Transcription factor GATA binding protein 2 (GATA2) plays critical roles in hematopoietic stem cell survival and proliferation, granulocyte-monocyte progenitor differentiation, and basophil and mast ...cell differentiation. However, precise roles of GATA2 in basophil and mast cell differentiation and maintenance have not been delineated. We have identified GATA2 as an essential transcription factor in differentiation of newly identified common basophil and mast cell progenitors into basophils and mast cells. We observed Gata2 haploinsufficiency for mast cell differentiation, but not for basophil differentiation. We examined the precise role of GATA2 in maintaining the expression of a wide range of genes that are important for performing basophil or mast cell functions. The effects of GATA2 on gene expression were broadly based. We demonstrated that GATA2 was required for maintaining Fcer1a mRNA and FcεRIα protein expression on both basophils and mast cells, as well as for maintaining Kit mRNA and c-Kit protein expression on mast cells. GATA2 was required for histamine synthesis and was also critical for Il4 mRNA expression in basophils and Il13 mRNA expression in mast cells. We demonstrate a STAT5-GATA2 connection, showing that the STAT5 transcription factor directly bound to the promoter and an intronic region of the Gata2 gene. Overexpression of the Gata2 gene was sufficient to direct basophil and mast cell differentiation in the absence of the Stat5 gene. Our study reveals that the STAT5-GATA2 pathway is critical for basophil and mast cell differentiation and maintenance.
The development of new materials and the understanding of the microstructure formation of electrodes have become increasingly important for improving Li-ion battery performance. In this study, we ...investigate the effect of solid content on the rheological properties of and the microstructures in the cathode slurry prepared from Ni-rich materials. With long-chain structures, PVDF molecules can change their configurations when they come into contact with the solid particles in slurries, and their bridging function can change with the solid content in the slurry. Below the optimum content, particle sedimentation easily takes place. Above the optimum content, excessive yield stress is created in the slurry, and this stress is not conducive to homogeneous distribution of the components. The rheological properties of the slurries vary greatly under different solid contents. We investigated the uniformity and stability of the slurry prepared from Ni-rich materials and found that the most suitable solid content of the slurry lies in the range from 63.9% to 66.3%. Our work might assist in the production of high-performance Li-ion batteries that are made using an electrode slurry.
There are three main situations in which the uniformity and microstructure of the slurry change with the solid content.
Hydrophobic thin films have gained significant attention due to their broad applications in self-cleaning, anti-corrosion, anti-icing, medicine, oil-water separation, and other fields. The target ...hydrophobic materials can be deposited onto various surfaces thanks to the scalable and highly reproducible nature of magnetron sputtering, which is comprehensively overviewed in this review. While alternative preparation methods have been extensively analyzed, a systematic understanding of hydrophobic thin films fabricated using magnetron sputtering deposition is still absent. After outlining the fundamental mechanism of hydrophobicity, this review briefly summarizes three types of sputtering-deposited thin films that originate from oxides, polytetrafluoroethylene (PTFE), and diamond-like carbon (DLC), respectively, primarily focusing on the recent advances in their preparation, characteristics, and applications. Finally, the future applications, current challenges, and development of hydrophobic thin films are discussed, and a brief perspective on future research directions is provided.
E3 ubiquitin ligases determine the substrate specificity and catalyze the ubiquitination of lysine residues. HUWE1 is a catalytic HECT domain-containing giant E3 ligase that contains a ...substrate-binding ring structure, and mediates the ubiquitination of more than 40 diverse substrates. HUWE1 serves as a central node in cellular stress responses, cell growth and death, signal transduction, etc. The expanding atlas of HUWE1 substrates presents a major challenge for the potential therapeutic application of HUWE1 in a particular disease. In addition, HUWE1 has been demonstrated to play contradictory roles in certain aspects of tumor progression in either an oncogenic or a tumor-suppressive manner. We recently defined novel roles of HUWE1 in promoting the activation of multiple inflammasomes. Inflammasome activation-mediated immune responses might lead to multifunctional effects on tumor therapy, inflammation, and autoimmune diseases. In this review, we summarize the known substrates and pleiotropic functions of HUWE1 in different types of cells and models, including its involvement in development, cancer, neuronal disorder and infectious disease. We also discuss the advances in cryo-EM-structural analysis for a functional-mechanistic understanding of HUWE1 in modulating the multitudinous diverse substrates, and introduce the possibility of revisiting the comprehensive roles of HUWE1 in multiple aspects within one microenvironment, which will shed light on the potential therapeutic application of targeting giant E3 ligases like HUWE1.
Pathogenic viral infections represent a major challenge to human health. Host immune responses to respiratory viruses are closely associated with microbiome and metabolism via the gut-lung axis. It ...has been known that host defense against influenza A virus (IAV) involves activation of the NLRP3 inflammasome, however, mechanisms behind the protective function of NLRP3 are not fully known. Here we show that an isolated bacterial strain, Bifidobacterium pseudolongum NjM1, enriched in the gut microbiota of Nlrp3
mice, protects wild-type but not Nlrp3 deficient mice against IAV infection. This effect depends on the enhanced production of type I interferon (IFN-I) mediated by NjM1-derived acetate. Application of exogenous acetate reproduces the protective effect of NjM1. Mechanistically, NLRP3 bridges GPR43 and MAVS, and promotes the oligomerization and signalling of MAVS; while acetate enhances MAVS aggregation upon GPR43 engagement, leading to elevated IFN-I production. Thus, our data support a model of NLRP3 mediating enhanced induction of IFN-I via acetate-producing bacterium and suggest that the acetate-GPR43-NLRP3-MAVS-IFN-I signalling axis is a potential therapeutic target against respiratory viral infections.
High-specific-capacity materials are crucial for the high-energy-density lithium-ion secondary batteries as the automakers and customers are both eager to extend the cruising range of electric ...vehicles. The current commercial silicon/carbon composites are based on the mechanical mixture of silicon and graphite, but this weak combination is not suitable for the higher-capacity materials. Here, low-cost raw materials are used for the preparation of a graphite/silicon@carbon composite negative electrode material, which synergizes ball milling, molten salts electrolysis and carbon coating. Silica is in situ electrochemically reduced to silicon on the flaky graphite serving as the conducting substrate during the electrolysis process. It is found that ball milling increases the active sites on the basal plane of graphite, which is beneficial for the nucleation and growth of the silicon, and enhances the bonding of silicon particles and graphite. As for the electrochemical results of coin-type cells, this graphite/silicon@carbon composite material exhibits a better cycle performance than the commercial Si/C 650 silicon-based composite material.
The commercial transfection reagent Lipofectamine has been widely used for cytoplasmic delivery of nucleic acids and for cytosolic engagement with intracellular innate immune sensors to trigger type ...I interferon (IFN) production. However, the effect of Lipofectamine alone on type I IFN response has not been studied in detail. Here, we show that Lipofectamine induced type I IFN signaling in both RAW 264.7 macrophage‐like cells and primary bone marrow‐derived macrophages. Type I IFN induction was dependent on interferon regulatory factor (IRF)3 and IRF7 and partially required the toll/interleukin‐1 receptor‐domain‐containing adapter‐inducing interferon‐β. In contrast, the transfection reagent Xfect did not activate type I IFN signaling. Our study highlights the potential confounding experimental interpretation when using Lipofectamine‐based transfection for delivering intracellular ligands and provides important insights into lipid signaling in innate immune responses.
We found that the transfection reagent Lipofectamine can induce type I interferon signaling in macrophages.
Inflammasome activation is essential for host immune responses during pathogenic infection and sterile signals insult, whereas excessive activation is injurious. Thus, inflammasome activation is ...tightly regulated at multiple layers. Ubiquitination is an important post-translational modification for orchestrating inflammatory immune responses during pathogenic infection, and a major target hijacked by pathogenic bacteria for promoting their survival and proliferation. This review summarizes recent insights into distinct mechanisms of the inflammasome activation and ubiquitination process triggered by bacterial infection. We discuss the complex regulatory of inflammasome activation mediated by ubiquitination machinery during bacterial infection, and provide therapeutic approaches for specifically targeting aberrant inflammasome activation.
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•15 metal dimers constructed by 5 3d metals (Fe-Zn) are systematically studied.•The OH group as a ligand significantly improves oxygen reduction reaction (ORR) activity.•Ligand OH ...weakens the scaling relationship of adsorption free energies of oxygenated species.•The volcanic plot predicts that the optimal overpotential is 0.29 V.
Various experimental investigation had proved that metal dimers possess excellent oxygen reduction reaction (ORR) activity compared to single metal atom catalysts, due to the synergistic effect exerted by two metal atoms. However, it is still unclear how the electrocatalytic activity is enhanced in a fundamental aspect. In this study, we systematically investigated five 3d transition metals (Fe, Co, Ni, Cu and Zn) by density functional theory (DFT) to explore the ability of metal dimers to catalyze the ORR. It is found that different combinations of different metal atoms have different adsorption strengths to oxygenated intermediates, which helps to screen suitable catalyst materials. The scaling relationship of the free energy of adsorption of oxygen-containing species was calculated for various metal-dimer systems. The classical volcanic diagram is derived, and it is found that the CoZnOH embedded nitrogen-doped graphene (the overpotential is 0.61 V) shows the best catalytic properties, and it is predicted that when the adsorption free energy of OH is equal to 0.95 eV, the optimal overpotential is 0.29 V. Electronic structure calculations show that the pairing of different metal atoms alters the d-band center which in turn change the adsorption properties and hence ORR catalytic performance.
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