45 research outputs found

    Developing a class of dual atom materials for multifunctional catalytic reactions

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    Dual atom catalysts, bridging single atom and metal/alloy nanoparticle catalysts, offer more opportunities to enhance the kinetics and multifunctional performance of oxygen reduction/evolution and hydrogen evolution reactions. However, the rational design of efficient multifunctional dual atom catalysts remains a blind area and is challenging. In this study, we achieved controllable regulation from Co nanoparticles to CoN4 single atoms to Co2N5 dual atoms using an atomization and sintering strategy via an N-stripping and thermal-migrating process. More importantly, this strategy could be extended to the fabrication of 22 distinct dual atom catalysts. In particular, the Co2N5 dual atom with tailored spin states could achieve ideally balanced adsorption/desorption of intermediates, thus realizing superior multifunctional activity. In addition, it endows Zn-air batteries with long-term stability for 800 h, allows water splitting to continuously operate for 1000 h, and can enable solar-powered water splitting systems with uninterrupted large-scale hydrogen production throughout day and night. This universal and scalable strategy provides opportunities for the controlled design of efficient multifunctional dual atom catalysts in energy conversion technologies

    Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

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    Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

    Transcription analysis on response of swine lung to H1N1 swine influenza virus

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    <p>Abstract</p> <p>Background</p> <p>As a mild, highly contagious, respiratory disease, swine influenza always damages the innate immune systems, and increases susceptibility to secondary infections which results in considerable morbidity and mortality in pigs. Nevertheless, the systematical host response of pigs to swine influenza virus infection remains largely unknown. To explore it, a time-course gene expression profiling was performed for comprehensive analysis of the global host response induced by H1N1 swine influenza virus in pigs.</p> <p>Results</p> <p>At the early stage of H1N1 swine virus infection, pigs were suffering mild respiratory symptoms and pathological changes. A total of 268 porcine genes showing differential expression (DE) after inoculation were identified to compare with the controls on day 3 post infection (PID) (Fold change ≥ 2, p < 0.05). The DE genes were involved in many vital functional classes, mainly including signal transduction, immune response, inflammatory response, cell adhesion and cell-cell signalling. Noticeably, the genes associated with immune and inflammatory response showed highly overexpressed. Through the pathway analysis, the significant pathways mainly concerned with Cell adhesion molecules, Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway and MAPK signaling pathway, suggesting that the host took different strategies to activate these pathways so as to prevent virus infections at the early stage. However, on PID 7, the predominant function classes of DE genes included signal transduction, metabolism, transcription, development and transport. Furthermore, the most significant pathways switched to PPAR signaling pathway and complement and coagulation cascades, showing that the host might start to repair excessive tissue damage by anti-inflammatory functions. These results on PID 7 demonstrated beneficial turnover for host to prevent excessive inflammatory damage and recover the normal state by activating these clusters of genes.</p> <p>Conclusions</p> <p>This study shows how the target organ responds to H1N1 swine influenza virus infection in pigs. The observed gene expression profile could help to screen the potential host agents for reducing the prevalence of swine influenza virus and further understand the molecular pathogenesis associated with H1N1 infection in pigs.</p

    An analysis of natural variants of tmRNA.

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    E. coli tmRNA, also known as 10Sa RNA or SsrA RNA, is a unique small RNA that possesses properties of both tRNA and mRNA. It has been postulated that tmRNA, through a mechanism called trans-translation, adds an eleven amino acid tag to prematurely terminated proteins. The tagged proteins are directed toward proteolytic degradation. The gene encoding tmRNA (ssrA) has been found in almost every bacterium examined, indicating that tmRNA may provide strong survival advantage for bacteria. Nevertheless, tmRNA has not been shown to be essential for any bacteria. E. coli mutants that do not express tmRNA exhibit some distinguishing phenotypic characteristics, including the failure to support the growth of some hybrid lambdoid phages, e. g., lambdaimmP22 hy25. This study characterizes the natural tmRNA variants from Vibrio cholerae and Neisseria gonorrhoeae. Although these two tmRNAs share different levels of homology with E. coli tmRNA, both of them function in E. coli as demonstrated by their ability, when expressed in E. coli, to support the growth of lambdaimmP22hy25. However, subtle differences were noted. V. cholerae derivatives lacking tmRNA are viable but under certain conditions exhibit differences in their growth patterns. Since I could not construct viable gonococcal derivatives lacking functional tmRNA, I conclude that tmRNA is an essential function in N. gonorrhoeae. Using N. gonorrhoeae tmRNA variants, I demonstrated that, while charged tmRNA is required for N. gonorrhoeae growth, tmRNA-mediated proteolytic degradation appears only to play an ancillary role. The results of these and other studies suggest that the essential roles of tmRNA in N. gonorrhoeae may include resolving stalled translation complexes and/or preventing depletion of free ribosomes by recycling ribosomes trapped in stalled translation complexes. N. gonorrhoeae with an E. coli ssrA gene as the sole functional ssrA gene in the chromosome grow only after the bacterium has apparently acquired some type of mutation(s). It appears, however, that N. gonorrhoeae expressing both tmRNA and SmpB (a protein shown to be required for tmRNA action) of E. coli origin does not have to acquire extragenic mutation(s) for growth. These results suggest that tmRNA may work preferentially with SmpB and/or other cellular elements from the same bacterial species.Ph.D.Biological SciencesHealth and Environmental SciencesImmunologyMolecular biologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/132379/2/9963809.pd

    Identification and analysis of senescence-related genes in caudal fin cells of triploid crucian carp

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    This research aims to identify the hub genes associated with the senescence of triploid caudal fin cells. Transcriptomic data are obtained from the high and low generation (P6, P60) of triploid crucian carp caudal fin cells by high-throughput sequencing technology. Initially, all differential genes between the high and low generations are screened, yielding 4140 significantly upregulated genes and 3724 significantly downregulated genes. Subsequently, an aging gene set containing 950 genes is downloaded from the CellAge database to extract the differentially expressed genes associated with caudal fin cell aging, totaling 29 genes. GO and KEGG enrichment analyses are performed on these 29 aging differential genes. The GO analysis shows enrichment mainly in cellular processes related to aging, such as regulation of cell division, chromatin organization, cell cycle regulation. KEGG analysis reveals that the 29 aging-related genes are primarily involved in cell cycle and cellular senescence pathways. A PPI network of aging-related genes is constructed using the STRING database and Cytoscape software. Top-ranked genes were identified by using Degree, MCC, MNC, and Closeness algorithms in the Cytohubba plugin in Cytoscape, resulting in hub genes EZH2, JUN, MYD88, RBL2, BMP4, CCND1, NFKB2, MMP9. Lastly, qRT-PCR validation of these eight hub genes further confirmed the involvement of four genes: EZH2, RBL2, BMP4, and CCND1. The hub gene screened in this study may become a potential biomarker of fish caudal fin cell senescence, which provides a valuable experimental basis for the senescence of fish caudal fin cells, especially the senescence of caudal fin cells in polyploid fish, and the reproduction and breeding improvement of polyploid fish. It also provides meaningful data for elucidating the molecular mechanism of polyploid formation in animals, as well as the formation of aging and tumour in human beings

    A TiO2 Coated Carbon Aerogel Derived from Bamboo Pulp Fibers for Enhanced Visible Light Photo-Catalytic Degradation of Methylene Blue

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    Carbon aerogels (CA) derived from bamboo cellulose fibers were coupled with TiO2 to form CA/TiO2 hybrids, which exhibited extraordinary performance on the photo-catalytic degradation of methylene blue (MB). The structure and morphology of CA/TiO2 were characterized by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and Raman spectrum. The CA displayed a highly porous and interconnected three-dimensional framework structure, while introducing the catalytic active sites of TiO2 onto the aerogel scaffold could remarkably enhance its photo-catalytic activity. The adsorption and photo-catalytic degradation of MB by the CA/TiO2 hybrid were investigated. The maximum adsorption capacity of CA/TiO2 for MB was 18.5 mg/g, which outperformed many similar materials reported in the literature. In addition, compared with other photo-catalysts, the present CA/TiO2 demonstrated superior photo-catalytic performance. Almost 85% of MB in 50 mL solution with a MB concentration of 10 mg/L could be effectively degraded by 15 mg CA/TiO2 in 300 min

    Integrated network pharmacology and metabolomics reveal the mechanisms of Jasminum elongatum in anti-ulcerative colitis

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    Abstract Jasminum elongatum (JE), an ethnic Chinese medicine, is widely used in the Lingnan region of China, because of its analgesic and antidiarrheal action, as well as its anti-inflammatory effects in gastrointestinal diseases. However, whether JE could against ulcerative colitis (UC) remains unclear. This research aims to reveal JE in treating UC and clarify the underlying mechanism. We used the 2.5% dextran sulfate sodium (DSS)-induced UC mice (C57BL/6J) to evaluate the therapeutic effects of JE. Metabolomics of serum and network pharmacology were combined to draw target-metabolite pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using immunohistochemistry. The pharmacodynamic results, including disease activity index (DAI), histological evaluation, and inflammatory cytokines in colon tissues, demonstrated that JE significantly relieved the physiological and pathological symptoms of UC. Network pharmacology analysis indicated 25 core targets, such as TNF, IL-6, PTGS2 and RELA, and four key pathways, including the NF-ÎşB signaling pathway and arachidonic acid metabolism pathway, which were the key connections between JE and UC. Metabolomics analysis identified 45 endogenous differential metabolites and 9 metabolic pathways by enrichment, with the arachidonic acid metabolism pathway being the main metabolism pathway, consistent with the prediction of network pharmacology. IÎşB, p65 and COX-2 were identified as key targets and this study demonstrated for the first time that JE reverses 2.5% DSS-induced UC in mice via the IÎşB/p65/COX-2/arachidonic acid pathway. This study reveals the complex mechanisms underlying the therapeutic effects of JE on UC and provides a new approach to identifying the underlying mechanisms of the pharmacological action of Chinese natural medicines such as JE

    Discovery of Pyrrolo[2,3-<i>c</i>]pyridines as Potent and Reversible LSD1 Inhibitors

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    http://deepblue.lib.umich.edu/bitstream/2027.42/178257/2/DiscoveryofPyrrolo[2,3‑c]pyridinesasPotentandReversibleLSD1Inhibitors.pdfPublished onlin
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