A portable molecularly imprinted polymer-modified microchip sensor for the rapid detection of perfluorooctanoic acid.

High-performance electrochemical sensors have attracted intensive interest in real-time environmental safety monitoring, the Internet of Things, and telemedicine applications. A key limitation to field measurement of pollutant distribution is the lack of a highly sensitive and selective monitoring platform, thus severely hindering the decentralized monitoring of pollutant exposure risk. Hence, a sensor was developed in this study by using a molecularly imprinted polymer (MIP). Specifically, Cu2O@C@NiCo2O4, with a large surface area and high conductivity, was coated onto the Au electrode surface and further modified by the anodic electro-polymerization of o-phenylenediamine (o-PD) using perfluorooctanoic acid (PFOA) as the template, followed by template removal for activation, thus obtaining the Au/Cu2O@C@NiCo2O4/MIP electrode. Particularly, an effective monitoring platform derived from this sensor was designed to achieve cost-effective pollution detection. Au/Cu2O@C@NiCo2O4/MIP was employed in a disposable microchip sensor for the sensitive detection of PFOA, exhibiting an ultra-low limit of detection (LOD) of 19.46 ng L-1 in a linear range of 207-4140 ng L-1 along with satisfactory sensitivity, selectivity, and reproducibility, which reveal its great potential in the low-cost and efficient field detection of PFOA in coastal seawater. These promising results indicate a bright future for such microchip-sensor-supported PFOA tele-sensing platforms in aiding environmental safety and blue earth protection. We will persist in refining this method to enhance the sensitivity of the sensor for PFOA detection in polluted coastal areas.

Dual adaptive learning multi-task multi-view for graph network representation learning.

Graph network analysis, which achieves widely application, is to explore and mine the graph structure data. However, existing graph network analysis methods with graph representation learning technique ignore the correlation between multiple graph network analysis tasks, and they need massive repeated calculation to obtain each graph network analysis results. Or they cannot adaptively balance the relative importance of multiple graph network analysis tasks, that lead to weak model fitting. Besides, most of existing methods ignore multiplex views semantic information and global graph information, which fail to learn robust node embeddings resulting in unsatisfied graph analysis results. To solve these issues, we propose a multi-task multi-view adaptive graph network representation learning model, called M2agl. The highlights of M2agl are as follows: (1) Graph convolutional network with the linear combination of the adjacency matrix and PPMI (positive point-wise mutual information) matrix is utilized as encoder to extract the local and global intra-view graph feature information of the multiplex graph network. Each intra-view graph information of the multiplex graph network can adaptively learn the parameters of graph encoder. (2) We use regularization to capture the interaction information among different graph views, and the importance of different graph views are learned by view attention mechanism for further inter-view graph network fusion. (3) The model is trained oriented by multiple graph network analysis tasks. The relative importance of multiple graph network analysis tasks are adjusted adaptively with the homoscedastic uncertainty. The regularization can be considered as an auxiliary task to further boost the performance. Experiments on real-worlds attributed multiplex graph networks demonstrate the effectiveness of M2agl in comparison with other competing approaches.

Hexokinase inhibitor 2-deoxyglucose coordinates citrullination of vimentin and apoptosis of fibroblast-like synoviocytes by inhibiting HK2 /mTORC1-induced autophagy.

High hexokinase 2 (HK2) expression is associated with aberrant activation of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA). However, the mechanism by which this occurs has not been fully elucidated. To investigate the role of HK2 and its underlying mechanism, adjuvant arthritis (AA) rats were treated with the HK2 inhibitor, 2-deoxyglucose (2-DG). In conjunction with HK2 knockdown experiments in FLSs, we evaluated the effect of HK2 on the citrullination of vimentin (cVIM), autophagy and apoptosis-associated protein expression, including that of cVIM, LC3, p62, Beclin1, Bax, Bcl2, and caspase 3. We further investigated the interaction of HK2 with downstream mTORC1 signaling effectors. Correlation analysis revealed that 2-DG treatment and HK2 knockdown upregulated the expression levels of caspase3, Bax, and p62 and downregulated the expression levels of LC3, Bcl2, and Beclin1, as well as decreasing vimentin citrullination. Furthermore, interactions between HK2 and mTOR decreased, coinciding with mTORC1 pathway activation. These findings suggest that the regulation of apoptosis and cVIM by HK2/mTORC1-dependent autophagy involves the inhibition of aberrant FLSs activation in the rat model of arthritis.

Plasma Retinol Binding Protein 4 as a Biomarker for Detecting Progressive Stroke and Prediction of Early Prognosis in Patients with Acute Ischemic Stroke.

Aim and Purpose: Progressive Stroke (PS) lacks effective treatment measures and leads to serious disability or death. Retinol binding protein 4 (RBP4) could be closely associated with acute ischemic stroke (AIS). We aimed to explore plasma RBP4 as a biomarker for detecting the progression in patients with AIS. METHODS: Participants of this retrospective study were 234 patients with AIS within the 48 h onset of disease. The primary endpoint was to ascertain if there was PS through the National Institute of Health stroke scale (NIHSS); the early prognosis was confirmed through the modified Rankin scale score (mRS) at discharge or 14 days after the onset of stroke, and the significance of demographic characteristics and clinical data was determined. RESULTS: In this study, 43 of 234 patients demonstrated PS. The level of plasma RBP4 in patients with progressive stroke was significantly lower (29 mg/L, 22.60-40.38 mg/L) than that without progression (38.70 mg/L, 27.28-46.40 mg/L, P = 0.003). In patients with lower plasma RBP4, the proportion of patients with progression (χ2 = 9.63, P = 0.008) and with mRS scores ≥2 (χ2 = 6.73, P = 0.035) was significantly higher. Multivariate logistic regression analysis showed that a lower RBP4 level on admission was an independent risk factor for progressive stroke during hospitalization with an OR value of 2.70 (P = 0.03, 95% CI: 1.12-6.52). CONCLUSION: A low plasma RBP4 level on admission could be an independent risk factor of PS during hospitalization.

Inhibition of glycolysis ameliorate arthritis in adjuvant arthritis rats by inhibiting synoviocyte activation through AMPK/NF-кB pathway.

OBJECTIVE: This study aimed to evaluate glycolysis inhibitor which can effectively ameliorate arthritis by inhibiting synoviocyte activation through AMPK/NF-кB pathway in AA rats. METHODS: Adjuvant arthritis (AA) rats were treated with 2-deoxyglucose (2-DG), glycolysis inhibitor. HE staining and radiological Examination were used for histopathology analysis and evaluation of joint destruction. HKII expression was quantified by immunostaining. Proliferation and migration of synoviocytes were assessed by synovicyte scores of joint, CCK8 and transwell assay. Inflammatory factors and levels of AMPK, p65 and IκBα were quantified by ELISA analysis and WB. RESULTS: We observed that HKII expression was positively correlated with synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction, and glycolysis inhibitor reduces the joint swelling degree, alleviates bone destruction, inhibits the proliferation and migration of synoviocyte, and reduces secretory function of synoviocytes in AA rats. In addition, we investigated that glycolysis inhibitor may inhibit activation of the NF-κB signaling pathway by activating the AMPK pathway. CONCLUSION: This study suggests the involvement of energy metabolism in the pathological inflammation process in RA joints. Glycolysis inhibitors might, therefore, provide an opportunity for therapeutic intervention.

Robust Cylindrical Panorama Stitching for Low-Texture Scenes Based on Image Alignment Using Deep Learning and Iterative Optimization.

Cylindrical panorama stitching is able to generate high resolution images of a scene with a wide field-of-view (FOV), making it a useful scene representation for applications like environmental sensing and robot localization. Traditional image stitching methods based on hand-crafted features are effective for constructing a cylindrical panorama from a sequence of images in the case when there are sufficient reliable features in the scene. However, these methods are unable to handle low-texture environments where no reliable feature correspondence can be established. This paper proposes a novel two-step image alignment method based on deep learning and iterative optimization to address the above issue. In particular, a light-weight end-to-end trainable convolutional neural network (CNN) architecture called ShiftNet is proposed to estimate the initial shifts between images, which is further optimized in a sub-pixel refinement procedure based on a specified camera motion model. Extensive experiments on a synthetic dataset, rendered photo-realistic images, and real images were carried out to evaluate the performance of our proposed method. Both qualitative and quantitative experimental results demonstrate that cylindrical panorama stitching based on our proposed image alignment method leads to significant improvements over traditional feature based methods and recent deep learning based methods for challenging low-texture environments.

Tooth loss as a risk factor for dementia: systematic review and meta-analysis of 21 observational studies.

BACKGROUND: Tooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk. METHODS: An electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model. RESULTS: The literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90-3.61, P < 0.001, I2 = 90.40%). The association remained noted when only adjusted results were pooled from 18 studies (OR 1.55, 95% CI 1.41-1.70, P = 0.13, I2 = 28.00%). Meta-regression analysis showed that study design explained about 16.52% of heterogeneity in the crude model. The overall quality rating scores of studies ranged from 11 to 16. CONCLUSIONS: Findings from this review evidenced that tooth loss is positively associated with an increased risk of dementia in adults. Future well-designed longitudinal researches examining the direct and indirect relationship between tooth loss and dementia risk are encouraged.

[2-deoxyglucose inhibits angiogenesis of rheumatoid arthritis via activating AMPK pathway].

OBJECTIVE: To observe the effects of 2-deoxyglucose inhibiting synovial pannus of adjuvant arthritis rats and to explore its potential mechanism of inhibiting angiogenesis by investigating proliferation, migration and matrigel tube formation assay in vitro. METHODS: The effect of 2-DG on synovial pannus was evaluated by histopathology of HE staining; HUVEC proliferation was determined by CCK-8 method; migration of FLS were determined by transwell; In vitro matrigel tube formation assay was made for assessing tube number of HUVEC; p-AMPK and Bcl-2 were detected by Western blot assay; AMPK signaling pathway in HUVEC was inhibited by compound C, which is an inhibitor of AMPK activation. RESULTS: 2-DG (200 mg/kg) obviously decreased appearance of synovial pannus (P < 0.01); in vitro, 2-DG (0.5 mmol/L and/or 5 mmol/L) obviously inhibited proliferation, migration and tube number of HUVEC (P < 0.01 or P < 0.001), and its effects on HUVEC were reversed by using AMPK antagonist (Compound C); Western blot showed that 2-DG (5 mmol/L) increased expression of p-AMPK and decreased expression of Bcl-2 (P < 0.05). CONCLUSIONS: Activating AMPK pathway and decreasing expression of Bcl-2 may the potential mechanism by which 2-DG contributes to anti-angiogenesis and effects of inhibiting proliferation, migration and tube number of HUVEC.

Aspirin inhibits the proliferation of human uterine leiomyoma cells by downregulation of K­Ras­p110α interaction.

Aspirin has been confirmed as an effective antitumor drug in various cancers. However, the relationship between aspirin and uterine leiomyoma is still underexplored. Here, we explored the effects of aspirin on human uterine leiomyoma cells and provide insights into the underlying mechanisms. Cell Counting Kit-8 (CCK-8) and flow cytometry analysis showed that aspirin treatment inhibited cell proliferation and promoted cell cycle arrest at G0/G1 phase in a dose- and time­dependent manner of human uterine leiomyoma cells. Further studies revealed that aspirin blocked the interaction between K-Ras and p110α by co-immunoprecipitation and immunofluorescence. Western blotting demonstrated K­Ras­p110α interaction was required for the effects of aspirin­induced inhibition on cell growth and cell cycle transition via cell cycle regulators, including cyclin D1 and cyclin-dependent kinase 2 (CDK2). PI3K/Akt/caspase signaling pathway was involved in human uterine leiomyoma cell growth under aspirin treatment. Taken together, these results suggest that aspirin inhibited human uterine leiomyoma cell growth by regulating K­Ras­p110α interaction. Aspirin which targeting on interaction between K-Ras and p110α may serve as a new therapeutic drug for uterine leiomyoma treatment.

Rectification of curved document images based on single view three-dimensional reconstruction.

Since distortions in camera-captured document images significantly affect the accuracy of optical character recognition (OCR), distortion removal plays a critical role for document digitalization systems using a camera for image capturing. This paper proposes a novel framework that performs three-dimensional (3D) reconstruction and rectification of camera-captured document images. While most existing methods rely on additional calibrated hardware or multiple images to recover the 3D shape of a document page, or make a simple but not always valid assumption on the corresponding 3D shape, our framework is more flexible and practical since it only requires a single input image and is able to handle a general locally smooth document surface. The main contributions of this paper include a new iterative refinement scheme for baseline fitting from connected components of text line, an efficient discrete vertical text direction estimation algorithm based on convex hull projection profile analysis, and a 2D distortion grid construction method based on text direction function estimation using 3D regularization. In order to examine the performance of our proposed method, both qualitative and quantitative evaluation and comparison with several recent methods are conducted in our experiments. The experimental results demonstrate that the proposed method outperforms relevant approaches for camera-captured document image rectification, in terms of improvements on both visual distortion removal and OCR accuracy.

Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells.

Tumor cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, which is therefore targeted by therapeutic agents. The compound 3-bromopyruvate (3-BrPA), a strong alkylating agent and hexokinase inhibitor, inhibits tumor cell glycolysis and the production of ATP, causing apoptosis. 3-BrPA induces apoptosis of nasopharyngeal carcinoma (NPC) cell lines HNE1 and CNE-2Z, which may be related to its molecular mechanisms. In the present study, we investigated the effects of 3-BrPA on the viability, reactive oxygen species (ROS), apoptosis and other types of programmed cell death in NPC cells in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD­fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis­resistant cancers.

Effects of a Chinese traditional formula Kai Xin San (KXS) on chronic fatigue syndrome mice induced by forced wheel running.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional medicine, Kai Xin San (KXS), composed of ginseng (Panax ginseng), hoelen (Wolfiporia cocos), polygala (Polygala tenuifolia) and Acorus gramineus, is famous for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. AIM OF THE STUDY: The present study investigated the effect of KXS on chronic fatigue syndrome (CFS) mice induced by forced wheel running. MATERIALS AND METHODS: Seventy two healthy adult male Kunming mice were randomly divided into six groups: home cage control group, CFS group, CFS group with Modafinil treatment at 13 mg/kg/d doge, KXS treatment at 175 mg/kg/d, 350 mg/kg/d and 700 mg/kg/d doge. CFS mice were induced by forced wheel running with higher speed for 4 weeks and then taken an exhausted exercise. The biochemical parameters including serum lactate dehydrogenase (LDH), serum urea nitrogen (SUN), serum testosterone (T), liver glycogen (LG), muscle glycogen (MG) and muscle lactic acid (MLA) were determined by using commercially available kits. The splenocytes proliferation from mice was examined by MTT method. The levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) secreted by splenocytes were determined by ELISA. RESULTS: CFS mice with KXS administration exhibited less electric shock time when compared with CFS group without drug treatment. The effect of KXS has after demonstrated reduction in SUN, LDH and MLA levels and an increase in T, LG and MG levels. CFS mice with KXS could improve the proliferation of splenocytes compared with CFS group without drug treatment. The cultured splenocytes from CFS mice without KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with home cage control mice. The cultured splenocytes of CFS mice with KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with CFS group without drug treatment. CONCLUSIONS: The results of this preliminary study provide evidence that KXS could ameliorate CFS by affecting the physiological markers for fatigue. This study also supported the use of KXS against CFS by improving the proliferation of splenocytes from CFS mice and modulating the disturbance of cytokines induced by CFS.