A Triazolotriazine-Based Dual GSK-3β/CK-1δ Ligand as a Potential Neuroprotective Agent Presenting Two Different Mechanisms of Enzymatic Inhibition

Glycogen synthase kinase 3β (GSK-3β) and casein kinase 1δ (CK-1δ) are emerging targets for the treatment of neuroinflammatory disorders, including Parkinson's disease. An inhibitor able to target these two kinases was developed by docking-based design. Compound 12 , 3-(7-amino-5-(cyclohexylamino)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-2-yl)-2-cyanoacrylamide, showed combined inhibitory activity against GSK-3β and CK-1δ [IC₅₀(GSK-3β)=0.17 μm ; IC₅₀(CK-1δ)=0.68 μm ]. In particular, classical ATP competition was observed against CK-1δ, and a co-crystal of compound 12 inside GSK-3β confirmed a covalent interaction between the cyanoacrylamide warhead and Cys199, which could help in the development of more potent covalent inhibitors of GSK-3β. Preliminary studies on in vitro models of Parkinson's disease revealed that compound 12 is not cytotoxic and shows neuroprotective activity. These results encourage further investigations to validate GSK-3β/CK-1δ inhibition as a possible new strategy to treat neuroinflammatory/degenerative diseases.     

噪声引起动物肝糖原变化

研究了噪声对大鼠肝糖原质量分数的影响,对未经过噪声暴露和经过噪声暴露的大鼠进行了肝糖原质量分数的测定。结果显示。大鼠受到噪声刺激后,起初反应剧烈,肝糖原质量分数远远低于正常值,随着时间的延长渐渐适应噪声环境并产生抵抗能力,使肝糖原质量分数逐渐接近正常值。     

污水强化生物除磷的生化模型研究进展

阐述了在污水强化生物除磷过程中生化模型的建立与发展,重点介绍了与聚磷菌有关的Mino模型,强调了在理解生化模型时应该注意的问题：所有聚磷菌生化模型都只是在试图描述发生在EBPR（Enhanced Biological Phosphorus Removal）生物群中的一些生物化学变化现象和规律（多聚磷酸盐的吸收和水解、PHA的合成与再利用）.另外,还都假设所有具有EBPR能力的细菌都有着共同的代谢特征.所以,尽管这些生化模型有助于对整个EBPR过程的理解,但不应该拘泥于这些生化模型,只有通过对聚磷菌纯培养获得最终成功才能够彻底解决整个问题.     

不同温度及厌氧/好氧运行条件对聚磷菌衰减特性的影响

以富含90%±2%纯度聚磷菌（PAOs）的强化生物除磷系统（EBPR）为研究对象,考察了10℃厌氧、10℃好氧、20℃厌氧、20℃好氧4种运行条件下PAOs的衰减特征。结果表明：温度越高对应衰减速率越快,4个系统在1~9 d里衰减速率的平均值分别为：10℃厌氧：0.053/d;10℃好氧：0.050/d;20℃厌氧：0.072/d;20℃好氧：0.145/d。其中4个系统由于细胞死亡引起的活性衰减速率分别为：10℃厌氧：0.019/d;10℃好氧：0.017/d;20℃厌氧：0.019/d;20℃好氧：0.03/d,占总活性衰减的比例分别为：35.8%、34%、26.4%、20.7%。在9 d饥饿衰减期间,污泥中所含PHA与糖原的量总体呈下降趋势。相同温度下,糖原在厌氧衰减过程中降解速率大于好氧;在同样的厌氧、好氧衰减条件下,温度越高糖原降解速率越快。     

海参肽对小鼠抗疲劳作用的研究

通过采用不同浓度的海参肽灌胃,研究海参肽对小鼠的抗疲劳作用.结果发现,海参肽对小鼠体重无显著影响,能明显延长小鼠的负重游泳时间和转棒时间,显著降低运动后小鼠的血尿素氮含量,提高了肝糖原含量.研究表明：海参肽具有明显的抗疲劳功效.     

牡蛎糖原的研究(II)——牡蛎糖原的分子结构

本文应用酶法研究了牡蛎糖原的精细分子结构。结果显示牡蛎糖原的分子结构参数-平均链长,外链和内链平均长分别为13、9和3;用异淀粉酶和普鲁兰酶对牡蛎糖原的β-极限糊精进行顺序脱支,结果表明牡蛎糖原的A,B链比值为0.88:1.0,分支化度为1.88。     

季铵盐化糖原衍生物/明胶复合水凝胶抗菌材料的制备及性能

首先,利用乙二胺对糖原进行氨基化修饰得到氨基化糖原衍生物（N-Gly）;接着,利用2,3-环氧丙基三甲基氯化铵（简称季铵盐）对N-Gly进行部分季铵盐化修饰,得到季铵盐化糖原衍生物（QA-N-Gly）;然后,以明胶为基材通过酰胺键交联制备季铵盐化糖原衍生物/明胶复合水凝胶（QA-N-Gly/Gel）。对糖原衍生物进行FTIR、1HNMR、粒径、Zeta电位以及微观形貌的考察,并对QA-N-Gly/Gel水凝胶进行了理化性能和生物性能评价。结果表明,糖原的氨基化和季铵盐化修饰成功,QA-N-Gly为均匀分散的纳米粒子,粒径分布在100～200 nm,Zeta电位为(93.9±1.7)m V,粒子带有明显的正电荷,具有抗菌性。糖原衍生物的加入可以提高明胶基水凝胶体系的机械强度和稳定性,QA-N-Gly/Gel的断裂应力为66.8 kPa,压缩模量为13.3 kPa。QA-N-Gly/Gel具有明显的抑菌作用,对金黄色葡萄球菌和大肠杆菌的抑菌率分别达到97%和50%。此外,QA-N-Gly/Gel无溶血性,细胞毒性低,NIH-3T3细胞的48 h存活率在80%以上。     

GSK3β Serine 389 Phosphorylation Modulates Cardiomyocyte Hypertrophy and Ischemic Injury

Prior studies show that glycogen synthase kinase 3β (GSK3β) contributes to cardiac ischemic injury and cardiac hypertrophy. GSK3β is constitutionally active and phosphorylation of GSK3β at serine 9 (S9) inactivates the kinase and promotes cellular growth. GSK3β is also phosphorylated at serine 389 (S389), but the significance of this phosphorylation in the heart is not known. We analyzed GSK3β S389 phosphorylation in diseased hearts and utilized overexpression of GSK3β carrying ser→ala mutations at S9 (S9A) and S389 (S389A) to study the biological function of constitutively active GSK3β in primary cardiomyocytes. We found that phosphorylation of GSK3β at S389 was increased in left ventricular samples from patients with dilated cardiomyopathy and ischemic cardiomyopathy, and in hearts of mice subjected to thoracic aortic constriction. Overexpression of either GSK3β S9A or S389A reduced the viability of cardiomyocytes subjected to hypoxia–reoxygenation. Overexpression of double GSK3β mutant (S9A/S389A) further reduced cardiomyocyte viability. Determination of protein synthesis showed that overexpression of GSK3β S389A or GSK3β S9A/S389A increased both basal and agonist-induced cardiomyocyte growth. Mechanistically, GSK3β S389A mutation was associated with activation of mTOR complex 1 signaling. In conclusion, our data suggest that phosphorylation of GSK3β at S389 enhances cardiomyocyte survival and protects from cardiomyocyte hypertrophy.     

酵母及其管理对乙醛的影响

研究了酵母及其管理对发酵末期乙醛含量的影响。酵母菌株对发酵后期乙醛的含量影响很大。上面酵母比下面酵母的乙醛含量低。不同代数的酵母产乙醛能力不一样,零代酵母的乙醛含量最高,一代酵母的乙醛含量最低。不当的酵母处理方式会导致种酵母的肝糖含量下降和乙醛含量的上升。