CRISPR/Cas9-Based Genome Editing for Disease Modeling and Therapy: Challenges and Opportunities for Nonviral Delivery

Wang, Hong-Xia,Li, Mingqiang,Lee, Ciaran M.,Chakraborty, Syandan,Kim, Hae-Won,Bao, Gang,Leong, Kam W. American Chemical Society 2017 Chemical reviews Vol.117 No.15

<P>Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety of cell types and organisms in vitro and in vivo. Herein, we review the rapidly developing CRISPR/Cas9-based technologies for disease modeling and gene correction and recent progress toward Cas9/guide RNA (gRNA) delivery based on viral and nonviral vectors. We discuss the relative merits of delivering the genome editing elements in the form of DNA, mRNA, or protein, and the opportunities of combining viral delivery of a transgene encoding Cas9 with nonviral delivery of gRNA. We highlight the lessons learned from nonviral gene delivery in the past three decades and consider their applicability for CRISPR/Cas9 delivery. We also include a discussion of bioinformatics tools for gRNA design and chemical modifications of gRNA. Finally, we consider the extracellular and intracellular barriers to nonviral CRISPR/Cas9 delivery and propose strategies that may overcome these barriers to realize the clinical potential of CRISPR/Cas9-based genome editing.</P>

Structural damage identification using an iterative two-stage method combining a modal energy based index with the BAS algorithm

Shuqing Wang,Yufeng Jiang,Mingqiang Xu,Yingchao Li,Zhixiong Li 국제구조공학회 2020 Steel and Composite Structures, An International J Vol.36 No.1

The purpose of this study is to develop an effective iterative two-stage method (ITSM) for structural damage identification of offshore platform structures. In each iteration, a new damage index, Modal Energy-Based Damage Index (MEBI), is proposed to help effectively locate the potential damage elements in the first stage. Then, in the second stage, the beetle antenna search (BAS) algorithm is used to estimate the damage severity of these elements. Compared with the well-known particle swarm optimization (PSO) algorithm and genetic algorithm (GA), this algorithm has lower computational cost. A modal energy based objective function for the optimization process is proposed. Using numerical and experimental data, the efficiency and accuracy of the ITSM are studied. The effects of measurement noise and spatial incompleteness of mode shape are both considered. All the obtained results show that under these influences, the ITSM can accurately identify the true location and severity of damage. The results also show that the objective function based on modal energy is most suitable for the ITSM compared with that based on flexibility and weighted natural frequency-mode shape.

DsbM, a Novel Disulfide Oxidoreductase Affects Aminoglycoside Resistance in Pseudomonas aeruginosa by OxyR-Regulated Response

Xuehan Wang,Mingxuan Li,Liwei Liu,Rui Mou,Xiuming Zhang,Yanling Bai,Haijin Xu,Mingqiang Qiao 한국미생물학회 2012 The journal of microbiology Vol.50 No.6

A Pseudomonas aeruginosa mutant strain M122 was isolated from a Mu transposon insertion mutant library. In our prophase research, we have found that PA0058, a novel gene encodes a 234-residue conserved protein, was disrupted in the M122 mutant. In this study, the bacteriostatic experiment in vitro indicates that M122 has abnormally high aminoglycoside resistance. We expressed PA0058 in E. coli and found that PA0058 oxidizes and reduces disulfide. This biochemical characterization suggests that PA0058 is a novel disulfide oxidoreductase. Hence, the protein was designated as DsbM. Microarray analysis of the M122 mutant showed its unusual phenotype might be related to the bacterial antioxidant defense system mediated by the oxyR regulon. Meanwhile, we detected –SH content in the periplasm of M122 and wild strain and found a lower –SH/S–S ratio in M122. Therefore, we consider that the loss of dsbM function decreased the –SH/S–S ratio, which then prolongs the OxyR-regulated response, thereby conferring high aminoglycoside resistance to the M122 mutant strain. Our findings have important implications for understanding the mechanisms underlying aminoglycoside resistance in P. aeruginosa.

Dynamic analysis of offshore wind turbines

Jianping Zhang,Mingqiang Wang,Zhen Gong,Fengfeng Shi 한국풍공학회 2020 Wind and Structures, An International Journal (WAS Vol.31 No.4

For large-scale 5MW offshore wind turbines, the discrete equation of fluid domain and the motion equation of structural domain with geometric nonlinearity were built, the three-dimensional modeling of the blade considering fluid-structure interaction (FSI) was achieved by using Unigraphics (UG) and Geometry modules, and the numerical simulation and the analysis of the vibration characteristics for wind turbine structure under rotating effect were carried out based on ANSYS software. The results indicate that the rotating effect has an apparent effect on displacement and Von Mises stress, and the response and the distribution of displacement and Von Mises stress for the blade in direction of wingspan increase nonlinearly with the equal increase of rotational speeds. Compared with the single blade model, the blade vibration period of the whole machine model is much longer. The structural coupling effect reduces the response peak value of the blade displacement and Von Mises stress, and the increase of rotational speed enhances this coupling effect. The maximum displacement difference between two models decreases first and then increases along wingspan direction, the trend is more visible with the equal increase of rotational speed, and the boundary point with zero displacement difference moves towards the blade root. Furthermore, the Von Mises stress difference increases gradually with the increase of rotational speed and decreases nonlinearly from the blade middle to both sides. The results can provide technical reference for the safe operation and optimal design of offshore wind turbines.

Acoustic system design and experimental research on the ultrasonic forming grinding gear

Xiao-bo Wang,Mingqiang Wu,Jiangwei Jin,Bo Zhao 대한기계학회 2023 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.37 No.8

In order to obtain high-performance gear elements with integrated shape, using non-resonant theory, the gear grinding experiment and ultrasound-assisted grinding acoustic system were established. Firstly, a theoretical model founded on the non-resonant proposed methodology was constructed. The frequency equation and displacement characteristics of the vibration system were established based on the specified boundary conditions, and the geometric size of the ultrasonic amplitude with a design frequency of 20 kHz was established. The acoustic system was simulated employing finite element software, and the analysis revealed that its frequency range was 19648 Hz, which was consistent with the design outcome. Meanwhile, the amplitude of the end surface of the tool gear reaches 5.59 μm, and the vibration was stable. Secondly, according to the solution of geometric parameters, the acoustic performance test was carried out. The error between resonant frequency (20387 Hz) and design frequency was 1.93 %, and the amplitude was 4.5 μm, which met the requirements of ultrasonic assisted grinding gear. Finally, the grinding test was carried out. The study results show that compared to conventional gear grinding, ultrasonic supported grinding lessens the grinding force by 11.5 % to 35.4 % and, at most, lowers the grinding temperature by 22.5 %.

A novel multistage approach for structural model updating based on sensitivity ranking

Yufeng Jiang,Yingchao Li,Shuqing Wang,Mingqiang Xu 국제구조공학회 2020 Smart Structures and Systems, An International Jou Vol.25 No.6

A novel multistage approach is developed for structural model updating based on sensitivity ranking of the selected updating parameters. Modal energy-based sensitivities are formulated, and maximum-normalized indices are designed for sensitivity ranking. Based on the ranking strategy, a multistage approach is proposed, where these parameters to be corrected with similar sensitivity levels are updated simultaneously at the same stage, and the complete procedure continues sequentially at several stages, from large to small, according to the predefined levels of the updating parameters. At every single stage, a previously developed cross model cross mode (CMCM) method is used for structural model updating. The effectiveness and robustness of the multistage approach are investigated by implementing it on an offshore structure, and the performances are compared with nonmultistage approach using numerical and experimental vibration information. These results demonstrate that the multistage approach is more effective for structural model updating of offshore platform structures even with limited information and measured noise. These findings serve as a preliminary strategy for structural model updating of an offshore platform in service.

Influence of structure coupling effect on damping coefficient of offshore wind turbine blades

Jianping Zhang,Zhen Gong,Haolin Li,Mingqiang Wang,Zhiwei Zhang,Fengfeng Shi 한국풍공학회 2019 Wind and Structures, An International Journal (WAS Vol.29 No.6

The aim of this study was to explore the influence of structure coupling effect on structural damping of blade based on the blade vibration characteristic. For this purpose, the scaled blade model of NREL 5 MW offshore wind turbine was processed and employed in the wind tunnel test to validate the reliability of theoretical and numerical models. The attenuation curves of maximum displacement and the varying curves of equivalent damping coefficient of the blade under the rated condition were respectively compared and analyzed by constructing single blade model and whole machine model. The attenuation law of blade dynamic response was obtained and the structure coupling effect was proved to exert a significant influence on the equivalent damping coefficient. The results indicate that the attenuation trend of the maximum displacement response curve of the single blade varies more obviously with the increase of elastic modulus as compared to that under the structure coupling effect. In contrast to the single blade model, the varying curve of equivalent damping coefficient with the period is relatively steep for the whole machine model. The findings are of great significance to guide the structure design and material selection for wind turbine blades.

Ultrafast epitaxial growth of metre-sized single-crystal graphene on industrial Cu foil

Xu, Xiaozhi,Zhang, Zhihong,Dong, Jichen,Yi, Ding,Niu, Jingjing,Wu, Muhong,Lin, Li,Yin, Rongkang,Li, Mingqiang,Zhou, Jingyuan,Wang, Shaoxin,Sun, Junliang,Duan, Xiaojie,Gao, Peng,Jiang, Ying,Wu, Xiaoson Elsevier 2017 Science bulletin Vol.62 No.15