Regulation of the Catabolic Cascade in Osteoarthritis by the Zinc-ZIP8-MTF1 Axis

SummaryOsteoarthritis (OA), primarily characterized by cartilage degeneration, is caused by an imbalance between anabolic and catabolic factors. Here, we investigated the role of zinc (Zn2+) homeostasis, Zn2+ transporters, and Zn2+-dependent transcription factors in OA pathogenesis. Among Zn2+ transporters, the Zn2+ importer ZIP8 was specifically upregulated in OA cartilage of humans and mice, resulting in increased levels of intracellular Zn2+ in chondrocytes. ZIP8-mediated Zn2+ influx upregulated the expression of matrix-degrading enzymes (MMP3, MMP9, MMP12, MMP13, and ADAMTS5) in chondrocytes. Ectopic expression of ZIP8 in mouse cartilage tissue caused OA cartilage destruction, whereas Zip8 knockout suppressed surgically induced OA pathogenesis, with concomitant modulation of Zn2+ influx and matrix-degrading enzymes. Furthermore, MTF1 was identified as an essential transcription factor in mediating Zn2+/ZIP8-induced catabolic factor expression, and genetic modulation of Mtf1 in mice altered OA pathogenesis. We propose that the zinc-ZIP8-MTF1 axis is an essential catabolic regulator of OA pathogenesis

Subchronic oral toxicity of silver nanoparticles

<p>Abstract</p> <p>Background</p> <p>The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems.</p> <p>Results</p> <p>This study tested the oral toxicity of silver nanoparticles (56 nm) over a period of 13 weeks (90 days) in F344 rats following Organization for Economic Cooperation and Development (OECD) test guideline 408 and Good Laboratory Practices (GLP). Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose (30 mg/kg), middle-dose (125 mg/kg), and high-dose (500 mg/kg). After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P < 0.05) in the body weight of male rats after 4 weeks of exposure, although there were no significant changes in food or water consumption during the study period. Significant dose-dependent changes were found in alkaline phosphatase and cholesterol for the male and female rats, indicating that exposure to more than 125 mg/kg of silver nanoparticles may result in slight liver damage. Histopathologic examination revealed a higher incidence of bile-duct hyperplasia, with or without necrosis, fibrosis, and/or pigmentation, in treated animals. There was also a dose-dependent accumulation of silver in all tissues examined. A gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in female kidneys compared to male kidneys.</p> <p>Conclusions</p> <p>The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level) of 30 mg/kg and LOAEL (lowest observable adverse effect level) of 125 mg/kg are suggested from the present study.</p

Chlorophyll and Total Suspended Materials Concentrations and Remote Sensing Reflectance Data measured at the Red Tide Area of Jinhae, Geoje, and East Sea during August from 1998 to 2003 and August 2013

The chlorophyll and total suspended materials concentrations and remote sensing reflectance data were observed for red tides occurring every summer in waters around the Korean Peninsula. In observation area and date, the field survey were performed (1) in the Jinhae and Geoje coasts during August 1998, August 1999, August 2001, and August 2003, (2) in East Sea coast during August 2013. The remote sensing reflectance data were obtained from portable spectroradiometer. The chlorophyll concentration data were obtained from spectrophotometric method and the total suspended materials concentration data were obtained from filter-weight difference method. The remote sensing reflectance data were validated using Moon et al.(2012). The chlorophyll concentration data were validated using baseline correction and subtraction of 750 nm value, and the total suspended materials concentration data were validated using variation of humidity

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

Extremely stable graphene electrodes doped with macromolecular acid

Although conventional p-type doping using small molecules on graphene decreases its sheet resistance (Rsh), it increases after exposure to ambient conditions, and this problem has been considered as the biggest impediment to practical application of graphene electrodes. Here, we report an extremely stable graphene electrode doped with macromolecular acid (perfluorinated polymeric sulfonic acid (PFSA)) as a p-type dopant. The PFSA doping on graphene provides not only ultra-high ambient stability for a very long time (&gt; 64 days) but also high chemical/thermal stability, which have been unattainable by doping with conventional small-molecules. PFSA doping also greatly increases the surface potential (similar to 0.8 eV) of graphene, and reduces its Rsh by similar to 56%, which is very important for practical applications. High-efficiency phosphorescent organic light-emitting diodes are fabricated with the PFSA-doped graphene anode (similar to 98.5 cd A(-1) without out-coupling structures). This work lays a solid platform for practical application of thermally-/chemically-/air-stable graphene electrodes in various optoelectronic devices

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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Measurement of the WZ production cross section in pp collisions at root s=13 Tev

Peer reviewe

Relative Modification of Prompt psi(2S) and J/psi Yields from pp to PbPb Collisions at root(S)(NN)=5.02 TeV

Peer reviewe