95,539 research outputs found

    Combination of biodegradable hydrogel and antioxidant bioadhesive for treatment of breast cancer recurrence and radiation skin injury

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    Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis, whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the prognosis of breast cancer. Herein, we design an internally implantable biodegradable hydrogel and extracutaneously applicable antioxidant bioadhesive to concurrently prevent postoperative tumor recurrence and radioactive skin injury after adjuvant radiotherapy. The biodegradable silk fibroin/perfluorocarbon hydrogel loading doxorubicin (DOX) formed by consecutive ultrasonication-induced β-sheets-crosslinked amphiphilic silk fibroin/perfluorocarbon/DOX nanoemulsion, exhibits continuous release of oxygen in physiological environment to improve hypoxia and sensitivity of radiotherapy, as well as simultaneous release of DOX to finally achieve effective anti-cancer effect. A stretchable bioadhesive is fabricated by copolymerization of α-thioctic acid and N, N-diacryloyl-l-lysine, and gold nanorods and gallic acid are loaded into the bioadhesive to afford gentle photothermal therapy and antioxidant functions. The near-infrared light-induced controlled release of gallic acid and mild photothermal therapy can efficiently eliminate excess free radicals generated by radiotherapy and promote radioactive wound healing. Ultimately, in vivo animal studies substantiate the efficacy of our methodology, wherein the post-tumor resection administration of hydrogel and concomitant application of an antioxidant bioadhesive patch effectively inhibit tumor recurrence and attenuate the progression of skin radiation damage

    Integrated modeling for retired mechanical product genes in remanufacturing: A knowledge graph-based approach

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    Retired mechanical product genes refer to a collection of information that describes the structure, status, and related characteristics of retired mechanical products. Leveraging this information, along with its implicit knowledge, is a key approach to enhance the intelligence and efficiency of the remanufacturing process. This study aims to automatically obtain and integrate multi-source, heterogeneous, multilayer, and multidimensional retired mechanical product information and its implicit knowledge through a knowledge graph to form a gene bank, providing data basis for the remanufacturing process. First, the conceptual model of retired mechanical product genes and overall modeling framework based on knowledge graph are established. Next, according to the gene characteristics on different product layers, appropriate modeling methods were designed for part genes, product function and structure genes, product performance and failure genes respectively. For implicit rules and knowledge that pose challenges for direct representation, we express them in the IF-THEN form and convert them into triples. Then, an information fusion method is employed to integrate genes information on various layers into a gene graph. Finally, the proposed integrated modeling approach was evaluated in a scenario of remanufacturing an eleven-roll straightening machine. The results indicate that it can automatically obtain part genes information quickly and effectively. Additionally, it was confirmed that the constructed gene graph exhibits good accuracy and completeness, demonstrating the promising application prospects of the proposed method in remanufacturing

    Efficient extraction of pectic polysaccharides from thinned unripe kiwifruits by deep eutectic solvent-based methods: Chemical structures and bioactivities

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    To promote the potentially industrial applications of thinned unripe kiwifruits, two deep eutectic solvent-based methods, including deep eutectic solvent-assisted extraction (DAE) and microwave-assisted deep eutectic solvent extraction (MDE), were optimized for the extraction of polysaccharides from thinned unripe kiwifruits (YKP). Results showed that the yields of YKP-D prepared by DAE and YKP-DM prepared by MDE were extremely higher than YKP-H prepared by hot water extraction. Furthermore, YKP-H, YKP-D, and YKP-DM were mainly composed of pectic polysaccharides, including homogalacturonan (HG) and rhamnogalacturonan I (RG I) domains. Besides, both YKP-D and YKP-DM exhibited stronger antioxidant, anti-glycosylation, and immunomodulatory effects than those of YKP-H, and their higher contents of uronic acids and bound polyphenols as well as lower molecular weights could partially contribute to their bioactivities. Overall, these results revealed that the developed MDE method could be utilized as a promising method for highly efficient extraction of YKP with superior beneficial effects

    Image_5_A prognostic model based on DNA methylation-related gene expression for predicting overall survival in hepatocellular carcinoma.png

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    BackgroundHepatocellular carcinoma (HCC) continues to increase in morbidity and mortality among all types of cancer. DNA methylation, an important epigenetic modification, is associated with cancer occurrence and progression. The objective of this study was to establish a model based on DNA methylation risk scores for identifying new potential therapeutic targets in HCC and preventing cancer progression.MethodsTranscriptomic, clinical, and DNA methylation data on 374 tumor tissues and 50 adjacent normal tissues were downloaded from The Cancer Genome Atlas–Liver Hepatocellular Carcinoma database. The gene expression profiles of the GSE54236 liver cancer dataset, which contains data on 161 liver tissue samples, were obtained from the Gene Expression Omnibus database. We analyzed the relationship between DNA methylation and gene expression levels after identifying the differentially methylated and expressed genes. Then, we developed and validated a risk score model based on the DNA methylation-driven genes. A tissue array consisting of 30 human hepatocellular carcinoma samples and adjacent normal tissues was used to assess the protein and mRNA expression levels of the marker genes by immunohistochemistry and qRT-PCR, respectively.ResultsThree methylation-related differential genes were identified in our study: GLS, MEX3B, and GNA14. The results revealed that their DNA methylation levels were negatively correlated with local gene expression regulation. The gene methylation levels correlated strongly with the prognosis of patients with liver cancer. This was confirmed by qRT-PCR and immunohistochemical verification of the expression of these genes or proteins in tumors and adjacent tissues. These results revealed the relationship between the level of relevant gene methylation and the prognosis of patients with liver cancer as well as the underlying cellular and biological mechanisms. This allows our gene signature to provide more accurate and appropriate predictions for clinical applications.ConclusionThrough bioinformatics analysis and experimental validation, we obtained three DNA methylation marker: GLS, MEX3B, and GNA14. This helps to predict the prognosis and may be a potential therapeutic target for HCC patients.</p

    <i>In Situ</i> Cas12a-Based Allele-Specific PCR for Imaging Single-Nucleotide Variations in Foodborne Pathogenic Bacteria

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    In situ profiling of single-nucleotide variations (SNVs) can elucidate drug-resistant genotypes with single-cell resolution. The capacity to directly “see” genetic information is crucial for investigating the relationship between mutated genes and phenotypes. Fluorescence in situ hybridization serves as a canonical tool for genetic imaging; however, it cannot detect subtle sequence alteration including SNVs. Herein, we develop an in situ Cas12a-based amplification refractory mutation system-PCR (ARMS-PCR) method that allows the visualization of SNVs related to quinolone resistance inside cells. The capacity of discriminating SNVs is enhanced by incorporating optimized mismatched bases in the allele-specific primers, thus allowing to specifically amplify quinolone-resistant related genes. After in situ ARMS-PCR, we employed a modified Cas12a/CRISPR RNA to tag the amplicon, thereby enabling specific binding of fluorophore-labeled DNA probes. The method allows to precisely quantify quinolone-resistant Salmonella enterica in the bacterial mixture. Utilizing this method, we investigated the survival competition capacity of quinolone-resistant and quinolone-sensitive bacteria toward antimicrobial peptides and indicated the enrichment of quinolone-resistant bacteria under colistin sulfate stress. The in situ Cas12a-based ARMS-PCR method holds the potential for profiling cellular phenotypes and gene regulation with single-nucleotide resolution at the single-cell level

    Assessing the refolding of Martini CGMD sampled ASPP-p53 complexes.

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    (A) Refolding is gauged by a RMSD metric, namely, starting from the moment when ASPP and p53 first contact, the subsequent complexes’ RMSDs with respect to the first contact complex were calculated. (B-C) Five Martini CGMD trajectories were randomly selected to assess the refolding for ASPP2 and iASPP in the binding of p53DBD, respectively.</p

    Search for vector-boson resonances decaying into a top quark and a bottom quark using pp collisions at s = 13 TeV with the ATLAS detector