Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.

A flexible BiFeO_(3)-based ferroelectric tunnel junction memristor for neuromorphic computing

Ferroelectric tunnel junctions(FTJs)as the artificial synaptic devices have been considered promising for constructing brain-inspired neuromorphic computing systems.However,the memristive synapses based on the flexible FTJs have been rarely studied.Here,we report a flexible FTJ memristor grown on a mica substrate,which consists of an ultrathin ferroelectric barrier of BiFeO_(3),a semiconducting layer of ZnO,and an electrode of SrRuO_(3).The obtained flexible FTJ memristor exhibits stable voltage-tuned multistates,and the resistive switchings are robust after 10^(3) bending cycles.The capability of the FTJ as a flexible synaptic device is demonstrated by the functionality of the spike-timing-dependent plasticity with bending,and the accurate conductance manipulation with small nonlinearity(-0.24)and low cycle-to-cycle variation(1.77%)is also realized.Especially,artificial neural network simulations based on experimental device behaviors reveal that the high recognition accuracies up to 92.8%and 86.2%are obtained for handwritten digits and images,respectively,which are close to the performances for ideal memristors.This work highlights the potential applications of FTJ as flexible electronics for data storage and processing.

Sulfur-vacancy-tunable interlayer magnetic coupling in centimeter-scale M0S2 bilayer

Endowing bilayer transition-metal dichalcogenides(TMDs)with tunable magnetism is significant to investigate the coupling of multiple electron degrees of freedom(DOFs).However,effectively inducing and tuning the magnetic interaction of bilayer TMDs are still challenges.Herein,we report a strategy to tune the interlayer exchange interaction of centimeter-scale MoS2 bilayer with substitutional doping of Co ion,by introducing sulfur vacancy(V_(s))to modulate the interlayer electronic coupling.This strategy could transform the interlayer exchange interaction from antiferromagnetism(AFM)to ferromagnetism(FM),as revealed by the magnetic measurements.Experimental characterizations and theoretical calculations indicate that the enhanced magnetization is mainly because the hybridization of Co 3d band and Vs-induced impurity band alters the forms of interlayer orbital hybridizations between the partial Co atoms in upper and lower layers,and also enhances the intralayer FM.Our work paves the way for tuning the interlayer exchange interaction with defects and could be extended to other two-dimensional(2D)magnetic materials.