Next generation of neurological therapeutics:Native and bioengineered extracellular vesicles derived from stem cells

Extracellular vesicles(EVs)-based cell-free therapy,particularly stem cell-derived extracellular vesicles(SC-EVs),offers new insights into treating a series of neurological disorders and becomes a promising candidate for alternative stem cell regenerative therapy.Currently,SC-EVs are considered direct therapeutic agents by themselves and/or dynamic delivery systems as they have a similar regenerative capacity of stem cells to promote neurogenesis and can easily load many functional small molecules to recipient cells in the central nervous system.Meanwhile,as non-living entities,SC-EVs avoid the uncontrollability and manufacturability limitations of live stem cell products in vivo(e.g.,low survival rate,immune response,and tumorigenicity)and in vitro(e.g.,restricted sources,complex preparation processes,poor quality control,low storage,shipping instability,and ethical controversy)by strict quality control system.Moreover,SC-EVs can be engineered or designed to enhance further overall yield,increase bioactivity,improve targeting,and extend their half-life.Here,this review provides an overview on the biological properties of SC-EVs,and the current progress in the strategies of native or bioengineered SC-EVs for nerve injury repairing is presented.Then we further summarize the challenges of recent research and perspectives for successful clinical application to advance SC-EVs from bench to bedside in neurological diseases.

Compact ultrabroadband light-emitting diodes based on lanthanide-doped lead-free double perovskites

Impurity doping is an effective approach to tuning the optoelectronic performance of host materials by imparting extrinsic electronic channels.Herein,a family of lanthanide(Ln^(3+))ions was successfully incorporated into a Bi:Cs_(2)AgInCl_(6) lead-free double-perovskite(DP)semiconductor,expanding the spectral range from visible(Vis)to near-infrared(NIR)and improving the photoluminescence quantum yield(PLQY).After multidoping with Nd,Yb,Er and Tm,Bi/Ln:Cs_(2)AgInCl_(6) yielded an ultrabroadband continuous emission spectrum with a full width at half-maximum of~365 nm originating from intrinsic self-trapped exciton recombination and abundant 4f-4f transitions of the Ln^(3+)dopants.Steady-state and transient-state spectra were used to ascertain the energy transfer and emissive processes.To avoid adverse energy interactions between the various Ln^(3+)ions in a single DP host,a heterogeneous architecture was designed to spatially confine different Ln^(3+)dopants via a“DP-in-glass composite”(DiG)structure.This bottom-up strategy endowed the prepared Ln^(3+)-doped DIG with a high PLQY of 40%(nearly three times as high as that of the multidoped DP)and superior long-term stability.Finally,a compact Vis-NIR ultrabroadband(400~2000 nm)light source was easily fabricated by coupling the DiG with a commercial UV LED chip,and this light source has promising applications in nondestructive spectroscopic analyses and multifunctional lighting.