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- 2019
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Tidskriftsartikel (refereegranskat)
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- Yang, Yaohua, et al.
(författare)
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Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk
- 2019
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:3, s. 505-517
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
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- Chen, Ke-Ling, et al.
(författare)
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Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury
- 2016
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 44:8, s. E664-E677
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
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- Liu, Junwei, et al.
(författare)
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Polymer synergy for efficient hole transport in solar cells and photodetectors
- 2023
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Ingår i: Energy & Environmental Science. - : ROYAL SOC CHEMISTRY. - 1754-5692 .- 1754-5706.
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Tidskriftsartikel (refereegranskat)abstract
- Hole transport materials (HTMs) have greatly advanced the progress of solution-based electronic devices in the past few years. Nevertheless, most devices employing dopant-free organic HTMs can only deliver inferior performance. In this work, we introduced a novel "polymer synergy" strategy to develop versatile dopant-free polymer HTMs for quantum dot/perovskite solar cells and photodetectors. With this synergy strategy, the optical, electrical and aggregation properties of polymer HTMs can be modulated, resulting in complementary absorption, high hole mobility, favorable energy landscape and moderate aggregation. Moreover, a clear orientational transition was observed for the developed HTMs with a 9-fold increase in the face-on/edge-on ratio, providing a highway-like carrier transport for electronic devices, as revealed by in situ characterization and ultrafast transient absorption. With these benefits, the photovoltaic and photodetection performance of quantum dot devices were boosted from 11.8% to 13.5% and from 2.95 x 10(12) to 3.41 x 10(13) Jones (over a 10-fold increase), respectively. Furthermore, the developed polymer HTMs can also significantly enhance the photovoltaic and photodetection performance of perovskite devices from 15.1% to 22.7% and from 2.7 x 10(12) to 2.17 x 10(13)Jones with the same device structure, indicating their great application potential in the emerging optoelectronics.
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- Liu, Yong, et al.
(författare)
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Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity
- 2017
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Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
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- Liu, Yong, et al.
(författare)
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Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury
- 2016
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : AMER PHYSIOLOGICAL SOC. - 0193-1857 .- 1522-1547. ; 310:5, s. G303-G309
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Tidskriftsartikel (refereegranskat)abstract
- Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-kappa B activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-alpha, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-kappa B activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-kappa B activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.
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- Wang, Shunfeng, 1991, et al.
(författare)
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Co-utilization of quarry tailings and fly ash for non-sintered ultra-lightweight aggregates (ULWAs) by autoclave technology
- 2022
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Ingår i: Construction and Building Materials. - : Elsevier BV. - 0950-0618. ; 346
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Tidskriftsartikel (refereegranskat)abstract
- Quarry tailings as solid waste with large output bring a heavy environmental and economic burden. The main objective of this study is to investigate the feasibility of co-utilizing quarry tailings and fly ash (FA) as the main sources in preparing the lightweight aggregates (LWAs). The expand perlite powder (characterized with low density and high surface area) and two chemical foaming agents (ammonium carbonate and Al powder) was added to reduce the density of LWAs furtherly and fabricate a type of ultra-lightweight aggregates (ULWAs) through autoclave curing. In spite of the basic properties (compressive strength, 1 h of water absorption, loose bulk density and apparent particle density), the evolution of pore structures in relation to the type of foaming agents were also determined by combining scanning electron microscope (SEM), mercury intrusion porosimetry (MIP) and Nuclear Magnetic Resonance (NMR). The results show that increasing the expand perlite content could increases the compressive strength and water absorption, decreases the loose bulk density, apparent density and the total porosity. The pores wall gradually reduces with the increase of chemical foaming agents. Isolated pores will transform into connected pores, which also increase the most probable pore diameter and total porosity. The loose bulk density of specimens with 3 wt% (NH4)2CO3 and Al powder are 873 kg/m3 and 798 kg/m3 compared to blank (1132 kg/m3). This work lays a solid foundation for the design and preparation of ULWAs from solid wastes.
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- Wang, Shunfeng, 1991, et al.
(författare)
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Resourceful utilization of quarry tailings in the preparation of non-sintered high-strength lightweight aggregates
- 2022
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Ingår i: Construction and Building Materials. - : Elsevier BV. - 0950-0618. ; 334
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Tidskriftsartikel (refereegranskat)abstract
- Quarry tailings are usually stockpiled due to stable crystalline structures below 100 °C and abundant sources, which lead to a serious environmental impacts and high ecological risks. This paper presents a study of transforming the fly ash and quarry tailings as the main raw materials into lightweight aggregates (LWAs) for using in civil engineering. A novel curing regime (autoclave technology) has been proposed to obtain higher compressive strength of LWAs. The effects of curing parameters (including temperature and steam pressure) on the properties (compressive strength, water absorption, loose bulk density, phase composition, pore structure and microstructure) of LWAs were systematically evaluated. On the other hand, this research also studies the effect of cement content on the basic properties of LWAs, which was decreased from 30 to 10 wt% for declining the CO2 emission. Results show that the strength sharply increases from 2.48 to 11.95 MPa and the water absorption decreases from 11.2 to 2.09% with increasing the elevated curing temperature from 25 to 190 °C. The LWA prepared with 70 wt% solid wastes (fly ash and quarry tailings) at 190 °C achieved the highest strength (11.95 MPa) and the lower loose bulk density (1160 kg/m3), which could meet the requirement of Chinese LWAs standard (GB/T 17431.1-2010). The water absorption of LWAs is below 5% except sample T25. The total porosity of LWAs decreases from 39.65% to 26.32% at 150 °C and from 42.54% to 27.24% at 190 °C while the cement content increases form 10 wt% to 30 wt%. At the same time, the percentage of pores (>50 nm) also gradually decreases. While the curing temperature, pressure and cement usage are above 150 °C, 1.00 MPa and 10 wt% respectively, will promote the formation of new phase composition (analcime). That also further increases the strength and percentage of harmless pores and few harmful pores. Therefore, this research offers a new curing method for producing LWAs from 70 to 90 wt% solid waste and is a rapid and sustainable solution for the large-scale recycling of quarry tailings.
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- Wang, Xiao-Cheng, et al.
(författare)
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Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer
- 2021
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Ingår i: Future Oncology. - : FUTURE MEDICINE LTD. - 1479-6694 .- 1744-8301. ; 17:23, s. 3087-3100
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers. Lay abstract: Previous evidence has indicated that the mRNA stem index (mRNAsi) is representative of the stemness of cancer stem cells (CSCs), whereas long noncoding RNAs (lncRNAs) may be crucial regulators in CSC phenotype. Nevertheless, the relationship between lncRNAs and mRNAsi in CRC is still unclear. Our results show that the mRNAsi was negatively related to pathological features and positively related to prognosis in CRC. Five mRNAsi-related lncRNAs were further identified and developed as a prognostic signature that could independently predict survival in CRC patients due to the five mRNAsi-related lncRNAs being involved in several pathways of CSCs and malignant cancer cell phenotypes, indicating the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.
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