Delayed peak of human infections and ongoing reassortment of H7N9 avian influenza virus in the newly affected western Chinese provinces during Wave Five.

Objectives: Eight additional provinces in western China reported human infections for the first time during the fifth wave of human H7N9 infections. The aim of this study was to analyze the epidemiological and virological characteristics of this outbreak.

Methods: The epidemiological data of H7N9 cases from the newly affected western Chinese provinces were collected and analyzed.

Comparison between human infections caused by highly and low pathogenic H7N9 avian influenza viruses in Wave Five: Clinical and virological findings.

Objective: The newly emerged highly pathogenic (HP) H7N9 avian influenza virus during Wave Five has caused 28 human infections, while differences in disease severity between low pathogenic (LP)- and HP-H7N9 human infections remain unclear.

Methods: Clinical data, concentrations of serum cytokines, dynamics of virus shedding and PaO/FiO from patients infected with LP-H7N9 (n = 7, LP group) and HP-H7N9 (n = 5, HP group) viruses during Wave Five were compared. In addition, critical mutations associated with H7N9 virulence in mammal/human were analyzed.

Clinical and Immunological Characteristics of Human Infections With H5N6 Avian Influenza Virus.

Background: H5N6 avian influenza virus (AIV) has caused sporadic, recurring outbreaks in China and Southeast Asia since 2013, with 19 human infections and 13 deaths. Seventeen of these infections occurred since December 2015, indicating a recent rise in the frequency of H5N6 cases.

Methods: To assess the relative threat of H5N6 virus to humans, we summarized and compared clinical data from patients infected with H5N6 (n = 19) against data from 2 subtypes of major public health concern, H5N1 (n = 53) and H7N9 (n = 160).

Development of a quadruple qRT-PCR assay for simultaneous identification of highly and low pathogenic H7N9 avian influenza viruses and characterization against oseltamivir resistance.

Background: During the fifth wave of human H7N9 infections, a novel highly pathogenic (HP) H7N9 variant emerged with an insertion of multiple basic amino acids in the HA cleavage site. Moreover, a neuraminidase inhibitor (NAI) resistance (R292K in NA) mutation was found in H7N9 isolates from humans, poultry and the environment. In this study, we set out to develop and validate a multiplex quantitative reverse transcript polymerase chain reaction (qRT-PCR) to simultaneously detect the presence of H7N9 and further identify the HP and NAI-resistance mutations.

Identification and functional analysis of heterogeneous FOXP3 Treg cell subpopulations in human pancreatic ductal adenocarcinoma.

CD4 CD25 regulatory T (Treg) cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity. Abundant Treg cell accumulation in tumors and tumor draining lymph nodes (TDLNs) has been reported to correlate with both poor and favorable prognosis in various cancers, which suggests that Tregs may have multiple effects on antitumor immunity. However, the heterogeneity of tumor- and TDLN-infiltrating Treg cells remains unclear.

DNMT1 cooperates with MBD4 to inhibit the expression of Glucocorticoid-induced TNFR-related protein in human T cells.

Glucocorticoid-induced TNFR-related protein (GITR) is constitutively expressed in T regulatory (Treg) cells and regulates their suppressive function. We identified two methylated CpG islands in the Gitr locus. Using a ChIP assay, we demonstrate that both DNMT1 and methyl-CpG-binding domain Protein 4 (MBD4) bind to the Gitr promoter.

USP4 interacts and positively regulates IRF8 function via K48-linked deubiquitination in regulatory T cells.

CD4 CD25 regulatory T (Treg) cells comprise a unique subset of T cells required for maintaining immune homeostasis. However, the molecular mechanisms associated with the functional variety of Treg cells are not fully delineated. In the present study, we demonstrate that ubiquitin-specific protease (USP)4 physically interacted with interferon regulatory factor 8 (IRF8) function via a K48-linked deubiquitinase, which stabilized IRF8 protein levels in Treg cells.

Novel avian influenza A (H5N6) viruses isolated in migratory waterfowl before the first human case reported in China, 2014.

In May 2014, China formally confirmed the first human infection with the novel H5N6 avian influenza virus (AIV) in Sichuan Province. Before the first human case was reported, surveillance of AIVs in wild birds resulted in the detection of three H5N6 viruses in faecal samples from migratory waterfowl in Chenhu wetlands, Hubei Province, China. Genetic and phylogenetic analyses revealed that these three novel viruses were closely related to the H5N6 virus that has caused human infections in China since 2014.

IL-17A Exacerbates Fibrosis by Promoting the Proinflammatory and Profibrotic Function of Orbital Fibroblasts in TAO.

Context: The development of thyroid-associated ophthalmopathy (TAO) is associated with self-immune dysfunction. Recent findings in TAO and Graves' disease indicate that IL-17A may also be involved in the autoimmunity of TAO.

Objective: We sought to investigate the pathogenic function of IL-17A-producing T cells in TAO.

Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses.

Human coronaviruses (HCoVs) were first described in the 1960s for patients with the common cold. Since then, more HCoVs have been discovered, including those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two pathogens that, upon infection, can cause fatal respiratory disease in humans. It was recently discovered that dromedary camels in Saudi Arabia harbor three different HCoV species, including a dominant MERS HCoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015.