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关键词： Focal segmental glomerulosclerosis   Serum immunoglobulin G   Class-switched memory B cells   Plasmablasts   GLOMERULAR SCLEROSIS   CHILDREN   IGG   PATHOGENESIS   EXCRETION   CD27  

摘要： Background: Focal segmental glomerulosclerosis (FSGS) is a kidney-specific autoimmune disease, but its pathogenesis is not fully known. The present study detected the frequencies of circulating memory B cells and plasmablasts and other clinical parameters in FSGS. Methods: We monitored 16 primary FSGS patients and 23 healthy controls (HC). Flow cytometry was used to analyze circulating memory B cell and plasmablasts percentages. Serum IgG levels were detected using a cytometric bead array (CBA). Results: The proportions of CD27 + IgD-class-switched memory B cells (P = 0.0002), CD27 + IgD-IgG + class-switched memory B cells (P < 0.0001), CD27hiCD38hi plasmablasts (P < 0.0001) and CD138 + plasma cells (P < 0.0001) were markedly elevated in FSGS patients, and the frequency of CD38 + IgG + plasmablasts (P < 0.0001) and serum IgG levels (P < 0.0001) were lower compared to HC. In the FSGS patients, the frequency of CD27 + IgD-IgG + class-switched memory B cells negatively correlated with CD38 + IgG + plasmablasts (P = 0.0183, R = -0.3375), serum IgG levels (P = 0.0061, R = -0.4263) and estimated glomerular filtration rate (eGFR) (P = 0.0074, R = -0.4114) but positively correlated with 24-h urinary protein levels (P = 0.0077, R = 0.4085). The proportion of CD38 + IgG + plasmablasts positively correlated with serum IgG levels (P = 0.0151, R = 0.3538). Conclusions: We speculate that alterations in the frequencies of CD27 + IgD-IgG + class-switched memory B cells and plasmablasts may be responsible for the etiopathogenesis of FSGS.

关键词： Asperuloside   Lipopolysaccharide   Chronic periodontitis   TLR 4   NF-KB   ACUTE LUNG INJURY   KAPPA-B   INFLAMMATORY RESPONSE   STEM-CELLS   PATHWAY   MAPK  

摘要： Objective: The mechanism underlying lipopolysaccharide (LPS)-induced primary human periodontal ligament (PDLC) cell injury is unclear. In this study, we focused on the therapeutic function of asperuloside (ASP) on LPSinduced cell injury. Design: The study enrolled 41 participants, including 18 healthy controls and 23 CP patients. Western blotting was used to measure the expression of Toll-like receptor 4 (TLR4), phosphorylated p65 (p-p65) and cyclin D1. Enzyme-linked immunosorbent assays (ELISAs) were utilized to evaluate the protein levels of proinflammatory factors interleukin (IL)-113, IL-6, IL-8 and tumor necrosis factor alpha (TNF-a). MTT assays and 5-ethynyl-2 ' deoxyuridine (EdU) staining were performed to investigate cell proliferation. Immunohistochemistry was used to detect TLR4 and p65 expression in gingival tissues. Results and conclusions: Asperuloside ameliorates lipopolysaccharide-induced PDLC cell injury by decreasing TLR4 expression and NF-KB activation, while this protective effect of ASP was reversed by TLR4 overexpression.

关键词： Cancer   Metastasis   Metastatic potential   Liver cancer   Primary tumor   Cancer cell lines  

摘要： Although metastases from original (primary) tumors are highly studied, metastases from metastatic sites (secondary tumors) are far less studied. Here, using data from metastasis map (MetMap) project reported in a recent study (Jin et al. in Nature 588(7837): 331-336. , 2020), we found that human cancer cell lines isolated from metastatic sites have higher potential to metastasize to another site in mice, compared to human cancer cell lines isolated from primary sites, for certain types of cancer including liver, lung and pancreas cancer. In contrast, for cancer types such as ovarian and skin cancer, human cancer cell lines originated from primary tumors have increased metastatic potential in mice, compared to human cancer cell lines originated from metastatic sites. This preliminary analysis points that the potential of metastases to further metastasize compared to that of primary tumors might be cancer type-dependent, and further research is needed to understand why certain cancer cell lines isolated from metastatic sites are more likely to spread to other organs.

关键词： cancer   chimeric antigen receptor   IKK epsilon   immunotherapy   lentivirus   natural killer   TBK1   VSV-G   T-CELLS   NK CELLS   GENE-TRANSFER   ACTIVATION   INHIBITOR   RECEPTORS   RESPONSES   SIGNALS   MURINE   TBK1  

摘要： Background aims: Vesicular stomatitis virus G (VSV-G)-pseudotyped lentiviral vectors (LVs) are widely used to reliably generate genetically modified, clinical-grade T-cell products. However, the results of genetically modifying natural killer (NK) cells with VSV-G LVs have been variable. The authors explored whether inhibition of the IKK-related protein kinases TBK1 and IKK epsilon, key signaling molecules of the endosomal TLR4 pathway, which is activated by VSV-G, would enable the reliable transduction of NK cells by VSV-G LVs. Methods: The authors activated NK cells from peripheral blood mononuclear cells using standard procedures and transduced them with VSV-G LVs encoding a marker gene (yellow fluorescent protein [YFP]) or functional genes (chimeric antigen receptors [CARs], co-stimulatory molecules) in the presence of three TBK1/IKK epsilon inhibitors (MRT67307, BX-795, amlexanox). NK cell transduction was evaluated by flow cytometry and/or western blot and the functionality of expressed CARs was evaluated in vitro. Results: Blocking TBK1/IKK epsilon during transduction of NK cells enabled their efficient transduction by VSV-G LVs as judged by YFPexpression of 40-50%, with half maximal effective concentrations of 1.1 mu M (MRT67307), 5 mu M (BX-795) and 24.8 mu M (amlexanox). Focusing on MRT67307, the authors successfully generated NK cells expressing CD19-CARs or HER2-CARs with an inducible co-stimulatory molecule. CAR NK cells exhibited increased cytolytic activity and ability to produce cytokines in comparison to untreated controls, confirming CAR functionality. Conclusions: The authors demonstrate that inhibition of TBK1/IKK epsilon enables the reliable generation of genetically modified NK cells using VSV-G LVs. The authors' protocol can be readily adapted to generate clinical-grade NK cells and thus has the potential to facilitate the clinical evaluation of genetically modified NK cell-based therapeutics in the future. (C) 2021 International Society for C

关键词： 建筑工程   新型   墙体节能材料   检测  

摘要： 近年来,建筑技术的进步推动了建筑工程行业的发展.墙体是建筑工程中重要组成部分,墙体质量会直接影响到建筑工程整体质量.为节省建筑材料能源、实现建筑工程领域可持续发展,新型墙体节能材料层出不穷,在墙体建设中发挥着重要的作用.为提升墙体建设质量,必须加强对节能材料的检测、分析,确保应用安全性,保障建筑工程的顺利实施.

关键词： 公路桥梁   伸缩缝施工   质量技术  

摘要： 做好道路桥梁,保证桥梁工程的质量,是道路桥梁工作的重要保障,在道路建设中我国逐步增加了道路桥梁建设的数量,对桥梁建设施工的质量要求也愈发严格,公路桥梁建设工作在我国经济发展过程中占有重要地位,保证伸缩缝施工的优良质量,提高施工的技术水平,使桥梁建筑行业在发展中能够越来越好.