Aims. Treatment for acute kidney injury (AKI) is challenging. Induced pluripotent stem cells (iPSCs) have great therapeutic potential. This study sought to determine whether iPSCs attenuate AKI and ...the role of reactive oxygen species (ROS). Results. We intravenously injected isogenic iPSCs into mice 2 h after renal ischemia-reperfusion injury (IRI). The cells were selectively trafficked to ischemia/reperfusion-injured kidney where they decreased kidney ROS and inflammatory cytokines and improved kidney function and morphology. Pretreating the cells with ROS inhibitors before administration decreased iPSC engraftment and abolished the protective effect of iPSCs. In contrast, pretreating iPSCs with hydrogen peroxide increased iPSC engraftment and therapeutic effect. Although the intravenously administered iPSCs trafficked to the IRI kidney, the cells did not differentiate into proximal or distal tubular epithelial cells. In vitro, the capabilities of the iPSC-released substances to promote proliferation and decrease apoptosis of renal epithelial cells were increased by ROS pretreatment of iPSCs. Moreover, pretreatment of the iPSCs with ROS inhibitor had the opposite effect. Similarly, moderate concentrations of ROS increased while ROS inhibitors decreased iPSC mobility, adhesion to the extracellular matrix, and mitochondrial metabolism. Innovation and Conclusion. iPSCs decreased renal ischemia/reperfusion injury mainly through iPSC-released substances. The therapeutic effect, mitochondrial metabolism, mobility, and kidney trafficking of iPSCs were ROS dependent.
碩士
國立成功大學
航空太空工程學系
102
In the recent years, the air pollution becomes more and more worse, and many people have the respiratory diseases, such as asthma. Investigating of the flow phenomena and ...particle deposition in lower bifurcating airway is very important and helpful for the mechanical design on the drug deliver devices. The experiment, theoretical analysis and numerical simulation are included to study this problem. By using the computational fluid dynamic technique, the steady three-dimensional incompressible Navier-Stokes equations are solved to study the particle deposition in normal and asthmatic airway models. In this work, the commercial code Ansys Fluent 14.5 is used to study the air way flow and particle behaviors. To evaluate the accuracy a single, symmetric airway bifurcation model is adopt first, and the computed solutions are compared with those in relate papers. Furthermore a double bifurcation is introduced, and the behaviors of particle deposition are observed. In addition to the investiga
Interleukin-6 (IL-6)/soluble IL-6 receptor (sIL-6R) promotes peritoneal angiogenesis by stimulating SP4-mediated vascular endothelial growth factor (VEGF) production in peritoneal dialysis (PD). ...Moreover, histone methyltransferase enhancer of zeste homologue 2 (EZH2) is involved in IL-6/sIL-6R signalling via the acceleration of vascular endothelial growth factor (VEGF)-induced angiogenesis. However, the molecular mechanism underlying how EZH2 epigenetically activates VFGF expression in IL-6/sIL-6R signalling during PD is still unclear.
In this study, we measured the expression of EZH2, DNMT3B and SP4 in human peritoneal mesothelial cells (HPMCs) treated with IL-6/sIL-6R stimulation and/or EZH2 overexpression, silencing or inhibition. Methylation of the CpG site in the SP4 promoter region and VEGF production were measured under these treatments in HPMCs. Moreover, tube formation in human umbilical vein endothelial cells (HUVECs) was detected following treatment with conditioned media from these stimulated HPMCs. The 5/6 nephrectomy (5/6Nx) rat model was established, and the rats were injected with peritoneal dialysate. EZH2, DNMT3B and SP4 expression and microvessels were analysed in 5/6Nx + PD rats treated with IL-6/sIL-6R and EZH2 overexpression. The results showed that IL-6/sIL-6R and EZH2 overexpression enhanced the expression of EZH2, DNMT3B and SP4, but EZH2 silencing/inhibition reduced these expression levels. The results for VEGF production and tube formation
followed the same trend. IL-6/sIL-6R and EZH2 overexpression increased the methylation percentage of the -170 bp CpG site in the SP4 promoter region in HPMCs. Moreover, IL-6/sIL-6R and EZH2 overexpression stimulated EZH2, DNMT3B and SP4 expression and promoted angiogenesis in 5/6Nx + PD rats.
Thus, this study indicated that EZH2 is involved in IL-6/sIL-6R signalling and epigenetically regulates SP4 expression, thereby stimulating VEGF production and angiogenesis in PD. Targeting EZH2 is expected to be a novel therapeutic approach for end-stage renal disease (ESRD) patients with PD treatment.
Flood retention lakes (RLs) are widely employed in rural‐urban catchments with low impacts on the natural environment. However, insights are lacking regarding the control of climate conditions on ...RLs' performances and how they are affected by different geographic configurations. This study applies a 2D hydrodynamic model to perform a catchment‐scale performance assessment of RLs beyond the scope of analytical and hydrological models. We conduct extensive numerical experiments of rainstorm‐induced flooding in a rural‐urban catchment with a constructed RL and blueprinted ones upstream. Results demonstrate an L‐shaped band of satisfactory performance of the current RL in the frequency‐duration diagram, which coincides with short return periods (<5 years) and long durations (>4 hr), or short durations (<3 hr) and moderate to long return periods (5–50 years); such L‐shaped pattern is also valid for additional RLs and their combinations. With the increase in event size, the first two modes of RL performance (out of four) correspond to effective flood mitigation. When working jointly, RLs with series configurations are more effective in reducing the mainstream flood peaks, while parallel connections provide a greater spatial extent of flood hazard mitigation. For both series and parallel configurations, the upstream‐weighted settings tend to outperform downstream‐weighted ones under more extreme events; the decentralized arrangement in the urban area yields more benefits in spatial flood hazard mitigation compared to the centralized case. The study highlights the critical role of rainstorm severity (with possible spatiotemporal variabilities) in controlling RL performances despite various configurations and hydraulic settings.
Key Points
An L‐shaped band on the frequency‐duration diagram indicates the dominance of climate conditions on retention lake (RL) performances
RLs configured in parallel mitigate flood hazard to a larger extent while those in series are superior for reducing mainstream flood peaks
RLs with upstream‐weighted capacities are more effective than downstream‐weighted ones in extreme events
Abstract
Defects from grain interiors and boundaries of perovskite films cause significant nonradiative recombination energy loss, and thus perovskite films with controlled crystallinity and large ...grains is critical for improvement of both photovoltaic performance and stability for perovskite-based solar cells. Here, a methylamine (MA
0
) gas-assisted crystallization method is developed for fabrication of methylammonium lead iodide (MAPbI
3
) perovskite films. In the process, the perovskite film is formed via controlled release of MA0 gas molecules from a liquid intermediate phase MAPbI
3
·xMA
0
. The resulting perovskite film comprises millimeter-sized grains with (110)-uniaxial crystallographic orientation, exhibiting much low trap density, long carrier lifetime, and excellent environmental stability. The corresponding perovskite solar cell exhibits a power conversion efficiency (PCE) of ~ 21.36%, which is among the highest reported for MAPbI
3
-based devices. This method provides important progress towards the fabrication of high-quality perovskite thin films for low-cost, highly efficient and stable perovskite solar cells.
Abstract Methacrylated biopolymers are unique and attractive in preparing photocrosslinkable hydrogels in biomedical applications. Here we report a novel chitosan (CS) derivative‐based injectable ...hydrogel with anti‐inflammatory capacity via methacrylation modification. First, ibuprofen (IBU) was conjugated to the backbone of CS by carbodiimide chemistry to obtain IBU‐CS conjugate, which converts water‐insoluble unmodified CS into water‐soluble IBU‐CS conjugate. The IBU‐CS conjugate did not precipitate at the pH of 7, which was beneficial to subsequent chemical modification with methacrylic anhydride to prepare IBU‐CS methacrylate (IBU‐CS‐MA) with significantly higher methacrylation substitution. Photocrosslinkable in situ gel formation of injectable IBU‐CS‐MA hydrogel was verified using lithium phenyl‐2,4,6‐trimethylbenzoylphosphinate (LAP) initiator under visible light. The IBU‐CS‐MA hydrogel showed good cytocompatibility as revealed by encapsulating and in vitro culturing murine fibroblasts within hydrogels. It promoted macrophage polarization toward M2 phenotype, as well as downregulated pro‐inflammatory gene expression and upregulated anti‐inflammatory gene expression of macrophages. The hydrogel also significantly reduced the reactive oxygen specifies (ROS) and nitrogen oxide (NO) produced by lipopolysaccharides (LPS)‐stimulated macrophages. Upon subcutaneous implantation in a rat model, it significantly mitigated inflammatory responses as shown by significantly lower inflammatory cell density, less cell infiltration, and much thinner fibrous capsule compared with CS methacrylate (CS‐MA) hydrogel. This study suggests that IBU‐CS conjugate represents a feasible strategy for preparing CS‐based methacrylate hydrogels for biomedical applications.
•We develop a bottom-up approach for urban flood hazard at multiple levels.•The pluvial flood dynamic model can map flood-affected zones at gridded level.•Upscaling mapping of inundation can reduce ...the effects of data bias or availability.•Coarser hazard mapping is less sensitive to the data quality and model uncertainty.
With increasing urban flood risk due to urbanisation and climate change, flood hazard prediction is ever more crucial for flood risk management and emergency response. However, when sufficient high-quality data are lacking, a standard flood inundation modelling approach has significant uncertainties. Therefore, this study develops a bottom-up approach for urban flood hazard mapping at multiple levels (grid-kilometre-district), built upon the integration of grid-based flood modelling with data acquisition from open sources. This reduces the adverse effects of data scarcity and quality on hazard modelling. In the paper, we first set out an integrated approach for gridded inundation mapping in an urban basin using a hydrodynamic model supported by crowd-sourced social media data. Then, applying the model to flooding in Chengdu in August 2020, we articulate how input data bias and parameter uncertainty both affect urban inundation modelling. The results show that the choice of terrain data and the quantification of urban drainage flows significantly influence the modelled urban inundation extent, depth and duration. This indicates the potential for large variation when using urban inundation mapping merely relying on a single-scale flood hydrodynamic modelling even when supported by crowd-sourced data. The multilevel hazard mapping approach developed here presents multi-layered and comprehensive inundation mapping; thus the effects of data bias or availability are reduced and the coarser hazard mapping shows less sensitivity to the data input quality and model uncertainty, indicating relatively higher reliability at this higher spatial scale. The grid-kilometre-district three level approach provides more reliable flood hazard mapping, which can support rainstorm-induced flood management in data scarce cities.
•We develop a distributed hydrodynamic model involving drainage flow effects.•A HD method can represent drainage flow effects even when pipe data is unavailable.•The model can simulate both urban ...flood hydrology and surface inundation.•Bed slope source treatments have marginal effects on real-world flood simulations.
Two-dimensional hydrodynamic models are increasingly used to predict overland surface water flooding in urban catchments. The complexity of urban surfaces and subsurface drainage systems poses great challenges to modelling urban rainfall-runoff and flood hydraulics. This work develops a spatially distributed hydrodynamic model framework incorporating both hydrological and hydraulic processes of surface and subsurface drainage processes during urban flooding. The model is built upon 2D full shallow water equations solved by a Godunov-type finite volume method with robust treatments of the bed source term. To properly involve drainage flow effects, we present three methods to quantify the drainage flow discharge and its delay time which affect both urban hydrology and surface inundation. Besides, a simple OpenMPI-based parallel algorithm is applied to accelerate the model and ensure computational efficiency when applied to real-world events. The model framework is justified through the validations with five benchmark cases. Benchmark results indicate that the well-balanced treatment of bed source term ensures the model applicability in irregular urban surfaces, the model can predict both urban surface inundation and flood hydrograph, and the proposed drainage flow treatments can well reproduce drainage flow hydrograph. The model framework is successfully applied to simulate rainstorm-induced flood events in a rural–urban catchment, the upper Shenzhen River catchment. Results further demonstrate the robust capability of the model in the quantification of flow exchange between surface and subsurface systems to some extent even in the absence of drainage information. Our framework provides a practical solution for urban flood simulation even when pipe data are scarce.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental and food contaminant generated as a byproduct of various industrial activities. It is found in a lot of foods, especially in ...dairy products, eggs, fish, and meat. Autophagy is a highly conserved cellular degradation and cycling process, which plays an important role in lipid metabolism. This study aimed to explore the effects of TCDD on autophagic flux and lipid metabolism in THP-1 macrophages. The data showed that TCDD promoted the accumulation of autophagosomes in THP-1 macrophages, and subsequent findings revealed that this autophagosome accumulation was caused by the inhibition of autophagic flux by testing the expression of LC3II, p62 levels, and mRFP-GFP-LC3. Further, we found that TCDD treatment significantly increased the amount of triglyceride (TG) and total cholesterol (TC) in THP-1 macrophages. Meanwhile, pretreatment with autophagy activator (rapamycin, Rapa) efficiently relieved TCDD-induced lipid accumulation. On the contrary, pretreatment with autophagy inhibitor (Chloroquine, CQ) promoted TCDD-induced lipid accumulation. In the experiment of co-localization of LC3 and lipid droplets, the co-localization of LC3 and lipid droplets increased after TCDD induction. These results indicated that TCDD promoted lipid accumulation in THP-1 macrophages by inhibiting autophagic flux. Our findings revealed new insights into the toxicity mechanisms of TCDD.
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