A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells

Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1–4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy.     

基于SQL Server数据库的安全性策略研究

从数据库系统的安全模型入手,讨论分析了SQL Server数据库使用中的安全问题,针对可能存在的安全问题,提出了一些具体的解决方法和建议,以提高用户对数据库安全的认识.     

用户初始服务密码管理方式

本文对用户初始服务密码管理困难的原因进行了深入的分析,提出了将初始服务密码印制在SIM卡涂层下的新型管理方式。     

体育场馆照明工程常见问题与解决方法

随着大量的各种类型的体育场馆的兴建,体育场馆的照明工程成为建筑电气行业的一个重要分支.在场馆建设时应根据实际需要进行照明设计和施工,做到场馆的照明满足体育赛事在安全、可靠、达标方面的要求,并且兼顾赛时与赛后照明设施的充分利用,达到既经济又实用的目的.体育场馆照明工程设计和施工中存在一些常见的缺陷,在设计和施工中应认真加以研究,以保证工程的质量.     

HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells

HDAC6 is overexpressed in ovarian cancer and is known to be correlated with tumorigenesis. Accordingly, ACY-241, a selective HDAC6 inhibitor, is currently under clinical trial and has been tested in combination with various drugs. HDAC8, another member of the HDAC family, has recently gained attention as a novel target for cancer therapy. Here, we evaluated the synergistic anticancer effects of PCI-34051 and ACY-241 in ovarian cancer. Among various ovarian cancer cells, PCI-34051 effectively suppresses cell proliferation in wild-type p53 ovarian cancer cells compared with mutant p53 ovarian cancer cells. In ovarian cancer cells harboring wild-type p53, PCI-34051 in combination with ACY-241 synergistically represses cell proliferation, enhances apoptosis, and suppresses cell migration. The expression of pro-apoptotic proteins is synergistically upregulated, whereas the expressions of anti-apoptotic proteins and metastasis-associated proteins are significantly downregulated in combination treatment. Furthermore, the level of acetyl-p53 at K381 is synergistically upregulated upon combination treatment. Overall, co-inhibition of HDAC6 and HDAC8 through selective inhibitors synergistically suppresses cancer cell proliferation and metastasis in p53 wild-type ovarian cancer cells. These results suggest a novel approach to treating ovarian cancer patients and the therapeutic potential in developing HDAC6/8 dual inhibitors.     

Melanocortin-5 Receptor: Pharmacology and Its Regulation of Energy Metabolism

As the most recent melanocortin receptor (MCR) identified, melanocortin-5 receptor (MC5R) has unique tissue expression patterns, pharmacological properties, and physiological functions. Different from the other four MCR subtypes, MC5R is widely distributed in both the central nervous system and peripheral tissues and is associated with multiple functions. MC5R in sebaceous and preputial glands regulates lipid production and sexual behavior, respectively. MC5R expressed in immune cells is involved in immunomodulation. Among the five MCRs, MC5R is the predominant subtype expressed in skeletal muscle and white adipose tissue, tissues critical for energy metabolism. Activated MC5R triggers lipid mobilization in adipocytes and glucose uptake in skeletal muscle. Therefore, MC5R is a potential target for treating patients with obesity and diabetes mellitus. Melanocortin-2 receptor accessory proteins can modulate the cell surface expression, dimerization, and pharmacology of MC5R. This minireview summarizes the molecular and pharmacological properties of MC5R and highlights the progress made on MC5R in energy metabolism. We poInt. out knowledge gaps that need to be explored in the future.     

Open-circuit fault detection for three-phase inverter based on backpropagation neural network

Neural Computing and Applications - To realize real-time fault detection in power devices and enhance reliability of inverter circuits, this paper proposes a detection method based on Park’s...     

需求管理及配置管理与项目范围管理

需求管理、配置管理和项目范围管理在软件项目管理中具有重要的地位和作用。透彻分析了需求管理、配置管理和项目范围管理知识理论中的基本概念,有助于形成对需求管理、配置管理和项目范围管理的深刻理解,有利于规范和促进日常项目管理工作。     

某铀矿井场抽注液控制的数字化技术应用

在地浸采铀生产过程中,控制抽注液平衡和高效识别抽注液异常状态是保障浸出效能和井场的安全重要措施。以内蒙古某铀矿为例,介绍了该铀矿抽注液平衡联动控制与抽注液异常监测方面数字化技术的应用情况,探讨了应用数字化技术前后该铀矿山抽注液管控效能的变化。结果表明,应用数字化技术进行抽注液平衡控制能有效解决抽注液调控过程中人工控制所存在的劳动强度大、调控不及时和精度不足的问题;合理的模型设计能够高效识别抽注液异常状态。建立抽注液数字化管控体系有助于实现精益化管控、提升井场生产效能、降低安全风险。     

贵州电网输电线路在线监测系统运行分析

通过介绍贵州电网输电线路在线监测系统的应用和运行情况,对系统在运行过程中发生的缺陷和故障进行了统计和梳理,通过对故障原因的分析,提出了相应的改进对策。