重组人干扰素γ联合弓形虫STAg鼻内免疫小鼠的免疫保护作用

目的观察重组人干扰素γ(IFNγ)联合可溶性速殖子抗原(STAg)鼻内免疫小鼠诱导的黏膜和系统免疫应答及抗弓形虫感染作用。方法将BALB/c小鼠随机分为STAg组、STAg+IFNγ组和对照组,分别用20μgSTAg、20μgSTAg+1000UIFNγ和20μlPBS鼻内免疫2次,间隔14d。末次免疫后第10天,用RH株弓形虫速殖子灌胃攻击(4×104个/只),观察小鼠存活情况,并计算存活率,攻击后第43天处死全部小鼠,计数肝、脑组织内弓形虫速殖子虫荷,分离并计数肠上皮淋巴细胞(iIELs)、派伊尔氏结(PP)和脾淋巴细胞,ELISA法检测小鼠粪便弓形虫特异性sIgA和血清IgG水平。结果IFNγ联合STAg鼻内免疫能保护小鼠抵抗弓形虫攻击,小鼠存活率(93%)明显高于STAg组(60%)和对照组(47%);小鼠iIELs(1.81×105)、PP(3.21×107)和脾(3.01×107)淋巴细胞均显著增生,明显高于STAg组和对照组;粪便中sIgA水平(A492=0.435)显著高于对照组(A492=0.047),血清IgG水平(A492=0.233)显著高于STAg组(A492=0.193)和对照组(A492=0.115);肝、脑组织内弓形虫速殖子虫荷显著减少,分别比对照组减少80.90%和64.50%。结论IFNγ联合STAg鼻内免疫效果优于单独STAg免疫,IFNγ能协同STAg有效诱导黏膜和系统免疫应答,提高弓形虫攻击小鼠的存活率,降低肝、脑组织内虫荷。     

Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of Ecklonia cava Fucoidan against Metastatic Lung Cancer

Although fucoidan, a well-studied seaweed-extracted polysaccharide, has shown immune stimulatory effects that elicit anticancer immunity, mucosal adjuvant effects via intranasal administration have not been studied. In this study, the effect of Ecklonia cava-extracted fucoidan (ECF) on the induction of anti-cancer immunity in the lung was examined by intranasal administration. In C57BL/6 and BALB/c mice, intranasal administration of ECF promoted the activation of dendritic cells (DCs), natural killer (NK) cells, and T cells in the mediastinal lymph node (mLN). The ECF-induced NK and T cell activation was mediated by DCs. In addition, intranasal injection with ECF enhanced the anti-PD-L1 antibody-mediated anti-cancer activities against B16 melanoma and CT-26 carcinoma tumor growth in the lungs, which were required cytotoxic T lymphocytes and NK cells. Thus, these data demonstrated that ECF functioned as a mucosal adjuvant that enhanced the immunotherapeutic effect of immune checkpoint inhibitors against metastatic lung cancer.     

一种具有混合编码的二进制差分演化算法

差分演化(DE)是Storn和Price于1997年提出的一种基于个体差异重组思想的演化算法,非常适用于求解连续域上的最优化问题.首先引入"差异算子"等概念,给出DE的一种简洁算法描述,并分析了它所具有的特性.然后,为了使DE能够求解离散域上的最优化问题,基于数学变换思想引入"辅助搜索空间"和"个体混合编码"等概念,通过定义一个特殊的满射变换,在辅助搜索空间的作用下将连续域上的高效差分演化搜索变换为离散域上的同步演化搜索,由此提出了第1个二进制差分演化算法:具有混合编码的二进制差分演化算法(HBDE).接着,给出了HBDE的依概率收敛和完全收敛的定义,并利用离散Markov随机理论证明了HBDE是完全收敛的. HBDE不仅完全具有DE的各种特性和所有优点,而且非常适用于求解离散域上的最优化问题,对随机生成的大规模3-SAT问题实例和典型0/1背包问题实例的数值计算表明:该算法具有很好的全局收敛性和稳定性,其性能远远超过二进制粒子群优化算法和遗传算法.     

白细胞介素-2基因佐剂对乙型肝炎疫苗免疫效果的影响

目的研究白细胞介素-2基因佐剂对乙型肝炎疫苗免疫效果的影响。方法利用分子生物学技术构建含IL-2基因的重组质粒pcDNA3.1/IL-2,经测序鉴定、碱裂解法大量提取及Sepharose4FF柱层析纯化,得到重组质粒pcDNA3.1/IL-2和pcDNA3.1/S,免疫豚鼠后,经ELISA检测豚鼠血清中抗HBsAg滴度,CTLL-2细胞株/MTT法检测IL-2活性。结果序列测定和分析结果表明重组质粒pcDNA3.1/IL-2构建正确。血清中抗HBsAg抗体滴度:铝佐剂+HBsAg组为2116mIU;IL-2+HBsAg组为1987mIU;质粒pcDNA3.1/IL-2+HBsAg组为2252mIU;质粒pcDNA3.1+IL-2+pcDNA3.1/S组为67·19mIU;质粒pcDNA3.1/S组为50·88mIU。重组质粒pcDNA3.1/IL-2免疫1周后,IL-2表达水平达高峰,以后逐渐降低,但1个月后IL-2水平仍高于空白对照组。对抗HBsAg抗体滴度和IL-2活性的检测结果进行统计学分析表明,各组间差异有显著意义(P<0·05)。结论IL-2基因佐剂可以增强乙肝重组疫苗和乙肝DNA疫苗的免疫效果。     

助剂对茎叶处理除草剂的增效作用

助剂的应用可以降低单位面积除草剂使用剂量，提高除草剂对杂草的控制效果，增加除草剂对人类、食品、环境和其它非靶标生物的安全性。沈阳化工研究院于2000年开始进行助剂对除草剂增效作用研究。从2004年开始对我院助剂品种SYP—G75在室内及田间进行了大量的试验。结果表明，在除草剂喷洒液中加入助剂SYP—G75后效果咀显好于除草剂单用，且用药量可以减少1／3—1／2左右。     

助剂在农药悬浮剂中的作用

根据农药悬浮剂的特点，对其助剂的作用进行了讨论，并指出要改变我国农药剂型的落后面貌，必须重视对农药助剂的研究开发。     

Pathogen‐Mimicking Polymeric Nanoparticles based on Dopamine Polymerization as Vaccines Adjuvants Induce Robust Humoral and Cellular Immune Responses

Aiming to enhance the immunogenicity of subunit vaccines, a novel antigen delivery and adjuvant system based on dopamine polymerization on the surface of poly(d ,l ‐lactic‐glycolic‐acid) nanoparticles (NPs) with multiple mechanisms of immunity enhancement is developed. The mussel‐inspired biomimetic polydopamine (pD) not only serves as a coating to NPs but also functionalizes NP surfaces. The method is facile and mild including simple incubation of the preformed NPs in the weak alkaline dopamine solution, and incorporation of hepatitis B surface antigen and TLR9 agonist unmethylated cytosine‐guanine (CpG) motif with the pD surface. The as‐constructed NPs possess pathogen‐mimicking manners owing to their size, shape, and surface molecular immune‐activating properties given by CpG. The biocompatibility and biosafety of these pathogen‐mimicking NPs are confirmed using bone marrow‐derived dendritic cells. Pathogen‐mimicking NPs hold great potential as vaccine delivery and adjuvant system due to their ability to: 1) enhance cytokine secretion and immune cell recruitment at the injection site; 2) significantly activate and maturate dendritic cells; 3) induce stronger humoral and cellular immune responses in vivo. Furthermore, this simple and versatile dopamine polymerization method can be applicable to endow NPs with characteristics to mimic pathogen structure and function, and manipulate NPs for the generation of efficacious vaccine adjuvants.     

Injectable and Pathogen‐Mimicking Hydrogels for Enhanced Protective Immunity against Emerging and Highly Pathogenic Influenza Virus

Seasonal emerging infectious diseases such as influenza A impose substantial risk and need new translational strategies to achieve active immunomodulation. Here, a novel injectable pathogen‐mimicking hydrogel (iPMH) that can enhance both cellular and humoral immune responses is suggested. By the help of poly(γ‐glutamic acid) that has abundant carboxylate groups and dispersion helper function, hydrophobic immunostimulatory 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPLA) molecules and viral antigens (PR8, W150) can be successfully combined as pathogen‐mimicking adjuvants. Polyelectrolyte complex between the poly(γ‐glutamic acid)‐based adjuvants and collagens generate in situ gel‐forming hydrogel at physiological temperature. When the iPMH are immunized, they act as a pathogen‐mimicking (MPLA, H1N1, H5N1) immune priming center and a depot for continuous stimulation of immune system, resulting in the induction of high levels (8.5 times higher) of antigen‐specific IgG titers in the sera of mice and the increased number of IFN‐γ‐producing cells (7.3 times higher) compared with those in the groups immunized with antigen plus clinically used aluminum gels. Following the intranasal infection of the mouse adapted virus (emerging infectious 2009 H1N1 and highly pathogenic 2006 H5N1) at 50 times the 50% lethal dose, the mice immunized with viral antigens plus iPMH exhibit 100% protective immunity against lethal virus challenge.     

Adjuvant Effect of Quillaja saponaria Saponin (QSS) on Protective Efficacy and IgM Generation in Turbot (Scophthalmus maximus) upon Immersion Vaccination

The adjuvant effect of Quillaja saponaria saponin (QSS) on protection of turbot fry was investigated with immersion vaccination of formalin-killed Vibrio anguillarum O1 and various concentrations of QSS (5, 25, 45 and 65 mg/L). Fish were challenged at days 7, 14 and 28 post-vaccination. Significantly high relative percent of survival (RPS) ((59.1 ± 13.6)%, (81.7 ± 8.2)%, (77.8 ± 9.6)%) were recorded in the fish that received bacterins immersion with QSS at 45 mg/L, which is comparable to the positive control group vaccinated by intraperitoneal injection (IP). Moreover, a remarkably higher serum antibody titer was also demonstrated after 28 days in the vaccinated fish with QSS (45 mg/L) than those vaccinated fish without QSS (p < 0.05), but lower than the IP immunized fish (p < 0.05). Significant upregulation of IgM gene expression has also been identified in the tissues of skin, gill, spleen and kidney from the immunized fish in comparison to the control fish. Taken together, the present study indicated that QSS was able to dramatically evoke systemic and mucosal immune responses in immunized fish. Therefore, QSS might be a promising adjuvant candidate for fish vaccination via an immersion administering route.     

铜基营养杀菌剂的合成工艺

铜基营养杀菌剂是一种可湿性粉剂,既可杀灭病菌又可为作物提供一定的微量营养元素。介绍了其研制原理和方法,并在辣椒疫霉病菌上对其进行了初步的药效对比试验。在60℃~70℃条件下氢氧化钙与硫酸铜反应,投料摩尔比约为3 :4,合成碱式硫酸铜,再依次加入载体填料、配方助剂、微量营养元素,100℃5℃条件下喷雾干燥即得成品。收率在85%以上。铜基营养杀菌剂对真菌辣椒疫霉菌具有良好的抑杀作用,其药效接近美国产品Kocide 2000,明显好于传统波尔多液和国内产品甲霜铝铜,这4种药剂的有效中浓度EC50分别为48.5、47.4、83.0、65.7mg/ml。