CRISPR/Cas9 systems:Delivery technologies and biomedical applications

The emergence of the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)genome-editing system has brought about a significant revolution in the realm of managing human diseases,establishing animal models,and so on.To fully harness the potential of this potent gene-editing tool,ensuring efficient and secure delivery to the target site is paramount.Consequently,developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research.In this review,we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system.We also provide an indepth analysis of physical,viral vector,and non-viral vector delivery strategies,including plasmid-,mRNA-and protein-based approach.In addition,we illustrate the biomedical applications of the CRISPR/Cas9 system.This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system,while also delineating future directions and prospects that could inspire innovative delivery strategies.This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.

Tumor microenvironment responsive drug delivery systems

Conventional tumor-targeted drug delivery systems(DDSs)face challenges,such as unsatisfied systemic circulation,low targeting efficiency,poor tumoral penetration,and uncontrolled drug release.Recently,tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas.With the introduction of several additional functionalities,the properties of these smart DDSs including size,surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting,and eventually achieve desired drug release for an optimized therapeutic efficiency.This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery.Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli,including pH,glutathione,adenosine-triphosphate,reactive oxygen species,enzyme and inflammatory factors are summarized.Special emphasis of this review is placed on their responsive mechanisms,drug loading models,drawbacks and merits.Several typical multi-stimuli responsive DDSs are listed.And the main challenges and potential future development are discussed.

Reinforcement learning based UAV formation control in GPS-denied environment

Highly accurate positioning is a crucial prerequisite of multi Unmanned Aerial Vehicle close-formation flight for target tracking,formation keeping,and collision avoidance.Although the position of a UAV can be obtained through the Global Positioning System(GPS),it is difficult for a UAV to obtain highly accurate positioning data in a GPS-denied environment(e.g.,a GPS jamming area,suburb,urban canyon,or mountain area);this may cause it to miss a tracking target or collide with another UAV.In particular,UAV close-formation control in GPS-denied environments faces difficulties owing to the low-accuracy position,close distance between vehicles,and nonholonomic dynamics of a UAV.In this paper,on the one hand,we develop an innovative UAV formation localization method to address the formation localization issues in GPS-denied environments;on the other hand,we design a novel reinforcement learning based algorithm to achieve the high-efficiency and robust performance of the controller.First,a novel Lidar-based localization algorithm is developed to measure the localization of each aircraft in the formation flight.In our solution,each UAV is equipped with Lidar as the position measurement sensor instead of the GPS module.The k-means algorithm is implemented to calculate the center point position of UAV.A novel formation position vector matching method is proposed to match center points with UAVs in the formation and estimate their position information.Second,a reinforcement learning based UAV formation control algorithm is developed by selecting the optimal policy to control UAV swarm to start and keep flying in a close formation of a specific geometry.Third,the innovative collision risk evaluation module is proposed to address the collision-free issues in the formation group.Finally,a novel experience replay method is also provided in this paper to enhance the learning efficiency.Experimental results validate the accuracy,effectiveness,and robustness of the proposed scheme.

Ab Initio Investigations for the Role of Compositional Complexities in Affecting Hydrogen Trapping and Hydrogen Embrittlement:A Review

ydrogen embrittlement(HE)seriously restricts the service safety of structural metallic materials applicate in aerospace,ocean,and transportation.Recent studies aiming at increasing the HE-resistance have been focusing on trapping diffusible H atoms by inherent microstructural features in materials.Alloying-induced compositional complexities,including different types of solute atoms,lattice chemical heterogeneities,and carbide precipitates,have attracted research efforts regarding the H trapping capabilities and potential to reduce the susceptibility to HE.In this paper,we review recent progress in exploiting compositional complexities to regulate the hydrogen trapping characteristics and mechanical properties in H-containing environments.The focus is placed on results and insights from ab initio calculations based on density functional theory(DFT).Quantitative predictions of trapping parameters and atomic scale details that are hardly to be gained through traditional experimental characterizations are provided.Additionally,we overview the electronic/atomistic mechanisms of H trapping energetics in metallic materials.Finally,we propose some key challenges and prospects in simulation of defect interactions,interpretation of experimental characterizations,and developing microstructure-based H diffusion prediction models.For the applications of first principle calculations,we illustrate how the DFT data can complement experimental characterizations to guide composition and microstructure design for better HE-resistant materials.

Influence of refined hierarchical martensitic microstructures on yield strength and impact toughness of ultra-high strength stainless steel

The hierarchical martensitic features in ultra-high strength stainless steel(UHSSS),including the prior austenite grains,martensite packets,blocks and laths with the descending size,were refined to various extents by employing different thermomechanical processes and then carefully characterized.Their relation to yield strength and impact toughness was analyzed.We conclude that the refinement of martensitic structures could lead to the significant increase of yield strength,which follows the Hall-Petch relation with the effect grain size defined by high angle boundaries(HABs).Impact toughness of UHSSS depends on the frequency and capability for retained austenite(RA)grains at both HABs and martensite lath boundaries to trap the propagating cracks via strain-induced transformation,in which the film-like RA grains at lath boundaries appear to make the greater contribution.

Living cell for drug delivery

The living cells have been emerged as useful platforms for drug delivery due to their advantages of good liquidity,stability,and low immunogenicity.In this review,we summarized the development of living cells-based drug delivery systems.The drug loading methods,applications,and advantages of living cell drug delivery systems were summarized.Different living cells for drug delivery,the mechanisms of action,therapeutic applications,as well as main features were summarized and highlighted.The recent research progress and challenges were discussed.The future directions and prospects were proposed.

Let-7i miRNA and platinum loaded nano-graphene oxide platform for detection/reversion of drug resistance and synergetic chemical-photothermal inhibition of cancer cell

The drug resistance of chemotherapy is a major challenge to overcome for antineoplastic agents and the reverse of drug resistant is essential for cancer therapy. Herein, we developed a drug delivery system which can simultaneously detect/reverse the drug resistance and perform synergetic treatment of cancer. In this work, we integrated cyanine5(Cy5) modified mi RNA(let-7 i)(Cy5-mi RNA) and platinum onto nano-graphene oxide(NGO)(30-50 nm) platform to achieve simultaneously detection/reversion of drug resistance and synergetic treatment of cisplatin resistant SKOV3 cells(SKOV3 DDP cells). The Cy5-mi RNA adsorbed on NGO could selectively bind the drug resistance related m RNA follow by suppress the expression of drug resistance m RNA, and the binding simultaneously induced the release of Cy5-mi RNA from the NGO, thus the fluorescence signal of Cy5 recovered and could be used for drug resistance monitoring.Moreover, the mi RNA suppressed the Cyclin D1 protein expressions thus reversed the drug resistance. The loaded platinum(Ⅳ)(Pt(Ⅳ)) was converted to the therapeutic platinum(Ⅱ)(Pt(Ⅱ)) in both tumor acidic and reductive environment responsive behavior. NGO furtherly performed photothermal therapy under near infrared(NIR) laser irradiation and enhanced the therapeutic effect. All in all, this nanoplatform realized detection/reversion of the drug resistance as well as synergetic chemical-photothermal treatment of ovarian cancer cells, which holds great promise in the treatment of drug resistant cancer cells.