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

This review focuses on the properties of POMs used in DSSCs, which are primarily dependent on their electronic structural diversity.

Tandem dye-sensitized photoelectrochemical cells (DSPECs) for water splitting are a promising method for sustainable energy conversion but so far have been limited by their lack of aqueous stability and photocurrent mismatch between the cathode and anode. In nature, membrane-enabled subcellular compartmentation is a general approach to control local chemical environments in the cell. The hydrophobic tails of the lipid make the bilayer impermeable to ions and hydrophilic molecules. Herein we report the use of an organic donor-acceptor dye that prevents both dye desorption and semiconductor degradation by mimicking the hydrophobic/hydrophilic properties of lipid bilayer membranes. The dual-functional photosensitizer (denoted as BH4) allows for efficient light harvesting while also protecting the semiconductor surface from protons and water via its hydrophobic π linker. The protection afforded by this membrane-mimicking dye gives this system excellent stability in extremely acidic (pH 0) conditions. The acidic stability also allows for the use of cubane molybdenum-sulfide cluster as the hydrogen evolution reaction (HER) catalyst. This system produces a proton-reducing current of 183 ± 36 μA/cm(2) (0 V vs NHE with 300 W Xe lamp) for an unprecedented 16 h with no degradation. These results introduce a method for developing high-current, low-pH DSPECs and are a significant move toward practical dye-sensitized solar fuel production.

Extracellular vesicles (EVs) are lipid membrane vesicles released by cells. They carry active biomolecules including DNA, RNA, and protein which can be transferred to recipient cells. Isolation and purification of EVs from culture cell media and biofluids is still a major challenge. The most widely used isolation method is ultracentrifugation (UC) which requires expensive equipment and only partially purifies EVs. Previously we have shown that heparin blocks EV uptake in cells, supporting a direct EV-heparin interaction. Here we show that EVs can be purified from cell culture media and human plasma using ultrafiltration (UF) followed by heparin-affinity beads. UF/heparin-purified EVs from cell culture displayed the EV marker Alix, contained a diverse RNA profile, had lower levels of protein contamination, and were functional at binding to and uptake into cells. RNA yield was similar for EVs isolated by UC. We were able to detect mRNAs in plasma samples with comparable levels to UC samples. In conclusion, we have discovered a simple, scalable, and effective method to purify EVs taking advantage of their heparin affinity.

International audienceObservations from 550 surface stations in China during 1961-2000 are used to evaluate the skill of seven global coupled climate models in simulating extreme temperature and precipitation indices. It is found that the models have certain abilities to simulate both the spatial distributions of extreme climate indices and their trends in the observed period. The models' abilities are higher overall for extreme temperature indices than for extreme precipitation indices. The well-simulated temperature indices are frost days (Fd), heat wave duration index (HWDI) and annual extreme temperature range (ETR). The well-simulated precipitation indices are the fraction of annual precipitation total due to events exceeding the 95th percentile (R95T) and simple daily intensity index (SDII). In a general manner, the multi-model ensemble has the best skill. For the projections of the extreme temperature indices, trends over the twenty-first century and changes at the end of the twenty-first century go into the same direction. Both frost days and annual extreme temperature range show decreasing trends, while growing season length, heat wave duration and warm nights show increasing trends. The increases are especially manifested in the Tibetan Plateau and in Southwest China. For extreme precipitation indices, the end of the twenty-first century is expected to have more frequent and more intense extreme precipitation. This is particularly visible in the middle and lower reaches of the Yangtze River, in the Southeast coastal region, in the west part of Northwest China, and in the Tibetan Plateau. In the meanwhile, accompanying the decrease in the maximum number of consecutive dry days in Northeast and Northwest, drought situation will reduce in these regions. © 2011 Springer Science+Business Media B.V