| 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. |
- Nikpay, Majid, et al.
(author)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
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Journal article (peer-reviewed)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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| 3. |
- Fischer, Katrin, et al.
(author)
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The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- During beta -adrenergic stimulation of brown adipose tissue (BAT), p38 phosphorylates the activating transcription factor 2 (ATF2) which then translocates to the nucleus to activate the expression of Ucp1 and Pgc-1 alpha. The mechanisms underlying ATF2 target activation are unknown. Here we demonstrate that p62 (Sqstm1) binds to ATF2 to orchestrate activation of the Ucp1 enhancer and Pgc-1 alpha promoter. P62(Delta 69-251) mice show reduced expression of Ucp1 and Pgc-1 alpha with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1 alpha expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62(Delta 69-251) mice, global p62(-/-) and Ucp1-Cre p62(flx/flx) mice. BAT dysfunction resulting from p62 deficiency is manifest after birth and obesity subsequently develops despite normal food intake, intestinal nutrient absorption and locomotor activity. In summary, our data identify p62 as a master regulator of BAT function in that it controls the Ucp1 pathway through regulation of ATF2 genomic binding. Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1 alpha. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1 alpha induction.
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| 4. |
- Gao, Yijun, et al.
(author)
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Enhancing PbS Colloidal Quantum Dot Tandem Solar Cell Performance by Graded Band Alignment
- 2019
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In: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185 .- 1948-7185. ; 10:19, s. 5729-5734
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Journal article (peer-reviewed)abstract
- Colloidal quantum dot solids are attractive candidates for tandem solar cells because of their widely tunable bandgaps. However, the development of the quantum dot tandem solar cell has lagged far behind that of its single-junction counterpart. One of the fundamental problems with colloidal quantum dot solar cells is the relatively small diffusion length, which limits the quantum dot absorbing layer thickness and hence the power conversion efficiency. In this research, guided by optical modeling and utilizing a graded band alignment strategy, a two-terminal monolithic solution-processed quantum dot tandem solar cell has been successfully fabricated and a power conversion efficiency of 6.8% has been achieved. The band grading approach utilized the complementary tuning of work functions and band alignment through judicious choices of the nanoparticle surface chemistry and quantum dot confined size. This work demonstrates a general approach to improving the efficiency for tandem thin-film solar cells.
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| 5. |
- Huang, Jianfeng, et al.
(author)
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High-Performance Low-Voltage Transparent Metal-Semiconductor-Metal Ultraviolet Photodetectors Based on Ultrathin Gold Asymmetric Interdigitated Electrodes
- 2023
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In: Micromachines. - : MDPI AG. - 2072-666X. ; 14:7
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Journal article (peer-reviewed)abstract
- A high-performance, low-voltage, transparent, metal-semiconductor-metal ultraviolet (UV) photodetector (PD) is proposed and experimentally demonstrated, based on gold (Au) asymmetric interdigitated (aIDT) electrodes with thicknesses well below 10 nm. A 7-nm-thick Au film, with a visible transmittance of 80.4% and a sheet resistance of 11.55 & omega;/sq, is patterned into aIDT electrodes on a ZnO active layer, whose average visible transmittance is up to 74.3%. Meshing the pads further improves the overall transmittance of the device. Among all fabricated devices, the PD with the aIDT finger width ratio of 1:4 performs the best. Very low dark currents are achieved at 0, 0.5 and 1 V, allowing for high responsivities and specific detectivities to the UV light. It is also a fast device, especially under the biases of 0.5 and 1 V. The comprehensive performances are comparable and even superior to those of the reported devices. The asymmetric Schottky junctions induced by the aIDT electrodes under UV illumination are the main mechanism for the low-voltage operation of our transparent PD, which is promising to be applied widely.
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| 6. |
- Lai, Qiwen, et al.
(author)
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Hydrogen Storage Materials for Mobile and Stationary Applications : Current State of the Art
- 2015
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In: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 8:17, s. 2789-2825
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Journal article (peer-reviewed)abstract
- One of the limitations to the widespread use of hydrogen as an energy carrier is its storage in a safe and compact form. Herein, recent developments in effective high-capacity hydrogen storage materials are reviewed, with a special emphasis on light compounds, including those based on organic porous structures, boron, nitrogen, and aluminum. These elements and their related compounds hold the promise of high, reversible, and practical hydrogen storage capacity for mobile applications, including vehicles and portable power equipment, but also for the large scale and distributed storage of energy for stationary applications. Current understanding of the fundamental principles that govern the interaction of hydrogen with these light compounds is summarized, as well as basic strategies to meet practical targets of hydrogen uptake and release. The limitation of these strategies and current understanding is also discussed and new directions proposed.
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| 7. |
- Lei, Qiyun, et al.
(author)
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Broadband transparent and flexible silver mesh for efficient electromagnetic interference shielding and high-quality free-space optical communication
- 2023
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In: Optical Materials Express. - : Optica Publishing Group. - 2159-3930 .- 2159-3930. ; 13:2, s. 469-483
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Journal article (peer-reviewed)abstract
- A broadband transparent and flexible silver (Ag) mesh is presented experimentally for the first time for both efficient electromagnetic interference (EMI) shielding in the X band and high-quality free-space optical (FSO) communication. High transmission is achieved in a broad wavelength range of 0.4-2.0 mu m. The transmittance of the Ag mesh relative to the substrate is around 92% and the sheet resistance is as low as 7.12 ohm/sq. The Ag mesh/polyethylene (PE) achieves a high average EMI shielding effectiveness (SE) of 28.8 dB in the X band with an overall transmittance of 80.9% at 550 nm. High-quality FSO communication with small power penalty is attributed to the high optical transmittance and the low haze at 1550 nm, superior to those of the Ag NW networks. With a polydimethylsiloxane (PDMS) coating, the average EMI SE is still up to 26.2 dB and the overall transmittance is increased to 84.5% at 550 nm due to antireflection. The FSO communication does not change much due to the nearly unchanged optical property at 1550 nm. Both the EMI shielding performance and the FSO communication function maintain after 2-hour chemical corrosions as well as after 1000 bending cycles and twisting. Our PDMS/Ag mesh/PE sandwiched film can be self-cleaned, suitable for outdoor applications.
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| 8. |
- Yao, Yao, et al.
(author)
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Flexible and Stretchable Organic Electrochemical Transistors for Physiological Sensing Devices
- 2023
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In: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 35:35
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Research review (peer-reviewed)abstract
- Flexible and stretchable bioelectronics provides a biocompatible interface between electronics and biological systems and has received tremendous attention for in situ monitoring of various biological systems. Considerable progress in organic electronics has made organic semiconductors, as well as other organic electronic materials, ideal candidates for developing wearable, implantable, and biocompatible electronic circuits due to their potential mechanical compliance and biocompatibility. Organic electrochemical transistors (OECTs), as an emerging class of organic electronic building blocks, exhibit significant advantages in biological sensing due to the ionic nature at the basis of the switching behavior, low driving voltage (<1 V), and high transconductance (in millisiemens range). During the past few years, significant progress in constructing flexible/stretchable OECTs (FSOECTs) for both biochemical and bioelectrical sensors has been reported. In this regard, to summarize major research accomplishments in this emerging field, this review first discusses structure and critical features of FSOECTs, including working principles, materials, and architectural engineering. Next, a wide spectrum of relevant physiological sensing applications, where FSOECTs are the key components, are summarized. Last, major challenges and opportunities for further advancing FSOECT physiological sensors are discussed.
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| 9. |
- Zhu, Changlian, 1964, et al.
(author)
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Irradiation to the immature brain attenuates neurogenesis and exacerbates subsequent hypoxic-ischemic brain injury in the adult.
- 2009
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In: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 111:6, s. 1447-1456
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Journal article (peer-reviewed)abstract
- Abstract Cranial radiotherapy is common in pediatric oncology. Our purpose was to investigate if irradiation (IR) to the immature brain would increase the susceptibility to hypoxic- ischemic injury in adulthood. The left hemisphere of postnatal day 10 (P10) mice was irradiated with 8 Gy and subjected to hypoxia-ischemia (HI) on P60. Brain injury, neurogenesis and inflammation were evaluated 30 days after HI. IR alone caused significant hemispheric tissue loss, or lack of growth (2.8 +/- 0.42 mm(3), p<0.001). Tissue loss after HI (18.2 +/- 5.8 mm(3), p<0.05) was synergistically increased if preceded by IR (32.0 +/- 3.5 mm(3), p<0.05). Infarct volume (5.1 +/- 1.6 mm(3)) nearly doubled if HI was preceded by IR (9.8 +/- 1.2 mm(3), p<0.05). Pathological scoring revealed that IR aggravated hippocampal, cortical and striatal, but not thalamic, injury. Hippocampal neurogenesis decreased >50% after IR but was unchanged by HI alone. The number of newly formed microglia was three times higher after IR+HI than after HI alone. In summary, IR to the immature brain produced long-lasting changes, including decreased hippocampal neurogenesis, subsequently rendering the adult brain more susceptible to HI, resulting in larger infarcts, increased hemispheric tissue loss and more inflammation than in non-irradiated brains.
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| 10. |
- Zhu, Changlian, 1964, et al.
(author)
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Isoflurane anesthesia induced persistent, progressive memory impairment, caused a loss of neural stem cells, and reduced neurogenesis in young, but not adult, rodents.
- 2010
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In: Journal of cerebral blood flow and metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 30, s. 1017-1030
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Journal article (peer-reviewed)abstract
- Isoflurane and related anesthetics are widely used to anesthetize children, ranging from premature babies to adolescents. Concerns have been raised about the safety of these anesthetics in pediatric patients, particularly regarding possible negative effects on cognition. The purpose of this study was to investigate the effects of repeated isoflurane exposure of juvenile and mature animals on cognition and neurogenesis. Postnatal day 14 (P14) rats and mice, as well as adult (P60) rats, were anesthetized with isoflurane for 35 mins daily for four successive days. Object recognition, place learning and reversal learning as well as cell death and cytogenesis were evaluated. Object recognition and reversal learning were significantly impaired in isoflurane-treated young rats and mice, whereas adult animals were unaffected, and these deficits became more pronounced as the animals grew older. The memory deficit was paralleled by a decrease in the hippocampal stem cell pool and persistently reduced neurogenesis, subsequently causing a reduction in the number of dentate gyrus granule cell neurons in isoflurane-treated rats. There were no signs of increased cell death of progenitors or neurons in the hippocampus. These findings show a previously unknown mechanism of neurotoxicity, causing cognitive deficits in a clearly age-dependent manner.Journal of Cerebral Blood Flow & Metabolism advance online publication, 13 January 2010; doi:10.1038/jcbfm.2009.274.
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