31 research outputs found

    Efficient Procedures of Sensitivity Analysis for Structural Vibration Systems with Repeated Frequencies

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    Derivatives of eigenvectors with respect to structural parameters play an important role in structural design, identification, and optimization. Particularly, calculation of eigenvector sensitivity is considered when the eigenvalues are repeated. A relaxation factor embedded in the combined approximations (CA) method makes it effective to the structural response at various modified designs. The proposed method is feasible after overcoming the defection of irreversibility of the characteristic matrix. Numerical examples show that it is easy to implement the computational procedure, and the method presented in this paper is efficient for the general linear vibration damped systems with repeated frequencies

    Confining the Sol-Gel Reaction at the Water/Oil Interface:Creating Compartmentalized Enzymatic Nano-Organelles for Artificial Cells

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    Living organisms compartmentalize their catalytic reactions in membranes for increased efficiency and selectivity. To mimic the organelles of eukaryotic cells, we develop a mild approach for in situ encapsulating enzymes in aqueous-core silica nanocapsules. In order to confine the sol-gel reaction at the water/oil interface of miniemulsion, we introduce an aminosilane to the silica precursors, which serves as both catalyst and an amphiphilic anchor that electrostatically assembles with negatively charged hydrolyzed alkoxysilanes at the interface. The semi-permeable shell protects enzymes from proteolytic attack, and allows the transport of reactants and products. The enzyme-carrying nanocapsules, as synthetic nano-organelles, are able to perform cascade reactions when enveloped in a polymer vesicle, mimicking the hierarchically compartmentalized reactions in eukaryotic cells. This in situ encapsulation approach provides a versatile platform for the delivery of biomacromolecules.</p

    Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma

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    Background/Aims: Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors, but the functions of specific lncRNAs and lncRNA-related ceRNA networks have not been fully elucidated for colon adenocarcinoma (COAD). In this study, we aimed to clarify the lncRNA-microRNA (miRNA)-mRNA ceRNA network and potential lncRNA biomarkers in COAD. Methods: We extracted data from The Cancer Genome Atlas (TCGA) and identified COAD-specific mRNAs, miRNAs, and lncRNAs. The biological processes in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for COAD-specific mRNAs. We then constructed a ceRNA network of COAD-specific mRNAs, miRNAs and lncRNAs and analyzed the correlation between expression patterns and clinical features of the lncRNAs involved. After identifying potential mRNA targets of 4 lncRNAs related to overall survival (OS), we conducted stepwise analysis of these targets through GO and KEGG. Using tissue samples from our own patients, we also verified certain analytical results using quantitative real-time PCR (qRT-PCR). Results: Data from 521 samples (480 tumor tissue and 41 adjacent non-tumor tissue samples) were extracted from TCGA. A total of 258 specific lncRNAs, 206 specific miRNAs, and 1467 specific mRNAs were identified (absolute log2 [fold change] &#x3e; 2, false discovery rate &#x3c; 0.01). Analysis of KEGG revealed that specific mRNAs were enriched in cancer-related pathways. The ceRNA network was constructed with 64 lncRNAs, 18 miRNAs, and 42 mRNAs. Among these lncRNAs involved in the network, 3 lncRNAs (LINC00355, HULC, and IGF2-AS) were confirmed to be associated with certain clinical features and 4 lncRNAs (HOTAIR, LINC00355, KCNQ1OT1, and TSSC1-IT1) were found to be negatively linked to OS (log-rank p &#x3c; 0.05). KEGG showed that the potential mRNA targets of these 4 lncRNAs may be concentrated in the MAPK pathway. Certain results were validated by qRT-PCR. Conclusion: This study providing novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential lncRNA biomarkers in COAD

    DNA methylation on N6-adenine in mammalian embryonic stem cells

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    It has been widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes. Here we identify N6-methyladenine as another form of DNA modification in mouse embryonic stem cells. Alkbh1 encodes a demethylase for N6-methyladenine. An increase of N6-methyladenine levels in Alkbh1-deficient cells leads to transcriptional silencing. N6-methyladenine deposition is inversely correlated with the evolutionary age of LINE-1 transposons; its deposition is strongly enriched at young (6 million years old) L1 elements. The deposition of N6-methyladenine correlates with epigenetic silencing of such LINE-1 transposons, together with their neighbouring enhancers and genes, thereby resisting the gene activation signals during embryonic stem cell differentiation. As young full-length LINE-1 transposons are strongly enriched on the X chromosome, genes located on the X chromosome are also silenced. Thus, N6-methyladenine developed a new role in epigenetic silencing in mammalian evolution distinct from its role in gene activation in other organisms. Our results demonstrate that N6-methyladenine constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes

    PPARĪ³ overexpression regulates cholesterol metabolism in human L02 hepatocytes

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    Peroxisome proliferator-activator receptor (PPAR) Ī³ is a nuclear hormone receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte function. It has been shown that activation of PPARĪ³ can reduce the incidence of gallstone. Herein we aimed to clarify the role of PPARĪ³ in the reduction of gallstones. The plasmid containing the coding sequence of PPARĪ³ was constructed and transfected in the human liver cell line (L02Ā cells). Western blot and RT-PCR were used to detect hydroxyl-methyl-glutaryl-CoA reductase (HMGCR), sterol regulatory element-binding proteins 2 (SREBP2), 7Ī±-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8) and liver X receptor Ī± (LXRĪ±). The Amplex Red cholesterol assay kit was used to detect the intracellular or extracellular cholesterol level. Our data showed that PPARĪ³ overexpression caused significant decreases in both extracellular and intracellular cholesterol in the L02Ā cells. The further studies indicated PPARĪ³ overexpression substantially decreased expression of HMGCR and SREBP-2, increased expression of CYP7A1, ABCG5, ABCG8 and LXRĪ±. These results indicated that upregulation of PPARĪ³ may reduce cholesterol levels through multiple-pathways including HMGCR/SREBP2-mediated biosynthesis, CYP7A1-mediated transformation, and ABCG5/ABCG8-mediated efflux. We thus suggest that PPARĪ³ might have beneficial effects for cholesterol gallstones diseases. Keywords: PPARĪ³, Cholesterol, HMGCR, CYP7A1 and ABCG5/

    Controlling Factors and Quantitative Characterization of Pore Development in Marine-Continental Transitional Shale

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    AbstractThe pore characteristics are studied in the overmatured marine-continental transitional (MCT) shale and simulated shale under different thermal maturity conditions, based on transitional and simulated shale samples in the eastern margin of Ordos Basin. The work uses high-pressure mercury intrusion (MICP), field emission scanning electron microscopy (FESEM), helium-mercury method, X-ray diffraction of whole-rock minerals, and hydrocarbon-generating thermal simulation to quantitatively analyze pore characteristics and main controlling factors of pore development. The results show that the shallow bay and lake facies (SBLF) shale has great exploration potential, while the delta facies (DF) shale has poor exploration potential. The SBLF shale is mainly characterized by pie shale, high quartz and carbonate, low clay, high porosity, and pore volume. The DF shale mainly develops dot shale with low quartz and carbonate content, high clay content, low porosity, and pore volume. Kaolinite has the strongest inhibition on MTC shale pore development. The pore volume of MTC shale decreases first and then increases with maturity. The pie shale is more conducive to the increase of pore volume than the dot shale. The effect of doubled TOC on porosity is greater than that of maturity in the dot shale. The effect of doubled TOC on porosity is less than that of maturity in the pie shale. Organic matter (OM) has the greatest impact on pore development, controlled by the OM content, sedimentary facies, and maturity. OM content, sedimentary facies, and maturity can be used to jointly characterize the MTC shale pore development, providing guidance for multiparameter quantitative characterization of pore development and determining the enrichment area of shale gas

    Integrated Proteomics and Metabolomic Analyses of Plasma Injury Biomarkers in a Serious Brain Trauma Model in Rats

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    Diffuse axonal injury (DAI) is a prevalent and serious brain injury with significant morbidity and disability. However, the underlying pathogenesis of DAI remains largely unclear, and there are still no objective laboratory-based tests available for clinicians to make an early diagnosis of DAI. An integrated analysis of metabolomic data and proteomic data may be useful to identify all of the molecular mechanisms of DAI and novel potential biomarkers. Therefore, we established a rat model of DAI, and applied an integrated UPLC-Q-TOF/MS-based metabolomics and isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to obtain unbiased profiling data. Differential analysis identified 34 metabolites and 43 proteins in rat plasma of the injury group. Two metabolites (acetone and 4-Hydroxybenzaldehyde) and two proteins (Alpha-1-antiproteinase and Alpha-1-acid glycoprotein) were identified as potential biomarkers for DAI, and all may play important roles in the pathogenesis of DAI. Our study demonstrated the feasibility of integrated metabolomics and proteomics method to uncover the underlying molecular mechanisms of DAI, and may help provide clinicians with some novel diagnostic biomarkers and therapeutic targets

    Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumorā€Associated Macrophages in Prostate Cancer

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    Abstract Tumorā€associated macrophages (TAMs) play an essential role in tumor therapeutic resistance. Although the lethal effect of ferroptosis on tumor cells is well reported, how TAMs inhibit the effect of ferroptosis in tumors has not been clearly defined. In this study, it is demonstrated that TAMā€secreted taurine suppresses ferroptosis in prostate cancer (PCa) by activating the Liver X receptor alpha/Stearoylā€Coenzyme A desaturase 1 (LXRĪ±/SCD1) pathway. Blocking taurine intake via inhibition of taurine transporter TauT restores the sensitivity to ferroptosis in tumors. Furthermore, LXRĪ± activates the transcription of both miRā€181aā€5p and its binding protein FUS to increase the recruitment of miRā€181aā€5p in tumorā€derived extracellular vesicles (EVs). It is observed that macrophages appear to be recipient cells of the miRā€181aā€5pā€enriched EVs. Intake of miRā€181aā€5p in macrophages promotes their M2 polarization and enhances the taurine export by inhibiting expression of its target gene lats1, which in turn inactivates the hippo pathway and results in a Yesā€associated protein (YAP) nuclear translocation for transcriptional activation of both M2 polarizationā€related genes such as ARG1 and CD163 and the taurine transport gene TauT. Taken together, the findings indicate a reciprocal interaction between PCa cells and TAMs as a positive feedbackā€loop to repress ferroptosis in PCa, mediated by TAMā€secreted taurine and tumor EVā€delivered miRā€181aā€5p
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