Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors

Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification.     

Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis

Gut microbiota encompasses a wide variety of commensal microorganisms consisting of trillions of bacteria, fungi, and viruses. This microbial population coexists in symbiosis with the host, and related metabolites have profound effects on human health. In this respect, gut microbiota plays a pivotal role in the regulation of metabolic, endocrine, and immune functions. Bacterial metabolites include the short chain fatty acids (SCFAs) acetate (C2), propionate (C3), and butyrate (C4), which are the most abundant SCFAs in the human body and the most abundant anions in the colon. SCFAs are made from fermentation of dietary fiber and resistant starch in the gut. They modulate several metabolic pathways and are involved in obesity, insulin resistance, and type 2 diabetes. Thus, diet might influence gut microbiota composition and activity, SCFAs production, and metabolic effects. In this narrative review, we discuss the relevant research focusing on the relationship between gut microbiota, SCFAs, and glucose metabolism.     

利用有机硅高沸物制备乳化硅油及脱膜剂

实验主要利用有机硅副产物高沸物生产系列有价值的下游产品乳化硅油及脱膜剂.介绍了实验的基本原理、主要工艺操作步骤、所使用原材料及产品质量标准,此产品在一些工业装置上使用效果较佳,有一定应用价值.     

Internet蠕虫防范技术研究与进展

当前蠕虫的频频爆发使得蠕虫问题已成为网络安全领域的焦点问题。分析了蠕虫的特征行为,研究了国内外几种最新的Internet蠕虫防范系统,并在此基础上展望了蠕虫攻防的发展趋势。     

可在单片机上实现的语音混沌保密通信方法

针对目前数字混沌保密方法中计算量大的不足,提出了一种可在单片机上实现的改进混沌保密方法,并将该方法用于数字语音混沌保密通信。分析了该方法中运用整数运算代替浮点运算降低计算量的原理与过程,着重说明了改进的混沌算法在单片机上的实现。最后,在AT89C51单片机上成功进行了数字语音的混沌保密通信实验并取得了令人满意的结果。     

Marching Cubes算法改进研究及应用

对MC算法进行了改进和优化,运用渐近线判别法解决了原有算法的二义性问题,改善了生成图形的质量;利用线性八叉树结构提高了图形的绘制速度,使实时绘制和交互操作成为可能。运用改进后的MC算法,结合某铁矿实测数据进行矿体表面三维重构,得到了满意的效果。     

基于Max-tree的连通区域标记新算法

采用灰度图像创建Maxtree的基本思想,提出一种新的二值图像连通区域标记算法。该算法主要采用8邻域搜索及排序队列方式实现,通过一次扫描二值图像即可完成连通区域标记。提出一种新的8邻域搜索策略,可以将邻域搜索次数由八次减少到平均四次以下,从而提高了系统效率。此外,还给出一种排序队列的快速实现方法,并将其应用到标记算法中。而且,该算法的运行时间仅与待标记图像的大小有关,与连通区数目和图像内容无关。该算法已应用于海藻图像识别,实验结果表明该算法是快速、高效的。     

Relative expression and regulation by short-term fasting of lysophosphatidic acid receptors and autotaxin in white and brown adipose tissue depots

Lysophosphatidic acid (lysoPtdOH) levels have previously been reported to decrease in rodents with short-term fasting. We investigated whether a 16 h fast would change expression of autotaxin, the predominant phospholipase D responsible for adipose-derived lysoPtdOH synthesis, or any of the lysophosphatidic acid receptors (1–6) in four white adipose tissue (WAT) depots and interscapular brown adipose tissue (BAT) in male C57Bl/6J mice fed ad libitum, or fasted for 16 h. Aside from small inductions of Lpar1 in epididymal WAT and Lpar2 in epididymal and inguinal WAT, no significant changes were observed in expression of the Lpar family members, or autotaxin in perirenal, retroperitoneal, epididymal, or inguinal WAT or BAT with fasting. Comparison of the relative expression of Lpar1-6 in various depots showed that Lpar6 was the predominant Lpar in both WAT and BAT, and suggests that further work on the adipose-specific role of Lpar6 is warranted.     

Comparison of two low-hazard organic solvents as individual and cosolvents for the fabrication of polysulfone membranes

Petroleum-derived solvents commonly used in membrane fabrication are often hazardous and toxic, so the investigation of safer alternatives is important. In this study, two low-hazard solvents, methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate (Rhodiasolv® PolarClean) and gamma-valerolactone (GVL), were investigated as sole solvents and as cosolvents to cast polysulfone membranes via nonsolvent induced phase inversion. Normalized viscosity was introduced as an indicator of dope solution homogeneity and was used to compare the required time of mixing to achieve full dissolution of the polymer in the different solvents/solvent mixtures. All dope solutions made with low-hazard solvents were found to be more viscous than those made with traditional solvents, which meant additional mixing time was needed, and that fabricated membranes were morphologically different. With respect to operation, membranes cast from dope solutions containing equal amounts of PolarClean and GVL displayed the most similar flux curves and solute rejection to those made using the traditional solvent tested.