| 1. |
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
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| 4. |
- Xie, Sisi, et al.
(författare)
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Dietary ketone body-escalated histone acetylation in megakaryocytes alleviates chemotherapy-induced thrombocytopenia
- 2022
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 14:673
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy-induced thrombocytopenia (CIT) is a severe complication in patients with cancer that can lead to impaired therapeutic outcome and survival. Clinically, therapeutic options for CIT are limited by severe adverse effects and high economic burdens. Here, we demonstrate that ketogenic diets alleviate CIT in both animals and humans without causing thrombocytosis. Mechanistically, ketogenic diet-induced circulating beta-hydroxybutyrate (beta-OHB) increased histone H3 acetylation in bone marrow megakaryocytes. Gain- and loss-of-function experiments revealed a distinct role of 3-beta-hydroxybutyrate dehydrogenase (BDH)-mediated ketone body metabolism in promoting histone acetylation, which promoted the transcription of platelet biogenesis genes and induced thrombocytopoiesis. Genetic depletion of the megakaryocyte-specific ketone body transporter monocarboxylate transporter 1 (MCT1) or pharmacological targeting of MCT1 blocked beta-OHB-induced thrombocytopoiesis in mice. A ketogenesis-promoting diet alleviated CIT in mouse models. Moreover, a ketogenic diet modestly increased platelet counts without causing thrombocytosis in healthy volunteers, and a ketogenic lifestyle inversely correlated with CIT in patients with cancer. Together, we provide mechanistic insights into a ketone body-MCT1-BDH-histone acetylation-platelet biogenesis axis in megakaryocytes and propose a non-toxic, low-cost dietary intervention for combating CIT.
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| 5. |
- Bhat, Goutam, et al.
(författare)
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NTIRE 2022 Burst Super-Resolution Challenge
- 2022
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Ingår i: 2022 IEEE/CVF CONFERENCE ON COMPUTER VISION AND PATTERN RECOGNITION WORKSHOPS (CVPRW 2022). - : IEEE. - 9781665487399 - 9781665487405 ; , s. 1040-1060
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Konferensbidrag (refereegranskat)abstract
- Burst super-resolution has received increased attention in recent years due to its applications in mobile photography. By merging information from multiple shifted images of a scene, burst super-resolution aims to recover details which otherwise cannot be obtained using a simple input image. This paper reviews the NTIRE 2022 challenge on burst super-resolution. In the challenge, the participants were tasked with generating a clean RGB image with 4x higher resolution, given a RAW noisy burst as input. That is, the methods need to perform joint denoising, demosaicking, and super-resolution. The challenge consisted of 2 tracks. Track 1 employed synthetic data, where pixel-accurate high-resolution ground truths are available. Track 2 on the other hand used real-world bursts captured from a handheld camera, along with approximately aligned reference images captured using a DSLR. 14 teams participated in the final testing phase. The top performing methods establish a new state-of-the-art on the burst super-resolution task.
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| 6. |
- Dou, Shihan, et al.
(författare)
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Decorrelate Irrelevant, Purify Relevant : Overcome Textual Spurious Correlations from a Feature Perspective
- 2022
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Konferensbidrag (refereegranskat)abstract
- Natural language understanding (NLU) models tend to rely on spurious correlations (i.e., dataset bias) to achieve high performance on in-distribution datasets but poor performance on out-of-distribution ones. Most of the existing debiasing methods often identify and weaken these samples with biased features (i.e., superficial surface features that cause such spurious correlations). However, down-weighting these samples obstructs the model in learning from the non-biased parts of these samples. To tackle this challenge, in this paper, we propose to eliminate spurious correlations in a fine-grained manner from a feature space perspective. Specifically, we introduce Random Fourier Features and weighted re-sampling to decorrelate the dependencies between features to mitigate spurious correlations. After obtaining decorrelated features, we further design a mutual-information-based method to purify them, which forces the model to learn features that are more relevant to tasks. Extensive experiments on two well-studied NLU tasks demonstrate that our method is superior to other comparative approaches.
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| 7. |
- He, Mao Qiang, et al.
(författare)
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Phylogenomics, divergence times and notes of orders in Basidiomycota
- 2024
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Ingår i: Fungal Diversity. - 1560-2745 .- 1878-9129. ; 126, s. 127-406
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Tidskriftsartikel (refereegranskat)abstract
- Basidiomycota is one of the major phyla in the fungal tree of life. The outline of Basidiomycota provides essential taxonomic information for researchers and workers in mycology. In this study, we present a time-framed phylogenomic tree with 487 species of Basidiomycota from 127 families, 47 orders, 14 classes and four subphyla; we update the outline of Basidiomycota based on the phylogenomic relationships and the taxonomic studies since 2019; and we provide notes for each order and discuss the history, defining characteristics, evolution, justification of orders, problems, significance, and plates. Our phylogenomic analysis suggests that the subphyla diverged in a time range of 443–490 Myr (million years), classes in a time range of 312–412 Myr, and orders in a time range of 102–361 Myr. Families diverged in a time range of 50–289 Myr, 76–224 Myr, and 62–156 Myr in Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina, respectively. Based on the phylogenomic relationships and divergence times, we propose a new suborder Mycenineae in Agaricales to accommodate Mycenaceae. In the current outline of Basidiomycota, there are four subphyla, 20 classes, 77 orders, 297 families, and 2134 genera accepted. When building a robust taxonomy of Basidiomycota in the genomic era, the generation of molecular phylogenetic data has become relatively easier. Finding phenotypical characters, especially those that can be applied for identification and classification, however, has become increasingly challenging.
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| 8. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 9. |
- 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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| 10. |
- Li, Shenpan, et al.
(författare)
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Hepatic injury and ileitis associated with gut microbiota dysbiosis in mice upon F–53B exposure
- 2024
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 248
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Tidskriftsartikel (refereegranskat)abstract
- Chlorinated polyfluorinated ether sulfonate (F–53B), a substitute of perfluorooctane sulfonic acid (PFOS), has attracted significant attention for its link to hepatotoxicity and enterotoxicity. Nevertheless, the underlying mechanisms of F–53B-induced enterohepatic toxicity remain incompletely understood. This study aimed to explore the role of F–53B exposure on enterohepatic injury based on the gut microbiota, pathological and molecular analysis in mice. Here, we exposed C57BL/6 mice to F–53B (0, 4, 40, and 400 μg/L) for 28 days. Our findings revealed a significant accumulation of F–53B in the liver, followed by small intestines, and feces. In addition, F–53B induced pathological collagen fiber deposition and lipoid degeneration, up-regulated the expression of fatty acid β-oxidation-related genes (PPARα and PPARγ, etc), while simultaneously down-regulating pro-inflammatory genes (Nlrp3, IL-1β, and Mcp1) in the liver. Meanwhile, F–53B induced ileal mucosal barrier damage, and an up-regulation of pro-inflammatory genes and mucosal barrier-related genes (Muc1, Muc2, Claudin1, Occludin, Mct1, and ZO-1) in the ileum. Importantly, F–53B distinctly altered gut microbiota compositions by increasing the abundance of Akkermansia and decreasing the abundance of Prevotellaceae_NK3B31_group in the feces. F–53B-altered microbiota compositions were significantly associated with genes related to fatty acid β-oxidation, inflammation, and mucosal barrier. In summary, our results demonstrate that F–53B is capable of inducing hepatic injury, ileitis, and gut microbiota dysbiosis in mice, and the gut microbiota dysbiosis may play an important role in the F–53B-induced enterohepatic toxicity.
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| 11. |
- Luo, Yang, et al.
(författare)
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Three-dimensional and temperature-dependent electronic structure of the heavy-fermion compound CePt2In7 studied by angle-resolved photoemission spectroscopy
- 2020
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Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 101:11
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Tidskriftsartikel (refereegranskat)abstract
- The three-dimensional and temperature-dependent electronic structures of the heavy-fermion superconductor CePt2In7 are investigated. Angle-resolved photoemission spectroscopy using variable photon energy establishes the existence of quasi-two- and three-dimensional Fermi surface topologies. Temperature-dependent 4d-4f on-resonance photoemission spectroscopies data reveal that heavy quasiparticle bands begin to form at a temperature well above the characteristic (coherence) temperature T+. The emergence of low-lying crystal electric field excitation may be responsible for the "relocalization" or the precursor to the establishment of heavy electrons coherence in heavy-fermion compounds. These findings provide critical insight into understanding the hybridization in heavy-fermion systems.
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| 12. |
- Song, Jiao-Jiao, et al.
(författare)
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The 4f-Hybridization Strength in CemMnIn3m+2n Heavy-Fermion Compounds Studied by Angle-Resolved Photoemission Spectroscopy
- 2021
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Ingår i: Chinese Physics Letters. - : IOP Publishing. - 0256-307X .- 1741-3540. ; 38:10
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Tidskriftsartikel (refereegranskat)abstract
- We systemically investigate the nature of Ce 4f electrons in structurally layered heavy-fermion compounds CemMnIn3m+2n (with M = Co, Rh, Jr, and Pt, m = 1, 2, n = 0-2), at low temperature using on-resonance angle-resolved photoemission spectroscopy. Three heavy quasiparticle bands f(0), f(7/2)(1) and f(5/2)(1), are observed in all compounds, whereas their intensities and energy locations vary greatly with materials. The strong f(0) states imply that the localized electron behavior dominates the Ce 4f states. The Ce 4f electrons are partially hybridized with the conduction electrons, making them have the dual nature of localization and itinerancy. Our quantitative comparison reveals that the f(5/2)(1)-f (0) intensity ratio is more suitable to reflect the 4f-state hybridization strength.
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| 13. |
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| 14. |
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| 15. |
- Wu, Jingnan, 1994, et al.
(författare)
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Modulating the nanoscale morphology on carboxylate-pyrazine containing terpolymer toward 17.8% efficiency organic solar cells with enhanced thermal stability
- 2022
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Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947. ; 446
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Tidskriftsartikel (refereegranskat)abstract
- It had been commonly accepted in the organic photovoltaic (OPV) community that subtle variations in the molecular structure of active layer materials would cause profound impacts on their aggregating structure and blend morphology and therefore the performance of such polymer solar cells (PSCs). Herein, we employed an electron-deficient building block 3,6-dithiophenyl-2-carboxylate pyrazine (DTCPz) for constructing one series of promising donor terpolymers of PMZ1, PMZ2, and PMZ3, respectively, gaining their relatively lower-lying highest occupied molecular orbital (HOMO) energy levels, more closed π-π stacking and enhanced crystallinity in thin films, and lower miscibility with acceptor Y6, in comparison with their parent polymer counterpart (namely PM6). Reaching DTCPz moieties up to 20% (mol/mol%) in its terpolymer composition, the resulting polymer (PMZ2) achieved more favorable phase separation with improved exciton dissociation, and charge transport and extraction. As a result, an outstanding fill factor of 77.2% and a promising power conversion efficiency of 17.8 % was achieved. Moreover, the corresponding device shows better thermal stability over the PM6-based one. This work suggests a facile method for significantly improving the thin film morphology of the active-layer materials via fine-tuning the chemical structure of electron-deficient units on the backbone of the wide bandgap donor polymer, therefore achieving enhanced photovoltaic performance and thermal stability for practical applications.
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| 16. |
- Wu, Qi-Zhen, et al.
(författare)
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Long-term exposure to major constituents of fine particulate matter and neurodegenerative diseases : a population-based survey in the Pearl River Delta Region, China
- 2024
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 470
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to PM2.5 has been linked to neurodegenerative diseases, with limited understanding of constituent-specific contributions.Objectives: To explore the associations between long-term exposure to PM2.5 constituents and neurodegenerative diseases.Methods: We recruited 148,274 individuals aged ≥ 60 from four cities in the Pearl River Delta region, China (2020 to 2021). We calculated twenty-year average air pollutant concentrations (PM2.5 mass, black carbon (BC), organic matter (OM), ammonium (NH4+), nitrate (NO3-) and sulfate (SO42-)) at the individuals' home addresses. Neurodegenerative diseases were determined by self-reported doctor-diagnosed Alzheimer's disease (AD) and Parkinson's disease (PD). Generalized linear mixed models were employed to explore associations between pollutants and neurodegenerative disease prevalence.Results: PM2.5 and all five constituents were significantly associated with a higher prevalence of AD and PD. The observed associations generally exhibited a non-linear pattern. For example, compared with the lowest quartile, higher quartiles of BC were associated with greater odds for AD prevalence (i.e., the adjusted odds ratios were 1.81; 95% CI, 1.45–2.27; 1.78; 95% CI, 1.37–2.32; and 1.99; 95% CI, 1.54–2.57 for the second, third, and fourth quartiles, respectively).Conclusions: Long-term exposure to PM2.5 and its constituents, particularly combustion-related BC, OM, and SO42-, was significantly associated with higher prevalence of AD and PD in Chinese individuals.Environmental implication: PM2.5 is a routinely regulated mixture of multiple hazardous constituents that can lead to diverse adverse health outcomes. However, current evidence on the specific contributions of PM2.5 constituents to health effects is scarce. This study firstly investigated the association between PM2.5 constituents and neurodegenerative diseases in the moderately to highly polluted Pearl River Delta region in China, and identified hazardous constituents within PM2.5 that have significant impacts. This study provides important implications for the development of targeted PM2.5 prevention and control policies to reduce specific hazardous PM2.5 constituents.
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| 17. |
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| 18. |
- Yuan, Ya Hua, et al.
(författare)
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Angle-resolved photoemission spectroscopy view on the nature of Ce 4f electrons in the antiferromagnetic Kondo lattice CePd5Al2
- 2021
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Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9969 .- 2469-9950. ; 103:12
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Tidskriftsartikel (refereegranskat)abstract
- We report an angle-resolved photoemission spectroscopy study of the antiferromagnetic Kondo lattice CePd5Al2, focusing on the quasi-two-dimensional k-space nature of its Fermi surface and, tuning photon energy to the Ce 4d-4f on-resonance transition, the hybridization of the Ce 4f state. A strong shoulder feature on the f0 peak was detected, suggesting hybridization between conduction and f bands. On-resonance spectra revealed narrow, yet hybridized quasiparticle bands with sharp peaks and ∼ 9 meV energy dispersion near the Fermi energy EF. The observed dispersive hybridized f band can be well described by a hybridization-band picture based on the periodic Anderson model (PAM). Hence, the 4f electrons in CePd5Al2 display a dual nature, with both localized and itinerant features, but with dominantly localized character.
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| 19. |
- Arun, K. G., et al.
(författare)
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New horizons for fundamental physics with LISA
- 2022
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Ingår i: Living Reviews in Relativity. - : Springer Science and Business Media LLC. - 1433-8351 .- 2367-3613. ; 25:1
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Forskningsöversikt (refereegranskat)abstract
- The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
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| 20. |
- Barausse, Enrico, et al.
(författare)
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Prospects for fundamental physics with LISA
- 2020
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Ingår i: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
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| 21. |
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| 22. |
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| 23. |
- Cai, Jing, et al.
(författare)
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Characterization of offline analysis of particulate matter with FIGAERO-CIMS
- 2023
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Ingår i: Atmospheric Measurement Techniques (AMT). - : Copernicus GmbH. - 1867-8610 .- 1867-8548 .- 1867-1381. ; 16:5, s. 1147-1165
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of the molecular composition of organic aerosol (OA) constituents improve our understanding of sources, formation processes, and physicochemical properties of OA. One instrument providing such data at a time resolution of minutes to hours is the chemical ionization time-of-flight mass spectrometer with filter inlet for gases and aerosols (FIGAERO-CIMS). The technique collects particles on a filter, which are subsequently desorbed, and the evaporated molecules are ionized and analyzed in the mass spectrometer. However, long-term measurements using this technique and/or field deployments at several sites simultaneously require substantial human and financial resources. The analysis of filter samples collected outside the instrument (offline) may provide a more cost-efficient alternative and makes this technology available for the large number of particle filter samples collected routinely at many different sites globally. Filter-based offline use of the FIGAERO-CIMS limits this method, albeit to particle-phase analyses, which is likely at a reduced time resolution compared to online deployments. Here we present the application and assessment of offline FIGAERO-CIMS, using Teflon and quartz fiber filter samples that were collected in autumn 2018 in urban Beijing. We demonstrate the feasibility of the offline application with a “sandwich” sample preparation for the over 900 identified organic compounds with (1) high signal-to-noise ratios, (2) high repeatability, and (3) linear signal response to the filter loadings. Comparable overall signals were observed between the quartz fiber and Teflon filters for 12 and 24h samples but with larger signals for semi-volatile compounds for the quartz fiber filters, likely due to adsorption artifacts. We also compare desorption profile (thermogram) shapes for the two filter materials. Thermograms are used to derive volatility qualitatively based on the desorption temperature at which the maximum signal intensity of a compound is observed (Tmax). While we find that Tmax can be determined with high repeatability (±5.7∘C) from the duplicate tests for one filter type, we observe considerable differences in Tmax between the quartz and Teflon filters, warranting further investigation into the thermal desorption characteristics of different filter types. Overall, this study provides a basis for expanding OA molecular characterization by FIGAERO-CIMS to situations where and when deployment of the instrument itself is not possible.
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| 24. |
- Delios, A., et al.
(författare)
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Examining the generalizability of research findings from archival data
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Tidskriftsartikel (refereegranskat)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 25. |
- Ding, Xue Bing, et al.
(författare)
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Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 411-418
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD). However, there is no direct evidence in humans to support this role1–5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD.
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| 26. |
- Fang, Xing, et al.
(författare)
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Microstructure and mechanical properties of the laser welded air-hardening steel joint
- 2024
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Ingår i: Materials Characterization. - : Elsevier BV. - 1044-5803 .- 1873-4189. ; 213
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Tidskriftsartikel (refereegranskat)abstract
- The decrease in mechanical properties of high-strength steel after welding is an important issue affecting the wide application of high-strength steel. Air-hardening steel is a high-strength steel suitable for lower body structural parts such as subframes. Its application process involves welding, hot forming and other processes. The present work investigates the microstructure and mechanical properties of the air-hardening steel laser welded joint that is air-cooled after hot forming in the two-phase zone (800 °C). The microstructure was characterized by electron backscattered diffraction (EBSD), scanning electron microscope (SEM) and transmission electron microscope (TEM). The results show that during hot forming, the welded joint transforms from martensite to ferrite and acicular martensite, and the base metal transforms from ferrite to polygonal martensite and ferrite. The difference in martensite morphology between the welded joint and the base metal is attributed to the nucleation positions of austenite. The structural evolution of the welded joint and the base metal is accompanied with the annihilation and reproduction of dislocations, which results in significant changes in hardness. The hardness value dropped from the highest 430 HV to 271 HV in the welded joint, while increased from the lowest 184 HV to 203 HV in the base metal. After hot forming, the tensile strength of the welded sample is reduced by only 36 MPa, and the total elongation is slightly decreased by about 1.5% compared with the unwelded sample. The welded joint and the base metal have similar plastic deformation capabilities, since the acicular martensite in the welded joint displays good plastic deformation ability, and the dislocation density of the welded joint and the base metal is similar. Overall, the microstructure and dislocation density of the air-hardening steel welded joint after hot forming are similar to those of the base metal, which is responsible for the good mechanical properties of air-hardening steel welded joint.
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| 27. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 28. |
- Ge, R, et al.
(författare)
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Normative Modeling of Brain Morphometry Across the Lifespan Using CentileBrain: Algorithm Benchmarking and Model Optimization
- 2023
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Normative modeling is a statistical approach to quantify the degree to which a particular individual-level measure deviates from the pattern observed in a normative reference population. When applied to human brain morphometric measures it has the potential to inform about the significance of normative deviations for health and disease. Normative models can be implemented using a variety of algorithms that have not been systematically appraised. Methods: To address this gap, eight algorithms were compared in terms of performance and computational efficiency using brain regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) collated from 87 international MRI datasets. Performance was assessed with the mean absolute error (MAE) and computational efficiency was inferred from central processing unit (CPU) time. The algorithms evaluated were Ordinary Least Squares Regression (OLSR), Bayesian Linear Regression (BLR), Generalized Additive Models for Location, Scale, and Shape (GAMLSS), Parametric Lambda, Mu, Sigma (LMS), Gaussian Process Regression (GPR), Warped Bayesian Linear Regression (WBLG), Hierarchical Bayesian Regression (HBR), and Multivariable Fractional Polynomial Regression (MFPR). Model optimization involved testing nine covariate combinations pertaining to acquisition features, parcellation software versions, and global neuroimaging measures (i.e., total intracranial volume, mean cortical thickness, and mean cortical surface area). Findings: Statistical comparisons across models at PFDR<0.05 indicated that the MFPR-derived sex- and region-specific models with nonlinear polynomials for age and linear effects of global measures had superior predictive accuracy; the range of the MAE of the models of regional subcortical volumes was 70-520 mm3 and the corresponding ranges for regional cortical thickness and regional cortical surface area were 0.09-0.26 mm and 24-560 mm2, respectively. The MFPR-derived models were also computationally more efficient with a CPU time below one second compared to a range of 2 seconds to 60 minutes for the other algorithms. The performance of all sex- and region-specific MFPR models plateaued at sample sizes exceeding 3,000 and showed comparable MAEs across distinct 10-year age-bins covering the human lifespan. Interpretation: These results provide an empirically benchmarked framework for normative modeling of brain morphometry that is useful for interpreting prior literature and supporting future study designs. The model and tools described here are freely available through CentileBrain (https://centilebrain.org/), a user-friendly web platform.
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| 29. |
- Gu, Yeqing, et al.
(författare)
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Consumption of ultraprocessed food and development of chronic kidney disease : the Tianjin Chronic Low-Grade Systemic Inflammation and Health and UK Biobank Cohort Studies
- 2023
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Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 117:2, s. 373-382
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMany ultraprocessed food (UPF)-derived by-products may play a role in the development of chronic kidney disease (CKD). Although several studies have assessed the association of UPFs with kidney function decline or CKD in various countries, no evidence has been shown in China and the United Kingdom.ObjectivesThis study aims to evaluate the association between UPF consumption and risk of CKD in 2 large cohort studies from China and the United Kingdom.MethodsIn total, 23,775 and 102,332 participants without baseline CKD were enrolled in the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) and UK Biobank cohort studies, respectively. Information on UPF consumption was obtained from a validated food frequency questionnaire in the TCLSIH and 24-h dietary recalls in the UK Biobank cohort. CKD was defined as an estimated glomerular filtration rate of ResultsAfter a median follow-up of 4.0 and 10.1 y, the incidence rates of CKD were around 1.1% and 1.7% in the TCLSIH and UK Biobank cohorts, respectively. The multivariable hazard ratio [95% confidence interval] of CKD across increasing quartiles (quartiles 1–4) of UPF consumption were 1 (reference), 1.24 (0.89, 1.72), 1.30 (0.91, 1.87), and 1.58 (1.07, 2.34) (P for trend = 0.02) in the TCLSIH cohort and 1 (reference), 1.14 (1.00, 1.31), 1.16 (1.01, 1.33), and 1.25 (1.09, 1.43) (P for trend < 0.01) in the UK Biobank cohort, respectively.ConclusionsOur finding indicated that higher UPF consumption is associated with a higher risk of CKD. Moreover, restricting UPF consumption may potentially benefit the prevention of CKD. Further clinical trials are required to clarify the causality.
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| 30. |
- Guo, Jianqiu, et al.
(författare)
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Early life triclosan exposure and neurodevelopment of children at 3 years in a prospective birth cohort
- 2020
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Ingår i: International journal of hygiene and environmental health. - : Urban & Fischer. - 1438-4639 .- 1618-131X. ; 224
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early life exposure to triclosan, an emerging endocrine disrupting chemical, may adversely impact childhood neurodevelopment, but limited epidemiologic studies have examined the associations.OBJECTIVE: We evaluated the associations between prenatal and postnatal triclosan exposure and child neurodevelopment at 3 years.METHODS: The study included 377 mother-child pairs who participated in Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. Triclosan concentrations in maternal and 3-year-old child urine samples were quantified using gas chromatography-tandem mass spectrometry (GC-MS/MS). Gesell Developmental Schedules (GDS) were used to assess child neurodevelopment at 3 years of age. Multivariate linear regression models were applied to estimate associations of prenatal and postnatal urinary triclosan concentrations with children's developmental quotients (DQs).RESULTS: Detection frequencies of triclosan in maternal and childhood urine samples were 100% and 99.5%, respectively. The median values of prenatal and postnatal urinary triclosan levels were 0.65 and 0.44 μg/L, respectively. One ln-unit increase of maternal urinary triclosan concentration was associated with increase of DQ scores in motor area of children (regression coefficient, β = 0.28, 95% confidence interval, CI: 0.03, 0.54; p = 0.03). In sex-stratified analyses, maternal urinary triclosan levels were significantly related to increases in DQ scores in motor area among boys (β = 0.25, 95%CI: 0.01, 0.50; p = 0.04), while postnatal urinary triclosan concentrations were inversely associated with DQ scores in social area in boys (β = -0.37, 95%CI: -0.72, -0.03; p = 0.03).CONCLUSIONS: The findings suggested that prenatal triclosan exposure predicted increases in motor scores, while postnatal triclosan exposure was related to reductions in social scores of 3-year-old children. These associations were only observed in boys. The biological mechanisms linking triclosan exposure to neurodevelopment await further studies.
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| 31. |
- Guo, Jianqiu, et al.
(författare)
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Maternal and childhood urinary phenol concentrations, neonatal thyroid function, and behavioral problems at 10 years of age : The SMBCS study
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 743
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Environmental phenols, bisphenol A (BPA), triclosan (TCS), and benzophenone-3 (BP-3), are known as emerging endocrine-disrupting chemicals; however, their impacts on thyroid hormones and children's neurobehaviors are still unclear.OBJECTIVES: We aimed to examine the associations of prenatal and childhood exposure to phenols with neonatal thyroid function and childhood behavioral problems aged 10 years.METHODS: A total of 386 mother-singleton pairs were included from Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. We quantified urinary BPA, TCS and BP-3 concentrations in maternal and 10-year-old children's urine samples using gas chromatography tandem mass spectrometry and thyroid function parameters in cord serum samples. Caregivers completed the Strength and Difficulties Questionnaire (SDQ) for their children at 10 years of age. Multivariable linear regression models and logistic regression models were applied to estimate associations of urinary phenol concentrations with thyroid hormones and risks of children's behavioral problems, respectively.RESULTS: The median values of urinary BPA, TCS and BP-3 concentrations for pregnant women were 1.75 μg/L, 0.54 μg/L and 0.37 μg/L, while 1.29 μg/L, 6.64 μg/L and 1.39 μg/L for children, respectively. Maternal urinary BPA concentrations were in associations with 1.00% [95% confidence interval (CI): 0.20%, 1.92%] increases in cord serum FT4 concentrations and significantly associated with increased risks of total difficulties [odds ratio (OR): 1.45, 95% CI: 1.07, 1.97], while maternal urinary levels of BP-3 were significantly related to poorer prosocial behaviors (OR: 1.58, 95% CI: 1.04, 2.39) of children at 10 years of age. In sex-stratified analyses, maternal urinary BPA concentrations were related to increased total difficulty subscales only in boys.CONCLUSIONS: The findings indicated that higher prenatal urinary BPA concentrations were associated with increased risks of total difficulties, especially in boys and maternal urinary BP-3 concentrations were related to poorer prosocial behaviors at 10 years.
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| 32. |
- Guo, J., et al.
(författare)
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Prenatal exposure to mixture of heavy metals, pesticides and phenols and IQ in children at 7 years of age : The SMBCS study
- 2020
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Prenatal exposure to heavy metals, pesticides and phenols has been suggested to interfere with neurodevelopment, but the neurotoxicity of their mixtures is still unclear. We aimed to elucidate the associations of maternal urinary concentrations of selected chemical mixtures with intelligence quotient (IQ) in children.Methods: Maternal urinary concentrations of selected heavy metals, pesticide metabolites, and phenols were quantified in pregnant women who participated in the Sheyang Mini Birth Cohort Study (SMBCS) from June 2009 to January 2010. At age 7 years, child's IQ score was assessed using the Chinese version of Wechsler Intelligence Scale for Children (C-WISC) by trained pediatricians. Generalized linear regression models (GLM), Bayesian kernel machine regression (BKMR) models and elastic net regression (ENR) models were used to assess the associations of urinary concentrations individual chemicals and their mixtures with IQ scores of the 7-year-old children.Results: Of 326 mother-child pairs, single-chemical models indicated that prenatal urinary concentrations of lead (Pb) and bisphenol A (BPA) were significantly negatively associated with full intelligence quotient (FIQ) among children aged 7 years [β = −2.31, 95% confidence interval (CI): −4.13, −0.48; p = 0.013, sex interaction p-value = 0.076; β = −1.18, 95% CI: −2.21, −0.15; p = 0.025; sex interaction p-value = 0.296, for Pb and BPA, respectively]. Stratified analysis by sex indicated that the associations were only statistically significant in boys. In multi-chemical BKMR and ENR models, statistically significant inverse association was found between prenatal urinary Pb level and boy's FIQ scores at 7 years. Furthermore, BKMR analysis indicated that the overall mixture was associated with decreases in boy's IQ when all the chemicals’ concentrations were at their 75th percentiles or higher, compared to at their 50th percentiles. ENR models revealed that maternal urinary Pb levels were statistically significantly associated with lower FIQ scores (β = −2.20, 95% CI: −4.20, −0.20; p = 0.031).Conclusions: Prenatal exposure to selected chemical mixtures may affect intellectual performance at 7 years of age, particularly in boys. Pb and BPA were suspected as primary chemicals associated with child neurodevelopment.
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| 33. |
- Guo, Jianqiu, et al.
(författare)
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Prenatal exposure to multiple phenolic compounds, fetal reproductive hormones, and the second to fourth digit ratio of children aged 10 years in a prospective birth cohort
- 2021
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Ingår i: Chemosphere. - : Pergamon Press. - 0045-6535 .- 1879-1298. ; 263
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Tidskriftsartikel (refereegranskat)abstract
- Select phenols are known to possess hormone-disrupting properties, but no previous study has addressed the potential effects of prenatal exposure to phenol mixtures on fetal reproductive hormones and children's second to fourth digit (2D: 4D) ratio, a marker for in utero testosterone (T) exposure. We aimed to explore interrelations of prenatal phenol exposures individually and in mixtures, cord serum reproductive hormones, and 2D: 4D ratio of children aged 10 years. Urinary 11 phenol concentrations were determined from 392 pregnant women participating in a longitudinal birth cohort. We estimated associations of prenatal phenol exposures individually and in mixtures with cord reproductive hormones and children's 2D:4D ratio using three statistical approaches, including generalized linear models (GLMs), elastic net regression (ENR) models and Bayesian kernel machine regression (BKMR) models. In female newborns, the three models showed that maternal triclosan (TCS) concentrations were significantly negatively associated with cord serum T levels [regression coefficient (β) = -0.076, 95% confidence interval (CI): 0.138, -0.013; p = 0.018]. Additionally, maternal urinary bisphenol A (BPA) levels were related to decreases in 2D:4D ratio of the left hand in girls by GLMs (β = -0.003, 95% CI: 0.007, -0.001; p = 0.024) and ENR models, but not BKMR models. We provided evidence that prenatal TCS exposure predicted lower cord serum T levels, and maternal BPA exposure was related to decreased 2D:4D ratio of the left hand in females.
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| 34. |
- Guo, J., et al.
(författare)
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Urinary bisphenol A concentrations and adiposity measures at age 7 years in a prospective birth cohort
- 2020
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Ingår i: Chemosphere. - : Pergamon Press. - 0045-6535 .- 1879-1298. ; 251
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A (BPA) exposure during early life may increase risk of childhood obesity, however, prospective evidence of birth cohort is limited and inconclusive. We aimed to explore the associations of maternal and childhood BPA exposure with child adiposity measures, including body mass index, waist circumference and skinfold thickness and waist to height ratio of children at 7 years. 430 mother-child pairs were examined from a population-based prospective cohort in a rural area of East China. BPA concentrations of spot urine samples were quantified in mothers and their children aged 3 and 7 years. Maternal urinary BPA concentration was significantly positively associated with waist circumference in children aged 7 years (β = 0.508 cm, 95% CI: 0.067, 0.950). These significant associations were not modified by child sex, but they were only observed among girls in sex-stratified analyses. Risk of central obesity related to prenatal BPA exposure was significantly higher in the second and the third tertile than those in the first tertile (odds ratio, OR = 2.510, 95% CI = 1.146, 5.499; OR = 2.584, 95% CI = 1.186, 5.631, respectively; p for trend = 0.022). The present findings suggested that prenatal exposure to BPA may enhance waist circumference of children and thereby increase risk of central obesity in school-age girls.
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| 35. |
- Han, Kun, et al.
(författare)
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Enhanced Metal-Insulator Transition in Freestanding VO2 Down to 5 nm Thickness
- 2021
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:14, s. 16688-16693
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Tidskriftsartikel (refereegranskat)abstract
- Ultrathin freestanding membranes with a pronounced metal-insulator transition (MIT) have huge potential for future flexible electronic applications as well as provide a unique aspect for the study of lattice-electron interplay. However, the reduction of the thickness to an ultrathin region (a few nm) is typically detrimental to the MIT in epitaxial films, and even catastrophic for their freestanding form. Here, we report an enhanced MIT in VO2-based freestanding membranes, with a lateral size up to millimeters and the VO2 thickness down to 5 nm. The VO2 membranes were detached by dissolving a Sr3Al2O6 sacrificial layer between the VO2 thin film and the c-Al2O3(0001) substrate, allowing the transfer onto arbitrary surfaces. Furthermore, the MIT in the VO2 membrane was greatly enhanced by inserting an intermediate Al2O3 buffer layer. In comparison with the best available ultrathin VO2 membranes, the enhancement of MIT is over 400% at a 5 nm VO2 thickness and more than 1 order of magnitude for VO2 above 10 nm. Our study widens the spectrum of functionality in ultrathin and large-scale membranes and enables the potential integration of MIT into flexible electronics and photonics.
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| 36. |
- He, Xiaohe, et al.
(författare)
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Real-time regulation of room temperature based on individual thermal sensation using an online brain–computer interface
- 2022
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Ingår i: Indoor Air. - : NLM (Medline). - 0905-6947 .- 1600-0668. ; 32:e13106
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of indoor temperature based on neurophysiological and psychological signals is one of the most promising technologies for intelligent buildings. In this study, we developed a system for closed-loop control of indoor temperature based on brain-computer interface (BCI) technology for the first time. Electroencephalogram (EEG) signals were collected from subjects for two room temperature categories (cool comfortable and hot uncomfortable) and used to build a thermal-sensation discrimination model (TSDM) with an ensemble learning method. Then, an online BCI system was developed based on the TSDM. In the online room temperature control experiment, when the TSDM detected that the subjects felt hot and uncomfortable, BCI would automatically turn on the air conditioner, and when the TSDM detected that the subjects felt cool and comfortable, BCI would automatically turn off the air conditioner. The results of online experiments in a hot environment showed that a BCI could significantly improve the thermal comfort of subjects (the subjective thermal comfort score decreased from 2.45 (hot uncomfortable) to 0.55 (cool comfortable), p < 0.001). A parallel experiment further showed that if the subjects wore thicker clothes during the experiment, the BCI would turn on the air conditioner for a longer time to ensure the thermal comfort of the subjects. This has further confirmed the effectiveness of TSDM model in evaluating thermal sensation under the dynamic change of room temperature and showed the model's good robustness. This study proposed a new paradigm of human-building interaction, which is expected to play a promising role in the development of human-centered intelligent buildings.
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| 37. |
- 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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| 38. |
- Huang, Shan, et al.
(författare)
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Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner
- 2023
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Ingår i: Cellular Oncology. - : Springer Science and Business Media LLC. - 2211-3428 .- 2211-3436. ; 46:4, s. 953-967
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Available evidence indicates that dipyridamole enhances the anti-thrombotic effects of aspirin for the prevention of secondary strokes. Aspirin is a well-known non-steroid anti-inflammatory drug. This anti-inflammatory property has turned aspirin into a potential drug for inflammation-related cancers such as colorectal cancer (CRC). Here, we aimed to explore whether the anti-cancer effect of aspirin against CRC could be improved by combined administration with dipyridamole.METHODS: Population-based clinical data analysis was conducted to assess a possible therapeutic effect of combined dipyridamole and aspirin treatment in inhibiting CRC compared with either monotherapy. This therapeutic effect was further verified in different CRC mouse models, i.e. an orthotopic xenograft mouse model, an AOM/DSS mouse model, an Apc min/+ mouse model and a patient derived xenograft (PDX) mouse model. The in vitro effects of the drugs on CRC cells were tested using CCK8 and flow cytometry assays. RNA-Seq, Western blotting, qRT-PCR and flow cytometry were used to identify the underlying molecular mechanisms. RESULTS: We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone. The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect.CONCLUSIONS: Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further clinical studies confirm our findings, these may be repurposed as adjuvant agents.
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| 39. |
- Huyghe, Jeroen R, et al.
(författare)
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Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
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Tidskriftsartikel (refereegranskat)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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| 40. |
- Imamura, Fumiaki, et al.
(författare)
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Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes : A pooled analysis of prospective cohort studies
- 2020
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:6
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDe novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D).Methods and findingsSeventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors.ConclusionsConcentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.
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| 41. |
- Ji, Yanzhu, et al.
(författare)
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Orthologous microsatellites, transposable elements, and DNA deletions correlate with generation time and body mass in neoavian birds
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:35
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Tidskriftsartikel (refereegranskat)abstract
- The rate of mutation accumulation in germline cells can be affected by cell replication and/or DNA damage, which are further related to life history traits such as generation time and body mass. Leveraging the existing datasets of 233 neoavian bird species, here, we investigated whether generation time and body mass contribute to the interspecific variation of orthologous microsatellite length, transposable element (TE) length, and deletion length and how these genomic attributes affect genome sizes. In nonpasserines, we found that generation time is correlated to both orthologous microsatellite length and TE length, and body mass is negatively correlated to DNA deletions. These patterns are less pronounced in passerines. In all species, we found that DNA deletions relate to genome size similarly as TE length, suggesting a role of body mass dynamics in genome evolution. Our results indicate that generation time and body mass shape the evolution of genomic attributes in neoavian birds.
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| 42. |
- Jiang, M., et al.
(författare)
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National level assessment of using existing airport infrastructures for photovoltaic deployment
- 2021
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Ingår i: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 298
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Tidskriftsartikel (refereegranskat)abstract
- The airport is one of the most fundamental infrastructures in our society, its terminal buildings and parking lots are ideal locations for photovoltaic (PV) installation. The future trend of the electrification of the aviation and automobile industries will increase the electricity demand at airports calls for the integration of PV systems with airport infrastructure. Understanding the benefits of airport PV systems is crucial for the stakeholders including investors, project developers and policymakers to promote PV sector development. Thus, evaluation of the PV potential and relevant economic performance of airports is essential. Combined with the geographic information system (GIS), the PV potential of the civil airports in China is investigated. The results show that potential PV capacity of China's 239 civil airports reaches up to 2.50 GW. The annual electricity demand of the aviation industry in 8 provinces can be self-satisfied via airport PV generation. Detailed economic analysis shows that all airport PV systems are profitable through appropriate investment and operation strategies. © 2021
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| 43. |
- Jiang, Shangsong, et al.
(författare)
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Cutting Force and Surface Roughness during Straight-Tooth Milling of Walnut Wood
- 2022
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Ingår i: Forests. - : MDPI. - 1999-4907. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Walnut (Juglans regia L.) is widely used in wood furnishings, and machinability is a key factor for improving product quality and enterprise benefits. This work focused on the influence of the rake angle, depth of cut, and cutting speed on the cutting force and machined surface roughness during the straight-tooth milling of walnut. On the basis of the experimental findings, a mathematical model was created using a response surface methodology to determine the relationship between the cutting force and the cutting conditions, as well as the relationship between the surface roughness and the cutting conditions. Variance analysis was used to study the significant contributions of the interactions of various factors and two-level interactions to the cutting force and surface roughness. The optimized combination of milling conditions, resulting in lowest cutting force and surface roughness, was determined to be a rake angle of 5°, a depth of cut of 0.6 mm, and a cutting speed of 45 m/s.
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| 44. |
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| 45. |
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| 46. |
- Lai, Heidi T. M., et al.
(författare)
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Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes : Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE)
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:4, s. 854-863
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.RESEARCH DESIGN AND METHODS: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged >= 18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.RESULTS: During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P >= 0.1).CONCLUSIONS: Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.
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| 47. |
- Li, Suyang, et al.
(författare)
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One-pot fabrication of Mo1-xWxS2 alloy nanosheets as SERS substrates with highly Raman enhancement effect and long-term stability
- 2022
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Ingår i: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy. - : Elsevier BV. - 1386-1425 .- 1873-3557. ; 279, s. 121465-
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Tidskriftsartikel (refereegranskat)abstract
- A new Mo1-xWxS2 two-dimensional nanosheets were prepared by the one-pot method. After certain Mo atoms in MoS2 were replaced by W ones in a hydrothermal reduction procedure, Mo1-xWxS2 was formed on the Mo foil. Well enhanced Mo1-xWxS2 nanosheets were prepared when the sodium tungstate concentration got under control. Various characterizations were carried out, which indicate that Mo1-xWxS2 nanosheets with good crystallinity. Compared with MoS2, the Raman intensity of Rhodamine 6G (10-6 M) was amplified by 1.7 times with Mo1-xWxS2 nanosheets as the substrate. The characteristic Raman peaks could still be clearly distinguished until the concentration of Rhodamine 6G (R6G), Methylene blue (MB) and Crystal violet (CV) down to 10-8, 10-8 and 10- 7 M, respectively. With abundant edge active sites that facilitate charge transfer, Mo1-xWxS2 nanosheets could better enhance SERS signals of target detection molecules and get a good linear relationship exists within the concentration and Raman peak strength. In addition, R6G SERS detection also shows excellent reproducibility and long-term stability of this TMDs SERS substrate.
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| 48. |
- Li, Wenting, et al.
(författare)
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Effects of prenatal exposure to five parabens on neonatal thyroid function and birth weight : Evidence from SMBCS study
- 2020
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Ingår i: Environmental Research. - : Academic Press. - 0013-9351 .- 1096-0953. ; 188
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parabens, suspected as endocrine-disrupting chemicals, are nearly ubiquitous in the human body and exposure to these chemicals during pregnancy may disrupt thyroid hormones homeostasis and even affect fetal growth, although the impacts are still unclear.OBJECTIVES: We aimed to estimate associations of maternal urinary paraben concentrations with cord serum thyroid hormones and birth weight.METHODS: A subset of 437 mother-newborn pairs were included from a prospective birth cohort with five parabens quantified in maternal urine and seven thyroid function indicators measured in cord serum samples. Multivariable linear regression models and elastic net regression (ENR) models were applied to explore associations between individual and mixtures of prenatal urinary paraben concentrations and thyroid hormones and birth weight, respectively.RESULTS: Maternal urinary ethyl-paraben (EtP) concentrations were associated with increased cord serum total triiodothyronine levels (TT3) [percent change: 1.51%; 95% confidence interval (CI): 0.20%, 2.74%; p=0.017]. Urinary propyl-paraben (PrP) levels predicted higher thyroid peroxidase antibodies (percent change: 4.19%, 95% CI: 0.20%, 8.44%; p=0.041). Maternal urinary EtP and butyl-paraben (BuP) concentrations were significantly positively associated with birth weight [regression coefficient, (β)=40.9g, 95% CI: 3.99, 76.6; p=0.030; β=62.1g, 95% CI: 8.70, 115; p=0.023, for EtP and BuP, respectively]. In sex-stratified analyses, positive relationship between EtP levels and birth weight was observed in boys. Urinary EtP concentrations predicted higher TT3 levels in cord serum samples, assessing parabens as a chemical mixture with ENR models.CONCLUSIONS: Prenatal exposure to parabens may affect thyroid hormone indicators with increased serum TT3 levels and associate with higher birth weight, especially in boys. The underlying biological mechanisms and effects of prenatal paraben exposures on disruption of thyroid function homeostasis and potential impacts of childhood growth and development needed to be further investigated.
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| 49. |
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| 50. |
- Li, Ziyue, et al.
(författare)
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Integrating life cycle assessment and a farmer survey of management practices to study environmental impacts of peach production in Beijing, China
- 2022
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Ingår i: Environmental Science and Pollution Research. - : Springer Nature. - 0944-1344 .- 1614-7499.
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Tidskriftsartikel (refereegranskat)abstract
- While intensive peach production has expanded rapidly in recent years, few studies have explored the environmental impacts associated with specific regional systems or the optimal management strategies to minimize associated environmental risks. Here, data from a survey of 290 native farmers were used to conduct a life cycle assessment to quantify the acidification potential (AP), global warming potential (GWP), eutrophication potential (EP), and reactive nitrogen (Nr) losses in peach production in Pinggu District, Beijing. Total annual Nr losses, and GWP, AP, and EP values for peach production in Pinggu District were respectively 10.7 kg N t−1, 857 kg CO2-eq t−1, 12.9 kg SO2-eq t−1, and 4.1 kg PO4-eq t−1. The principal driving factors were fertilizer production, transportation, and application, which together accounted for 94%, 67%, 75%, and 94% of Nr losses, GWP, AP, and EP, respectively. In the high yield, high nitrogen-use efficiency (HH) group, relative values of Nr losses, GWP, AP, and EP were respectively 33%, 25%, 39%, and 32% lower than the overall averages for 290 orchards. Further analyses indicate that improved farming practices such as decreasing application rates of fertilizers, increasing proportion of base fertilization rate, and proper fertilization frequency in the HH group were the main reasons for these orchards’ better performance in peach yields and partial factor productivity of nitrogen fertilizer, and their reduced environmental impacts. These results highlight the need to optimize nutrient management in peach production in order simultaneously to realize both environmental sustainability and high productivity in the peach production system.
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