A Deep Dive into VDAC1 Conformational Diversity Using All-Atom Simulations Provides New Insights into the Structural Origin of the Closed States

The voltage-dependent anion channel 1 (VDAC1) is a crucial mitochondrial transporter that controls the flow of ions and respiratory metabolites entering or exiting mitochondria. As a voltage-gated channel, VDAC1 can switch between a high-conducting “open” state and a low-conducting “closed” state emerging at high transmembrane (TM) potentials. Although cell homeostasis depends on channel gating to regulate the transport of ions and metabolites, structural hallmarks characterizing the closed states remain unknown. Here, we performed microsecond accelerated molecular dynamics to highlight a vast region of VDAC1 conformational landscape accessible at typical voltages known to promote closure. Conformers exhibiting durable subconducting properties inherent to closed states were identified. In all cases, the low conductance was due to the particular positioning of an unfolded part of the N-terminus, which obstructed the channel pore. While the N-terminal tail was found to be sensitive to voltage orientation, our models suggest that stable low-conducting states of VDAC1 predominantly take place from disordered events and do not result from the displacement of a voltage sensor or a significant change in the pore. In addition, our results were consistent with conductance jumps observed experimentally and corroborated a recent study describing entropy as a key factor for VDAC gating.     

簇状分布的刚性双层植被明渠紊流特性分析

采用RNG k-ε 紊流模型,对簇状分布的刚性双层植被明渠水流进行了模拟和分析;根据时间及空间的双平均方法对植被明渠水流的流速及紊动参数进行了统计。结果表明:簇状分布的植被明渠水流可以分为植物区、间隙区及主流区,不同区域时均流速的大小和分布各异;双层植被明渠水流中,时均流速垂线分布在近床面、低植物顶部附近及高植物顶部附近均出现拐点,脉动强度和紊动能的最大值出现在高植物顶部附近。     

体型参数对旋流排沙渠道水沙特性的影响

为明确关键体型参数对渠道和排沙洞内水沙特性的影响,在模型试验研究的基础上开展了旋流排沙渠道的水沙两相流数值模拟。结果表明:起旋室高度对截沙率影响较为显著,最大相差5.41%;排沙洞直径、倾角和起旋室出口宽度对分流比影响显著,最大相差8.13%,增大倾角后改善了原排沙洞封闭端因壁面条件影响而产生的泥沙淤积;起旋室出口宽度对渠道内水沙特性基本无影响;不同体型下旋流排沙渠道均可高效、持续排沙,截沙率均大于90%,经过起旋室后,高含沙水流从排沙洞流出,下游渠道含沙量急剧减小。     

5×5棒束通道内流动转捩特性研究

棒束通道的特殊结构导致其内部流动转捩情况较为复杂,探究其内部流动转捩规律具有重要意义。本文针对棒束通道内的流动转捩特性开展实验与CFD模拟研究,通过实验获得了棒束通道内沿程阻力系数的变化规律;采用不同湍流模型进行了数值模拟。结果表明,SST k-ω模型能较好地反映实验结果。进一步对比了不同雷诺数工况下通道内不同位置的沿程阻力系数与湍流强度,发现对于不同子通道,中心子通道湍流强度与沿程阻力系数高于边角子通道;对于同一子通道,子通道中心处湍流强度与壁面切应力高于子通道边缘处。这一结果说明,受壁面影响,棒束内湍流强度、壁面切应力、阻力特性具有不均匀性,这些空间上的不均匀性相互作用会引起总体上棒束转捩点不明显。     

Variation of lipid and tocopherol composition in three strains of channel catfish (Ictalurus punctatus)

Three strains of channel catfish (Ictalurus punctatus), which were designated as ‘AQUA’, ‘LSU’ and ‘MSU’, were examined for their lipid and tocopherol composition to delineate if genetic strains exhibited the potential to vary in their susceptibility to lipid oxidation. Since age, diet and environmental conditions were similar for all strains, growth and compositional differences were ascribed to genetic factors. Significant differences were noted between strains in their muscle tissue for triacylglycerol (TG) levels, fatty acid composition, and tocopherol levels. The largest quantity of TG was found in the LSU strain whereas the smallest quantity was found in the AQUA strain. Levels of polyunsaturated fatty acids (PUFA) in the TG and total lipid (TL) fraction were highest in the AQUA strain and lowest in the MSU strain. Similarly, a peroxidizability index, which took into account the differences in susceptibility of unsaturated fatty acids to oxidize, was highest in AQUA and lowest in MSU for the TG and TL fractions. The peroxidizability index for the phospholipid fraction did not vary between strains. Adopting a relative antioxidant effectiveness value of 0.31 for γ-tocopherol, the LSU, MSU and AQUA catfish strains were calculated to contain 37.72, 22.79 and 42.49 nmol of α-tocopherol equivalents, respectively. The MSU catfish strain exhibited the highest ratio (nmol PUFA/nmol α-tocopherol equivalents) suggesting that its tissue would be the least stable to oxidation.     

Cation Permeability of Voltage-Gated Hair Cell Ca2+ Channels of the Vertebrate Labyrinth

Some hearing, vestibular, and vision disorders are imputable to voltage-gated Ca²⁺ channels of the sensory cells. These channels convey a large Ca²⁺ influx despite extracellular Na⁺ being 70-fold more concentrated than Ca²⁺; such high selectivity is lost in low Ca²⁺, and Na⁺ can permeate. Since the permeation properties and molecular identity of sensory Ca²⁺ channels are debated, in this paper, we examine the Na⁺ current flowing through the L- and R-type Ca²⁺ channels of labyrinth hair cells. Ion currents and cytosolic free Ca²⁺ concentrations were simultaneously monitored in whole-cell recording synchronous to fast fluorescence imaging. L-type and R-type channels were present with different densities at selected sites. In 10 nM Ca²⁺, the activation and deactivation time constants of the L-type Na⁺ current were accelerated and its maximal amplitude increased by 6-fold compared to physiological Ca²⁺. The deactivation of the R-type Na⁺ current was not accelerated, and its current amplitude increased by 2.3-fold in low Ca²⁺; moreover, it was partially blocked by nifedipine in a voltage- and time-dependent manner. In conclusion, L channel gating is affected by the ion species permeating the channel, and its selectivity filter binds Ca²⁺ more strongly than that of R channel; furthermore, external Ca²⁺ prevents nifedipine from perturbing the R selectivity filter.     

Research and development of advanced structured packing in a rotating packed bed

As the core component of the rotating packing bed, packing is a place for efficient gas–liquid mixing and mass transfer. In this paper, a 3D structured packing composed of a mesh structure and a support structure was designed. The mesh structure is a ring-shaped mesh surrounded by triangular meshes, which is stable in structure and can achieve a high degree of dispersion and aggregation of the liquid phase. The support structure is composed of ring-shaped structural units arranged at a certain a...     

Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells

TRPV4 (transient receptor potential vanilloid 4), a calcium permeable TRP ion channel, is known to play a key role in endocytosis. However, whether it contributes to exocytosis remains unclear. Here, we report that activation of TRPV4 induced massive exocytosis in both melanoma A375 cell and heterologous expression systems. We show here that, upon application of TRPV4-specific agonists, prominent vesicle priming from endoplasmic reticulum (ER) was observed, followed by morphological changes of mitochondrial crista may lead to cell ferroptosis. We further identified interactions between TRPV4 and folding/vesicle trafficking proteins, which were triggered by calcium entry through activated TRPV4. This interplay, in turn, enhanced TRPV4-mediated activation of folding and vesicle trafficking proteins to promote exocytosis. Our study revealed a signaling mechanism underlying stimulus-triggered exocytosis in melanoma and highlighted the role of cellular sensor TRPV4 ion channel in mediating ferroptosis.     

基于照度与场景纹理注意力图的低光图像增强

目的 现有的低照度图像增强算法常存在局部区域欠增强、过增强及色彩偏差等情况,且对于极低照度图像增强,伴随着噪声放大及细节信息丢失等问题。对此,提出了一种基于照度与场景纹理注意力图的低光图像增强算法。方法 首先,为了降低色彩偏差对注意力图估计模块的影响,对低光照图像进行了色彩均衡处理;其次,试图利用低照度图像最小通道约束图对正常曝光图像的照度和纹理进行注意力图估计,为后续增强模块提供信息引导;然后,设计全局与局部相结合的增强模块,用获取的照度和场景纹理注意力估计图引导图像亮度提升和噪声抑制,并将得到的全局增强结果划分成图像块进行局部优化,提升增强性能,有效避免了局部欠增强和过增强的问题。结果 将本文算法与2种传统方法和4种深度学习算法比较,主观视觉和客观指标均表明本文增强结果在亮度、对比度以及噪声抑制等方面取得了优异的性能。在VV（Vasileios Vonikakis）数据集上,本文方法的BTMQI（blind tone-mapped quality index）和NIQMC（no-reference image quality metric for contrast distortion）指标均达到最优值;在178幅普通低照度图像上本文算法的BTMQI和NIQMC均取得次优值,但纹理突出和噪声抑制优势显著。结论 大量定性及定量的实验结果表明,本文方法能有效提升图像亮度和对比度,且在突出暗区纹理时,能有效抑制噪声。本文方法用于极低照度图像时,在色彩还原、细节纹理恢复和噪声抑制方面均具有明显优势。代码已共享在Github上：https://github.com/shuanglidu/LLIE_CEIST.git。     

联合多重对抗与通道注意力的高安全性图像隐写

目的 现有基于对抗图像的隐写算法大多只能针对一种隐写分析器设计对抗图像,且无法抵御隐写分析残差网络(steganalysis residual network,SRNet)、Zhu-Net等最新基于卷积神经网络隐写分析器的检测。针对这一现状,提出了一种联合多重对抗与通道注意力的高安全性图像隐写方法。方法 采用基于U-Net结构的生成对抗网络生成对抗样本图像,利用对抗网络的自学习特性实现多重对抗隐写网络参数迭代优化,并通过针对多种隐写分析算法的对抗训练,生成更适合内容隐写的载体图像。同时,通过在生成器中添加多个轻量级通道注意力模块,自适应调整对抗噪声在原始图像中的分布,提高生成对抗图像的抗隐写分析能力。其次,设计基于多重判别损失和均方误差损失相结合的动态加权组合方案,进一步增强对抗图像质量,并保障网络快速稳定收敛。结果 实验在BOSS Base 1.01数据集上与当前主流的4种方法进行比较,在使用原始隐写图像训练后,相比于基于U-Net结构的生成式多重对抗隐写算法等其他4种方法,使得当前性能优异的5种隐写分析器平均判别准确率降低了1.6%;在使用对抗图像和增强隐写图像再训练后,相比其他4种方法,仍使得当前性能优异的5种隐写分析器平均判别准确率降低了6.8%。同时也对对抗图像质量进行分析,基于测试集生成的2 000幅对抗图像的平均峰值信噪比(peak signal-tonoise ratio,PSNR)可达到39.925 1 dB,实验结果表明本文提出的隐写网络极大提升了隐写算法的安全性。结论 本文方法在隐写算法安全性领域取得了较优秀的性能,且生成的对抗图像具有很高的视觉质量。