Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses in head and neck squamous cell carcinoma

The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced IL-1β production in an HNSCC mouse model and reduced the numbers of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased the numbers of CD4⁺ and CD8⁺ T cells in HNSCC mice. Notably, the numbers of exhausted PD-1⁺ and Tim3⁺ T cells were significantly reduced. A human HNSCC tissue microarray showed that NLRP3 inflammasome expression was correlated with the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results demonstrate that the NLRP3 inflammasome/IL-1β pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells. Thus, inhibition of the tumor microenvironment through the NLRP3 inflammasome/IL-1β pathway may provide a novel approach for HNSCC therapy.     

尾水管水力振动的监测与故障判断

从模型及真机试验结果出发，叙述混流式水轮机一般的水力故障形式，研究了尾水管的水力振动特点及振动随运行工况而变化的情况，介绍了以压力脉动频率及幅值作为特征参量对尾水管进行振动监测及故障判断的方法。     

酸性硅溶胶沉淀法制备超微细活性白炭黑

对酸性硅溶胶沉淀法生产超微细活性白炭黑的工艺进行了研究；探讨了生产过程中硅溶胶的ｐＨ值，反应终点ｐＨ值，反应温度以及分散剂等条件；制备了较高品质的产品，其性能接近或超过国外同类产品．     

C60偶联多孔硅系统的蓝光发射

用G60作为表面钝化剂，与多孔硅进行偶联．发现当C60偶联多孔硅系统在空气中存储一年后，能够发射460nm左右的强烈蓝光．经过系统的测量和分析，认为蓝光起源的发光中心与SiO2体材料中的“自捕获激子”模型类似．它是由一个氧空位和一个间隙氧组成的，间隙氧同时和相邻的晶格氧形成过氧连接．光激发载流子来自于Si纳米晶粒的核心，辐射复合过程则在多孔硅表面的发光中心进行．进一步的电子束辐照和臭氧辐照实验证明了这个发光中心的存在．从FTIR谱的分析，推测是样品表面Si=O双键的缓慢变化促使了蓝光中心的自发产生．     

An efficient algorithm to generate candidates in discovering frequent episodes

0 IntroductionData mining is widely used in many research fieldssuch as decision supporting systems[1], bio-informationanalysis[2]and knowledge engineering[3-5]. Most data col-lected from scientific experiments or telecommunicationnetworks have inherent sequential nature inthemand canthus be abstractly viewed as a sequence of events . Onebasic problemin miningsuchevent sequencesis discoveryof recurrent combinations of events , which are calledepisodes. Once frequent episodes are discovered,rul…     

电子线路的数值优化设计

研究了电子线路的数值化设计方法.它是一种自动化程度高、通用性强、精度高的电路设计方法。介绍了电子线路数值优化设计软件系统YJX—1.它具有广泛的通用性和快速收敛的特点。     

梯形水平折梁的内力分析

本文对梯形水平折梁（０≤α＜∏２）和矩形水平折架（α＝∏２）用最小余能原理进行了内力分析，并导出了相应的计算公式，可在工程结构设计中采用     

产品原理方案的功能设计法──“管接头标记自动压印机”的原理方案设计

本文通过“管接头标记自动压印机”原理方案的构思过程，说明产品原理方案设计的功能论方法的一般原理和特点及其应用。     

约束条件下直动凸轮机构最佳偏距的程序优化

在直动从动件盘形凸轮的设计中，减少推程压力角可改善凸轮的受力条件，适当的偏置可以减少压力角。本文通过计算机设计方法来确定具有最小凸轮机构尺寸时的最佳偏距。