The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore,ADMET, Molecular Docking and Molecular Dynamics Study

Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen out better natural compounds, pharmacophore models were first generated, then the absorption, distribution, metabolism, elimination, and toxicity (ADMET) were tested, followed by molecular docking. Finally, molecular dynamics simulation was carried out to verify the binding characteristics of the selected compounds. Results: Eighty-seven marine small molecules were screened based on the pharmacophore model. Then, compounds 41369 and 50843 were selected according to the ADMET and molecular docking score for further kinetic simulation evaluation. Finally, through molecular dynamics analysis, it was confirmed that compound 50843 maintained a stable conformation with the target protein, so it has the opportunity to become an inhibitor of CDK4/6. Conclusion: Through structure-based pharmacophore modeling, ADMET, the molecular docking method and molecular dynamics (MD) simulation, marine natural compound 50843 was proposed as a promising marine inhibitor of CDK4/6.     

齿兰环斑病毒与建兰花叶病毒分子检测研究

齿兰环斑病毒（Odontoglossum ringspot virus,ORSV）与建兰花叶病毒（Cymbidium mosaic virus, CyMV）是严重危害兰科植物的两种主要病毒。本研究根据病毒外壳蛋白基因设计特异性引物,应用ELISA、普通RT-PCR、巢式RT-PCR和免疫捕获RT-PCR4种方法进行了检测研究与比较。结果表明：普通RT-PCR与ELISA方法检测灵敏度相当;巢式RT-PCR检测灵敏度要比普通RT-PCR与ELISA方法高出104倍以上;免疫捕获RT-PCR检测灵敏度介于普通RT-PCR和巢式RT-PCR之间。采用巢式RT-PCR方法对我国台湾进境的蝴蝶兰植株样本检测,1号样本出现与阳性对照一致的特异条带。双向测序分析,扩增产物序列与ORSV外壳蛋白基因具有100％的同源性,表明1号蝴蝶兰样本携带ORSV。     

基因打靶备乳腺生物反应器研究进展

基因打靶技术是建立在胚胎干细胞和同源重组技术之上,可对基因组进行定点修饰的实验方法。用基因打靶技术制备乳腺生物反应器,克服了显微注射法的众多缺陷。本文简述了制备乳腺生物反应器过程中基因打靶的策略、靶细胞、打靶位点及国内外研究进展和展望等。     

The 16MΔvjbR as an ideal live attenuated vaccine candidate for differentiation between Brucella vaccination and infection

Brucellosis brings great economic burdens for developing countries. Live attenuated vaccines are the most efficient means for prevention and control of animal Brucellosis. However, the difficulties of differentiating of infection from vaccine immunization, which is essential for eradication programs, limit their applications. Therefore, the development of a vaccine that could differentiate infection from immunization will overcome the limitations and get extensive application. VjbR is a quorum sensing regulator involving in Brucella's intracellular survival. The vjbR∷Tn5 mutants have been proven effective against wild type strain challenge, implying its possibility of use in vaccine candidate development. To further evaluate this candidate gene, in the present study, the antigenicity of purified recombinant VjbR protein was analyzed. Antibodies to Brucella melitensis VjbR could be detected in sera from patients and animals with brucellosis but not in control ones, implying the potential use of this protein as a diagnostic antigen. Then a vjbR mutant of B. melitensis 16M was constructed by replacing the vjbR with kanamycin gene. The mutant showed reduced survival in macrophage and mice. Vaccination of BALB/c mice with 16MΔvjbR conferred significant protective immunity against B. melitensis strain 16M challenges, being equivalent to which induced by the license vaccine Rev.1. The vjbR deletion mutant elicited an anti-Brucella-specific immunoglobulin G response and induced the secretion of gamma interferon and interleukin-10. The most importance is that, the use of vjbR mutants as vaccines in association with diagnostic tests based on the VjbR antigen would allow the serological differentiation between infected and vaccinated animals. These results suggest that 16MΔvjbR is an ideal live attenuated vaccine candidate against B. melitensis and deserves further evaluation for vaccine development.     

实验性猕猴1型糖尿病模型的建立及评价

7～10岁健康猕猴15只,随机分为Ⅰ、Ⅱ、Ⅲ组,每组5只,分别按照100、125、150mg/kg的剂量一次性静脉注射链脲菌素,连续观察血糖、血浆C肽和胰岛素浓度的动态变化,观察期15周.结果:与注射链脲菌素前比较,注射后1周,Ⅰ组猕猴血糖浓度明显升高,血浆C肽和胰岛素浓度显著下降(P＜0.01),随后趋于正常水平,而Ⅱ、Ⅲ组猕猴血糖浓度明显升高并在随后的时间内持续维持在高水平,血浆C肽和胰岛素浓度持续维持在低水平(P＜0.001),Ⅲ组动物至15周全部死亡.结论:按照125mg/kg的剂量一次性给猕猴静脉注射链脲菌素,可成功复制1型糖尿病动物模型,其维持高血糖和低胰岛素及C肽浓度至少15周.     

非洲猪瘟自然弱毒株演变进程

自2018年非洲猪瘟(African swine fever,ASF)传入中国以来疫情得到了有效控制.但2021年以后,我国的ASF流行情况出现了新的变化,临床中出现了"自然变异株".这些毒株可能导致感染后临床症状不典型,容易与其他疫病混淆等问题.这与国外的流行演变规律一致,即当ASF在一个国家或地区流行较长时间后,其...     

钢质渔船的腐蚀研究

本文根据对实船测厚数据的统计分析,阐述了钢质渔船船体外板的腐蚀特点,分析了造成腐蚀的原因,并对渔船易腐部位的防护提出了建议。     

两种除草剂对紫背浮萍的生长抑制活性研究

本文以叶状体数为测试指标,在实验室条件下研究了除草剂草甘膦、二甲戊灵对紫背浮萍生长的影响。结果表明:在一定范围内,两种除草剂均对紫背浮萍的生长具有明显的抑制作用,抑制率都随浓度的增加而增大,处理168h后,草甘膦、二甲戊灵对紫背浮萍叶状体的EC50分别为12.817、0.483mg/L。     

多不饱和脂肪酸与免疫的关系

许多营养素如维生素、微量元素、某些氨基酸和多不饱和脂肪酸等都可以影响动物机体的免疫反应。脂肪酸是一种重要的营养素,是机体能量的主要来源,发挥着重     

病死畜禽处理的现状及其无害化处理技术

近年来出现的"黄浦江漂猪事件"和"江西高安病死猪事件",引发了人们对病死畜禽无害化处理问题的担忧。病死畜禽的无害化处理还存在养殖者不受重视、政府部门监管不到位、补贴政策落实不到位和处理技术落后等问题。本文分析了当前病死畜禽处理的现状,阐述了五种病死畜禽的无害化处理技术,并提出了4点对策建议。