RIG-I is a critical RNA virus sensor that serves to initiate antiviral innate immunity. However, posttranslational regulation of RIG-I signaling remains to be fully understood. We report here that RNA viruses, but not DNA viruses or bacteria, specifically upregulate lectin family member Siglecg expression in macrophages by RIG-I- or NF-κB-dependent mechanisms. Siglec-G-induced recruitment of SHP2 and the E3 ubiquitin ligase c-Cbl to RIG-I leads to RIG-I degradation via K48-linked ubiquitination at Lys813 by c-Cbl. By increasing type I interferon production, targeted inactivation of Siglecg protects mice against lethal RNA virus infection. Taken together, our data reveal a negative feedback loop of RIG-I signaling and identify a Siglec-G-mediated immune evasion pathway exploited by RNA viruses with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of Siglec-G, a known adaptive response regulator, in innate immunity.

Multi-component tungsten carbide-based hybrid materials featuring different heteroatom dopants coated with X,N dual-doped carbonl ayers (X/W 2 C@X,N-C,X WXNC) were prepared by selecting Keggin-type polyoxometalates (POMs) (NH 4 ) n [XW 12 O 40 ]( X= Co, Si, Ge, B, and P) and dicyandiamide (DCA) as precursors. The electrocatalytic activity of these nanocomposites as counter electrode (CE) catalysts for dye-sensitized solar cells (DSSCs) was systematicallyi nvestigated. Structure characterizations show that X,N heteroatoms were successfully introduced into the W 2 Ca nd carbon frameworks. The obtained X,N dual-dopedc arbon layers were modifieda nd loaded with W 2 Cn anoparticles, promoting the improvement of catalytic performance by as ynergistic effect.T he consequence of photoelectricc onversion efficiency( PCE) is CoWCoNC (6.68 %) > SiWSiNC (6.56 %) > GeW-GeNC (6.49 %) > BWBNC( 6.45 %) > PWPNC (6.20 %) > WNC (6.05 %). With the increase in electronegativity of the dopants, the photovoltaic performance decreases in ar everse order.T his work provides as hortcutt ot he rational design of highly efficient and cost-effective catalysts for DSSCs.

Proton reduction is one of the most fundamental and important reactions in nature. MoS2 edges have been identified as the active sites for hydrogen evolution reaction (HER) electrocatalysis. Designing molecular mimics of MoS2 edge sites is an attractive strategy to understand the underlying catalytic mechanism of different edge sites and improve their activities. Herein we report a dimeric molecular analogue [Mo2 S12 ](2-) , as the smallest unit possessing both the terminal and bridging disulfide ligands. Our electrochemical tests show that [Mo2 S12 ](2-) is a superior heterogeneous HER catalyst under acidic conditions. Computations suggest that the bridging disulfide ligand of [Mo2 S12 ](2-) exhibits a hydrogen adsorption free energy near zero (-0.05 eV). This work helps shed light on the rational design of HER catalysts and biomimetics of hydrogen-evolving enzymes.

The Toll-like receptor (TLR)4 receptor complex, TLR4/MD-2, plays an important role in the inflammatory response against lipopolysaccharide, a ubiquitous membrane component in Gram-negative bacteria. Ligand recognition by TLR4 initiates multiple intracellular signaling pathways, leading to production of proinflammatory mediators and type I IFN. Ligand interaction also leads to internalization of the surface receptor complex into lysosomes, leading to the degradation of TLR4 and the termination of LPS response. However, surface level of TLR4 receptor complex is maintained via continuous replenishment of TLR4 from intracellular compartments like Golgi and endosomes. Here we show that continuous replenishment of TLR4 from Golgi to plasma membrane is regulated by the small GTPase Rab10, which is essential for optimal macrophage activation following LPS stimulation. Expression of Rab10 is inducible by LPS. Blockade of Rab10 function leads to decreased membrane TLR4 expression and diminished production of inflammatory cytokines and interferons upon LPS stimulation. These findings suggest that Rab10 expression provides a mechanism to refine TLR4 signaling by regulating the trafficking rate of TLR4 onto the plasma membrane. In addition, we show that altered Rab10 expression in macrophages influences disease severity in an in vivo model of LPS-induced acute lung injury, suggesting Rab10 as a possible therapeutic target for human acute respiratory distress syndrome (ARDS).small GTPases | membrane trafficking | LPS | acute respiratory distress syndrome