616 research outputs found

    Urbanisation and health in China.

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    China has seen the largest human migration in history, and the country's rapid urbanisation has important consequences for public health. A provincial analysis of its urbanisation trends shows shifting and accelerating rural-to-urban migration across the country and accompanying rapid increases in city size and population. The growing disease burden in urban areas attributable to nutrition and lifestyle choices is a major public health challenge, as are troubling disparities in health-care access, vaccination coverage, and accidents and injuries in China's rural-to-urban migrant population. Urban environmental quality, including air and water pollution, contributes to disease both in urban and in rural areas, and traffic-related accidents pose a major public health threat as the country becomes increasingly motorised. To address the health challenges and maximise the benefits that accompany this rapid urbanisation, innovative health policies focused on the needs of migrants and research that could close knowledge gaps on urban population exposures are needed

    Case report: Visibly curative effect of dabrafenib and trametinib on advanced thyroid carcinoma in 2 patients

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    BackgroundDifferentiated thyroid cancer accounts for the majority of thyroid cancers and has a good prognosis after standard treatment. However, there are still some complex and refractory thyroid cancers, including locally advanced differentiated thyroid carcinoma and medullary carcinoma (MTC), poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC). Here, we report the therapeutic response of 2 advanced thyroid carcinoma patients treated with dabrafenib and trametinib.Case presentationTwo elderly females presented to the clinic with neck masses, dyspnea, and dysphagia. Signs of the trachea and esophageal compression were markedly visible in computed tomography (CT) scan and ultrasonography. Pathologic diagnoses of PDTC were confirmed for both patients through ultrasound-guided fine-needle aspiration (US-FNA). Both patients were significantly relieved from dyspnea and dysphagia after a course of treatment with dabrafenib and trametinib, and their tumors gradually shrank during the follow-up period.ConclusionOverall, this treatment modality is rare, but effective. By sharing these 2 case reports, we hope to provide a reference for the treatment of clinically similar patients with advanced thyroid carcinoma

    p70S6K1 (S6K1)-Mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I \u3cem\u3eγ\u3c/em\u3e Degradation and Cell Invasion

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    Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKIγ90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 with Ala promoted PIPKIγ90 ubiquitination but enhanced the stability of PIPKIγ90, and depletion of S6K1 also enhanced the stability of PIPKIγ90, indicating that PIPKIγ90 ubiquitination alone is insufficient for its degradation. These data suggest that S6K1-mediated PIPKIγ90 phosphorylation regulates cell migration and invasion by controlling PIPKIγ90 degradation

    Apocynum Tablet Protects against Cardiac Hypertrophy via Inhibiting AKT and ERK1/2 Phosphorylation after Pressure Overload

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    Background. Cardiac hypertrophy occurs in many cardiovascular diseases. Apocynum tablet (AT), a traditional Chinese medicine, has been widely used in China to treat patients with hypertension. However, the underlying molecular mechanisms of AT on the hypertension-induced cardiac hypertrophy remain elusive. The current study evaluated the effect and mechanisms of AT on cardiac hypertrophy. Methods. We created a mouse model of cardiac hypertrophy by inducing pressure overload with surgery of transverse aortic constriction (TAC) and then explored the effect of AT on the development of cardiac hypertrophy using 46 mice in 4 study groups (combinations of AT and TAC). In addition, we evaluated the signaling pathway of phosphorylation of ERK1/2, AKT, and protein expression of GATA4 in the cardioprotective effects of AT using Western blot. Results. AT inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, Ser473 site of AKT, and protein expression of GATA4 and significantly inhibited cardiac hypertrophy and cardiac fibrosis at 2 weeks after TAC surgery (P<0.05). Conclusions. We experimentally demonstrated that AT inhibits cardiac hypertrophy via suppressing phosphorylation of ERK1/2 and AKT

    DEF-Net: A Dual-Encoder Fusion Network for Fundus Retinal Vessel Segmentation

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    The deterioration of numerous eye diseases is highly related to the fundus retinal structures, so the automatic retinal vessel segmentation serves as an essential stage for efficient detection of eye-related lesions in clinical practice. Segmentation methods based on encode-decode structures exhibit great potential in retinal vessel segmentation tasks, but have limited feature representation ability. In addition, they don’t effectively consider the information at multiple scales when performing feature fusion, resulting in low fusion efficiency. In this paper, a newly model, named DEF-Net, is designed to segment retinal vessels automatically, which consists of a dual-encoder unit and a decoder unit. Fused with recurrent network and convolution network, a dual-encoder unit is proposed, which builds a convolutional network branch to extract detailed features and a recurrent network branch to accumulate contextual features, and it could obtain richer features compared to the single convolution network structure. Furthermore, to exploit the useful information at multiple scales, a multi-scale fusion block used for facilitating feature fusion efficiency is designed. Extensive experiments have been undertaken to demonstrate the segmentation performance of our proposed DEF-Net

    Analysis of anisotropy anomalies identification in apparent resistivity observation

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    Since 1966, China has been using apparent resistivity observation to forecast strong aftershocks of the Xingtai earthquake. Retrospective studies of subsequent strong earthquakes have shown that anomalies in apparent resistivity observation before earthquakes usually exhibit anisotropic characteristics. In addition to the anisotropic changes in apparent resistivity before earthquakes, factors such as subway operation near the observation area, metal pipeline networks, and changes in water levels have also been found to cause anisotropic changes. These factors are called environmental interference factors. Therefore, distinguishing between anisotropic changes before earthquakes and anisotropic changes caused by interference and eliminating the effects of interference is crucial for using apparent resistivity observations for forecasting. Taking the observation of Hefei seismic station in Anhui Province as an example, a model is constructed using the finite element method to try to establish a method for analyzing anisotropy in apparent resistivity before earthquakes, and the data from other provincial stations are used for verification. In the modeling process, the influence coefficient is a measure of the relationship between the variation in apparent resistivity and the changes in the medium of the measurement area. The following results are obtained by calculating the influence coefficient using the finite element method: the influence coefficient between the power supply electrode and the measuring electrode of the apparent resistivity observation is negative, and the rest are positive, and the distribution of the influence coefficient shows obvious symmetry, with the axis of symmetry being the line connecting the electrodes and its midline, and the absolute value of the influence coefficient is inversely proportional to the distance from the electrodes. In addition, according to the constructed finite element model, the amplitude of anisotropic changes caused by interference can be quantitatively calculated. Given that interference is ubiquitous in various regions of the world, this study can provide a reference for international earthquake forecasters to quantitatively remove environmental interference in anisotropy. Moreover, when building apparent resistivity stations in seismic areas for earthquake prediction, it is best to avoid areas with larger local influence coefficients to ensure that the anomalous data before the earthquake is true and reliable

    Developing and applying a gene functional association network for anti-angiogenic kinase inhibitor activity assessment in an angiogenesis co-culture model

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    <p>Abstract</p> <p>Background</p> <p>Tumor angiogenesis is a highly regulated process involving intercellular communication as well as the interactions of multiple downstream signal transduction pathways. Disrupting one or even a few angiogenesis pathways is often insufficient to achieve sustained therapeutic benefits due to the complexity of angiogenesis. Targeting multiple angiogenic pathways has been increasingly recognized as a viable strategy. However, translation of the polypharmacology of a given compound to its antiangiogenic efficacy remains a major technical challenge. Developing a global functional association network among angiogenesis-related genes is much needed to facilitate holistic understanding of angiogenesis and to aid the development of more effective anti-angiogenesis therapeutics.</p> <p>Results</p> <p>We constructed a comprehensive gene functional association network or interactome by transcript profiling an in vitro angiogenesis model, in which human umbilical vein endothelial cells (HUVECs) formed capillary structures when co-cultured with normal human dermal fibroblasts (NHDFs). HUVEC competence and NHDF supportiveness of cord formation were found to be highly cell-passage dependent. An enrichment test of Biological Processes (BP) of differentially expressed genes (DEG) revealed that angiogenesis related BP categories significantly changed with cell passages. Built upon 2012 DEGs identified from two microarray studies, the resulting interactome captured 17226 functional gene associations and displayed characteristics of a scale-free network. The interactome includes the involvement of oncogenes and tumor suppressor genes in angiogenesis. We developed a network walking algorithm to extract connectivity information from the interactome and applied it to simulate the level of network perturbation by three multi-targeted anti-angiogenic kinase inhibitors. Simulated network perturbation correlated with observed anti-angiogenesis activity in a cord formation bioassay.</p> <p>Conclusion</p> <p>We established a comprehensive gene functional association network to model in vitro angiogenesis regulation. The present study provided a proof-of-concept pilot of applying network perturbation analysis to drug phenotypic activity assessment.</p

    A flexible dual-mode pressure sensor with ultra-high sensitivity based on BTO@MWCNTs core-shell nanofibers

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    Wearable flexible sensors have developed rapidly in recent years because of their improved capacity to detect human motion in wide-ranging situations. In order to meet the requirements of flexibility and low detection limits, a new pressure sensor was fabricated based on electrospun barium titanate/multi-wall carbon nanotubes (BTO@MWCNTs) core-shell nanofibers coated with styrene-ethylene-butene-styrene block copolymer (SEBS). The sensor material (BTO@MWCNTs/SEBS) had a SEBS to BTO/MWCNTs mass ratio of 20:1 and exhibited an excellent piezoelectricity over a wide range of workable pressures from 1 to 50 kPa, higher output current of 56.37 nA and a superior piezoresistivity over a broad working range of 20 to 110 kPa in compression. The sensor also exhibited good durability and repeatability under different pressures and under long-term cyclic loading. These properties make the composite ideal for applications requiring monitoring subtle pressure changes (exhalation, pulse rate) and finger movements. The pressure sensor developed based on BTO@MWCNTs core-shell nanofibers has demonstrated great potential to be assembled into intelligent wearable devices
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