Target binding and residence:a new determinant of DNA double-strand break repair pathway choice in CRISPR/Cas9 genome editing

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)is widely used for targeted genomic and epigenomic modifications and imaging in cells and organisms,and holds tremendous promise in clinical applications.The efficiency and accuracy of the technology are partly determined by the target binding affinity and residence time of Cas9-single-guide RNA(sgRNA)at a given site.However,little attention has been paid to the effect of target binding affinity and residence duration on the repair of Cas9-induced DNA double-strand breaks(DSBs).We propose that the choice of DSB repair pathway may be altered by variation in the binding affinity and residence duration of Cas9-sgRNA at the cleaved target,contributing to significantly heterogeneous mutations in CRISPR/Cas9 genome editing.Here,we discuss the effect of Cas9-sgRNA target binding and residence on the choice of DSB repair pathway in CRISPR/Cas9 genome editing,and the opportunity this presents to optimize Cas9-based technology.

Mechanical regulation of bone regeneration during distraction osteogenesis

Distraction osteogenesis(DO)is a mechanobiological process of regenerating bone tissue by tension stress.DO is used clinically to lengthen bones or to treat critical size bone defects.Although DO provides satisfactory results in many cases,the prolonged period of treatment remains a major challenge that needs to be overcome.Various attempts have been devoted to accelerating bone regeneration during DO.One common approach is manipulation of the applied mechanical loading by altering distraction strategies.In this article,we reviewed relevant in vivo animal studies exploring the effects of changing mechanical environments,by varying distraction parameters(e.g.,rate and frequency)or adding compression loading,on bone regeneration in DO.We further presented how the mechanically-regulated bone regeneration process during DO could be simulated by in silico models incorporating mechano-regulatory tissue differentiation rules.A comprehensive review of those in vivo and in silico studies may not solely provide important references for development of improved DO protocols in clinic,but also promote a deeper understanding of the mechanobiological mechanism of bone regeneration.

Lumped parameter model based surgical planning for CABG

The current 3D CABG model is time consuming,a lumped parameter CABG model may solve this problem.A coronary lumped parameter model without stenosis and graft was constructed.The stenosis resistance was calculated and graft model was constructed.After calculation,the graft flow results of CABG lumped parameter model fit well with 3D CABG model results.