石杉碱甲片联合丁苯酞软胶囊对轻度阿尔茨海默病患者认知功能的疗效观察

目的 评价石杉碱甲片联合丁苯酞软胶囊对阿尔茨海默病患者认知功能的临床疗效.方法 将100例轻度阿尔茨海默病(Alzheimer's disease,AD)患者随机分为石杉碱甲片联合丁苯酞软胶囊组(治疗组)及单独应用石杉碱甲组(对照组).治疗前及治疗90 d后分别评价两组患者简易智力状态检查(Mini-mental State Examination,MMSE)量表、事件诱发电位P300潜伏期、波幅及不良反应.结果 石杉碱甲片联合丁苯酞软胶囊组治疗90 d后,MMSE评分和P300潜伏期、波幅与治疗前比较差异均具有统计学意义(P<0.05);与单独应用石杉碱甲组比较差异具有统计学意义(P<0.05).结论 石杉碱甲片联合丁苯酞软胶囊对轻度阿尔茨海默病患者认知功能有明显改善,且优于单独应用石杉碱甲片组.     

Prion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression

Neurogenesis continues in the post-developmental brain throughout life. The ability to stimulate the production of new neurones requires both quiescent and actively proliferating pools of neural stem cells (NSCs). Actively proliferating NSCs ensure that neurogenic demand can be met, whilst the quiescent pool makes certain NSC reserves do not become depleted. The processes preserving the NSC quiescent pool are only just beginning to be defined. Herein, we identify a switch between NSC proliferation and quiescence through changing intracellular redox signalling. We show that N-terminal post-translational cleavage products of the prion protein (PrP) induce a quiescent state, halting NSC cellular growth, migration, and neurite outgrowth. Quiescence is initiated by the PrP cleavage products through reducing intracellular levels of reactive oxygen species. First, inhibition of redox signalling results in increased mitochondrial fission, which rapidly signals quiescence. Thereafter, quiescence is maintained through downstream increases in the expression and activity of superoxide dismutase-2 that reduces mitochondrial superoxide. We further observe that PrP is predominantly cleaved in quiescent NSCs indicating a homeostatic role for this cascade. Our findings provide new insight into the regulation of NSC quiescence, which potentially could influence brain health throughout adult life.     

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.     

Attack and Defense Strategies in Complex Networks Based on Game Theory

To investigate the attack and defense strategies in complex networks, the authors propose a two-player zero-sum static game model with complete information which considers attack and defense strategies simultaneously. The authors assume that both the attacker and defender have two typical strategies: Targeted strategy and random strategy. The authors explore the Nash equilibriums of the attacker-defender game and demonstrate that when the attacker's attack resources are not so significantly abundant as the defender's resources, there exists a pure-strategy Nash equilibrium in both model networks and real-world networks, in which the defender protects the hub targets with large degrees preferentially, while the attacker prefers selecting the targets randomly. When the attack resources are much higher than defense resources, both the attacker and the defender adopt the targeted strategy in equilibriums. This paper provides a new theoretical framework for the study of attack and defense strategies in complex networks.     

Loewy矩阵与几乎Koszul代数

几乎Koszul代数作为Koszul代数的推广,在代数周期性和分次自入射代数的研究中起到了重要的作用.几乎Koszul代数的刻画是一个复杂的计算问题,而Loewy矩阵为Koszul代数的刻画带来了较为直观的计算方法.通过经典的Loewy矩阵和构造增广Loewy矩阵,利用分次代数分次模的两种不同Loewy维数向量得到了一个分次模成为d-线性模的充分必要条件,并得到了一个有限维分次代数成为几乎Koszul代数的充分必要条件,从而推广郭晋云利用Loewy矩阵刻画Koszul代数的相关结果.     

基于目标跟踪与轨迹聚类的行人移动数据挖掘方法研究

随着物联网、大数据、人工智能等技术在安防领域不断取得突破性进展,公共视频监测系统近年来得到飞跃式发展.基于监控设备产生海量的非结构化视频数据,通过对监控视频中的行人轨迹进行分析和研究,可以挖掘出其中蕴含的行为模式,这对人群行为研究有着重要的研究价值.本文使用基于目标检测的多目标跟踪算法对地铁站出口,商场出口等场景中的行人移动轨迹进行提取,并在此基础上对行人的轨迹模式进行分析.针对行人轨迹的特点,在基于点密度聚类算法的基础上,提出并实现了基于轨迹相似度的轨迹聚类方法.结果表明,该方法能够有效的提取行人轨迹,并且从大规模轨迹数据中提取出轨迹模式.     

东濮凹陷胡庆地区原油地球化学特征与油源分析

研究东濮凹陷胡庆地区原油地球化学特征及其来源.利用有机地球化学分析方法,对原油与烃源岩进行饱和烃色谱、饱和烃与芳烃色谱-质谱分析,剖析了两者的分子地球化学特征及油源.研究表明:胡庆地区发育3类原油,第一类原油具有极高伽马蜡烷,质量色谱图中甾烷呈"L"形特征,来自第二台阶的沙一段烃源岩,在沙一段储层中富集形成自生自储常温常压油藏;第二类原油为具有较高伽马蜡烷、三环萜烷以C23为主峰、甾烷呈不对称"V"形特征的中质油,来自第二台阶的沙三下亚段烃源岩,近源聚集形成常温常压油藏;第三类原油为具有较低伽马蜡烷、三环萜烷以C21为主峰、甾烷呈不对称"V"形特征的轻质油,是第一台阶的海通集洼陷沙三中亚段烃源岩生成,在第一台阶优质砂体中聚集形成的高温高压油藏.3类油藏由浅至深形成了3个独立的油气成藏系统,海通集洼陷并没有向第二台阶供烃.     

Ordinary language philosophy,explanation, and the historical turn in philosophy of science

Taking a cue from remarks Thomas Kuhn makes in 1990 about the historical turn in philosophy of science, I examine the history of history and philosophy of science within parts of the British philosophical context in the 1950s and early 1960s. During this time, ordinary language philosophy's influence was at its peak. I argue that the ordinary language philosophers' methodological recommendation to analyze actual linguistic practice influences several prominent criticisms of the deductive-nomological model of scientific explanation and that these criticisms relate to the historical turn in philosophy of science. To show these connections, I primarily examine the work of Stephen Toulmin, who taught at Oxford from 1949 to 1954, and Michael Scriven, who completed a dissertation on explanation under Gilbert Ryle and R.B. Braithwaite in 1956. I also consider Mary Hesse's appeal to an ordinary language-influenced account of meaning in her account of the role of models and analogies in scientific reasoning, and W.H. Watson's Wittgensteinian philosophy of science, an early influence on Toulmin. I think there are two upshots to my historical sketch. First, it fills out details of the move away from logical positivism to more historical- and practice-focused philosophies of science. Second, questions about linguistic meaning and the proper targets and aims of philosophical analysis are part and parcel of the historical turn, as well as its reception. Looking at the philosophical background during which so-called linguistic philosophers also had a hand in bringing these questions to prominence helps us understand why.