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

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

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

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

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

Preparation of jet fuel range hydrocarbons by catalytic transformation of bio-oil derived from fast pyrolysis of straw stalk

The growing demand of commercial jet fuels, in combination with the strict environmental legislations, has led to immense interest in developing aviation biofuels. This work demonstrated that the bio-oil derived from fast pyrolysis of straw stalk was able to be converted into the jet and diesel fuel range hydrocarbons by a designed transformation route. This transformation included three reaction steps: (i) the catalytic cracking of bio-oil into low-carbon aromatics and light olefins, (ii) the synthesis of C8-C15 aromatic hydrocarbons by the alkylation of low-carbon aromatics with light olefins, and (iii) the production of C8-C15 cyclic alkanes by the hydrogenation of C8-C15 aromatics. It was also demonstrated that the production of the desired C8-C15 aromatics with a high selectivity of 88.4% was achieved by the low temperature alkylation reactions of the bio-oil-derived aromatics using the ionic liquid of [bmim]Cl-2AlCl(3) (1-butyl-3-methylimidazolium chloroaluminate). The synthetic biofuels basically met the main technical specifications of jet fuels based on the combustion heat, viscosity, freeze point and other characteristics of fuels. (C) 2015 Elsevier Ltd. All rights reserved

DataSheet_1_Case report: A collision tumor of clear cell renal cell carcinoma and clear cell papillary renal cell tumor.pdf

We report the case of a 51-year-old woman who was initially hospitalized in the respiratory department with cough and fever. Urinary computed tomography (CT) showed two different incidental masses in the right kidney. The patient underwent a radical right nephrectomy without lymph node dissection and postoperative adjuvant treatment. The pathological examination of the surgical specimens showed a collision tumor composed of a clear cell renal cell carcinoma (CCRCC) and a clear cell papillary renal cell tumor (CCPRCT). To the best of our knowledge, this is the first such case reported to date. No recurrence of local or distant metastasis was found during routine follow-up 14 months after the operation.</p