Conjugate of ibrutinib with a TLR7 agonist suppresses melanoma progression and enhances antitumor immunity

The use of large molecules for immunotherapy has led to exciting developments in cancer treatment, such as the development of PD-1/PD-L1 antibodies. However, small molecule targeted therapies still lack effective immune-functional classes. Ideal anticancer drugs should simultaneously generate immune memory when killing cancer cells to prevent tumor relapse and metastasis. To this end, we carried out a rationally designed strategy to develop novel classes of small molecule compounds with bifunctional targeting and immunostimulatory abilities by conjugating targeting compounds with TLR7 agonists, generating immune-targeting conjugates (ImmunTacs). GY161, as a representative ImmunTac, was synthesized via chemical conjugation of ibrutinib with a TLR7 agonist. In vitro, GY161 stimulated the production of cytokines by mouse spleen lymphocytes, promoted the maturation of dendritic cells (DCs), and inhibited the growth and induced the apoptosis of B16 melanoma cells by regulating the c-Met/β-catenin pathway. In vivo, GY161 enhanced the frequency of CD8⁺ T cells in spleens and tumors, suppressed the growth of B16 melanoma cell-derived tumors and prolonged the survival time of mice. In summary, GY161 could prevent melanoma progression through direct tumor killing and by triggering specific immunity. These results strongly suggest that ImmunTacs are a reliable and promising strategy for developing small molecule immunogenic anticancer drugs.     

Production and characterisation of the intergeneric hybrids between Dendranthema morifolium and Artemisia vulgaris exhibiting enhanced resistance to chrysanthemum aphid (Macrosiphoniella sanbourni)

Aphids represent the most destructive of chrysanthemum pests to cultivation. Reliable variety sources of resistance and control methods are limited, so development of highly resistant breeding lines is desirable. An intergeneric hybrid between Dendranthema morifolium (chrysanthemum) variety ‘Zhongshanjingui’ and Artemisia vulgaris (mugwort) ‘Variegata’ was attempted. Most of the hybrid embryos aborted at an early developmental stage. Embryo rescue allowed the generation of hybrid plants, whose hybridity was confirmed by a combination of morphological, cytological and GISH analysis. The hybrids were vigorous, flowered normally, and their flower and leaf shape resembled those of the chrysanthemum more than those of the mugwort parent. The hybrids showed much higher resistance to chrysanthemum aphid (Macrosiphoniella sanbourni) than maternal chrysanthemum by inoculation test. The leaves of the hybrid developed a higher density of trichomes and secretory glands compared to the maternal chrysanthemum. GC–MS analysis revealed that ~51% of the essential oil in the hybrid leaves were monoterpenoids and sesquiterpenoids, while the proportion in the chrysanthemum was ~37%, and in the mugwort was ~90%. It is inferred that higher aphid resistance in the hybrid mainly owed to the leaf micromorphology and bioactive essential oil content.     

32个切花菊品种的耐低磷特性

本研究利用砂培试验对32个切花菊品种进行了苗期耐低磷筛选和鉴定。结果表明,供试切花菊品种耐低磷能力存在明显的基因型差异,表现在幼苗相对干重（低磷胁迫/正常供磷）、相对磷含量和相对磷积累量存在较大的基因型间变异(CV分别为12.14%、20.99%和26.41%),相对干重、相对磷含量和相对磷积累量之间均呈极显著正相关(P<0.01)。通过聚类分析可将32份供试品种的耐低磷胁迫能力分为极强、强、中等、弱、极弱5个级别,‘南农银山’对低磷的忍耐能力最强,属耐低磷能力极强的品种;‘南农红枫’、‘南农香槟’和‘优香’对低磷胁迫的忍耐能力最差,属耐低磷能力极弱的品种。相对干重、相对磷含量和相对磷积累量可作为切花菊耐低磷特性的筛选指标,为切花菊育种、栽培管理、磷营养学研究提供参考。     

东海赤潮高发区沉积物中叶绿素的分析

研究分析了2002年8～9月“赤潮973”航次所采集的沉积物中叶绿素a及其降解产物脱镁叶绿酸含量与分布．结果表明。叶绿素a和脱镁叶绿酸是同源的;随深度增加叶绿素a和脱镁叶绿酸的含量呈递减趋势,到一定深度后含量不再变化。个别站位叶绿素a和脱镁叶绿酸的垂直分布出现了许多小突跃,可能是由生物扰动引起;表层沉积物(0～0．5cm)中的叶绿素a和脱镁叶绿酸的变化幅度分别为0．14～1．17和0．83～5．58μg·g-1。平均值分别为0．54和2．45μg·g-1;并初步探讨水深(光强)、盐度、温度、含水量对叶绿素水平分布的影响;脱镁叶绿酸作为叶绿素的主要降解产物,到一定深度后,成为叶绿素的主要存在形式,约占80％～90％;由于水温的不同,夏季沉积物中的叶绿素a和脱镁叶绿酸含量是春季的3倍之多;比较了上层水柱中的叶绿素和沉积物中的叶绿素的相对含量,平均而言,沉积物中叶绿素占上层水柱中叶绿素的31％．     

Antitumor and immunomodulatory activity of arabinoxylans: a major constituent of wheat bran

We aimed to investigate the antitumor activity of wheat bran arabinoxylans, including the role of its immunostimulatory effect. In S180 tumor-bearing mice arabinoxylan administration significantly inhibited the growth of mouse transplantable tumors and remarkably promoted thymus and spleen indexes, splenocyte proliferation, natural killer cell and macrophage phagocytosis activity, interleukin 2 production, and delayed-type hypersensitivity reaction. In addition, it increased peripheral leukocyte count, and bone-marrow cellularity in tumor-bearing mice. As the antitumor activity of arabinoxylans may be mediated via the improvement in the immune response, they can be considered an antitumor agent with immunomodulatory activity.     

Generation and Characterization of a scFv Antibody Against T3SS Needle of Vibrio parahaemolyticus

Vibrio parahaemolyticus, a halophilic gram-negative bacterium, is a food-borne pathogen that largely inhabits marine and estuarine environments, and poses a serious threat to human and animal health all over the world. The hollow “needle” channel, a specific assemble of T3SS which exists in most of gram-negative bacteria, plays a key role in the transition of virulence effectors to host cells. In this study, needle protein VP1694 was successfully expressed and purified, and the fusion protein Trx-VP1694 was used to immunize Balb/c mice. Subsequently, a phage single-chain fragment variable antibody (scFv) library was constructed, and a specific scFv against VP1694 named scFv-FA7 was screened by phage display panning. To further identify the characters of scFv, the soluble expression vector pACYC-scFv-skp was constructed and the soluble scFv was purified by Ni²⁺ affinity chromatography. ELISA analysis showed that the scFv-FA7 was specific to VP1694 antigen, and its affinity constant was 1.07 × 10⁸ L/mol. These results offer a molecular basis to prevent and cure diseases by scFv, and also provide a new strategy for further research on virulence mechanism of T3SS in V. parahaemolyticus by scFv.     

浅蓝霉素产生菌海洋异壁放线菌WH1-2216-6 遗传操作体系的建立

摘要: 【目的】建立二联吡啶类抗生素浅蓝霉素的产生菌海洋异壁放线菌Actinoalloteichus sp. WH1-2216-6的遗传操作体系,以便对浅蓝霉素的相关生物合成基因进行体内敲除和基因回补等遗传操作。【方法】以整合型质粒pSET152 为外源DNA,探索和优化了异壁放线菌WH1-2216-6 菌株与大肠杆菌进行接合转移实验的方法和条件,以此为基础,利用PCR-targeting 系统在体外构建了一个浅蓝霉素二羟基苯甲酸甲酯AMP 连接酶基因敲除的cosmid 质粒pCSG2104,并在优化后的     

黄土高原半湿润区苜蓿草地土壤干层形成及水分恢复

研究了黄土高原地区不同生长年限苜蓿草地0～1000 cm土层土壤水分消耗规律.结果表明,荒地与苜蓿草地土壤干层出现的区域及发生的程度不同:荒地在80～100 cm土层深度,出现轻度干层;生长年限低于8a(含8a)的苜蓿草地,在250～350 cm土层出现轻度干层,生长年限超过8a,出现中度干层,干层范围延至500 cm土层以下.苜蓿生长超过18a,0～200 cm上层土壤水分开始恢复,年均恢复1.49%;但在200～1000 cm土壤深层,18、26年生苜蓿草地土壤含水量仅为10.20%,深层土壤通体干化,水分难以恢复.     

菊属与蒿属植物苗期抗蚜虫性鉴定

为发掘对蚜虫有抗性的菊花近缘种属植物,对11份菊属及蒿属植物苗期进行了田间和室内抗蚜虫性鉴定。结果发现:在田间鉴定条件下,随着平均蚜害指数(I*)值的升高,蚜虫抗性等级逐渐降低,其中:黄金艾蒿、黄蒿、香蒿的I*值为0.00,属于免疫性;牡蒿的I*值为0.13,属于高抗性;大岛野路菊的I*值为0.25,属于抗性;异色菊的I*值为0.37,属于中抗性;那贺川野菊、龙脑菊的I*值为0.51—0.75,属于感性;泡黄金菊、紫花野菊、菊花脑的I*值>0.75,属于高感性;在室内鉴定条件下,不同材料对蚜虫的抗性表现出很大差异,根据繁殖倍率的不同,11份材料分为5个抗性等级,其中黄金艾蒿、牡蒿、黄蒿、香蒿繁殖倍率为0.00,属于极高抗性;大岛野路菊繁殖倍率为5.86,属于中抗性;异色菊、那贺川野菊、龙脑菊繁殖倍率为7—10,属于低抗性;泡黄金菊、紫花野菊、菊花脑繁殖倍率>10,属于无抗性。综合分析表明:田间鉴定与室内鉴定结果基本一致,其中黄金艾蒿、黄蒿等8份材料田间和室内鉴定结果无差别;牡蒿田间鉴定表现为高抗性,而室内鉴定表现为极高抗性;大岛野路菊田间鉴定表现为抗性,而室内鉴定表现为中抗性;异色菊田间鉴定表现为中抗性,而室内鉴定表现为低抗性。黄金艾蒿、黄蒿、牡蒿、香蒿、大岛野路菊对蚜虫表现良好抗性,可用于栽培菊花抗蚜性遗传改良。