54,079 research outputs found

    Advances in extracellular vesicle-based combination therapies for spinal cord injury

    No full text
    Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits. The currently available treatments involve surgical, medical, and rehabilitative strategies. However, none of these techniques can markedly reverse neurological deficits. Recently, extracellular vesicles from various cell sources have been applied to different models of spinal cord injury, thereby generating new cell-free therapies for the treatment of spinal cord injury. However, the use of extracellular vesicles alone is still associated with some notable shortcomings, such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons. Therefore, this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury, including the combination of extracellular vesicles with nanoparticles, exogenous drugs and/or biological scaffold materials, which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles. We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury

    Performance of the local reconstruction algorithms for the CMS hadron calorimeter with Run 2 data

    Get PDF
    A description is presented of the algorithms used to reconstruct energy deposited in the CMS hadron calorimeter during Run 2 (2015–2018) of the LHC. During Run 2, the characteristic bunch-crossing spacing for proton-proton collisions was 25 ns, which resulted in overlapping signals from adjacent crossings. The energy corresponding to a particular bunch crossing of interest is estimated using the known pulse shapes of energy depositions in the calorimeter, which are measured as functions of both energy and time. A variety of algorithms were developed to mitigate the effects of adjacent bunch crossings on local energy reconstruction in the hadron calorimeter in Run 2, and their performance is compared

    GSH/pH-Sensitive Poly(glycerol sebacate dithiodiglycolate) Nanoparticle as a Ferroptotic Inducer through Cooperation with Fe<sup>3+</sup>

    No full text
    Ferroptosis is an iron-dependent, non-apoptotic cell death induced by an overload of iron initiated through Fenton and Haber–Weiss reactions. These two reactions lead to lethal levels of intracellular reactive oxygen species (ROS) and lipid peroxidation. In contrast, glutathione (GSH) and glutathione peroxidase 4 (GPX4) suppress ferroptosis by inhibiting lipid peroxidation. Herein, the ferric ion (Fe3+) carriers, poly(glycerol sebacate dithiodiglycolate) nanoparticles (PGSDTG NPs), were prepared via nanoprecipitation. The GSH/pH-dual sensitive Fe3+/PGSDTG NPs would disintegrate via the cleavage of disulfide and ester bonds in the presence of GSH and acidic conditions. The cleaved polymer segments along with released Fe3+ rendered cancer cells showing ferroptosis characteristics including ROS production, transferrin receptor 1 (TfR1) expression, and iron accumulation after treatment with Fe3+/PGSDTG NPs. The PGSDTG NPs played an important role in ferroptosis by triggering the oxidation of intracellular GSH and reducing the GPX4 expression. An in vivo experiment also showed that Caenorhabditis elegans (C. elegans) exhibited a shortened lifespan after treatment with NPs. These results indicated that the PGSDTG NPs were potential GSH/pH-sensitive metal ion carriers for anticancer treatment by inducing ferroptosis

    Extracting the speed of sound in the strongly interacting matter created in ultrarelativistic lead-lead collisions at the LHC