1,721,726 research outputs found

    Exosomes from human fibroblasts and HaCaT cells cocultured on 3D silk fibroin nonwovens electrospun hybrids stimulate neoangiogenesis and regulate inflammation-related cytokines release

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    Background: Silk fibroin (SF), as a natural biomacromolecule, has good biocompatibility, degradability, and potentiality for use as a tissue engineering scaffold material. Previous work suggested that adult human dermal fibroblasts(HDFs) can adhere to a novel type of 3D silk fibroin nonwovens (3D-SFnws) and release exosomes promoting neoangiogenesis. By combining a layer of electrospun SF nanofibers with the original 3D-SFnws scaffolds, we obtained the novel 3D-SFnws/ES hybrid scaffolds. The present study used cocultures of HDFs and human keratinocytes (HaCaT cells) on this new scaffold to assess whether the released exosomes contained factors promoting neoangiogenesis and regulating inflammatory responses. Method: The features of novel 3D-SFnws/ES hybrids were defined by electron microscopy imaging and specific physical tests. HDFs and HaCaT cells were separately cultured on the opposite sides of this scaffolds and on polystyrene plates using a medium with exosome-depleted FBS. The growth and metabolic activities of the two types of cells on the scaffold were explored by tests assessing DNA amounts and D-glucose consumption. The total exosomes were isolated respectively from conditioned media of HDFs and HaCaT cells cocultured on 3D-SFnws/ES hybrids and on Transwell 1 2 plates. The exosomes’ expression of their specific surface markers CD9 and CD81 was verified using two ELISA kits. Analyses using human cytokines antibody arrays assessed the expression of Inflammation factors (IFs) and Angiogenic growth factors (AGFs) transported by equal quantities of exosomes from the two groups. A tube formation assay was also used to evaluate the exosomes’ angiogenic ability by using in vitro cultures of human dermal microvascular endothelial cells (HDMVECs). Results: Not only the novel 3D-SFnws/ES hybrids imitated the epithelial-mesenchymal structure of normal skin, but also met the typical biomechanical requirements of human soft tissues implants. Compared with experimental day 3, at day experimental 15 in vitro HDFs adhering to the 3D-SFnws side of the new scaffold had increased by 4.7-fold in numbers and metabolized 5.3-fold more D-glucose. Also HaCaT cells growing on the scaffold's ES side had increased by 6.5-fold in numbers and metabolized 6.2-fold more D-glucose between day 3 and 15 in vitro. Exosomes from HDFs and HaCaT cells cocultured on 3D-SFnws/ES hybrids carried significantly higher amounts of IFs than the Transwell group, such as Interleukin-8 (IL-8), IL-10, Monocyte Chemoattractant Protein-1 (MCP-1), Macrophage Inflammatory Protein-1α (MIP-1α), Eosinophil chemotactic protein 2 (Eotaxin-2), Macrophage Colony-Stimulating Factor (M-CSF), and Tissue Inhibitor of MetalloProteinase-2 (TIMP-2). And the amounts of AGFs, such as Growth-Regulated Oncogene (GRO), Monocyte Chemoattractant Protein-1 (MCP-1), TIMP-1, TIMP-2, and Matrix MetalloPeptidase 9 (MMP-9), were significantly increased in the exosomes isolated from the 3D-SFnws/ES hybrids group. At concentrations from 0.5 to 5 μg/mL, the latter exosomes showed their angiogenic power by inducing HDMVECs to form tubes in vitro. However, an alike effect (P > 0.05) brought about the exosomes from the Transwell group. Conclusions: The novel scaffold we obtained by combining a layer of electrospun SF nanofibers with the 3D-SFnws scaffolds not only kept the good physical features of original ones, but also allowed HDFs and HaCaT cells to adhere and proliferate on their opposite sides having different structures. HDFs and HaCaT cells co-grown on these scaffolds released exosomes carrying several AGFs which swiftly induced HDMVECs to form tubes in vitro. The same exosomes conveyed IFs capable of promoting and orderly regulating inflammatory response. Thus, we posit that once implanted in vivo this new composite SF scaffold could promote skin wound healing by promoting human keratinocytes and HDFs growth and metabolism, advancing vascularization, and modulating local inflammation

    Backward Stochastic Evolution Equations in UMD Banach Spaces

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    Extending results of Pardoux–Peng and Hu–Peng, we prove well-posedness results for backward stochastic evolution equations in UMD Banach spaces.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Analysi

    Supplemental Material - Chinese Cancer Patients’ Attitudes Toward Psychotherapy and Their Willingness to Participate in Clinical Trials of Psychotherapy

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    Supplemental Material for Chinese Cancer Patients’ Attitudes Toward Psychotherapy and Their Willingness to Participate in Clinical Trials of Psychotherapy by Zhi Zeng, Yaotiao Deng, Jie Liu, Keyi Yang, Hu Peng, Yu Jiang in Cancer Control</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Danger‐Sensing/Pattern Recognition Receptors and Neuroinflammation in Alzheimer’s Disease

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    Fibrillar aggregates and soluble oligomers of both Amyloid‐β peptides (Aβs) and hyperphosphorylated Tau proteins (p‐Tau‐es), as well as a chronic neuroinflammation are the main drivers causing progressive neuronal losses and dementia in Alzheimer’s disease (AD). However, the underlying pathogenetic mechanisms are still much disputed. Several endogenous neurotoxic ligands, including Aβs, and/or p‐Tau‐es activate innate immunity‐related danger‐sensing/pattern recognition receptors (PPRs) thereby advancing AD’s neuroinflammation and progression. The major PRR families involved include scavenger, Toll‐like, NOD‐like, AIM2‐like, RIG‐like, and CLEC‐ 2 receptors, plus the calcium‐sensing receptor (CaSR). This quite intricate picture stresses the need to identify the pathogenetically topmost Aβ‐activated PRR, whose signaling would trigger AD’s three main drivers and their intra‐brain spread. In theory, the candidate might belong to any PRR family. However, results of preclinical studies using in vitro nontumorigenic human cortical neurons and astrocytes and in vivo AD‐model animals have started converging on the CaSR as the pathogenetically upmost PRR candidate. In fact, the CaSR binds both Ca2+ and Aβs and promotes the spread of both Ca2+ dyshomeostasis and AD’s three main drivers, causing a progressive neurons’ death. Since CaSR’s negative allosteric modulators block all these effects, CaSR’s candidacy for topmost pathogenetic PRR has assumed a growing therapeutic potential worth clinical testing

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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