In vivo Targeting of DNA Vaccines to Dendritic Cells via the Mannose Receptor Induces Long-Lasting Immunity against Melanoma

Herein, we report effective, C-type lectin mannose receptor (MR)-selective, in vivo dendritic cell (DC)-targeting lipid nanoparticles (LNPs) of a novel lipid-containing mannose-mimicking di-shikimoyl- and guanidine head group and two n-hexadecyl hydrophobic tails (DSG). Subcutaneous administration of LNPs of the DSG/p-CMV-GFP complex showed a significant expression of green fluorescence protein in the CD11c⁺ DCs of the neighboring lymph nodes compared to the control LNPs of the BBG/p-CMV-GFP complex. Mannose receptor-facilitated in vivo DC-targeted vaccination (s.c.) with the electrostatic complex of LNPs of DSG/pCMV-MART1 stimulated long-lasting (270 days post B16F10 tumor challenge) antimelanoma immunity under prophylactic conditions. Remarkably, under therapeutic settings, vaccination (s.c.) with LNPs of the DSG/pCMV-MART1 complex significantly delayed melanoma growth and improved the survival of mice with melanoma. These findings demonstrate that this nonviral delivery system offers a resilient and potential approach to deliver DNA vaccines encoding tumor antigens to DCs in vivo with high efficacy.     

Expression of Opioid Receptors in Cells of the Immune System

The observation of the immunomodulatory effects of opioid drugs opened the discussion about possible mechanisms of action and led researchers to consider the presence of opioid receptors (OR) in cells of the immune system. To date, numerous studies analyzing the expression of OR subtypes in animal and human immune cells have been performed. Some of them confirmed the expression of OR at both the mRNA and protein level, while others did not detect the receptor mRNA either. Although this topic remains controversial, further studies are constantly being published. The most recent articles suggested that the expression level of OR in human peripheral blood lymphocytes could help to evaluate the success of methadone maintenance therapy in former opioid addicts, or could serve as a biomarker for chronic pain diagnosis. However, the applicability of these findings to clinical practice needs to be verified by further investigations.     

Mechanisms of Reciprocal Regulation of Gonadotropin-Releasing Hormone (GnRH)-Producing and Immune Systems: The Role of GnRH,Cytokines and Their Receptors in Early Ontogenesis in Normal and Pathological Conditions

Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders.     

建筑结构控制爆破拆除的力学分析与应用

应用运动学、动力学理论建立建(构)筑物控爆坍落过程的力学模型,进而研究在非定常约束条件下坍落结构的力学特征。首次提出了采用延时起爆技术时,非自由质点系及其广义坐标应是建立在每一段位上的瞬间虚位移。在此基础上,分析求解运动过程中时控单元的质点自由度,为精确选定爆破部位及时序提供了设计理论和计算依据。同时,结合振动理论,将控爆时差、结构载荷分布调制为振动系统,形成坍落结构梁板单元的强迫振动,充分实现在运动中进一步解体、破碎其自身结构,并形成具有明显缓冲效果的下落过程。应用实践结果证明力学分析是正确的,为工程结构爆破拆除计算机辅助设计及动态模拟技术的有效应用奠定了基础。     

A novel pre-dilution,swirling jet diffuser to enhance effluent mixing: Hydrodynamics and dilution performance

Diffusers are widely-used to quickly dilute effluents in receiving water bodies. This study proposed a novel diffuser that pre-mixes effluent with ambient water before discharging and that uses the swirling jet to further enhance near-field dilution. The nozzle of the diffuser was examined in two ambient flow conditions: co-flow and counter-flow that are commonly-met in the environment such as oceans due to tidal effect. Physical experiments were first conducted in co-flow on its dilution performance and hydrodynamics, using heated water as the effluent. A 3-D CFD model was developed and calibrated the co-flow scenarios, and then used to investigate the diffuser in counter-flow. The results showed that the nozzle can effectively reduce the maximum temperature rise of the effluent by about 50 % before discharging. The swirling jet from the outlet has a larger shear area, half-width and entrainment rate, enabling the effluent to be rapidly diluted to a minimum of around 10 times at x/D = 6 in co-flow, whereas the dilution for conventional nozzles is about 1 because of the potential core. The flow amplification ratio (α) decreases gradually with increasing velocity ratio in co-flow but increases with increasing velocity ratio in counter-flow. The counter-flow reduces the water drawn into the device; however, the pre-dilution effect at the outlet remains stable. The near-field dilution in counter-flow was significantly enhanced than that in co-flow. Environmental regulations at outfalls and mixing zones can be more easily met using this novel diffuser.     

以新发展理念引领高校专业基础课教学改革

以“创新、协调、绿色、开放、共享”为内核的新发展理念，是对马克思主义发展理念的继承和发扬，极具时代精神，富含问题意识，为高校思想政治教育发展、教育教学改革实践提供了强大的理论支撑。本文以“通信原理”为例，阐述了新发展理念在课程改革中的思路和方法，实现了思想政治教育与专业基础课程有机融合，为深化高校教学改革、创新人才培养模式提供了思路。     

Acceptive Immunity: The Role of Fucosylated Glycans in Human Host–Microbiome Interactions

The growth in the number of chronic non-communicable diseases in the second half of the past century and in the first two decades of the new century is largely due to the disruption of the relationship between the human body and its symbiotic microbiota, and not pathogens. The interaction of the human immune system with symbionts is not accompanied by inflammation, but is a physiological norm. This is achieved via microbiota control by the immune system through a complex balance of pro-inflammatory and suppressive responses, and only a disturbance of this balance can trigger pathophysiological mechanisms. This review discusses the establishment of homeostatic relationships during immune system development and intestinal bacterial colonization through the interaction of milk glycans, mucins, and secretory immunoglobulins. In particular, the role of fucose and fucosylated glycans in the mechanism of interactions between host epithelial and immune cells is discussed.     

Lactobacillus plantarum BC299 can alleviate dextran sulphate sodium-induced colitis by regulating immune response and modulating gut microbiota

It is well known that probiotics are effective in relieving inflammatory bowel disease (IBD). However, their exact mechanism is still unclear. Herein, we evaluated the effect of novel Lactobacillus plantarum BC299 on dextran sodium sulphate (DSS)-induced colitis model mice and investigated the molecular mechanism. We found BC299 could regulate immune response and reduce immunosuppression by enhancing the expression of Th1 T cells in cyclophosphamide-induced immunosuppressive model mice. Meanwhile, DSS-induced colitis model mice were furtherly constructed. The results displayed BC299 can restore bodyweight and relieve colon morphology of colitis mice. Real-time quantitative polymerase chain reaction results demonstrated BC299 can regulate immune response by reducing the expression of TNF-α and IL-1β mRNA and increasing the expression of IL-10 and TGF-β mRNA. Moreover, BC299 administration reshaped and increased the diversity of gut microbiota in IBD mice. Therefore, BC299 can alleviate colitis by regulating immune response and modulating gut microbiota.     

Effects of Eltrombopag on In Vitro Macrophage Polarization in Pediatric Immune Thrombocytopenia

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug.