Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells

We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.     

基于IDA方法的地铁车站结构抗震性能评价

针对目前大型地下结构抗震性能评价尚不完善,提出了一种基于非线性增量动力分析(incremental dynamic analysis,IDA)的多层多跨地下结构横断面地震易损性分析的方法.选用典型三层三跨地铁车站建立土-结构二维整体分析有限元模型,采取等效线性化模型模拟土体在地震作用下的剪切模量退化和阻尼增加特性,纤维梁单元模拟多层地下结构在地震作用下的滞回特性.基于PEER强震记录数据库的21条地表地震动峰值加速度中位值,将其统一调幅到不同强度水平,作为非线性IDA的输入地震动.根据IDA结果的统计分析,对于浅埋多层地下结构而言,地表峰值加速度和峰值速度是有效且合适的地震动强度指标,可以用来构建地下结构的易损性曲线.通过与现有的矩形地下结构经验地震易损性曲线和数值地震易损性曲线比较,验证了数值模拟得到的地震易损性曲线的有效性,可以作为快速评价地下结构抗震性能的有效工具.     

走滑断层黏滑错动下隧道破坏的模型试验研究

为了探究断层错动对隧道及围岩的损伤机理及破坏特性,以滇中引水工程香炉山隧洞为依托,通过开展隧道穿越断层破碎带的黏滑错动模型试验,并采用ABAQUS进行数值建模,对试验结果进行验证分析.研究结果表明:断层错动过程中,衬砌主要发生受拉破坏,局部位置衬砌受压破坏;衬砌发生变形及破坏的区域,主要集中在破碎带范围内,以错动面处衬砌变形、破坏最为突出,衬砌的变形随距错动面距离的增大而减少,衬砌横断面内拱顶、右腰位置破坏最为严重;断层错动起始时刻,破碎带中间部位拱顶处衬砌拉损伤已经达到较高量级,衬砌局部开裂破坏,随着断层错动量的增加,损伤不断累积,当错动量达25 mm(相当于实际错动量1 m)时,衬砌整体损伤已累积到较高量级,此时衬砌的破坏接近试验的最终状况.岩体的破裂区域主要集中在距错动面两侧30 cm范围内,围岩变形随着距错动面距离的增加而逐渐减小.     

The Role of Chronic Inflammation in Various Diseases and Anti-inflammatory Therapies Containing Natural Products

Chronic inflammation represents a long-term reaction of the body's immune system to noxious stimuli. Such a sustained inflammatory response sometimes results in lasting damage to healthy tissues and organs. In fact, chronic inflammation is implicated in the development and progression of various diseases, including cardiovascular diseases, respiratory diseases, metabolic diseases, neurodegenerative diseases, and even cancers. Targeting nonresolving inflammation thus provides new opportunities for treating relevant diseases. In this review, we will go over several chronic inflammation-associated diseases first with emphasis on the role of inflammation in their pathogenesis. Then, we will summarize a number of natural products that exhibit therapeutic effects against those diseases by acting on different markers in the inflammatory response. We envision that natural products will remain a rich resource for the discovery of new drugs treating diseases associated with chronic inflammation.     

陕北±800 kV换流站高填方湿陷性黄土地基处理方案研究

陕北±800 kV换流站用地为原循环工业经济园区挖黄土梁卯、填深沟给出的一块台阶式场地,场地覆盖一层厚度0~50 m的素填土,密实度差异较大,土质极不均匀,填土完成约5年半时间,是一种欠固结土,在其自身重度和大气降水的入渗作用下有自行密实的特点,影响位于填方区建(构)筑物地基的承载力和稳定性。基于该工程特殊的岩土地质情况,除挖方区采用天然地基外,从处理填方区大面积欠固结土和消除部分地基土湿陷性、提高地基土承载力、减小场地沉降变形的角度,对不同地基处理及桩基方案进行技术经济综合比选,提出适合本工程的经济合理的地基处理方案。     

基于主成分分析与Wasserstein距离的低压用户相别识别

负载不平衡会导致电能质量差、功率损耗增加、变压器使用寿命缩短等问题,而准确识别用户相别可调整部分用户相别,尽可能达到三相负载平衡,因此提出一种基于主成分分析与Wasserstein距离的低压用户相别识别方法.首先利用主成分分析提取低压用户电压主成分进行聚类,然后计算聚类中值与关口各相电压Wasserstein距离进行相别归属.实测数据证明该方法对相别识别准确性较高,且相较于传统相似度算法在判别相别时具有明显区分度.     

Robust Superhydrophobic Fabric for Durability,Self-Cleaning,and Oil/Water Separation via Thiol–Acrylate Polymerization

In recent years, highly efficient oil/water separation materials have brought much attention. It requests superhydrophobic surfaces with a rapid and facile separation process, excellent durability, and large-scale fabrication. Herein, a facile vapor-liquid sol-gel, and free radical polymerization reaction method to prepare the durable and robust superhydrophobic cotton fabric is proposed. Moreover, the fabric can be used for highly efficient and various oil/water separation. It is prepared via a simple two-step process, including a vapor-liquid sol-gel process to deposit with thiols particles, and then followed a free radical polymerization reaction to graft 2,2,3,4,4,4-hexafluorobutyl methacrylate. Scanning electron microscopy and Fourier transform infrared spectrometry prove that the rough structures are generated from the hydrolysis condensation reaction between tetraethyl orthosilicate and 3-mercaptopropyltriethoxysilane. As a result, the synthetic chemical composition provided by the natural fabric and silica nanoparticles synergistically construct a superhydrophobic surface with water contact angles and shedding angle of 158° and 9°, respectively. Additionally, the treated fabric exhibits excellent chemical resistance and self-cleaning ability. Remarkably, the fabric still retains superhydrophobic and excellent mechanical robustness after 30 cycles of various oil/water separation. In summary, the resultant fabrics with excellent chemical resistance, remarkable mechanical robustness, and versatile separation abilities have potential applications in various oil/water separations.     

成都奥力公司率53人考察团赴德国埃森国际焊接与切割展会

九月，秋高气爽的日子，同时也是“第十六届德国埃森国际焊接与切割展览会”盛大举办的日子。这个极负盛名的国际展会每四年举行一次，享誉全球，吸引着来自世界知名的焊接与切割生产厂商、用户集聚德国埃森，共同分享世界先进的焊接与切割技术。本届德国埃森国际焊接展于9月12—17日在德国埃森市举办。     

粉煤灰基混凝剂的制备及在大麻废水中的应用

采用酸溶法以粉煤灰为基础原料 ,通过添加一定量的硫铁矿烧渣 ,制备成粉煤灰基复合混凝剂 ,确定了最佳工艺条件 .实验结果表明 ,影响混凝剂制备的主要因素是粉煤灰与硫铁矿渣的质量比、酸用量、浸取时间和温度 .此混凝剂对大麻废水中 CODcr去除率达 88% ,色度去除率可达 96.6%以上 ,具有沉淀快和污泥体积小等优点 .