41 research outputs found

    NADPH oxidase 4 mediates insulin-stimulated HIF-1α and VEGF expression, and angiogenesis in vitro

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    Acute intensive insulin therapy causes a transient worsening of diabetic retinopathy in type 1 diabetes patients and is related to VEGF expression. Reactive oxygen species (ROS) have been shown to be involved in HIF-1α and VEGF expression induced by insulin, but the role of specific ROS sources has not been fully elucidated. In this study we examined the role of NADPH oxidase subunit 4 (Nox4) in insulin-stimulated HIF-1α and VEGF expression, and angiogenic responses in human microvascular endothelial cells (HMVECs). Here we demonstrate that knockdown of Nox4 by siRNA reduced insulin-stimulated ROS generation, the tyrosine phosphorylation of IR-β and IRS-1, but did not change the serine phosphorylation of IRS-1. Nox4 gene silencing had a much greater inhibitory effect on insulin-induced AKT activation than ERK1/2 activation, whereas it had little effect on the expression of the phosphatases such as MKP-1 and SHIP. Inhibition of Nox4 expression inhibited the transcriptional activity of VEGF through HIF-1. Overexpression of wild-type Nox4 was sufficient to increase VEGF transcriptional activity, and further enhanced insulin-stimulated the activation of VEGF. Downregulation of Nox4 expression decreased insulin-stimulated mRNA and protein expression of HIF-1α, but did not change the rate of HIF-1α degradation. Inhibition of Nox4 impaired insulin-stimulated VEGF expression, cell migration, cell proliferation, and tube formation in HMVECs. Our data indicate that Nox4-derived ROS are essential for HIF-1α-dependent VEGF expression, and angiogenesis in vitro induced by insulin. Nox4 may be an attractive therapeutic target for diabetic retinopathy caused by intensive insulin treatment

    Synergistic strategy with hyperthermia therapy based immunotherapy and engineered exosomes−liposomes targeted chemotherapy prevents tumor recurrence and metastasis in advanced breast cancer

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    Advanced breast cancer with recurrent and distal organ metastasis is aggressive and incurable. The current existing treatment strategies for advanced breast cancer are difficult to achieve synergistic treatment of recurrent tumors and distant metastasis, resulting in poor clinical outcomes. Herein, a synergistic therapy strategy composed of biomimetic tumor-derived exosomes (TEX)-Liposome-paclitaxel (PTX) with lung homing properties and gold nanorods (GNR)-PEG, was designed, respectively. GNR-PEG, with well biocompatibility, cured recurrent tumors effectively by thermal ablation under the in situ NIR irradiation. Meanwhile, GNR-mediated thermal ablation activated the adaptive antitumor immune response, significantly increased the level of CD8+ T cells in lungs and the concentration of serum cytokines (tumor necrosis factor-α, interlekin-6, and interferon-γ). Subsequently, TEX-Liposome-PTX preferentially accumulated in lung tissues due to autologous tumor-derived TEX with inherent specific affinity to lung, resulting in a better therapeutic effect on lung metastasis tumors with the assistance of adaptive immunotherapy triggered by GNR in vivo. The enhanced therapeutic efficacy in advanced breast cancer was a combination of thermal ablation, adaptive antitumor immunotherapy, and targeted PTX chemotherapy. Hence, the synergistic strategy based on GNR and TEX-Liposome provides selectivity to clinical treatment of advanced breast cancer with recurrent and metastasis

    Particle Filter Target Tracking Algorithm Based on Dynamic Niche Genetic Algorithm

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    Using the RESC Model and Diversity Indexes to Assess the Cross-Scale Water Resource Vulnerability and Spatial Heterogeneity in the Huai River Basin, China

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    Performing a multiscale assessment of water resource vulnerability on the basis of political boundaries and watersheds is necessary for adaptive water resources management. Using the Risk-Exposure-Sensitivity-Adaptability model (RESC model), the water resource vulnerability of the Huai River Basin was assessed using four scales, namely, Class II, Class III, Province-Class II, and Municipality-Class III WRR (Water Resources Region). Following this, the spatial heterogeneity of the vulnerability of the above four scales was evaluated with the Theil and the Shannon-Weaver index. The results demonstrate that, instead of moving towards convergence, water resource vulnerability presents different grades which change together with the change in scale, and in turn, tend to weaken from east to west. Of the four scales, the scale of Municipality-Class III WRR shows the most significant spatial diversity, whereas that of Class II WRR shows the least diversity. With spatial downscaling, the vulnerability demonstrates high spatial heterogeneity and diversity. Herein, an innovative cross-scales vulnerability assessment is proposed and the RESC model characteristics and uncertainties as well as the employment of cross-scale water resource vulnerability are discussed

    Land-Use Spatio-Temporal Change and Its Driving Factors in an Artificial Forest Area in Southwest China

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    Understanding the driving factors of land-use spatio-temporal change is important for the guidance of rational land-use management. Based on land-use data, household surveys and social economic data in 2000, 2005, 2010, and 2015, this study adopted the Binary Logistic Regression Model (BLRM) to analyze the driving factors of land-use spatio-temporal change in a large artificial forest area in the Ximeng County, Yunnan province, in Southwest China. Seventeen factors were used to reflect the socio-economic and natural environment conditions in the study area. The results show a land use pattern composed of forestland, dry cropland, and rubber plantation in Ximeng County. Over the past fifteen years, the area of artificial forests increased rapidly due to the “Grain for Green„ policy, which has led to increases in rubber plantations, tea gardens, eucalyptus forests, etc. In contrast, the area of natural forest and dry cropland decreased due to reclamations for farming and constructions. The BLRM approach helped to identify the main driving factors of land-use spatio-temporal change, which includes land-use policies (protection of basic farmlands and natural reserves), topography (elevation and slope), accessibility (distance to the human settlements), and potential productivity (fertility and irrigation). The study revealed the relationship between land-use spatio-temporal change and its driving factors in mountainous Southwest China, providing a decision-making basis for rational land-use management and optimal allocation of land resources

    The conflicts of agricultural water supply and demand under climate change in a typical arid land watershed of Central Asia

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    Study Region. The Bosten Lake basin. Study Focus. The irrigated agriculture distributed in arid/semi-arid areas is of great significance for. food security and sustainable development. However, the shortage of water resources. limits agricultural development in these areas, and the water distribution pattern under. climate change is also uncertain. In this research, the Bosten Lake basin was selected. as the study area, and the monthly agricultural water supply (AWS) and demand. (AWD) in the historical and future periods were evaluated. New Hydrological Insights for the Region. Supported by the hydrological model and evapotranspiration model, the AWS and. AWD of the watershed were first evaluated, and 37 GCMs under CMIP6 were used to. expand the study to future periods, a novel downscaling scheme consisting of IDW and. BMA is used to increase the reliability of the results. The supply and demand of. agricultural water in the future scenarios within the region are revealed. In the. forthcoming future (the 2030 s), the watershed will maintain the warming and wetting. trend in the historical period. In the long-term future (the 2060 s), agricultural water. scarcity will become more severe, especially under the high emission scenario. (ssp585). The adaption strategies to address climate change have also been. proposed, and efficient water conveyance is highly recommended. This study is. expected to provide a reference for water resources management in arid/semi-arid. watersheds

    The mechanism and scenarios of how mean annual runoff varies with climate change in Asian monsoon areas

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    National Natural Science Foundation of China 51279140;National Basic Research Program of China 2010CB428406/2012CB956204<p class="FR_field"> Understanding the effects of climate change on runoff is important for the sustainable management of water resources. However, the mechanism of such effects in the Asian monsoon region remains unclear. This study revisits Fu&#39;s two-parameter climate elasticity index and enhances it by using the Gardner function to strengthen the former&#39;s prediction reliability when the future climate condition is beyond the historical range. Then the improved method was applied to study the elasticity change with temperature and precipitation in the eastern monsoon basins of China, whereas to explore the mechanism of climate change on runoff. Furthermore, the runoff change and the elasticity of the study area from 2020 to 2050 under representative concentration pathways (RCPs) were predicted. Results show that the trend of elasticity change assumes a centrosymmetric picture with the symmetric point (0,0). Different catchments respond differently to the same climate change scenario: the sensitivity of the Haihe Basin is the highest; those of Yellow, Huaihe, Liaohe, Songhua, Pearl, Yangtze, and Southeast Rivers are lower, in descending order. The changing mode of precipitation and temperature differs greatly to keep the runoff unchanged. For semi-humid regions in which the mean annual temperature ranges from 0.71 degrees C to 9.0 degrees C, such as the basins of Songhua, Liaohe, Haihe, and Yellow, a 1 degrees C increase in temperature requires a corresponding 3.2-4.0% increase in precipitation to keep the runoff unchanged. However, in wet regions, such as the basins of Yangtze, Southeast Rivers, and Pearl, the same change in temperature requires a less than 2.8% increase in precipitation to keep the runoff unchanged. In the future, the runoff in most basins may decrease in different degrees. The decreasing velocity of the runoff is the fastest in the RCP8.5 scenario and the decreasing trend of the runoff slows down under the RCP4.5 and RCP2.6 scenarios. The proposed method can be applied to other basins to assess potential climate change effects on annual runoff. The results of the basins studies can inform planning of long-term basin water management strategies taking into account global change scenarios. (C) 2014 Elsevier B.V. All rights reserved.</p

    Nox4 mediates insulin-induced VEGF mRNA and protein expression.

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    <p>HMVECs were transfected with Nox4 siRNA or the control siRNA for 24 h. The cells were growth arrested and then treated with 100 nM insulin. (A) In 12 hours, VEGF 165 mRNA level was analyzed by real time-PCR. (B) In 24 hours, the VEGF protein levels in the supernatants were determined by ELISA assay. *<i>P</i><0.05, **<i>P</i><0.01 vs. the control siRNA group; #<i>P</i><0.05, ##<i>P</i><0.01 vs. the insulin+control siRNA group.</p

    Liquid-Crystalline Thermally Activated Delayed Fluorescence : Design, Synthesis, and Application in Solution-Processed Organic Light-Emitting Diodes

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    Realizing both high efficiency and liquid crystallinity in one molecule remains a challenge in thermally activated delayed fluorescence (TADF) emission. Herein, two isomeric compounds- m-DPSAc-LC and p-DPSAc-LC with different connection positions between donor and acceptor moieties- were synthesized and characterized. Diphenylsulfone (DPS) was used as the acceptor, acridine (Ac) was used as the donor, and biphenyl derivatives (LC) were employed as the mesogenic group. Both compounds showed a smectic mesophase evidenced by differential scanning calorimetry (DSC), polarized optical microscopy (POM), and temperature-dependent small-angle X-ray scattering (SAXS). The compound p-DPSAc-LC clearly exhibited thermally activated delayed fluorescence due to the much more distorted geometry, whereas m-DPSAc-LC showed simple fluorescence. Compared to the parent TADF molecules without appended mesogenic groups (DPS-Ac), these liquid-crystalline emitters possessed higher hole mobilities and improved device performance. The OLEDs fabricated via solution processing using the liquid-crystalline compound p-DPSAc showed a maximum external quantum efficiency of ∼15% and as such is the first example of a liquid-crystalline TADF material in an OLED device
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