Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility

Small molecule inhibitors of osteoarthritis: Current development and future perspective

Osteoarthritis (OA) is one of the common degenerative joint diseases in clinic. It mainly damages articular cartilage, causing pain, swelling and stiffness around joints, and is the main cause of disability of the elderly. Due to the unclear pathogenesis of osteoarthritis and the poor self-healing ability of articular cartilage, the treatment options for this disease are limited. At present, NSAIDs, Glucocorticoid and Duloxetine are the most commonly used treatment choice for osteoarthritis. Although it is somewhat effective, the adverse reactions are frequent and serious. The development of safer and more effective anti-osteoarthritis drugs is essential and urgent. This review summarizes recent advances in the pharmacological treatment of OA, focusing on small molecule inhibitors targeting cartilage remodeling in osteoarthritis as well as the research idea of reducing adverse effects by optimizing the dosage form of traditional drugs for the treatment of osteoarthritis. It should provide a reference for exploration of new potential treatment options

Measurement Invariance of the Depression Anxiety Stress Scales-21 Across Gender in a Sample of Chinese University Students

The Depression Anxiety Stress Scales-21 (DASS-21) has three 7-item subscales (depression, anxiety, and stress). The current study aims assess the gender-based measurement invariance of the DASS-21 questionnaire in a Chinese university student sample from five different cities. The sample was composed of 13208 participants (62.3% female, mean age of 19.7 years, and SD age = 1.8). Multi-group confirmatory factor analysis supported full measurement invariance for the three subscales. The findings support the measurement invariance of DASS-21 scores across gender. Future research on the DASS should include additional validation across ethnicities and testing of all versions of the DASS

An Updated Search of Steady TeV γ−\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV $\gamma-$ray point sources has now been updated by a factor of 2.8 improved statistics. From $0.0^{\circ}$ to $60.0^{\circ}$ in declination (Dec) range, no new TeV $\gamma-$ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV $\gamma-$ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration

Background: non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion. Results: we performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the colorectal cancer patients' overall survival. Conclusions: the primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of biomarkers and therapeutic targets that are primate-specific

Amplitude analysis and branching fraction measurement of the decay \boldmath Ds+→K+π+π−π0D_{s}^{+} \to K^+\pi^{+}\pi^{-}\pi^{0}

The singly Cabibbo-suppressed decay $D_{s}^{+} \to K^+\pi^{+}\pi^{-}\pi^{0}$ is observed, using a data set corresponding to an integrated luminosity of 6.32 $\rm fb^{-1}$ recorded by the BESIII detector at the centre-of-mass energies between 4.178 and 4.226 GeV. The first amplitude analysis of $D_{s}^{+} \to K^+\pi^{+}\pi^{-}\pi^{0}$ reveals the sub-structures in this decay and determines the fractions and relative phases of different intermediate processes. The dominant intermediate process is $D_s^+ \to K^{*0}\rho^+$, with a fit fraction of $(40.5\pm2.8_{\rm{stat.}}\pm1.5_{\rm{syst.}})\%$. With the detection efficiency based on our amplitude analysis, the absolute branching fraction for $D_{s}^{+} \to K^+\pi^{+}\pi^{-}\pi^{0}$ is measured to be $(9.75\pm0.54_{\rm{stat.}}\pm0.17_{\rm{syst.}})\times 10^{-3}$

Observation of the Y(4230)Y(4230) and evidence for a new vector charmonium-like state Y(4710)Y(4710) in e+e−→KS0KS0J/ψe^{+}e^{-}\to K_{S}^{0} K_{S}^{0} J/\psi

Cross sections for the process $e^{+} e^{-} \to K_{S}^{0} K_{S}^{0} J/\psi$ at center-of-mass energies from $4.128$ to $4.950$ GeV are measured using data samples with a total integrated luminosity of 21.2 fb$^{-1}$ collected by the BESIII detector operating at the BEPCII storage ring. The $Y(4230)$ state is observed in the energy dependence of the $e^{+} e^{-} \to K_{S}^{0} K_{S}^{0} J/\psi$ cross section for the first time with a statistical significance of 26.0$\sigma$. In addition, an enhancement around $4.710$ GeV, called the $Y(4710)$, is seen with a statistical significance of 4.2$\sigma$. There is no clear structure around $4.484$ GeV. Using a fit with a coherent sum of three Breit-Wigner functions, we determine the mass and width of the $Y(4230)$ state to be $4226.9 \pm 6.6 \pm 21.9$ MeV/$c^{2}$ and $71.7 \pm 16.2 \pm 31.4$ MeV, respectively, and the mass and width of the $Y(4710)$ state to be $4704.0 \pm 52.3 \pm 69.5$ MeV/$c^{2}$ and $183.2 \pm 114.0 \pm 90.8$ MeV, respectively, where the first uncertainties are statistical and the second are systematic. In addition, the average Born cross section ratio of $e^{+} e^{-} \to K_{S}^{0} K_{S}^{0} J/\psi$ to $e^{+} e^{-} \to K^{+} K^{-} J/\psi$ is measured to be $0.388_{-0.028}^{+0.035}\pm0.016$, or $0.426_{-0.031}^{+0.038}\pm0.018$ if three-body phase space is considered.Comment: Update draft based the comments from PRD refere

Precise Measurements of Decay Parameters and CPCP Asymmetry with Entangled Λ−Λˉ\Lambda-\bar{\Lambda} Pairs

Based on 10 billion $J/\psi$ events collected at the BESIII experiment, a search for $CP$ violation in $\Lambda$ decay is performed in the difference between $CP$-odd decay parameters $\alpha_{-}$ for $\Lambda \rightarrow p\pi^-$ and $\alpha_{+}$ for $\bar\Lambda \rightarrow \bar{p}\pi^+$ by using the process $e^+e^- \to J/\psi \rightarrow \Lambda \bar\Lambda$. With a five-dimensional fit to the full angular distributions of the daughter baryon, the most precise values for the decay parameters are determined to be $\alpha_{-} = 0.7519 \pm 0.0036 \pm 0.0024$ and $\alpha_{+} = -0.7559 \pm 0.0036 \pm 0.0030$, respectively. The $\Lambda$ and $\bar{\Lambda}$ averaged value of the decay parameter is extracted to be $\alpha_{\rm{avg}} = 0.7542 \pm 0.0010 \pm 0.0024$ with unprecedented accuracy. The $CP$ asymmetry $A_{CP}=(\alpha_{-}+\alpha_{+})/(\alpha_{-}-\alpha_{+})$ is determined to be $-0.0025 \pm 0.0046 \pm 0.0012$, which is one of the most precise measurements in the baryon sector. The reported results for the decay parameter will play an important role in the studies of the polarizations and $CP$ violations for the strange, charmed and beauty baryons