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
This study proposes a low-energy pulse current(LEPC)rapid solution treatment method,which can dis-solve more primaryγ'phase in a shorter time and effectively suppress abnormal grain growth,thereby successfully ac...This study proposes a low-energy pulse current(LEPC)rapid solution treatment method,which can dis-solve more primaryγ'phase in a shorter time and effectively suppress abnormal grain growth,thereby successfully achieving microstructure optimization and property enhancement.The microstructure anal-ysis showed that,compared with the 62.5%dissolution rate of the standard traditional solution treat-ment(1100℃/4 h),LEPC achieved an 88.9%dissolution of the primaryγ'phase in just 5 min at the same temperature.Furthermore,due to the rapidity of the LEPC treatment and its“targeted dissolution effect”on theγ'phase,excessivegrain growthwas effectivelysuppressed,resultingingrain sizecom-parable to those obtained with traditional solution treatment.Mechanical property testing indicated that the alloy treated with LEPC had a hardness of 531 HV at room temperature,while the yield strength,Ultimate strength,and maximum strain reached 994 MPa,1030 MPa,and 5.1%at the service tempera-ture(750℃).Compared to the standard traditional solution treatment,these properties were improved by 10.4%,11.1%,10.4%,and 17.5%,respectively.Finally,theoretical calculations revealed that the non-thermal effect of LEPC reduced the dissolution-free energy by approximately 49.4 kJ/mol and increased the diffusion coefficient by about 76 times,which was the fundamental reason for the accelerated disso-lution of the primaryγ’phase.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
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 Key R&D Program of China(Nos.2020YFA0714901 and 2020YFA0714904).
文摘This study proposes a low-energy pulse current(LEPC)rapid solution treatment method,which can dis-solve more primaryγ'phase in a shorter time and effectively suppress abnormal grain growth,thereby successfully achieving microstructure optimization and property enhancement.The microstructure anal-ysis showed that,compared with the 62.5%dissolution rate of the standard traditional solution treat-ment(1100℃/4 h),LEPC achieved an 88.9%dissolution of the primaryγ'phase in just 5 min at the same temperature.Furthermore,due to the rapidity of the LEPC treatment and its“targeted dissolution effect”on theγ'phase,excessivegrain growthwas effectivelysuppressed,resultingingrain sizecom-parable to those obtained with traditional solution treatment.Mechanical property testing indicated that the alloy treated with LEPC had a hardness of 531 HV at room temperature,while the yield strength,Ultimate strength,and maximum strain reached 994 MPa,1030 MPa,and 5.1%at the service tempera-ture(750℃).Compared to the standard traditional solution treatment,these properties were improved by 10.4%,11.1%,10.4%,and 17.5%,respectively.Finally,theoretical calculations revealed that the non-thermal effect of LEPC reduced the dissolution-free energy by approximately 49.4 kJ/mol and increased the diffusion coefficient by about 76 times,which was the fundamental reason for the accelerated disso-lution of the primaryγ’phase.
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.
