MicroRNA-208a silencing against myocardial ischemia/reperfusion injury mediated by reversibly camouflaged biomimetic nanocomplexes

MicroRNA-208a(miR-208a)plays critical roles in the severe fibrosis and heart failure post myocardial ischemia/reperfusion(IR)injury.MiR-208a inhibitor(mI)with complementary RNA sequence can silence the expression of miR-208a,while it is challenging to achieve efficient and myocardium-targeted delivery.Herein,biomimetic nanocomplexes(NCs)reversibly coated with red blood cell membrane(RM)were developed for the myocardial delivery of mI.To construct the NCs,membrane-penetrating helical polypeptide(PG)was first adopted to condense mI and form the cationic inner core,which subsequently adsorbed catalase(CAT)via electrostatic interaction followed by surface coating with RM.The membrane-coated NCs enabled prolonged blood circulation after systemic administration,and could accumulate in the injured myocardium via passive targeting.In the oxidative microenvironment of injured myocardium,CAT decomposed H_(2)O_(2)to produce O_(2)bubbles,which drove the shedding of the outer RM to expose the positively charged inner core,thus facilitated effective internalization by cardiac cells.Based on the combined contribution of mI-mediated miR-208a silencing and CAT-mediated alleviation of oxidative stress,NCs effectively ameliorated the myocardial microenvironment,hence reducing the infarct size as well as fibrosis and promoting recovery of cardiac functions.This study provides an effective strategy for the cytosolic delivery of nucleic acid cargoes in the myocardium,and it renders an enlightened approach to resolve the blood circulation/cell internalization dilemma of cell membrane-coated delivery systems.

Accelerated Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydride via Inorganic Nano-initiators

While the accelerated polymerization of N-carboxyanhydrides (NCAs) has been utilized to synthesize versatile polypeptide materials in an efficient manner with minimized side reactions, the preparation of polypeptide-based inorganic/organic hybrid materials with the acceleration strategy remained largely unexplored. Herein, we report the accelerated ring-opening polymerization (ROP) of NCAs mediated by amine-modified inorganic nano-initiators, such as mesoporous silica nanoparticles (MSN-NH2), which is driven by the cooperative effect of the neighboring α-helical polypeptide chains in a dichloromethane (DCM)/water biphasic system. Well-defined nano-hybrids were prepared within 15 min from non-purified NCA monomers, through in situ purification and subsequent ultrafast polymerization process. NCAs can be rapidly initiated by amino groups of MSN uniformly dispersed at the interface of DCM and water, and subsequently formed the well-defined polypeptides within 15 min. The prepared inorganic/organic nano-hybrid with MSN as the core and polypeptide as the shell adopted spherical morphology and uniform size distribution due to the excellent controllability of ROP. Besides, this system is also suitable for a variety of NCAs and inorganic nano-initiators. This research allows efficient and rapid preparation of inorganic/organic nano-hybrids, and further promotes the extensive application of this material in the biomedical fields.

基于开环聚合的聚氨基酸材料的二级结构效应及调控

聚氨基酸是一类蛋白模拟物,近年来在诸多领域都有着广泛的应用.同天然的蛋白质一样,聚氨基酸的主链氢键作用也赋予其丰富的二级结构,而二级结构的调控对材料的功能以及组装等都有着十分重要的意义.本文结合聚氨基酸近几年的最新研究进展,分析了聚氨基酸二级结构的形成机制以及侧基功能化对二级结构的影响,总结了二级结构的影响因素,在此基础上,详细阐述了二级结构的调控方法,并探讨了二级结构的形成对穿膜、基因递送、抗菌性能、自组装行为以及蛋白修饰的影响.

Equipment remaining useful life prediction oriented symbiotic simulation driven by real-time degradation data

As an emerging simulation technology in the field of system modeling and simulation,the equipment symbiotic simulation has become research emphasis.In the field of equipment maintenance support,the outstanding problem of equipment remaining useful life(RUL)prediction is analyzed,i.e.,the stable model parameters without self-evolution ability,which has become the primary factor that hinders self-adaptive prediction of equipment RUL.Combined with parallel systems theory,the equipment RUL prediction oriented symbiotic simulation framework is proposed on the basis of modeling analysis and Wiener state space model(SSM)is taken as the basic simulation model in the framework.Driven by the dynamic injected equipment degradation observation data,the model parameters are updated online by using expectation maximum(EM)algorithm and the data assimilation between simulation outputs and observation data is executed by using Kalman filter,so as to realize dynamic evolution of the simulation model.The simulation model evolution which makes the simulation outputs close to equipment real degradation state provides high fidelity model and data for predicting equipment RUL accurately.The framework is verified by the performance degradation data of a bearing.The simulation results show that the symbiotic simulation method can accurately simulate the equipment performance degradation process and the self-adaptive prediction of equipment RUL is realized on the basis of improving prediction accuracy,proving the feasibility and effectiveness of symbiotic simulation method.