| 1. |
- Yang, Zhijian, et al.
(författare)
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Genetic Landscape of the ACE2 Coronavirus Receptor
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
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| 2. |
- Chen, Zhiwen, et al.
(författare)
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Well-defined CoSe2@MoSe2 hollow heterostructured nanocubes with enhanced dissociation kinetics for overall water splitting
- 2020
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Ingår i: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 12:1, s. 326-335
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Tidskriftsartikel (refereegranskat)abstract
- Hollow heterostructures have tremendous advantages in electrochemical energy storage and conversion areas due to their unique structure and composition characteristics. Here, we report the controlled synthesis of hollow CoSe2 nanocubes decorated with ultrathin MoSe2 nanosheets (CoSe2@MoSe2) as an efficient and robust bifunctional electrocatalyst for overall water splitting in a wide pH range. It is found that integrating ultrathin MoS2 nanosheets with hollow CoSe2 nanocubes can provide abundant active sites, promote electron/mass transfer and bubble release and facilitate the migration of charge carriers. Additionally, the surface electron coupling in the heterostructures enables it to serve as a source of sites for H+ and/or OH- adsorption, thus reducing the activation barrier for water molecules adsorption and dissociation. As a result, the title compound, CoSe2@MoSe2 hollow heterostructures, exhibits an overpotential of 183 mV and 309 mV at a current density of 10 mA cm(-2) toward hydrogen evolution reactions and oxygen evolution reactions in 1.0 M KOH, respectively. When applied as both cathode and anode for overall water splitting, a low battery voltage of 1.524 V is achieved along with excellent stability for at least 12 h. This work provides a new idea for the design and synthesis of high-performance catalysts for electrochemical energy storage and conversion.
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| 3. |
- Huan, Tianxiao, et al.
(författare)
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Genome-wide identification of DNA methylation QTLs in whole blood highlights pathways for cardiovascular disease
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Identifying methylation quantitative trait loci (meQTLs) and integrating them with disease-associated variants from genome-wide association studies (GWAS) may illuminate functional mechanisms underlying genetic variant-disease associations. Here, we perform GWAS of >415 thousand CpG methylation sites in whole blood from 4170 individuals and map 4.7 million cis- and 630 thousand trans-meQTL variants targeting >120 thousand CpGs. Independent replication is performed in 1347 participants from two studies. By linking cis-meQTL variants with GWAS results for cardiovascular disease (CVD) traits, we identify 92 putatively causal CpGs for CVD traits by Mendelian randomization analysis. Further integrating gene expression data reveals evidence of cis CpG-transcript pairs causally linked to CVD. In addition, we identify 22 trans-meQTL hotspots each targeting more than 30 CpGs and find that trans-meQTL hotspots appear to act in cis on expression of nearby transcriptional regulatory genes. Our findings provide a powerful meQTL resource and shed light on DNA methylation involvement in human diseases.
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| 4. |
- Liu, Heng, et al.
(författare)
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Defect Management and Ion Infiltration Barrier Enable High-Performance Perovskite Solar Cells
- 2024
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Ingår i: ACS Energy Letters. - 2380-8195. ; 9:6, s. 2790-2799
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Tidskriftsartikel (refereegranskat)abstract
- The stability of perovskite solar cells (PSCs) has been considered as one of the major obstacles toward practical application. Defects in the perovskite layer and ion infiltration from the hole transport layer (HTL) can trigger degradation of n-i-p PSCs. Herein, phenylhydrazine-4-sulfonic acid (PHPA) was employed as an additive to modulate perovskite crystallization during film formation, enlarging the perovskite crystal grain sizes to ∼3 μm. Density functional theory (DFT) calculations revealed that PHPA could effectively inhibit the formation of iodine vacancies (VI) and passivate the under-coordinated Pb2+ ions. Additionally, perfluorooctanoic acid (PFOA) was adopted to passivate the surface located dangling Pb2+ defects, improve the surface hydrophobicity, and inhibit Li+ ion migration from the HTL to the bottom perovskite, thus enhancing the device’s environmental and operational stability. Consequently, the resulting devices delivered a champion efficiency of 25.1% with an excellent maximum-power-point (MPP) tracking stability.
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| 5. |
- McKeown, Nicola M., et al.
(författare)
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Comparison of plasma alkylresorcinols (AR) and urinary AR metabolites as biomarkers of compliance in a short-term, whole-grain intervention study
- 2016
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 55:3, s. 1235-1244
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Tidskriftsartikel (refereegranskat)abstract
- Alkylresorcinols (AR) are phenolic lipids present in the bran of wheat and rye. Plasma AR and their urinary metabolites may be suitable biomarkers of whole-grain (WG) wheat and rye consumption. The objective of this study was to examine plasma AR and urinary AR metabolites in response to WG wheat consumption. In a randomized crossover study, 19 subjects (10 males, 9 females; BMI 22.0 kg/m(2); age 26 years) incorporated either 3 servings (48 g) or 6 servings (96 g) of WG wheat daily into their regular diet for 1 week. Subjects completed a 2-week washout period, abstaining from all WG consumption, before each intervention. Fasting blood and 24-h urine were collected before and after each intervention. Plasma AR homologues (C19:0, C21:0, C23:0) were quantified by GC-MS after diethyl ether and solid phase extraction and derivatization. Urinary AR metabolites [3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-propanoic acid] were determined using HPLC with electrochemical detection after enzymatic deconjugation and ethyl acetate extraction. Urinary total AR metabolites were significantly higher after 6 compared with 3 servings of WG wheat (56 vs. 32 mu mol/day, P < 0.001). This dose-response relationship was independent of age, sex, energy intake, and baseline urinary AR metabolite concentration. Plasma total AR tended to be higher after 6 compared with 3 servings of WG wheat (103.0 vs. 86.9 nmol/L), but this difference was not significant (P = 0.42). The results suggest that urinary AR metabolites from 24-h urine collections may be useful as biomarkers of compliance in intervention studies of WG wheat.
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| 6. |
- McKeown, Nicola M., et al.
(författare)
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Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway : a meta-analysis
- 2018
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:2, s. 317-330
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits. Methods: Data from 11 cohorts (six discovery and five replication) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided association and interaction results from 34,748 adults of European descent. SSB intake (soft drinks, fruit punches, lemonades or other fruit drinks) was derived from food-frequency questionnaires and food diaries. In fixed-effects meta-analyses, we quantified: (1) the associations between SSBs and glycaemic traits (fasting glucose and fasting insulin); and (2) the interactions between SSBs and 18 independent SNPs related to the ChREBP-FGF21 pathway. Results: In our combined meta-analyses of discovery and replication cohorts, after adjustment for age, sex, energy intake, BMI and other dietary covariates, each additional serving of SSB intake was associated with higher fasting glucose (β ± SE 0.014 ± 0.004 [mmol/l], p = 1.5 × 10−3) and higher fasting insulin (0.030 ± 0.005 [loge pmol/l], p = 2.0 × 10−10). No significant interactions on glycaemic traits were observed between SSB intake and selected SNPs. While a suggestive interaction was observed in the discovery cohorts with a SNP (rs1542423) in the β-Klotho (KLB) locus on fasting insulin (0.030 ± 0.011 loge pmol/l, uncorrected p = 0.006), results in the replication cohorts and combined meta-analyses were non-significant. Conclusions/interpretation: In this large meta-analysis, we observed that SSB intake was associated with higher fasting glucose and insulin. Although a suggestive interaction with a genetic variant in the ChREBP-FGF21 pathway was observed in the discovery cohorts, this observation was not confirmed in the replication analysis. Trial registration: Trials related to this study were registered at clinicaltrials.govas NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT00005487 (Multi-Ethnic Study of Atherosclerosis) and NCT00005152 (Nurses’ Health Study).
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| 7. |
- Repetto, Linda, et al.
(författare)
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Genetic mechanisms of 184 neuro-related proteins in human plasma.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.
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| 8. |
- Repetto, Linda, et al.
(författare)
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Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders.
- 2023
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Ingår i: Nature Portfolio. - : Research Square Platform LLC.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
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| 9. |
- Wang, Shangdai, et al.
(författare)
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Multi-functional NiS2/FeS2/N-doped carbon nanorods derived from metal-organic frameworks with fast reaction kinetics for high performance overall water splitting and lithium-ion batteries
- 2019
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Ingår i: Journal of Power Sources. - : ELSEVIER. - 0378-7753 .- 1873-2755. ; 436
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Tidskriftsartikel (refereegranskat)abstract
- The development of cost-effective, highly efficient and robust multi-functional electrode materials can dramatically reduce the overall cost of electrochemical devices. We here report the controlled synthesis of NiS2/FeS2 nanoparticles encapsulated in N-doped carbon nanorods (NiS2/FeS2/NC) through carbonization and sulfurization of Fe/Ni-based bimetallic metal-organic frameworks. Benefiting from both structural and compositional characteristics, the resulting NiS2/FeS2/NC nanorods possess abundant active sites, high electrical conductivity and rapid mass transfer, thereby delivering 10 and 20 mA cm(-2) at overpotential of 172 mV and 231 mV towards the hydrogen evolution reaction and oxygen evolution reaction with robust stability in 1.0 M KOH solution, respectively. When employed as a bifunctional electrocatalyst for overall water splitting, it requires only 1.58 V to deliver a current density of 10 mA cm(-2) in 1.0 M KOH, outperforming that of the commercial Pt/C parallel to RuO2. Additionally, lithium-ion batteries tests also show high reversible capacity (718 mA h g(-1) at 100 mA g(-1)) and excellent cycling stability and rate performance. The work in this paper not only provides a promising strategy for designing efficient multi-functional electrode materials with similar morphology and structure, but also can be extended to the synthesis of other mixed metal sulfides for energy conversion and storage.
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