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.     

低临界胶束浓度PEGMA-b-PCL的制备及其 药物缓释性能

以ε-己内酯（ε-CL）为疏水链段,聚乙二醇甲醚甲基丙烯酸酯（PEGMA）为亲水链段,4-氰基-4-[(十二烷基硫基硫羰基)硫基]戊酸（CDPA）为可逆加成-断裂链转移（RAFT）试剂,在以甲苯为溶剂、N2氛围、80 ℃、反应24 h的条件下,通过RAFT聚合法制备了两嵌段聚合物PEGMA-b-PCL。将其自组装为胶束用作纳米药物载体,并以姜黄素（Cur）为胶束负载药物。考察了两嵌段聚合物结构、分子量及分布,表征了胶束载体粒径、形貌,测试了胶束载体的载药和释药性能。结果表明,不同嵌段聚合物相对分子质量范围为478~7318,此类聚合物具有较低的临界胶束浓度（CMC）,在常规条件下（pH=7.4）其范围为0.920~1.600 μg/mL。胶束载体粒径范围为:68.34~186.30 nm。当n(CDPA)∶n(ε-CL)=1∶200时,胶束载药量和包封率最高,可达12.05%和75.26%。在不同pH值环境下,药物缓释性能可达15 d,其中pH=5.0时释药量可达35.38%。     

CAR T Cell Therapy in Hematological Malignancies: Implications of the Tumor Microenvironment and Biomarkers on Efficacy and Toxicity

Chimeric antigen receptor (CAR) T cell therapy has ushered in a new era in cancer treatment. Remarkable outcomes have been demonstrated in patients with previously untreatable relapsed/refractory hematological malignancies. However, optimizing efficacy and reducing the risk of toxicities have posed major challenges, limiting the success of this therapy. The tumor microenvironment (TME) plays an important role in CAR T cell therapy’s effectiveness and the risk of toxicities. Increasing research studies have also identified various biomarkers that can predict its effectiveness and risk of toxicities. In this review, we discuss the various aspects of the TME and biomarkers that have been implicated thus far and discuss the role of creating scoring systems that can aid in further refining clinical applications of CAR T cell therapy and establishing a safe and efficacious personalised medicine for individuals.     

55t均火炉的温度检测及铸锭均火工艺参数确定

介绍新建的均匀化退火炉的空炉温度和带料温度测试,以及铸锭均火工艺参数的制定方法,并指出确定铸锭均火工艺参数的原则。     

Erythropoietin in Optic Neuropathies: Current Future Strategies for Optic Nerve Protection and Repair

Erythropoietin (EPO) is known as a hormone for erythropoiesis in response to anemia and hypoxia. However, the effect of EPO is not only limited to hematopoietic tissue. Several studies have highlighted the neuroprotective function of EPO in extra-hematopoietic tissues, especially the retina. EPO could interact with its heterodimer receptor (EPOR/βcR) to exert its anti-apoptosis, anti-inflammation and anti-oxidation effects in preventing retinal ganglion cells death through different intracellular signaling pathways. In this review, we summarized the available pre-clinical studies of EPO in treating glaucomatous optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy and traumatic optic neuropathy. In addition, we explore the future strategies of EPO for optic nerve protection and repair, including advances in EPO derivates, and EPO deliveries. These strategies will lead to a new chapter in the treatment of optic neuropathy.     

Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases

Differential evolution of apoptosis, programmed necrosis, and autophagy, parthanatos is a form of cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1), which is caused by DNA damage. PARP1 hyper-activation stimulates apoptosis-inducing factor (AIF) nucleus translocation, and accelerates nicotinamide adenine dinucleotide (NAD⁺) and adenosine triphosphate (ATP) depletion, leading to DNA fragmentation. The mechanisms of parthanatos mainly include DNA damage, PARP1 hyper-activation, PAR accumulation, NAD⁺ and ATP depletion, and AIF nucleus translocation. Now, it is reported that parthanatos widely exists in different diseases (tumors, retinal diseases, neurological diseases, diabetes, renal diseases, cardiovascular diseases, ischemia-reperfusion injury...). Excessive or defective parthanatos contributes to pathological cell damage; therefore, parthanatos is critical in the therapy and prevention of many diseases. In this work, the hallmarks and molecular mechanisms of parthanatos and its related disorders are summarized. The questions raised by the recent findings are also presented. Further understanding of parthanatos will provide a new treatment option for associated conditions.     

燃气埋地钢制管道外防腐层完整性检测的应用及探讨

本文简要介绍了燃气埋地钢制管道外防腐层完整性检测的基本原理和方法,通过新、旧管道的完整性检测案例,叙述了完整性检测的过程,并分析了需要注意的因素和存在的问题,提出了解决外防腐层完整性检测的一些建议,希望对今后其他类似工程提供一定的参考.