Distinct Pharmacological Properties of Gaseous CO and CO-Releasing Molecule in Human Platelets

Carbon monoxide (CO)—gaseous or released by CO-RMs—both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO—delivered by gaseous CO–saturated buffer (CO_G) and generated by CORM-A1—on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of CO_G on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. In turn, CO_G did not affect, whereas CORM-A1 substantially inhibited energy metabolism in platelets. Even though activation of sGC by BAY 41-2272 or BAY 58-2667 inhibited significantly platelet aggregation, their effects on energy metabolism in platelets were absent or weak and could not contribute to antiplatelet effects of sGC activation. In contrast, vasodilatation of murine aortic rings, induced either by CO_G or CORM-A1, was dependent on sGC. We conclude that the source (CO_G vs. CORM-A1) and kinetics (rapid vs. slow) of CO delivery represent key determinants of the mechanism of antiplatelet action of CO, involving either impairment of energy metabolism or activation of sGG.     

AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions

Tumor cell aggregation is critical for cell survival following the loss of extracellular matrix attachment and dissemination. However, the underlying mechanotransduction of clustering solitary tumor cells is poorly understood, especially in non-small cell lung cancers (NSCLC). Here, we examined whether cell surface protrusions played an important role in facilitating the physical contact between floating cells detached from a substrate. We employed poly-2-hydroxyethyl methacrylate-based 3D culture methods to mimic in vivo tumor cell cluster formation. The suprastructural analysis of human NSCLC A549 cell spheroids showed that finger-like protrusions clung together via the actin cytoskeleton. Time-lapse holotomography demonstrated that the finger-like protrusions of free-floating cells in 3D culture displayed exploratory coalescence. Global gene expression analysis demonstrated that the genes in the organic hydroxyl transport were particularly enriched in the A549 cell spheroids. Particularly, the knockdown of the water channel aquaporin 3 gene (AQP3) impaired multicellular aggregate formation in 3D culture through the rearrangement of the actomyosin cytoskeleton. Moreover, the cells with reduced levels of AQP3 decreased their transmigration. Overall, these data indicate that cell detachment-upregulated AQP3 contributes to cell surface protrusions through actomyosin cytoskeleton remodeling, causing the aggressive aggregation of free-floating cells dependent on the property of the substratum and collective metastasis.     

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

激光在线测厚振动分析与精度优化

激光测厚具有安全可靠、测量精度高、测量范围大等优点,广泛应用于纸张、电池极片等薄膜类材料厚度的在线测量。带材宽幅方向扫描测厚时由于扫描架往复运动会产生机械振动,影响在线测厚精度。针对该问题,以锂离子电池极片厚度测量为例,使用双激光差动式测厚平台对电池极片和铜箔分别进行厚度测量,然后对测厚数据进行频谱分析,探究其振动规律的相似性,并基于频谱分析结果采用滑动带阻滤波方式对测厚数据进行处理,滤波后极片和铜箔的厚度极差分别降低了33.4%和73.8%,有效过滤了机械振动导致的测量误差,可满足极片和铜箔厚度测量的精度要求。     

The microstructure and magnetic properties of Ca2+ ion doped GdCrO3

In this paper, the crystal structure, vacancy defect, local electron density and magnetic properties of Gd_1-xCa_xCrO₃ (0 ≤ x ≤ 0.3) polycrystalline samples were investigated systematically. The crystal structural analyses show that all the samples are orthorhombic phase and a structural distortion happens around x = 0.3. Due to the formation of Cr⁴⁺ ions, both the lattice constant and the Cr–O bond length decrease. The results of positron annihilation spectrum reveals that the vacancy defect concentration increases and the local electron structure changes with the introduction of Ca²⁺ ions. The field-cooled (FC) and zero-field cooled (ZFC) curves of Gd_1-xCa_xCrO₃ samples measured under H = 100 Oe exhibits negative magnetization characteristics due to the interaction between Gd³⁺ and Cr³⁺ ions, and the magnetism can be affected by the structural distortion.     

一种低载噪比突发扩频信号的快速捕获方法实现

针对突发扩频信号用户资源扩大、终端功率降低、系统容量提升等需求,提出了一种低载噪比突发扩频信号的快速捕获硬件实现方法。采用分段匹配滤波器加多普勒并行相干积累的方法,基于硬件实现从算法到工程进行全流程优化设计,最终实现最优的捕获性能。应用结果表明,该硬件设计实现方案的快速捕获性能优越,设计方案正确、可行,已成功应用于工程建设中。     

Experimental evaluation of the luminescence performance of fired clay brick coated with SrAl2O4:Eu/Dy phosphor

This study evaluates the luminescence performance of fired clay bricks coated with SrAl₂O₄:Eu/Dy phosphor. To do so, SrAl₂O₄:Eu/Dy phosphor was first produced using the traditional solid-state reaction synthesis technique. The prepared phosphor was then used for coating fired clay bricks to analyze the luminescence performance via spectral analysis, decay characteristics, and microstructure of the bricks. The results reveal that excitation and emission spectra of the phosphor coated bricks range from 200 to 480 nm and 455 to 650 nm, respectively, suggesting that the phosphor coated bricks have the capacity of absorbing light with a wide range of wavelengths. The peak wavelength projected at 511 nm in the emission spectrum is achieved, which indicates 4f⁶5 d¹-4f⁷ transition of Europium (Eu²⁺). The repeated excitation and deexcitation of Eu²⁺ by using hole traps and trap levels offered by Dysprosium (Dy³⁺), exist between the ground and the excited state of Eu²⁺ leads to luminescent phenomenon. Moreover, the decay characteristics has revealed that phosphor coated bricks can emit light for a considerable amount of time (>8.5 min) upon the removal of the excitation source. The results reveal that phosphor coated bricks has the potential of increasing energy efficiency of residential and commercial buildings.     

Deterministic and probabilistic ship pitch prediction using a multi-predictor integration model based on hybrid data preprocessing,reinforcement learning and improved QRNN

The deterministic and probabilistic prediction of ship motion is important for safe navigation and stable real-time operational control of ships at sea. However, the volatility and randomness of ship motion, the non-adaptive nature of single predictors and the poor coverage of quantile regression pose serious challenges to uncertainty prediction, making research in this field limited. In this paper, a multi-predictor integration model based on hybrid data preprocessing, reinforcement learning and improved quantile regression neural network (QRNN) is proposed to explore the deterministic and probabilistic prediction of ship pitch motion. To validate the performance of the proposed multi-predictor integrated prediction model, an experimental study is conducted with three sets of actual ship longitudinal motions during sea trials in the South China Sea. The experimental results indicate that the root mean square errors (RMSEs) of the proposed model of deterministic prediction are 0.0254°, 0.0359°, and 0.0188°, respectively. Taking series #2 as an example, the prediction interval coverage probabilities (PICPs) of the proposed model of probability predictions at 90%, 95%, and 99% confidence levels (CLs) are 0.9400, 0.9800, and 1.0000, respectively. This study signifies that the proposed model can provide trusted deterministic predictions and can effectively quantify the uncertainty of ship pitch motion, which has the potential to provide practical support for ship early warning systems.     

不同段数爆破地震波的反应谱分析

为了研究段数对反应谱特性的影响,基于某石方控制爆破工程爆破振动实测数据,对不同段数爆破振动信号进行了反应谱分析。首先,利用实测的爆破振动速度信号采用直接微分法获得了加速度信号,并利用EEMD分解对加速度信号进行低通滤波去噪处理,获得了准确清晰的加速度曲线。然后,利用精确法求得了不同段数下爆破振动信号的速度反应谱和标准速度反应谱。分析结果表明:不同段数的爆破振动质点峰值速度与速度反应谱的峰值速度并不存在对应关系,因此分段数的选择应综合考虑结构对爆破振动的动态响应。     

YOLSO: You Only Look Small Object

Small object detection is challenging and far from satisfactory. Most general object detectors suffer from two critical issues with small objects: (1) Feature extractor based on classification network cannot express the characteristics of small objects reasonably due to insufficient appearance information of targets and a large amount of background interference around them. (2) The detector requires a much higher location accuracy for small objects than for general objects. This paper proposes an effective and efficient small object detector YOLSO to address the above problems. For feature representation, we analyze the drawbacks in previous backbones and present a Half-Space Shortcut(HSSC) module to build a background-aware backbone. Furthermore, a coarse-to-fine Feature Pyramid Enhancement(FPE) module is introduced for layer-wise aggregation at a granular level to enhance the semantic discriminability. For loss function, we propose an exponential L1 loss to promote the convergence of regression, and a focal IOU loss to focus on prime samples with high classification confidence and high IOU. Both of them significantly improves the location accuracy of small objects. The proposed YOLSO sets state-of-the-art results on two typical small object datasets, MOCOD and VeDAI, at a speed of over 200 FPS. In the meantime, it also outperforms the baseline YOLOv3 by a wide margin on the common COCO dataset.