一类离散时间复杂网络系统的输出同步

利用线性稳定性理论和Lyapunov函数方法,研究了一类离散时间复杂网络系统的输出同步问题,得到了系统输出指数同步的充分性条件,数值算例表明了方法的有效性.     

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.     

Defining G protein-coupled receptor peptide ligand expressomes and signalomes in human and mouse islets

Introduction

Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.

Materials and methods

GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.

Results

We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.

Discussion

The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.

     

The modernity of Dedekind’s anticipations contained in What are numbers and what are they good for?

Archive for History of Exact Sciences - We show that Dedekind, in his proof of the principle of definition by mathematical recursion, used implicitly both the concept of an inductive cone from an...     

页岩气低伤害超临界CO2凝胶压裂液研究

针对常规水压裂液会对页岩造成伤害，容易产生水锁，不易返排，还造成水资源消耗和污染环境等问题，制备了低伤害二氧化碳凝胶压裂液。将自备的F2EU和F4EU增稠剂加入到超临界CO₂基液中，探究两种增稠剂的加入量对CO₂凝胶压裂液黏度的影响，综合考虑成本与效果，优选了2%的F4EU增稠剂，可将CO₂的黏度增至15.4 mPa·s。研究了温度、压力以及剪切速率对凝胶压裂液黏度的影响。实验结果表明，随着温度升高黏度总体降低，但中间出现一个短暂升高阶段；随着压力上升压裂液黏度增加；随着剪切速率的增加压裂液黏度下降，属于一种典型的剪切变稀的假塑性流体。F4EU超临界CO₂凝胶压裂液的平均伤害率为1.39%，远远小于常规压裂液对岩芯的伤害率。实验表明，F4EU超临界CO₂凝胶压裂液在页岩气压裂开采中具有良好的应用前景。     

The expansion of GPCR transactivation-dependent signalling to include serine/threonine kinase receptors represents a new cell signalling frontier

G protein-coupled receptor (GPCR) signalling is mediated through transactivation-independent signalling pathways or the transactivation of protein tyrosine kinase receptors and the recently reported activation of the serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Since the original observation of GPCR transactivation of protein tyrosine kinase receptors, there has been considerable work on the mechanism of transactivation and several pathways are prominent. These pathways include the “triple membrane bypass” pathway and the generation of reactive oxygen species. The recent recognition of GPCR transactivation of serine/threonine kinase receptors enormously broadens the GPCR signalling paradigm. It may be predicted that the transactivation of serine/threonine kinase receptors would have mechanistic similarities with transactivation of tyrosine kinase pathways; however, initial studies suggest that these two transactivation pathways are mechanistically distinct. Important questions are the relative importance of tyrosine and serine/threonine transactivation pathways, the contribution of transactivation to overall GPCR signalling, mechanisms of transactivation and the range of cell types in which this phenomenon occurs. The ultimate significance of transactivation-dependent signalling remains to be defined but it appears to be prominent and if so will represent a new cell signalling frontier.     

基于风廓线雷达的降水云分类方法在海南地区的应用

将风廓线雷达用于热带降水云体进行垂直探测,可以实时对热带地区降水云体进行较准确分类.通过对海口地区降水云系特征(2017年1月～12月)进行统计分析,提出一套基于风廓线雷达探测数据(回波强度、垂直速度和速度谱宽)的热带降水云体分类方法.以该方法为基础,结合天气雷达等观测资料,对2017年发生在海口地区的两次降水过程展开详细分析.结果表明:风廓线雷达具备较好体现降水云体垂直结构的能力,相比于天气雷达,风廓线雷达探测数据可以更精细地描述降水云系的变化趋势;相比于传统降水分类方案,采用以风廓线雷达探测数据为基础的分类方案可以提高对复杂降水类型识别的正确率;风廓线雷达可以更好地描述快速过境的高空微弱对流系统.