCG, wild-type BCG (wBCG), wild-type BCG and IFN--2b were coincubated with PBMCs respectively , and the proliferation of PBMC was detected with MTT in different time. BAK cells have the ability to kill bladder tumor cells, and the antitumor activity of effecter cells was determined by LDH release assay. The result of MTT showed that the proliferation of PBMC in the recombinant BCG group was more powerful than in the other two groups (<0.05). The result of LDH release assay showed that the antitumor activity of BAK cells stimulated by Recombinant BCG was the highest in all groups. We conclude that the recombinant BCG can activate more PBMCs to anti-bladder cancer than wild-type BCG does.

关键词： Urology     powerful     2b-BCG     Tianjin institute     wild-type    

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流体内磁驱动微米机器人运动前沿研究综述 Review Article

苗佳淼1,2,王潇朴2,周燕2,叶敏2,赵洪宇2,许若愚1,钱辉环1,2

《信息与电子工程前沿（英文）》 2023年 第24卷 第11期   页码 1520-1540 doi: 10.1631/FITEE.2300054

摘要： 磁驱动微米机器人能够在人体内局部低侵入性地执行特定任务。为到达体内病灶区域，微米机器人常常需要在比静止液体更为复杂的流动血液内进行导航运动。因此，相应的精准控制方案设计更具挑战性。

关键词： 微米机器人；流体；动力学建模；控制    

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SARS-CoV-2 侵入因子——ACE2 和TMPRSS2 在围着床期胚胎和母胎界面存在表达 Article

陈伟,袁鹏,杨铭,严智强,孔思明,严杰,柳溪溪,陈依东,乔杰,闫丽盈

《工程（英文）》 2020年 第6卷 第10期   页码 1162-1169 doi: 10.1016/j.eng.2020.07.013

摘要：

在全球肆虐的严重急性呼吸系统综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2,SARS-CoV-2）导致了大量人群感染，血管紧张素转化酶2（angiotensin-converting enzyme 2, ACE2）是SARS-CoV和SARS-CoV-2的受体蛋白。然而是否存在SARS-CoV-2的垂直传播仍颇有争议。为了探讨SARS-CoV-2垂直传播的潜在风险，我们利用已发表的单细胞转录组数据观察了围着床期胚胎和母胎界面上ACE2和TMPRSS2（编码跨膜丝氨酸蛋白酶2）的转录表达情况ACE2阳性表达的STB细胞中存在明显的性别差异。

关键词： SARS-CoV-2     ACE2     垂直传播     胎盘     围着床期    

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Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination

《医学前沿（英文）》 2023年 第17卷 第4期   页码 747-757 doi: 10.1007/s11684-022-0954-x

摘要： Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

关键词： COVID-19 convalescent     SARS-CoV-2     inactivated vaccination     neutralizing antibody     B cell response    

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标题 作者 时间 类型 操作

一种通过计算机辅助抗体设计技术获得的靶向人表皮生长因子受体2的新型全人抗体HF

乔春霞, 吕明, 李新颖, 郞小玲, 吕守芹, 龙勉, 黎燕, 耿树生, 林周, 沈倍奋, 冯健男

期刊论文

resistance to endocrine therapy in hormone receptor-positive human epidermal growth factor receptor 2-

Wenjie Zhu, Binghe Xu

期刊论文

星突江鲽胰岛素样生长因子I的体外重组表达及生物活性分析

徐永江,臧 坤,柳学周,史 宝,陈圣毅

期刊论文

左炔诺孕酮宫内释放系统对胰岛素样生长因子-1的影响与预防盆腔炎的相关性研究

吴晓杰,刘霞,陶跃平,王洁

期刊论文

延长腺相关病毒递送药物的半衰期提高治疗效果

吴会芳, 胡丹, 李泉晓, 王春雨, 朱晓艺, 李威, 陈宾凡, 季萍, 黄可可, 黄爱玲, 黄竞荷, Dimiter S. Dimitrov, 吴艳玲, 应天雷

期刊论文

Fenton oxidation of 2,4- and 2,6-dinitrotoluene and acetone inhibition

HE Yiliang, ZHAO Bin, HUGHES Joseph B., HAN Sung Soo

期刊论文

金属网栅透明导电膜光电性能综合评价因子

张怡蕾1,2,曹瑾璇1,2,陆振刚1,2,王赫岩1,2,谭久彬1,2

期刊论文

Anti-β glycoprotein I antibodies in complex with β2 glycoprotein I induce platelet activation via tworeceptors: apolipoprotein E receptor 2' and glycoprotein I bα

null

期刊论文

Detection of maternal serum thromboxane B2 in different durations of pregnancy and prediction of preeclampsia

Geqing XIA MD, Zehua WANG MD, Li ZOU MD, Chaoying WU MS, Yu HU MD,

期刊论文

第三届环境、工业和能源工程国际会议(EI2E 2019)

2019年09月19日

会议信息

>In situ growth of phosphorized ZIF-67-derived amorphous CoP/Cu2O@CF electrocatalyst

期刊论文

Study of recombinant human IFN-α-2b bacilli Calmette–Guerin activated killer cells and against bladder

FAN Xiaodong, HAN Ruifa

期刊论文

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