IL28B is associated with outcomes of chronic HBV infection

Purpose The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. Materials and Methods IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. Results Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p&#60;0.01; cirrhosis vs. controls, p&#60;0.01; HCC vs. controls, p&#60;0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p&#60;0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p&#60;0.001). Conclusion Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.</p

Research Progress on Essential Oils from Lauraceae Plants

There are various species of plants in the Lauraceae family, and these plants are widely distributed in China. Their essential oils have many biological activities, such as bacteriostatic, antioxidant and insect repellent activities and are ideal natural preservatives, effective antioxidants, and green insect repellents. Therefore, they are of research significance and have broad application prospects. The effects of the growth cycle, plant parts, extraction methods, and geographical environment on the major components of essential oils from Lauraceae plants (LEO) are reviewed with a focus on the antimicrobial, antioxidant and insect repellent activities and mechanisms of LEO. In addition, common edible coatings, microencapsulation, and nano-emulsion technologies based on LEO for food packaging and preservation are summarized. We hope that this review will provide a theoretical basis for the application of LEO in food preservation

High Frequency of CD4+CXCR5+ TFH Cells in Patients with Immune-Active Chronic Hepatitis B

BACKGROUND: T follicular helper (TFH) cells are a special subpopulation of T helper cells and can regulate humoral immune responses. This study examined whether the frequency of CD4(+)CXCR5(+) TFH cells could be associated with active immunity in chronic hepatitis B (CHB) patients. METHODOLOGY AND FINDINGS: The frequencies of peripheral blood CD4(+)CXCR5(+) TFH cells, inducible T cell costimulator (ICOS), and/or programmed death 1 (PD-1) positive CD4(+)CXCR5(+) TFH cells in immune-active (IA), immune-tolerant (IT) CHB, and healthy controls (HC) were characterized by flow cytometry analysis. The effect of adevofir dipivoxil treatment on the frequency of CD4(+)CXCR5(+) TFH cells, the concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-21, ALT, AST, HBsAg, HBsAb, HBeAg, HBeAb and HBV loads in IA patients were determined. The potential association of the frequency of CD4(+)CXCR5(+) TFH cells with clinical measures was analyzed. In addition, the frequency of splenic and liver CD4(+)CXCR5(+) TFH cells in HBV-transgenic mice was examined. We found that the frequency of CD4(+)CXCR5(+) TFH cells in IA patients was significantly higher than that of IT patients and HC, and the percentages of CD4(+)CXCR5(+) TFH in IA patients were positively correlated with AST. Furthermore, the percentages of ICOS(+), PD-1(+), and ICOS(+)PD-1(+) in CD4(+)CXCR5(+) TFH cells in CHB patients were significantly higher than that of HC. Treatment with adefovir dipivoxil reduced the frequency of CD4(+)CXCR5(+) TFH, PD-1(+)CD4(+)CXCR5(+) TFH cells and the concentrations of HBsAg and HBeAg, but increased the concentrations of HBsAb, HBeAb, IL-2 and IFN-γ in IA patients. Moreover, the frequency of splenic and liver CD4(+)CXCR5(+) TFH cells in HBV-transgenic mice was higher than that of wild-type controls. CONCLUSIONS: These data indicate that CD4(+)CXCR5(+) TFH cells may participate in the HBV-related immune responses and that high frequency of CD4(+)CXCR5(+) TFH cells may be a biomarker for the evaluation of active immune stage of CHB patients

IL28B Genetic Variation Is Associated with Spontaneous Clearance of Hepatitis C Virus, Treatment Response, Serum IL-28B Levels in Chinese Population

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The interleukin-28B gene (IL28B) locus has been associated with host resistance to hepatitis C virus (HCV) infection and response to PEG-IFN/RBV treatment in western populations. This study was to determine whether this gene variant is also associated with spontaneous clearance of HCV infection, treatment response and IL-28B protein production in Chinese patients.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We genotyped IL28B genetic variations (rs12980275, rs8103142, rs8099917 and rs12979860) by pyrosequencing DNA samples from cohorts consisting of 529 subjects with persistent HCV infection, 196 subjects who cleared the infection, 171 healthy individuals and 235 chronic HCV patients underwent IFN/RBV treatment. The expression of IL-28B were measured by ELISA and RT-PCR.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; We found that the four IL28B variants were in complete linkage disequilibrium (r2 = 0.97–0.98). The rs12979860 CC genotype was strongly associated with spontaneously HCV clearance and successful IFN/RBV treatment compared to the CT/TT. IL-28B levels in persistent HCV patients were significantly lower than subjects who spontaneously resolved HCV and healthy controls and were also associated with high levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase). IL-28B levels were also significantly lower in individuals carrying T alleles than CC homozygous.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Thus, the rs12979860-CC variant upstream of IL28B gene is associated with spontaneous clearance of HCV, susceptible to IFN/RBV treatment and increased IL-28B levels in this Chinese population.&lt;/p&gt

Ultralight Polymer-Derived Ceramic Aerogels With Wide Bandwidth And Effective Electromagnetic Absorption Properties

In this work, ultralight polymer-derived ceramic aerogels (PDCA) were prepared by a facile method of hydrosilylation crosslink and freeze drying. The electromagnetic absorption properties of ultralight PDCA were investigated for the first time. The PDCA pyrolyzed at 1000 °C shows a uniform three-dimensional (3D) framework with a low bulk density of ∼0.19 g/cm3 and high surface area of 134.48 m2/g. The electromagnetic properties of PDCA were characterized by a vector network analyzer. The minimum reflection and absorption bandwidth of PDCA pyrolyzed at 1000 °C, 1200 °C and 1400 °C are −43.37 dB @ 7.6 GHz, −42.01 [email protected] GHz, and −31.69 [email protected] GHz and 3.8 GHz, 6.6 GHz and 4.2 GHz, respectively, at the frequency range of 2–18 GHz. The strong electromagnetic absorption and wide bandwidth features of PDCA could be attributed to the multiple reflections of microwaves in the 3D framework, as well as the high dielectric loss and proper conductivity

Robust Graph Meta-Learning via Manifold Calibration with Proxy Subgraphs

Graph meta-learning has become a preferable paradigm for graph-based node classification with long-tail distribution, owing to its capability of capturing the intrinsic manifold of support and query nodes. Despite the remarkable success, graph meta-learning suffers from severe performance degradation when training on graph data with structural noise. In this work, we observe that the structural noise may impair the smoothness of the intrinsic manifold supporting the support and query nodes, leading to the poor transferable priori of the meta-learner. To address the issue, we propose a new approach for graph meta-learning that is robust against structural noise, called Proxy subgraph-based Manifold Calibration method (Pro-MC). Concretely, a subgraph generator is designed to generate proxy subgraphs that can calibrate the smoothness of the manifold. The proxy subgraph compromises two types of subgraphs with two biases, thus preventing the manifold from being rugged and straightforward. By doing so, our proposed meta-learner can obtain generalizable and transferable prior knowledge. In addition, we provide a theoretical analysis to illustrate the effectiveness of Pro-MC. Experimental results have demonstrated that our approach can achieve state-of-the-art performance under various structural noises

A spatially defined human Notch receptor interaction network reveals Notch intracellular storage and Ataxin-2-mediated fast recycling

Summary: The Notch signaling pathway controls cell growth, differentiation, and fate decisions. Dysregulation of Notch signaling has been linked to various human diseases. Notch receptor resides in multiple cellular compartments, and its translocation plays a central role in pathway activation. However, the spatial regulation of Notch receptor functions remains largely elusive. Using TurboID-based proximity labeling followed by affinity purification and mass spectrometry, we establish a spatially defined human Notch receptor interaction network. Notch receptors interact with different proteins in distinct subcellular compartments to perform specific cellular functions. This spatially defined interaction network also reveals that a large fraction of NOTCH is stored at the endoplasmic reticulum (ER)-Golgi intermediate compartment and recruits Ataxin-2-dependent recycling machinery for rapid recycling, Notch signaling activation, and leukemogenesis. Our work provides insights into dynamic Notch receptor complexes with exquisite spatial resolution, which will help in elucidating the detailed regulation of Notch receptors and highlight potential therapeutic targets for Notch-related pathogenesis

An analysis of abnormalities in the B cell receptor repertoire in patients with systemic sclerosis using high-throughput sequencing

Systemic sclerosis is a chronic multisystem autoimmune disease that is associated with polyclonal B cell hyperreactivity. The CDR3 of BCRs is the major site of antigen recognition. Therefore, we analyzed the BCR repertoire of patients with SSc. The BCR repertoires in 12 subjects including eight SSc patients and four healthy controls were characterized by high-throughput sequencing, and bioinformatics analysis were studied. The average CDR3 length in the SSc group was significantly shorter. The SSc patient displayed more diverse BCR. Moreover, SSc patients with mild skin sclerosis, anti-Scl70, interstitial lung disease or female sex were more diversified. B cells from the SSc patients showed a differential V and J gene usage. SSc patients had distinct BCR repertoires.These findings reflected the differences of BCR repertoires between SSc patients and controls. The higher-usage genes for the BCR sequence might be potential biomarkers of B cell-targeted therapies or diagnosis for SSc