Objective: To explore and investigate the selection of effective antisense oligodeoxynuleotides with the help of computer and RNAstructure folding software. Methods: Bcl-2 gene was used as the target gene and five a...Objective: To explore and investigate the selection of effective antisense oligodeoxynuleotides with the help of computer and RNAstructure folding software. Methods: Bcl-2 gene was used as the target gene and five antisense oligodeoxynuleotides were designed to be bound to Bcl-2 mRNA optimal secondary structure regions that were predicted free from intramolecular fold or instability of free energy. The five antisense oligodeoxynucleotides were studied with experimental assay of leukemia cells, including cell grow assay with tropan blue exclusion, expression of Bcl-2 protein detected with immunochemistry and flowcytometry, Bcl-2 mRNA content detected with RT-PCR technique, as well as apoptosis observed and determined with morphonological method, electrophoresis and flowcytometry. Results: The results showed that two of the five antisense oligodeoxynucleotides were effective antisense oligodeoxynucleotides, which were able to inhibit cell growth in leukemia, to decrease the level of Bcl-2 mRNA and protein, to induce apoptosis of leukemia cells significantly. Conclusion: The computational prediction of antisense efficacy is faster than other methods and more efficient, which can potentially speed the development of sequences for both research and clinical applications.展开更多
Fine-grain Mg95.50Zn3.71Y0.79 alloy was prepared by high pressure solidification. By comparison with the conventional cast-ing alloy, the true stress-strain curve characteristic and deformation microstructure of Mg95....Fine-grain Mg95.50Zn3.71Y0.79 alloy was prepared by high pressure solidification. By comparison with the conventional cast-ing alloy, the true stress-strain curve characteristic and deformation microstructure of Mg95.50Zn3.71Y0.79 alloy solidified under high pressure were studied via unilateralism compress tests under the strain rate of 0.001–1 s–1 and deformation temperature of 523–623 K. Constitutive equations were constructed. According to the experimental results, compared to the conventional casting alloy, the true stress-strain curve of the fine-grain alloy solidified under high pressure not only had the high strain hardening characteristic but the dynamic recrystallization softening after the peak stress was more than the working hardening and would soon reach a stable flow stress - strain state. The deformation activation energy of the alloy solidified under high pressure was 151 kJ/mol, around 49 kJ/mol lower than that of the conventional casting alloy. The fine-grain Mg-Zn-Y alloy solidified under high pressure could obtain 95 percent of dynamic recrystallization grain at 573 K during hot deformation process.展开更多
文摘Objective: To explore and investigate the selection of effective antisense oligodeoxynuleotides with the help of computer and RNAstructure folding software. Methods: Bcl-2 gene was used as the target gene and five antisense oligodeoxynuleotides were designed to be bound to Bcl-2 mRNA optimal secondary structure regions that were predicted free from intramolecular fold or instability of free energy. The five antisense oligodeoxynucleotides were studied with experimental assay of leukemia cells, including cell grow assay with tropan blue exclusion, expression of Bcl-2 protein detected with immunochemistry and flowcytometry, Bcl-2 mRNA content detected with RT-PCR technique, as well as apoptosis observed and determined with morphonological method, electrophoresis and flowcytometry. Results: The results showed that two of the five antisense oligodeoxynucleotides were effective antisense oligodeoxynucleotides, which were able to inhibit cell growth in leukemia, to decrease the level of Bcl-2 mRNA and protein, to induce apoptosis of leukemia cells significantly. Conclusion: The computational prediction of antisense efficacy is faster than other methods and more efficient, which can potentially speed the development of sequences for both research and clinical applications.
基金Project supported by National Natural Science Foundation of China(51475486)Hebei Province Natural Science Fund(E2013501096)
文摘Fine-grain Mg95.50Zn3.71Y0.79 alloy was prepared by high pressure solidification. By comparison with the conventional cast-ing alloy, the true stress-strain curve characteristic and deformation microstructure of Mg95.50Zn3.71Y0.79 alloy solidified under high pressure were studied via unilateralism compress tests under the strain rate of 0.001–1 s–1 and deformation temperature of 523–623 K. Constitutive equations were constructed. According to the experimental results, compared to the conventional casting alloy, the true stress-strain curve of the fine-grain alloy solidified under high pressure not only had the high strain hardening characteristic but the dynamic recrystallization softening after the peak stress was more than the working hardening and would soon reach a stable flow stress - strain state. The deformation activation energy of the alloy solidified under high pressure was 151 kJ/mol, around 49 kJ/mol lower than that of the conventional casting alloy. The fine-grain Mg-Zn-Y alloy solidified under high pressure could obtain 95 percent of dynamic recrystallization grain at 573 K during hot deformation process.