Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells

The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an n-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine the antiproliferative function and investigated possible mechanisms of SK2 acting on oral cancer cells. SK2 preferentially killed oral cancer cells but caused no harmful effect on non-malignant oral cells. After the SK2 exposure of oral cancer cells, cells in the sub-G1 phase accumulated. This apoptosis-like outcome of SK2 treatment was validated to be apoptosis via observing an increasing annexin V population. Mechanistically, apoptosis signalers such as pancaspase, caspases 8, caspase 9, and caspase 3 were activated by SK2 in oral cancer cells. SK2 induced oxidative-stress-associated changes. Furthermore, SK2 caused DNA damage (γH2AX and 8-hydroxy-2′-deoxyguanosine). In conclusion, a novel nitrated [6,6,6]tricycle-derived compound, SK2, exhibits a preferential antiproliferative effect on oral cancer cells, accompanied by apoptosis, oxidative stress, and DNA damage.     

QUANTIFICATION OF SHEAR DAMAGE EVOLUTION IN ALUMINIUM ALLOY 2024T3

Shear damage may occur in the process of metal machining such as blanking and cutting, where localized shear deformation is developed. Experimental findings indicate that microscopic shear damage evolution in aluminium alloy 2024T3 (A1 2024T3) is a multi-stage mechanism, including particle cracking, micro-shear banding, matrix microcracking and coalescence of microcracks. This study is an attempt to use a set of equations to describe the multi-stage shear damage evolution in Al 2024T3. The shear damage variables in terms of multi-couple parameters of a power-law hardening material have been defined. An evolution curve of shearing damage has been calculated from experimental data. The values of the shear damage variable at different stages of damage have also been calculated. By making use of the findings, the relation between the microscopic shear damage evolution and the macroscopic shear response of the material has been discussed.     

高铁锻钢制动盘热疲劳裂纹扩展仿真及寿命评价

巨大的制动热能导致高铁制动盘面出现热斑或热点,形成沿径向扩展的热疲劳裂纹,严重危及行车安全.通过仿真获得热疲劳裂纹扩展规律,据此制定出合适、经济的检测周期,具有重要意义.基于断裂力学理论,采用扩展有限单元法和自主研发的裂尖网格加密技术,得到热点形成规律,植入半椭圆形裂纹进行热疲劳断裂仿真,得到制动速度为400 km/h...     

考虑车辆随机停放的停车楼减震设计与可靠度分析

在停车楼的设计中通常将车辆荷载以活荷载的方式均匀分布到结构上,实际上受车辆随机停放的影响,停车楼结构整体质量中心偏移,一旦结构遭遇罕遇地震时,车辆的随机停放可能造成停车楼结构发生扭转破坏.本文在传统减震设计方法的基础上考虑车辆活荷载的随机性,并从可靠度的角度验算减震结构在大震作用下的倒塌概率.结果表明,相同的减震设计布...     

基于高斯曲率极值点的桥梁结构损伤识别方法

目前中小桥梁日常安全巡检存在对检查人员依赖性高、缺乏可量化的科学依据等不足.针对这些问题,本文提出了一种利用高斯曲率极值点对结构进行损伤识别的方法.将桥面视为受弯弹性薄板,根据弹性薄板的弯曲理论得到了在荷载作用下结构刚度变化与桥面弯曲程度(高斯曲率)的理论关系,并由此推导了高斯曲率对结构刚度损伤的敏感程度公式.通过有限...     

基于同步辐射原位CT的水牛角结构性能关系研究

为探究水牛角的结构性能关系,基于上海同步辐射光源搭建了高分辨原位CT系统,对水牛角角鞘进行初始表征和准静态压缩下的实时表征,并通过Top-Hat方法提取了角鞘内孔洞三维形貌.结果显示,水牛角角鞘孔隙率在1％左右,椭圆柱状孔洞沿牛角生长方向排列成线,首尾相连却并未连通,均匀分布在波浪状片层之间.孔洞特征椭球的轴长分布满足...     

Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability

All-trans-retinoic acid (ATRA), the active metabolite of vitamin A, plays a pivotal role in cell differentiation, proliferation and embryonic development. It is an effective therapy for dermatological disorders and malignancies. ATRA is prone to isomerization and oxidation, which can affect its activity and selectivity. Novel diphenylacetylene-based ATRA analogues with increased stability can help to overcome these problems and may offer significant potential as therapeutics for a variety of cancers and neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we investigated the effects of these retinoids on cell viability and genotoxicity in the widely used model system of the rapidly proliferating Chinese hamster ovary cell line. DC360 is a fluorescent ATRA analogue and DC324 is a non-active derivative of DC360. EC23, DC525, DC540, DC645, and DC712 are promising analogues with increased bioactivity. The cytotoxic activity of the compounds was evaluated by ATP assay and DNA damage was tested by comet assay. No cytotoxicity was observed in the 10⁻⁶–10⁻⁵ M concentration range. All compounds induced DNA migration similar to ATRA, but DC324, DC360 and EC23 did so to a greater extent, particularly at higher concentrations. We believe that retinoid receptor-independent genotoxicity is a general characteristic of these compounds; however, further studies are needed to identify the molecular mechanisms and understand their complex biological functions.     

基于改进云推理算法的塔架结构损伤识别

为了解决塔架结构的损伤识别问题,提出了基于应变能和改进云推理算法的损伤识别方法。首先描述了云模型的基本理论和数字特征,并给出了模态应变能的基本公式;然后分析了X条件云发生器和Y条件云发生器的基本算法和运行步骤,借助灰云模型建立相应的前件云和后件云规则,考虑了测量噪声的影响,利用云发生器生成多组云滴,并利用多模式下云滴的确定度和生成值构建了基本云推理算法及其损伤识别指标。基本云推理算法中常会产生不均匀发散的云滴,从而使计算结果产生一定的偏差,为了降低云滴发散产生的偏差影响,提出了基于损伤模式数量加权的云推理改进策略。计算结果表明:云推理算法可以较好地应用于塔架结构的损伤识别,其识别结果明显优于传统的应变能耗散率指标方法;而改进云推理算法进一步提高了识别的精度,优于基本云推理算法。     

复合材料层合板冲击损伤及剩余强度分析方法

应用三维逐渐累积损伤理论和分析技术对层合板的冲击及冲击后含损伤的层合板在拉伸载荷下损伤扩展的全过程进行分析.分析中取消了以往研究者对冲击后层合板损伤状态所做的人为假设,将冲击后层合板的实际损伤状态直接用于剩余拉伸强度研究.通过与已有文献结果比较,验证了方法的正确性.     

变温场中具损伤粘弹性矩形板的非线性动力响应分析

基于热粘弹性理论、Von Karman板理论和连续损伤力学,导出了二维状态下各向同性材料的变温粘弹性本构方程,建立了含损伤效应的各向同性粘弹性矩形板在变温场中的非线性运动控制方程,且应用有限差分法对问题进行求解.算例中,讨论了损伤演化及温度场等因素对粘弹性矩形板非线性动力学行为的影响,得出一些有意义的结论.