Extracellular HMGB1 augments macrophage inflammation by facilitating the endosomal accumulation of ALD-DNA via TLR2/4-mediated endocytosis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unclear pathogenesis. We previously reported that syngenetic, activated lymphocyte-derived DNA (ALD-DNA) could robustly elicit macrophage activation, which plays an important role in the pathogenesis of murine lupus nephritis. In addition, extracellular HMGB1 obviously facilitated the accumulation of ALD-DNA in endosomes and promoted macrophage inflammation. While the detailed mechanism was still unknown. In this study, we found that HMGB1 could obviously change the DNA uptake pathways in macrophages. ALD-DNA alone was mainly uptake by the low efficient and unselective macropinocytosis, while extracellular HMGB1 potently promoted the more efficient and specific clathrin-/caveolin-1-dependent receptor-mediated endocytosis pathways, and led to the rapid and abundant aggregation of ALD-DNA in endosomes. This effect relied on the DNA binding ability and TLR2/TLR4 of HMGB1. Our study not only helped us to understand the promotion mechanisms of extracellular HMGB1 on ALD-DNA-induced macrophage inflammation, but also provided some clues to the pathogenesis of SLE.     

A Plasmopara viticola RXLR effector targets a chloroplast protein PsbP to inhibit ROS production in grapevine

Pathogens secrete a large number of effectors that manipulate host processes to create an environment conducive to pathogen colonization. However, the underlying mechanisms by which Plasmopara viticola effectors manipulate host plant cells remain largely unclear. In this study, we reported that RXLR31154, a P. viticola RXLR effector, was highly expressed during the early stages of P. viticola infection. In our study, stable expression of RXLR31154 in grapevine (Vitis vinifera) and Nicotiana benthamiana promoted leaf colonization by P. viticola and Phytophthora capsici, respectively. By yeast two-hybrid screening, the 23-kDa oxygen-evolving enhancer 2 (VpOEE2 or VpPsbP), encoded by the PsbP gene, in Vitis piasezkii accession Liuba-8 was identified as a host target of RXLR31154. Overexpression of VpPsbP enhanced susceptibility to P. viticola in grapevine and P. capsici in N. benthamiana, and silencing of NbPsbPs, the homologs of PsbP in N. benthamiana, reduced P. capcisi colonization, indicating that PsbP is a susceptibility factor. RXLR31154 and VpPsbP protein were co-localized in the chloroplast. Moreover, VpPsbP reduced H₂O₂ accumulation and activated the ¹O₂ signaling pathway in grapevine. RXLR31154 could stabilize PsbP. Together, our data revealed that RXLR31154 reduces H₂O₂ accumulation and activates the ¹O₂ signaling pathway through stabilizing PsbP, thereby promoting disease.     

基于多源数据的“安全公正空间”在大通湖流域环境管理中的应用

如何在确保生态系统安全的同时有效地开发和利用资源、保障人类福祉是当前面临的挑战。近年来兴起的“安全公正空间”(Safe and Just Operating Space, SJOS)理论框架为人类可持续发展提供了有效的评估方法, 即充分利用自然资源来提高人类社会福祉的同时确保环境生态安全。研究以长江中下游地区大通湖流域为例, 根据流域内的社会经济数据、环境监测数据和湖泊沉积记录, 从社会基础和环境系统两个方面构建该流域的SJOS框架, 并利用环境库兹涅兹曲线来揭示总体环境变化特征。结果表明: 流域内淡水利用、空气质量、水质均突破环境上限, 处于危险的状态, 此外流域内无贫困和产业创新两个社会基础维度的完成度相对较低。环境库兹涅兹曲线揭示了大通湖流域内社会-生态系统大致分为初始阶段(1950s—1980s)、严重退化阶段(1980s—2000s)和逐步改善(2000s后)三个阶段。研究为维持区域可持续发展提供了重要的参考信息, 同时也为区域SJOS框架的构建提供了一种有效的方法。