目的探讨上调可诱导共刺激分子(ICOS)信号对感染日本血吸虫小鼠CD28/CD86的表达及Th1/Th2极化的影响。方法建立ICOS转基因(ICOS-Tg)小鼠及野生型FVB/NJ小鼠日本血吸虫病模型,应用流式细胞术分析感染前(0周)和感染后(4～20周)小鼠的脾CD...目的探讨上调可诱导共刺激分子(ICOS)信号对感染日本血吸虫小鼠CD28/CD86的表达及Th1/Th2极化的影响。方法建立ICOS转基因(ICOS-Tg)小鼠及野生型FVB/NJ小鼠日本血吸虫病模型,应用流式细胞术分析感染前(0周)和感染后(4～20周)小鼠的脾CD4+T淋巴细胞上CD28与脾CD19+B淋巴细胞上CD86的表达水平。应用免疫组化法检测同期小鼠肝脏虫卵肉芽肿周围炎性浸润细胞上CD28、CD86表达水平变化。取同期小鼠脾淋巴细胞用SEA进行诱导培养72 h后,采用ELISA法检测培养上清中Th1(IFN-γ、IL-12)及Th2(IL-4、IL-13)细胞因子表达水平。采集同期小鼠的血清,应用ELISA法检测血清中SEA特异性抗体IgG及其亚类IgG1、IgG2a的表达水平。应用HE染色法观察小鼠肝脏虫卵肉芽肿病变动态变化。结果ICOS-Tg小鼠脾CD4+T细胞上CD28和脾CD19+B细胞上CD86的水平与同期野生型FVB/NJ小鼠相比明显升高,且分别在感染4周后(50.57±7.54 vs 40.38±5.43,P<0.05)及在感染12周后(76.46±10.55 vs 65.10±10.17,P<0.05)差异显著。ICOS-Tg小鼠肝脏虫卵肉芽肿的CD28、CD86表达亦高于野生型FVB/NJ小鼠的水平,且分别在感染7周后(0.485±0.094 vs 0.357±0.078,P<0.05)及感染12周后(0.649±0.072 vs 0.537±0.064,P<0.05)差异显著。ICOS-Tg小鼠Th2细胞因子(IL-4、IL-13)水平从感染7周后比野生型FVB/NJ小鼠显著升高(皆P<0.05);ICOS-Tg小鼠血清SEA特异性抗体IgG及其亚类IgG1、IgG2a的水平显著高于野生型FVB/NJ小鼠的水平(P<0.05、0.01、0.001不等);ICOS-Tg小鼠Th2分化指数与IgG1/IgG2a的比值亦高于野生型小鼠,分别在感染7、12、16、20周后(P<0.05、0.001)及12、16周后(皆P<0.05)具有显著性差异。在整个病程中,ICOS-Tg小鼠肝脏虫卵肉芽肿体积显著大于野生型FVB/NJ小鼠。结论感染日本血吸虫的ICOS-Tg小鼠CD28、CD86表达及其Th2免疫应答显著上调,并伴随肝虫卵肉芽肿病变增强,表明ICOS信号对CD28-CD86信号通路具有一定的调控作用,且在介导Th2极化及肝虫卵肉芽肿的发生、发展中发挥重要作用。展开更多
This review synthesizes 48 academic studies on Initial Coin Offerings(ICOs)from 2018 to 2023,employing bibliometric and content analyses to illuminate their complexities and innovation in entrepreneurial finance.It id...This review synthesizes 48 academic studies on Initial Coin Offerings(ICOs)from 2018 to 2023,employing bibliometric and content analyses to illuminate their complexities and innovation in entrepreneurial finance.It identifies four key themes:(1)regulatory intricacies,market transformation,and strategic implications for emerging ventures;(2)the opportunities and challenges presented,and key factors influencing the success of ICOs;(3)ICOs and entrepreneurial finance;and finally,(4)review of reviews.By examining the intersection of legal frameworks,disruptive potential,and stakeholder challenges,this interdisciplinary perspective captures the essence of ICOs and charts a course for future inquiry.It serves as a pivotal reference for researchers,practitioners,and regulators to understand the multifaceted ICO landscape and its implications for the future of finance.展开更多
文摘目的探讨上调可诱导共刺激分子(ICOS)信号对感染日本血吸虫小鼠CD28/CD86的表达及Th1/Th2极化的影响。方法建立ICOS转基因(ICOS-Tg)小鼠及野生型FVB/NJ小鼠日本血吸虫病模型,应用流式细胞术分析感染前(0周)和感染后(4～20周)小鼠的脾CD4+T淋巴细胞上CD28与脾CD19+B淋巴细胞上CD86的表达水平。应用免疫组化法检测同期小鼠肝脏虫卵肉芽肿周围炎性浸润细胞上CD28、CD86表达水平变化。取同期小鼠脾淋巴细胞用SEA进行诱导培养72 h后,采用ELISA法检测培养上清中Th1(IFN-γ、IL-12)及Th2(IL-4、IL-13)细胞因子表达水平。采集同期小鼠的血清,应用ELISA法检测血清中SEA特异性抗体IgG及其亚类IgG1、IgG2a的表达水平。应用HE染色法观察小鼠肝脏虫卵肉芽肿病变动态变化。结果ICOS-Tg小鼠脾CD4+T细胞上CD28和脾CD19+B细胞上CD86的水平与同期野生型FVB/NJ小鼠相比明显升高,且分别在感染4周后(50.57±7.54 vs 40.38±5.43,P<0.05)及在感染12周后(76.46±10.55 vs 65.10±10.17,P<0.05)差异显著。ICOS-Tg小鼠肝脏虫卵肉芽肿的CD28、CD86表达亦高于野生型FVB/NJ小鼠的水平,且分别在感染7周后(0.485±0.094 vs 0.357±0.078,P<0.05)及感染12周后(0.649±0.072 vs 0.537±0.064,P<0.05)差异显著。ICOS-Tg小鼠Th2细胞因子(IL-4、IL-13)水平从感染7周后比野生型FVB/NJ小鼠显著升高(皆P<0.05);ICOS-Tg小鼠血清SEA特异性抗体IgG及其亚类IgG1、IgG2a的水平显著高于野生型FVB/NJ小鼠的水平(P<0.05、0.01、0.001不等);ICOS-Tg小鼠Th2分化指数与IgG1/IgG2a的比值亦高于野生型小鼠,分别在感染7、12、16、20周后(P<0.05、0.001)及12、16周后(皆P<0.05)具有显著性差异。在整个病程中,ICOS-Tg小鼠肝脏虫卵肉芽肿体积显著大于野生型FVB/NJ小鼠。结论感染日本血吸虫的ICOS-Tg小鼠CD28、CD86表达及其Th2免疫应答显著上调,并伴随肝虫卵肉芽肿病变增强,表明ICOS信号对CD28-CD86信号通路具有一定的调控作用,且在介导Th2极化及肝虫卵肉芽肿的发生、发展中发挥重要作用。
文摘This review synthesizes 48 academic studies on Initial Coin Offerings(ICOs)from 2018 to 2023,employing bibliometric and content analyses to illuminate their complexities and innovation in entrepreneurial finance.It identifies four key themes:(1)regulatory intricacies,market transformation,and strategic implications for emerging ventures;(2)the opportunities and challenges presented,and key factors influencing the success of ICOs;(3)ICOs and entrepreneurial finance;and finally,(4)review of reviews.By examining the intersection of legal frameworks,disruptive potential,and stakeholder challenges,this interdisciplinary perspective captures the essence of ICOs and charts a course for future inquiry.It serves as a pivotal reference for researchers,practitioners,and regulators to understand the multifaceted ICO landscape and its implications for the future of finance.
