As versatile and robust genome editing tools,clustered regularly interspaced short palindromic repeats(CRISPR)technologies have been broadly used in basic research,biotechnology,and therapeutic development.Off-target ...As versatile and robust genome editing tools,clustered regularly interspaced short palindromic repeats(CRISPR)technologies have been broadly used in basic research,biotechnology,and therapeutic development.Off-target mutagenesis by CRISPR systems has been demonstrated,and various methods have been developed to markedly increase their specificity.In this review,we highlight the efforts of producing and modifying guide RNA(gRNA)to minimize off-target activities,including sequence and structure design,tuning expression and chemical modification.The modalities of gRNA engineering can be applied across CRISPR systems.In conjunction with CRISPR protein effectors,the engineered gRNA enables efficient and precise genome editing.展开更多
To improve the effect of destroying time-sensitive target （TST）, a method of operational effectiveness evaluation is presented and some influential factors are analyzed based on the combat flow of system for destroy...To improve the effect of destroying time-sensitive target （TST）, a method of operational effectiveness evaluation is presented and some influential factors are analyzed based on the combat flow of system for destroying TST. Considering the possible operation modes of the system, a waved operation mode and a continuous operation mode are put forward at first. At the same time, some relative formulas are modified. In examples, the influential factors and operation modes are analyzed based on the system effectiveness. From simulation results, some design and operation strategies of the system for destroying time sensitive targets are concluded, which benefit to the improvement of the system effectiveness.展开更多
A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and D...A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and DOX （an antitumor drug） were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate （ALG-mOEG） for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1：1 （W：W） ratio of GA-ALG-mOEG and DOX-ALG-mOEG （NPs-3） showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth （88.37% reduction in tumor weight） 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.展开更多
活性横向效应增强弹(Penetrator with Enhanced Lateral Effect,PELE)在侵彻钢筋混凝土靶的过程中会发生剧烈的爆燃反应,较惰性芯体PELE对靶板的扩孔效应更加显著。为揭示活性PELE侵彻钢筋混凝土靶扩孔增强机理,建立活性PELE侵彻钢筋混...活性横向效应增强弹(Penetrator with Enhanced Lateral Effect,PELE)在侵彻钢筋混凝土靶的过程中会发生剧烈的爆燃反应,较惰性芯体PELE对靶板的扩孔效应更加显著。为揭示活性PELE侵彻钢筋混凝土靶扩孔增强机理,建立活性PELE侵彻钢筋混凝土靶扩孔分析模型,模型充分考虑径向稀疏波和活性材料的冲击爆燃反应。开展5种撞击速度下的活性PELE侵彻钢筋混凝土靶实验,综合实验和理论对活性PELE芯体反应特性、壳体变形角度-长度演化及扩孔增强行为进行讨论。研究结果表明:新的分析模型能够有效预测活性PELE壳体变形和钢筋混凝土靶扩孔,平均误差分别为6.9%和8.5%;活性PELE壳体表现出双弯曲变形和卷曲变形两种典型变形模式,给出壳体变形角度-长度演化过程;当撞击压力大于2.32 GPa时,忽略径向稀疏波会高估活性PELE芯体反应程度和壳体径向变形,验证了考虑径向稀疏波的必要性;量化比较后发现活性材料的爆燃反应使钢筋混凝土靶的最大开孔提高了24.3%。展开更多
基金supported by the National Key Research and Development Program of China(2018YFA0801401 and 2019YFA0802801)the National Natural Science Foundation of China 31871345+1 种基金the Young Thousand Talented Program from Wuhan Universitythe startup funding from Wuhan University to H.Y.
文摘As versatile and robust genome editing tools,clustered regularly interspaced short palindromic repeats(CRISPR)technologies have been broadly used in basic research,biotechnology,and therapeutic development.Off-target mutagenesis by CRISPR systems has been demonstrated,and various methods have been developed to markedly increase their specificity.In this review,we highlight the efforts of producing and modifying guide RNA(gRNA)to minimize off-target activities,including sequence and structure design,tuning expression and chemical modification.The modalities of gRNA engineering can be applied across CRISPR systems.In conjunction with CRISPR protein effectors,the engineered gRNA enables efficient and precise genome editing.
基金supported by the National Natural Science Foundation of China (60774064)the Aerospace Science Foundation (05D53022)the Youth for NPU Teachers Scientific and Technological Innovation Foundation (W016210)
文摘To improve the effect of destroying time-sensitive target （TST）, a method of operational effectiveness evaluation is presented and some influential factors are analyzed based on the combat flow of system for destroying TST. Considering the possible operation modes of the system, a waved operation mode and a continuous operation mode are put forward at first. At the same time, some relative formulas are modified. In examples, the influential factors and operation modes are analyzed based on the system effectiveness. From simulation results, some design and operation strategies of the system for destroying time sensitive targets are concluded, which benefit to the improvement of the system effectiveness.
基金financially supported by the National Natural Science Foundation of China(Nos.51073080 and 51273095)Natural Science Foundation of Tianjin(No.13JCYBJC25100)and PCSIRT(No.IRT1257)
文摘A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and DOX （an antitumor drug） were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate （ALG-mOEG） for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1：1 （W：W） ratio of GA-ALG-mOEG and DOX-ALG-mOEG （NPs-3） showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth （88.37% reduction in tumor weight） 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.
