41 research outputs found

    Molecular Design Strategy to Construct the Near-Infrared Fluorescent Probe for Selectively Sensing Human Cytochrome P450 2J2

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    Cytochrome P450 2J2 (CYP2J2), a key enzyme responsible for oxidative metabolism of various xenobiotics and endogenous compounds, participates in a diverse array of physiological and pathological processes in humans. Its biological role in tumorigenesis and cancer diagnosis remains poorly understood, owing to the lack of molecular tools suitable for real-time monitoring CYP2J2 in complex biological systems. Using molecular design principles we were able to modify the distance between the catalytic unit and metabolic recognition moiety, allowing us to develop a CYP2J2 selective fluorescent probe using a near-infrared fluorophore (E)-2-(2-(6-hydroxy-2, 3-dihydro-1H-xanthen-4-yl)vinyl)-3,3- dimethyl-1-propyl-3H-indol-1-ium iodide (HXPI). To improve the reactivity and isoform specificity, a self-immolative linker was introduced to the HXPI derivatives in order to better fit the narrow substrate channel of CYP2J2, the modification effectively shortened the spatial distance between the metabolic moiety (O-alkyl group) and catalytic center of CYP2J2. After screening a panel of O-alkylated HXPI derivatives, BnXPI displayed the best combination of specificity, sensitivity and applicability for detecting CYP2J2 in vitro and in vivo. Upon O-demethylation by CYP2J2, a self-immolative reaction occurred spontaneously via 1,6-elimination of p-hydroxybenzyl resulting in the release of HXPI. Allowing BnXPI to be successfully used to monitor CYP2J2 activity in real-time for various living systems including cells, tumor tissues, and tumor-bearing animals. In summary, our practical strategy could help the development of a highly specific and broadly applicable tool for monitoring CYP2J2, which offers great promise for exploring the biological functions of CYP2J2 in tumorigenesis.</p

    Molecular Design Strategy to Construct the Near-Infrared Fluorescent Probe for Selectively Sensing Human Cytochrome P450 2J2

    Get PDF
    Cytochrome P450 2J2 (CYP2J2), a key enzyme responsible for oxidative metabolism of various xenobiotics and endogenous compounds, participates in a diverse array of physiological and pathological processes in humans. Its biological role in tumorigenesis and cancer diagnosis remains poorly understood, owing to the lack of molecular tools suitable for real-time monitoring CYP2J2 in complex biological systems. Using molecular design principles, we were able to modify the distance between the catalytic unit and metabolic recognition moiety, allowing us to develop a CYP2J2 selective fluorescent probe using a near-infrared fluorophore (E)-2-(2-(6-hydroxy-2, 3-dihydro-1H-xanthen-4-yl)­vinyl)-3,3-dimethyl-1-propyl-3H-indol-1-ium iodide (HXPI). To improve the reactivity and isoform specificity, a self-immolative linker was introduced to the HXPI derivatives in order to better fit the narrow substrate channel of CYP2J2, the modification effectively shortened the spatial distance between the metabolic moiety (O-alkyl group) and catalytic center of CYP2J2. After screening a panel of O-alkylated HXPI derivatives, BnXPI displayed the best combination of specificity, sensitivity and applicability for detecting CYP2J2 in vitro and in vivo. Upon O-demethylation by CYP2J2, a self-immolative reaction occurred spontaneously via 1,6-elimination of p-hydroxybenzyl resulting in the release of HXPI. Allowing BnXPI to be successfully used to monitor CYP2J2 activity in real-time for various living systems including cells, tumor tissues, and tumor-bearing animals. In summary, our practical strategy could help the development of a highly specific and broadly applicable tool for monitoring CYP2J2, which offers great promise for exploring the biological functions of CYP2J2 in tumorigenesis

    Enhanced performance of GaN-based long-wavelength blue light-emitting diodes with graphene-ITO composite film as transparent conductive electrode

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    We present enhanced performance of GaN-based long-wavelength blue light emitting diodes (LEDs) with hybrid transparent conductive electrodes (TCE) made of graphene and indium tin oxide (ITO) composite. The nearly 100% transmittance TCE were gained when graphene grown by chemical-vapor-deposition was annealed with ITO on the top of it. Compared to conventional LEDs, the work voltage was reduced to 3.5 V at 5 mA forward current. The light emission power was improved about 190%. The good peformance can be attributed to the improved lateral current spreading over the composite graphene-ITO TCE before p-GaN layer injected by carriers

    Comparison of Usage and Influencing Factors between Governmental Public Bicycles and Dockless Bicycles in Linfen City, China

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    Automobile traffic has shifted the use of bicycles in many developed regions to being mainly for sport, recreation and commuting. Due to the desire to mitigate the impacts of climate change and alleviate traffic jams, bicycle sharing is booming in China. Governmental public bicycles and dockless bicycles are the main types of bicycle sharing in China, each with different types of management and pricing. Field research has found that many bicycle sharing networks are idle and wasteful, and thus we investigated which type is more popular and suitable for Chinese cities. This research comparatively analyzes the application of governmental public bicycles and dockless bicycles, mainly focusing on the cycling destination, cycling frequency, and cycling factors, taking Linfen City as an example. The results show that: (1) The purpose is different between governmental public bicycles and dockless bicycles. On the one hand, the aim of riding a governmental public bicycle to work represents the largest proportion at about 29%, mainly because of the fixed route of travel, and the fact that the fixed placement of governmental public bicycles makes them more available compared to the random arbitrariness of dockless bicycles. On the other hand, the aim of riding a dockless bicycle for entertainment accounts for the largest proportion, at about 34%, mainly due to the ease of borrowing and returning a bike, and mobile payment. (2) In terms of frequency, the public’s choice of riding a dockless bicycle or a governmental public bicycle has no essential difference, given that there are only two options for citizens in Linfen. (3) The response to the two kinds of bicycle sharing is different; the governmental public bicycle has the advantage of lower cost, but the dockless bicycle has more advantages in the procedure of borrowing and returning the bicycle

    Spatial–Temporal Heterogeneity and the Related Influencing Factors of Tourism Efficiency in China

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    Tourism efficiency is an effective index of measuring the development quality of the tourism industry. In this study, the tourism efficiency of 30 provinces in China during the period from 2006 to 2018 was measured with the SBM model and Malmquist index. On the basis of ESDA and GWR models, we explored the spatial pattern of China’s tourism efficiency and the spatial heterogeneity of the influencing factors in depth. The results revealed that China’s tourism efficiency has been constantly enhanced with an increasingly balanced pattern. Meanwhile, the utilization degrees of various input factors have constantly been improving. Both technological efficiency and technological progress jointly promote rapid growth of total-factor productivity. Accompanied with constant enhancement of the spatial agglomeration effect, the local spatial pattern also showed obvious differentiation. In general, low-efficiency regions were mainly concentrated in northern China, while high-efficiency regions were concentrated in southern China. The distinct spatial–temporal differentiation characteristics of tourist economic efficiency can be attributed to different influencing strengths of various factors in various regions and different action tendencies. The level of economic development, traffic conditions, the professional level of tourism, and openness degree can significantly promote tourism efficiency. Tourism resource endowment and environmental cost impose slight effects and differ in action direction, thereby inhibiting the tourism efficiency of many regions

    Simulation of the Riprap Movement Using the Continuous-Time Random Walking Method

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    During the implementation of the riprap project, the underwater migration process of the stones is quite uncertain because of its difficulty to observe. The process of stone transportation is discrete, which makes it unsuitable to be described by a continuous differential equation. Therefore, considering the distribution of stone jumping and waiting, a continuous-time random walk (CTRW) model is established. Based on the actual engineering data, five schemes simulate the one-dimensional motion of riprap underwater and further discuss the spatial distribution and particle size of the riprap. The results show that the CTRW model can effectively predict the riverbed elevation change behavior caused by the riprap project. The suitability of the model for the prediction of riprap movement decreases first and then increases with the increase in the selected width. This indicates that the randomness of the motion of the riprap causes the width of the observation zone to have a significant effect on the overall behavior of riprap movement. When the width is large enough, the influence of the randomness of the motion can be reduced by the average movement behavior within the observation zone. While the observation time of riprap movement is from a short to long time scale, the transport behavior changes from subdiffusion to normal diffusion behavior
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