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.     

南方丝绸之路对大理的影响及当前的对策

大理历史悠久,文化灿烂,风光秀丽,古道纵横。过去南方丝绸之路对大理的经济、政治、交通、文化、宗教等有较大的影响,今天在国家"一带一路"的大战略背景下,大理应该怎么办,大理学院应该怎么办,这是当代学人的新课题。以古代南方丝绸之路为出发点,建议今天大理的"一带一路"定位为交往之路、人情之路。     

上海黄浦江两支流河流甲烷含量研究

甲烷是一种重要的温室气体,虽然目前大气中含量远小于二氧化碳,但排放增长率却大于后者.研究区域为上海市黄浦江支流苏州河和淀浦河,通过实验数据对比城郊春夏的甲烷排放的差异,探讨甲烷产生的机制及其与环境因子的关系,这将有助于研究河流甲烷排放对于环境变化的影响.研究结果认为河流甲烷主要来源于水中沉积物,其产生与水质、温度等因素相关;同时甲烷摩尔浓度与硝酸根离子质量体积比存在负相关性,与铵根离子质量体积比和有机碳质量分数存在正相关性.     

Study on the Centralization Strategy of the Blood Allocation Among Different Departments within a Hospital

By far, the researches on how to distribute blood products among different departments in hospital have not been further studied, though the problem of blood shortage and wastage that caused by improper blood allocation is severe, which may endanger patient’s lives and impose considerable costs on hospitals. In order to solve this problem, this paper mainly studies on how to distribute the blood items among different departments within a hospital and investigates the allocation approach with the novel management method by centralizing the inventory of several different departments. By integrating the blood inventory requirements of some departments, the hospital could reduce the rate of blood shortage and wastage effectively, release the pressure of the occupancy of resources and reduce the bullwhip effect of blood products. This paper illustrates the centralization principle in hospital and formulates the mixed integer programming model to work out the optimal allocation network scheme and the optimal inventory setting for every department. And the results of the numerical example demonstrate that this centralization method could considerably reduce blood shortage and wastage in hospital by about 72% and 90% respectively. Furthermore, it could decrease the total cost by about 108,540 RMB a month on blood supply chain management in the hospital and improve the effect of some certain surgeries by transfusing the fresh blood to patients.     

基于稳健协方差矩阵的ADS-B压制式干扰抑制

压制式干扰是广播式自动相关监视(automatic dependent surveillance broadcast, ADS-B)系统面临的最常见且最有威胁的干扰之一。提出基于稳健协方差矩阵估计的ADS-B压制式干扰抑制算法。首先,考虑了ADS-B信号的脉冲特性,将协方差矩阵的求解转化成凸优化问题。然后,利用求解凸优化问题得到的稳健协方差矩阵设计最优权矢量。最后,对观测信号进行空域滤波,完成ADS-B的压制式干扰抑制,并对抑制结果进行性能分析。提供的仿真实验结果也验证了算法的有效性,该方法不需要知道ADS-B信号来向,且在非高斯噪声情况下同样有效。     

金属间化合物(Mg,Zn)_(12)Ce与(Mg,Zn)_(11)Ce的研究

对300℃时Mg-Zn-Ce系富镁侧化合物的成分特征、结构和相平衡关系进行了研究.结果表明,Mg-Zn-Ce富镁角存在一个Mg12Ce的二元置换固溶体(Mg,Zn)12Ce,还存在一个三元线性化合物(Mg,Zn)11Ce(τ相).(Mg,Zn)12Ce中Zn的范围为0~7.3%(原子分数),其晶体结构为体心四方晶格.三元线性化合物τ相含Zn为8.5%~43.5%(原子分数),其晶体结构为C底心正交晶格.(Mg,Zn)12Ce和τ相均与α(Mg)存在稳定的两相平衡,且在Mg-Zn-Ce系富镁角还存在三相平衡Mg+(Mg,Zn)12Ce+τ.     

以双城市周家镇为例探讨以产业发展带动小城镇建设

发展小城镇是我国的走城市化道路的必然选择,而城市化必须有经济建设为支撑,双城市周家镇被确定为国家级小城镇综合改革试点镇后,就成了双城的经济特区,通过分析双城周家镇的区位优势及产业优势,对周家镇小城镇建设提出几点建议.     

Reconsideration on Homogeneous Quadratic Riemann Boundary Value Problem

The homogeneous quadratic Riemann boundary value problem (1) with Hoelder continuous coefficients for the normal case was considered by the author in 1997. But the solutions obtained there are incomplete. Here its general method of solution is obtained.     

女大学生排球选修课教学之我见

本文依据大学生生理、心理的阶段特征，通过变换组织教法以及增强学生主体、教师主导的双边作用，分析排球课的项目特点。使技能学习和人格发展相结合，培养身心健康发展的大学生。     

高等师范院校内部管理人文关怀问题初探

“强规强序”型内部管理体制深刻地制约着师范教育品质的进一步提升；主动调整管理策略，在管理中注入“人关怀”意识是变革教育模式、提升教育品质的重要举措。具体讲，可从四个方面实现突破：把尊重师生的个性差异作为制定管理规范的基本准则；把激发师生的个体潜能作为谋划管理策略的最终目标；把师生参与管理作为支持内部管理变革的主要方法；把营造宽松、和谐的人际氛围作为内部管理的激活措施。