Downregulation of the AU-Rich RNA-Binding Protein ZFP36 in Chronic HBV Patients: Implications for Anti-Inflammatory Therapy

Inflammation caused by chronic hepatitis B virus (HBV) infection is associated with the development of cirrhosis and hepatocellular carcinoma; however, the mechanisms by which HBV infection induces inflammation and inflammatory cytokine production remain largely unknown. We analyzed the gene expression patterns of lymphocytes from chronic HBV-infected patients and found that the expression of ZFP36, an AU-rich element (ARE)-binding protein, was dramatically reduced in CD4+ and CD8+ T lymphocytes from chronic HBV patients. ZFP36 expression was also reduced in CD14+ monocytes and in total PBMCs from chronic HBV patients. To investigate the functional consequences of reduced ZFP36 expression, we knocked down ZFP36 in PBMCs from healthy donors using siRNA. siRNA-mediated silencing of ZFP36 resulted in dramatically increased expression of multiple inflammatory cytokines, most of which were also increased in the plasma of chronic HBV patients. Furthermore, we found that IL-8 and RANTES induced ZFP36 downregulation, and this effect was mediated through protein kinase C. Importantly, we found that HBsAg stimulated PBMCs to express IL-8 and RANTES, resulting in decreased ZFP36 expression. Our results suggest that an inflammatory feedback loop involving HBsAg, ZFP36, and inflammatory cytokines may play a critical role in the pathogenesis of chronic HBV and further indicate that ZFP36 may be an important target for anti-inflammatory therapy during chronic HBV infection

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Diversification of Genes Encoding Granule-Bound Starch Synthase in Monocots and Dicots Is Marked by Multiple Genome-Wide Duplication Events

Starch is one of the major components of cereals, tubers, and fruits. Genes encoding granule-bound starch synthase (GBSS), which is responsible for amylose synthesis, have been extensively studied in cereals but little is known about them in fruits. Due to their low copy gene number, GBSS genes have been used to study plant phylogenetic and evolutionary relationships. In this study, GBSS genes have been isolated and characterized in three fruit trees, including apple, peach, and orange. Moreover, a comprehensive evolutionary study of GBSS genes has also been conducted between both monocots and eudicots. Results have revealed that genomic structures of GBSS genes in plants are conserved, suggesting they all have evolved from a common ancestor. In addition, the GBSS gene in an ancestral angiosperm must have undergone genome duplication ∼251 million years ago (MYA) to generate two families, GBSSI and GBSSII. Both GBSSI and GBSSII are found in monocots; however, GBSSI is absent in eudicots. The ancestral GBSSII must have undergone further divergence when monocots and eudicots split ∼165 MYA. This is consistent with expression profiles of GBSS genes, wherein these profiles are more similar to those of GBSSII in eudicots than to those of GBSSI genes in monocots. In dicots, GBSSII must have undergone further divergence when rosids and asterids split from each other ∼126 MYA. Taken together, these findings suggest that it is GBSSII rather than GBSSI of monocots that have orthologous relationships with GBSS genes of eudicots. Moreover, diversification of GBSS genes is mainly associated with genome-wide duplication events throughout the evolutionary course of history of monocots and eudicots

First Observation of a Three-Resonance Structure in e+e−→e^+e^-\rightarrow{non-open} Charm Hadrons

We report the measurement of the cross sections for $e^+e^-$$\rightarrow${nOCH} (nOCH stands for non-open charm hadrons) with improved precision at center-of-mass energies from 3.645 to 3.871 GeV. We observe for the first time a three-resonance structure in the energy-dependent lineshape of the cross sections, which are $\mathcal R(3760)$, $\mathcal R(3780)$ and $\mathcal R(3810)$ with significances of $9.4\sigma$, $15.7\sigma$, and $9.8\sigma$, respectively. The $\mathcal R(3810)$ is observed for the first time. We found two solutions in analysis of the cross sections. For solution I [solution II], we measure the mass, the total width and the product of electronic width and nOCH decay branching fraction to be $(3805.8 \pm 1.1 \pm 2.7)$ [$(3805.8 \pm 1.1 \pm 2.7)$] MeV/$c^2$, $(11.6 \pm 2.6 \pm 1.9)$ [$(11.5 \pm 2.5 \pm 1.8)$] MeV, and $(10.8\pm 3.2\pm 2.3)$ [$(11.0\pm 2.9\pm 2.4)$] eV for the $\mathcal R(3810)$, respectively. In addition, we measure the branching fractions ${\mathcal B}({\mathcal R}(3760)$$\rightarrow${nOCH}$)=(24.5 \pm 13.4 \pm 27.4)\% [(6.8 \pm 5.4 \pm 7.6)\%]$ for the first time, and ${\mathcal B}(\mathcal R(3780)$$\rightarrow${nOCH}$)=(11.6 \pm 5.8 \pm 7.8)\% [(10.3 \pm 4.5 \pm 6.9)\%]$. Moreover, we determine the open-charm (OC) branching fraction ${\mathcal B}({\mathcal R}$$(3760)\rightarrow${OC}$)=(75.5 \pm 13.4 \pm 27.4)\% [(93.2 \pm 5.4 \pm 7.6)\%]$, which supports the interpretation of $\mathcal R(3760)$ as an OC pair molecular state, but contained a simple four-quark state component. The first uncertainties are from fits to the cross sections, and the second are systematic

Search for an invisible muon philic scalar X0X_{0} or vector X1X_{1} via J/ψ→μ+μ−+invisibleJ/\psi\to\mu^+\mu^-+\rm{invisible} decay at BESIII

A light scalar $X_{0}$ or vector $X_{1}$ particles have been introduced as a possible explanation for the $(g-2)_{\mu}$ anomaly and dark matter phenomena. Using $(8.998\pm 0.039)\times10^9$ \jpsi events collected by the BESIII detector, we search for a light muon philic scalar $X_{0}$ or vector $X_{1}$ in the processes $J/\psi\to\mu^+\mu^- X_{0,1}$ with $X_{0,1}$ invisible decays. No obvious signal is found, and the upper limits on the coupling $g_{0,1}'$ between the muon and the $X_{0,1}$ particles are set to be between $1.1\times10^{-3}$ and $1.0\times10^{-2}$ for the $X_{0,1}$ mass in the range of $1<M(X_{0,1})<1000$~MeV$/c^2$ at 90$\%$ confidence level.Comment: 9 pages 7 figure

Study of e+e−→π+π−π0e^{+}e^{-}\rightarrow\pi^{+}\pi^{-}\pi^{0} at s\sqrt{s} from 2.00 to 3.08 GeV at BESIII

With the data samples taken at center-of-mass energies from 2.00 to 3.08 GeV with the BESIII detector at the BEPCII collider, a partial wave analysis on the $e^{+}e^{-}\rightarrow\pi^{+}\pi^{-}\pi^{0}$ process is performed. The Born cross sections for $e^{+}e^{-}\rightarrow\pi^{+}\pi^{-}\pi^{0}$ and its intermediate processes $e^{+}e^{-}\rightarrow\rho\pi$ and $\rho(1450)\pi$ are measured as functions of $\sqrt{s}$. The results for $e^{+}e^{-}\rightarrow\pi^{+}\pi^{-}\pi^{0}$ are consistent with previous results measured with the initial state radiation method within one standard deviation, and improve the uncertainty by a factor of ten. By fitting the line shapes of the Born cross sections for the $e^{+}e^{-}\rightarrow\rho\pi$ and $\rho(1450)\pi$, a structure with mass $M = 2119\pm11\pm15\ {\rm MeV}/c^2$ and width $\Gamma=69\pm30\pm5 {\rm MeV}$ is observed with a significance of $5.9\sigma$, where the first uncertainties are statistical and the second ones are systematic. This structure can be intepreteted as an excited $\omega$ state