A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest that microglial TRPV4 channels reside at the center of the neuroimmune axis in the spinal cord, which transforms peripheral nerve injury into central sensitization and neuropathic pain, thereby identifying TRPV4 as a potential new target for the treatment of chronic pain

Carbon Nanodots with Nearly Unity Fluorescent Efficiency Realized via Localized Excitons

Carbon nanodots (CDs) have emerged as an alternative option for traditional nanocrystals due to their excellent optical properties and low toxicity. Nevertheless, high emission efficiency is a long-lasting pursuit for CDs. Herein, CDs with near-unity emission efficiency are prepared via atomic condensation of doped pyrrolic nitrogen, which can highly localize the excited states thus lead to the formation of bound excitons and the symmetry break of the π–electron conjugation. The short radiative lifetimes (<8 ns) and diffusion lengths (<50 nm) of the CDs imply that excitons can be efficiently localized by radiative recombination centers for a defect-insensitive emission of CDs. By incorporating the CDs into polystyrene, flexible light-converting films with a high solid-state quantum efficiency of 84% and good resistance to water, heating, and UV light are obtained. With the CD–polymer films as light conversion layers, CD-based white light-emitting diodes (WLEDs) with a luminous efficiency of 140 lm W−1 and a flat-panel illumination system with lighting sizes of more than 100 cm2 are achieved, matching state-of-the-art nanocrystal-based LEDs. These results pave the way toward carbon-based luminescent materials for solid-state lighting technology.Carbon nanodots (CDs) with near-unity emission efficiency are prepared via atomic condensation of doped pyrrolic nitrogen, which can highly localize the excited states thus lead to the formation of bound excitons and the symmetry break of the π–electron conjugation. These results pave the way toward carbon-based luminescent materials for solid-state lighting technology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175115/1/advs4414-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175115/2/advs4414_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175115/3/advs4414.pd

Estrogen metabolites increase nociceptor hyperactivity in a mouse model of uterine pain

Pain emanating from the female reproductive tract is notoriously difficult to treat, and the prevalence of transient pelvic pain has been placed as high as 70%-80% in women surveyed. Although sex hormones, especially estrogen, are thought to underlie enhanced pain perception in females, the underlying molecular and cellular mechanisms are not completely understood. Here, we showed that the pain-initiating TRPA1 channel was required for pain-related behaviors in a mouse model of estrogen-induced uterine pain in ovariectomized female mice. Surprisingly, 2- and 4-hydroxylated estrogen metabolites (2- and 4-HEMs) in the estrogen hydroxylation pathway, but not estrone, estradiol, or 16-HEMs, directly increased nociceptor hyperactivity through TRPA1 and TRPV1 channels, and picomolar concentrations of 2- and 4-hydroxylation estrone (2- or 4-OHE1) could sensitize TRPA1 channel function. Moreover, both TRPA1 and TRPV1 were expressed in uterine-innervating primary nociceptors, and their expression was increased in the estrogen-induced uterine pain model. Importantly, pretreatment with 2- or 4-OHE1 recapitulated estrogen-induced uterine pain-like behaviors, and intraplantar injections of 2- and 4-OHE1 directly produced a TRPA1-dependent mechanical hypersensitivity. Our findings demonstrated that TRPA1 is critically involved in estrogen-induced uterine pain-like behaviors, which may provide a potential drug target for treating female reproductive tract pain

Observations of Forbush Decreases of Cosmic-Ray Electrons and Positrons with the Dark Matter Particle Explorer

The Forbush decrease (FD) represents the rapid decrease of the intensities of charged particles accompanied with the coronal mass ejections or high-speed streams from coronal holes. It has been mainly explored with the ground-based neutron monitor network, which indirectly measures the integrated intensities of all species of cosmic rays by counting secondary neutrons produced from interaction between atmospheric atoms and cosmic rays. The space-based experiments can resolve the species of particles but the energy ranges are limited by the relatively small acceptances except for the most abundant particles like protons and helium. Therefore, the FD of cosmic-ray electrons and positrons have just been investigated by the PAMELA experiment in the low-energy range (<5 GeV) with limited statistics. In this paper, we study the FD event that occurred in 2017 September with the electron and positron data recorded by the Dark Matter Particle Explorer. The evolution of the FDs from 2 GeV to 20 GeV with a time resolution of 6 hr are given. We observe two solar energetic particle events in the time profile of the intensity of cosmic rays, the earlier, and weaker, one has not been shown in the neutron monitor data. Furthermore, both the amplitude and recovery time of fluxes of electrons and positrons show clear energy dependence, which is important in probing the disturbances of the interplanetary environment by the coronal mass ejections