Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.

Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre- <i>Pparb/d</i> <sup>-/-</sup> ) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 ( <i>Lrg1</i> ), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of <i>Lrg1</i> by PPARβ/δ in fibroblasts is an important signaling conduit integrating PPARβ/δ and TGFβ1-signaling networks in skin health and disease. Thus, the FSPCre- <i>Pparb/d</i> <sup>-/-</sup> mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis

High Altitude test of RPCs for the ARGO-YBJ experiment

A 50 m**2 RPC carpet was operated at the YangBaJing Cosmic Ray Laboratory (Tibet) located 4300 m a.s.l. The performance of RPCs in detecting Extensive Air Showers was studied. Efficiency and time resolution measurements at the pressure and temperature conditions typical of high mountain laboratories, are reported.Comment: 16 pages, 10 figures, submitted to Nucl. Instr. Met

Partial Wave Analysis of J/ψ→γ(K+K−π+π−)J/\psi \to \gamma (K^+K^-\pi^+\pi^-)

BES data on $J/\psi \to \gamma (K^+K^-\pi^+\pi^-)$ are presented. The $K^*\bar K^*$ contribution peaks strongly near threshold. It is fitted with a broad $0^{-+}$ resonance with mass $M = 1800 \pm 100$ MeV, width $\Gamma = 500 \pm 200$ MeV. A broad $2^{++}$ resonance peaking at 2020 MeV is also required with width $\sim 500$ MeV. There is further evidence for a $2^{-+}$ component peaking at 2.55 GeV. The non-$K^*\bar K^*$ contribution is close to phase space; it peaks at 2.6 GeV and is very different from $K^{*}\bar{K^{*}}$.Comment: 15 pages, 6 figures, 1 table, Submitted to PL

Public mental health problems during COVID-19 pandemic: a large-scale meta-analysis of the evidence

The coronavirus disease 2019 (COVID-19) pandemic has exposed humans to the highest physical and mental risks. Thus, it is becoming a priority to probe the mental health problems experienced during the pandemic in different populations. We performed a meta-analysis to clarify the prevalence of postpandemic mental health problems. Seventy-one published papers (n = 146,139) from China, the United States, Japan, India, and Turkey were eligible to be included in the data pool. These papers reported results for Chinese, Japanese, Italian, American, Turkish, Indian, Spanish, Greek, and Singaporean populations. The results demonstrated a total prevalence of anxiety symptoms of 32.60% (95% confidence interval (CI): 29.10-36.30) during the COVID-19 pandemic. For depression, a prevalence of 27.60% (95% CI: 24.00-31.60) was found. Further, insomnia was found to have a prevalence of 30.30% (95% CI: 24.60-36.60). Of the total study population, 16.70% (95% CI: 8.90-29.20) experienced post-traumatic stress disorder (PTSD) symptoms during the COVID-19 pandemic. Subgroup analysis revealed the highest prevalence of anxiety (63.90%) and depression (55.40%) in confirmed and suspected patients compared with other cohorts. Notably, the prevalence of each symptom in other countries was higher than that in China. Finally, the prevalence of each mental problem differed depending on the measurement tools used. In conclusion, this study revealed the prevalence of mental problems during the COVID-19 pandemic by using a fairly large-scale sample and further clarified that the heterogeneous results for these mental health problems may be due to the nonstandardized use of psychometric tools.Action Contro

An Ionic Molecular Glass as Electron Injection Layer for Efficient Polymer Light-Emitting Diode

An ionic molecular glass based on a dendronized monoammonium salt has been facilely synthesized and utilized as an interfacial electron-injection layer in a light-emitting diode (LED). The characterization of a yellow-green LED that involves an Al cathode and a thin layer of the new compound spin cast from a methanol solution has shown device performances comparable to those obtained with a Ba/Al cathode. Photovoltaic measurements under white light irradiation reveal that a thin layer of the new compound can significantly increase the built-in potential and thus facilitate electron injection from an Al cathode. Furthermore, it is interesting to observe that the new ionic salt could undergo reorganization on the emissive conjugated polymer layer, which leads to the formation of nearly uniform nanoaggregates

Gene Expression Profiling Identifies Two Chordoma Subtypes Associated with Distinct Molecular Mechanisms and Clinical Outcomes

PURPOSE: Chordoma is a rare bone tumor with a high recurrence rate and limited treatment options. The aim of this study was to identify molecular subtypes of chordoma that may improve clinical management. EXPERIMENTAL DESIGN: We conducted RNA sequencing in 48 tumors from patients with Chinese skull-base chordoma and identified two major molecular subtypes. We then replicated the classification using a NanoString panel in 48 patients with chordoma from North America. RESULTS: Tumors in one subtype were more likely to have somatic mutations and reduced expression in chromatin remodeling genes, such as PBRM1 and SETD2, whereas the other subtype was characterized by the upregulation of genes in epithelial-mesenchymal transition and Sonic Hedgehog pathways. IHC staining of top differentially expressed genes between the two subtypes in 312 patients with Chinese chordoma with long-term follow-up data showed that the expression of some markers such as PTCH1 was significantly associated with survival outcomes. CONCLUSIONS: Our findings may improve the understanding of subtype-specific tumorigenesis of chordoma and inform clinical prognostication and targeted options

ARGO-YBJ constraints on very high energy emission from GRBs

The ARGO-YBJ (Astrophysical Radiation Ground-based Observatory at YangBaJing) experiment is designed for very high energy $\gamma$-astronomy and cosmic ray researches. Due to the full coverage of a large area ($5600 m^2$) with resistive plate chambers at a very high altitude (4300 m a.s.l.), the ARGO-YBJ detector is used to search for transient phenomena, such as Gamma-ray bursts (GRBs). Because the ARGO-YBJ detector has a large field of view ($\sim$2 sr) and is operated with a high duty cycle ($>$90%), it is well suited for GRB surveying and can be operated in searches for high energy GRBs following alarms set by satellite-borne observations at lower energies. In this paper, the sensitivity of the ARGO-YBJ detector for GRB detection is estimated. Upper limits to fluence with 99% confidence level for 26 GRBs inside the field of view from June 2006 to January 2009 are set in the two energy ranges 10$-$100 GeV and 10 GeV$-$1 TeV.Comment: accepted for publication in Astroparticle Physic

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits — The Hispanic/Latino Anthropometry Consortium

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification

Galaxy Clusters Associated with Short GRBs. II. Predictions for the Rate of Short GRBs in Field and Cluster Early-Type Galaxies

We determine the relative rates of short GRBs in cluster and field early-type galaxies as a function of the age probability distribution of their progenitors, P(\tau) \propto \tau^n. This analysis takes advantage of the difference in the growth of stellar mass in clusters and in the field, which arises from the combined effects of the galaxy stellar mass function, the early-type fraction, and the dependence of star formation history on mass and environment. This approach complements the use of the early- to late-type host galaxy ratio, with the added benefit that the star formation histories of early-type galaxies are simpler than those of late-type galaxies, and any systematic differences between progenitors in early- and late-type galaxies are removed. We find that the ratio varies from R(cluster)/R(field) ~ 0.5 for n = -2 to ~ 3 for n = 2. Current observations indicate a ratio of about 2, corresponding to n ~ 0 - 1. This is similar to the value inferred from the ratio of short GRBs in early- and late-type hosts, but it differs from the value of n ~ -1 for NS binaries in the Milky Way. We stress that this general approach can be easily modified with improved knowledge of the effects of environment and mass on the build-up of stellar mass, as well as the effect of globular clusters on the short GRB rate. It can also be used to assess the age distribution of Type Ia supernova progenitors.Comment: ApJ accepted versio