Orthotopic and heterotopic tracheal transplantation model in studying obliterative bronchiolitis

AbstractBackgroundSeveral animal models have been established to investigate the mechanisms of obliterative bronchiolitis after lung transplantation. In this study, we compared three prevalent murine models of obliterative bronchiolitis in terms of several basic pathologic changes in a relatively short span of time after transplantation.MethodsEach of the recipient mice simultaneously received orthotopic, intra-omental and subcutaneous tracheal transplantation in both syngeneic and allogeneic settings. No immunosuppressive treatment was administered. Tracheal grafts were harvested on Day 14, 21 and 28 after transplantation for histological and immunohistochemical analyses.ResultsSyngeneic tracheal grafts from different transplant sites retained normal histologic structures, while their corresponding allografts demonstrated more occlusion of the airway lumen as well as more infiltration of CD4+/CD8+ mononuclear cells and myofibroblasts, but less regenerative epithelium and neovascularized vessels at indicated times (P<0.05). Compared with two heterotopic allografts, orthotopic allografts had less occlusion of the tracheal lumen as well as less infiltration of CD4+/CD8+ mononuclear cells and myofibroblasts, but more regenerative epithelium and neovascularized vessels (P<0.05).ConclusionsOrthotopic tracheal transplantation in mice can be considered as a model to study early stages of obliterative bronchiolitis, and heterotopic tracheal transplantation can be a model for late stages of obliterative bronchiolitis

Observations of aerosol optical properties at a coastal site in Hong Kong, South China

Temporal variations in aerosol optical properties were investigated at a coastal station in Hong Kong based on the field observation from February 2012 to February 2015. At 550 nm, the average light-scattering (151 +/- 100Mm(-1) / and absorption coefficients (8.3 +/- 6.1Mm(-1) / were lower than most of other rural sites in eastern China, while the single-scattering albedo (SSA = 0.93 +/- 0.05) was relatively higher compared with other rural sites in the Pearl River Delta (PRD) region. Correlation analysis confirmed that the darkest aerosols were smaller in particle size and showed strong scattering wavelength dependencies, indicating possible sources from fresh emissions close to the measurement site. Particles with D-p of 200-800 nm were less in number, yet contributed the most to the light-scattering coefficients among submicron particles. In summer, both Delta BC / Delta CO and SO2 / BC peaked, indicating the impact of nearby combustion sources on this site. Multi-year backward Lagrangian particle dispersion modeling (LPDM) and potential source contribution (PSC) analysis revealed that these particles were mainly from the air masses that moved southward over Shenzhen and urban Hong Kong and the polluted marine air containing ship exhausts. These fresh emission sources led to low SSA during summer months. For winter and autumn months, contrarily, Delta BC / Delta CO and SO2 / BC were relatively low, showing that the site was more under influence of well-mixed air masses from long-range transport including from South China, East China coastal regions, and aged aerosol transported over the Pacific Ocean and Taiwan, causing stronger abilities of light extinction and larger variability of aerosol optical properties. Our results showed that ship emissions in the vicinity of Hong Kong could have visible impact on the light-scattering and absorption abilities as well as SSA at Hok Tsui.Peer reviewe

Screening of prognostic biomarkers for endometrial carcinoma based on a ceRNA network

Objective This study aims to reveal the regulation network of lncRNAs-miRNAs-mRNA in endometrial carcinoma (EC), to investigate the underlying mechanisms of EC occurrence and progression, to screen prognostic biomarkers. Methods RNA-seq and miRNA-seq data of endometrial carcinoma were downloaded from the TCGA database. Edge.R package was used to screen differentially expressed genes. A database was searched to determine differentially expressed lncRNA-miRNA and miRNA-mRNA pairs, to construct the topological network of ceRNA, and to elucidate the key RNAs that are for a prognosis of survival. Results We screened out 2632 mRNAs, 1178 lncRNAs and 189 miRNAs that were differentially expressed. The constructed ceRNA network included 97 lncRNAs, 20 miRNAs and 73 mRNAs. Analyzing network genes for associations with prognosies revealed 169 prognosis-associated RNAs, including 92 lncRNAs, 16miRNAs and 61 mRNAs. Conclusion Our results reveal new potential mechanisms underlying the carcinogenesis and progression of endometrial carcinoma

Volatility of mixed atmospheric humic-like substances and ammonium sulfate particles

The volatility of organic aerosols remains poorly understood due to the complexity of speciation and multiphase processes. In this study, we extracted humic-like substances (HULIS) from four atmospheric aerosol samples collected at the SORPES station in Nanjing, eastern China, and investigated the volatility behavior of particles at different sizes using a Volatility Tandem Differential Mobility Analyzer (VTDMA). In spite of the large differences in particle mass concentrations, the extracted HULIS from the four samples all revealed very high-oxidation states (O : C > 0.95), indicating secondary formation as the major source of HULIS in Yangtze River Delta (YRD). An overall low volatility was identified for the extracted HULIS, with the volume fraction remaining (VFR) higher than 55% for all the regenerated HULIS particles at the temperature of 280 degrees C. A kinetic mass transfer model was applied to the thermodenuder (TD) data to interpret the observed evaporation pattern of HULIS, and to derive the mass fractions of semi-volatile (SVOC), low-volatility (LVOC) and extremely low-volatility components (ELVOC). The results showed that LVOC and ELVOC dominated (more than 80 %) the total volume of HULIS. Atomizing processes led to a size-dependent evaporation of regenerated HULIS particles, and resulted in more ELVOC in smaller particles. In order to understand the role of interaction between inorganic salts and atmospheric organic mixtures in the volatility of an organic aerosol, the evaporation of mixed samples of ammonium sulfate (AS) and HULIS was measured. The results showed a significant but nonlinear influence of ammonium sulfate on the volatility of HULIS. The estimated fraction of ELVOC in the organic part of the largest particles (145 nm) increased from 26 %, in pure HULIS samples, to 93% in 1 : 3 (mass ratio of HULIS : AS) mixed samples, to 45% in 2 : 2 mixed samples, and to 70% in 3 : 1 mixed samples, suggesting that the interaction with ammonium sulfate tends to decrease the volatility of atmospheric organic compounds. Our results demonstrate that HULIS are important low-volatility, or even extremely low-volatility, compounds in the organic-aerosol phase. As important formation pathways of atmospheric HULIS, multiphase processes, including oxidation, oligomerization, polymerization and interaction with inorganic salts, are indicated to be important sources of low-volatility and extremely low-volatility species of organic aerosols.Peer reviewe

Rationale and Design of the RESTORE Trial: A Multicenter, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled Trial to Evaluate the Effect of Shenfu Injection on Myocardial Injury in STEMI Patients After Primary PCI

BACKGROUND: The mortality following ST-segment elevation myocardial infarction (STEMI) remains substantial in the reperfusion era. Shenfu injection, as a traditional Chinese herbal formula, can alleviate ischemia-reperfusion injury through multiple pharmacologic effects. However, no robust data are available regarding the role of Shenfu injection in reducing infarct size for patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). METHODS/DESIGN: This RESTORE trial is a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (NCT04493840). A total of 326 eligible patients with first-time anterior STEMI undergoing PPCI within 12 h of symptom onset will be enrolled from 10 centers in mainland China. Patients are randomized in a 1:1 fashion to receive either intravenous Shenfu injection (80mL Shenfu injection + 70mL 5% glucose injection) or placebo group (150mL 5% glucose injection) before reperfusion and followed by once a day until 5 days after PPCI. The primary end point is infarct size assessed by cardiac magnetic resonance (CMR) imaging 5±2 days after PPCI. The major secondary end points include enzymatic infarct size, microvascular obstruction, intramyocardial hemorrhage, left ventricular volume and ejection fraction assessed by CMR, as well as cardiovascular events at 30 days. CONCLUSIONS: The RESTORE trial is sufficiently powered to demonstrate the clinical effects of Shenfu injection on myocardial injury in STEMI patients undergoing PPCI in the contemporary era

Direct Measurements of the Branching Fractions for D0→K−e+νeD^0 \to K^-e^+\nu_e and D0→π−e+νeD^0 \to \pi^-e^+\nu_e and Determinations of the Form Factors f+K(0)f_{+}^{K}(0) and f+π(0)f^{\pi}_{+}(0)

The absolute branching fractions for the decays $D^0 \to K^-e ^+\nu_e$ and $D^0 \to \pi^-e^+\nu_e$ are determined using $7584\pm 198 \pm 341$ singly tagged $\bar D^0$ sample from the data collected around 3.773 GeV with the BES-II detector at the BEPC. In the system recoiling against the singly tagged $\bar D^0$ meson, $104.0\pm 10.9$ events for $D^0 \to K^-e ^+\nu_e$ and $9.0 \pm 3.6$ events for $D^0 \to \pi^-e^+\nu_e$ decays are observed. Those yield the absolute branching fractions to be $BF(D^0 \to K^-e^+\nu_e)=(3.82 \pm 0.40\pm 0.27)$ and $BF(D^0 \to \pi^-e^+\nu_e)=(0.33 \pm 0.13\pm 0.03)$. The vector form factors are determined to be $|f^K_+(0)| = 0.78 \pm 0.04 \pm 0.03$ and $|f^{\pi}_+(0)| = 0.73 \pm 0.14 \pm 0.06$. The ratio of the two form factors is measured to be $|f^{\pi}_+(0)/f^K_+(0)|= 0.93 \pm 0.19 \pm 0.07$.Comment: 6 pages, 5 figure

The σ\sigma pole in J/ψ→ωπ+π−J/\psi \to \omega \pi^+ \pi^-

Using a sample of 58 million $J/\psi$ events recorded in the BESII detector, the decay $J/\psi \to \omega \pi^+ \pi^-$ is studied. There are conspicuous $\omega f_2(1270)$ and $b_1(1235)\pi$ signals. At low $\pi \pi$ mass, a large broad peak due to the $\sigma$ is observed, and its pole position is determined to be $(541 \pm 39)$ - $i$ $(252 \pm 42)$ MeV from the mean of six analyses. The errors are dominated by the systematic errors.Comment: 15 pages, 6 figures, submitted to PL

Liver-heart crosstalk controls IL-22 activity in cardiac protection after myocardial infarction.

Interleukin (IL)-22 regulates tissue inflammation and repair. Here we report participation of the liver in IL-22-mediated cardiac repair after acute myocardial infarction (MI). Methods: We induced experimental MI in mice by ligation of the left ascending artery and evaluated the effect of IL-22 on post-MI cardiac function and ventricular remodeling. Results: Daily subcutaneous injection of 100 µg/kg mouse recombinant IL-22 for seven days attenuated adverse ventricular remodeling and improved cardiac function in mice at 28 days after left anterior descending coronary artery ligation-induced MI. Pharmacological inhibition of signal transducer and activator of transcription (STAT3) muted these IL-22 activities. While cardiomyocyte-selective depletion of STAT3 did not affect IL-22 activities in protecting post-MI cardiac injury, hepatocyte-specific depletion of STAT3 fully muted these IL-22 cardioprotective activities. Hepatocyte-derived fibroblast growth factor (FGF21) was markedly increased in a STAT3-dependent manner following IL-22 administration and accounted for the cardioprotective benefit of IL-22. Microarray analyses revealed that FGF21 controlled the expression of cardiomyocyte genes that are involved in cholesterol homeostasis, DNA repair, peroxisome, oxidative phosphorylation, glycolysis, apoptosis, and steroid responses, all of which are responsible for cardiomyocyte survival. Conclusions: Supplementation of IL-22 in the first week after acute MI effectively prevented left ventricular dysfunction and heart failure. This activity of IL-22 involved crosstalk between the liver and heart after demonstrating a role of the hepatic STAT3-FGF21 axis in IL-22-induced post-MI cardiac protection