Hepatitis C virus (HCV) exhibits significant genetic diversity and is a of cause severe liver complications, including liver failure and hepatocellular carcinoma. The envelope glycoproteins E1 and E2 of HCV are the primary targets for the humoral immune response and have the highest sequence diversity in the HCV genome. The humoral immune response to HCV infection may be modulated by host and virus genetic factors. Here, using virus sequencing and host genetic data, as well as antibody binding and neutralization assays from 54 patients infected with HCV subtype 3a virus, we investigated the factors associated with antibody binding and neutralization. Genetic variation in the host IFNL4 gene were associated with antibody binding response, with the IFNλ4-P70 variant associated with reduced binding relative to IFNλ4-Null variant. Testing for association between all variable amino acids in HCV E1 and E2 glycoproteins and antibody response, we discovered two sites in or near the CD81 binding sites in E2 (sites 501 and 533) that were associated with neutralization sensitivity, along with an additional site in E2 (653) that was associated with binding. Additionally, motifs at two glycosylation sites (N476 and N234) were associated with binding and/or neutralisation. Furthermore, an increase in intra-patient hypervariable region 1 (HVR1) diversity was associated with stronger binding response. By considering the complex factors that influence antibody binding and neutralization, future vaccine strategies can be designed to elicit a robust immune response against a diverse range of HCV strains, addressing the needs of a diverse population.
Objective:To study the anti-inflammatory and analgesic effects of Qishen Jiangu Granule.Method: Models of xylene-induced mice ear edema,albumin-induced rats paw edema were performed to study the anti-inflammatory effect.Acetic acid-induced writhing and hot-plate test in mice were used to study the analgeic effect.Result: The inhibitory rates of low,medium and high dose of Qishen Jiangu Granule on mice ear edema were 13%,12%,and 16% respectively.Albumin-induced rat paw edema were significantly suppressed by Qishen Jiangu Granule(the medium dose was the optimum one).The writhing time of mice induced by hot plate and acetic acid-induced writhing were remarkably improved in a dose-dependent manner.(The inhibitory rate of which were 18%,39%,93%,73% and 12%,25%,48%,79%).Conclusion: Qishen Jiangu Granule has obvious anti-inflammatory and pain-relieving effect.
Objective Monospecific autoantibodies to dense fine speckles 70 (DFS70) antigen are purported to aid in excluding systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). However, the non-isolated anti-DFS70 still has a certain prevalence in SLE patients, and the clinical significance remains unclear. We aimed to investigate the prevalence, clinical relevance, and value of long-term monitoring of anti-DFS70 antibodies in SLE patients. Methods Anti-DFS70 antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in 851 SLE patients, 211 healthy individuals, and 194 patients with other SARD (except SLE). Demographic, serological, and clinical associations of anti-DFS70 antibodies were analyzed by a stepwise multivariable logistic regression model. The correlation of anti-DFS70 with anti-dsDNA, anti-C1q, and SLE Disease Activity Index 2000 (SLEDAI-2K) was analyzed. Sixty-one SLE patients with follow-up time ranging from 2 to 57 months were measured anti-DFS70 antibodies using both ELISA and line immunoassay. The dynamic variations of anti-DFS70 antibodies were evaluated with anti-dsDNA, anti-C1q, and SLEDAI-2K during the follow-up. Results The prevalence of anti-DFS70 was significantly higher in SLE (20.7% (176/851)) than in healthy individuals (9.5% (20/211), p = 0.0002) and other SARD (10.8% (21/194), p = 0.002). Multivariable analysis revealed that anti-DFS70-positive SLE patients were associated with younger age (odds ratio (OR) = 0.982; 95% confidence interval (CI) = 0.969, 0.995), higher frequencies of anti-dsDNA (OR 1.598; 95% CI 1.107, 2.306) and anti-PCNA (OR 6.101; 95% CI 2.534, 14.688), and higher levels of serum IgG (OR 1.097; 95% CI 1.067, 1.129) and were more likely to be accompanied by mucosal ulcers (OR 5.921; 95% CI 1.652, 21.215). The O.D. value of anti-DFS70 positively correlated with levels of anti-dsDNA ( r = 0.183, p < 0.0001) and anti-C1q ( r = 0.181, p < 0.0001), respectively, but not with SLEDAI-2K ( p = 0.920). During the follow-up, 49 (42 negative and 7 positive) patients remained stable with anti-DFS70 levels. The other 12 patients experienced significant changes in anti-DFS70, and 83.3% (10/12) of them showed similar trends between anti-DFS70 and anti-dsDNA by evaluation of dynamic variations. Conclusion Anti-DFS70 antibodies seem to be prevalent in Chinese SLE patients. The positive association of anti-DFS70 with anti-dsDNA and consistent dynamic variation between anti-DFS70 and anti-dsDNA during the follow-up suggested a potential relationship between anti-DFS70 and anti-dsDNA in patients with SLE.
literary Suzhou is a brief history of Chinese literature,whose framework,structural characteristics and expressions all follow the moderate principle in writing literary history.The survey in each chapter in this book is clear and concise,and two-thirds of each chapter is devoted to literary works,which reflect the features of taking history as guidance and focusing more on reading so that the reader can benefit much from both the history and the literature simultaneously.This book will offer much enlightenment for writing literary history in the present unrestrained and sloppy literary writing.
The author introduces an intriguing possibility in the article, suggesting the establishment of a theological connection point within the framework of physical ontology to enhance theological legitimacy.However, it is imperative to remind the author to thoroughly understand the self-consistency and limitations of modern scientific physical ontology.Only through a nuanced understanding of this aspect can an appropriate perspective be identified for the intervention of theological ontology, thereby delineating a reasonable space for its incorporation.Engaged in research related to cognitive science of religion, I am aware that the concept of God is often considered a supernatural autonomous entity, and attributes such as omniscience and omnipotence are more akin to subjective experiences of individual believers.Moreover, traces of the origin of this entity and its characteristics can be found in the evolutionary history of the human brain and behavior.Consequently, the plausibility of its existence in a physical sense may be challenged.In other words, the author may need to provide additional evidence from physical, physiological, and anthropological perspectives to bolster the rationale for their position.In my view, this issue is both excessively broad and intricately complex.If the author remains interested in exploring this topic further, it might be worthwhile to contemplate the level of acceptance scientists would have for such a proposition and compare it with the behavioral characteristics attributed to God by religious authorities.Identifying common ground for discussion between the two realms before proposing a possibility could potentially be a fruitful approach.
Prosperous Tang Dynasty manifested its flourishing age not only on its extremely prosperous national power,but on the all-around harmony of society,that is harmony between human and culture,between people and people,between human and nature,which is an outstanding character different from other flourishing ages.And the atmosphere of all-around harmonious society and culture shaped the leisure tone specific in Prosperous Tang Dynasty,which led to poets' leisure state and natural emotion.With the prosperity of the country and beautification of the natural landscape,the specific aesthetics form of scenery poetry in prosperous Tang dynasty gradually came into being and finally the poets' especial language system and poetry peak also formed.
This paper describes the status quo and the predicament of inheriting folktales by quoting the tales dictated by the interviewee,Tan Zhen-shan.Therefore,it studies the development strategies of inheriting folktales in the intangible cultural heritage preservation,which is based on the experiment of dictating stories to the story tellers and constructing the story telling context.In this way,it puts forward the author's suggestions to get rid of the predicament.
Chronic inflammation, oxidative stress, and apoptosis play critical roles in chronic obstructive pulmonary disease (COPD) pathogenesis. Here, we attempted to determine whether aerobic exercise (AE) could improve COPD by counteracting the COPD-associated inflammatory response, oxidative stress, and apoptosis in mice.Thirty male ICR mice were assigned into one of three groups: control (Con), COPD, and COPD + AE. COPD was simulated by intratracheal injection of lipopolysaccharide (LPS) for 4 weeks. Low-intensity AE was performed for 4 weeks. Bronchoalveolar lavage fluid (BALF) cell counts and the levels of inflammatory cytokine in BALF and serum were detected. Hematoxylin and eosin (HE), Masson trichrome, and Sirius Red staining as well as terminal deoxynucleotidyl transferase dUTP nick end labeling were performed to identify the degree of pulmonary emphysema, bronchial mucus cell hyperplasia, pulmonary fibrosis, and cell apoptosis. Oxidative stress parameters were measured. Furthermore, gene expression levels for the CXCL1, IL-1β, IL-10, IL-17, matrix metalloproteinase (MMP)9, TGF-β, TNF-α, and silent information regulator (sirt)1 were detected in mice lung tissues.AE improved LPS-induced emphysema, pulmonary fibrosis, bronchial mucus cell hyperplasia, bronchoconstriction, and cell apoptosis. AE prevented an LPS-induced increase in the total cell, neutrophil, and macrophage counts. AE decreased malondialdehyde (MDA) and myeloperoxidase (MPO) levels but increased glutathione (GSH) and superoxide dismutase (SOD) levels. AE decreased BALF levels of IL-1β, TNF-α, and TGF-β but increased BALF IL-10 levels. AE suppressed the gene expression levels of pro-inflammatory factors CXCL1, IL-1β, IL-17, and TNF-α and profibrotic factors MMP-9 and TGF-β but activated those of anti-inflammatory factor IL-10 and lung-protective factor sirt1.AE is a potential therapeutic approach for COPD. AE improved emphysema, bronchial mucus cell hyperplasia, and pulmonary fibrosis in mice with COPD by alleviating the inflammatory response, oxidative stress injury, and cell apoptosis as well as activating sirt1.
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