Summary
Background
Vitiligo is a skin disorder characterized by loss of melanocytes from the epidermis. A recent study reported that CXCL10 is critical for the progression and maintenance of ...depigmentation in a mouse model of vitiligo, but there is very limited clinical data regarding this issue and little is known about the dynamic changes or correlations with disease severity of these chemokines throughout the disease course.
Objectives
To present clinical data that supports and identifies the pathway of CXCR3 and its ligands in T‐lymphocytic cell recruitment in vitiligo.
Methods
Cytometric bead array, flow cytometry, quantitative real‐time polymerase chain reaction and immunohistology were used to examine their systemic and local expression in 80 patients with vitiligo and 40 controls.
Results
We showed that serum CXCL9 and CXCL10 were significantly elevated in patients with vitiligo and were higher in patients in progressive stages than in stable stages. The relative expression of CXCR3 mRNA in peripheral blood mononuclear cells was higher in vitiligo. There were higher percentages of both circulating CXCR3+CD4+ and CXCR3+CD8+ T cells in patients with progressive vitiligo compared with controls, while only the expression of CXCR3+CD8+ T cells increased in patients with stable vitiligo. Histological findings also demonstrated an abundance of CXCR3+ cells within vitiligo lesions. Furthermore, serum CXCL10 levels were associated with Vitiligo Area Scoring Index scores of patients with progressive vitiligo and were reduced after successful treatment.
Conclusions
The CXCL10/CXCR3 axis mediates T‐cell recruitment into the skin in progressive vitiligo. Blocking this chemotactic mechanism may present a new form of therapy. Serum CXCL10 may be a novel biomarker in monitoring disease activity and guiding treatment of progressive vitiligo.
What's already known about this topic?
A T‐cell‐mediated immune response is responsible for melanocyte destruction in vitiligo.
CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo.
What does this study add?
CXCL9 and CXCL10, in parallel with their receptor, CXCR3, are present in patients with vitiligo and correlate with disease activity and severity.
Serum CXCL10 may be a novel biomarker in monitoring disease activity and guiding treatment of progressive vitiligo.
What is the translational message?
Blocking the CXCL10/CXCR3 chemotactic mechanism may present a new form of therapy for progressive vitiligo.
Linked Comment: Rashighi and Harris. Br J Dermatol 2016; 174: 1190–1191.
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•The passive current for amorphous steel increased with temperature distinctly.•Reduction of Cr2O3 in the passive film of amorphous steel was observed.•Direct evidence of the ...heterogeneous passive film on 316 LSS was provided.•The initiation and growth of the pits for the amorphous steel were inhibited.
Temperature dependence of corrosion behaviour in simulated wet storage conditions for spent nuclear fuels were investigated systematically by comparing SAM2X5 amorphous steel and 316 L SS. Results indicated that with elevating temperature, the passive current for the amorphous steel increased distinctly but without pitting corrosion. The sensitivity of the passive current with temperature for the amorphous steel was related to the reduction of Cr2O3 content and altered semiconductor characteristics for its passive film, and the prominent pitting resistance at higher temperatures was associated with the remarkably inhibited pit initiation by the uniform passive film and the suppressed stable growth of metastable pits.
The evolutions of MHD instability behaviors and enhancement of both electrostatic and electromagnetic turbulence towards the plasma disruption have been clearly observed in the HL-2A plasmas. Two ...types of plasma disruptive discharges have been investigated for similar equilibrium parameters: one with a distinct stage of a small central temperature collapse (Formula: see text 5-10%) around 1 millisecond before the thermal quench (TQ), while the other without. For both types, the TQ phase is preceded by a rotating 2/1 tearing mode, and it is the development of the cold bubble from the inner region of the 2/1 island O-point along with its inward convection that causes the massive energy loss. In addition, the micro-scale turbulence, including magnetic fluctuations and density fluctuations, increases before the small collapse, and more significantly towards the TQ. Also, temperature fluctuations measured by electron cyclotron emission imaging enhances dramatically at the reconnection site and expand into the island when approaching the small collapse and TQ, and the expansion is more significant close to the TQ. The observed turbulence enhancement near the X-point cannot be fully interpreted by the linear stability analysis by GENE. Evidences suggest that nonlinear effects, such as the reduction of local Formula: see text shear and turbulence spreading, may play an important role in governing turbulence enhancement and expansion. These results imply that the turbulence and its interaction with the island facilitate the stochasticity of the magnetic flux and formation of the cold bubble, and hence, the plasma disruption.
The magnetoresistance (MR) of a material is typically insensitive to reversing the applied field direction and varies quadratically with magnetic field in the low-field limit. Quantum effects, ...unusual topological band structures, and inhomogeneities that lead to wandering current paths can induce a cross-over from quadratic to linear MR with increasing magnetic field. Here we explore a series of metallic charge- and spin-density-wave systems that exhibit extremely large positive linear MR. By contrast to other linear MR mechanisms, this effect remains robust down to miniscule magnetic fields of tens of Oersted at low temperature. We frame an explanation of this phenomenon in a semiclassical narrative for a broad category of materials with partially gapped Fermi surfaces due to density waves.
The CDEX-1 experiment conducted a search of low-mass (< 10GeV/c super(2)) weakly interacting massive particles dark matter at the China Jinping Underground Laboratory using a p-type point-contact ...germanium detector with a fiducial mass of 915 g at a physics analysis threshold of 475 eVee. We report the hardware setup, detector characterization, data acquisition, and analysis procedures of this experiment. No excess of unidentified events is observed after the subtraction of the known background. Using 335.6 kg-days of data, exclusion constraints on the weakly interacting massive particle-nucleon spin-independent and spin-dependent couplings are derived.
GCMs are used by many national weather services to produce seasonal outlooks of atmospheric and oceanic conditions and fluxes. Postprocessing is often a necessary step before GCM forecasts can be ...applied in practice. Quantile mapping (QM) is rapidly becoming the method of choice by operational agencies to postprocess raw GCM outputs. The authors investigate whether QM is appropriate for this task. Ensemble forecast postprocessing methods should aim to 1) correct bias, 2) ensure forecasts are reliable in ensemble spread, and 3) guarantee forecasts are at least as skillful as climatology, a property called “coherence.” This study evaluates the effectiveness of QM in achieving these aims by applying it to precipitation forecasts from the POAMA model. It is shown that while QM is highly effective in correcting bias, it cannot ensure reliability in forecast ensemble spread or guarantee coherence. This is because QM ignores the correlation between raw ensemble forecasts and observations. When raw forecasts are not significantly positively correlated with observations, QM tends to produce negatively skillful forecasts. Even when there is significant positive correlation, QM cannot ensure reliability and coherence for postprocessed forecasts. Therefore, QM is not a fully satisfactory method for postprocessing forecasts where the issues of bias, reliability, and coherence pre-exist. Alternative postprocessing methods based on ensemble model output statistics (EMOS) are available that achieve not only unbiased but also reliable and coherent forecasts. This is shown with one such alternative, the Bayesian joint probability modeling approach.
HIAF (High Intensity heavy ion Accelerator Facility), a new facility planned in China for heavy ion related researches, consists of two ion sources, a high intensity Heavy Ion Superconducting Linac ...(HISCL), a 45 Tm Accumulation and Booster Ring (ABR-45) and a multifunction storage ring system. The key features of HIAF are unprecedented high pulse beam intensity and versatile operation mode. The HIAF project aims to expand nuclear and related researches into presently unreachable region and give scientists possibilities to conduct cutting-edge researches in these fields. The general description of the facility is given in this article with a focus on the accelerator design.
Summary
Background
Systemic sclerosis (SSc) is a complex autoimmune disease that involves dysregulation of immune homeostasis. The failure of impaired regulatory T cells (Tregs) to maintain immune ...homeostasis plays a major role in the development of SSc. Transcriptional silencing of the forkhead box protein 3 gene (FOXP3) via hypermethylation of regulatory regions has been identified as a hallmark of committed Tregs and several autoimmune disorders.
Objectives
To investigate whether aberrant expression and methylation of FOXP3 occurs in CD4+ T cells of patients with SSc and their roles in the pathogenesis of SSc.
Methods
FOXP3 expression in CD4+ T cells was measured by real‐time quantitative reverse‐itranscriptase polymerase chain reaction and western blot. Bisulfite sequencing was performed to determine the methylation status of the FOXP3 proximal promoter sequence. The percentage of Treg cells was estimated by flow cytometry.
Results
Decreased FOXP3 expression was observed in CD4+ T cells from patients with SSc. The methylation levels of the FOXP3 regulatory sequences were elevated and inversely correlated with FOXP3 mRNA expression in patients with SSc. The number of Tregs was significantly reduced in patients with SSc. Treatment of SSc CD4+ T cells with a DNA methylation inhibitor, 5‐azacytidine, reduced the mean methylation levels, and enhanced FOXP3 expression and Treg generation. The promoter methylation status and expression level of FOXP3 are significantly associated with disease activity.
Conclusions
The contribution of the hypermethylation of the FOXP3 promoter to decreased FOXP3 expression and the subsequent quantitative defects of Tregs may mediate the immune dysfunction in SSc.
What's already known about this topic?
The failure of impaired regulatory T cells (Tregs) to maintain immune homeostasis has been implicated in the pathogenesis of systemic sclerosis (SSc).
Transcription factor forkhead box protein (FOXP)3 is important for the developmental and functional stability of Tregs and plays a role in autoimmune diseases.
FOXP3 expression is decreased in patients with SSc.
What does this study add?
Contribution of the hypermethylation of the FOXP3 promoter to decreased FOXP3 expression and the subsequent quantitative defects of Tregs may mediate the immune dysfunction in SSc.
Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense ...examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.
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