多重网络中的创意扩散模型研究

基于线上线下多种渠道的创意扩散研究是企业管理的新兴研究热点之一.为此,引入多重网络理论与传播动力学理论,考虑工作中线下沟通、工作中通过企业社交媒体在线沟通及非工作时间电子沟通三种渠道,构建多种渠道构成的多重网络中的创意扩散模型.研究创意在多重网络中持续扩散的阈值条件,并对创意在多重网络中的扩散过程进行仿真实验.结果表明:1)当员工在单位时间内通过以上各渠道沟通的平均次数较接近时,在多重网络中创意扩散的速度较快,创意扩散的范围较广;2)与匀质网络相比,当非工作时间电子沟通子网络是无标度网络时,在多重网络中创意扩散的速度较快,扩散的范围较广;3)增大子网络层间创意扩散的相互促进作用对整个多重网络中创意的有效扩散有积极影响.     

基于最小二乘法对GM(1.1)模型的研究及应用

针对提高股票未来价格的预测精度,提出区间模糊数的整体GM(1.1)预测模型.利用最优解求解定义方程,得到区间模糊数的预测公式.基于区间模糊数满意度对投资组合选择模型进行优化,得到单目标规划投资选择模型.通过实例分析,给定不同的满意度得到不同的投资组合,证明模型具有一定的柔性.     

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.     

Microsatellite instability in gastric cancer: molecular bases,clinical perspectives,and new treatment approaches

Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.     

General mechanisms of drought response and their application in drought resistance improvement in plants

Plants often encounter unfavorable environmental conditions because of their sessile lifestyle. These adverse factors greatly affect the geographic distribution of plants, as well as their growth and productivity. Drought stress is one of the premier limitations to global agricultural production due to the complexity of the water-limiting environment and changing climate. Plants have evolved a series of mechanisms at the morphological, physiological, biochemical, cellular, and molecular levels to overcome water deficit or drought stress conditions. The drought resistance of plants can be divided into four basic types-drought avoidance, drought tolerance, drought escape, and drought recovery. Various drought-related traits, including root traits, leaf traits, osmotic adjustment capabilities, water potential, ABA content, and stability of the cell membrane, have been used as indicators to evaluate the drought resistance of plants. In the last decade, scientists have investigated the genetic and molecular mechanisms of drought resistance to enhance the drought resistance of various crops, and significant progress has been made with regard to drought avoidance and drought tolerance. With increasing knowledge to comprehensively decipher the complicated mechanisms of drought resistance in model plants, it still remains an enormous challenge to develop water-saving and drought-resistant crops to cope with the water shortage and increasing demand for food production in the future.     

利用SRTM数据修测高山区地貌的探讨

在高海拔区域测制地形图,如青藏高原地区,所获取的遥感影像局部存在着大范围的高山阴影或云雪覆盖,造成立体观测地貌困难的现象,探讨应用SRTM数据对这类特殊区域地貌进行修测补绘。介绍了数据处理的作业过程,并对实验区SRTM与SPOT5影像立体测图成果进行实验对比分析,成果符合要求。     

循环作用对马蹄寺石窟群岩体性能的影响

马蹄寺石窟群地处河西走廊中部,气候条件十分恶劣。由于常年受到温度、湿度、酸碱盐等作用的影响,石窟岩体性能出现了不同程度的劣化现象。通过开展室内模拟试验,研究以上多种恶劣环境的循环作用对于岩体抗压强度、波速、质量的影响规律,同时使用X射线衍射仪(X-ray diffraction,XRD)、X射线荧光光谱(X-ray fluorescence,XRF)和扫描电子显微镜(scanning electron microscope,SEM)对循环作用过程中样品的矿物组分、元素含量和微观形貌进行分析研究。研究结果表明,循环作用使样品中的长石类矿物和方解石含量降低,黏土类矿物含量增加,胶结程度下降,孔隙逐渐发展成为横向微裂隙,导致样品的性能出现不同程度的劣化现象。循环作用对岩体性能的影响程度从大到小依次为冻融循环、耐盐循环、耐碱循环、耐酸循环和温湿循环。     

Junctional adhesion molecule-A: functional diversity through molecular promiscuity

Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) regulate important processes such as cell proliferation, differentiation and morphogenesis. This activity is primarily due to their ability to initiate intracellular signaling cascades at cell–cell contact sites. Junctional adhesion molecule-A (JAM-A) is an IgSF-CAM with a short cytoplasmic tail that has no catalytic activity. Nevertheless, JAM-A is involved in a variety of biological processes. The functional diversity of JAM-A resides to a large part in a C-terminal PDZ domain binding motif which directly interacts with nine different PDZ domain-containing proteins. The molecular promiscuity of its PDZ domain motif allows JAM-A to recruit protein scaffolds to specific sites of cell–cell adhesion and to assemble signaling complexes at those sites. Here, we review the molecular characteristics of JAM-A, including its dimerization, its interaction with scaffolding proteins, and the phosphorylation of its cytoplasmic domain, and we describe how these characteristics translate into diverse biological activities.     

Current knowledge on exosome biogenesis and release

Exosomes are nanosized membrane vesicles released by fusion of an organelle of the endocytic pathway, the multivesicular body, with the plasma membrane. This process was discovered more than 30 years ago, and during these years, exosomes have gone from being considered as cellular waste disposal to mediate a novel mechanism of cell-to-cell communication. The exponential interest in exosomes experienced during recent years is due to their important roles in health and disease and to their potential clinical application in therapy and diagnosis. However, important aspects of the biology of exosomes remain unknown. To explore the use of exosomes in the clinic, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are better understood. We have here summarized what is presently known about how exosomes are formed and released by cells. Moreover, other cellular processes related to exosome biogenesis and release, such as autophagy and lysosomal exocytosis are presented. Finally, methodological aspects related to exosome release studies are discussed.