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81.
Jang Mi Han Jae Kyung Sohng Woo-Haeng Lee Tae-Jin Oh Hye Jin Jung 《International journal of molecular sciences》2021,22(5)
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. 相似文献
82.
为了减少海上集装箱货物运输中风浪造成的损坏,提出刚柔混合驱动主动式波浪补偿并联机构. 基于刚柔混合并联机构的动定平台的矩阵旋转原理和几何封闭法建立位置逆解数学模型;利用空间几何原理构建机构位置正解数学模型;利用求导法则对位置逆解进行求导,建立速度雅可比矩阵与加速度的二阶影响矩阵;基于绳子是柔性变形体推导出系统刚度矩阵,探究影响系统刚度的因素和增加系统刚度的原则. 利用数值模拟仿真对运动学和系统刚度进行验证,结果表明位置正逆解的输入输出误差不超过实际误差的2.25%;发现理论仿真曲线和样机仿真曲线较吻合,误差不超过7.4%,验证了运动学模型的正确性;根据刚度矩阵发现刚度影响因素对系统刚度的影响规律. 通过对绳驱动刚柔混合驱动波浪补偿并联机构的实验验证,发现该机构的补偿效果均高于90%. 证明研究结果为刚柔混合主动式波浪补偿并联机构的运动和机构设计提供了理论支持. 相似文献
83.
WAVE FIELD EXTRAPOLATION IN VISCOELASTIC MEDIUM AND VARIABLE FOCUS METHOD TO SEPARATE SEISMIC COMPOUND WAVE 总被引:2,自引:0,他引:2
WAVEFIELDEXTRAPOLATIONINVISCOELASTICMEDIUMANDVARIABLEFOCUSMETHODTOSEPARATESEISMICCOMPOUNDWAVE¥SongShougen;YuanXiugui;HeJishan... 相似文献
84.
从热力学第二定律出发, 指出清洁生产的热力学本质是控制物质由有序结构向无序转化并从中获取最大效益, 其优劣可由过程熵增反映。 引用复杂体系非平衡定态过程最小熵产生原理,推导出依据与外界交换的物流和热流信息定量计算化工复杂系统过程熵增的方法, 并定义过程熵增指数ζ 。 评价了化工过程对环境热力学状态的综合影响。选择以硫和以氨为载能原料的磷复肥工艺为例进行了计算和对比,其过程熵增指数分别为6.753和4.571,反映出载能原料硫作为废物排放对环境热力学状态产生更大的影响。 相似文献
85.
[目的]解决30%三唑锡悬浮剂分散稳定性的问题。[方法]为提高30%三唑锡悬浮剂分散稳定性,采用流点法对不同类型的分散剂进行初步筛选并测试表面张力,通过测试SC粒径、Zeta电势、悬浮率、流变性能确定分散剂配比与用量并对分散稳定机理进行分析。[结果]与单一分散剂制备SC相比,聚羧酸盐分散剂SD-816和聚氧乙烯醚磷酸酯分散剂SD-208复配体系制备的SC性能较优,其表观黏度、Zeta电势、粒径和悬浮率分别为386 mPa·s、-37.2 mV、2.58μm及98.4%。并且提出了聚羧酸盐分散剂和聚氧乙烯醚磷酸酯分散剂对农药三唑锡可能的分散机理。[结论]聚羧酸盐SD-816和聚氧乙烯醚磷酸酯SD-208的复配体系可同时提供静电排斥作用和空间位阻,明显改善SC体系的悬浮稳定性。 相似文献
86.
Martyna Zagrska-Dziok Patrycja Kleczkowska Ewa Oldzka Ramona Figat Marcin Sobczak 《International journal of molecular sciences》2021,22(7)
Polymeric hydrogels play an increasingly important role in medicine, pharmacy and cosmetology. They appear to be one of the most promising groups of biomaterials due to their favorable physicochemical properties and biocompatibility. The objective of the presented study was to synthesize new poly(chitosan-ester-ether-urethane) hydrogels and to study the kinetic release of genistein (GEN) from these biomaterials. In view of the above, six non-toxic hydrogels were synthesized via the Ring-Opening Polymerization (ROP) and polyaddition processes. The poly(ester-ether) components of the hydrogels have been produced in the presence of the enzyme as a biocatalyst. In some cases, the in vitro release rate of GEN from the obtained hydrogels was characterized by near-zero-order kinetics, without “burst release” and with non-Fickian transport. It is important to note that developed hydrogels have been shown to possess the desired safety profile due to lack of cytotoxicity to skin cells (keratinocytes and fibroblasts). Taking into account the non-toxicity of hydrogels and the relatively highly controlled release profile of GEN, these results may provide fresh insight into polymeric hydrogels as an effective dermatological and/or cosmetological tool. 相似文献
87.
Lei Wang Charlotte E. Pelgrim Daniël H. Swart Guido Krenning Adrianus C. van der Graaf Aletta D. Kraneveld Thea Leusink-Muis Ingrid van Ark Johan Garssen Gert Folkerts Saskia Braber 《International journal of molecular sciences》2021,22(9)
Chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) is featured by oxidative stress and chronic inflammation. Due to the poor efficacy of standard glucocorticoid therapy, new treatments are required. Here, we investigated whether the novel compound SUL-151 with mitoprotective properties can be used as a prophylactic and therapeutic treatment in a murine CS-induced inflammation model. SUL-151 (4 mg/kg), budesonide (500 μg/kg), or vehicle were administered via oropharyngeal instillation in this prophylactic and therapeutic treatment setting. The number of immune cells was determined in the bronchoalveolar lavage fluid (BALF). Oxidative stress response, mitochondrial adenosine triphosphate (ATP) production, and mitophagy-related proteins were measured in lung homogenates. SUL-151 significantly decreased more than 70% and 50% of CS-induced neutrophils in BALF after prophylactic and therapeutic administration, while budesonide showed no significant reduction in neutrophils. Moreover, SUL-151 prevented the CS-induced decrease in ATP and mitochondrial mtDNA and an increase in putative protein kinase 1 expression in the lung homogenates. The concentration of SUL-151 was significantly correlated with malondialdehyde level and radical scavenging activity in the lungs. SUL-151 inhibited the increased pulmonary inflammation and mitochondrial dysfunction in this CS-induced inflammation model, which implied that SUL-151 might be a promising candidate for COPD treatment. 相似文献
88.
文章基于二极管-电容倍压单元,提出了一种新型高增益升压变换器。该拓扑在实现高增益的同时可以避免使用极大的占空比,并且有效地降低开关管和二极管的电压应力。分析了变换器的工作原理,推导了变换器工作在连续状态(CCM)和断续状态(DCM)下的电压增益、开关器件的电压应力和电感电流纹波。CCM状态下与传统的Boost变换器相比电压增益是其(5-D)倍,电感电流纹波近似减小为原来的一半。最后通过仿真与样机实验验证了理论分析的正确性,表明提出的变换器具有良好的综合性能。 相似文献
89.
90.
针对配电网发生单相接地故障且分布式电源(distributed generations, DGs)大量接入后,配电网结构和运行方式复杂多变、故障后电气量不明显、故障特征弱等特点,提出一种基于改进局部均值分解(improved local mean decomposition, ILMD)和能量相对熵的主动配电网故障定位方法。首先,利用镜像延拓将信号在两端延拓,消除LMD存在的端点效应,同时,在信号中加入自适应噪声,克服LMD存在的模态混叠问题,对各区段暂态零序电流进行ILMD分解;然后对分解后所有乘积函数(product function, PF)的能量相对熵进行计算,所有PF分量的相对能量熵之和即为区段间的相对能量熵,通过所设置的定位判据,对故障区段进行判断。仿真结果表明,所提算法在10 kV小电流接地系统和改进的IEEE33节点系统中,在不同的仿真条件下故障定位结果准确率高,验证了所提方法的准确性。 相似文献