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异戊二烯焦磷酸 1

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Mechanism of arterial remodeling in chronic allograft vasculopathy

Qichang Zheng, Shanglong Liu, Zifang Song

《医学前沿（英文）》 2011年第5卷第3期页码 248-253 doi: 10.1007/s11684-011-0149-3

摘要： Chronic allograft vasculopathy (CAV) remains a major obstacle for long-term survival of grafts even though therapeutic strategies have improved considerably in recent years. CAV is characterized by concentric and diffuse neointimal formation, medial apoptosis, infiltration of lymphocyte or inflammatory cells, and deposition of extracellular matrix both in arteries and veins. Recent studies have shown that stem cells derived from the recipient contribute to neointimal formation under the regulation of chemokines and cytokines. Arterial remodeling in allografts eventually causes ischemic graft failure. The pathogenesis is multi-factorial with both immunologic and non-immunological factors being involved. The immunological factors have been discussed extensively in other articles. This review focuses mainly on the arterial remodeling that occurs in 3 layers of vessel walls including intimal injury, accumulation of smooth muscle-like cells in the neointimal, medial smooth muscle cell apoptosis, adventitial fibrosis, and deposition of extracellular matrix.

关键词： transplantation chronic rejection neointimal immunology arterial remodeling allograft vasculopathy

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Nanovaccines for remodeling the suppressive tumor microenvironment: New horizons in cancer immunotherapy

Kai Shi, Matthew Haynes, Leaf Huang

《化学科学与工程前沿（英文）》 2017年第11卷第4期页码 676-684 doi: 10.1007/s11705-017-1640-4

摘要： Despite limited successes in clinical development, therapeutic cancer vaccines have experienced resurgence in recent years due to an enhanced emphasis upon co-mitigating factors underlying immune response. Specifically, reversing the immune-suppressive effects of the tumor microenvironment, mediated by a variety of cellular and molecular signaling mechanisms, has become fundamental toward enhancing therapeutic efficacy. Therein, our lab has implemented various nano-vaccines based on the lipid-coated calcium phosphate platform for combined immunotherapy, in which antigenic, epitope-associated peptides as well as immune-suppression inhibitors can be co-delivered, often functioning through the same formulation. In probing the mechanism of action of such systems and , an improved effect synergy can be elucidated, inspiring future preclinical efforts and hope for clinical success.

关键词： vaccine nanoparticle tumor immunotherapy microenvironment

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Long-term remodeling of anterior alveolar bone from treatment to retention

Yan LIU MD, Jiuhui JIANG MD, Tianmin XU MD, Haiping ZHANG MD,

《医学前沿（英文）》 2009年第3卷第4期页码 408-414 doi: 10.1007/s11684-009-0069-7

摘要： Bone remodeling in orthodontic treatment has been one of the most concerned issues. The purpose of this study was to characterize the changes in bone remodeling on both labial and lingual aspects of the anterior teeth during treatment and retention. Data of 55 extraction cases (41 females and 14 males) were collected at pretreatment, post-treatment, and follow-up stages. Bone thickness on both labial and lingual aspects of the upper and lower incisors were measured at the level of the center of resistance (UC and LC) and that of 3mm apical to the upper and lower incisors’ center of resistance (UAC and LAC). For LC, with the significant lingual movement of point LIR (center of resistance of lower incisor; <0.001), no statistically significant changes in alveolar width on the labial aspect were detected, whereas the reduction of lingual alveolar width was statistically significant (<0.001). In retention, no significant movement of point LIR appeared to occur, while an increase in alveolar width on the lingual aspect was found at this stage. For LAC, the changes in alveolar width as well as the displacement of point LIA (apex of lower incisor) were similar to those of LC. On the maxilla, with the control lingual tipping movement of upper incisor, most of the anterior alveolar changes surrounding the upper incisor were analogous to those of lower incisor. But differently, during treatment, labial bone thickness was increased significantly as the upper incisor moved lingually, and in retention, no statistically significant changes were found on both labial and lingual bone thickness as the upper incisor labially proclined. It was concluded that, with lingual movement of the incisors, bone apposition on the lingual aspect may lag behind the incisor movement. In retention, the lower incisors are in a stable position, with sequential bone apposition being presented on the lingual aspect. However, the upper incisors turn out to be labially relapsed along with the lingual bone resorption and labial bone apposition occurring simultaneously.

关键词： alveolus remodeling orthodontics extraction

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Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

《医学前沿（英文）》 2020年第14卷第6期页码 726-745 doi: 10.1007/s11684-020-0746-0

摘要： Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

关键词： CAR T cells immunoregulatory molecules endogenous immune response solid malignancies

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Compound C620-0696, a new potent inhibitor targeting BPTF, the chromatin-remodeling factor in non-small-cell

Jiahui Xu, Qianqian Wang, Elaine Lai Han Leung, Ying Li, Xingxing Fan, Qibiao Wu, Xiaojun Yao, Liang Liu

《医学前沿（英文）》 2020年第14卷第1期页码 60-67 doi: 10.1007/s11684-019-0694-8

摘要： Bromodomain PHD-finger transcription factor (BPTF) is the largest subunit of the nucleosome remodeling factor and plays an important role in chromatin remodeling for gene activation through its association with histone acetylation or methylation. BPTF is also involved in oncogene transcription in diverse progressions of cancers. Despite clinical trials for inhibitors of bromodomain and extra-terminal family proteins in human cancers, no potent and selective inhibitor targeting the BPTF bromodomain has been discovered. In this study, we identified a potential inhibitor, namely, C620-0696, by computational docking modeling to target bromodomain. Results of biolayer interferometry revealed that compound C620-0696 exhibited high binding affinity to the BPTF bromodomain. Moreover, C620-0696 was cytotoxic in BPTF with a high expression of non-small-cell lung cancer (NSCLC) cells. It suppressed the expression of the BPTF target gene c-MYC, which is known as an oncogenic transcriptional regulator in various cancers. C620-0696 also partially inhibited the migration and colony formation of NSCLC cells owing to apoptosis induction and cell cycle blockage. Thus, our study presents an effective strategy to target a bromodomain factor-mediated tumorigenesis in cancers with small molecules, supporting further exploration of the use of these inhibitors in oncology.

关键词： BPTF small molecule epigenetics non-small-cell lung cancer

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柔性材料对爆炸载荷的缓冲效应研究

于少娟,李永池,刘颢文,孙宇新,胡秀章

《中国工程科学》 2007年第9卷第4期页码 75-78

摘要：

建立了柔性材料桙钢复合壳体在爆炸载荷作用下应力波传播问题的完备方程组；使用有限元方法完成了对复合壳体在爆炸载荷作用下应力波传播规律的系列数值模拟，并着重讨论了不同炸药层和柔性材料层厚度对柔性材料与钢交界面载荷的影响。

关键词：柔性材料爆炸载荷载荷改造数值模拟

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重构异戊二烯焦磷酸代谢以促进萜类化合物的合成 Article

徐显皓, 吕雪芹, 崔世修, 刘延峰, 夏洪志, 李江华, 堵国成, 李兆丰, Rodrigo Ledesma-Amaro, 陈坚, 刘龙

《工程（英文）》 2023年第28卷第9期页码 166-178 doi: 10.1016/j.eng.2023.03.019

摘要：

萜类化合物是最大的一类天然产物。它们以异戊二烯焦磷酸(IPP)作为基本单元构建而成。使用细胞工厂合成萜类化合物已经引起了极大关注。而迄今为止，IPP的供应不足仍然是高效合成萜类化合物的主要挑战。在本项研究中，我们发现在枯草芽孢杆菌（Bacillus subtilis）中，中心代谢和IPP供应之间的代谢通量分配不平衡阻碍了IPP的积累。因此，我们构建了一系列响应丙酮酸和/或丙二酰辅酶A的双输入多输出（two-input-multi-output, TIMO）基因回路对IPP的代谢途径进行了改造，使IPP的积累增加了将近4倍。随后，设计了一种IPP代谢网络重构策略以提高三种萜类化合物的产量，包括维生素K2 (MK-7, 4.1倍)、番茄红素(9倍)和β-胡萝卜素（0.9倍）。在50-L的生物反应器中，MK-7的产量达到1549.6 mg∙L⁻¹，是迄今为止报道的最高产量。本文提出了一种基于TIMO基因回路的IPP代谢网络重构框架，可用于复杂代谢网络的协同精细调控，从而实现萜类化合物的高效合成。

关键词：萜类基因回路枯草芽孢杆菌异戊二烯焦磷酸