Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in term...Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1：20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, A UC0-8 of 372.77 ±49.62 ng·h·mL^-1 and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution （P〈0.01）. Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.展开更多
Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivo...Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.展开更多
支持等式测试的标识加密(identity-based encryption with equality test, IBEET)体制解决了传统等式测试方案中证书管理的问题,得到了广泛的关注.但现有的IBEET体制难以抵抗渗透攻击,且都是基于国外密码算法设计,不具有自主知识产权....支持等式测试的标识加密(identity-based encryption with equality test, IBEET)体制解决了传统等式测试方案中证书管理的问题,得到了广泛的关注.但现有的IBEET体制难以抵抗渗透攻击,且都是基于国外密码算法设计,不具有自主知识产权.基于此,提出一种支持等式测试并具有密码逆向防火墙的SM9标识加密方案(SM9 identity-based encryption scheme with equality test and cryptographic reverse firewalls, SM9-IBEET-CRF).该方案在用户与云服务器的上行信道间部署密码逆向防火墙(cryptographic reverse firewalls,CRF),对用户发出的信息执行重随机化以达到抵抗渗透攻击的作用.该方案拓展国密算法SM9至IBEET领域中,提升其运行效率并丰富国密算法在云计算领域的研究.给出了SM9-IBEET-CRF的形式化定义和安全模型,并在随机预言机模型中考虑2种不同的敌手将此方案在选择密文攻击下的不可区分性与单向性分别形式化地规约到BDH困难假设上.同时,该方案通过考虑第3种敌手证明CRF的部署为其带来维持功能性、保留安全性以及抵抗渗透性.实验仿真和分析结果展示了该方案的有效性.展开更多
基金National Natural Science Foundation of China (GrantNo.30430760)the 985 projects (Phase II) of the State Key Labo-ratory of Natural and Biomimetic Drugs (Peking University, China).
文摘Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1：20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, A UC0-8 of 372.77 ±49.62 ng·h·mL^-1 and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution （P〈0.01）. Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.
基金supported by 1RO1EY032959-01 and RO1 supplement from NIH,Schuellein Chair Endowment Fund and STEM Catalyst Grant from the University of Dayton(to AS).
文摘Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.
文摘支持等式测试的标识加密(identity-based encryption with equality test, IBEET)体制解决了传统等式测试方案中证书管理的问题,得到了广泛的关注.但现有的IBEET体制难以抵抗渗透攻击,且都是基于国外密码算法设计,不具有自主知识产权.基于此,提出一种支持等式测试并具有密码逆向防火墙的SM9标识加密方案(SM9 identity-based encryption scheme with equality test and cryptographic reverse firewalls, SM9-IBEET-CRF).该方案在用户与云服务器的上行信道间部署密码逆向防火墙(cryptographic reverse firewalls,CRF),对用户发出的信息执行重随机化以达到抵抗渗透攻击的作用.该方案拓展国密算法SM9至IBEET领域中,提升其运行效率并丰富国密算法在云计算领域的研究.给出了SM9-IBEET-CRF的形式化定义和安全模型,并在随机预言机模型中考虑2种不同的敌手将此方案在选择密文攻击下的不可区分性与单向性分别形式化地规约到BDH困难假设上.同时,该方案通过考虑第3种敌手证明CRF的部署为其带来维持功能性、保留安全性以及抵抗渗透性.实验仿真和分析结果展示了该方案的有效性.
