Role of lipid rafts in innate immunity and phagocytosis of polystyrene latex microspheres

Understanding of the association of phagocytosis of polymers with signaling of innate immunity of macrophages is the major purpose of this study. Polymer conjugates have been utilized for clinical therapy of cancer and infections, such as Mycobacterium tuberculosis, as effective vectors of drug-delivery systems. They are incorporated through phagocytosis into macrophages and activate innate immunity signaling, which plays a crucial role in its therapeutic and side effects. Macrophage phagocytosis of polystyrene latex microspheres was examined and assayed by treatment of macrophages with the cholesterol depletor methyl-β-cyclodextrin (MβCD) or the sphingolipid depletor n-octyl-β-D-glucopyranoside (OGP). Expressions of various mRNAs during phagocytosis were quantified by real-time PCR. Phagocytosis of polystyrene latex microspheres by various macrophages, such as murine monocyte-derived macrophage J774, rat alveolar macrophage NR8383, and murine Kupffer cell KC13-2, was suppressed by treatment with MβCD or OGP in a concentration-dependent manner. The expression of mRNAs of TNFα, IL-1β, IL-6 and CXCL10 genes induced by lipopolysaccharide (LPS) was not suppressed by treatment with MβCD in J774 cells. Moreover, genes that were induced by LPS were up-regulated even in the absence of LPS by the phagocytosis of polymer conjugates, but such up-regulations were not suppressed by the treatment with MβCD. It was shown that lipid rafts play a significant role in incorporation of polymer conjugates through phagocytosis of macrophages, but their association with signal transduction in innate immunity is very limited.     

GJB151B CS115的电路仿真分析(一)--校准设备指标需求分析北大核心CSCD

GJB151B CS115给出了开展脉冲传导敏感度试验的校准平台构成和校准波形标准,但未明确校准平台各设备(脉冲源、电流注入环、校准夹具等)的具体指标需求。为解决这一问题,本文在前期脉冲电流注入电路仿真研究工作的基础上,构建了校准平台的时域电路模型,通过逐一改变模型参数的方法,仿真分析了脉冲源内部回路电感、电流注入环等效电感/电阻/电容等对校准波形前沿、半宽以及平顶降的影响,得出了平台各设备应达到的技术指标。该工作是对GJB151B CS115的有益补充,为搭建CS115试验平台,开展电子设备脉冲传导敏感度试验提供了技术支撑。     

Analysis of an SVEIS epidemic model with partial temporary immunity and saturation incidence rate

In this paper, an SVEIS epidemic model for an infectious disease that spreads in the host population through horizontal transmission is investigated. The role that temporary immunity (natural, disease induced, vaccination induced) plays in the spread of disease, is incorporated in the model. The total host population is bounded and the incidence term is of the Holling-type II form. It is shown that the model exhibits two equilibria, namely, the disease-free equilibrium and the endemic equilibrium. The global dynamics are completely determined by the basic reproduction number R₀. If R₀<1, the disease-free equilibrium is globally stable which leads to the eradication of disease from population. If R₀>1, a unique endemic equilibrium exists and is globally stable in the feasible region under certain conditions. Further, the transcritical bifurcation at R₀=1 is explored by projecting the flow onto the extended center manifold. We use the geometric approach for ordinary differential equations which is based on the use of higher-order generalization of Bendixson’s criterion. Further, we obtain the threshold vaccination coverage required to eradicate the disease. Finally, taking biologically relevant parametric values, numerical simulations are performed to illustrate and verify the analytical results.     

一类具有体液免疫反应,且染病细胞存在返回期的HIV模型的全局稳定性分析

研究了具有Beddington-DeAngelis发生率和体液免疫反应的HIV模型的全局性.模型包含了一个染病细胞返回期,在这个时期,染病细胞可能有一部分会返回到健康细胞当中.得到模型的基本再生数R0和免疫基本再生数R1.通过建立适当的Lyapunov函数,得出无病平衡点Q0,无免疫平衡点Q1和免疫平衡点Q2是全局渐近稳定的.     

可变聚类无标度网络上的谣言免疫策略

提出一种聚类免疫策略,使用改进的经典谣言传播模型,在可变聚类无标度网络上研究其免疫效果.研究发现,聚类免疫的效果随着网络聚类系数的增加而变好.在不同聚类系数下,比较目标免疫、介数免疫、紧密度免疫和聚类免疫的免疫效果发现,无论网络的聚类特性如何,介数免疫始终是几种免疫策略中效果最好的,当网络聚类系数较大时,聚类免疫的效果超过紧密度免疫接近目标免疫,进一步增大网络的聚类系数,聚类免疫的效果超过目标免疫而接近介数免疫.     

Antitumor Effects of Newcastle Disease Virus Hemagglutinin-neuraminidase Used as a Molecular Adjuvant

Gene therapy is a potentially powerful tool used in cancer therapy. The strength of immune responses induced by some strategies is usually low, therefore, the development of agents capable of enhancing these responses is highlighted. The authors investigated the potential of an approach based on the hemagglutinin-neuraminidase(HN) of Newcastle disease virus(NDV) as a potential immune adjuvant. It was found that recombinant adenovirus(Ad) infected SGC7901 cells expressing HN exhibited both hemagglutinin(HA) and neuraminidase(NA) activities. It was demonstrated that administration of HN induced higher levels of the effector cytokines TNF-α, IFN-α and IFN-γ and increased natural killer(NK) cell activity. Based on the therapeutic tumor model, the results show that the administration of HN with Apoptin led to improved survival and tumor suppression. In conclusion, this study indicates that HN stimulates innate immune responses to make the activity of NK cells increased, which highlights the potential adjuvant activity of HN in cancer gene therapy.     

承继关系下多资源受限多项目选择计划模型及其智能决策方案

综合多资源、项目权重和承继因素,以充分利用资源和均衡分配计划期内资源为目标,提出含多重资源约束的多项目选择计划混合优化决策模型;进而,基于体液免疫应答中B细胞应答抗原的运行机制和机理,提取简化的应答框架并结合资源约束设计算子模块,获得寻求多资源受限多项目选择计划问题的最优决策方案的隐并行免疫算法;数值实验比较结果显示该算法能获得满足资源限制的最佳决策方案,论证了该决策模型的合理性和应用潜力.     

Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small‐Molecule TLR7/8 Agonists

Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes of small‐molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage of the inherent serum‐protein‐binding property of lipid motifs and their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid–polymer conjugates that suppress systemic inflammation but provoke potent lymph‐node immune activation. This work provides a rational basis for the design of lipid–polymer amphiphiles for optimized lymphoid targeting.     

Toward Understanding the Molecular Recognition of Fungal Chitin and Activation of the Plant Defense Mechanism in Horticultural Crops

Large volumes of fruit and vegetable production are lost during postharvest handling due to attacks by necrotrophic fungi. One of the promising alternatives proposed for the control of postharvest diseases is the induction of natural defense responses, which can be activated by recognizing molecules present in pathogens, such as chitin. Chitin is one of the most important components of the fungal cell wall and is recognized through plant membrane receptors. These receptors belong to the receptor-like kinase (RLK) family, which possesses a transmembrane domain and/or receptor-like protein (RLP) that requires binding to another RLK receptor to recognize chitin. In addition, these receptors have extracellular LysM motifs that participate in the perception of chitin oligosaccharides. These receptors have been widely studied in Arabidopsis thaliana (A. thaliana) and Oryza sativa (O. sativa); however, it is not clear how the molecular recognition and plant defense mechanisms of chitin oligosaccharides occur in other plant species or fruits. This review includes recent findings on the molecular recognition of chitin oligosaccharides and how they activate defense mechanisms in plants. In addition, we highlight some of the current advances in chitin perception in horticultural crops.     

Role of Specialized Pro-Resolving Mediators in Modifying Host Defense and Decreasing Bacterial Virulence

Bacterial infection activates the innate immune system as part of the host’s defense against invading pathogens. Host response to bacterial pathogens includes leukocyte activation, inflammatory mediator release, phagocytosis, and killing of bacteria. An appropriate host response requires resolution. The resolution phase involves attenuation of neutrophil migration, neutrophil apoptosis, macrophage recruitment, increased phagocytosis, efferocytosis of apoptotic neutrophils, and tissue repair. Specialized Pro-resolving Mediators (SPMs) are bioactive fatty acids that were shown to be highly effective in promoting resolution of infectious inflammation and survival in several models of infection. In this review, we provide insight into the role of SPMs in active host defense mechanisms for bacterial clearance including a new mechanism of action in which an SPM acts directly to reduce bacterial virulence.