Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS,a Natural Vasoprotective Combination,for the Phytotherapy of Coronary Artery Disease

Phytotherapy offers obvious advantages in the intervention of Coronary Artery Disease (CAD), but it is difficult to clarify the working mechanisms of the medicinal materials it uses. DGS is a natural vasoprotective combination that was screened out in our previous research, yet its potential components and mechanisms are unknown. Therefore, in this study, HPLC-MS and network pharmacology were employed to identify the active components and key signaling pathways of DGS. Transgenic zebrafish and HUVECs cell assays were used to evaluate the effectiveness of DGS. A total of 37 potentially active compounds were identified that interacted with 112 potential targets of CAD. Furthermore, PI3K-Akt, MAPK, relaxin, VEGF, and other signal pathways were determined to be the most promising DGS-mediated pathways. NO kit, ELISA, and Western blot results showed that DGS significantly promoted NO and VEGFA secretion via the upregulation of VEGFR2 expression and the phosphorylation of Akt, Erk1/2, and eNOS to cause angiogenesis and vasodilation. The result of dynamics molecular docking indicated that Salvianolic acid C may be a key active component of DGS in the treatment of CAD. In conclusion, this study has shed light on the network molecular mechanism of DGS for the intervention of CAD using a network pharmacology-driven strategy for the first time to aid in the intervention of CAD.     

An Integrated Mass Spectrometry-Based Glycomics-Driven Glycoproteomics Analytical Platform to Functionally Characterize Glycosylation Inhibitors

Cancer progression is linked to aberrant protein glycosylation due to the overexpression of several glycosylation enzymes. These enzymes are underexploited as potential anticancer drug targets and the development of rapid-screening methods and identification of glycosylation inhibitors are highly sought. An integrated bioinformatics and mass spectrometry-based glycomics-driven glycoproteomics analysis pipeline was performed to identify an N-glycan inhibitor against lung cancer cells. Combined network pharmacology and in silico screening approaches were used to identify a potential inhibitor, pictilisib, against several glycosylation-related proteins, such as Alpha1-6FucT, GlcNAcT-V, and Alpha2,6-ST-I. A glycomics assay of lung cancer cells treated with pictilisib showed a significant reduction in the fucosylation and sialylation of N-glycans, with an increase in high mannose-type glycans. Proteomics analysis and in vitro assays also showed significant upregulation of the proteins involved in apoptosis and cell adhesion, and the downregulation of proteins involved in cell cycle regulation, mRNA processing, and protein translation. Site-specific glycoproteomics analysis further showed that glycoproteins with reduced fucosylation and sialylation were involved in apoptosis, cell adhesion, DNA damage repair, and chemical response processes. To determine how the alterations in N-glycosylation impact glycoprotein dynamics, modeling of changes in glycan interactions of the ITGA5–ITGB1 (Integrin alpha 5-Integrin beta-1) complex revealed specific glycosites at the interface of these proteins that, when highly fucosylated and sialylated, such as in untreated A549 cells, form greater hydrogen bonding interactions compared to the high mannose-types in pictilisib-treated A549 cells. This study highlights the use of mass spectrometry to identify a potential glycosylation inhibitor and assessment of its impact on cell surface glycoprotein abundance and protein–protein interaction.     

Prisoner’s Dilemma Game with Cooperation-Defection Dominance Strategies on Correlational Multilayer Networks

As multilayer networks are widely applied in modern society, numerous studies have shown the impact of a multilayer network structure and the network nature on the proportion of cooperators in the network. In this paper, we use Barabási–Albert scale-free networks (BA) and Watts and Strogatz networks (WS) to build a multilayer network structure, and we propose a new strategy-updating rule called “cooperation-defection dominance”, which can be likened to dominant and recessive traits in biogenetics. With the newly constructed multilayer network structure and the strategy-updating rules, based on the simulation results, we find that in the BA-BA network, the cooperation dominance strategy can make the networks with different rs show a cooperative trend, while the defection dominance strategy only has an obvious effect on the network cooperation with a larger r. When the BA network is connected to the WS network, we find that the effect of strategy on the proportion of cooperators in the network decreases, and the main influencing factor is the structure of the network. In the three-layer network, the cooperation dominance strategy has a greater impact on the BA network, and the proportion of the cooperators is enhanced more than under the natural evolution strategy, but the promotion effect is still smaller than that of the two-layer BA network because of the WS network. Under the defection dominance strategy, the WS layer appears different from the first two strategies, and we conclude through simulation that when the payoff parameter is at the middle level, its cooperator proportion will be suppressed, and we deduce that the proportion of cooperators and defectors, as well as the payoff, play an important role.     

Adversarial Data Hiding in Digital Images

In recent studies of generative adversarial networks (GAN), researchers have attempted to combine adversarial perturbation with data hiding in order to protect the privacy and authenticity of the host image simultaneously. However, most of the studied approaches can only achieve adversarial perturbation through a visible watermark; the quality of the host image is low, and the concealment of data hiding cannot be achieved. In this work, we propose a true data hiding method with adversarial effect for generating high-quality covers. Based on GAN, the data hiding area is selected precisely by limiting the modification strength in order to preserve the fidelity of the image. We devise a genetic algorithm that can explore decision boundaries in an artificially constrained search space to improve the attack effect as well as construct aggressive covert adversarial samples by detecting “sensitive pixels” in ordinary samples to place discontinuous perturbations. The results reveal that the stego-image has good visual quality and attack effect. To the best of our knowledge, this is the first attempt to use covert data hiding to generate adversarial samples based on GAN.     

Forecasting COVID-19 Epidemic Trends by Combining a Neural Network with Rt Estimation

On 31 December 2019, a cluster of pneumonia cases of unknown etiology was reported in Wuhan (China). The cases were declared to be Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 has been defined as SARS Coronavirus 2 (SARS-CoV-2). Some countries, e.g., Italy, France, and the United Kingdom (UK), have been subjected to frequent restrictions for preventing the spread of infection, contrary to other ones, e.g., the United States of America (USA) and Sweden. The restrictions afflicted the evolution of trends with several perturbations that destabilized its normal evolution. Globally, Rt has been used to estimate time-varying reproduction numbers during epidemics. Methods: This paper presents a solution based on Deep Learning (DL) for the analysis and forecasting of epidemic trends in new positive cases of SARS-CoV-2 (COVID-19). It combined a neural network (NN) and an Rt estimation by adjusting the data produced by the output layer of the NN on the related Rt estimation. Results: Tests were performed on datasets related to the following countries: Italy, the USA, France, the UK, and Sweden. Positive case registration was retrieved between 24 February 2020 and 11 January 2022. Tests performed on the Italian dataset showed that our solution reduced the Mean Absolute Percentage Error (MAPE) by 28.44%, 39.36%, 22.96%, 17.93%, 28.10%, and 24.50% compared to other ones with the same configuration but that were based on the LSTM, GRU, RNN, ARIMA (1,0,3), and ARIMA (7,2,4) models, or an NN without applying the Rt as a corrective index. It also reduced MAPE by 17.93%, the Mean Absolute Error (MAE) by 34.37%, and the Root Mean Square Error (RMSE) by 43.76% compared to the same model without the adjustment performed by the Rt. Furthermore, it allowed an average MAPE reduction of 5.37%, 63.10%, 17.84%, and 14.91% on the datasets related to the USA, France, the UK, and Sweden, respectively.     

Conserved Control Path in Multilayer Networks

The determination of directed control paths in complex networks is important because control paths indicate the structure of the propagation of control signals through edges. A challenging problem is to identify them in complex networked systems characterized by different types of interactions that form multilayer networks. In this study, we describe a graph pattern called the conserved control path, which allows us to model a common control structure among different types of relations. We present a practical conserved control path detection method (CoPath), which is based on a maximum-weighted matching, to determine the paths that play the most consistent roles in controlling signal transmission in multilayer networks. As a pragmatic application, we demonstrate that the control paths detected in a multilayered pan-cancer network are statistically more consistent. Additionally, they lead to the effective identification of drug targets, thereby demonstrating their power in predicting key pathways that influence multiple cancers.     

An Improvement to Conformer-Based Model for High-Accuracy Speech Feature Extraction and Learning

Owing to the loss of effective information and incomplete feature extraction caused by the convolution and pooling operations in a convolution subsampling network, the accuracy and speed of current speech processing architectures based on the conformer model are influenced because the shallow features of speech signals are not completely extracted. To solve these problems, in this study, we researched a method that used a capsule network to improve the accuracy of feature extraction in a conformer-based model, and then, we proposed a new end-to-end model architecture for speech recognition. First, to improve the accuracy of speech feature extraction, a capsule network with a dynamic routing mechanism was introduced into the conformer model; thus, the structural information in speech was preserved, and it was input to the conformer blocks via sequestered vectors; the learning ability of the conformed-based model was significantly enhanced using dynamic weight updating. Second, a residual network was added to the capsule blocks, thus, the mapping ability of our model was improved and the training difficulty was reduced. Furthermore, the bi-transformer model was adopted in the decoding network to promote the consistency of the hypotheses in different directions through bidirectional modeling. Finally, the effectiveness and robustness of the proposed model were verified against different types of recognition models by performing multiple sets of experiments. The experimental results demonstrated that our speech recognition model achieved a lower word error rate without a language model because of the higher accuracy of speech feature extraction and learning using our model architecture with a capsule network. Furthermore, our model architecture benefited from the advantage of the capsule network and the conformer encoder, and also has potential for other speech-related applications.     

出境旅游网络关注度时空演变及影响因素研究——以泰国为例

网络关注度是测量潜在旅游者对目的地旅游关注情况及需求变化的重要手段之一。基于百度指数,以我国31个省（区、市）（不含港、澳、台）的泰国旅游网络关注度为研究对象,运用季节性强度指数、地理集中度指数、赫芬达尔-赫希曼指数、地理探测器等方法,探讨我国居民对泰国旅游网络关注度的时空演化规律及其影响因素。结果表明：从时序演化上看,2011—2019年泰国旅游网络关注度呈波动上升态势,可划分为快速上升期和平稳发展期2个阶段,地区季节性差异显著,3月、7月、12月为泰国旅游网络关注度的高峰时段;从空间分异上看,泰国旅游网络关注度空间分异变化不大,空间集聚趋于分散状态,整体呈“东高-西低”的阶梯状递减特征,高关注度地区主要集中在东部地区及四川省,低关注度地区则主要分布于除四川省外的西部省份;从影响因素上看,经济发展水平（人均可支配收入、GDP）、交通便利程度、贸易开放度以及国际旅游开放度共同影响泰国旅游网络关注度的空间分布格局。     

Anion-controlled geometrically different Cu(II) ion-based coordination polymers and green synthetic route for copper nanoparticles: a combined experimental and computational insight

Abstract

The Cu(II) ion-based polymeric complexes [Cu(2,2′-bpy).(N₃)₂]_n (I), [Cu₂(2,2′-bpy)₂.(N₃)₄]_n (II), and monomeric complex [Cu(2,2′-bpy).(NO₃)₂].5H₂O (III) have been synthesized with rigid (–N₃) and aromatic (2,2′-bpy = 2,2′-bipyridyl) ligand. The rigid azide group is responsible for the formation of 1-D extended structures in complexes I and II where as in the case of complex III, a monomeric complex is formed due to lack of a bridging group like –N₃, resulting in limitation in dimensionality. The thermal stability of the 1-D complexes is comparatively higher than monomeric complex III. Hirshfeld surface analysis has also been applied to investigate other weak interactions and compared with the results from single-crystal X-ray data. Due to the presence of paramagnetic metal centers and long metal···metal distances in complexes I and II and presence of lattice water molecules in complex III, decrease in luminescence intensities have been observed. To attain further insights into the aforementioned interesting species, some chemical concepts such as highest occupied molecular orbital–lowest unoccupied molecular orbital gap, electronic chemical potential, chemical hardness, and electrophilicity index, identified as a derivative of electronic energy, have also been emphasized employing the quantum chemical calculations in the framework of the density functional theory method using the M06-2X/ 6-31G** level of study. Further, these complexes have been used to synthesize copper nanoparticles by applying a green synthetic route.     

基于改进U-Net的量子点STM图像分割

为提升量子点图像分割精度,降低特征识别误差,提出一种基于改进U-Net的量子点图像分割方法.首先,在预处理阶段,设计了以色彩通道为权值的灰度化算法,以提升后续分割效果.其次,在STM图像分割部分,在原始U-Net结构上引入中间过渡层以均衡网络各层特征.而后,建立数据集,并通过实验对比不同分割算法的精确度、召回率、F-measure.最后,将分割算法应用于量子点的特征识别,并测试了不同分割方式对应用的影响.实验结果显示,改进灰度化方法保留细节信息丰富,明显提升了量子点分割精度;改进U-Net的平均精确率、召回率、F-measure相较原始网络分别提升了13.83%、2.16%、8.13%.同时,实验数据表明由于分割精度的提升,量子点数量、纵横比等特征参数的识别更加精确.