Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by extensive inflammation in the central nervous system (CNS) and disruption of the blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the BBB disruption are not known. Here, using a mouse model of intravenous JEV infection, we show that virus titers increased exponentially in the brain from 2 to 5 days postinfection. This was accompanied by an early, dramatic increase in the level of inflammatory cytokines and chemokines in the brain. Enhancement of BBB permeability, however, was not observed until day 4, suggesting that viral entry and the onset of inflammation in the CNS occurred prior to BBB damage. In vitro studies revealed that direct infection with JEV could not induce changes in the permeability of brain microvascular endothelial cell monolayers. However, brain extracts derived from symptomatic JEV-infected mice, but not from mock-infected mice, induced significant permeability of the endothelial monolayer. Consistent with a role for inflammatory mediators in BBB disruption, the administration of gamma interferon-neutralizing antibody ameliorated the enhancement of BBB permeability in JEV-infected mice. Taken together, our data suggest that JEV enters the CNS, propagates in neurons, and induces the production of inflammatory cytokines and chemokines, which result in the disruption of the BBB. IMPORTANCEJapanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in which approximately 20 to 30% of cases are fatal, and a high proportion of patients survive with serious neurological and psychiatric sequelae. Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB dysfunction; however, the mechanism is not clear. Thus, understanding the mechanisms of BBB disruption in JEV infection is important. Our data demonstrate that JEV gains entry into the CNS prior to BBB disruption. Furthermore, it is not JEV infection per se, but the inflammatory cytokines/ chemokines induced by JEV infection that inhibit the expression of TJ proteins and ultimately result in the enhancement of BBB permeability. Neutralization of gamma interferon (IFN-␥) ameliorated the enhancement of BBB permeability in JEV-infected mice, suggesting that IFN-␥ could be a potential therapeutic target. This study would lead to identification of potential therapeutic avenues for the treatment of JEV infection. J apanese encephalitis (JE) is an acute zoonotic, mosquito-borne infectious disease caused by JE virus (JEV) infection. JEV is a single-stranded, positive-sense RNA virus, belonging to the genus Flavivirus of the family Flaviviridae (1, 2). JEV is a neurotropic virus and infection causes an acute encephalopathy. JE commonly affects children in the South Pacific regions of Asia (3, 4). Of nearly 70,000 cases of JE reported each year, ca. 20 to 30% of cases are fatal, and a high proport...

In a strongly-coupled quark-gluon plasma, collective excitations of gluons and quarks should dominate over the excitation of individual quasi-free gluon and quark modes. To explore this possibility, we computed screening masses for ground-state light-quark mesons and baryons at leading-order in a symmetry-preserving truncation scheme for the Dyson-Schwinger equations using a confining formulation of a contact-interaction at nonzero temperature. Meson screening masses are obtained from Bethe-Salpeter equations; and baryon analogues from a novel construction of the Faddeev equation, which employs an improved quark-exchange approximation in the kernel. Our treatment implements a deconfinement transition that is coincident with chiral symmetry restoration in the chiral limit, when both transitions are second order. Despite deconfinement, in all T = 0 bound-state channels, strong correlations persist above the critical temperature, T > Tc; and, in the spectrum defined by the associated screening masses, degeneracy between parity-partner correlations is apparent for T 1.3 Tc. Notwithstanding these results, there are reasons (including Golberger-Treiman relations) to suppose that the inertial masses of light-quark bound-states, when they may be defined, vanish at the deconfinement temperature; and that this is a signal of bound-state dissolution. Where a sensible comparison is possible, our predictions are consistent with results from contemporary numerical simulations of lattice-regularised QCD.

No abstract

The impact of nutritional status on survival among elderly esophageal squamous cell carcinoma (ESCC) patients undergoing radiotherapy is unclear. In this study, we aimed at validating the performance of the geriatric nutritional risk index (GNRI) in predicting overall survival time in elderly ESCC patients with radiotherapy. A retrospective cohort study was conducted on 239 ESCC patients aged 60 and over admitted consecutively from January 2008 to November 2014 in the Department of Radiotherapy, Henan Tumor Hospital (Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan, China. All patients were subjected to nutritional screening using GNRI, and were followed for the occurrence of lymphatic node metastasis, radiation complication and mortality. The Kaplan–Meier method with Log-rank test was used to estimate survival curves. Univariable Cox regression analysis was used to identify variables associated with overall survival time. Among the 239 patients, 184 patients (76.9%) took no nutritional risk, 32 patients (13.4%) took moderate risk of malnutrition, and 23 patients (9.7%) took a high risk of malnutrition. Univariable Cox regression showed that both high nutritional risk group and moderate nutritional risk group were significantly less likely to survive than no nutritional risk patients (hazard ratio (HR) = 1.688, 95% confidence interval (CI) = 1.019–2.798 for moderate risk group, and HR = 2.699, 95% CI = 1.512–4.819 for high risk group, respectively). The GNRI is an independent prognostic factor for overall survival time in elderly ESCC patients with radiotherapy. A GNRI ≤98 can be suggested as an indicator of surviving less.

No abstract

No abstract

Resveratrol (RES) is natural polyphenol with a strong biological activity, but its disadvantages, such as poor water solubility, susceptibility to oxidative decomposition and rapid metabolism in the body, which substantially restricts in vivo bioavailability, need to be resolved. This study used carboxymethyl chitosan (CMCS) as a drug carrier and utilized emulsion cross-linking to prepare RES-loaded CMCS nanoparticles (RES-CMCSNPs). A single-factor experiment was performed to optimize the preparation of these particles; in vitro and in vivo characteristics were evaluated. Spherical RES-CMCSNPs were prepared under optimal conditions, in which average particle size, potential, drug loading and encapsulation efficiency were (155.3 ± 15.2) nm, (À10.28 ± 6.4) mV, (5.1 ± 0.8)% and (44.5 ± 2.2)%, respectively. FTIR, DSC and XRD showed that RES molecules were wrapped in the nanoparticles. In vitro DPPH radical scavenging abilities showed RES-CMCSNPs were better than RES raw powder. The nanoparticles improved the solubility of RES, thereby greatly improving the antioxidant activity of the drug. In vitro release experiments of RES and RES-CMCSNPs by simulating the human gastrointestinal tract were performed, in which RES-CMCSNPs rendered better releasing effects than raw RES. Raw RES and RES-CMCSNPs results were in line with those obtained for the single-chamber model for pharmacokinetic studies in rats. Compared with the bulk drugs, the RES-CMCSNPs exhibited increased in vivo absorption, prolonged duration of action and increased relative bioavailability by 3.516 times more than those of the raw RES. In addition, the residual chloroform is less than the ICH limit for class 2 solvents.

No abstract