USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase

Lys63-linked polyubiquitination of RIG-I is essential in antiviral immune defense, yet the molecular mechanism that negatively regulates this critical step is poorly understood. Here, we report that USP21 acts as a novel negative regulator in antiviral responses through its ability to bind to and deubiquitinate RIG-I. Overexpression of USP21 inhibited RNA virus–induced RIG-I polyubiquitination and RIG-I–mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-α/β production, and antiviral responses in MEFs in response to RNA virus infection. USP21 also restricted antiviral responses in peritoneal macrophages (PMs) and bone marrow–derived dendritic cells (BMDCs). USP21-deficient mice spontaneously developed splenomegaly and were more resistant to VSV infection with elevated production of IFNs. Chimeric mice with USP21-deficient hematopoietic cells developed virus-induced splenomegaly and were more resistant to VSV infection. Functional comparison of three deubiquitinases (USP21, A20, and CYLD) demonstrated that USP21 acts as a bona fide RIG-I deubiquitinase to down-regulate antiviral response independent of the A20 ubiquitin-editing complex. Our studies identify a previously unrecognized role for USP21 in the negative regulation of antiviral response through deubiquitinating RIG-I

Building instance knowledge network for word sense disambiguation

In this paper, a new high precision focused word sense disambiguation (WSD) approach is proposed, which not only attempts to identify the proper sense for a word but also provides the probabilistic evaluation for the identification confidence at the same time. A novel Instance Knowledge Network (IKN) is built to generate and maintain semantic knowledge at the word, type synonym set and instance levels. Related algorithms based on graph matching are developed to train IKN with probabilistic knowledge and to use IKN for probabilistic word sense disambiguation. Based on the Senseval-3 all-words task, we run extensive experiments to show the performance enhancements in different precision ranges and the rationality of probabilistic based automatic confidence evaluation of disambiguation. We combine our WSD algorithm with five best WSD algorithms in senseval-3 all words tasks. The results show that the combined algorithms all outperform the corresponding algorithms

RNA-Sequencing Analyses Demonstrate the Involvement of Canonical Transient Receptor Potential Channels in Rat Tooth Germ Development

Tooth development depends on multiple molecular interactions between the dental epithelium and mesenchyme, which are derived from ectodermal and ectomesenchymal cells, respectively. We report on a systematic RNA sequencing analysis of transcriptional expression levels from the bud to hard tissue formation stages of rat tooth germ development. We found that GNAO1, ENO1, EFNB1, CALM1, SIAH2, ATP6V0A1, KDELR2, GTPBP1, POLR2C, SORT1, and members of the canonical transient receptor potential (TRPC) channel family are involved in tooth germ development. Furthermore, Cell Counting Kit 8 (CCK8) and Transwell migration assays were performed to explore the effects of these differentially expressed genes (DEGs) on the proliferation and migration of dental pulp stem cells. Immunostaining revealed that TRPC channels are expressed at varying levels during odontogenesis. The identified genes represent novel candidates that are likely to be vital for rat tooth germ development. Together, the results provide a valuable resource to elucidate the gene regulatory mechanisms underlying mammalian tooth germ development

Regulation of neuroinflammation through programed death-1/programed death ligand signaling in neurological disorders

Immune responses in the central nervous system (CNS), which involve both resident glial cells and infiltrating peripheral immune cells, play critical roles in the progress of brain injuries and neurodegeneration. To avoid inflammatory damage to the compromised brain, the immune cell activities in the CNS are controlled by a plethora of chemical mediators and signal transduction cascades, such as inhibitory signaling through programed death-1 (PD-1) and programed death ligand (PD-L) interactions. An increasing number of recent studies have highlighted the importance of PD-1/PD-L pathway in immune regulation in CNS disorders such as ischemic stroke, multiple sclerosis, and Alzheimer\u27s disease. Here, we review the current knowledge of the impact of PD-1/PD-L signaling on brain injury and neurodegeneration. An improved understanding of the function of PD-1/PD-L in the cross-talk between peripheral immune cells, CNS glial cells, and non-immune CNS cells is expected to shed further light on immunomodulation and help develop effective and safe immunotherapies for CNS disorders. © 2014 Zhao, Li, Leak, Chen and Hu

Palladium-nickel catalysts based on ordered titanium dioxide nanorod arrays with high catalytic peformance for formic acid electro-oxidation

Ordered titanium dioxide nanorod arrays are prepared by a hydrothermal method and applied to the catalyst supports of the palladium-nickel catalysts (Pd2Ni3-TiO2) for formic acid oxidation. Due to the three-dimensional catalytic structure and alloying effect, the Pd2Ni3-TiO2 exhibits superior mass activity and long-term stability than those of Pd-TiO2 and commercial PdC catalysts. The present work opens a new approach to design catalysts with superior catalytic performance and durability for direct formic acid fuel cells with three-dimensional catalytic structure

Enhanced sulfur dioxide electrooxidation performance on a modified XC-72 carbon catalyst

Vulcan XC-72 is a carbon catalyst that is widely used in electrochemistry. The electrooxidation of SO2 plays a significant role in the domain of environmental protection. In this work, successive thermal and pyrolytic processes were applied to Vulcan XC-72 in order to obtain a modified catalyst that promotes SO2 electrooxidation to a much greater degree than Vulcan XC-72 does. The preparation of this modified XC-72 involved three steps: doping, pore creation, and carbonization. These modification processes were shown to greatly increase the catalytic activity of the modified XC-72 during SO2 electrooxidation. The catalytic performance of the modified XC-72 towards SO2 electrooxidation was characterized via linear sweep voltammograms and cyclic voltammograms; the results showed that the onset potential and the E (imax/2) obtained with the modified XC-72 were 60 mV and 128 mV lower, respectively, than attained with Vulcan XC-72. The structural and physical properties of the modified XC-72 were characterized using TEM, XPS, and BET. The increased surface area and optimized pore structure of the modified XC-72, as well as the presence of pyridinic N constituents in this material, are believed to contribute to its enhanced capacity to catalyze the electrooxidation of SO2

Increased SO2 electrooxidation activity on a copper-nitrogen doped catalyst and its active sites analysis

It's a meaningful work to develop a highly active nonprecious SO2 electrooxidation catalyst, replacing the Pt-based ones. Here, a novel Cu-N doped carbon-based catalyst is synthesized by pyrolyzing the imidazole chelated copper ions on the chitosan modified carbon BP2000. During the preparation, metallic Cu is developed and encapsulated in the carbon lattices, and transformed into the CuNx structures on the catalyst surface, simultaneously. Metallic Cu plays significant role in the doping and developing of active sites, which have vital effects on the catalysis activity. The prereduction of Cu2+ by NaBH4 during the preparation of Doping(I)-Cu@N-C makes great contribution to the development of metallic Cu, which highly dispersive anchor in the carbon lattices. This as-synthesized Doping(I)-Cu@N-C catalyst exhibits excellent SO2 electrooxidation activity. Its SO2 oxidation currents are remarkably increased with the elevation of applied potentials, and the oxidation performances prominently surpass the commercial Pt/C, when the potential is above 0.822 V. The peak SO2 oxidation current (i(p)) of Doping(I)-Cu@N-C is 7.17 mA cm(-2) @ 0.684 V, much higher than the 3.03 mA cm(-2)@ 0.584 V of Pt/C with the same mass loading. In the chronoamperometry tests under 1.2 V, the terminal oxidation current of Doping(I)-Cu@N-C was 1.74 times as high as that of Pt/C, indicating that this prepared catalyst also displays much better SO2 electrooxidation activity than Pt/C under constant applied potentials. (C) 2018 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved

Excellent Sulfur Dioxide Electrooxidation Performance and Good Stability on a Fe-N-Doped Carbon-Cladding Catalyst in H2SO4

This work developed a non-precious carbon-cladding catalyst with excellent SO2 electrooxidation performance, which was synthesized through pyrolyzing a BP2000 supported composite precursor of melamine and Pluronic F127 dispersed FeCl3. This Fe-N-doped catalyst displays the onset and half-wave SO2 oxidation potential of 0.516 V and 0.629 V, respectively, which are particularly close to those of the Pt/C (JM, 20%). This carbon-cladding catalyst exhibits the higher SO2 catalytic activity than Pt/ C, when the applied oxidation potential is above 1.194 V. Furthermore, stability of this catalyst is also better than Pt/ C after the accelerated durability tests in H2SO4. Based on physical characterizations, the effectively doped Fe-N, well embedded Fe3C substances as well as the high surface area, large pore volume and mesoporous structures in the catalyst are synergetic responsible for its excellent SO2 electrooxidation performance and better stability. (C) 2017 The Electrochemical Society. All rights reserved