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- 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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4. |
- Liu, Yi, et al.
(författare)
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Effect of fluorine atoms on optoelectronic, aggregation and dielectric constants of 2,1,3-benzothiadiazole-based alternating conjugated polymers
- 2021
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Ingår i: Dyes and Pigments. - : Elsevier BV. - 0143-7208 .- 1873-3743. ; 193
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Tidskriftsartikel (refereegranskat)abstract
- Three 2,1,3-benzothiadiazole-based conjugated copolymers named PBDT-0F-BTs, PBDT-2F-BTs and PBDT-6F-FBTs, which were derived from 4,8-bis(4,5-dioctylthiophen-2-yl)benzo[1,2-b:4,5-b′]dithiophene and (3,4′-bis(2-hexyl- decyl)-2,2′-dithiophene-5-yl) substituted 2,1,3-benzothiadiazole and/or 5,6-difluoro- 2,1,3-benzothiadiazole derivatives with 2,2′-dithiophene and/or 3,3′-difluoro- 2,2′-dithiophene as π-linkers, were prepared and characterized. The copolymers PBDT-0F-BTs, PBDT-2F-BTs and PBDT-6F-FBTs exhibited the highest occupied molecular orbital (HOMO) and lowest unoccupied orbital (LUMO) energy levels of −5.38 eV/−3.57 eV, −5.45 eV/−3.65 eV and −5.55 eV/−3.78 eV, with the light response from 300 nm to 720–750 nm, alongside with the similar aggregation, except that the charge transporting mobilities were successively increased, and the dielectric constants were gradually improved from 3.3 to 4.8 to 5.9 at 1 KHz, while the fluorine atoms in the each repeat unit of polymers were varied from 0 to 2 and then up to 6, respectively. Beyond that, it has also been found that the power conversion efficiencies and exciton dissociation probability (P(E,T)) of the bulk heterojunction organic photovoltaic cells (BHJ-OPVs) from the blend films of polymers paired with Y6 (2,2'-((2Z,2'Z)-((12,13-bis(2-ethylhexyl)-3,9-diundecyl12,13-dihydro[1,2,5]thia- diazolo[3,4-e]thieno[2'',3'':4',5']thieno[2',3':4,5]pyrrolo[3,2-g]thieno[2',3':4,5]thieno[3,2-b]indole-2,10-diyl)bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-ind-ene-2,1-diylidene))dimalononitrile), were varied from 7.83% and 85.9%, to 9.22% and 90.2% and then up to 12.34% and 91.4%. The results indicated that the continuous insertion of the fluorine atoms into the repeat units of the conjugated polymers would result in the consecutively deepening the HOMO energy levels, increase dielectric constants and charge mobilities, thus devote to the enhancement of the P(E,T) and the performance of the BHJ-OPVs.
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