| 1. |
- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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| 2. |
- Chang, Yanhai, et al.
(författare)
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Inflammatory cytokine of IL-1β is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/β-catenin signaling
- 2017
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Ingår i: Molecular Immunology. - : Elsevier. - 0161-5890 .- 1872-9142. ; 91, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- Mycotoxin T-2 exerts a causative role in Kashin-Beck disease (KBD) suffering chondrocyte apoptosis and cartilage matrix homeostasis disruption. Recent research corroborated the aberrant levels of pro-inflammatory cytokine IL-1ß in KBD patients and mycotoxin environment. In the present study, we investigated the relevance of IL-1ß in T-2 toxin-evoked chondrocyte cytotoxic injury and aberrant catabolism. High levels of IL-1ß were detected in serum and cartilages from KBD patients and in T-2-stimulated chondrocytes. Moreover, knockdown of IL-1ß antagonized the adverse effects of T-2 on cytotoxic injury by enhancing cell viability and inhibiting apoptosis. However, exogenous supplementation of IL-1β further aggravated cell damage in response to T-2. Additionally, cessation of IL-1β rescued T-2-elicited tilt of matrix homeostasis toward catabolism by elevating the transcription of collagen II and aggrecan, promoting release of sulphated glycosaminoglycans (sGAG) and TIMP1, and suppressing matrix metalloproteinases production including MMP-1, MMP-3 and MMP-13. Conversely, IL-1β stimulation deteriorated T-2-induced disruption of matrix metabolism balance toward catabolism. Mechanistic analysis found the high activation of Wnt/β-catenin in KBD patients and chondrocytes upon T-2. Furthermore, this activation was mitigated after IL-1β inhibition, but further enhanced following IL-1β precondition. Importantly, blocking this pathway by transfection with β-catenin alleviated the adverse roles of IL-1β on cytotoxic injury and metabolism disorders under T-2 conditioning. Together, this study elucidates a new insight into how T-2 deteriorates the pathological progression of KBD by regulating inflammation-related pathways, indicating a promising anti-inflammation strategy for KBD therapy.
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| 3. |
- Mu, Cuicui, et al.
(författare)
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Ecosystem CO2 Exchange and Its Economic Implications in Northern Permafrost Regions in the 21st Century
- 2023
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Ingår i: Global Biogeochemical Cycles. - 0886-6236. ; 37:11
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming increases carbon assimilation by plant growth and also accelerates permafrost CO2 emissions; however, the overall ecosystem CO2 balance in permafrost regions and its economic impacts remain largely unknown. Here we synthesize in situ measurements of net ecosystem CO2 exchange to assess current and future carbon budgets across the northern permafrost regions using the random forest model and calculate their economic implications under the Shared Socio-economic Pathways (SSPs) based on the PAGE-ICE model. We estimate a contemporary CO2 emission of 1,539 Tg C during the nongrowing season and CO2 uptake of 2,330 Tg C during the growing season, respectively. Air temperature and precipitation exert the most control over the net ecosystem exchange in the nongrowing season, while leaf area index plays a more important role in the growing season. This region will probably shift to a carbon source after 2,057 under SSP5-8.5, with a net emission of 17 Pg C during 2057–2100. The net economic benefits of CO2 budget will be $4.5, $5.0, and $2.9 trillion under SSP1-2.6, SSP2-4.5, and SSP5-8.5, respectively. Our results imply that a high-emission pathway will greatly reduce the economic benefit of carbon assimilation in northern permafrost regions.
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| 4. |
- Lei, Xiaoqin, et al.
(författare)
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A generalized interpolation material point method for modelling coupled thermo-hydro-mechanical problems
- 2021
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Ingår i: Computer Methods in Applied Mechanics and Engineering. - : Elsevier BV. - 0045-7825. ; 386
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Tidskriftsartikel (refereegranskat)abstract
- This paper proposes a Generalized Interpolation Material Point Method (GIMP) for modelling coupled thermo-hydro-mechanical (THM) processes within unsaturated porous media. The governing equations for the coupled thermo-hydro-mechanical problems are derived based on the conservation laws of mass, momentum and energy, and are discretized within the framework of the explicit three-phase single-point GIMP. The proposed THM-coupled GIMP is validated against available analytical solutions and FEM-based numerical solutions, and is used for simulating a climate-driven slope failure process involving both temperature variation and rainfall infiltration. The proposed THM-coupled GIMP is proved to be capable to capture the fully coupled thermo-hydro-mechanical process within unsaturated porous media associated with large deformations.
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| 5. |
- Li, Xiaoqing, et al.
(författare)
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Antihyperuricemic Effect of Green Alga Ulva lactuca Ulvan through Regulating Urate Transporters
- 2021
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 69:38, s. 11225-11235
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Tidskriftsartikel (refereegranskat)abstract
- A novel polysaccharide from Ulva lactuca (ULP) was purified using a Sepharose CL-4B column. Fourier transform infrared spectroscopy, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy were employed to analyze the structure of ULP. It consisted of rhamnose (Rha), glucuronic acid (GluA), galactose (Gal), and xylose (Xyl) at a molar ratio of 32.75:22.83:1.07:6.46 with the molecular weight of 2.24 x 10(5) Da. The four major glycosidic residues found in ULP were -> 2,3)-alpha-L-Rhap-(1 ->, -> 4)-beta-D-GlcpA-(1 ->, -> 2,6)-beta-D-Galp-(1 ->, and -> 4)-beta-D-Xylp-(1 ->. The antihyperuricemic activity of ULP was exhibited by detecting related biochemical indexes, urate transporter gene expressions, renal histopathology, and intestinal microbiota shifts. ULP obviously decreased the levels of serum uric acid (UA), blood urea nitrogen, and creatinine, while inhibited serum and hepatic xanthine oxidase activities as well as improved renal injury in hyperuricemic mice. Furthermore, the upregulation of UA excretion genes ABCG2/OAT1 and downregulation of UA resorption genes URAT1 and GLUT9 were detected. In addition, ULP exerted its antihyperuricemic effect through regulating the intestinal microbiome, characterized by elevating the helpful microbial abundance, meanwhile declining the harmful bacterial abundance and restoring the gut microbiome homeostasis. This study demonstrates the antihyperuricemic activity of ULP and its potential effect for the treatment of hyperuricemia-related diseases.
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| 6. |
- Sun, Zhengyi, 1982-, et al.
(författare)
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Buffer-enhanced electron injection in organic light-emitting devices with copper cathode
- 2013
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Ingår i: Organic electronics. - Amsterdam : Elsevier. - 1566-1199 .- 1878-5530. ; 14:2, s. 511-515
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Tidskriftsartikel (refereegranskat)abstract
- We explore in this work the use of Cu as a cathode material in organic light-emitting devices (OLEDs) and find a dual electron–injection enhancement mechanism derived from the LiF layer. Different from what observed previously in Ag- and Au-cathode devices, the LiF buffer layer in the Cu-cathode OLEDs starts to play its role in performance improvement when it is much thinner than 3 nm, the optimal value of buffer thickness, and in the case of optimal thickness, the device exhibits excellent performance comparable to conventional Al-cathode device. The phenomenon observed is ascribed to enhanced electron injection as a result of combined effect of interfacial reaction and tunneling barrier reduction mechanism: while chemical reaction plays a key role at the very beginning of interface formation, tunneling dominates in the subsequent stage leading to the tremendous improvement of the characteristics.
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| 7. |
- Zhou, Wencai, et al.
(författare)
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The Role of Grain Boundaries on Ion Migration and Charge Recombination in Halide Perovskites
- 2024
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Ingår i: Small. - : WILEY-V C H VERLAG GMBH. - 1613-6810 .- 1613-6829.
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Tidskriftsartikel (refereegranskat)abstract
- Grain boundaries (GBs) have a significant role in polycrystalline perovskite solar cells (PSCs). However, there is ongoing debate regarding the impact of GBs on the performance and long-term stability of PSCs. Employing the first-principles molecular dynamics for perovskites, the iodine vacancy defect migrations both in bulk and at GBs are investigated. i) The positive iodine vacancy (VI+) is found that have both lower formation energy (1.4 eV) and activation energy (0.18 eV) than those of neutral iodine vacancy (VI), statistically. It indicated the VI+ acts as the dominant migrated iodine vacancy rather than VI; ii) the iodine vacancy at GBs has approximate to 0.48 eV higher activation energy than those in bulk, which leads to the accumulation of iodine vacancy at GBs; iii) the presence of VI+ result in a 3-fold increase in charge recombination ratio at GBs, compared to pristine PSCs. Based on quantum molecular dynamics statistical results, which are consistent with experimental measurements, insights into iodine vacancy migration both at GBs and in the bulk are gained. This understanding can be valuable for defects engineering related to ion migration, in order to improve the long-term stability and promote the performance of PSCs. Understanding defects engineering related to ion migration is crucial for enhancing the long-term stability and performance of hybrid perovskite solar cells. Iodine vacancies accumulate at grain boundaries due to lower formation energy and higher migration potential barrier compared to those in the bulk, which further increase the nonradiative recombination. image
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