Potential Treatment of Lysosomal Storage Disease through Modulation of the Mitochondrial—Lysosomal Axis

Lysosomal storage disease (LSD) is an inherited metabolic disorder caused by enzyme deficiency in lysosomes. Some treatments for LSD can slow progression, but there are no effective treatments to restore the pathological phenotype to normal levels. Lysosomes and mitochondria interact with each other, and this crosstalk plays a role in the maintenance of cellular homeostasis. Deficiency of lysosome enzymes in LSD impairs the turnover of mitochondrial defects, leading to deterioration of the mitochondrial respiratory chain (MRC). Cells with MRC impairment are associated with reduced lysosomal calcium homeostasis, resulting in impaired autophagic and endolysosomal function. This malicious feedback loop between lysosomes and mitochondria exacerbates LSD. In this review, we assess the interactions between mitochondria and lysosomes and propose the mitochondrial–lysosomal axis as a research target to treat LSD. The importance of the mitochondrial–lysosomal axis has been systematically characterized in several studies, suggesting that proper regulation of this axis represents an important investigative guide for the development of therapeutics for LSD. Therefore, studying the mitochondrial–lysosomal axis will not only add knowledge of the essential physiological processes of LSD, but also provide new strategies for treatment of LSD

Preparation and Characterization of Carbon Fibers from Lyocell Precursors Grafted with Polyacrylamide via Electron-Beam Irradiation

Carbon fibers, which act as reinforcements in many applications, are often obtained from polyacrylonitrile (PAN). However, their production is expensive and results in waste problems. Therefore, we focused on producing carbon fibers from lyocell, a cellulose-based material, and analyzed the effects of the process parameters on their mechanical properties and carbon yields. Lyocell was initially grafted with polyacrylamide (PAM) via electron-beam irradiation (EBI) and was subsequently stabilized and carbonized. Thermal analysis showed that PAM grafting increased the carbon yields to 20% at 1000 °C when compared to that of raw lyocell, which degraded completely at about 600 °C. Stabilization further increased this yield to 55%. The morphology of the produced carbon fibers was highly dependent on PAM concentration, with fibers obtained at concentrations ≤0.5 wt.% exhibiting clear, rigid, and round cross-sections with smooth surfaces, whereas fibers obtained from 2 and 4 wt.% showed peeling surfaces and attachment between individual fibers due to high viscosity of PAM. These features affected the mechanical properties of the fibers. In this study, carbon fibers of the highest tensile strength (1.39 GPa) were produced with 0.5 wt.% PAM, thereby establishing the feasibility of using EBI-induced PAM grafting on lyocell fabrics to produce high-performance carbon fibers with good yields

Fly Ash-Incorporated Polystyrene Nanofiber Membrane as a Fire-Retardant Material: Valorization of Discarded Materials

Reusing or recycling waste into new useful materials is essential for environmental protection. Herein, we used discarded polystyrene (PS) and fly-ash (FA) particles and a fabricated fly-ash incorporated polystyrene fiber (FA/PS fiber) composite. The electrospinning process produced continuous PS fibers with a good distribution of FA particles. The prepared nanofibers were characterized by state-of-the-art techniques. The performances of the composite nanofibers were tested for fire-retardant applications. We observed that the incorporation of FA particles into the PS fibers led to an improvement in the performance of the composite as compared to the pristine PS fibers. This study showed an important strategy in using waste materials to produce functional nanofibers through an economical procedure. We believe that the strategy presented in this paper can be extended to other waste materials for obtaining nanofiber membranes for various environmental applications

Central connectivity of transient receptor potential melastatin 8-expressing axons in the brain stem and spinal dorsal horn.

Transient receptor potential melastatin 8 (TRPM8) ion channels mediate the detection of noxious and innocuous cold and are expressed by primary sensory neurons, but little is known about the processing of the TRPM8-mediated cold information within the trigeminal sensory nuclei (TSN) and the spinal dorsal horn (DH). To address this issue, we characterized TRPM8-positive (+) neurons in the trigeminal ganglion and investigated the distribution of TRPM8+ axons and terminals, and their synaptic organization in the TSN and in the DH using light and electron microscopic immunohistochemistry in transgenic mice expressing a genetically encoded axonal tracer in TRPM8+ neurons. TRPM8 was expressed in a fraction of small myelinated primary afferent fibers (23.7%) and unmyelinated fibers (76.3%), suggesting that TRPM8-mediated cold is conveyed via C and Aδ afferents. TRPM8+ axons were observed in all TSN, but at different densities in the dorsal and ventral areas of the rostral TSN, which dominantly receive sensory afferents from intra- and peri-oral structures and from the face, respectively. While synaptic boutons arising from Aδ and non-peptidergic C afferents usually receive many axoaxonic contacts and form complex synaptic arrangements, TRPM8+ boutons arising from afferents of the same classes of fibers showed a unique synaptic connectivity; simple synapses with one or two dendrites and sparse axoaxonic contacts. These findings suggest that TRPM8-mediated cold is conveyed via a specific subset of C and Aδ afferent neurons and is processed in a unique manner and differently in the TSN and DH

Control Efficacy of Nano-silver Liquid on Oak Wilt Caused by Raffaelea sp. in the Field

In other previous in vitro tests, the hyphal growth of Raffaelea quercivorus was inhibited by the treatments of various concentration of nano-silver. In this field tests, treatment of different concentrations of nano-silver to oak trees in Cheolwon and Hongcheon sites showed the inhibition effects against wilt disease caused by Raffaelea quercivorus. However, nano-silver-treated oak tree in Chuncheon site showed mild wilt symptoms with no phytotoxicity. Scanning electron microscope (SEM) observation confirmed that the spore and hypha of Raffaelea sp. inside the vessels were damaged by nano-silver. This result indicates the application of nanosilver is effective for control of Raffaelea quercivorus in the field

Complications Following Colonoscopy in a Nationwide Standard Cohort: A Retrospective Case-control Study

Background : /Aims: Despite the many reports of colonoscopy complications worldwide, few studies have been performed at the population level in Korea. In this study, a population-based study was performed to evaluate the incidence of post-colonoscopy perforations compared to a control group. Methods : : Between January 2011 and December 2011, data for all cases (age over 45) who underwent a colonoscopy were collected from National Health Insurance Service using a random sampling method. The clinical characteristics and perforation incidence (within 30 days after the colonoscopy) of cases were identified, and cases were then compared with controls who had not undergone a colonoscopy. Results : : Among 1,380,000 subjects, 31,177 cases and 62,354 controls were identified. Perforation occurred in 14 patients (0.04%) in the case group and one patient (<0.01%) in the control group (RR, 28.0; 95% CI 3.7-212.9, p<0.001). Subgroup analysis was followed according to the endoscopic procedure, gender and age. In subgroup analysis, colonoscopy-associated perforations occurred more in the therapeutic procedure (RR, 26; 95% CI 1.46-461.46), male (RR, 50; 95% CI 2.96-844.41), and age of 45-60 years (RR, 30; 95% CI 1.71-525.23). Conclusion : s: A colonoscopy procedure is related to an increased risk of perforation at the population level. In addition, the therapeutic procedure, male, and age of 45-60 years appeared to be associated with an increased risk of perforation

ATM mediated-p53 signaling pathway forms a novel axis for senescence control

Previously, we uncovered a novel mechanism in which senescence is controlled by mitochondrial functional recovery upon Ataxia-telangiectasia mutated (ATM) inhibition. However, it remains elusive how ATM controls signaling pathways to achieve restorative effect. In this study, we performed microarray and found that p53 pathway was differentially expressed upon ATM inhibition. We found that ATM inhibition yields senescence amelioration through p53-dependent manner. The restorative effect was also afforded by direct p53 inhibition. Furthermore, mitochondrial metabolic reprogramming via p53 inhibition was a prerequisite for senescence amelioration. Taken together, our data indicated that p53 pathway functions as potential target for ATM-mediated senescence amelioration. © 2020 Elsevier B.V. and Mitochondria Research Society1