| 1. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)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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| 2. |
- Ma, Xiaotong, et al.
(author)
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Association of sdLDL-C With Incident Carotid Plaques With Stable and Vulnerable Morphology : A Prospective Cohort Study
- 2024
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In: Stroke. - 0039-2499 .- 1524-4628. ; 55:3, s. 576-585
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Journal article (peer-reviewed)abstract
- BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) particles are more atherogenic than large and intermediate low-density lipoprotein cholesterol (LDL-C) subfractions. We sought to investigate the association of sdLDL-C and the sdLDL-C/LDL-C ratio with incident carotid plaques with stable and vulnerable morphology in rural China.METHODS: This community-based cohort study used data from the RICAS study (Rose Asymptomatic Intracranial Artery Stenosis), which enrolled 887 participants (aged ≥40 years) who were living in Kongcun Town, Pingyin County, Shandong, and free of carotid plaques and had no history of clinical stroke or transient ischemic attack at baseline (2017). Incident carotid plaques and their vulnerability were detected by carotid ultrasound at follow-up (2021). Multivariable logistic regression models were used to explore the association of sdLDL-C or sdLDL-C/LDL-C ratio with incident carotid plaques while adjusting for demographic factors, vascular risk factors, and follow-up time.RESULTS: Of the 887 participants (mean age [SD], 53.89 [8.67%] years; 54.34% women), 179 (20.18%) were detected with incident carotid plaques during an average follow-up of 3.94 years (SD=0.14). Higher sdLDL-C or sdLDL-C/LDL-C ratio, but not LDL-C, was significantly associated with an increased risk of incident carotid plaques. The upper tertile of sdLDL-C (versus lower tertile) was associated with the multivariate-adjusted odds ratio of 2.48 (95% CI, 1.00–6.15; P=0.049; P for linear trend=0.046) for carotid plaques with vulnerable morphology (n=41), and the association remained significant in participants with normal LDL-C (<130 mg/dL; n=693; upper versus lower tertile: odds ratio, 3.38 [95% CI, 1.15–9.90]; P=0.027; P for linear trend=0.025). Moreover, the sdLDL-C/LDL-C ratio was associated with a higher odds ratio of incident carotid plaques in participants without diabetes (P for interaction=0.014).CONCLUSIONS: Higher sdLDL-C was associated with an increased risk of incident carotid plaques, especially carotid plaques with vulnerable morphology, even in participants with normal LDL-C. This suggests the potential of sdLDL-C as a therapeutic target for stroke prevention.
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| 3. |
- Bi, Chenghao, et al.
(author)
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Stable CsPb1- xZn xI3Colloidal Quantum Dots with Ultralow Density of Trap States for High-Performance Solar Cells
- 2020
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In: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 32:14, s. 6105-6113
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Journal article (peer-reviewed)abstract
- All inorganic halide perovskites in the form of colloidal quantum dots (QDs) have come into people's view as one of the potential materials for the high-efficiency solar cells; nevertheless, the high surface trap density and poor stability of QDs restrict the performance improvement and application. Here, we obtain colloidal inorganic perovskite CsPb1-xZnxI3 QDs by the hot-injection synthesis process with the addition of ZnCl2. Synchrotron-based X-ray absorption fine structures demonstrate that the guest Zn2+ ions are doped into the CsPbI3 structure to improve the local ordering of the lattice of the perovskite, reducing the octahedral distortions. The increase of the Goldschmidt tolerance factor and the Pb-I bond energy also enhance the stability of the perovskite structure. Furthermore, the Cl- ions from ZnCl2 occupy the iodide vacancies of the perovskite to decrease the nonradiative recombination. The synergistic effect of doping and defect passivation makes for stable colloidal CsPb0.97Zn0.03I3 QDs with ultralow density of trap states. The champion solar cell based on the QDs shows a power conversion efficiency of 14.8% and a largely improved stability under ambient conditions.
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| 4. |
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| 5. |
- Wang, Congying, et al.
(author)
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Adsorption of deoxyribonucleic acid (DNA) by willow wood biochars produced at different pyrolysis temperatures
- 2014
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In: Biology and Fertility of Soils. - : Springer Science and Business Media LLC. - 0178-2762 .- 1432-0789. ; 50:1, s. 87-94
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Journal article (peer-reviewed)abstract
- Adsorption of DNA by biochars was investigated in the present study. Biochars were produced from air-dried willow wood chips at 300, 400, 500, and 600 A degrees C under limited oxygen supply. The resulting products, referred to as BC300, BC400, BC500, and BC600, respectively, were characterized for their elemental composition, cation exchange capacity (CEC), specific surface areas (SSA), and microporosity. According to a Langmuir isotherm, maximum DNA adsorption capacity of biochars was ranked as BC500 > BC600 > BC400 > BC300. Increasing solution pH (from 4.0 to 9.0) faintly decreased DNA adsorption onto biochars. The addition of Na+, Mg2+, and Ca2+ slightly increased the adsorption of DNA, and the effect decreased by increasing the pyrolysis temperature of biochars, indicating that electrostatic interaction was not the main driving force for DNA adsorption onto those biochars. Correlation analysis showed that SSA and micropore surface area were the main factors influencing DNA adsorption on biochars.
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| 8. |
- Wu, Lang, et al.
(author)
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Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk : A Transcriptome-Wide Association Study in over 140,000 European Descendants
- 2019
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In: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:13, s. 3192-3204
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Journal article (peer-reviewed)abstract
- Genome-wide association study-identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many of these identified associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at P < 2.61 x 10(-6), a Bonferroni-corrected threshold, including nine genes that remained significant at P < 2.61 x 10(-6) after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology. Significance: This study identifies novel prostate cancer genetic loci and possible causal genes, advancing our understanding of the molecular mechanisms that drive prostate cancer.
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| 9. |
- Yu, Guimei, et al.
(author)
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Structure of Arabidopsis SOQ1 lumenal region unveils C-terminal domain essential for negative regulation of photoprotective qH
- 2022
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In: Nature Plants. - : Nature Publishing Group. - 2055-0278. ; 8:7, s. 840-855
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Journal article (peer-reviewed)abstract
- Non-photochemical quenching (NPQ) plays an important role for phototrophs in decreasing photo-oxidative damage. qH is a sustained form of NPQ and depends on the plastid lipocalin (LCNP). A thylakoid membrane-anchored protein SUPPRESSOR OF QUENCHING1 (SOQ1) prevents qH formation by inhibiting LCNP. SOQ1 suppresses qH with its lumen-located thioredoxin (Trx)-like and NHL domains. Here we report structural data, genetic modification and biochemical characterization of Arabidopsis SOQ1 lumenal domains. Our results show that the Trx-like and NHL domains are associated together, with the cysteine motif located at their interface. Residue E859, required for SOQ1 function, is pivotal for maintaining the Trx–NHL association. Importantly, the C-terminal region of SOQ1 forms an independent β-stranded domain that has structural homology to the N-terminal domain of bacterial disulfide bond protein D and is essential for negative regulation of qH. Furthermore, SOQ1 is susceptible to cleavage at the loops connecting the neighbouring lumenal domains both in vitro and in vivo, which could be a regulatory process for its suppression function of qH.
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| 10. |
- Yu, Guimei, et al.
(author)
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Structure of SOQ1 lumenal domains identifies potential disulfide exchange for negative regulation of photoprotection, qH
- 2024
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Other publication (other academic/artistic)abstract
- Non-photochemical quenching (NPQ) plays an important role for phototrophs in decreasing photo-oxidative damage. qH is a sustained component of NPQ and depends on the plastid lipocalin (LCNP). A thylakoid membrane-anchored protein SUPPRESSOR OF QUENCHING1 (SOQ1) prevents qH formation by inhibiting LCNP. SOQ1 suppresses qH with its lumen-located C-terminal Trx-like and NHL domains. Here we report crystal structures and biochemical characterization of SOQ1 lumenal domains. Our results show that the Trx-like and NHL domains are stably associated, with the potential redox-active motif located at their interface. Residue E859 essential for SOQ1 function is pivotal for mediating the inter-domain interaction. Moreover, the C-terminal region of SOQ1 forms an independent β-stranded domain, which possibly interacts with the Trx-like domain through disulfide exchange. Furthermore, SOQ1 is susceptible to cleavage at the loops connecting the neighboring domains both in vitro and in vivo, which could be a regulatory process for its suppression function of qH.
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