C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3.

The rapidly emerging human health crisis associated with the Zika virus (ZIKV) epidemic and its link to severe complications highlights the growing need to identify the mechanisms by which ZIKV accesses hosts. Interferon response protects host cells against viral infection, while the cellular factors that mediate this defense are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified, only a few have been characterized for their antiviral potential, target specificity and mechanisms of action.

Long-chain fatty acyl-coenzyme A suppresses hepatitis C virus infection by targeting virion-bound lipoproteins.

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and end-stage liver diseases. Mature HCV virions are bound by host-derived lipoproteins. Lack of an HCV vaccine warrants a major role of antiviral treatment in the global elimination of hepatitis C.

Stem-like tumor cells involved in heterogeneous vasculogenesis in breast cancer.

Sorafenib, a small-molecule tyrosine kinase inhibitor with antiangiogenic activity, has been used in liver cancer and kidney cancer treatments. However, clinical trials with sorafenib for breast cancer were stopped in phase III due to limited efficacy. The existence of heterogeneous vasculatures involving tumor cells, such as vessel-like structures formed by vasculogenic mimicry and mosaic vessels, and their resistance to antiangiogenic therapy are thought to be a possible reason for failure of sorafenib therapy.

Differential regulatory network-based quantification and prioritization of key genes underlying cancer drug resistance based on time-course RNA-seq data.

Drug resistance is a major cause for the failure of cancer chemotherapy or targeted therapy. However, the molecular regulatory mechanisms controlling the dynamic evolvement of drug resistance remain poorly understood. Thus, it is important to develop methods for identifying key gene regulatory mechanisms of the resistance to specific drugs.

Identification of a Novel Betacoronavirus () in Amur Hedgehogs from China.

While dromedaries are the immediate animal source of Middle East Respiratory Syndrome (MERS) epidemic, viruses related to MERS coronavirus (MERS-CoV) have also been found in bats as well as hedgehogs. To elucidate the evolution of MERS-CoV-related viruses and their interspecies transmission pathway, samples were collected from different mammals in China. A novel coronavirus related to MERS-CoV, hedgehog coronavirus HKU31 (-HedCoV HKU31), was identified from two Amur hedgehogs.

Active Ingredients and Action Mechanisms of Yi Guan Jian Decoction in Chronic Hepatitis B Patients with Liver Fibrosis.

Background And Aim: The progression of liver fibrosis in chronic hepatitis B (CHB) patients is currently insufficiently controlled worldwide. The Yi Guan Jian decoction (YGJD) has been widely used in the treatment of liver fibrosis in CHB cases. Although animal studies have reported the antifibrotic effects of the decoction, the active ingredients of the YGJD remain unknown.

Viruses and Oxidative Stress: Implications for Viral Pathogenesis.

Oxidative stress is induced once the balance of generation and neutralization of reactive oxygen species (ROS) is broken in the cell, and it plays crucial roles in a variety of natural and diseased processes. Infections of viruses trigger oxidative stress, which affects both the cellular metabolism and the life cycle of the viruses. Oxidative stress associated with specific viral proteins, experimental culture systems, and patient infections, as well as its correlations with the viral pathogenesis attracts much research attention.

Single-cell transcriptome-based multilayer network biomarker for predicting prognosis and therapeutic response of gliomas.

Occurrence and development of cancers are governed by complex networks of interacting intercellular and intracellular signals. The technology of single-cell RNA sequencing (scRNA-seq) provides an unprecedented opportunity for dissecting the interplay between the cancer cells and the associated microenvironment. Here we combined scRNA-seq data with clinical bulk gene expression data to develop a computational pipeline for identifying the prognostic and predictive signature that connects cancer cells and microenvironmental cells.

Combined alignments of sequences and domains characterize unknown proteins with remotely related protein search PSISearch2D.

Iterative homology search has been widely used in identification of remotely related proteins. Our previous study has found that the query-seeded sequence iterative search can reduce homologous over-extension errors and greatly improve selectivity. However, iterative homology search remains challenging in protein functional prediction.

Risk assessment and genomic characterization of Zika virus in China and its surrounding areas.

Background: Zika virus (ZIKV) has emerged as a global pathogen causing significant public health concerns. China has reported several imported cases where ZIKV were carried by travelers who frequently travel between China and ZIKV-endemic regions. To fully characterize the ZIKV strains isolated from the cases reported in China and assess the risk of ZIKV transmission in China, comprehensive phylogenetic and genetic analyses were performed both on all ZIKV sequences of China and on a group of scientifically selected ZIKV sequences reported in some of the top interested destinations for Chinese travelers.

Elevated Serum IgG Levels Positively Correlated with IL-27 May Indicate Poor Outcome in Patients with HBV-Related Acute-On-Chronic Liver Failure.

Background And Aims: Serum immunoglobulins are frequently increased in patients with chronic liver disease, but little is known about the role of serum immunoglobulins and their correlations with interleukin-27 (IL-27) in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). This study was aimed at determining the role of serum immunoglobulin (IgG, IgA, and IgM) levels and their associations with IL-27 in noncirrhotic patients with HBV-ACLF.

Methods: Samples were assessed from thirty patients with HBV-ACLF, twenty-four chronic hepatitis B (CHB) subjects, and eighteen normal controls.

Multiscale modeling reveals angiogenesis-induced drug resistance in brain tumors and predicts a synergistic drug combination targeting EGFR and VEGFR pathways.

Background: Experimental studies have demonstrated that both the extracellular vasculature or microenvironment and intracellular molecular network (e.g., epidermal growth factor receptor (EGFR) signaling pathway) are important for brain tumor growth.

Development of an ORF45-Derived Peptide To Inhibit the Sustained RSK Activation and Lytic Replication of Kaposi's Sarcoma-Associated Herpesvirus.

The lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV) requires sustained extracellular signal-regulated kinase (ERK)-p90 ribosomal S6 kinase (RSK) activation, which is induced by an immediate early (IE) gene-encoded tegument protein called ORF45, to promote the late transcription and translation of viral lytic genes. An ORF45-null or single-point F66A mutation in ORF45 abolishes ORF45-RSK interaction and sustained ERK-RSK activation during lytic reactivation and subsequently results in a significant decrease in late lytic gene expression and virion production, indicating that ORF45-mediated RSK activation plays a critical role in KSHV lytic replication. Here, we demonstrate that a short ORF45-derived peptide in the RSK-binding region is sufficient for disrupting ORF45-RSK interaction, consequently suppressing lytic gene expression and virion production.

Clonorchiasis sinensis detected by laparoscopic exploration of biliary tracts in two patients with obstructive jaundice.

Background: Hepatic clonorchiasis is one of the most prevalent food-borne parasitic diseases worldwide. Clonorchis sinensis, the pathogen, is the major parasitic trigger contributing to cholangitis, cholelithiasis, and even cholangiocarcinoma. Unfortunately, unspecific clinical manifestations of patients with hepatic clonorchiasis tend to mislead clinicians to neglect or misdiagnose them, following ignorance of appropriate therapy.

Spiramycin and azithromycin, safe for administration to children, exert antiviral activity against enterovirus A71 in vitro and in vivo.

Hand-foot-mouth disease (HFMD) is a common viral disease in young children, mainly caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Specific antiviral agents are not commercially available yet. Here we report that the macrolide antibiotics spiramycin (SPM) and azithromycin (AZM) possess antiviral activities against EV-A71 and CV-A16.

LncRNA DUXAP9-206 directly binds with Cbl-b to augment EGFR signaling and promotes non-small cell lung cancer progression.

Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumours, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of their specific association with NSCLC have not been fully elucidated. Here, we report that a cytoplasmic lncRNA, DUXAP9-206 is overexpressed in NSCLC cells and closely related to NSCLC clinical features and poor patient survival.

Increased CCR7PD-1CXCR5CD4 T Cells in Peripheral Blood Mononuclear Cells Are Correlated with Immune Activation in Patients with Chronic HBV Infection.

T follicular helper cells (Tfh cells) affect essential immune pathogenesis in chronic hepatitis B virus (HBV) infection. The CCR7PD-1 Tfh subset has a partial Tfh effector phenotype and is associated with active Tfh differentiation, whereas the CCR7PD-1 Tfh subset is a resting phenotype. We recruited 20 healthy volunteers and 77 patients with chronic HBV infection, including those in the immune tolerant (IT) phase (n=19), immune clearance (IC) phase (n=20), low replicative (LR) phase (n=18), and reactivation (RA) phase (n=20).

Th17 cells over 5.9% at admission indicate poor prognosis in patients with HBV-related acute-on-chronic liver failure.

Our previous study demonstrated that Th17 cells increased significantly in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). However, their prognostic role in HBV-ACLF patients remains unknown.Sixty-eight consecutive HBV-ACLF patients were enrolled in this cohort study.

MYEOV functions as an amplified competing endogenous RNA in promoting metastasis by activating TGF-β pathway in NSCLC.

Non-small cell lung cancer (NSCLC) remains a major cause of death worldwide. As metastatic disease is primarily responsible for the poor clinical outcome of NSCLC, it is important to understand the process, and its underlying molecular mechanism as well, via which NSCLC cells disseminate. In this study, we identified a new competing endogenous RNA (ceRNA), namely, the MYEOV transcript, and found that it is upregulated in NSCLC and associated with a poor prognosis of the disease.

EGF-induced nuclear localization of SHCBP1 activates β-catenin signaling and promotes cancer progression.

Aberrant activation of EGFR represents a common event in non-small cell lung carcinoma (NSCLC) and activates various downstream signaling pathways. While EGFR activation of β-catenin signaling was previously reported, the mediating mechanism remains unclear. Our current study found that EGFR activation in NSCLC cells releases SHC-binging protein 1 (SHCBP1) from SHC adaptor protein 1 (SHC1), which subsequently translocates into the nucleus and directly promotes the transactivating activity of β-catenin, consequently resulting in development of NSCLC cell stemness and malignant progression.

Correction: Deficiency of pigment epithelium-derived factor in nasopharyngeal carcinoma cells triggers the epithelial-mesenchymal transition and metastasis.

The PDF and HTML versions of the article have been updated to include the Creative Commons Attribution 4.0 International License information.Correction to: Cell Death Dis.

Increased IL-27/IL-27R expression in association with the immunopathology of murine ocular toxoplasmosis.

Interleukin 27 (IL-27) is a member of the IL-6/IL-12 family, and IL-27 receptor (IL-27R) consists of WSX-1 (the IL-27Rα subunit) and the signal-transducing subunit gp130. Human and mouse mast cells (MCs) express the IL-27R. To explore the expressions of IL-27/IL-27R subunits (WSX-1 and gp130) during acute ocular toxoplasmosis (OT), we established mouse model by intraocular injection of 500 Toxoplasma gondii RH strain tachyzoites.