The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21^Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.     

Red-shift and improved afterglow of Sr3Al2-xBxO5Cl2:Eu2+, Dy3+ phosphors via a cation substitution strategy

Sr₃Al_2-xB_xO₅Cl₂:Eu²⁺, Dy³⁺ (x = 0, 0.2, 0.4) long persistent phosphors were prepared via solid-state process. The pristine Sr₃Al₂O₅Cl₂:Eu²⁺, Dy³⁺ phosphor exhibits orange/red broad band emission around 609 nm, which can be attributed to the electric radiation transitions 4f⁶5 d¹→4f⁷ of Eu²⁺. Upon the same excitation, the B³⁺-doped Sr₃Al_2-xB_xO₅Cl₂:Eu²⁺, Dy³⁺ phosphors display red-shift from 609 nm to 625 nm with increasing B³⁺ concentrations. The XRD patterns show that Al³⁺ can be replaced by B³⁺ in the host lattice at the tetrahedral site, which causes lattice contraction and crystal field enhancement, and thereafter achieves the red-shift on the emission spectrum. The XPS investigation provides direct evidence of the dominant 2-valent europium in the phosphor, which can be ascribed for the broad band emission of the prepared phosphors. The afterglow of all phosphors show standard double exponential decay behavior, and the afterglow of Sr₃Al₂O₅Cl₂:Eu²⁺, Dy³⁺is rather weak, while the sample co-doped with B³⁺shows longer and stronger afterglow, as confirmed after the curve simulation. The analysis of thermally stimulated luminescence showed that, when B³⁺ is introduced, a much deeper trap is created, and the density of the electron trap is also significantly increased. As a result, B³⁺ ions caused redshift and enhanced afterglow for the Sr₃Al_2-xB_xO₅Cl₂:Eu²⁺, Dy³⁺ phosphor.     

Electromagnetism-like algorithms for optimized tool path planning in 5-axis flank machining

Optimization of tool path planning using metaheuristic algorithms such as ant colony systems (ACS) and particle swarm optimization (PSO) provides a feasible approach to reduce geometrical machining errors in 5-axis flank machining of ruled surfaces. The optimal solutions of these algorithms exhibit an unsatisfactory quality in a high-dimensional search space. In this study, various algorithms derived from the electromagnetism-like mechanism (EM) were applied. The test results of representative surfaces showed that all EM-based methods yield more effective optimal solutions than does PSO, despite a longer search time. A new EM-MSS (electromagnetism-like mechanism with move solution screening) algorithm produces the most favorable results by ensuring the continuous improvement of new searches. Incorporating an SPSA (simultaneous perturbation stochastic approximation) technique further improves the search results with effective initial solutions. This work enhances the practical values of tool path planning by providing a satisfactory machining quality.     

Restructuring bank networks after mergers and acquisitions: A capacitated delocation model for closing and resizing branches

During restructuring processes, due to mergers and acquisitions, banks frequently face the problem of having redundant branches competing in the same market. In this work, we introduce a new Capacitated Branch Restructuring Model which extends the available literature in delocation models. It considers both closing down and long term operations׳ costs, and addresses the problem of resizing open branches in order to maintain a constant service level. We consider, as well, the presence of competitors and allow for ceding market share whenever the restructuring costs are prohibitively expensive.We test our model in a real life scenario, obtaining a reduction of about 40% of the network size, and annual savings over 45% in operation costs from the second year on. We finally perform a sensitivity analysis on critical parameters. This analysis shows that the final design of the network depends on certain strategic decisions concerning the redundancy of the branches, as well as their proximity to the demand nodes and to the competitor׳s branches. At the same time, this design is quite robust to changes in the parameters associated with the adjustments on service capacity and with the market reaction.     

胸腺五肽辅助治疗肺癌对免疫功能影响及其疗效的系统评价

为了系统地评价胸腺五肽作为辅助药物治疗各种肺癌的疗效及其对机体免疫功能的影响，利用电子检索收集有关胸腺五肽联合放疗或化疗方案治疗肺癌的临床随机对照试验文献，对符合纳入标准的文献，采用RevMan5.3 软件进行系统评价。最终共纳入文献 9 篇，总样本量 784 例。Meta 分析结果表明，胸腺五肽作为辅助药物治疗各种肺癌提高总有效率的差异无统计学意义[OR ＝ 1.44, 95%CI(0.99, 2.10), P ＝0.06 ＞ 0.05]。在对免疫功能的影响方面，胸腺五肽的使用显著增高外周血中的 CD3+ 细胞水平[OR ＝ 5.88, 95% CI(2.34, 9.42), P ＝0.001]，CD4+ 细胞水平也显著上升[OR ＝8.32, 95%CI(5.22, 11.42), P ＜ 0.00001] , CD4＋ /CD8＋比值也有明显的提高[OR ＝ 0.38, 95% CI(0.18, 0.59), P＝0.0002]，但 CD8+ 细胞水平的差异无统计学意义[OR ＝－3.12, 95% CI ( －9.02, 2.79), P ＞0.05]。总的来说，本研究在一定程度上反映了在辅助治疗肺癌方面，胸腺五肽能显著提高外周血中的 CD3+ 细胞水平、CD4+ 细胞水平、CD4+/CD8+ 比值。而对于治疗的有效率、CD8+ 细胞水平，差异无统计学意义。     

Experimental research on dynamic response of PZT-5H under impact load

In order to improve the stability of PZT-based sensors, the mechanical, dielectric, ferroelectric and piezoelectric properties of PZT-5H under impact load were studied experimentally by using the separated Hopkinson pressure bar (SHPB) with an electrical output measurement device. At the same time, the experimental study on the material properties of PZT-5H before and after the impact was carried out. The effect of impact cracks on the output voltage of PZT-5H was also analyzed. The results show that the dynamic piezoelectric constants of PZT-5H under low stress impact (10–50 MPa) are different from those under quasi-static state, and the empirical relationship between them and the peak stress is obtained through experiments. The dielectric properties of PZT-5H did not change under low stress impact, but micro-cracks occurred in the material and dielectric loss increased at high frequencies. Under short circuit, the residual polarization intensity of PZT-5H decreases sharply due to impact load. While the impact load causes the secondary polarization and the increase of the residual polarization intensity of PZT under open circuit. When the stress is over 45 MPa, the PZT-5H breaks. The formation of cracks causes abnormal discharge voltage and gap discharge.     

Random poly(ε‐caprolactone‐L‐alanine) by direct melt copolymerization

A series of random polyesteramides (PEAs) with a range of molar composition from 90/10 to 50/50 were synthesized by direct melt polycondensation of ε‐caprolactone and l ‐alanine. Their structure was fully characterized by Fourier transform IR and NMR spectroscopy. The resulting copolymers are completely amorphous with the exception of PEA‐90/10 which possesses a semicrystalline structure. These PEAs present increasing glass transition temperatures at increasing l ‐alanine contents and exhibit fairly good thermal stability with 10% mass loss temperatures reaching 315 °C. © 2020 Society of Industrial Chemistry     

Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis

Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor–stroma crosstalk is instructed by the genetic alterations of the tumor cells—the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor–stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor–host communication within the entire organism so as to promote metastatic tumor cell dissemination.     

番禺30-1砂岩强水驱气藏储层非均质性研究

针对垂向非均质性严重且边底水能量强的番禺30-1气田面临的潜在开发问题，通过岩心分析及测井二次解释，对其夹层特征及储层非均质性等进行了研究，划分出19个流动单元并定量描述了各流动单元的特征参数，建立了该气田的精细地质模型。综合评价表明，新建的地质模型具有较高的精度，为该气藏合理开发提供了坚实的地质基础。