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

Mendelian randomization and Bayesian model averaging of autoimmune diseases and Long COVID

BackgroundFollowing COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated.MethodsSummary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn’s disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA).ResultsThe evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00–1.11, p = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01–1.19, p = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03–1.13, p = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD.ConclusionThis MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations

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

Facile Synthesis of Co₂P Nanoparticles Embedded in N- and P‑Doped Mesoporous Carbon Composite as an Efficient Electrocatalyst for Oxygen Evolution Reaction

Developing highly efficient and affordable nonprecious metal catalysts is extremely significant to facilitate the electrochemical oxygen evolution reaction (OER). Herein, we constructed an N- and P-doped material decorated with embedded Co2P nanoparticles (termed as Co2P@NPC) by a facile and environmentally friendly method. The composite has abundant mesopores, rich heteroatom-doped species (such as pyridinic N, graphitic N, and P–C), and coupled Co2P nanoparticles. The desirable nanoarchitecture and composition endow the composite with promising catalytic activity for the OER. Interestingly, the electrocatalytic performance can be effectively boosted by surface self-reconstruction from Co2P into Co (oxy)hydroxide active species during the alkaline OER test. Consequently, the as-prepared Co2P@NPC after the electrochemical activation can afford a low delivery operation potential of 1.587 V at 10 mA cm–2, surpassing that of the commercial RuO2. Furthermore, the Co2P@NPC||Pt/C-based overall water splitting cell can achieve a voltage of as low as 1.580 V at 10 mA cm–2 and also shows exceptional stability

Production of jet fuel range paraffins by low temperature polymerization of gaseous light olefins using ionic liquid

This work demonstrated a novel catalytic transformation of gaseous olefins into jet fuel range isoparaffins by the low-temperature olefin polymerizations under atmospheric conditions. The production of the desired C-8-C-15 iso-paraffins with the selectivity of 80.6 C mol% was achieved by the room temperature polymerizations of gaseous light olefins using the [BMIM]Al2C17 ionic liquid. The influences of the reaction conditions on the olefinic polymerizations were investigated in detail. The properties of hydrocarbons in the synthetic fuels were determined by the GC-MS analyses combined with H-1 NMR, and C-13 NMR analyses. The formation of C-8-C-15 hydrocarbons from gaseous light olefins was illustrated by the identified products and the functional groups. This transformation potentially provides a useful avenue for the production of the most important components of iso-paraffins required in jet fuels. (C) 2016 Elsevier Ltd. All rights reserved

Case report: A collision tumor of clear cell renal cell carcinoma and clear cell papillary renal cell tumor

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

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

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