| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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
-
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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| 6. |
- Ao, Hong, et al.
(författare)
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Orbital climate variability on the northeastern Tibetan Plateau across the Eocene-Oligocene transition
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The first major build-up of Antarctic glaciation occurred in two consecutive stages across the Eocene-Oligocene transition (EOT): the EOT-1 cooling event at similar to 34.1-33.9Ma and the Oi-1 glaciation event at similar to 33.8-33.6Ma. Detailed orbital-scale terrestrial environmental responses to these events remain poorly known. Here we present magnetic and geochemical climate records from the northeastern Tibetan Plateau margin that are dated precisely from similar to 35.5 to 31Ma by combined magneto- and astro-chronology. These records suggest a hydroclimate transition at similar to 33.7Ma from eccentricity dominated cycles to oscillations paced by a combination of eccentricity, obliquity, and precession, and confirm that major Asian aridification and cooling occurred at Oi-1. We conclude that this terrestrial orbital response transition coincided with a similar transition in the marine benthic delta O-18 record for global ice volume and deep-sea temperature variations. The dramatic reorganization of the Asian climate system coincident with Oi-1 was, thus, a response to coeval atmospheric CO2 decline and continental-scale Antarctic glaciation. Marine records indicate a greenhouse to icehouse climate transition at similar to 34 million years ago, but how the climate changed within continental interiors at this time is less well known. Here, the authors show an orbital climate response shift with aridification on the northeastern Tibetan Plateau during this time.
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| 7. |
- Dennhag, Nils, 1989-, et al.
(författare)
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fhl2b mediates extraocular muscle protection in zebrafish models of muscular dystrophies and its ectopic expression ameliorates affected body muscles
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- In muscular dystrophies, muscle fibers loose integrity and die, causing significant suffering and premature death. Strikingly, the extraocular muscles (EOMs) are spared, functioning well despite the disease progression. Although EOMs have been shown to differ from body musculature, the mechanisms underlying this inherent resistance to muscle dystrophies remain unknown. Here, we demonstrate important differences in gene expression as a response to muscle dystrophies between the EOMs and trunk muscles in zebrafish via transcriptomic profiling. We show that the LIM-protein Fhl2 is increased in response to the knockout of desmin, plectin and obscurin, cytoskeletal proteins whose knockout causes different muscle dystrophies, and contributes to disease protection of the EOMs. Moreover, we show that ectopic expression of fhl2b can partially rescue the muscle phenotype in the zebrafish Duchenne muscular dystrophy model sapje, significantly improving their survival. Therefore, Fhl2 is a protective agent and a candidate target gene for therapy of muscular dystrophies.
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| 8. |
- He, Haoran, et al.
(författare)
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Deciphering microbiomes dozens of meters under our feet and their edaphoclimatic and spatial drivers
- 2024
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Ingår i: Global Change Biology. - 1354-1013. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbes inhabiting deep soil layers are known to be different from their counterpart in topsoil yet remain under investigation in terms of their structure, function, and how their diversity is shaped. The microbiome of deep soils (>1 m) is expected to be relatively stable and highly independent from climatic conditions. Much less is known, however, on how these microbial communities vary along climate gradients. Here, we used amplicon sequencing to investigate bacteria, archaea, and fungi along fifteen 18-m depth profiles at 20–50-cm intervals across contrasting aridity conditions in semi-arid forest ecosystems of China's Loess Plateau. Our results showed that bacterial and fungal α diversity and bacterial and archaeal community similarity declined dramatically in topsoil and remained relatively stable in deep soil. Nevertheless, deep soil microbiome still showed the functional potential of N cycling, plant-derived organic matter degradation, resource exchange, and water coordination. The deep soil microbiome had closer taxa–taxa and bacteria–fungi associations and more influence of dispersal limitation than topsoil microbiome. Geographic distance was more influential in deep soil bacteria and archaea than in topsoil. We further showed that aridity was negatively correlated with deep-soil archaeal and fungal richness, archaeal community similarity, relative abundance of plant saprotroph, and bacteria–fungi associations, but increased the relative abundance of aerobic ammonia oxidation, manganese oxidation, and arbuscular mycorrhizal in the deep soils. Root depth, complexity, soil volumetric moisture, and clay play bridging roles in the indirect effects of aridity on microbes in deep soils. Our work indicates that, even microbial communities and nutrient cycling in deep soil are susceptible to changes in water availability, with consequences for understanding the sustainability of dryland ecosystems and the whole-soil in response to aridification. Moreover, we propose that neglecting soil depth may underestimate the role of soil moisture in dryland ecosystems under future climate scenarios.
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| 9. |
- Jiao, Yiping, et al.
(författare)
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LYSTO: The Lymphocyte Assessment Hackathon and Benchmark Dataset
- 2024
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Ingår i: IEEE journal of biomedical and health informatics. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 2168-2194 .- 2168-2208. ; 28:3, s. 1161-1172
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Tidskriftsartikel (refereegranskat)abstract
- We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzhen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform.
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| 10. |
- Meng, Qinglai, et al.
(författare)
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Rapid personalized AMR diagnostics using two-dimensional antibiotic resistance profiling strategy employing a thermometric NDM-1 biosensor
- 2021
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Ingår i: Biosensors and Bioelectronics. - : Elsevier BV. - 0956-5663. ; 193
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) threatens global public health and modern surgical medicine. Expression of β-lactamase genes is the major mechanism by which pathogens become antibiotic resistant. Pathogens expressing extended spectrum β-lactamases (ESBL) and carbapenemases (CP) are especially difficult to treat and are associated with increased hospitalization and mortality rates. Despite considerable effort, identification of ESBLs and CPs in a clinically relevant timeframe remains challenging. In this study, a two-dimensional AMR profiling assay strategy was developed employing panels of antibiotics (penicillins, cephamycins, oximino-cephalosporins and carbapenems) and β-lactamases inhibitors (avibactam and EDTA). The assay required the development of a novel biosensor that employed New Delhi metallo-β-lactamase-1 (NDM-1) as the sensing element. Functionally probing β-lactamase activity using substrates and inhibitors combinatorically increased the informational content that enabled the development of assays capable of simultaneous, differential identification of multiple β-lactamases expressed in a single bacterial isolate. More specifically, the assay enabled the simultaneous identification of ESBL and CP in mock samples, as well as in an engineered construct which co-expressed these β-lactamases. The NDM-1 biosensor assay was 16 times and 8 times more sensitive than the ESBL Nordmann/Dortet/Poirel (NDP) and Carba Nordmann/Poirel (NP) assays, respectively. In a retrospective study, NDM-1 biosensor assays were able to differentially identify ESBLs, metallo-CPs and serine-CPs β-lactamases in 23 clinical isolates with 100% accuracy. An assay algorithm was developed which accelerated data analytics reducing turnaround to <1 h. The assay strategy integrated with AI-based data analytics has the potential to provide physicians with a comprehensive readout of patient AMR status.
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| 11. |
- Peng, Xu-Biao, et al.
(författare)
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Application of topological soliton in modeling protein folding : Recent progress and perspective
- 2020
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Ingår i: Chinese Physics B. - : IOP Publishing. - 1674-1056. ; 29:10
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Forskningsöversikt (refereegranskat)abstract
- Proteins are important biological molecules whose structures are closely related to their specific functions. Understanding how the protein folds under physical principles, known as the protein folding problem, is one of the main tasks in modern biophysics. Coarse-grained methods play an increasingly important role in the simulation of protein folding, especially for large proteins. In recent years, we proposed a novel coarse-grained method derived from the topological soliton model, in terms of the backbone C(alpha)chain. In this review, we will first systematically address the theoretical method of topological soliton. Then some successful applications will be displayed, including the thermodynamics simulation of protein folding, the property analysis of dynamic conformations, and the multi-scale simulation scheme. Finally, we will give a perspective on the development and application of topological soliton.
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| 12. |
- Ren, Yaojia, et al.
(författare)
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A comparative study on microstructure, nanomechanical and corrosion behaviors of AlCoCuFeNi high entropy alloys fabricated by selective laser melting and laser metal deposition
- 2022
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Ingår i: Journal of Materials Science and Technology. - : Elsevier BV. - 1005-0302. ; 131, s. 221-230
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the microstructure, nanomechanics, and corrosion behavior of AlCoCuFeNi high entropy alloys fabricated by selective laser melting (SLM) and laser metal deposition (LMD). The microstructure of SLM-processed specimens was mainly composed of columnar-grained BCC matrix (∼90 µm in width) and Cu-rich twinned FCC phase. The columnar grains grew epitaxially along the building direction and exhibited a strong {001} texture. In comparison, a coarse columnar-grained BCC matrix (∼150 µm in width) with a stronger 〈001〉 texture, rod-like B2 precipitates, and large core-shell structured FCC phases were formed in the LMD-processed specimens due to the higher heat accumulation effect. Consequently, the LMD-processed specimens showed a lower hardness, wear resistance, and corrosion resistance, but higher creep resistance and reduced Young's modulus than the SLM-processed specimens. Hot cracks occurred in both types of specimens, which could not be completely suppressed due to Cu segregation.
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| 13. |
- Song, Jiao-Jiao, et al.
(författare)
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Relocalization of uranium 5f electrons in the antiferromagnetic heavy-fermion superconductor UPd2Al3 : Insights from angle-resolved photoemission spectroscopy
- 2024
-
Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 109:20
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the antiferromagnetic heavy fermion superconductor UPd2Al3, employing angle-resolved photoemission spectroscopy to unravel the complex electronic structure of its U 5? electrons. We observe unexpected characteristics that challenge the conventional temperature-dependent behavior of heavy fermion systems, revealing unexpected characteristics. At temperatures above the anticipated coherence temperature (?*), we observe itinerant U 5? electrons at temperatures higher than previously postulated. Additionally, a previously unidentified dispersionless band emerges around 600 meV below the Fermi energy, potentially linked to spin-orbit splitting within the U 5? states. Hybridization between the 5? electrons and conduction band was observed with an energy dispersion of 10 meV at low temperatures, suggesting that U 5? electrons near and at the Fermi surface have an itinerant nature. Temperature-dependent 5?−5? resonance spectra reveal that the 5? electron spectrum weight increases with lowering temperature and begins to decrease at temperatures significantly higher than the Néel temperature (??). We further show that the competition between the Kondo effect and Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions may be responsible for the relocalization of 5? electrons, making relocalization a precursor to the establishment of magnetic order at lower temperatures. Our experiments also provide evidence that 5? electrons with the same orbital are involved in both the Kondo effect and RKKY interactions, suggesting that the two coexist at lower temperatures.
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| 14. |
- Wan, Guihong, et al.
(författare)
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Prediction of early-stage melanoma recurrence using clinical and histopathologic features
- 2022
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Ingår i: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Prognostic analysis for early-stage (stage I/II) melanomas is of paramount importance for customized surveillance and treatment plans. Since immune checkpoint inhibitors have recently been approved for stage IIB and IIC melanomas, prognostic tools to identify patients at high risk of recurrence have become even more critical. This study aims to assess the effectiveness of machine-learning algorithms in predicting melanoma recurrence using clinical and histopathologic features from Electronic Health Records (EHRs). We collected 1720 early-stage melanomas: 1172 from the Mass General Brigham healthcare system (MGB) and 548 from the Dana-Farber Cancer Institute (DFCI). We extracted 36 clinicopathologic features and used them to predict the recurrence risk with supervised machine-learning algorithms. Models were evaluated internally and externally: (1) five-fold cross-validation of the MGB cohort; (2) the MGB cohort for training and the DFCI cohort for testing independently. In the internal and external validations, respectively, we achieved a recurrence classification performance of AUC: 0.845 and 0.812, and a time-to-event prediction performance of time-dependent AUC: 0.853 and 0.820. Breslow tumor thickness and mitotic rate were identified as the most predictive features. Our results suggest that machine-learning algorithms can extract predictive signals from clinicopathologic features for early-stage melanoma recurrence prediction, which will enable the identification of patients that may benefit from adjuvant immunotherapy.
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| 15. |
- Xue, Jiao, et al.
(författare)
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Influence of Thermal Environment on Attendance and Adaptive Behaviors in Outdoor Spaces : A Study in a Cold-Climate University Campus
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:11
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Tidskriftsartikel (refereegranskat)abstract
- Creating a favorable thermal environment in an outdoor space is essential for attracting more occupants to outdoor areas and vitalizing a city. It is possible to study occupants' needs in an outdoor thermal environment by observing their attendance and behaviors, since people may exhibit certain adaptive measures, such as seeking shade, using parasols, etc., "vote with their feet", or even leave the space, if they feel uncomfortable. In order to investigate the influence of thermal environment on attendance and adaptive behaviors in outdoor spaces, in this study we carried out field campaigns in a university campus in a cold-climate city. The thermal environment was monitored, while surveys of thermal perceptions and observations of attendance and adaptive behaviors were conducted. Through the data analyses, it was found that the thermal environment had a great impact on the attendance of optional activities, but necessary activities were not influenced. The greatest influence on attendance came from air temperature. The influences of wind and humidity on attendance were found to be coupled with that of air temperature. Adaptive behaviors, such as seeking shade, using parasols, changing clothes, and changing the lengths of stay, were also greatly influenced by air temperature.
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| 16. |
- Yang, Qinsong, et al.
(författare)
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Genomic basis of the distinct biosynthesis of β-glucogallin, a biochemical marker for hydrolyzable tannin production, in three oak species
- 2024
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Ingår i: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137. ; 242:6, s. 2702-2718
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Tidskriftsartikel (refereegranskat)abstract
- Hydrolyzable tannins (HTs), predominant polyphenols in oaks, are widely used in grape wine aging, feed additives, and human healthcare. However, the limited availability of a high-quality reference genome of oaks greatly hampered the recognition of the mechanism of HT biosynthesis. Here, high-quality reference genomes of three Asian oak species (Quercus variabilis, Quercus aliena, and Quercus dentata) that have different HT contents were generated. Multi-omics studies were carried out to identify key genes regulating HT biosynthesis. In vitro enzyme activity assay was also conducted. Dual-luciferase and yeast one-hybrid assays were used to reveal the transcriptional regulation. Our results revealed that β-glucogallin was a biochemical marker for HT production in the cupules of the three Asian oaks. UGT84A13 was confirmed as the key enzyme for β-glucogallin biosynthesis. The differential expression of UGT84A13, rather than enzyme activity, was the main reason for different β-glucogallin and HT accumulation. Notably, sequence variations in UGT84A13 promoters led to different trans-activating activities of WRKY32/59, explaining the different expression patterns of UGT84A13 among the three species. Our findings provide three high-quality new reference genomes for oak trees and give new insights into different transcriptional regulation for understanding β-glucogallin and HT biosynthesis in closely related oak species.
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| 17. |
- Zhang, Yuehui, et al.
(författare)
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Hyperandrogenism and insulin resistance modulate gravid uterine and placental ferroptosis in PCOS-like rats. : Uterine and placental ferroptosis in pregnant PCOS-like rats
- 2020
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Ingår i: The Journal of endocrinology. - 1479-6805. ; 246:3, s. 247-63
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies in rats showed that maternal exposure to 5α-dihydrotestosterone (DHT) and insulin (INS) from gestational day 7.5 to 13.5 induces hyperandrogenism and insulin resistance (HAIR) and subsequently leads to placental insufficiency and fetal loss. We therefore hypothesized that maternal HAIR triggers ferroptosis in the uterus and placenta in association with fetal loss in pregnant rats. Compared with controls, we found that co-exposure to DHT and INS led to decreased levels of Gpx4 and glutathione (GSH), increased GSH+glutathione disulfide (GSSG) and malondialdehyde (MDA), aberrant expression of ferroptosis-associated genes (Acsl4, Tfrc, Slc7a11, and Gclc), increased iron deposition, and activated ERK/p38/JNK phosphorylation in the gravid uterus. However, in the placenta, DHT and INS exposure only partially altered the expression of ferroptosis-related markers (e.g., Gpx4, GSH+GSSG, MDA, Gls2 and Slc7a11 mRNAs, and phosphorylated p38 levels). In the uteri co-exposed to DHT and INS, we also observed shrunken mitochondria with electron-dense cristae, and increased Dpp4 mRNA expression. In contrast, in placentas co-exposed to DHT and INS we found decreased Dpp4 mRNA expression and increased Cisd1 mRNA expression. Further, DHT+INS-exposed pregnant rats exhibited decreased apoptosis in the uterus and increased necroptosis in the placenta. Our findings suggest that maternal HAIR causes the activation of ferroptosis in the gravid uterus and placenta, although this is mediated via different mechanisms operating at the molecular and cellular levels. Furthermore, our data suggest other cell death pathways may play a role in coordinating or compensating for HAIR-induced ferroptosis when the gravid uterus and placenta are dysfunctional.
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| 18. |
- Zhang, Yuehui, et al.
(författare)
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Hyperandrogenism and insulin resistance modulate gravid uterine and placental ferroptosis in PCOS-like rats.
- 2020
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 246:3, s. 247-263
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies in rats showed that maternal exposure to 5α-dihydrotestosterone (DHT) and insulin (INS) from gestational day 7.5 to 13.5 induces hyperandrogenism and insulin resistance (HAIR) and subsequently leads to placental insufficiency and fetal loss. We therefore hypothesized that maternal HAIR triggers ferroptosis in the uterus and placenta in association with fetal loss in pregnant rats. Compared with controls, we found that co-exposure to DHT and INS led to decreased levels of Gpx4 and glutathione (GSH), increased GSH+glutathione disulfide (GSSG) and malondialdehyde (MDA), aberrant expression of ferroptosis-associated genes (Acsl4, Tfrc, Slc7a11, and Gclc), increased iron deposition, and activated ERK/p38/JNK phosphorylation in the gravid uterus. However, in the placenta, DHT and INS exposure only partially altered the expression of ferroptosis-related markers (e.g., Gpx4, GSH+GSSG, MDA, Gls2 and Slc7a11 mRNAs, and phosphorylated p38 levels). In the uteri co-exposed to DHT and INS, we also observed shrunken mitochondria with electron-dense cristae, and increased Dpp4 mRNA expression. In contrast, in placentas co-exposed to DHT and INS we found decreased Dpp4 mRNA expression and increased Cisd1 mRNA expression. Further, DHT+INS-exposed pregnant rats exhibited decreased apoptosis in the uterus and increased necroptosis in the placenta. Our findings suggest that maternal HAIR causes the activation of ferroptosis in the gravid uterus and placenta, although this is mediated via different mechanisms operating at the molecular and cellular levels. Furthermore, our data suggest other cell death pathways may play a role in coordinating or compensating for HAIR-induced ferroptosis when the gravid uterus and placenta are dysfunctional.
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| 19. |
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| 20. |
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| 21. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 22. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 23. |
- Bu, Junling, et al.
(författare)
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Catalytic promiscuity of O-methyltransferases from Corydalis yanhusuo leading to the structural diversity of benzylisoquinoline alkaloids
- 2022
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Ingår i: Horticulture Research. - : Oxford University Press (OUP). - 2662-6810 .- 2052-7276. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- O-methyltransferases play essential roles in producing structural diversity and improving the biological properties of benzylisoquinoline alkaloids (BIAs) in plants. In this study, Corydalis yanhusuo, a plant used in traditional Chinese medicine due to the analgesic effects of its BIA-active compounds, was employed to analyze the catalytic characteristics of O-methyltransferases in the formation of BIA diversity. Seven genes encoding O-methyltransferases were cloned, and functionally characterized using seven potential BIA substrates. Specifically, an O-methyltransferase (CyOMT2) with highly efficient catalytic activity of both 4′- and 6-O-methylations of 1-BIAs was found. CyOMT6 was found to perform two sequential methylations at both 9- and 2-positions of the essential intermediate of tetrahydroprotoberberines, (S)-scoulerine. Two O-methyltransferases (CyOMT5 and CyOMT7) with wide substrate promiscuity were found, with the 2-position of tetrahydroprotoberberines as the preferential catalytic site for CyOMT5 (named scoulerine 2-O-methyltransferase) and the 6-position of 1-BIAs as the preferential site for CyOMT7. In addition, results of integrated phylogenetic molecular docking analysis and site-directed mutation suggested that residues at sites 172, 306, 313, and 314 in CyOMT5 are important for enzyme promiscuity related to O-methylations at the 6- and 7-positions of isoquinoline. Cys at site 253 in CyOMT2 was proved to promote the methylation activity of the 6-position and to expand substrate scopes. This work provides insight into O-methyltransferases in producing BIA diversity in C. yanhusuo and genetic elements for producing BIAs by metabolic engineering and synthetic biology.
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| 24. |
- Chen, Yaqi, et al.
(författare)
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Insight into the Extreme Side Reaction between LiNi0.5Co0.2Mn0.3O2 and Li1.3Al0.3Ti1.7(PO4)3 during Cosintering for All-Solid-State Batteries
- 2023
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Ingår i: Chemistry of Materials. - 1520-5002 .- 0897-4756. ; 35:22, s. 9647-9656
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Tidskriftsartikel (refereegranskat)abstract
- All-solid-sate batteries (ASSBs) with a NASICON-type solid-state electrolyte (SSE) of Li1.3Al0.3Ti1.7(PO4)3 (LATP) can be accepted as a promising candidate to significantly improve safety and energy density due to their high oxidation potential and high ionic conductivity. However, thermodynamic instability between the cathode and LATP is scarcely investigated during cosintering preparation for the integrated configuration of ASSBs. Herein, the structural compatibility between commercially layered LiNi0.5Co0.2Mn0.3O2 (NCM523) and LATP SSE was systematically investigated by cosintering at 600 °C. It is noticeable that an extreme side reaction between Li from NCM523 and phosphate from LATP happens during its cosintering process, leading to a severe phase transition from a layered to a spinel structure with high Li/Ni mixing. Consequently, the capacity of NCM523 is lost during the preparation of the NCM523-LATP composite cathode. Based on this, we suggested that the interface modification of the NCM523/LATP interface is valued significantly to inhibit this extreme side reaction, quickening the application of LATP-based ASSBs.
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| 25. |
- Cheng, Shi-Ping, et al.
(författare)
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Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger
- 2021
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Ingår i: Horticulture Research. - : Springer Nature. - 2052-7276. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.
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| 26. |
- Dong, Jiao, et al.
(författare)
-
Dental pulp stem cell-derived small extracellular vesicle in irradiation-induced senescence
- 2021
-
Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 575, s. 28-35
-
Tidskriftsartikel (refereegranskat)abstract
- Small extracellular vesicles (sEV) facilitate signaling molecule transfer among cells. We examined the therapeutic efficacy of human dental pulp stem cell-derived sEV (hDPSC-sEV) against cellular senescence in an irradiated-submandibular gland mouse model. Seven-week-old mice were exposed to 25 Gy radiation and randomly assigned to control, phosphate-buffered saline (PBS), or hDPSC-sEV groups. At 18 days post-irradiation, saliva production was measured; histological and reverse transcription-quantitative PCR analyses of the submandibular glands were performed. The salivary flow rate did not differ significantly between the PBS and hDPSC-sEV groups. AQP5-expressing acinar cell numbers and AQP5 expression levels in the submandibular glands were higher in the hDPSC-sEV group than in the other groups. Furthermore, compared with non-irradiated mice, mice in the 25 Gy + PBS group showed a high senescence-associated-β-galactosidase-positive cell number and upregulated senescence-related gene (p16INK4a, p19Arf, p21) and senescence-associated secretory phenotypic factor (MMP3, IL-6, PAI-1, NF-κB, and TGF-β) expression, all of which were downregulated in the hDPSC-sEV group. Superoxide dismutase levels were lower in the PBS group than in the hDPSC-sEV group. In summary, hDPSC-sEV reduced inflammatory cytokine and senescence-related gene expression and reversed oxidative stress in submandibular cells, thereby preventing irradiation-induced cellular senescence. Based on these results, we hope to contribute to the development of innovative treatment methods for salivary gland dysfunction that develops after radiotherapy for head and neck cancer.
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| 27. |
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| 28. |
- Jia, Kai-Hua, et al.
(författare)
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Chromosome-scale assembly and evolution of the tetraploid Salvia splendens (Lamiaceae) genome
- 2021
-
Ingår i: Horticulture Research. - : Oxford University Press (OUP). - 2052-7276 .- 2662-6810. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Polyploidization plays a key role in plant evolution, but the forces driving the fate of homoeologs in polyploid genomes, i.e., paralogs resulting from a whole-genome duplication (WGD) event, remain to be elucidated. Here, we present a chromosome-scale genome assembly of tetraploid scarlet sage (Salvia splendens), one of the most diverse ornamental plants. We found evidence for three WGD events following an older WGD event shared by most eudicots (the γ event). A comprehensive, spatiotemporal, genome-wide analysis of homoeologs from the most recent WGD unveiled expression asymmetries, which could be associated with genomic rearrangements, transposable element proximity discrepancies, coding sequence variation, selection pressure, and transcription factor binding site differences. The observed differences between homoeologs may reflect the first step toward sub- and/or neofunctionalization. This assembly provides a powerful tool for understanding WGD and gene and genome evolution and is useful in developing functional genomics and genetic engineering strategies for scarlet sage and other Lamiaceae species.
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| 29. |
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| 30. |
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| 31. |
- Jiao, Xingxing, et al.
(författare)
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Electro-chemo-mechanical failure of solid-state electrolyte caused from intergranular or transgranular damage propagation in polycrystalline aggregates
- 2024
-
Ingår i: Acta Materialia. - 1359-6454. ; 265
-
Tidskriftsartikel (refereegranskat)abstract
- Electro-chemo-mechanical failure of solid-state electrolytes (SEs) caused by the internal growth of lithium dendrites significantly impedes the application of solid-state batteries under high applied current density. The grain boundary is usually the key to the mechanical properties of polycrystalline ceramic SEs. Here, strength and width of grain boundary in SEs that are exampled by garnet-type Li7La3Zr2O12 are evaluated under the deposition of lithium by visualizing the stress field, damage accumulation and crack propagation. The enhancement of grain boundary strength triggers a dramatic increase stress when the ratio of tensile strength between grain boundary and grain (λ) is lower than 0.9. With the variation of λ, three damage processes are revealed as intergranular-damage, inter/transgranular-damage and transgranular-damage, leading to different propagation of cracks and the transformation of intergranular failure to transgranular failure. Furthermore, the width of the grain boundary is found to induce more transgranular-damage with its widening. A critical value of grain boundary width for the formation of displacement is obtained under various strengths, as δ = 21 nm for λ = 0.2, δ = 25 nm for λ = 0.5 and δ = 31 nm for λ = 0.9. The findings in this work indicate the coupling effect of grain boundary width and strength on the failure of SEs, providing an insightful perspective for the future design of solid-state batteries.
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| 32. |
- Jiao, Xingxing, et al.
(författare)
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Grain size and grain boundary strength: Dominative role in electro-chemo-mechanical failure of polycrystalline solid-state electrolytes
- 2024
-
Ingår i: Energy Storage Materials. - 2405-8297. ; 65
-
Tidskriftsartikel (refereegranskat)abstract
- Solid-state batteries with lithium metal anode have been accepted extensively as the competitive option to fulfill the upping requirement for safe and efficient energy devices. Nevertheless, its wide-ranging application has been impeded by the failure of solid-state electrolyte (SSE) induced by development of lithium (Li) filament. Based on the nature of polycrystalline ceramic SSE with varying grain size and boundary strength, the constitutive equation coupled with electrochemical kinetics was applied to picture the propagation of damage and corresponding disintegration caused by the development of Li filament. Based on the results, we found that the stress generated along with the growth of Li filament spreads away via the opening and sliding of grain boundary. Thus, damage occurs along grain boundaries, of which propagation behavior and damage level are controlled by grain size. Especially, over-refinement and under-refinement of grains of SSE can cause flocculent damage with inordinate damage degree and accelerate the failure time of SSE, respectively. On the other hand, the failure time is powerfully prolongated through strengthening the grain boundary of SSE. Eventually, grain size of 0.2 μm and tensile strength of grain boundary of 0.8-time-of-grain are posted as the threshold to realize the postponed failure of NASICON-based SSE. Inspiringly, electro-chemo-mechanical model in this contribution is generally applicable to other type of ceramic SSE to reveal the failure process and provide the design guideline, fostering the improvement of solid-state batteries.
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| 33. |
- Jiao, Xingxing, et al.
(författare)
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Highly Energy-Dissipative, Fast Self-Healing Binder for Stable Si Anode in Lithium-Ion Batteries
- 2021
-
Ingår i: Advanced Functional Materials. - : Wiley. - 1616-3028 .- 1616-301X. ; 31:3
-
Tidskriftsartikel (refereegranskat)abstract
- A double-wrapped binder has been rationally designed with high Young's modulus polyacrylic acid (PAA) inside and low Young's modulus bifunctional polyurethane (BFPU) outside to address the large inner stress of silicon anode with drastic volume changes during cycling. Harnessing the "hard to soft" gradient distribution strategy, the rigid PAA acts as a protective layer to dissipate the inner stress first during lithiation, while the elastic binder BFPU serves as a buffer layer to disperse residual stress, and thus avoids structural damage of rigid PAA. Moreover, the introduction of BFPU with fast self-healing ability can dynamically recover the microcracks arising from large stress, further ensuring the integrity of silicon anode. This multifunctional binder with smart design of double-wrapped structure provides enlightenment on enlarging the cycling life of high-energy-density lithium-ion batteries that suffer enormous volume change during the cycling process.
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| 34. |
- Jiao, Xingxing, et al.
(författare)
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Insight of electro-chemo-mechanical process inside integrated configuration of composite cathode for solid-state batteries
- 2023
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Ingår i: Energy Storage Materials. - 2405-8297. ; 61
-
Tidskriftsartikel (refereegranskat)abstract
- The complicated electro-chemo-mechanical process that occurs inside the composite cathode for solid-state batteries (SSBs), is of first importance to be insighted for the development of SSBs to seek higher energy density. Herein, exampled with layered transition-metal oxide of LiNixCoyMn1-x-yO2 (NCM), an electro-chemo-mechanical model containing electrochemical kinetics, finite-strain constitutive model and cohesive zone model was built to uncover the impact of ionic conductivity and Young's modulus (E) of solid-state electrolyte (SE) on the electro-chemo-mechanical process inside composite cathode and the intergranular failure of single cathode particle. The intergranular failure of NCM particles is powerfully determined by the Young's modulus of SE and the primary particle size, which is postponed by the coarse-primary NCM with soft SE of E=∼2 GPa. Compared with Young's modulus, increasing the ionic conductivity can uniform the distribution of both Li-ion and stress in the whole composite NCM cathode, realizing improved electrochemical performance with larger normalized capacity and lower the interfacial impendence. Hence, high-adequate ionic conductivity of 5 × 10−4 S cm−1 and soft mechanical property of E=∼2 GPa can be proposed as the guideline of SE for great electrochemical performance with prolongated lifespan of composite NCM cathode, paving an avenue to foster the application of SSBs.
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| 35. |
- Jiao, Xingxing, et al.
(författare)
-
Morphology evolution of electrodeposited lithium on metal substrates
- 2023
-
Ingår i: Energy Storage Materials. - 2405-8297. ; 61
-
Tidskriftsartikel (refereegranskat)abstract
- Lithium (Li) metal is deemed to be the high-energy-density anode material for next generation batteries, but its practical application is impeded by the uneven electrodeposition during charge of battery, which leads to the low Coulombic efficiency and potential safety issue. Here, multiscale modeling is fabricated to understand the morphology evolution of Li during electrodeposition process, from the self-diffusion of Li adatoms on electrode surface, to the nucleation process, and to the formation of Li microstructures, revealing the correlation between final morphology and deposition substrates. Energy batteries and self-diffusion of Li adatom on various substrates (lithium, copper, nickel, magnesium, and silver) result in the different nucleation size, which is calculated by kinetic Monte Carlo simulation based on classical nucleation theory. Formation of Li substructures that are grown from Li nuclei, is revealed by phase field modeling coupled with cellular automaton method. Our results show that larger Li nuclei is obtained under faster self-diffusion of Li adatom, leading to the low aspect ratio of Li substructures and the subsequent morphology evolution of electrodeposited Li. Furthermore, the electrodeposition of Li is strongly regulated by the selection of substrates, giving the practical guideline of anode design in rechargeable Li metal batteries. It is worthy to mention that this method to investigate the electro-crystallization process involving nucleation and growth can be transplanted to the other metallic anode, such as sodium, potassium, zinc, magnesium, calcium and the like.
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| 36. |
- Jiao, Xingxing, et al.
(författare)
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Multi-Physical Field Simulation: A Powerful Tool for Accelerating Exploration of High-Energy-Density Rechargeable Lithium Batteries
- 2023
-
Ingår i: Advanced Energy Materials. - 1614-6840 .- 1614-6832. ; In Press
-
Forskningsöversikt (refereegranskat)abstract
- To meet the booming demand of high-energy-density battery systems for modern power applications, various prototypes of rechargeable batteries, especially lithium metal batteries with ultrahigh theoretical capacity, have been intensively explored, which are intimated with new chemistries, novel materials and rationally designed configurations. What happens inside the batteries is associated with the interaction of multi-physical field, rather than the result of the evolution of a single physical field, such as concentration field, electric field, stress field, morphological evolution, etc. In this review, multi-physical field simulation with a relatively wide length and timescale is focused as formidable tool to deepen the insight of electrodeposition mechanism of Li metal and the electro-chemo-mechanical failure of solid-state electrolytes based on Butler-Volmer electrochemical kinetics and solid mechanics, which can promote the future development of state-of-the-art Li metal batteries with satisfied energy density as well as lifespan.
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| 37. |
- Jiao, Xingxing, et al.
(författare)
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Viability of all-solid-state lithium metal battery coupled with oxide solid-state electrolyte and high-capacity cathode
- 2024
-
Ingår i: Journal of Energy Chemistry. - 2095-4956. ; 91, s. 122-131
-
Tidskriftsartikel (refereegranskat)abstract
- Owing to the utilization of lithium metal as anode with the ultrahigh theoretical capacity density of 3860 mA h g−1 and oxide-based ceramic solid-state electrolytes (SE), e.g., garnet-type Li7La3Zr2O12 (LLZO), all-state-state lithium metal batteries (ASLMBs) have been widely accepted as the promising alternatives for providing the satisfactory energy density and safety. However, its applications are still challenged by plenty of technical and scientific issues. In this contribution, the co-sintering temperature at 500 °C is proved as a compromise method to fabricate the composite cathode with structural integrity and declined capacity fading of LiNi0.5Co0.2Mn0.3O2 (NCM). On the other hand, it tends to form weaker grain boundary (GB) inside polycrystalline LLZO at inadequate sintering temperature for LLZO, which can induce the intergranular failure of SE during the growth of Li filament inside the unavoidable defect on the interface of SE. Therefore, increasing the strength of GB, refining the grain to 0.4 μm, and precluding the interfacial defect are suggested to postpone the electro-chemo-mechanical failure of SE with weak GB. Moreover, the advanced sintering techniques to lower the co-sintering temperature for both NCM-LLZO composite cathode and LLZO SE can be posted out to realize the viability of state-of-the-art ASLMBs with higher energy density as well as the guaranteed safety.
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| 38. |
- Jiao, Zhejing, et al.
(författare)
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InAs triangular quantum wells grown on InP/SiO 2 /Si heterogeneous substrate for mid-infrared emission
- 2021
-
Ingår i: Materials Science in Semiconductor Processing. - : Elsevier BV. - 1369-8001. ; 136
-
Tidskriftsartikel (refereegranskat)abstract
- The properties of InAs/In0.53Ga0.37As triangular quantum wells (QWs) grown on an InP/SiO2/Si integrated substrate by ion-slicing technology are investigated. The material structure and growth quality are characterized by the X-ray diffraction (XRD) and transmission electron microscope measurements. The photoluminescence (PL) spectra at various temperatures are also analyzed. The PL peak wavelengths red-shift from 1.94 to 2.13 μm with the increase of temperature from 12.4 to 300 K. The experimental results of the QWs on InP/SiO2/Si substrate are found to be comparable with the performance of the same QWs grown on an InP substrate. The results are promising for future integration of Si with InP-based optical devices for the applications of light emission in mid-infrared wavelength range.
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| 39. |
- Liu, Jiao, et al.
(författare)
-
Altered Sarcomeric Structure and Function in Woody Breast Myopathy of Avian Pectoralis Major Muscle
- 2020
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- The “Woody” or “Wooden” breast disease is a severe myopathy of pectoralis major muscle recently identified within rapidly growing broiler lines all around the world with a prevalence rate around 20%, or even higher. Although of significant ethical and economic impact, little is known regarding the structural and functional aspects of the contractile apparatus in the woody breast muscle. The aim of the present study was to determine physiological properties of the contractile system in the morphologically intact muscle fibers of focally damaged woody breast in comparison with normal muscle fibers to gain insight into the muscle function of the animal and possibly mechanisms involved in the disease development. Muscle samples were taken from woody breast (non-lesioned areas) and normal breast muscles from broilers. Length-tension curves, maximal active stress, maximal shortening velocity, calcium sensitivity, rate of tension development, lattice spacing and muscle biochemical composition were investigated on single skinned fibers. Sarcomeres of woody breast fibers were more compliant, which is very likely related to the wider spacing (18% wider compared to controls) between thick and thin filament. No differences were found in optimal sarcomere length (2.68 ± 0.04 vs. 2.65 ± 0.05 μm) nor in maximal active stress (116 ± 17 vs. 125 ± 19 mN mm–2). However, woody breast fibers had less steep descending arm as shown in length-tension curve. Woody breast muscle fibers had 40% bigger sarcomeric volume compared to controls. Content of contractile proteins (myosin and actin), and maximal shortening velocity were unchanged indicating that the growth in woody breast muscle fiber was associated with synthesis of new contractile units with unaltered kinetics. Calcium sensitivity was decreased in woody breast muscle fibers significantly. In conclusion, the results show that the rapid growth of muscle in woody breast disease is associated with significant structural and functional changes in the pectoralis major musculature, associated with alterations in the mechanical anchoring of contractile filaments.
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| 40. |
- Liu, Jiao, et al.
(författare)
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Longitudinal vibration interferes with cross-bridge attachment and prevents muscle fibre shrinkage under PSE-like conditions
- 2021
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Ingår i: Meat Science. - : Elsevier BV. - 0309-1740. ; 179
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of longitudinal vibration on cross-bridge attachments between myofilaments was investigated in single fibres and intact muscle. Sinusoidal length vibration (frequency 50 Hz, amplitude 5% of fibre length) reduced active force by 40% when fibres were activated by elevation of [Ca2+], but did not alter the force when fibres were in rigor state. When vibrated for 30 min in rigor at pH 5.5 and 38 °C (PSE conditions), the lateral shrinkage of the fibres was significantly reduced, suggesting a potential positive influence of vibration on water-holding capacity. In whole muscle incubated at 38 °C until 8 h post mortem, the progress of rigor onset was accessed by measuring the increase in muscle stiffness. Vibration applied 3-5 h post mortem postponed rigor development, but did not have significant influence on water-holding capacity compared with non-vibrated conditions. In conclusion, the results suggest that muscle vibration can be a future technique to delay rigor development and prevent muscle fibre shrinkage and PSE development after slaughter.
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| 41. |
- Liu, Kehong, et al.
(författare)
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Conditioned medium of human mesenchymal stem cells affects stem cell senescence in osteoporosis
- 2024
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Ingår i: Biochemical and Biophysical Research Communications. - 0006-291X. ; 711
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine effects of early (P5) and late (P17) passage hMSCs in vitro, as well as the preventive benefits of early passage hMSCs-CM in osteoporosis model triggered by ovariectomy. Our results indicate that long-term cultured hMSCs contributed to the progression of inflammatory transcriptional programs in P5 hMSCs, ultimately impairing their functionality and enhancing senescence-related characteristics. Conversely, early passage hMSCs reversed these alterations. Moreover, early passage hMSCs-CM infused intravenously in a postmenopausal osteoporosis mouse model suppressed bone degeneration and prevented osteoporosis by reducing ovariectomy-induced senescence in bone marrow MSCs and reducing the expression of senescence-associated secretory phenotype-related cytokines. Our findings highlight the high translational value of early passage hMSCs-CM in antiaging intervention and osteoporosis prevention.
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| 42. |
- Liu, Wen, et al.
(författare)
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Colorectal cancer risk susceptibility loci in a Swedish population
- 2022
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Ingår i: Molecular Carcinogenesis. - : Wiley. - 0899-1987 .- 1098-2744. ; 61:3, s. 288-300
-
Tidskriftsartikel (refereegranskat)abstract
- To search for colorectal cancer (CRC) risk loci, Swedish samples were used for a genome-wide haplotype analysis. A logistic regression model was employed in 2663 CRC cases and 1642 controls in the discovery analysis. Three analyses were done, on all, familial-, and nonfamilial CRC samples and only results with odds ratio (OR) > 1 were analyzed. single nucleotide polymorphism (SNP) analysis did not generate any statistically significant results. Haplotype analysis suggested novel loci, on chromosome 2q36.1 (OR = 1.71, p value = 5.6924 × 10-8 ) in all CRC samples, chromosome 1q43 (OR = 4.04 p value = 3.24 × 10-8 ) in familial CRC samples, and two hits in nonfamilial CRC samples, chromosomes 2q36.1 (OR = 1.71 p value = 5.69 × 10-8 ) and 3p24.3 (OR = 1.62 p value = 6.21 × 10-9 ). Moreover, one locus on chromosome 20q13.33 was suggested in analyses of all samples, and five more novel loci were suggested on chromosomes 10q25.3, 15q,22.31, 17p11.2, 1p34.2, and 3q24. The haplotypes from the analysis of all samples were replicated in a second study of CRC cases and controls from the same part of Sweden. In summary, using haplotype analysis in Swedish CRC samples, the best hits were novel loci and the locus on chromosomes 2q36.1 and 20q13.33 suggested in the analysis of all samples were confirmed in a second cohort. The ORs were often higher than ORs from published genome-wide association study (GWAS). The study suggested it was possible that a risk locus could involve more than one gene, and that haplotypes could give information on the gene or genes possibly involved in the risk at specific locus.
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| 43. |
- Liu, Xiuyu, et al.
(författare)
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Characterization of CYP82 genes involved in the biosynthesis of structurally diverse benzylisoquinoline alkaloids in Corydalis yanhusuo
- 2024
-
Ingår i: Plant Molecular Biology. - 0167-4412 .- 1573-5028. ; 114:2
-
Tidskriftsartikel (refereegranskat)abstract
- Benzylisoquinoline alkaloids (BIAs) represent a significant class of secondary metabolites with crucial roles in plant physiology and substantial potential for clinical applications. CYP82 genes are involved in the formation and modification of various BIA skeletons, contributing to the structural diversity of compounds. In this study, Corydalis yanhusuo, a traditional Chinese medicine rich in BIAs, was investigated to identify the catalytic function of CYP82s during BIA formation. Specifically, 20 CyCYP82-encoding genes were cloned, and their functions were identified in vitro. Ten of these CyCYP82s were observed to catalyze hydroxylation, leading to the formation of protopine and benzophenanthridine scaffolds. Furthermore, the correlation between BIA accumulation and the expression of CyCYP82s in different tissues of C. yanhusuo was assessed their. The identification and characterization of CyCYP82s provide novel genetic elements that can advance the synthetic biology of BIA compounds such as protopine and benzophenanthridine, and offer insights into the biosynthesis of BIAs with diverse structures in C. yanhusuo.
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| 44. |
- Liu, Xiuyu, et al.
(författare)
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Functional characterization of (S)–N-methylcoclaurine 3′-hydroxylase (NMCH) involved in the biosynthesis of benzylisoquinoline alkaloids in Corydalis yanhusuo
- 2021
-
Ingår i: Plant Physiology and Biochemistry. - : Elsevier BV. - 0981-9428. ; 168, s. 507-515
-
Tidskriftsartikel (refereegranskat)abstract
- Benzylisoquinoline alkaloids (BIAs) are compounds naturally found in plants and can have significant value in clinical settings. Metabolic engineering and synthetic biology are both promising approaches for the heterologous acquisition of benzylisoquinoline alkaloids. (S)–N-methylcoclaurine 3′-hydroxylase (NMCH), a member of the CYP80 family of CYP450, is the penultimate catalytic enzyme that forms the central branch-point intermediate (S)-reticuline and plays a key role in the biosynthesis of BIAs. In this study, an NMCH gene was cloned from Corydalis yanhusuo, while in vitro reactions demonstrated that CyNMCH can catalyze (S)–N-methylcoclaurine to produce (S)-3′-hydroxy-N-methylcoclaurine. The Km and Kcat of CyNMCH were estimated and compared with those identified in Eschscholzia californica and Coptis japonica. This newly discovered CyNMCH will provide alternative genetic resources for the synthetic biological production of benzylisoquinoline alkaloids and provides a foundation to help analyze the biosynthetic pathway of BIAs biosynthesis in C. yanhusuo.
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| 45. |
- Liu, Xiuyu, et al.
(författare)
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Structure-function analysis of CYP719As involved in methylenedioxy bridge-formation in the biosynthesis of benzylisoquinoline alkaloids and its de novo production
- 2023
-
Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Benzylisoquinoline alkaloids (BIAs) are a type of secondary metabolite with clinical application value. (S)-stylopine is a special BIA which contains methylenedioxy bridge structures. CYP719As could catalyze the methylenedioxy bridge-formation on the A or D rings of protoberberine alkaloids, while displaying significant substrate regiospecificity. To explore the substrate preference of CYP719As, we cloned and identified five CyCYP719A candidates from Corydalis yanhusuo. Two CyCYP719As (CyCYP719A39 and CyCYP719A42) with high catalytic efficiency for the methylenedioxy bridge-formation on the D or A rings were characterized, respectively. The residues (Leu 294 for CyCYP719A42 and Asp 289 for CyCYP719A39) were identified as the key to controlling the regioselectivity of CYP719As affecting the methylenedioxy bridge-formation on the A or D rings by homology modeling and mutation analysis. Furthermore, for de novo production of BIAs, CyCYP719A39, CyCYP719A42, and their mutants were introduced into the (S)-scoulerine-producing yeast to produce 32 mg/L (S)-stylopine. These results lay a foundation for understanding the structure-function relationship of CYP719A-mediated methylenedioxy bridge-formation and provide yeast strains for the BIAs production by synthetic biology.
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| 46. |
- Liu, Y., et al.
(författare)
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Inorganic carbon and alkalinity biogeochemistry and fluxes in an intertidal beach aquifer: Implications for ocean acidification
- 2021
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694. ; 595
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Tidskriftsartikel (refereegranskat)abstract
- While submarine groundwater discharge (SGD) is well known to release large amounts of dissolved nutrients and organic carbon into the ocean, the contribution of SGD to the marine inorganic carbon cycle is poorly understood. Here, the biogeochemistry of inorganic carbon in an intertidal aquifer and related SGD-derived fluxes into Tolo Harbor, Hong Kong was investigated over tidal and seasonal time scales. The results revealed the production of total alkalinity (TAlk) and dissolved inorganic carbon (DIC) in the intertidal aquifer over the entire salinity range. The locally produced TAlk and DIC in the intertidal aquifer contributed to >50% of the TAlk and DIC discharged with SGD to the ocean. The distributions of TAlk and DIC in the transition (mangrove) and high salinity (bare beach) zones were different due to the distinct hydrogeological and geochemical conditions. In the organic-rich mangrove zone, TAlk and DIC productions were driven by biotic processes such as aerobic respiration, denitrification, and sulfate reduction. In the organic-poor bare beach zone, TAlk and DIC productions were likely driven by abiotic processes such as precipitation/dissolution of carbonate minerals. Temperature, pH, physical mixing, and iron cycling in the intertidal aquifer also considerably influenced the carbonate biogeochemistry. TAlk inventory in the intertidal aquifer was seasonally stable but TAlk discharged with SGD was similar to 60% greater in the wet season than in the dry season (73.3 vs. 45.6 mol d(-1) per m coastline). The DIC inventory in the intertidal aquifer and DIC discharged with SGD were similar to 24% and 95% higher, respectively, in the wet season than dry season. Overall, through analyzing TAlk:DIC ratios and related fluxes, SGD was thought to reduce the CO2 buffering capacity of the receiving ocean, and act as a local driver of ocean acidification.
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| 47. |
- Liu, Yangyang, et al.
(författare)
-
Insight into the Critical Role of Exchange Current Density on Electrodeposition Behavior of Lithium Metal
- 2021
-
Ingår i: Advanced Science. - : Wiley. - 2198-3844 .- 2198-3844. ; 8:5
-
Tidskriftsartikel (refereegranskat)abstract
- Due to an ultrahigh theoretical specific capacity of 3860 mAh g−1, lithium (Li) is regarded as the ultimate anode for high-energy-density batteries. However, the practical application of Li metal anode is hindered by safety concerns and low Coulombic efficiency both of which are resulted fromunavoidable dendrite growth during electrodeposition. This study focuses on a critical parameter for electrodeposition, the exchange current density, which has attracted only little attention in research on Li metal batteries. A phase-field model is presented to show the effect of exchange current density on electrodeposition behavior of Li. The results show that a uniform distribution of cathodic current density, hence uniform electrodeposition, on electrode is obtained with lower exchange current density. Furthermore, it is demonstrated that lower exchange current density contributes to form a larger critical radius of nucleation in the initial electrocrystallization that results in a dense deposition of Li, which is a foundation for improved Coulombic efficiency and dendrite-free morphology. The findings not only pave the way to practical rechargeable Li metal batteries but can also be translated to the design of stable metal anodes, e.g., for sodium (Na), magnesium (Mg), and zinc (Zn) batteries.
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| 48. |
- Liu, Yangyang, et al.
(författare)
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Promoted rate and cycling capability of Li–S batteries enabled by targeted selection of co-solvent for the electrolyte
- 2020
-
Ingår i: Energy Storage Materials. - : Elsevier BV. - 2405-8297. ; 25, s. 131-136
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Tidskriftsartikel (refereegranskat)abstract
- Lithium sulfur (Li–S) batteries are considered as promising candidates for high-energy-density battery systems owing to the high theoretical capacity of sulfur (1675 mAh g−1) and low cost of raw materials. However, their practical application is hampered by low rate capability and rapid degradation of capacity, arising from the passivation of the cathode by lithium sulfides (Li2S2/Li2S) deposited during discharge and low interfacial stability of the Li anode. Herein, we report on a comprehensive strategy to select co-solvent to the electrolyte to regulate the deposition of lithium sulfides during charge-discharge process. We show that addition of a co-solvent with high solubility, and strong interaction with Li2S to a conventional electrolyte effectively mitigates the formation of a passivating layer on the sulfur cathode and dramatically improves the interfacial stability of the Li anode. We demonstrate that Sulfolane (SL) has these properties and that a Li–S cell with an electrolyte containing 6 vol% SL exhibits outstanding cyclic performance (0.083% decay per cycle) and rate capability (capacity density of 765 mAh g−1 at rate of 1.0C). Thus, we provide a facile strategy for the selection of co-solvent for improved performance of Li–S batteries, realizing their practical application for high-energy-density battery systems.
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| 49. |
- Liu, Yangyang, et al.
(författare)
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Role of Interfacial Defects on Electro–Chemo–Mechanical Failure of Solid-State Electrolyte
- 2023
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Ingår i: Advanced Materials. - 0935-9648 .- 1521-4095. ; 35:24
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Tidskriftsartikel (refereegranskat)abstract
- High-stress field generated by electroplating of lithium (Li) in pre-existing defects is the main reason for mechanical failure of solid-state electrolyte because it drives crack propagation in electrolyte, followed by Li filament growth inside and even internal short-circuit if the filament reaches another electrode. To understand the role of interfacial defects on mechanical failure of solid-state electrolyte, an electro–chemo–mechanical model is built to visualize distribution of stress, relative damage, and crack formation during electrochemical plating of Li in defects. Geometry of interfacial defect is found as dominating factor for concentration of local stress field while semi-sphere defect delivers less accumulation of damage at initial stage and the longest failure time for disintegration of electrolyte. Aspect ratio, as a key geometric parameter of defect, is investigated to reveal its impact on failure of electrolyte. Pyramidic defect with low aspect ratio of 0.2–0.5 shows branched region of damage near interface, probably causing surface pulverization of solid-state electrolyte, whereas high aspect ratio over 3.0 will trigger accumulation of damage in bulk electrolyte. The correction between interfacial defect and electro–chemo–mechanical failure of solid-state electrolyte is expected to provide insightful guidelines for interface design in high-power-density solid-state Li metal batteries.
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| 50. |
- Liu, Yangyang, et al.
(författare)
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Stable Li metal anode by crystallographically oriented plating through in-situ surface doping
- 2020
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Ingår i: Science China Materials. - : Springer Science and Business Media LLC. - 2199-4501 .- 2095-8226. ; 63:6, s. 1036-1045
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Tidskriftsartikel (refereegranskat)abstract
- Lithium (Li) metal is regarded as the holy grail anode material for high-energy-density batteries owing to its ultrahigh theoretical specific capacity. However, its practical application is severely hindered by the high reactivity of metallic Li against the commonly used electrolytes and uncontrolled growth of mossy/dendritic Li. Different from widely-used approaches of optimization of the electrolyte and/or interfacial engineering, here, we report a strategy of in-situ cerium (Ce) doping of Li metal to promote the preferential plating along the [200] direction and remarkably decreased surface energy of metallic Li. The in-situ Ce-doped Li shows a significantly reduced reactivity towards a standard electrolyte and, uniform and dendrite-free morphology after plating/stripping, as demonstrated by spectroscopic, morphological and electrochemical characterizations. In symmetric half cells, the in-situ Ce-doped Li shows a low corrosion current density against the electrolyte and drastically improved cycling even at a lean electrolyte condition. Furthermore, we show that the stable Li LiCoO2 full cells with improved coulombic efficiency and cycle life are also achieved using the Ce-doped Li metal anode. This work provides an inspiring approach to bring Li metal towards practical application in high energy-density batteries.
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