| 1. |
- Archambault, Alexi N., et al.
(author)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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| 2. |
- Feng, Guitao, et al.
(author)
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“Double-Cable” Conjugated Polymers with Linear Backbone toward High Quantum Efficiencies in Single-Component Polymer Solar Cells
- 2017
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In: Journal of the American Chemical Society. - : AMER CHEMICAL SOC. - 0002-7863 .- 1520-5126. ; 139:51, s. 18647-18656
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Journal article (peer-reviewed)abstract
- A series of "double-cable" conjugated polymers were developed for application in efficient single-component polymer solar cells, in which high quantum efficiencies could be achieved due to the optimized nanophase separation between donor and acceptor parts. The new double-cable polymers contain electron-donating poly(benzodithiophene) (BDT) as linear conjugated backbone for hole transport and pendant electron-deficient perylene bisimide (PBI) units for electron transport, connected via a dodecyl linker. Sulfur and fluorine substituents were introduced to tune the energy levels and crystallinity of the conjugated polymers. The double-cable polymers adopt a "face-on" orientation in which the conjugated BDT backbone and the pendant PBI units have a preferential pi-pi stacking direction perpendicular to the substrate, favorable for interchain charge transport normal to the plane. The linear conjugated backbone acts as a scaffold for the crystallization of the PBI groups, to provide a double-cable nanophase separation of donor and acceptor phases. The optimized nanophase separation enables efficient exciton dissociation as well as charge transport as evidenced from the high-up to 80%-internal quantum efficiency for photon-to-electron conversion. In single-component organic solar cells, the double-cable polymers provide power conversion efficiency up to 4.18%. This is one of the highest performances in single-component organic solar cells. The nanophase-separated design can likely be used to achieve high-performance single-component organic solar cells.
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| 3. |
- Marouli, Eirini, et al.
(author)
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Rare and low-frequency coding variants alter human adult height
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Journal article (peer-reviewed)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 4. |
- Turcot, Valerie, et al.
(author)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 5. |
- Bouras, Emmanouil, et al.
(author)
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Genome-wide interaction analysis of folate for colorectal cancer risk
- 2023
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In: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 118:5, s. 881-891
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Journal article (peer-reviewed)abstract
- Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO).Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate.Conclusions: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.
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| 6. |
- Gai, Fangyuan, et al.
(author)
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Novel Schiff base (DBDDP) selective detection of Fe (III) : Dispersed in aqueous solution and encapsulated in silica cross-linked micellar nanoparticles in living cell
- 2018
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In: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 514, s. 357-363
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Journal article (peer-reviewed)abstract
- This work demonstrated the synthesis of (4E)-4-(4-(diphenylamino)benzylideneamino)-1,2-dihydro-1,5- dimethyl-2-phenylpyrazol-3-one (DBDDP) for Fe (III) detection in aqueous media and in the core of silica cross-linked micellar nanoparticles in living cells. The free DBDDP performed fluorescence enhancement due to Fe (III)-promoted hydrolysis in a mixed aqueous solution, while the DBDDP-doped silica cross-linked micellar nanoparticles (DBDDP-SCMNPs) performed an electron-transfer based fluorescence quenching of Fe (III) in living cells. The quenching fluorescence of DBDDP-SCMNPs and the concentration of Fe (III) exhibited a linear correlation, which was in accordance with the Stern-Volmer equation. Moreover, DBDDP-SCMNPs showed a low limit of detection (LOD) of 0.1 ppm and an excellent selectivity against other metal ions. Due to the good solubility and biocompatibility, DBDDP-SCMNPs could be applied as fluorescence quenching nanosensors in living cells.
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| 7. |
- Miao, Yanfeng, et al.
(author)
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Stable and bright formamidinium-based perovskite light-emitting diodes with high energy conversion efficiency
- 2019
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Journal article (peer-reviewed)abstract
- Solution-processable perovskites show highly emissive and good charge transport, making them attractive for low-cost light-emitting diodes (LEDs) with high energy conversion efficiencies. Despite recent advances in device efficiency, the stability of perovskite LEDs is still a major obstacle. Here, we demonstrate stable and bright perovskite LEDs with high energy conversion efficiencies by optimizing formamidinium lead iodide films. Our LEDs show an energy conversion efficiency of 10.7%, and an external quantum efficiency of 14.2% without outcoupling enhancement through controlling the concentration of the precursor solutions. The device shows low efficiency droop, i.e. 8.3% energy conversion efficiency and 14.0% external quantum efficiency at a current density of 300 mA cm(-2), making the device more efficient than state-of-the-art organic and quantum-dot LEDs at high current densities. Furthermore, the half-lifetime of device with benzylamine treatment is 23.7 hr under a current density of 100 mA cm(-2), comparable to the lifetime of near-infrared organic LEDs.
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| 8. |
- Qi, Jing, et al.
(author)
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Levels, distribution, childhood exposure assessment, and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust from nine cities in China
- 2023
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 874
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Journal article (peer-reviewed)abstract
- Household dust is an important source of premature exposure to polybrominated diphenyl ethers (PBDEs), especially for children. In this onsite study, 246 dust samples were collected from 224 households in nine Chinese cities during 2018–2019. Questionnaires were administered to explore the association between household-related information and PBDEs in household dust. The median concentration of Σ12PBDEs in household dust from 9 cities was 138 ng/g (94–227 ng/g), with the arithmetic mean of 240 ± 401 ng/g. Among the nine cities, the highest median concentration of Σ12PBDEs in household dust was found in Mianyang (295.57 ng/g), while the lowest was found in Wuxi (23.15 ng/g). BDE-71 was the most dominant congener, ranging from 42.08 % to 98.15 % of the 12 PBDE congeners among 9 cities. Three potential sources for the indoor environment were Penta-BDE, Octa-BDE commercial products, and photolytic bromine from Deca-BDEs based on the largest contribution (81.24 %). Under the moderate exposure scenario, the exposure levels through ingestion and dermal absorption for children were 7.30 × 10−1 ng/kg BW/day and 3.26 × 10−2 ng/kg BW/day, respectively. Temperature, CO2, years of residence, income, family size, household size, use of computers, heating, use of insecticide, and use of humidifiers were influential factors for PBDE concentrations in household dust. Based on the evidence of the correlation between PBDEs and these household parameters, it can be applied to reduce PBDE concentrations in household dust, which is a basis for controlling PBDEs pollution in Chinese households and protecting population health.
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| 9. |
- Wang, Chao, et al.
(author)
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Characterization and sources of childhood PAEs exposure from residential airborne dust in China cities
- 2025
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In: Journal of Environmental Sciences(China). - : Elsevier. - 1001-0742 .- 1878-7320. ; 152, s. 1-13
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Journal article (peer-reviewed)abstract
- To explore the multicenter characteristics of endocrine-like phthalate esters (PAEs) in household dust and propose effective control strategies for global indoor public health. An on-site observational investigation was conducted in nine Chinese cities from 2018 to 2019. A total of 246 household dust samples were collected and analyzed for ten PAE congeners using Gas Chromatography-Mass Spectrometry (GC-MS). Questionnaires were used to gather information on building conditions, indoor behaviors, and ventilation habits. In residential dust from the nine cities, the total concentrations of the ten PAE congeners (∑PAEs) ranged from 0.921 to 29097.297 µg/g. Dicyclohexyl phthalate (DCHP) and di (2-ethylhexyl) phthalate (DEHP) were the dominant congeners in ∑PAEs. Childhood exposure to PAEs through dust ingestion was four orders of magnitude higher than through inhalation, with a carcinogenic risk of 5.47 × 10−6 for DEHP exposure in household dust. Higher ∑PAEs concentrations were associated with higher temperature, double glazing, wall paint usage, television and computer use, and indoor plant growth. This multicenter on-site investigation confirmed PAE pollution characteristics and uncovered the inacceptable risk of daily DEHP exposure in household dust under real living conditions. Effective mitigation measures based on household-related information, residential characteristics, decoration materials, and lifestyle should be taken to build a healthy household environment.
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| 10. |
- Wang, Xinqi, et al.
(author)
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Levels, distribution, sources and children health risk of PAHs in residential dust : A multi-city study in China
- 2023
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 862
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Journal article (peer-reviewed)abstract
- Background: Polycyclic aromatic hydrocarbons (PAHs) are typical residential pollutants mainly from biofuel combustion that impose inevitable risk to children. The PAHs in residential dust is universal in most Chinese households with an obvious public health concern.Methods: In this observational study, a total of 235 residential dust samples from 8 Chinese cities (Panjin, Shijiazhuang, Lanzhou, Luoyang, Xi'an, Wuxi, Mianyang, and Shenzhen) were collected from April 2018 to March 2019, which were extracted and analyzed for 16 priority PAHs by HPLC/FD-UV. Diagnostic ratios, hierarchical clustering analysis and principal component analysis were applied simultaneously for source apportionments. Incremental lifetime cancer risk was employed to estimate children's health risks based on the assumed exposure scenarios. Spearman correlation, Mann-Whitney U test, Kruskal-Wallis H test and Partial Least Squares were used to screen the factors affecting the concentration of PAHs in residential dust.Results: The median concentration of ∑16PAHs in residential dust from 8 cities was 44.11 μg/g (0.04 - 355.79 μg/g). ∑16PAHs were found both higher in dust samples in heating season and from downwind households only in Mianyang (p < 0.05). The leading two sources of PAHs were combustion processes and automobile exhaust emissions based on four principal components that accounted for 74.29 % of the total variance. Indoor air environmental factors, household characteristics, and residents' behavioral lifestyles may be the influencing factors of residential dust PAHs. The carcinogenic risk of children aged 0 - 5 years, under the moderate exposure level of PAHs in residential dust, exceeded the acceptable level (10−5 - 10−4 for dermal contact and 10−6 - 10−5 for ingestion).Conclusions: There was serious PAHs pollution in residential dust under actual living conditions in eight cities across China. More evidence-based measures were needed to control PAHs pollution to safeguard children's health according to appointed sources and influencing factors in residential dust.
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