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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Li, Peng, et al.
(författare)
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Transcriptional reactivation of OTX2, RX1 and SIX3 during reprogramming contributes to the generation of RPE cells from human iPSCs
- 2016
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Ingår i: International Journal of Biological Sciences. - : Ivyspring International Publisher. - 1449-2288. ; 12:5, s. 505-517
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Tidskriftsartikel (refereegranskat)abstract
- Directed differentiation of human induced pluripotent stem cells (iPSCs) into retinal pigmented epithelium (RPE) holds great promise in cell replacement therapy for patients suffering from degenerative eye diseases, including age-related macular degeneration (AMD). In this study, we generated iPSCs from human dermal fibroblasts (HDFs) by electroporation with episomal plasmid vectors encoding OCT4, SOX2, KLF4, L-MYC together with p53 suppression. Intriguingly, cell reprogramming resulted in a metastable transcriptional activation and selective demethylation of neural and retinal specification-associated genes, such as OTX2, RX1 and SIX3. In contrast, RPE progenitor genes were transcriptionally silent in HDFs and descendant iPSCs. Overexpression of OCT4 and SOX2 directly stimulated the expression of OTX2, RX1 and SIX3 in HDFs and iPSCs. Luciferase and chromatin immunoprecipitation (ChIP) assays further identified an OCT4- and two SOX2-binding sites located in the proximal promoter of OTX2. Histone acetylation and methylation on the local promoter also participated in the reactivation of OTX2. The transcriptional conversion of RX1 and SIX3 genes partially attributed to DNA demethylation. Subsequently, iPSCs were induced into the RPE cells displaying the characteristics of polygonal shapes and pigments, and expressing typical RPE cell markers. Taken together, our results establish readily efficient and safe protocols to produce iPSCs and iPSC-derived RPE cells, and underline that the reactivation of anterior neural transcription factor OTX2, eye field transcription factor RX1 and SIX3 in iPSCs is a feature of pluripotency acquisition and predetermines the potential of RPE differentiation.
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| 4. |
- Cai, P., et al.
(författare)
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Effects of including electron-withdrawing atoms on the physical and photovoltaic properties of indacenodithieno 3,2-b thiophene-based donor-acceptor polymers: towards an acceptor design for efficient polymer solar cells
- 2017
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 7:33, s. 20440-20450
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Tidskriftsartikel (refereegranskat)abstract
- Three new D-A polymers PIDTT-DTBO, PIDTT-DTBT and PIDTT-DTFBT, using indacenodithieno[3,2-b] thiophene (IDTT) as the electron-rich unit and benzoxadiazole (BO), benzodiathiazole (BT) or difluorobenzothiadiazole (FBT) as the electron-deficient unit, were synthesized via a Pd-catalyzed Stille polymerization. The included electron-withdrawing atoms of the acceptor portion were varied between O, S, and F for tailoring the optical and electrochemical properties and the geometry of structures. Their effects on the film topography, photovoltaic and hole-transporting properties of the polymers were thoroughly investigated via a range of techniques. As expected, the stronger electron-withdrawing BO unit affords red-shifted absorption, low-lying HOMO and LUMO levels for the polymer PIDTT-DTBO. However, it depicts lower hole mobility and a less efficient charge collection in the active layer compared to the polymer PIDTT-DTBT. In addition, degradation of the solubility is observed in the fluorinated polymer PIDTT-DTFBT. As a result, a BHJ PSC (ITO/PEDOT: PSS/polymer: PC71BM/interlayer/ Al) fabricated with PIDTT-DTBT attains the best power conversion efficiency (PCE) of 4.91%. These results thus demonstrate the potential effects of electronegative atoms on IDTT-based polymers and the structure-function correlations of such electron-donor materials for efficient PSCs.
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| 5. |
- Chen, Wen, 1988, et al.
(författare)
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VLBI Astrometry of radio stars to link radio and optical celestial reference frames. I. HD 199178 & AR Lacertae
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 524:4, s. 5357-5367
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Tidskriftsartikel (refereegranskat)abstract
- To accurately link the radio and optical Celestial Reference Frames (CRFs) at optical bright end, i.e. with GaiaG-band magnitude ≾13, increasing number and improving sky distribution of radio stars with accurate astrometric parameters from both Very Long Baseline Interferometry (VLBI) and Gaia measurements are mandatory. We selected two radio stars HD 199178 and AR Lacertae as the target for a pilot program for the frame link, using the Very Long Baseline Array at 15 GHz at six epochs spanning about 1 yr, to measure their astrometric parameters. The measured parallax of HD 199178 is 8.949 ± 0.059 mas and the proper motion is μαcos δ = 26.393 ± 0.093 and μδ = −0.950 ± 0.083 mas yr−1, while the parallax of AR Lac is 23.459 ± 0.094 mas and the proper motion is μαcos δ = −51.906 ± 0.138 and μδ = 46.732 ± 0.131 mas yr−1. Our VLBI measured astrometric parameters have accuracies about 4–5 times better than the corresponding historic VLBI measurements and comparable accuracies with those from Gaia, validating the feasibility of frame link using radio stars. With the updated astrometric parameters for these two stars, there is a ∼25 per cent reduction of the uncertainties on the Y-axis for both orientation and spin parameters.
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| 6. |
- Cui, Luqing, et al.
(författare)
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Low Cycle Fatigue Behavior and Microstructural Evolution of Nickel-based Superalloy M951G at Elevated Temperatures
- 2020
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Ingår i: Materials Characterization. - : Elsevier. - 1044-5803 .- 1873-4189. ; 163
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Tidskriftsartikel (refereegranskat)abstract
- Low cycle fatigue (LCF) tests of the newly developed nickel-based superalloy M951G have been conducted at 900 and 1000 °C under different total strain amplitudes. Results show that the fatigue properties, fracture mechanisms as well as coarsening of γ′ precipitates are dependent on testing temperatures and strain amplitudes. Fatigue life and cyclic stress response under the same total strain amplitude at 1000 °C are lower than that at 900 °C, which is due to the degradation of microstructures, shearing of γ′ precipitates by dislocations and serious oxidation. Fracture modes change from intergranular cracking to the mixed mode cracking as the strain amplitude increases. At low strain amplitudes, M951G alloy fails in the form of intergranular cracking owing to the oxidation of surface carbides and the relatively low deformation rate. At higher strain amplitudes, the strain localization in grain interior, the distribution of broken carbides and eutectics as well as the relatively higher strain rate are the main reasons for the formation of transgranular microcracks. Ultimately, the effects of fatigue conditions on coarsening of cubic γ′ precipitates are also analyzed from the aspect of γ′ volume fraction, fatigue life and flow stress difference between the γ/γ′ interfaces.
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| 7. |
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| 8. |
- Huang, Hongyun, et al.
(författare)
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Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)
- 2018
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 27:2, s. 310-324
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Forskningsöversikt (refereegranskat)abstract
- Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.
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| 9. |
- Jackson, Shaun W., et al.
(författare)
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Disordered purinergic signaling inhibits pathological angiogenesis in Cd39/Entpd1-Null mice
- 2007
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 171:4, s. 1395-1404
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Tidskriftsartikel (refereegranskat)abstract
- CD39/ecto-nucleoside triphosphate diphosphohydrolase-type-1 (ENTPD1) is the dominant vascular ectonucleotidase that catalyzes the phosphohydrolysis of extracellular nucleotides in the blood and extracellular space. This ecto-enzymatic process modulates endothelial cell, leukocyte, and platelet purinergic receptor-mediated responses to extracellular nucleotides in the setting of thrombosis and vascular inflammation. We show here that deletion of Cd39/Entpd1 results in abrogation of angiogenesis, causing decreased growth of implanted tumors and inhibiting development of pulmonary metastases. Qualitative abnormalities of Cd39-null endothelial cell adhesion and integrin dysfunction were demonstrated in vitro. These changes were associated with decreased activation of focal adhesion kinase and extracellular signaling-regulated kinase-1 and -2 in endothelial cells. Our data indicate novel links between CD39/ENTPD1, extracellular nucleotide-mediated signaling, and vascular endothelial cell integrin function that impact on angiogenesis and tumor growth.
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| 10. |
- Jiang, Qianer, et al.
(författare)
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A review on the gastrointestinal protective effects of tropical fruit polyphenols
- 2023
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Ingår i: Critical reviews in food science and nutrition. - : Taylor & Francis. - 1040-8398 .- 1549-7852. ; 63:24, s. 7197-7223
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Forskningsöversikt (refereegranskat)abstract
- Tropical fruits are popular because of their unique, delicious flavors and good nutritional value. Polyphenols are considered to be the main bioactive ingredients in tropical fruits, and these exert a series of beneficial effects on the human gastrointestinal tract that can enhance intestinal health and prevent intestinal diseases. Moreover, they are distinct from the polyphenols in fruits grown in other geographical zones. Thus, the comprehensive effects of polyphenols in tropical fruits on gut health warrant in-depth review. This article reviews, first, the biological characteristics of several representative tropical fruits, including mango, avocado, noni, cashew apple, passion fruit and lychee; second, the types and content of the main polyphenols in these tropical fruits; third, the effects of each of these fruit polyphenols on gastrointestinal health; and, fourth, the protective mechanism of polyphenols. Polyphenols and their metabolites play a crucial role in the regulation of the gut microbiota, increasing intestinal barrier function, reducing oxidative stress, inhibiting the secretion of inflammatory factors and regulating immune function. Thus, review highlights the value of tropical fruits, highlighting their significance for future research on their applications as functional foods that are oriented to gastrointestinal protection.
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