| 1. |
- 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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| 2. |
- Jin, Ying-Hui, et al.
(författare)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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| 3. |
- Qian, Yan, et al.
(författare)
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Quantification for total demethylation potential of environmental samples utilizing the EGFP reporter gene
- 2016
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 306, s. 278-285
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The demethylation potential of pollutants is arguably an innate component of their toxicity in environmental samples. A method was developed for determining the total demethylation potential of food samples (TDQ). The demethylation epigenetic toxicity was determined using the Hep G2 cell line transfected with pEGFP-C3 plasmids containing a methylated promoter of the EGFP reporter gene. The total demethylation potential of the sample extracts (the 5-AZA-CdR demethylation toxic equivalency) can be quantified within one week by using a standard curve of the 5-AZA-CdR demethylation agent. To explore the applicability of TDQ for environmental samples, 17 groundwater samples were collected from heavy polluted Kuihe river and the total demethylation potentials of the sample extracts were measured successfully. Meaningful demethylation toxic equivalencies ranging from 0.00050 to 0.01747 μM were found in all groundwater sample extracts. Among 19 kinds of inorganic substance, As and Cd played important roles for individual contribution to the total demethylation epigenetic toxicity. The TDQ assay is reliable and fast for quantifying the DNA demethylation potential of environmental sample extracts, which may improve epigenetic toxicity evaluations for human risk assessment, and the consistent consuming of groundwater alongside the Kuihe river pose unexpected epigenetic health risk to the local residents.
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| 4. |
- Wang, Jin, et al.
(författare)
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Conjugated heat transfer analysis of a film cooling passage with turbulator ribs
- 2016
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Ingår i: Heat Transfer Research. - 1064-2285. ; 47:2, s. 89-103
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the adiabatic film cooling effectiveness and conjugate heat transfer characteristics for a circular hole are investigated numerically. Seven turbulator ribs are located on the internal wall, and a film cooling hole between two adjacent ribs has an inclination angle of 30°. The secondary flow rate is affected by the internal channel flow velocity, and the external film cooling is combined with the internal channel flow conditions. In the conjugate heat transfer research, two different plate materials are considered to analyze the heat conduction characteristics. The results show that the turbulator ribs enhance the downstream heat transfer and provide a more extensive coverage area and effective cooling protection. More blade-wall heat is transferred by heat conduction, which makes the area-average wall temperature for the high thermal conductivity case to decrease along the secondary flow direction. The wall temperature distribution and film cooling effectiveness are affected significantly by heat conduction.
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| 5. |
- Cao, Jianyin, et al.
(författare)
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W-band high-gain low profile circularly polarized magneto-electric dipole antenna array with gap waveguide feeding technology
- 2018
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Ingår i: IET Conference Publications. ; 2018:CP741
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Konferensbidrag (refereegranskat)abstract
- In this paper, a high gain circularly polarized (CP) aperture-coupled magneto-electric (ME) dipole antenna array excited by the air cavity in gap waveguide (GWG) feeding technology in W-band is proposed. This antenna array is composed of two layers, upper CP ME-dipole antenna subarrays and lower metallic GWG feeding networks. The planar antenna array structure is realized by the high mode air cavity feeding network, which is realized by extending the 1×2 cavity to 3×2 cavity using more shorted pins to split the electromagnetic field. The whole single-layer GWG feeding network is composed of a ridge gap waveguide (RGWG) transmission structure and short-ended vertical polarized groove gap waveguide (VP-GGWG) high mode air cavities. The transmission loss caused by the coupling and the fabrication tolerance can be reduced by combining the RGWG and GGWG in the same layer. In addition, the feeding network is fabricated all in metal with no substrate loss. Transverse slots are etched at the right position of the printed circuit board (PCB) backside to excite the CP ME-dipoles. The antenna element has stable radiation patterns and wide axial-ratio (AR) bandwidth. The proposed 3×8 planner antenna array has a maximum boresight gain of 22 dBi and an AR bandwidth of 10.8% for AR < 3 dB. In the frequency band from 87.7 to 97.7 GHz, a boresight gain above 20 dBi is achieved.
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| 6. |
- He, Chunmei, et al.
(författare)
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PROSPECT-GPR : Exploring spectral associations among vegetation traits in wavelength selection for leaf mass per area and water contents
- 2023
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Ingår i: Science of Remote Sensing. - 2666-0172. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Leaf mass per area (LMA) and equivalent water thickness (EWT) are key indicators providing information on plant growth status and agricultural management, and their retrieval is commonly done through radiative transfer models (RTMs) such as the PROSPECT model. However, the PROSPECT model is frequently hampered by the ill-posed problem as a consequence of measurement and model uncertainties. Here, we propose a wavelength selection method to improve the inversion of EWT and LMA by integrating PROSPECT with a machine learning algorithm (Gaussian process regression (GPR); PROSPECT-GPR for short). The GPR model conducted sorting of wavelengths and the PROSPECT-D was used to determine the optimal number of characteristic wavelengths. The results demonstrated that the estimation of EWT (R2 = 0.80; RMSE = 0.0021) and LMA (R2 = 0.71; RMSE = 0.0021) using the proposed wavelengths and PROSPECT inversion all exhibited superior accuracy in comparison with those from previous studies. The efficacy of PROSPECT-GPR in exploring the spectral linkage among vegetation traits was demonstrated by selecting wavelengths associated with leaf structure parameter N and EWT (1368 nm) that turn out to contribute to the estimation of LMA. The findings lay a strong foundation for understanding the spectral linkage among vegetation traits, and the proposed wavelength selection method provides valuable insights for selecting informative spectral wavelengths for RTMs inversion and designing future remote sensors.
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| 7. |
- Huang, Ke, et al.
(författare)
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Tailoring magnetic order via atomically stacking 3d/5d electrons to achieve high-performance spintronic devices
- 2020
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Ingår i: Applied Physics Reviews. - : AMER INST PHYSICS. - 1931-9401. ; 7:1
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Forskningsöversikt (refereegranskat)abstract
- The ability to tune magnetic orders, such as magnetic anisotropy and topological spin texture, is desired to achieve high-performance spintronic devices. A recent strategy has been to employ interfacial engineering techniques, such as the introduction of spin-correlated interfacial coupling, to tailor magnetic orders and achieve novel magnetic properties. We chose a unique polar-nonpolar LaMnO3/SrIrO3 superlattice because Mn (3d)/Ir (5d) oxides exhibit rich magnetic behaviors and strong spin-orbit coupling through the entanglement of their 3d and 5d electrons. Through magnetization and magnetotransport measurements, we found that the magnetic order is interface-dominated as the superlattice period is decreased. We were able to then effectively modify the magnetization, tilt of the ferromagnetic easy axis, and symmetry transition of the anisotropic magnetoresistance of the LaMnO3/SrIrO3 superlattice by introducing additional Mn (3d) and Ir (5d) interfaces. Further investigations using in-depth first-principles calculations and numerical simulations revealed that these magnetic behaviors could be understood by the 3d/5d electron correlation and Rashba spin-orbit coupling. The results reported here demonstrate a new route to synchronously engineer magnetic properties through the atomic stacking of different electrons, which would contribute to future applications in high-capacity storage devices and advanced computing.
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| 8. |
- Li, Qishuang, et al.
(författare)
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Identification of the cytochrome P450s responsible for the biosynthesis of two types of aporphine alkaloids and their de novo biosynthesis in yeast
- 2024
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Ingår i: Journal of Integrative Plant Biology. - 1672-9072 .- 1744-7909. ; 66:8, s. 1703-1717
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Tidskriftsartikel (refereegranskat)abstract
- Aporphine alkaloids have diverse pharmacological activities; however, our understanding of their biosynthesis is relatively limited. Previous studies have classified aporphine alkaloids into two categories based on the configuration and number of substituents of the D-ring and have proposed preliminary biosynthetic pathways for each category. In this study, we identified two specific cytochrome P450 enzymes (CYP80G6 and CYP80Q5) with distinct activities toward (S)-configured and (R)-configured substrates from the herbaceous perennial vine Stephania tetrandra, shedding light on the biosynthetic mechanisms and stereochemical features of these two aporphine alkaloid categories. Additionally, we characterized two CYP719C enzymes (CYP719C3 and CYP719C4) that catalyzed the formation of the methylenedioxy bridge, an essential pharmacophoric group, on the A- and D-rings, respectively, of aporphine alkaloids. Leveraging the functional characterization of these crucial cytochrome P450 enzymes, we reconstructed the biosynthetic pathways for the two types of aporphine alkaloids in budding yeast (Saccharomyces cerevisiae) for the de novo production of compounds such as (R)-glaziovine, (S)-glaziovine, and magnoflorine. This study provides key insight into the biosynthesis of aporphine alkaloids and lays a foundation for producing these valuable compounds through synthetic biology.
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| 9. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 10. |
- Shao, Xue-Feng, et al.
(författare)
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Screening of sugar alcohols and their binary eutectic mixtures as phase change materials for low-to-medium temperature thermal energy storage. (II) : Isothermal melting and crystallization behaviors
- 2019
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Ingår i: Energy. - : Elsevier. - 0360-5442 .- 1873-6785. ; 180, s. 572-583
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Tidskriftsartikel (refereegranskat)abstract
- Based on the non-isothermal phase change behaviors of twenty-one pure and mixture sugar alcohols presented in our previous study (Part 1), the isothermal melting and crystallization behaviors were further tested in this supplemental work for five selected pure sugar alcohols (xylitol, erythritol, dmannitol, d-dulcitol and inositol) and their five binary eutectic mixtures to make an advanced screening of these candidates for low-to-medium temperature latent heat storage. The isothermal melting and crystallization behaviors of these ten candidates were tested at a constant degree of superheat (10 degrees C) and various degrees of subcooling up to 210 degrees C. The phase change temperatures, degrees of supercooling and durations of phase change were determined by the recorded temperature-history curves. It was found that the incrystallizable xylitol and its eutectic mixture of xylitol (75 mol%) + erythritol with low melting points under 100 degrees C are also unable to crystallize during isothermal cool-down at any degrees of subcooling (30-90 degrees C) due to the unavailability to nucleation. The rest eight crystallizable candidates all suffer from severe supercooling and are unable to crystallize at low degrees of subcooling (<20 degrees C). They undergo both one-phase supercooling due to poor nucleation performance and two-phase supercooling, which was unable to be obtained previously by non-isothermal cooling, due to slow crystallization kinetics. However, it seems difficult to find a correlation between the observed degrees of supercooling in both the liquid and solid phases and the prescribed degrees of subcooling by only three consecutive isothermal melting and crystallization cycles, as a result of the randomness of nucleation and large size of samples. The duration of crystallization was shown to decrease with increasing the degree of subcooling for both pure and mixture sugar alcohols due to the enhanced driving force for crystallization. The durations of crystallization of the mixture sugar alcohols appear to be longer than those of their pure compounds, due to the lower thermal conductivity and higher dynamic viscosity of the mixtures. Combining the present isothermal and the previous non-isothermal test results, it has been confirmed that the difficulty in crystallization and the severe supercooling are the primary issues for sugar alcohols, which must be addressed before they can be used in real-world latent heat storage systems.
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