Serum HBsAg and HBcrAg is associated with inflammation in HBeAg-positive chronic hepatitis B patients

Backgrounds & aimsLiver inflammation is the main risk factor for developing liver fibrosis, cirrhosis, and even hepatocellular carcinoma in chronic hepatitis B (CHB) patients. To replace biopsy, additional non-invasive biomarkers to diagnose and grade liver necroinflammation are urgently required in clinical practice.MethodNinety-four CHB patients, including 74 HBeAg-positive and 20 HBeAg-negative patients, were enrolled and started entecavir or adefovir therapy. Serum HBV RNA, HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), ALT and AST levels, as well as intrahepatic HBV DNA and cccDNA were measured at baseline and during treatment. Liver inflammation was assessed at baseline and month 60 by liver biopsy. Inflammation regression was defined as a ≥1-grade decrease according to the Scheuer scoring system.ResultsIn HBeAg-positive CHB patients, at baseline, serum HBsAg and HBcrAg levels negatively correlated with inflammation grade, while ALT and AST levels positively correlated with inflammation grade. AST plus HBsAg exhibited excellent diagnostic ability for significant inflammation with an AUROC of 0.896. After 60 months of antiviral treatment, almost all the patients’ liver inflammation ameliorated to G1, and no patients had inflammation progression.ConclusionBesides ALT and AST, serum HBsAg and HBcrAg correlated with inflammation grade in HBeAg-positive CHB patients before NAs treatment. Moreover, the combination of HBsAg and AST exhibited excellent diagnostic ability for significant inflammation

Neonatal rhesus monkey is a potential animal model for studying pathogenesis of EV71 infection

AbstractData from limited autopsies of human patients demonstrate that pathological changes in EV71-infected fatal cases are principally characterized by clear inflammatory lesions in different parts of the CNS; nearly identical changes were found in murine, cynomolgus and rhesus monkey studies which provide evidence of using animal models to investigate the mechanisms of EV71 pathogenesis. Our work uses neonatal rhesus monkeys to investigate a possible model of EV71 pathogenesis and concludes that this model could be applied to provide objective indicators which include clinical manifestations, virus dynamic distribution and pathological changes for observation and evaluation in interpreting the complete process of EV71 infection. This induced systemic infection and other collected indicators in neonatal monkeys could be repeated; the transmission appears to involve infecting new monkeys by contact with feces of infected animals. All data presented suggest that the neonatal rhesus monkey model could shed light on EV71 infection process and pathogenesis

Dual modification of Alzheimer’s disease PHF-tau protein by lysine methylation and ubiquitylation: a mass spectrometry approach

In sporadic Alzheimer’s disease (AD), neurofibrillary lesion formation is preceded by extensive post-translational modification of the microtubule associated protein tau. To identify the modification signature associated with tau lesion formation at single amino acid resolution, immunopurified paired helical filaments were isolated from AD brain and subjected to nanoflow liquid chromatography–tandem mass spectrometry analysis. The resulting spectra identified monomethylation of lysine residues as a new tau modification. The methyl-lysine was distributed among seven residues located in the projection and microtubule binding repeat regions of tau protein, with one site, K254, being a substrate for a competing lysine modification, ubiquitylation. To characterize methyl lysine content in intact tissue, hippocampal sections prepared from post mortem late-stage AD cases were subjected to double-label confocal fluorescence microscopy using anti-tau and anti-methyl lysine antibodies. Anti-methyl lysine immunoreactivity colocalized with 78 ± 13% of neurofibrillary tangles in these specimens. Together these data provide the first evidence that tau in neurofibrillary lesions is post-translationally modified by lysine methylation

Inexact Restoration Methods for Semivectorial Bilevel Programming Problem on Riemannian Manifolds

For a better understanding of the bilevel programming on Riemannian manifolds, a semivectorial bilevel programming scheme is proposed in this paper. The semivectorial bilevel programming is firstly transformed into a single-level programming problem by using the Karush–Kuhn–Tucker (KKT) conditions of the lower-level problem, which is convex and satisfies the Slater constraint qualification. Then, the single-level programming is divided into two stages: restoration and minimization, based on which an Inexact Restoration algorithm is developed. Under certain conditions, the stability and convergence of the algorithm are analyzed

Inexact Restoration Methods for Semivectorial Bilevel Programming Problem on Riemannian Manifolds

For a better understanding of the bilevel programming on Riemannian manifolds, a semivectorial bilevel programming scheme is proposed in this paper. The semivectorial bilevel programming is firstly transformed into a single-level programming problem by using the Karush–Kuhn–Tucker (KKT) conditions of the lower-level problem, which is convex and satisfies the Slater constraint qualification. Then, the single-level programming is divided into two stages: restoration and minimization, based on which an Inexact Restoration algorithm is developed. Under certain conditions, the stability and convergence of the algorithm are analyzed

Point Cloud Registration Algorithm Based on Adaptive Neighborhood Eigenvalue Loading Ratio

Traditional iterative closest point (ICP) registration algorithms are sensitive to initial positions and easily fall into the trap of locally optimal solutions. To address this problem, a point cloud registration algorithm is put forward in this study based on adaptive neighborhood eigenvalue loading ratios. In the algorithm, the resolution of the point cloud is first calculated and used as an adaptive basis to determine the raster widths and radii of spherical neighborhoods in the raster filtering; then, the adaptive raster filtering is implemented to the point cloud for denoising, while the eigenvalue loading ratios of point neighborhoods are calculated to extract and match the contour feature points; subsequently, sample consensus initial alignment (SAC-IA) is used to carry out coarse registration; and finally, a fine registration is delivered with KD-tree-accelerated ICP. The experimental results of this study demonstrate that the feature points extracted with this method are highly representative while consuming only 35.6% of the time consumed by other feature point extraction algorithms. Additionally, in noisy and low-overlap scenarios, the registration error of this method can be controlled at a level of 0.1 mm, with the registration speed improved by 56% on average over that of other algorithms. Taken together, the method in this study cannot only ensure strong robustness in registration but can also deliver high registration accuracy and efficiency

Churn K Effect of Flow Baffles on the Dialysate Flow Distribution of Hollow-Fiber Hemodialyzers: A Nonintrusive Experimental Study Using MRI

We used an innovative, nonintrusive MRI technique called the two-dimensional (2D

IsoQuant: A Software Tool for Stable Isotope Labeling by Amino Acids in Cell Culture-Based Mass Spectrometry Quantitation

Accurate protein identification and quantitation are critical when interpreting the biological relevance of large-scale shotgun proteomics data sets. Although significant technical advances in peptide and protein identification have been made, accurate quantitation of high-throughput data sets remains a key challenge in mass spectrometry data analysis and is a labor intensive process for many proteomics laboratories. Here, we report a new SILAC-based proteomics quantitation software tool, named IsoQuant, which is used to process high mass accuracy mass spectrometry data. IsoQuant offers a convenient quantitation framework to calculate peptide/protein relative abundance ratios. At the same time, it also includes a visualization platform that permits users to validate the quality of SILAC peptide and protein ratios. The program is written in the C# programming language under the Microsoft .NET framework version 4.0 and has been tested to be compatible with both 32-bit and 64-bit Windows 7. It is freely available to noncommercial users at http://www.proteomeumb.org/MZw.html

An Internal Standard-Assisted Synthesis and Degradation Proteomic Approach Reveals the Potential Linkage between VPS4B Depletion and Activation of Fatty Acid β-Oxidation in Breast Cancer Cells

The endosomal/lysosomal system, in particular the endosomal sorting complexes required for transport (ESCRTs), plays an essential role in regulating the trafficking and destination of endocytosed receptors and their associated signaling molecules. Recently, we have shown that dysfunction and down-regulation of vacuolar protein sorting 4B (VPS4B), an ESCRT-III associated protein, under hypoxic conditions can lead to the abnormal accumulation of epidermal growth factor receptor (EGFR) and aberrant EGFR signaling in breast cancer. However, the pathophysiological consequences of VPS4B dysfunction remain largely elusive. In this study, we used an internal standard-assisted synthesis and degradation mass spectrometry (iSDMS) method, which permits the direct measurement of protein synthesis, degradation and protein dynamic expression, to address the effects of VPS4B dysfunction in altering EGF-mediated protein expression. Our initial results indicate that VPS4B down-regulation decreases the expression of many proteins involved in glycolytic pathways, while increased the expression of proteins with roles in mitochondrial fatty acid β-oxidation were up-regulated in VPS4B-depleted cells. This observation is also consistent with our previous finding that hypoxia can induce VPS4B down-regulated, suggesting that the adoption of fatty acid β-oxidation could potentially serve as an alternative energy source and survival mechanism for breast cancer cells in response to hypoxia-mediated VPS4B dysfunction