Roles of circulating soluble interleukin (IL)-6 receptor and IL-6 receptor expression on CD4+ T cells in patients with chronic hepatitis B

SummaryObjectivesThe objective of this study was to investigate the potential clinical roles of circulating soluble interleukin (IL)-6 receptor (sIL-6R) and IL-6R expression on CD4+ T cells (CD4+ IL-6R+ T cells) in chronic hepatitis B (CHB) patients.MethodsOne hundred and thirty-three subjects, including 72 CHB patients, 27 asymptomatic carriers, eight acute hepatitis B (AHB) patients, and 26 healthy donors were included in this study. Plasma IL-6 and sIL-6R levels were measured by enzyme-linked immunosorbent assay (ELISA); the frequency of CD4+ IL-6R+ T cells was detected by flow cytometry analysis.ResultsOur data showed a significant increase in plasma sIL-6R levels and the frequency of CD4+ IL-6R+ T cells in peripheral blood in CHB patients compared to asymptomatic carriers and healthy controls (both p<0.05). The elevated prevalence of CD4+ IL-6R+ T cells was positively associated with increased serum alanine aminotransferase levels in CHB patients (r = 0.316, p = 0.007), but was not correlated with serum hepatitis B virus (HBV) DNA load. Moreover, CHB patients with an HBV DNA load >1.0×106 copies/ml had a lower level of plasma sIL-6R than those with an HBV DNA load <1.0×106 copies/ml.ConclusionsCirculating sIL-6R and CD4+ IL-6R+ T cells were increased in CHB patients. Elevated plasma sIL-6R is probably associated with HBV elimination, and CD4+ IL-6R+ T cells in peripheral blood might contribute to the pathogenesis of liver injury in CHB patients

NLH: A Blind Pixel-level Non-local Method for Real-world Image Denoising

Non-local self similarity (NSS) is a powerful prior of natural images for image denoising. Most of existing denoising methods employ similar patches, which is a patch-level NSS prior. In this paper, we take one step forward by introducing a pixel-level NSS prior, i.e., searching similar pixels across a non-local region. This is motivated by the fact that finding closely similar pixels is more feasible than similar patches in natural images, which can be used to enhance image denoising performance. With the introduced pixel-level NSS prior, we propose an accurate noise level estimation method, and then develop a blind image denoising method based on the lifting Haar transform and Wiener filtering techniques. Experiments on benchmark datasets demonstrate that, the proposed method achieves much better performance than previous non-deep methods, and is still competitive with existing state-of-the-art deep learning based methods on real-world image denoising. The code is publicly available at https://github.com/njusthyk1972/NLH.Comment: 14 pages, 9 figures, 10 tables, accept by IEEE TI

Brain anomaly networks uncover heterogeneous functional reorganization patterns after stroke

Stroke has a large physical, psychological, and financial burden on patients, their families, and society. Based on functional networks (FNs) constructed from resting state fMRI data, network connectivity after stroke is commonly conjectured to be more randomly reconfigured. We find that this hypothesis depends on the severity of stroke. Head movement-corrected, resting-state fMRI data were acquired from 32 patients after stroke, and 37 healthy volunteers. We constructed anomaly FNs, which combine time series information of a patient with the healthy control group. We propose data-driven techniques to automatically identify regions of interest that are stroke relevant. Graph analysis based on anomaly FNs suggests consistently that strong connections in healthy controls are broken down specifically and characteristically for brain areas that are related to sensorimotor functions and frontoparietal control systems, but new links in stroke patients are rebuilt randomly from all possible areas. Entropic measures of complexity are proposed for characterizing the functional connectivity reorganization patterns, which are correlated with hand and wrist function assessments of stroke patients and show high potential for clinical use

Elevated IL-6 Receptor Expression on CD4+ T Cells contributes to the increased Th17 Responses in patients with Chronic Hepatitis B

<p>Abstract</p> <p>Background</p> <p>Increased numbers of Interleukin-17-producing CD4⁺T cells (Th17) have been found in association with hepatitis B virus (HBV)-induced liver injury. However, the mechanism underlying the increase of Th17 responses in patients with HBV infection remains unclear. In this study, we investigate the possible regulatory mechanisms of increased Th17 responses in patients with chronic hepatitis B(CHB).</p> <p>Methods</p> <p>Th17 response and IL-6R expression on CD4⁺T cells in peripheral blood samples were determined by flow cytometry. Cytokines TGF-β, IL-1β, IL-6 and IL-17 in plasma and/or supernatant samples were determined by ELISA and the IL-17 and IL-6R mRNA levels were quantified by quantitative real-time reverse polymerase chain reaction.</p> <p>Results</p> <p>All these data indicated that the frequency of periphery Th17 cells is significantly correlated with the percentage of CD4<b>⁺</b>T cells expressing IL-6R in CHB patients. CD4⁺T cells from patients with CHB, but not those from healthy donors, produced higher levels of IL-17 and had more IL-6R expression upon stimulation with the HBV core antigen (HBcAg) in vitro. The PMA/ionomycin and HBcAg -stimulated up-regulation of IL-17 production by CD4⁺T cells could be reversed by a neutralizing antibody against IL-6R.</p> <p>Conclusion</p> <p>we showed that enhancement of IL-6R expression on CD4⁺T cells upon HBV infection contributes to increased Th17 response in patients with CHB.</p

MicroRNA-483 amelioration of experimental pulmonary hypertension.

Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA-seq and bioinformatics analyses showed that miR-483 targets several PAH-related genes, including transforming growth factor-β (TGF-β), TGF-β receptor 2 (TGFBR2), β-catenin, connective tissue growth factor (CTGF), interleukin-1β (IL-1β), and endothelin-1 (ET-1). Overexpression of miR-483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1. In contrast, inhibition of miR-483 increased these genes in ECs. Rats with EC-specific miR-483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR-483. These results indicate that PAH is associated with a reduced level of miR-483 and that miR-483 might reduce experimental PH by inhibition of multiple adverse responses

Diversity analysis of agronomic and nutritional traits of hybrid offspring of forage bermudagrass

Because of its excellent stress resistance and forage quality, the forage bermudagrass hybrid population had attracted the attention of scientific researchers in recent years. Studying its diversity could promote the breeding of desirable varieties. The variability in agronomic traits including fresh weight, dry weight, ash content, crude protein content, crude fat, phosphorus content, and relative feed value for 56 bermudagrass was investigated using Wrangler as an experimental reference. Grey correlation analysis and cluster analysis were employed to screen bermudagrass with high yield and superior quality. WCF-34 had the highest 2-year fresh weight (109,773.3 kg/ha), WCF-37 had the highest 2-year dry weight (31,951.6 kg/ha), WCF-24 had the lowest Ash content (7.46%), WCF-26 had the highest crude protein content (16.27%), WCF-27 had the highest curde fat content (3.58%), WCF-13 had the highest P content (0.45%), and WCF-42 had the highest relative feed value (95.32). Combining the results of grey relational analysis and cluster analysis, WCF-42, WCF-34, WCF-38, WCF-37, and WCF-40 were selected as high-quality bermudagrass. Through comprehensive analysis of the agronomic characters of bermudagrass, five bermudagrass were selected, the outcomes of this study would provide a theoretical basis for the breeding and genetic enhancement of bermudagrass

AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1

AIDA最早是由林圣彩教授团队首先鉴定和命名的。2007年林圣彩教授团队与孟安明院士团队合作发现AIDA在斑马鱼体轴发育中的功能(Rui, 2007)。2018年，林圣彩教授团队首次发现了AIDA在哺乳动物中的功能，即AIDA介导的内质网降解途径通过降解脂肪合成途径中的关键酶，而限制膳食脂肪在肠道的吸收这一内在抵御肥胖(Luo, 2018)。而本次成果揭示了AIDA在棕色脂肪组织中特定的功能。这些工作将AIDA引入了脂质应激代谢的重要环节，包括脂质吸收和依赖于脂质的产热过程。该论文的共同第一作者为生命科学学院博士生史猛和硕士生黄晓羽，林圣彩教授和林舒勇教授则为共同通讯作者。【Abstract】The sympathetic nervous system–catecholamine–uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1.Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice.The PKA–AIDA–UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.We thank Y. Li, E. Gnaiger, T. Kuwaki, J. R. B. Lighton, E. T. Chouchani and D. Jiang for technical instruction; X. Li and X.-D. Jiang (Core Facility of Biomedical, Xiamen University) for raising the p-S161-AIDA antibody; the Xiamen University Laboratory Animal Center for the mouse in vitro fertilization service and all the other members of S.C.L. laboratory for their technical assistance. This work was supported by grants from the National Key Research and Development Project of China (grant no. 2016YFA0502001) and the National Natural Science Foundation of China (grant nos 31822027, 31871168, 31690101, 91854208 and 82088102), the Fundamental Research Funds for the Central Universities (grant nos 20720190084 and 20720200069), Project ‘111’ sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (grant no. BP2018017), the Youth Innovation Fund of Xiamen (grant no. 3502Z20206028), the Natural Science Foundation of Fujian Province of China (grant no. 2017J01364) and XMU Training Program of Innovation and Entrepreneurship for Undergraduates (grant no. 2019×0666). 该工作得到了厦门大学实验动物中心和生物医学学部仪器平台的重要协助和国家重点研究和发展项目，国家自然科学基金，厦门大学校长基金等的支持