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.     

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。     

从线粒体DNA控制区基因探讨红腹锦鸡和白腹锦鸡的分类关系

用聚合链式反应(PCR)和直接测序的方法测定红腹锦鸡(Chrysolophus pictus)和白腹锦鸡(C.amherstiae)各5个样本线粒体DNA控制区的468 bp的序列,共发现26个变异位点.红腹锦鸡的序列变异率为0.90%,白腹锦鸡的序列变异率是0.17%,两者差异极显著.红腹锦鸡和白腹锦鸡的3种碱基(A,T,C)含量差异显著.根据Kumar双参数法计算两种锦鸡的遗传距离为0.035±0.008,按线粒体DNA控制区的进化速率2%/Myr计算,它们的分歧进化的时间大约是(1.75±0.40)Myr,结果支持它们是两个独立的种.红腹锦鸡和白腹锦鸡可能分别起源于秦岭以南地区和横断山脉.     

项目投资时机及投资概率分析

针对实物期权理论中存在的不足,运用鞅理论分析研究了市场环境下的确定性和不确定性因素对实物资产项目投资决策的影响.首先,通过鞅方法建立了反映投资时机和投资回报临界值之间关系的投资时机模型;然后,使用测度变换评价了项目投资能够被实施的可能性.研究结果表明确定性因素对投资时机和投资回报临界值具有相反作用的影响,不确定性因素则均具有正向作用的影响,且在确定性因素取值较小情况下,不确定性对投资却具有促进作用.     

表征高温性能的沥青纯粘性稠度

利用自行研发的沥青稠度测试仪,对沥青高温流动和粘弹特性进行分析可知,粘性成分是沥青抵抗变形的关键.为此引入了0.1 s-1剪变率时的纯粘性稠度,并提出了计算方法.将高温时0.1 s-1纯粘性稠度与沥青常规高温指标和沥青混合料动稳定度进行了比较分析,结果表明:高温时0.1 s-1纯粘性稠度克服了常规指标不适宜评价改性沥青的缺点,适合作为沥青高温性能新指标.最后,分析并推荐了沥青高温0.1 s-1纯粘性稠度标准的建议值.     

Genome-wide association studies of 14 agronomic traits in rice landraces

Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ～ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ～ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice.