This study aims to identify the inhibitory role of the spinal glucagon like peptide-1 receptor (GLP-1R) signaling in pain hypersensitivity and its mechanism of action in rats and mice. First, GLP-1Rs were identified to be specifically expressed on microglial cells in the spinal dorsal horn, and profoundly upregulated after peripheral nerve injury. In addition, intrathecal GLP-1R agonists GLP-1(7-36) and exenatide potently alleviated formalin-, peripheral nerve injury-, bone cancer-, and diabetes-induced hypersensitivity states by 60 -90%, without affecting acute nociceptive responses. The antihypersensitive effects of exenatide and GLP-1 were completely prevented by GLP-1R antagonism and GLP-1R gene knockdown. Furthermore, exenatide evoked ␤-endorphin release from both the spinal cord and cultured microglia. Exenatide antiallodynia was completely prevented by the microglial inhibitor minocycline, ␤-endorphin antiserum, and opioid receptor antagonist naloxone. Our results illustrate a novel spinal dorsal horn microglial GLP-1R/␤-endorphin inhibitory pathway in a variety of pain hypersensitivity states.

Flat panel displays enjoy 100 billion‐dollar markets with significant penetration in daily life, which require efficient, color‐saturated blue, green, and red light‐emitting diodes (LEDs). The recently emerged halide perovskites have demonstrated low‐cost and outstanding performance for potential LED applications. However, the performance of blue perovskite LEDs (PeLEDs) lags far behind red and green cousins, particularly for color coordinates approaching (0.131, 0.046) that fulfill the Rec. 2020 specification for blue emitters. Here, a high‐efficiency, lead‐free perovskite, CsEuBr3, is reported that exhibits bright blue exciton emission centered at 448 nm with a color coordinates of (0.15, 0.04), contributed from Eu‐5d→Eu‐4f/Br‐4p transition with an optical band gap of 2.85 eV. Further optical characterizations reveal its short excited‐state lifetime of 151 ns, excellent exciton diffusion diffusivity of 0.0227 cm2 s−1, and high quantum yield of ≈69%. Inspired by these findings, deep‐blue PeLEDs based on all‐vacuum processing methods, which have been demonstrated as the most successful approach for the organic LED industry, are constructed. The devices show a maximum external quantum efficiency of 6.5% with an operating half‐lifetime of 50 mins at an initial brightness of 15.9 cd m−2. It is anticipated that this work will inspire further research on lanthanide‐based perovskites for next‐generation LED applications.

Remodeling of cytoskeleton structures, such as microtubule assembly, is believed to be crucial for growth cone initiation and regrowth of injured axons. Autophagy plays important roles in maintaining cellular homoeostasis, and its dysfunction causes neuronal degeneration. The role of autophagy in axon regeneration after injury remains speculative. Here we demonstrate a role of autophagy in regulating microtubule dynamics and axon regeneration. We found that autophagy induction promoted neurite outgrowth, attenuated the inhibitory effects of nonpermissive substrate myelin, and decreased the formation of retraction bulbs following axonal injury in cultured cortical neurons. Interestingly, autophagy induction stabilized microtubules by degrading SCG10, a microtubule disassembly protein in neurons. In mice with spinal cord injury, local administration of a specific autophagy-inducing peptide, Tat-beclin1, to lesion sites markedly attenuated axonal retraction of spinal dorsal column axons and cortical spinal tract and promoted regeneration of descending axons following long-term observation. Finally, administration of Tat-beclin1 improved the recovery of motor behaviors of injured mice. These results show a promising effect of an autophagyinducing reagent on injured axons, providing direct evidence supporting a beneficial role of autophagy in axon regeneration.autophagy | microtubule stabilization | axon regeneration I t is generally believed that the inability of adult central nervous system (CNS) neurons to regenerate their axons following injury is due to the presence of abundant inhibitory factors in extrinsic milieu and the lack of intrinsic growth ability (1-5). A number of extrinsic growth-inhibitory factors have been identified, including oligodendrocyte-derived myelin-associated glycoprotein (MAG), Nogo, OMgp, or astrocyte-derived chondroitin sulfate proteoglycans (CSPGs), which act through their respective receptors to suppress axon growth and regeneration (6-11). However, genetic ablation or elimination of these inhibitory receptors does not promote axon regeneration (12, 13) or shows marginal effects (14, 15).Many inhibitory factors act through signaling cascades to modulate cytoskeletal dynamics (16,17). Indeed, it has been observed that CNS axons form numerous retraction bulbs (RBs) with a disorganized array of microtubules (MTs), whereas peripheral nervous system (PNS) axons rapidly form a growth cone with stable, well-organized bundling of MTs following injury (18). In line with this notion, pharmacological stabilization of MTs promotes axon regeneration after spinal cord injury (SCI) (19,20). In addition, analyses of gene-targeted mice have led to identification of several intrinsic inhibitors of axon regeneration in the adult CNS, including phosphatase and tensin homolog (PTEN) and the suppressor of cytokine signaling 3 (SOCS3) (21,22). However, manipulating individual proteins or in combinations allows limited axonal regeneration or sprouting, which is usually associated with temporary improvement ...