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.     

Metabolic Profiling and In Vitro Assessment of the Biological Activities of the Ethyl Acetate Extract of Penicillium chrysogenum “Endozoic of Cliona sp. Marine Sponge” from the Red Sea (Egypt)

Marine sponge-derived endozoic fungi have been gaining increasing importance as promising sources of numerous and unique bioactive compounds. This study investigates the phytochemical profile and biological activities of the ethyl acetate extract of Penicillium chrysogenum derived from Cliona sp. sponge. Thirty-six compounds were tentatively identified from P. chrysogenum ethyl acetate extract along with the kojic acid (KA) isolation. The UPLC-ESI-MS/MS positive ionization mode was used to analyze and identify the extract constituents while 1D and 2D NMR spectroscopy were used for kojic acid (KA) structure confirmation. The antimicrobial, antioxidant, and cytotoxic activities were assessed in vitro. Both the extract and kojic acid showed potent antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa with MIC 250 ± 0.82 µg/mL. Interestingly, the extract showed strong antifungal activity against Candida albicans and Cryptococcus neoformans with MIC 93.75 ± 0.55 and 19.53 ± 0.48 µg/mL, respectively. Furthermore, KA showed the same potency against Fusarium oxysporum and Cryptococcus neoformans with MIC 39.06 ± 0.85 and 39.06 ± 0.98 µg/mL, respectively. Ultimately, KA showed strong antioxidant activity with IC₅₀ 33.7 ± 0.8 µg/mL. Moreover, the extract and KA showed strong cytotoxic activity against colon carcinoma (with IC₅₀ 22.6 ± 0.8 and 23.4 ± 1.4 µg/mL, respectively) and human larynx carcinoma (with equal IC₅₀ 30.8 ± 1.3 and ± 2.1 µg/mL, respectively), respectively. The current study represents the first insights into the phytochemical profile and biological properties of P. chrysoenum ethyl acetate extract, which could be a promising source of valuable secondary metabolites with potent biological potentials.     

府谷县兽用抗菌药减量化实施经验总结

为深入贯彻落实习近平总书记关于食品药品安全“四个最严”要求,全面提升畜禽绿色健康养殖水平,府谷县以《全国兽用抗菌药使用减量化行动方案（2021—2025年）》为契机,与西北农林科技大学畜禽无抗养殖技术团队合作,签订“府谷县畜禽减抗替抗养殖技术示范推广”项目合作协议,在府谷县全面开展抗生素减量化示范推广,得到了府谷县委县政府和榆林市科技局的大力支持,从饲料端禁抗、养殖端减抗替抗和粪污端无抗三个方面遏制抗菌药的使用,经过2年的技术示范推广,取得了一定的经验和成果。     

海洋SOD抗疲劳作用动物实验方法初探

超氧化物歧化酶(SOD)具有防止细胞过度氧化的生理功能,从海洋生物中提取的SOD,可用于清除运动产生的自由基,起到抗疲劳作用.本文探讨了SOD抗疲劳作用的动物实验方法,为验证SOD抗疲劳效果建立技术平台.     

Distribution De Quelques Espèces De Cercopithecidae En Relation Avec Les Zones De Végétation De L’Afrique

The reproductive physiology of the impala was studied in the Kruger National Park. The data concerning the hypophysial hormones, the androgenic hormones and ovarian histology are discussed in relation to the behaviour of the animal.

It was found that the male animal shows the most profound behavioural changes which occur during the mating season. These changes are induced by an increase of interstitial cell-stimulating hormone which leads to an increase in androgenic hormone. The female shows relatively few behavioural changes during the mating season, the only change being at the time of oestrus.

On the basis of the data presented and information reported for domestic animals, it is postulated that the behaviour of the male impala plays an important role in determining the breeding season.     

蚕茧价格、蚕种饲养量与蚕药用量关系的格兰杰因果检验

研究蚕桑产业经济中蚕茧价格(CAP)、蚕种饲养量(简称发种量,SSQ)、蚕药用量(SMQ)3个变量之间的关系,有助于科学预测蚕桑产业经济的发展变化规律。选取1991-2009年江苏省海安县蚕桑生产的年度数据,应用格兰杰因果关系检验(Granger causality test)方法,对上述3个变量进行平稳性检验、变量的一阶差分与单位根检验和格兰杰因果关系检验。结果表明,蚕茧价格与发种量、发种量与蚕药用量之间存在格兰杰因果关系,蚕茧价格与蚕药用量之间不存在格兰杰因果关系,即:蚕茧价格增长能引起发种量的增加,但发种量增加却不是蚕茧价格增长的原因,蚕茧价格对发种量的影响滞后期为2年,到第3年影响程度已逐渐弱化;发种量增加能引起蚕药用量的增加,但影响滞后期只有1年,超过1年后的影响不显著;蚕茧价格与蚕药用量之间从实际趋势看有一定的关联性,但相互之间的影响关系不是直接的,难以建立函数关系。研究结果与蚕桑产业发展变化的实际情况基本相符,认为格兰杰因果关系检验方法可应用于蚕桑产业经济相关因素的发展变化规律研究。     

志贺氏菌的耐药性研究及防治对策

志贺氏菌能感染雏鸡，主要引起雏鸡拉脓血样粪便，该菌耐药性在兽医领域报道较少，本试验通过药敏试验，试管二倍稀释法测定三代头孢抗生素诱导志贺氏菌后可产生多重耐药性。     

兽药的合理使用

科学、高效、安全地使用兽药,不但能及时预防和治疗动物疾病,提高养殖效益,而且对控制和减少药物残留、提高动物产品质量具有重要意义。