Gene Transfer of Calcitonin Gene-Related Peptide Inhibits Macrophages and Inflammatory Mediators in Vein Graft Disease

Vein graft disease is a chronic inflammatory disease and limits the late results of coronary revascularization. Calcitonin gene-related peptide (CGRP) inhibits macrophages infiltrated and inflammatory mediators, we hypothesized that transfected CGRP gene inhibits macrophages infiltrated and inflammatory mediators in vein graft disease. Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of mosaic adeno-associated virus vectors containing CGRP gene (AAV2/1.CGRP) 、escherichia coli lac Z gene (AAV2/1.LacZ) or saline and then interposed in the carotid artery. Intima/media ratio were evaluated at postoperative 4 weeks, Macrophages were marked with CD68 antibody by immunocytochemistry. Inflammatory mediators were mensurated with real-time PCR. Neointimal thickening was significantly suppressed in AAV2/1.CGRP group. Macrophages infiltrated and inflammatory mediators monocyte chemoattractant protein-1 (MCP-1)、tumor necrosis factorα(TNF-α)、inducible nitricoxide synthase (iNOS)、matrix metalloproteinase-9 (MMP-9) was significantly suppressed in AAV2/1.CGRP group.Gene transfected AAV2/1.CGRP suppressed neointimal hyperplasia in vein graft disease by suppressed macrophages infiltrated and inflammatory mediators

Distinguishing s±s^{\pm} and s++s^{++} electron pairing symmetries by neutron spin resonance in superconducting NaFe0.935_{0.935}Co0.045_{0.045}As

A determination of the superconducting (SC) electron pairing symmetry forms the basis for establishing a microscopic mechansim for superconductivity. For iron pnictide superconductors, the $s^\pm$-pairing symmetry theory predicts the presence of a sharp neutron spin resonance at an energy below the sum of hole and electron SC gap energies ($E\leq 2\Delta$) below $T_c$. On the other hand, the $s^{++}$-pairing symmetry expects a broad spin excitation enhancement at an energy above $2\Delta$ below $T_c$. Although the resonance has been observed in iron pnictide superconductors at an energy below $2\Delta$ consistent with the $s^\pm$-pairing symmetry, the mode has also be interpreted as arising from the $s^{++}$-pairing symmetry with $E\ge 2\Delta$ due to its broad energy width and the large uncertainty in determining the SC gaps. Here we use inelastic neutron scattering to reveal a sharp resonance at E=7 meV in SC NaFe$_{0.935}$Co$_{0.045}$As ($T_c = 18$ K). On warming towards $T_c$, the mode energy hardly softens while its energy width increases rapidly. By comparing with calculated spin-excitations spectra within the $s^{\pm}$ and $s^{++}$-pairing symmetries, we conclude that the ground-state resonance in NaFe$_{0.935}$Co$_{0.045}$As is only consistent with the $s^{\pm}$-pairing, and is inconsistent with the $s^{++}$-pairing symmetry.Comment: 9 pages, 8 figures. submitted to PR

Characterizing Spatiotemporal Dynamics of Methane Emissions from Rice Paddies in Northeast China from 1990 to 2010

BACKGROUND: Rice paddies have been identified as major methane (CH(4)) source induced by human activities. As a major rice production region in Northern China, the rice paddies in the Three-Rivers Plain (TRP) have experienced large changes in spatial distribution over the recent 20 years (from 1990 to 2010). Consequently, accurate estimation and characterization of spatiotemporal patterns of CH₄ emissions from rice paddies has become an pressing issue for assessing the environmental impacts of agroecosystems, and further making GHG mitigation strategies at regional or global levels. METHODOLOGY/PRINCIPAL FINDINGS: Integrating remote sensing mapping with a process-based biogeochemistry model, Denitrification and Decomposition (DNDC), was utilized to quantify the regional CH(4) emissions from the entire rice paddies in study region. Based on site validation and sensitivity tests, geographic information system (GIS) databases with the spatially differentiated input information were constructed to drive DNDC upscaling for its regional simulations. Results showed that (1) The large change in total methane emission that occurred in 2000 and 2010 compared to 1990 is distributed to the explosive growth in amounts of rice planted; (2) the spatial variations in CH₄ fluxes in this study are mainly attributed to the most sensitive factor soil properties, i.e., soil clay fraction and soil organic carbon (SOC) content, and (3) the warming climate could enhance CH₄ emission in the cool paddies. CONCLUSIONS/SIGNIFICANCE: The study concluded that the introduction of remote sensing analysis into the DNDC upscaling has a great capability in timely quantifying the methane emissions from cool paddies with fast land use and cover changes. And also, it confirmed that the northern wetland agroecosystems made great contributions to global greenhouse gas inventory

Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

Background: Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings: Male balb/c mice were assigned randomly to either sham burn (control) or 30 % total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression

Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model

BackgroundThe prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients’ leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients.MethodsPatients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model.ResultsThere are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts.ConclusionsThe CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management

Accessibility of Healthcare Resources to Public Housing in Shenzhen, China: Indirect Map Service and Optimized Two-Step Floating Catchment Area Method

In China, the equal accessibility of social infrastructure, especially public housing and healthcare, has become a prominent concern in solving the problems of rapid but uneven growth-oriented urbanization in the post-reform era. However, few studies have focused on the accessibility of various healthcare resources to different types of public housing using different transport modes. Utilizing Internet map services, this study first calculated the travel time from talent, economically affordable, and public rental housing to hospitals using three transport modes—walking, public transport, and driving—in Shenzhen, China. Subsequently, the optimized two-step floating catchment area method (2SFCA) was employed to comprehensively evaluate the accessibility of healthcare resources to public housing and explore differences in healthcare accessibility among different populations. The results reveal that: (1) Public housing is located far away from healthcare resources, with 15% of public housing unable to access AAA hospitals within 30 minutes by car, and only 10% able to access ordinary hospitals within 15 minutes. (2) Accessibility of healthcare resources to public housing exhibits spatial heterogeneity, gradually declining from special to non-special economic zones. (3) Talent housing experiences the best accessibility, followed by affordable and public rental housing. (4) Public transportation and walking exhibit greater spatial variation in accessibility than driving. Theoretically, the current public housing accessibility in Shenzhen reflects the common problems of public housing accessibility throughout the country. In the process of promoting the equal accessibility of basic public services, focus on its accessibility should be emphasized. This study proposes an optimized 2SFCA by introducing a Gaussian distance decay function, establishing a multilevel search radius, considering supply and demand-side competition effects, and using real-time traffic big data. Our methodological framework simultaneously considers differences among various types of public housing, hospitals with different service capacities, and diverse travel modes. This provides a new research perspective for a comprehensive and thorough understanding of the equal accessibility of basic public services