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.     

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.     

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。     

力作甜味剂产品的引导者——专访苏卡斯(瑞士)调味技术有限公司全球技术研发总监罗伯·爱比先生

<正>苏卡斯(瑞士)调味技术有限公司为全球首家专业、专注于饲料甜味剂的研发、生产和销售的企业。紧紧围绕动物味觉生理研究进展,以甜     

Studies on amoebae and cysts associated with the isolation of Spongospora subterranea f.sp. subterranea in vitro

New evidence is presented to support the contention that the amoeba/cyst colonies isolated from surface-sterilized Spongospora subterranea f.sp. subterranea -infected potato tubers and spore balls have a saprophytic phase but are contaminants and not S. subterranea. Amoebae isolated from infected tissues and spore balls formed colonies associated with bacteria on 1% water agar at 18°C and encysted after 5–7 days. These cysts were morphologically distinct from the resting spores of S. subterranea and were formed singly or in a layer, unlike the spore ball (cystosorus) of S. subterranea . Amoebae, cysts and mixtures of amoebae and cysts in primary, secondary and tertiary subcultures failed to infect tomato roots. PCR amplification of DNA from amoebae, cysts and spore balls using the S. subterranea -specific primer pair SsF/R generated a 434-bp product from S. subterranea spore balls only and not from amoebae or cysts. When an amoeba/cyst-specific primer pair AmF/R was designed and used for PCR amplification, a single 411-bp product was generated from DNA of amoebae and cysts, but not from DNA of S. subterranea spore balls. These results are discussed in relation to earlier reports claiming the successful isolation of S. subterranea and other plasmodiophorids in vitro .     

2004年我国种用植物产品进出口贸易分析

随着我国农业生产水平的不断提高和植物产品知识产权保护意识的日益增强,近年来我国种用植物产品的贸易规模在扩大.2004年我国种用植物产品贸易总额19 346.15万美元,其中从57个国家和地区进口了40类种用植物产品,进口总额13 225.36万美元;向69个国家和地区出口了46类种用植物产品,出口总额6 120.79万美元.2003年种用植物产品进出口贸易总额16 485.45万美元（进口11 899.98万美元,出口4 585.47万美元）.同比2003、2004年我国种用植物产品贸易总额增加17.4%,其中进口增加11.1%,出口增加33.5%.总的说来,进口和出口的规模都在扩大,但出口增幅显著.     

水稻机插秧育秧基质研究进展

基质育秧是水稻机插秧的关键技术,育秧的好坏直接关系到水稻机插秧的质量和产量。为了给水稻机插秧技术的完善提供参考,本文综述了水稻机插秧基质育秧的现状、优点、类型;归纳了市场上常见基质的配方,对基质的物理性状、化学性状和生物性状等进行阐述;也指出了基质育秧存在的问题,并对其在今后农业生产上的应用进行了展望。     

基于超星学习通的混合式教学模式应用研究—— 以发酵工程课程为例

为了提高发酵工程课程的教学质量和教学效果,针对发酵工程课程的内容和特点,将互联网+技术与教学相结合,进行了基于超星学习通平台的混合式线上线下教学方式的改革,结果表明:在增强了学生自主学习能力的同时,也促进了教师的自我提升.     

Prevalence and analysis of potential risk factors for Cryptosporidium parvum infection in lambs in Zaragoza (northeastern Spain)

An epidemiologic study was carried out to investigate the prevalence of and to identify factors associated with the risk of Cryptosporidium infection in sheep in Zaragoza (northeastern Spain). Faecal samples from 583 lambs aged from 1 day to 3 months and 205 ewes older than 1 year were collected at 89 farms in the two regions of the province of Zaragoza with the highest sheep population (Zaragoza and Ejea de los Caballeros). In every sheep farm, data of the factors potentially associated with the likelihood of C. parvum infection were analysed: geographical location, season, size of herd, number of lambs in the herd at sampling time, lambing period, cleaning of lambing area and presence of diarrhoeic lambs in the farm. C. parvum oocysts were identified by using the Ziehl-Neelsen technique in 344 lambs (59%) from 75 farms (84.4%). Infected lambs ranged from less than 7 days to 90 days of age, although the percentage of animals shedding oocysts peaked at 8-14 days of age (76.2%). Statistical analysis showed that infection rates were significantly higher in lambs aged between 1 and 21 days (66.4%) than in those aged between 22 and 90 days (23%) (P<0.0001, chi(2)). Analysis of correlation between excretion of oocysts and diarrhoea revealed a relationship in all age groups and the probability of presenting diarrhoea was significantly higher for lambs shedding oocysts (86.3%) than for those which did not excrete the parasite (32.2%) (P<0.0001, chi(2)). Similarly, cryptosporidial infection rates were significantly higher in diarrhoeic (79.4%) than in non-diarrhoeic lambs (22.4%). Furthermore, infection intensity was correlated with the presence of clinical symptoms. Presence of diarrhoeic lambs in the farm was the only factor significantly associated with an increased risk of infection since the percentage of herds testing positive was significantly higher in farms with diarrhoeic lambs (91.3%) than in those without cases of neonatal diarrhoea (12.5%) (P<0.0001, chi(2)). Factors associated with a decreased risk of C. parvum infection in lambs included low numbers of lambs in the farm and cleaning of the lambing area. Additionally, lambs 8-14 days of age were less likely to be infected at the first lambing period and in spring/autumn. Cryptosporidial infection was also detected in 16 ewes (7.8%) which excreted few oocysts and without diarrhoea.