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.     

Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer

Since the creation of Dolly via somatic cell nuclear transfer (SCNT), more than a dozen species of mammals have been cloned using this technology. One hypothesis for the limited success of cloning via SCNT (1%-5%) is that the clones are likely to be derived from adult stem cells. Support for this hypothesis comes from the findings that the reproductive cloning efficiency for embryonic stem cells is five to ten times higher than that for somatic cells as donors and that cloned pups cannot be produced directly from cloned embryos derived from differentiated B and T cells or neuronal cells. The question remains as to whether SCNT-derived animal clones can be derived from truly differentiated somatic cells. We tested this hypothesis with mouse hematopoietic cells at different differentiation stages: hematopoietic stem cells, progenitor cells and granulocytes. We found that cloning efficiency increases over the differentiation hierarchy, and terminally differentiated postmitotic granulocytes yield cloned pups with the greatest cloning efficiency.     

六垛南闸闸下淤积现状分析

针对我国在滨海河口地区修建的挡潮闸在河口建闸后普遍存在的泥沙淤积问题,根据苏北灌溉总渠入海口六垛南闸等处的实测资料,分析该挡潮闸下潮汐引河通道冲淤特性,指出挡潮闸下引河的潮流特性、潮流挟沙特性及引河淤积的原因。认为对闸门进行科学合理的控制、有效利用上游有限的泄水量和闸下落潮水流拖淤来防淤减淤是较为简便易行且经济的措施。     

Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation

Epigenetic silencing in cancer cells is mediated by at least two distinct histone modifications, polycomb-based histone H3 lysine 27 trimethylation (H3K27triM) and H3K9 dimethylation. The relationship between DNA hypermethylation and these histone modifications is not completely understood. Using chromatin immunoprecipitation microarrays (ChIP-chip) in prostate cancer cells compared to normal prostate, we found that up to 5% of promoters (16% CpG islands and 84% non-CpG islands) were enriched with H3K27triM. These genes were silenced specifically in prostate cancer, and those CpG islands affected showed low levels of DNA methylation. Downregulation of the EZH2 histone methyltransferase restored expression of the H3K27triM target genes alone or in synergy with histone deacetylase inhibition, without affecting promoter DNA methylation, and with no effect on the expression of genes silenced by DNA hypermethylation. These data establish EZH2-mediated H3K27triM as a mechanism of tumor-suppressor gene silencing in cancer that is potentially independent of promoter DNA methylation.     

一种脉冲压缩信号旁瓣抑制方法

给出了一种在脉冲压缩技术中实现低的压缩脉冲距离旁瓣的方法,由希望的压缩脉冲波形来设计加权滤波器。导出了可实现低的压缩脉冲距离旁瓣的条件。实验用声表面波(SAW)器件实现时,对线性调频信号,其压缩脉冲最大主旁瓣比为50dB。而用数字方法实现时,压缩脉冲最大旁瓣电平还受A/D及D/A变换器位数的限制。     

任意结构阵列基于高阶累积量的信号频率和二维角联合估计算法

提出了一种基于高阶累积量的信号频率和二维角估计算法。假设阵列中存在3个特性完全一致的阵元,此时使用高阶累积量实现的阵列虚拟展宽相当于存在两个和实际阵列相同的虚拟平移阵列,因而在其它阵元位置和响应特性未知的情况下也能实现空间信号频率和二维角估计。推导了使用PRO-ESPRIT算法实现联合估计的过程,并给出了相应的信号配对方法,计算机模拟结果证实了该算法的有效性。     

开关电容网络灵敏度分析的传递函数法

给出了一种开关电容网络(SCN)灵敏度分析的新方法。只要能写出SCN的z域改进节点电压方程,并且该方程系数矩阵在将z为e     

基于神经网络数据融合的目标跟踪简化算法

分析了基于神经网络数据融合的目标跟踪算法 ,指出了传统的融合算法计算量大 ,神经网络目标向量不易选取等缺点 ,并提出了一种简化的算法。应用理论分析和蒙特卡洛仿真方法 ,对标准卡尔曼滤波算法和简化的滤波算法进行了比较 ,并给出了均方根误差的统计值。该简化算法原理简单 ,数据处理量小 ,速度快 ,误差小 ,特别适用于多传感器的处理 ,将融合结果反馈给单传感器 ,可提高各单传感器的跟踪精度     

基于小波变换和凸集投影的数据恢复和建模算法

在过程控制中,当参数仅能以低采样率获得时,数据恢复就在建模中显得非常重要.本文提出了基于小波变换和凸集投影的数据恢复和建模算法.待恢复数据的先验知识采用凸集表达,并利用向凸集迭代投影(POCSProjection onto Convex