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11.
Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9
LIUCHENG WU YI WANG LILI DU GUIQING JI RUI ZHOU ZEYI ZHAO JUN CHEN SHUNXING ZHU 《Biocell》2021,45(6):1501-1507
Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value. 相似文献
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针对伊拉克米桑油田盐膏层巨厚、钻井液密度窗口窄、存在高压盐水层,储层段漏塌同层导致复杂时效高等问题,通过对比分析国内外盐膏层和窄压力窗口地层钻井技术,总结了米桑油田钻井面临的主要技术难点,从井身结构优化、钻井提速和复杂预防等方面入手,研究形成了适合米桑油田的钻井关键技术,并进行了现场试验应用,取得了显著的效果.伊拉克米桑油田钻井关键技术对该地区钻井技术方案设计和钻井提速提效具有较强的借鉴和指导作用. 相似文献
14.
随着对环保及自用水率的要求日益严格,水厂生产废水的减排已成为发展趋势.但既有水厂用地紧张和生产废水的处理工艺占地多存在矛盾,制约了水厂新增生产废水处理工艺的可行性.文中引入斜管沉淀提升沉淀效率、取消浓缩池、使用叠螺脱水机代替离心脱水机的优化设计方案,相较原设计的传统分离式生产废水处理工艺,生产废水停留时间减少75%,占地面积减少约48%.实践证明,该优化设计方案能够有效解决水厂生产废水处理工艺设计过程中遇到的用地不足问题,并有效地降低建设投资. 相似文献
15.
为研究铁塔公司发布的最新《低成本铁塔标准图集V1.0》的共享改造能力,文章选取了单斜撑三管塔0.65 kN/m2基本风压下的系列塔图,从各塔段的主管应力比和塔顶位移角两个角度,考虑新增天线设备、馈线、爬梯荷载,以及天线设备之间的相互遮挡,利用有限元软件SAP2000对每种塔型进行了常规设计分析和改造增载后的研究分析.由分析结果可知,每种塔型均有可共享改造能力,且随着塔身高度的增加,共享改造的能力逐渐降低. 相似文献
16.
Wenyan Ma Lian-Wei Luo Peihua Dong Peiyun Zheng Xiuhua Huang Chong Zhang Jia-Xing Jiang Yong Cao 《Advanced functional materials》2021,31(45):2105027
Recent studies have demonstrated that dihydrophenazine (Pz) with high redox-reversibility and high theoretical capacity is an attractive building block to construct p-type polymer cathodes for dual-ion batteries. However, most reported Pz-based polymer cathodes to date still suffer from low redox activity, slow kinetics, and short cycling life. Herein, a donor–acceptor (D–A) Pz-based conjugated microporous polymer (TzPz) cathode is constructed by integrating the electron-donating Pz unit and the electron-withdrawing 2,4,6-triphenyl-1,3,5-triazine (Tz) unit into a polymer chain. The D–A type structure enhances the polymer conjugation degree and decreases the band gap of TzPz, facilitating electron transportation along the polymer skeletons. Therefore the TzPz cathode for dual-ion battery shows a high reversible capacity of 192 mAh g−1 at 0.2 A g−1 with excellent rate performance (108 mAh g−1 at 30 A g−1), which is much higher than that of its counterpart polymer BzPz produced from 1,3,5-triphenylbenzene (Bz) and Pz (148 and 44 mAh g−1 at 0.2 and 10 A g−1, respectively). More importantly, the TzPz cathode also shows a long and stable cyclability of more than 10 000 cycles. These results demonstrate that the D–A structural design is an efficient strategy for developing high-performance polymer cathodes for dual-ion batteries. 相似文献
17.
Chaozhong Sun Xiaoying Guo Rui Ji Changzheng Hu Laijun Liu Liang Fang Zhenxiang Cheng Nengneng Luo 《Ceramics International》2021,47(4):5038-5043
The triboelectric effect has recently demonstrated its great potential in environmental remediation and even new energy applications for triggering a number of catalytic reactions by utilizing trivial mechanical energy. In this study, Ba4Nd2Fe2Nb8O30 (BNFN) submicron powders were used to degrade organic dyes via the tribocatalytic effect. Under the frictional excitation of three PTFE stirring rods in a 5 mg/L RhB dye solution, BNFN demonstrates a high tribocatalytic degradation efficiency of 97% in 2 h. Hydroxyl radicals (?OH) and superoxide radicals (?O2-) were also detected during the catalysis process, which proves that triboelectric energy stimulates BNFN to generate electron-hole pairs. The tribocatalysis of tungsten bronze BNFN submicron powders provides a novel and efficient method for the degradation of wastewater dye by utilizing trivial mechanical energy. 相似文献
18.
针对表壳具有较多复杂曲面及三端加工特点及需求,通过对球铁水表壳的外形及加工特点进行分析,提出合理的设计加工工序方案,选用特种加工设备及专业的工装夹具.通过针对表壳外形及加工工艺特点设计专业的工装夹具达到一次装夹多工序同时加工,有效解决了传统加工工艺的多工序多道加工,提高加工效率并确保加工质量. 相似文献
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20.
Saier Liu Guangxiao Li Minjing Shang Zheng-Hong Luo Yuanhai Su 《American Institute of Chemical Engineers》2021,67(11):e17362
Hydrodynamics characteristics of a fast and highly exothermic liquid–liquid oxidation process with in situ gas production in microreactors were studied using a newly developed experimental method. In the adipic acid synthesis through the K/A oil (the mixture of cyclohexanol and cyclohexanone) oxidation with nitric acid, bubble generation modes were divided into four categories. The gas production became more intensive, unstable, even explosive with increasing the oil phase feed rate and the temperature. A novel automatic image processing method was developed to monitor the instantaneous velocity online by tracking the gas–liquid interface. The axial velocity at the same location was unstable due to the changing gas production rate. Furthermore, the actual residence time was obtained easily with being only 36% of the space–time minimally, beneficial for establishing accurate kinetics and mass transfer models with time participation. Finally, an empirical correlation was developed to predict the actual residence time under different conditions. 相似文献