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.     

木质素单体模化物的热解与产物分析

采用苯酚、邻苯二酚、愈创木酚和紫丁香酚为木质素单体模化物,利用两段裂解反应器-在线气相色谱仪（GCs）进行热解实验和产物分析,采用多色谱柱对无机气体（IGs）、C₁~C₅烃（C₁~C₅ LHs）、非芳基含氧化合物、酚和芳烃进行定量分析,以确定羟基和甲氧基对木质素热解过程中开环反应及产物分布的影响. 结果显示：羟基和甲氧基可以提高模化物的转化率,且羟基和甲氧基的存在影响芳基开环反应、芳基取代反应和重排反应间的竞争关系,使热解产物分布存在明显差异. 4种模化物热解产物主要是芳环的开环反应产物,包括IGs（质量分数为27.29%~33.56%）和C₁~C₅烃（20.46%~39.51%）. 一氧化碳产率（23.82%~29.18%）随羟基数增加而升高,随甲氧基数增加而降低;二氧化碳产率（0.19%~9.61%）随甲氧基数增加而升高. 羟基和甲氧基的存在降低了C₁~C₅烃的质量选择性,促进了烷基苯、大分子化合物和焦炭的形成.     

WAVE FIELD EXTRAPOLATION IN VISCOELASTIC MEDIUM AND VARIABLE FOCUS METHOD TO SEPARATE SEISMIC COMPOUND WAVE

ＷＡＶＥＦＩＥＬＤＥＸＴＲＡＰＯＬＡＴＩＯＮＩＮＶＩＳＣＯＥＬＡＳＴＩＣＭＥＤＩＵＭＡＮＤＶＡＲＩＡＢＬＥＦＯＣＵＳＭＥＴＨＯＤＴＯＳＥＰＡＲＡＴＥＳＥＩＳＭＩＣＣＯＭＰＯＵＮＤＷＡＶＥ￥ＳｏｎｇＳｈｏｕｇｅｎ；ＹｕａｎＸｉｕｇｕｉ；ＨｅＪｉｓｈａｎ...     

化工过程熵增指数及其在磷复肥清洁生产评价中的应用

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。     

30%三唑锡悬浮剂的研制及作用机理分析

[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。     

吡唑醚菌酯悬浮剂的研制及配方中表面活性剂的复配性能分析

[目的]开发吡唑醚菌酯悬浮剂,并对较优配方中表面活性剂复配性能进行研究。[方法]采用湿法研磨工艺,通过粒径及稳定性等指标的测试,对配方中的润湿分散剂、增稠剂和防冻剂等进行了筛选,并采用表面张力法对表面活性剂组合的复配性能进行了研究。[结果]当表面活性剂8561与G5000的用量为5%和1%时,即摩尔比为4:1时,可制得合格的15%和25%吡唑醚菌酯悬浮剂。在该比例下,2种表面活性剂具有强烈的相互作用,与宏观现象相符。[结论]将复配表面活性剂协同增效理论与农药悬浮剂的研制相结合,对农药制剂研究工作有一定的指导意义。     

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

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.     

多功能橡胶助剂HT918在载重子午线轮胎胎面胶中的应用

研究多功能橡胶助剂HT918在载重子午线轮胎胎面胶中的应用。结果表明:在胎面胶中加入多功能橡胶助剂HT918,胶料的t10和t90缩短,交联密度增大,抗硫化返原性提高;硫化胶的定伸应力和拉伸强度增大,拉断伸长率和撕裂强度减小,耐老化性能、耐屈挠性能和耐磨性能提高,压缩生热降低;轮胎的抗湿滑性能和耐久性能提高,滚动阻力降低;多功能橡胶助剂HT918的综合性能等同或优于国外同类产品。     

Synthesis and XPS investigation of superdense lithium-graphite intercalation compound, LiC2

The superdense lithium-graphite intercalation compound (GIC),LiC₂, first synthesized by the author was prepared by the original technique in a piston-cylinder high-pressure chamber with internal heater. Cleaved surfaces of this compound, LiC₃, LiC₆ and pristine graphite were studied by the X-ray photoelectron spectroscopy (XPS) technique. It was shown that chemical shifts of carbon do not vary in the range LiC₆ to LiC₂ which suggests that the additional lithium intercalation into LiC₆ gives no significant change in the charge transfer rate per carbon atom. Carbon/lithium atom ratios were obtained for freshly cleaved surfaces and for the surfaces after argon ion bombardment. It was shown that the bombardment results in the surface decomposition of LiC₂-GIC.     

复合变质处理对铸造热锻模具钢力学性能的影响

研究了变质处理对铸造热锻模具钢力学性能的影响。结果表明：在相同热处理条件下，经RE和RE—Nb复合变质处理后，其冲击韧性与变质处理前相比分别提高了9．7和14．5J／cm^2，常温抗拉强度σb分别提高了82和234MPa，高温抗拉强度分别达到了976和994MPa，而硬度变化不大。