| 1. |
- Jiang, Jingjing, et al.
(författare)
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Sino-European Differences in the Genetic Landscape and Clinical Presentation of Pheochromocytoma and Paraganglioma
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 105:10
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Tidskriftsartikel (refereegranskat)abstract
- Context: Pheochromocytomas and paragangliomas (PPGLs) are characterized by distinct genotype-phenotype relationships according to studies largely restricted to Caucasian populations.Objective: To assess for possible differences in genetic landscapes and genotype-phenotype relationships of PPGLs in Chinese versus European populations.Design: Cross-sectional study.Setting: 2 tertiary-care centers in China and 9 in Europe.Participants: Patients with pathologically confirmed diagnosis of PPGL, including 719 Chinese and 919 Europeans.Main Outcome Measures: Next-generation sequencing performed in tumor specimens with mutations confirmed by Sanger sequencing and tested in peripheral blood if available. Frequencies of mutations were examined according to tumor location and catecholamine biochemical phenotypes.Results: Among all patients, higher frequencies of HRAS, FGFR1, and EPAS1 mutations were observed in Chinese than Europeans, whereas the reverse was observed for NF1, VHL, RET, and SDHx. Among patients with apparently sporadic PPGLs, the most frequently mutated genes in Chinese were HRAS (16.5% [13.6-19.3] vs 9.8% [7.6-12.1]) and FGFR1 (9.8% [7.6-12.11 vs 2.2% [1.1-3.3]), whereas among Europeans the most frequently mutated genes were NF1 (15.9% [13.2-18.6) vs 6.6% [4.7-8.5)) and SDHx (10.7% [8.4-13.0] vs 4.2% [2.6-5.7]). Among Europeans, almost all paragangliomas lacked appreciable production of epinephrine and identified gene mutations were largely restricted to those leading to stabilization of hypoxia inducible factors. In contrast, among Chinese there was a larger proportion of epinephrine-producing paragangliomas, mostly due to HRAS and FGFR1 mutations.Conclusions: This study establishes Sino-European differences in the genetic landscape and presentation of PPGLs, including ethnic differences in genotype-phenotype relationships indicating a paradigm shift in our understanding of the biology of these tumors.
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| 2. |
- Chen, Baoqing, et al.
(författare)
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The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 159:6, s. 2146-2162
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Tidskriftsartikel (refereegranskat)abstract
- Background & AimsChromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer–associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.MethodsWe performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2′-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.ResultsHigh expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.ConclusionsWe found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.
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| 3. |
- Guo, Jiawei, et al.
(författare)
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Bimetallic Sulfides with Vacancy Modulation Exhibit Enhanced Electrochemical Performance
- 2024
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Ingår i: Advanced Functional Materials. - 1616-3028 .- 1616-301X. ; In Press
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Tidskriftsartikel (refereegranskat)abstract
- Transition bimetallic sulfides show significant promise for energy-related applications because of their plentiful active sites and synergistic redox activity. However, limited pore size and low-conductivity issues hinder their application. The structure of NiCo-S with rich sulfur vacancies is first predicted by density functional theory (DFT) calculations. Different sulfur vacancy concentrations are modeled by DFT calculations, and the results confirm that sulfur vacancies enhance the conductivity of the electrode material and are more beneficial for the adsorption of OH* species. It is verified by the differential charge density that the electric field formed on the surface of the electrode can lead to strong interfacial interactions by electron aggregation, which promotes electron/ion transfer kinetics. Furthermore, NiCo-S nanosheets are prepared on carbon cloth enriched with different concentrations of sulfur vacancies (denoted as NiCo-Sv-x, with x representing the concentration of sulfur vacancies) by sulfide etching NiCo-MOF and annealing under H2/Ar atmosphere. The NiCo-Sv-x electrodes obtained are applied to the cathode of supercapacitors and the anode of the oxygen evolution reaction. Through combining experimental and theoretical analysis, the effect of vacancy defect engineering on the electrochemical performance of the electrode materials is further confirmed. This work constructs transition metal sulfides with different sulfur vacancy concentrations through DFT model prediction and experimental validation, further confirming the effect of vacancy defect engineering on the electrochemical performance of electrode materials. Therefore, this modulation of sulfur vacancy concentration by vacancy defects contributes to the construction of electrode materials with excellent performance for energy applications.
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| 4. |
- Xi, Fengming, et al.
(författare)
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Substantial global carbon uptake by cement carbonation
- 2016
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 9:12, s. 880-883
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Tidskriftsartikel (refereegranskat)abstract
- Calcination of carbonate rocks during the manufacture of cement produced 5% of global CO 2 emissions from all industrial process and fossil-fuel combustion in 2013. Considerable attention has been paid to quantifying these industrial process emissions from cement production, but the natural reversal of the process - carbonation - has received little attention in carbon cycle studies. Here, we use new and existing data on cement materials during cement service life, demolition, and secondary use of concrete waste to estimate regional and global CO 2 uptake between 1930 and 2013 using an analytical model describing carbonation chemistry. We find that carbonation of cement materials over their life cycle represents a large and growing net sink of CO 2, increasing from 0.10 GtC yr â '1 in 1998 to 0.25 GtC yr â '1 in 2013. In total, we estimate that a cumulative amount of 4.5 GtC has been sequestered in carbonating cement materials from 1930 to 2013, offsetting 43% of the CO 2 emissions from production of cement over the same period, not including emissions associated with fossil use during cement production. We conclude that carbonation of cement products represents a substantial carbon sink that is not currently considered in emissions inventories.
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| 5. |
- Xiao, Manjun, et al.
(författare)
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Approaching 19% efficiency and stable binary polymer solar cells enabled by a solidification strategy of solvent additive
- 2023
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Ingår i: Science in China Series B. - : SCIENCE PRESS. - 1674-7291 .- 1869-1870. ; 66, s. 1500-1510
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Tidskriftsartikel (refereegranskat)abstract
- Additives play a crucial role in enhancing the photovoltaic performance of polymer solar cells (PSCs). However, the typical additives used to optimize blend morphology of PSCs are still high boiling-point solvents, while their trace residues may reduce device stability. Herein, an effective strategy of "solidification of solvent additive (SSA)" has been developed to convert additive from liquid to solid, by introducing a covalent bond into low-cost solvent diphenyl sulfide (DPS) to synthesize solid dibenzothiophene (DBT) in one-step, which achieves optimized morphology thus promoting efficiency and device stability. Owing to the fine planarity and volatilization of DBT, the DBT-processed films achieve ordered molecular crystallinity and suitable phase separation compared to the additive-free or DPS-treated ones. Importantly, the DBT-processed device also possesses improved light absorption, enhanced charge transport, and thus a champion efficiency of 11.9% is achieved in the PM6:Y6-based PSCs with an excellent additive component tolerance, reproducibility, and stability. Additionally, the DBT-processed PM6:L8-BO-based PSCs are further fabricated to study the universality of SSA strategy, offering an impressive efficiency approaching 19% as one of the highest values in binary PSCs. In conclusion, this article developed a promising strategy named SSA to boost efficiency and improve stability of PSCs.
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