Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9

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.     

A Bi-Enzymatic Cascade Pathway towards Optically Pure FAHFAs**

Recently discovered endogenous mammalian lipids, fatty acid esters of hydroxy fatty acids (FAHFAs), have been proved to have anti-inflammatory and anti-diabetic effects. Due to their extremely low abundancies in vivo, forging a feasible scenario for FAHFA synthesis is critical for their use in uncovering biological mechanisms or in clinical trials. Here, we showcase a fully enzymatic approach, a novel in vitro bi-enzymatic cascade system, enabling an effective conversion of nature-abundant fatty acids into FAHFAs. Two hydratases from Lactobacillus acidophilus were used for converting unsaturated fatty acids to various enantiomeric hydroxy fatty acids, followed by esterification with another fatty acid catalyzed by Candida antarctica lipase A (CALA). Various FAHFAs were synthesized in a semi-preparative scale using this bi-enzymatic approach in a one-pot two-step operation mode. In all, we demonstrate that the hydratase-CALA system offers a promising route for the synthesis of optically pure structure-diverse FAHFAs.     

氮含量及固溶温度对21-6-9奥氏体不锈钢组织和硬度的影响

为了探讨氮含量及固溶温度对21-6-9不锈钢组织和硬度的影响,分别在950、1000、1050和1100 ℃对3种不同氮含量的热轧态21-6-9不锈钢进行1 h固溶处理,通过光学显微镜观察其组织结构,结合Thermo-Calc热力学计算对试验钢的微观组织进行分析,并对其进行硬度测试。结果表明,0.20%~0.28%N的21-6-9不锈钢热轧后沿轧制方向析出铁素体,且钢中铁素体经950~1100 ℃固溶处理可消除,当N含量达到0.34%时,试验钢中不再出现铁素体。随着固溶处理温度的升高,21-6-9不锈钢的晶粒组织长大,硬度降低。N含量的增加可显著提高固溶态21-6-9不锈钢的硬度,其增加程度随固溶处理温度的升高而减弱。     

川中地区侏罗系沙溪庙组致密气处理和解释关键技术与应用

四川盆地蕴含丰富的致密砂岩气资源，近期利用高精度三维资料开展侏罗系沙溪庙组河道砂体勘探取得突出成效。沙溪庙组河道砂体具有横向变化快、储层非均质性强的特点，因此提高河道砂体的边界识别及其含气性预测精度是致密气地震勘探的关键。通过开展AVO特征低频保护的“六分法”（分类、分频、分时、分域、分步和分区）高保真叠前去噪、近地表Q补偿和OVT域叠前时间偏移等技术攻关，形成了一套针对川中地区侏罗系沙溪庙组致密气藏的“双高”（高保真、高分辨率）地震处理技术，并创新应用“双亮点”属性及多波、多分量砂体含气性地震预测等解释技术，提高了含气砂体预测精度。该技术系列在川中沙溪庙组致密气预测应用成果显著，地震数据频带得到了拓宽，低频信息更加丰富，资料信噪比明显提升，河道边界及其含气性预测的精度大幅提高，钻井成功率超过83%，应用成果有力地支撑了该地区沙溪庙组致密气的增储上产。     

A Highly Sensitive,Reversible, and Bidirectional Humidity Actuator by Calcium Carbonate Ionic Oligomers Incorporated Poly(Vinylidene Fluoride)

Sensitivity and multi-directional motivation are major two factors for developing optimized humidity-response materials, which are promising for sensing, energy production, etc. Organic functional groups are commonly used as the water sensitive units through hydrogen bond interactions with water molecules in actuators. The multi-coordination ability of inorganic ions implies that the inorganic ionic compounds are potentially superior water sensitive units. However, the particle forms of inorganic ionic compounds produced by classical nucleation limit the number of exposed ions to interact with water. Recent progress on the inorganic ionic oligomers has broken through the limitation of classical nucleation, and realized the molecular-scaled incorporation of inorganic ionic compounds into an organic matrix. Here, the incorporation of hydrophilic calcium carbonate ionic oligomers into hydrophobic poly(vinylidene fluoride) (PVDF) is demonstrated. The ultra-small calcium carbonate oligomers within a PVDF film endow it with an ultra-sensitive, reversible, and bidirectional response. The motivation ability is superior to other bidirectional humidity-actuators at present, which realizes self-motivation on an ice surface, converting the chemical potential energy of the humidity gradient from ice to kinetic energy.     

Facile Fabrication of Luminescent Eu(III) Functionalized HOF Hydrogel Film with Multifunctionailities: Quinolones Fluorescent Sensor and Anticounterfeiting Platform

The luminescent hydrogen-bonded organic framework (HOF) based films have become one of the most remarkable materials for optical application, thus, developing facile synthesis methods and establishing multifunctional applications for HOF-based luminescent materials are essential. Herein, a dual-emitting Eu³⁺-functionalized HOF hydrogel film ( 1 ) is fabricated successfully. 1 emits a blue-green long afterglow when turning off the UV lamp, and the long afterglow lifetime gets to 1.99 s. 1 performs great selectivity, high sensitivity, and low detection limit toward ofloxacin and flumequine, and the sensing toward ofloxacin and flumequine is in accord with the chroma and ratio modes. The fluorescent response mechanisms of 1  toward ofloxacin and flumequine are investigated in depth, which are further utilized to build an anticounterfeiting platform with high-level security. The film-based anticounterfeiting platform can conduct information encryption on demand inline with different fluorescent responses and can also fetch specific information by controlling the long afterglow intensity and excited light. This study not only provides a representative case of the fabrication of dual-emitting Eu³⁺-functionalized HOF-based hydrogel film but also opens the possibility of HOF-based film as intelligent luminescent materials with multifunctionalities.     

基于智能建造的某大型安置房项目安全管理方法应用

某大型安置房项目施工中,应用智能建造包含的综合管理平台技术、5G传输技术、无人塔式起重机智能安装技术、智能机器人和区块链技术,降低了安全风险,提高了安全管理水平.     

装配式混凝土木混合结构体系简述

上海电气研混凝土(如皋)建筑科技有限公司——建筑工业化智能创新基地项目,采用装配式混凝土木混合结构,该结构是一种新型的建筑结构体系.其承重的部分采用混凝土结构且可在工厂进行预制,围护结构采用木材制成,可在满足使用等功能的同时降低造价、减轻自重、保护环境,具有很大的发展潜力.     

石墨涂层载量对碱性锌锰电池电性能的影响

使用喷涂不同量石墨的钢壳组装碱性锌锰电池,考察石墨涂层载量对电池初始期及高温储存后电性能的影响.石墨涂层载量超过0.70 mg/cm2,会造成开路电压及放电性能下降,下降幅度随石墨涂层载量的增加及高温储存时间的延长而增大.     

课程思政在现代学徒制煤化工专业课程中的教学探索——以"煤质分析及煤化工产品检验"课程为例

现代学徒制是一项深化产教融合、校企合作的育人机制,是创新技术技能人才的现代培养模式.山西铁道职业技术学院与山西安泰控股集团有限公司深度合作开展山西省现代学徒制试点项目,合作目的之一是培养企业煤化工专业人才.学校教师结合学生(员工)在企业车间岗位上的技能知识,系统地讲授煤化工专业课程"煤质分析及煤化工产品检验"理论知识,同时针对企业员工日常学习思想政治知识较少的实际,润物细无声地加入思政元素,实现专业知识与实践技能相结合,技能知识与思政教育相融合,真正培养知识型、技能型、创新型高素质技能人才,努力构建职业教育产业发展命运共同体.