Patients with DM had a larger FAZ, and patients with more severely damaged retinas had a much larger FAZ. OCT angiography is a new convenient and noninvasive method for studying the FAZ. This novel examination will yield considerable amounts of data that cannot be obtained using previous research methods.
Human innate immunity responds to viral infection by activating the production of interferons (IFNs) and proinflammatory cytokines. The mitochondrial adaptor molecule MAVS plays a critical role in innate immune response to viral infection. In this study, we show that TRIM21 (tripartite motif-containing protein 21) interacts with MAVS to positively regulate innate immunity. Under viral infection, TRIM21 is upregulated through the IFN/JAK/STAT signaling pathway. Knockdown of TRIM21 dramatically impairs innate immune response to viral infection. Moreover, TRIM21 interacts with MAVS and catalyzes its K27-linked polyubiquitination, thereby promoting the recruitment of TBK1 to MAVS. Specifically, the PRY-SPRY domain of TRIM21 is the key domain for its interaction with MAVS, while the RING domain of TRIM21 facilitates the polyubiquitination chains of MAVS. In addition, the MAVS-mediated innate immune response is enhanced by both the PRY-SPRY and RING domains of TRIM21. Mutation analyses of all the lysine residues of MAVS further revealed that Lys325 of MAVS is catalyzed by TRIM21 for the K27-linked polyubiquitination. Overall, this study reveals a novel mechanism by which TRIM21 promotes the K27-linked polyubiquitination of MAVS to positively regulate innate immune response, thereby inhibiting viral infection.
IMPORTANCE
Activation of innate immunity is essential for host cells to restrict the spread of invading viruses and other pathogens. MAVS plays a critical role in innate immune response to RNA viral infection. In this study, we demonstrated that TRIM21 targets MAVS to positively regulate innate immunity. Notably, TRIM21 targets and catalyzes K27-linked polyubiquitination of MAVS and then promotes the recruitment of TBK1 to MAVS, leading to upregulation of innate immunity. Our study outlines a novel mechanism by which the IFN signaling pathway blocks RNA virus to escape immune elimination.
Having a reasonable environmental management system is key to achieve regional green development. This article integrates environmental decentralization into an environmental/economic analytical framework, introducing a fiscal decentralization indicator to explore the mechanism of environmental decentralization and regional green development, and then tests this concept using Chinese provincial penal data. The results show that the spillover effect of green development is significant: Improving regional green development will promote green development in neighboring regions. At the national level, different categories of environmental decentralization have different effects, and these can also affect green development through both direct and indirect paths. There is also a positive interaction mechanism between these two variables. Moreover, the interaction between environmental and fiscal decentralization has a negative effect on regional green development, with the impact varying across regions. These findings play an important role in green development, industrial transformation, and advancement, especially in China.
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