Molecular Dynamic Simulation Insights into the Normal State and Restoration of p53 Function

As a tumor suppressor protein, p53 plays a crucial role in the cell cycle and in cancer prevention. Almost 50 percent of all human malignant tumors are closely related to a deletion or mutation in p53. The activity of p53 is inhibited by over-active celluar antagonists, especially by the over-expression of the negative regulators MDM2 and MDMX. Protein-protein interactions, or post-translational modifications of the C-terminal negative regulatory domain of p53, also regulate its tumor suppressor activity. Restoration of p53 function through peptide and small molecular inhibitors has become a promising strategy for novel anti-cancer drug design and development. Molecular dynamics simulations have been extensively applied to investigate the conformation changes of p53 induced by protein-protein interactions and protein-ligand interactions, including peptide and small molecular inhibitors. This review focuses on the latest MD simulation research, to provide an overview of the current understanding of interactions between p53 and its partners at an atomic level.     

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.     

Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway

Ubiquitin-specific protease 39 (USP39), a member of the deubiquitinating enzyme family, has been reported to participate in cytokinesis and metastasis. Previous studies determined that USP39 functions as an oncogenic factor in various types of cancer. Here, we reported that USP39 is frequently overexpressed in human lung cancer tissues and non-small-cell lung cancer (NSCLC) cell lines. USP39 knockdown inhibited the proliferation and colony formation of A549 and HCC827 cells and decreased tumorigenic potential in nude mice. Specifically, knocking down USP39 resulted in cell cycle arrest at G2/M and subsequent apoptosis through the activation of the p53 pathway, including upregulation of p21, cleaved-cas3, cleaved-cas9 and downregulation of CDC2 and CycinB1. Moreover, USP39 knockdown significantly inhibited migration and invasion of A549 and HCC827 cells, also via activation of the p53 pathway, and downregulation of MMP2 and MMP9. Importantly, we verified these results in metastasis models in vivo. Collectively, these results not only establish that USP39 functions as an oncogene in lung cancer, but reveal that USP39 has an essential role in regulating cell proliferation and metastasis via activation of the p53 pathway.     

Photocatalytic degradation of diclofenac using hybrid MIL-53(Al)@TiO2 and MIL-53(Al)@ZnO catalysts

In this work, TiO₂ and ZnO were incorporated successfully into a MIL-53(Al) metal–organic framework (MOF) to form nanocomposites via a facile post-modification technique. The hybrid MIL-53(Al)@TiO₂ and MIL-53(Al)@ZnO were characterized by several characterization tests. The X-ray diffraction (XRD), Fourier-transform infrared (FTIR), and field-emission scanning electron microscopy (FE-SEM) analyses showed evidence of the successful incorporation of TiO₂ and ZnO within the MIL-53(Al) framework. The thermal gravimetric analysis (TGA) analysis demonstrated the excellent thermal stability of MIL-53(Al)@TiO₂ and MIL-53(Al)@ZnO, while diffuse reflectance spectroscopy (DRS) determined the direct optical band gaps of MIL-53(Al)@ZnO and MIL-53(Al)@TiO₂ to be 3.24 and 3.34 eV, respectively. The composites were also tested for the photocatalytic degradation of diclofenac (DCF) as a micropollutant. The DCF degradation efficiency of the photocatalysts was ranked in the following order: MIL-53(Al)@TiO₂ > MIL-53(Al) > TiO₂ > ZnO > MIL-53(Al)@ZnO. The incorporation of TiO₂ enhanced the optical properties of MIL-53 (Al), which was confirmed with the superior photodegradation efficiency of MIL-53(Al)@TiO₂ (>85% in 2 h) as compared to the pristine MIL-53(Al) (around 80% in 2 h). The improvement in the photodegradation of the hybrid-MOF is mostly associated with the possible dual function of the adsorption and photodegradation mechanisms. The reusability of MIL-53(Al) and its composites was inspected over 3 cycles of photodegradation experiments with DCF. The photocatalytic activity of MIL-53(Al)@TiO₂ remained unchanged (>90%), while for MIL-53(Al) and MIL-53(Al)@ZnO a slight drop was observed over three cyclic degradation experiments. Fluorescence measurements revealed that the hydroxyl radical is an important reactive oxygen species produced by all the photocatalysts that aid in the photodegradation of DCF. Furthermore, the kinetic modelling of the photoreaction identified a second-order kinetics for all catalysts. Experiments with scavengers showed that hydroxyl radicals played a major role in the photocatalytic process, and it was found that only 2 h of treatment was sufficient to obtain a considerable chemical oxygen demand (COD) reduction of 58%.     

TAM胶粘剂中铅镉汞铬砷有害元素的同时测定

研究了HF +HCl消解样品 ,试液用ICP -AES法同时测定TAM胶粘剂中铅、镉、汞、铬、砷的新方法。在选定的最佳条件下测铅、镉、汞、铬、砷的检出限分别为 0 .0 0 15、0 .0 0 0 8、0 .0 0 11、0 .0 0 17、0 .0 0 0 9μg·L- 1 ,回收率为 93 .5 %～ 10 8.3 % ,RSD为 0 .62 %～ 5 .65 %。该法准确、快速、简便 ,应用于TAM胶粘剂的测定 ,结果满意     

亚光涤纶DTY研制与开发

采用高TiO2 含量聚酯切片 ,选择合适的熔融纺丝和加弹工艺路线 ,可以生产具有柔和光泽和一定抗紫外效果的亚光DTY长丝     

某雷达天线反射器的轻量化研制

本项目采用化学蚀刻法制作副反射器栅面图形替代原来的绷丝工艺;用高强度聚氨酯泡沫、J-164填充胶、低密度纤维粉等材料制作天线反射器法兰和加强筋部分;采用一体化成型法兰的方法既节约了两套法兰模具、缩短了天线制作周期,又减轻了天线的重量,采用合理的后处理工艺使天线反射器的型面精度达到图纸要求。     

Bioaccumulation of As(III)/As(V) ions by living cells of Corynebacterium glutamicum MTCC 2745

Significant factors on simultaneous growth and bioaccumulation of arsenic ions by living cells of bacteria, Corynebacterium glutamicum MTCC 2745, were explored in growth media under experimental conditions like pH and concentrations of arsenic ions. Combined effects of the initial concentrations of peptone and arsenic (either As(III) or As(V)) ions on the specific growth rate and arsenic bioaccumulation competence of the bacteria were studied and optimized using the Response Surface Methodology. Optimum combination predicted via RSM demonstrated that the bacteria were capable of bioaccumulating As(III) and As(V) in the growth medium containing 1000 mg/L arsenic and 9 g/L peptone up to 78.4% and 77.6%, respectively.     

Metal‐organic gels of simple chemicals and their high efficacy in removing arsenic(V) in water

Metal‐organic gels (MOGs) have emerged as a class of functional materials that show great potential applications in the field of catalysis, energy storage, template synthesis, and environmental technology. The construction of functional MOGs and the control of functionality are still challenging due to complicated chemicals or routes involved in previous works. Here we report a series of tunable multifunctional MOGs by directly gelating between Fe³⁺ and simple chemicals, propanedioic acid (H₂PA), succinic acid (H₂SA), glutaric acid (H₂GA), and fumaric acid (H₂FA) in ethanol. The obtained MOGs exhibit self‐healing property and good conductivity, and were used for high efficacy removal of arsenic (As) in water. The ease, low cost, and scalability of the assembly process combined with multifunctionality make these MOGs be potentially applied in the fields of energy storage and sewage disposal. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3719–3727, 2018     

NiCoFe三元金属基LDHs对水中三价砷的吸附性能研究

采用共沉淀法制备了硝酸根型层状复合金属氢氧化物NiCoFe-LDHs,研究其对水中的三价砷的吸附性能,系统研究溶液初始浓度、吸附时间以及溶液pH值等因素对吸附性能的影响。结果表明,当As(Ⅲ)溶液浓度为2 mg/L时,吸附率达到了81.1%,吸附量在As(Ⅲ)溶液浓度为4 mg/L时,达到了15.72 mg/g,而溶液pH值为8时,吸附性能最好,且吸附过程在30 min内可以达到平衡。热力学和等温吸附式的研究表明NiCoFe-LDHs对As(Ⅲ)的吸附过程,符合Langmuir模型和伪二级动力学模型,因此吸附过程发生在吸附剂表面,且吸附过程为化学吸附。