Long non-coding RNA (lncRNA) PTCSC3 is characterized as a tumor suppressor in thyroid cancer and glioma. The present study aimed to investigate the role of PTCSC3 in triple-negative breast cancer (TNBC). A total of 82 patients with TNBC were enrolled in the present study. The results showed that PTCSC3 was downregulated, while lncRNA MIR100HG was upregulated in tumor tissues compared with that in adjacent non-cancerous tissues of patients with TNBC. The follow-up study showed that low expression levels of PTCSC3 and high expression levels of MIR100HG were closely associated with poor survival of patients with TNBC. The expression levels of MIR100HG were decreased with the clinic stages of TNBC, while the expression levels of MIR100HG showed the opposite trend. Correlation analysis showed that the expression levels of PTCSC3 and MIR100HG were significantly correlated in both tumor tissues and adjacent non-cancerous tissues. The overexpression of PTCSC3 inhibited the expression level of MIR100HG in TNBC cells, while the expression level of PTCSC3 was unaffected. Cell Counting Kit-8 and Annexin V-FITC Apoptosis flow cytometry assays showed that overexpression of PTCSC3 led to inhibition, while overexpression of MIR100HG led to the promotion of TNBC cells viability and inhibited apoptosis of TNBC cells. In addition, overexpression of MIR100HG attenuated the effects of PTCSC3 overexpression on cancer cell viability. However, the overexpression of PTCSC3 did not affect cancer cell migration and invasion. Western-blot analysis showed that PTCSC3 suppressed viability and promoted apoptosis of TNBC cells through the Hippo signaling pathway. Thus, the present study demonstrated that lncRNA PTCSC3 inhibits cancer cell viability and promotes cancer cell apoptosis in TNBC by downregulating MIR100HG.

Background CD40 is a 48 kDa type I transmembrane protein that is constitutively expressed on hematopoietic cells such as dendritic cells, macrophages, and B cells. Engagement of CD40 by CD40L expressed on T cells results in the production of proinflammatory cytokines, induces T helper cell function, and promotes macrophage activation. The involvement of CD40 in chronic immune activation has resulted in CD40 being proposed as a therapeutic target for a range of chronic inflammatory diseases. CD40 antagonists are currently being explored for the treatment of autoimmune diseases and several anti-CD40 agonist mAbs have entered clinical development for oncological indications. Results To better understand the mode of action of anti-CD40 mAbs, we have determined the x-ray crystal structures of the ABBV-323 (anti-CD40 antagonist, ravagalimab) Fab alone, ABBV-323 Fab complexed to human CD40 and FAB516 (anti-CD40 agonist) complexed to human CD40. These three crystals structures 1) identify the conformational CD40 epitope for ABBV-323 recognition 2) illustrate conformational changes which occur in the CDRs of ABBV-323 Fab upon CD40 binding and 3) develop a structural hypothesis for an agonist/antagonist switch in the LCDR1 of this proprietary class of CD40 antibodies. Conclusions The structure of ABBV-323 Fab demonstrates a unique method for antagonism by stabilizing the proposed functional antiparallel dimer for CD40 receptor via novel contacts to LCDR1, namely residue position R32 which is further supported by a closely related agonist antibody FAB516 which shows only monomeric recognition and no contacts with LCDR1 due to a mutation to L32 on LCDR1. These data provide a structural basis for the full antagonist activity of ABBV-323.

空袭目标突防航路预测是进行防空兵力部署方案评估的辅助手段之一.在分析突防航路预测问题的基础上建立了空袭目标突防航路预测模型,并针对传统进化算法将航路作为一个整体后导致先前候选航路中高质量航路点利用效果较差的问题,提出了基于航路点进化的空袭目标突防航路预测算法.首先通过改进传统进化算法框架与评价函数使航路点可被分别进化和评价,然后使用自适应差分进化算法(JADE)实现航路点的进化,最后采用多准则决策方法实现航路点的评价与选择,从而提升了高质量航路点的利用效果.为了测试算法的性能,设置了障碍数目分别为15、30、60、120的4个仿真情景,仿真结果表明算法能够有效实现空袭目标突防航路的预测,并且在障碍数目较多的情景中其性能优于遗传算法.