Distinct expression of SARS‐CoV‐2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps

Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS‐CoV‐2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS‐CoV‐2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP. Methods The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. Results ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN‐γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN‐γ up‐regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co‐expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. Conclusion These findings indicate that ACE2 expression, regulated by IFN‐γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation

A Review of Fluid-Induced Excitations in Centrifugal Pumps

This paper describes the related research work in the field of fluid-induced vibration of centrifugal pumps conducted by many researchers. In recent years, all walks of life have put forward higher demands for the vibration performance of pumps which drives the investigation on the root cause of pump vibration and the development of guidelines for the design of low-vibration pumps. Fluid-induced excitation is the most important and significant source of pump vibration. Understanding its generation mechanism and dominant characteristics is important for developing low-vibration pump design methodology. This paper starts with the analysis of unsteady flow in the centrifugal pump and summarizes unsteady flow characteristics such as jet–wake structure, secondary flow, and rotational stall in the operating pump. Based on the understanding of the unsteady flow structure in the pump, the fluid-induced excitation mechanism and its characteristics based on the investigation of unsteady pressure pulsation and excitation forces in the pump are summarized. For the pump operating at nominal flow rate, the excitation at blade passing frequency (BPF) dominates and related suppression methods are classified and summarized to provide reference for the design of a low-vibration pump

Asiatic acid improves high-fat-diet-induced osteoporosis in mice via regulating SIRT1/FOXO1 signaling and inhibiting oxidative stress

Asiatic acid can attenuate osteoporosis through suppressing adipogenic differentiation and osteoclastic differentiation. Oxidative stress enhances osteoclastic differentiation but represses osteogenic differentiation to promote osteoporosis. However, the role and mechanism of asiatic acid in osteoporosis have not been reported. Firstly, mice were fed with high-fatdiet (HFD) with or without asiatic acid for 16 weeks. Data from an automatic biochemical analyzer showed that HFD induced down-regulation of high-density lipoprotein (HDL) and an increase of serum levels of triglyceride (TG), total cholesterol (TC) and low-density lipoprotein (LDL). However, asiatic acid administration attenuated the decrease of HDL and increase of serum TG, TC and LDL in osteoporotic mice. Secondly, HFD induced high levels of malondialdehyde (MDA) and reactive oxygen species (ROS), low levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in osteoporotic mice. However, the levels of MDA, ROS, SOD and GSH-Px in osteoporotic mice were reversed by asiatic acid administration. (this section is unclear and requires revision) Asiatic acid administration reduced expression of c-telopeptide of type 1 collagen (CTX-1), enhanced alkaline phosphatase (ALP) and procollagen type 1 N-terminal propeptide (P1NP) in HFD-induced osteoporotic mice. (this section is unclear and requires revision) Thirdly, asiatic acid promoted calcium deposition in bone marrow cells and osteogenic differentiation in osteoporotic mice, but decreased ALP in bone marrow cells. Lastly, asiatic acid enhanced SIRT1 and nuclear FOXO1 (Nu-FOXO1) expression, while it reduced Acetyl FOXO1 (AcFOXO1) in osteoporotic mice. In conclusion, asiatic acid might inhibit oxidative stress and promote osteogenic differentiation through activating SIRT1/FOXO1 to attenuate HFD-induced osteoporosis in mice

Association between component-resolved diagnosis of house dust mite and efficacy of allergen immunotherapy in allergic rhinitis patients

Abstract Data regarding clinical relevance of house dust mite (HDM) components over allergen immunotherapy (AIT) for allergic rhinitis (AR) are lacking. 18 adult AR patients receiving HDM-AIT for 52 weeks were followed up to assess serum levels of sIgE and sIgG4 to HDM components. The study showed that Der p1, p2, p23, Der f1 and f2, are important sensitizing components of HDM, of which Der p1 appears to be the most clinically relevant allergenic component for effective AIT

Reduced Expression of Antimicrobial Protein Secretory Leukoprotease Inhibitor and Clusterin in Chronic Rhinosinusitis with Nasal Polyps

Introduction. Antimicrobial peptides and proteins (AMPs) constitute the first line of defense against pathogenic microorganisms in the airway. The association between AMPs and chronic rhinosinusitis with nasal polyps (CRSwNP) requires further investigations. This study is aimed at investigating the expression and regulation of major dysregulated AMPs in the nasal mucosa of CRSwNP. Methods. The expression of AMPs was analyzed in nasal tissue from patients with eosinophilic (E) CRSwNP and nonECRSwNP and healthy subjects using RNA sequencing. The 10 most abundant AMPs expressed differentially in CRSwNP patients were verified by real-time PCR, and of these, the expression and regulation of secretory leukoprotease inhibitor (SLPI) and clusterin (CLU) were investigated further. Results. The 10 most abundant AMPs expressed differentially in CRSwNP compared to healthy control, regardless of subtypes, included BPIFA1, BPIFB1, BPIFB2, CLU, LTF, LYZ, and SLPI, which were downregulated, and S100A8, S100A9, and HIST1H2BC, which were upregulated. ELISA and immunofluorescence confirmed the decreased expression of SLPI and CLU levels in CRSwNP. SLPI is expressed in both nasal epithelial cells and glandular cells, whereas CLU is mainly expressed in glandular cells. AB/PAS staining further demonstrated that both SLPI and CLU were mainly produced by mucous cells in submucosal glands. Furthermore, the numbers of submucosal glands were significantly decreased in nasal polyp tissue of CRSwNP compared to nasal tissue of controls. SLPI was downregulated by TGF-β1 and IL-4 in cultured nasal tissues in vitro, while CLU expression was inhibited by TGF-β1. Glucocorticoid treatment for 2 weeks significantly increased the expression of all downregulated AMPs, but not LYZ. Additionally, budesonide significantly increased the expression of SLPI and CLU in cultured nasal tissues. Conclusion. The expression of major antimicrobial proteins is significantly decreased in nasal tissue of CRSwNP. The expression of SLPI and CLU is correlated with the numbers of submucosal glands and regulated by inflammatory cytokines and glucocorticoids

Modeling of SOL helical current filaments induced by biased electrode on J-TEXT

It has been demonstrated in J-TEXT experiments that a biased electrode or electrode biasing (EB) in the scrape-off layer (SOL) can drive SOL helical current filaments (HCFs). The bright helical radiation belts of carbon impurities in the SOL indicate that SOL current flows along the magnetic field lines. Based on the experimental phenomenon, three SOL current models (model A, B, C) have been set-up in order to understand the spatial structure of SOL current and the perturbed magnetic field it generates. Model A is a simplified calculation of HCFs in the cylindrical geometry, and takes into account the presence of cross-field current by a linear decay of current along magnetic field lines. Model B take into account the actual toroidal geometry and the complex path of HCFs connected from the electrode to the limiters. By including the radial dependence of the resistivity into model B, model C is developed and describes the SOL current more perfectly than the other two models. Furthermore, the model C shows that SOL helical current can produces stronger boundary resonant magnetic perturbations (RMPs) at the last closed flux surface (LCFS) due to the consistent helixity of SOL current filaments and the boundary rational surface, which may be a new way to generate RMPs to control the edge-localized modes (ELMs). The equivalent inductance and resistance of HCFs at different edge safety factor qa are measured by applying a square wave voltage. The results show that the inductance and resistance of the HCFs are related to qa and the radial position of the biased electrode rEB, in a qualitatively consistent manner as that predicted by model C