Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.     

Nacre-Inspired,Liquid Metal-Based Ultrasensitive Electronic Skin by Spatially Regulated Cracking Strategy

The realization of liquid metal-based wearable systems will be a milestone toward high-performance, integrated electronic skin. However, despite the revolutionary progress achieved in many other components of electronic skin, liquid metal-based flexible sensors still suffer from poor sensitivity due to the insufficient resistance change of liquid metal to deformation. Herein, a nacre-inspired architecture composed of a biphasic pattern (liquid metal with Cr/Cu underlayer) as “bricks” and strain-sensitive Ag film as “mortar” is developed, which breaks the long-standing sensitivity bottleneck of liquid metal-based electronic skin. With 2 orders of magnitude of sensitivity amplification while maintaining wide (>85%) working range, for the first time, liquid metal-based strain sensors rival the state-of-art counterparts. This liquid metal composite features spatially regulated cracking behavior. On the one hand, hard Cr cells locally modulate the strain distribution, which avoids premature cut-through cracks and prolongs the defect propagation in the adjacent Ag film. On the other hand, the separated liquid metal cells prevent unfavorable continuous liquid-metal paths and create crack-free regions during strain. Demonstrated in diverse scenarios, the proposed design concept may spark more applications of ultrasensitive liquid metal-based electronic skins, and reveals a pathway for sensor development via crack engineering.     

Single image dehazing using a new color channel

Images with hazy scene suffer from low-contrast, which reduces the visible quality of the scene, thus making object detection a more challenging task. Low-contrast can result from foggy weather conditions during image acquisition. Dehazing is a process of removal of haze from the photography of a hazy scene. Single-image dehazing based on dark channel priors are well-known techniques in this field. However, the performance of such techniques is limited to priors or constraints. Moreover, this type of method fails when images have sky-region. So, a method is proposed, which can restore the visibility of hazy images. First, a hazy image is divided into blocks of size 32 × 32, then the score of each block is calculated to select a block having the highest score. Atmospheric light is calculated from the selected block. A new color channel is considered to remove atmospheric scattering, obtained channel value and atmospheric light are then used to calculate the transmission map in the second step. Third, radiance is computed using a transmission map and atmospheric light. The illumination scaling factor is adopted to enhance the quality of a dehazed image in the final step. Experiments are performed on six datasets namely, I-HAZE, O-HAZE, BSDS500, FRIDA, RESIDE dataset and natural images from Google. The proposed method is compared against 11 state-of-the-art methods. The performance is analyzed using fourteen quantitative evaluation metrics. All the results demonstrate that the proposed method outperforms 11 state-of-the-art methods in most of the cases.     

自重湿陷性黄土地基预钻孔浸水处理的可靠度设计方法

为解决传统预浸水法存在的浸水时间长、浸水处理范围难以确定等不足,基于土体中水分运移规律,依据可靠度理论、极限状态设计方法及复合 Poisson 过程原理,提出一种消除黄土湿陷性的处理浸水方法——预钻孔浸水法。给出了利用预钻孔浸水法对自重湿陷性黄土地基进行浸水时,水平向及竖直向浸水影响范围的确定模型;在此基础上结合达西定律给出了浸水孔设计参数如孔深、孔间距及浸水孔个数的确定方法。结合铜川某工程,设计进行了现场预钻孔浸水试验,对该方法的合理性进行了验证,并通过现场钻探、现场勘探、室内湿陷性试验等方法对该方法的处理效果进行了评价。该浸水方法具有浸水时间短、浸水影响范围可根据浸水孔布设进行控制等优点,且浸水处理效果良好,完全符合施工要求。     

剪切解络-超滤分离金属关键指标预测与验证

根据剪切解络-超滤过程中金属离子的动态浓度关系和质量守恒定律,采用CodeBlocks17.12软件编写程序,建立了剪切解络-超滤工艺关键指标预测模型,实现了金属离子浓度、回收率、体积稀释倍数等指标的预测,并用实验加以验证。依次在转速800 r/min、1 400 r/min、3 000 r/min下回收模拟废水中43 μg/L的Co²⁺、995 μg/L的Ni²⁺和88 μg/L的La³⁺,3种金属的回收率均达99.8%以上时,超滤过程体积稀释倍数的预测值分别为7.0、7.5、5.75,实验值分别为7.5、7.25、6.25,可见预测值与实验值基本一致。本模型对研究方案制定和调整有实际指导意义。     

双对苯醌的抗氧化活性分析及其固体发酵条件优化

为探索生物活性未知的双对苯醌（2,7-dihydroxy-3,6,9-trimethyl-9H-xanthene-1,4,5,8-tetraone，DTXT）的抗氧化活性，并提高其发酵产量，考察DTXT的还原力以及对超氧阴离子自由基、羟自由基、1,1-二苯基-2-三硝基苯肼（1,1-diphenyl-2-picrylhydrazyl，DPPH）自由基的清除效果，在单因素试验基础上，采用响应面法优化了DTXT产生菌瓶生顶孢霉（Acremonium cavaraeanum）CA022菌株的固体发酵培养基。结果表明：在200 μg/mL质量浓度下，DTXT的还原力与芦丁差异不显著，高于VE和2,6-二叔丁基-4甲基苯酚，对超氧阴离子自由基清除率达到67.00%，对羟自由基清除率达到78.83%，对DPPH自由基清除率达到76.53%。通过响应面试验，得到最佳培养基配方为葡萄糖0.773%、硝酸钠0.185%、H3BO3 0.032%、VB1 100 μg/100 g，在此条件下实际获得的DTXT产量为4 150.8 mg/kg，是优化前产量的（2 864.83 mg/kg）1.45 倍。     

A Fusion Kalman Filter and UFIR Estimator Using the Influence Function Method

In this paper, the Kalman filter (KF) and the unbiased finite impulse response (UFIR) filter are fused in the discrete-time state-space to improve robustness against uncertainties. To avoid the problem where fusion filters may give up some advantages of UFIR filters by fusing based on noise statistics, we attempt to find a way to fuse without using noise statistics. The fusion filtering algorithm is derived using the influence function that provides a quantified measure for disturbances on the resulting filtering outputs and is termed as an influence finite impulse response (IFIR) filter. The main advantage of the proposed method is that the noise statistics of process noise and measurement noise are no longer required in the fusion process, showing that a critical feature of the UFIR filter is inherited. One numerical example and a practice-oriented case are given to illustrate the effectiveness of the proposed method. It is shown that the IFIR filter has adaptive performance and can automatically switch from the Kalman estimate to the UFIR estimates according to operating conditions. Moreover, the proposed method can reduce the effects of optimal horizon length on the UFIR estimate and can give the state estimates of best accuracy among all the compared methods.