C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

基于3D-motif法的刮研表面形貌表征

针对刮研表面微观特性和功能机理研究中缺少表面形貌量化表征方法的问题,采用3D-motif法对刮研表面形貌进行表征。使用LI-3型接触式三维表面形貌测量仪对刮研表面进行测量,并利用三维点云数据生成刮研表面的二维灰度图像。然后,根据3D-motif法中集水盆地的定义,采用分水岭算法对刮研表面的灰度图像进行motif分割与合并。以不同精度等级的刮研表面的整体纹理区域motif分割结果为对象,定义了特征显著度并提取计算了刮研表面在2种不同面积尺度(25 mm^(2)和0.25 mm^(2))上的深度、面积、方向角、各向异性率、扁平系数和特征显著度等6项motif参数。结合部分motif参数的分布情况和motif数量的变化趋势,从形貌特征的尺寸和形态两个方面对刮研表面进行了表征和分析,实现了以较少参数完整表征刮研表面的三维形貌。研究结果可为后续刮研表面微观特性的深入分析提供理论基础。

基于Motif的图采样算法

图采样通过对图数据进行约简操作,获得比原图的规模更小的图结构,进而服务于图谱分析、图可视化等下游任务.现有的图采样算法侧重于保留图中显著的结构特征而忽略了节点属性,导致采样图在许多下游任务如频繁模式挖掘等,难以取得预期效果.为此,提出基于Motif的节点有偏采样算法(Motif-Based Node Biased Sampling,MNBS),利用频繁Motif结构重新定义图中节点的重要性,随后进行有偏节点采样,实现融合节点属性与结构特征的采样.为了快速识别频繁Motif模式,设计了具有“提前终止”特性的Motif模式快速发现算法(Fast Motif-Pattern Discovery,FMPD),能高效且准确地发现Motif模式以支持图采样.实验表明,MNBS采样算法在多项指标上优于其他基线算法,其对数归一化累积组相关性指标平均降低0.54,使用包含“提前终止”特性策略的FMPD算法的时间消耗和内存消耗比基线算法分别降低56.1%和29.8%.

Multi-layer network embedding on scc-based network with motif

Interconnection of all things challenges the traditional communication methods,and Semantic Communication and Computing(SCC)will become new solutions.It is a challenging task to accurately detect,extract,and represent semantic information in the research of SCC-based networks.In previous research,researchers usually use convolution to extract the feature information of a graph and perform the corresponding task of node classification.However,the content of semantic information is quite complex.Although graph convolutional neural networks provide an effective solution for node classification tasks,due to their limitations in representing multiple relational patterns and not recognizing and analyzing higher-order local structures,the extracted feature information is subject to varying degrees of loss.Therefore,this paper extends from a single-layer topology network to a multi-layer heterogeneous topology network.The Bidirectional Encoder Representations from Transformers(BERT)training word vector is introduced to extract the semantic features in the network,and the existing graph neural network is improved by combining the higher-order local feature module of the network model representation network.A multi-layer network embedding algorithm on SCC-based networks with motifs is proposed to complete the task of end-to-end node classification.We verify the effectiveness of the algorithm on a real multi-layer heterogeneous network.

Docking of Human Band 3 Anion Transporter Proteins with Their Plasmodium falciparum Interactors Based on Short Linear Motifs

Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. Protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3AT) protein is considered the main invasive pathway for the parasite in erythrocytes that causes clinical symptoms for malaria in humans. The interactions between P. falciparum parasites and erythrocytes along this receptor have previously been explored. Short linear motifs (SLIMs) are short linear mediator sequences that involve several biological processes, acting as mediators of protein interactions identifiable by computational tools such as SLiMFinder. For a given protein, the identification of SLIMs allows predicting its interactors. Using the SLIMs approach, protein-protein interaction network analyses between P. falciparum and its human host, were used to identify a tryptophan-rich protein, A5K5E5_PLAVS as an essential interactor of B3AT. To better understand the interaction mechanism, a guided protein-protein docking approach based on SLIM motifs was performed for human B3AT and A5K5E5_PLAVS. The highlights of this important interaction between P. falciparum and its human host have the potential to pave the way to identify new therapeutic candidates.

Targeting neuronal PAS domain protein 2 and KN motif/ankyrin repeat domains 1:Advances in type 2 diabetes therapy

This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore their potential as therapeutic targets,and discuss the implications for new treatment strategies.We offer valuable insights into relevant gene regulation and cellular mechanisms relevant for the targeted management of T2D.

The Classic Shaping of Typical Female Images by Mulan Motif in Historical Times-Historical Review and Textual Sorting of the Motif

The image of Mulan is well known to the public as an important symbol in the dissemination of Chinese excellent traditional culture.This paper aims to summarise the mother-title from traditional canonical texts,to explore the content and value of sustainable IP development,and to study a large number of derivatives with the image of Mulan as the mother-title,based on the wide circulation of the prototype of the mother-title“The Poem of Mulan”(木兰辞)and the positive values conveyed by the content.Through the processing and imagination of scholars and writers on the mother text in the past generations,the image of Mulan has gradually formed a relatively stable cultural communication theme in the process of dissemination in China’s historical period,and many adaptations with international influence based on the mother title of Mulan have emerged in the foreign dissemination,so through the combing and summarisation of the textual works of various periods both at home and abroad,we will dig out the textual transmission of the mother title of Mulan,which is representative of the mother title of China’s excellent traditional culture,and the development of the Chinese spiritual core.The Development of the Chinese Spiritual Kernel.This paper adopts research methods such as documentary evidence method and discourse analysis to show the textual flow of Mulan’s parent theme in a more diversified form.

基于motif连通性的社区搜索方法

社区搜索的目标是从数据图中得到包含查询顶点的紧密子图,在社会学、生物学等领域有着广泛应用。针对现有基于子图连通性的社区模型的基础连通结构都是完全连通图,无法满足实际应用中用户对社区结构多样性的需求的问题,提出一种基于motif连通性的社区搜索方法,其中包括基于motif连通性的社区(MCC)模型以及两个相应的社区搜索算法——MPCS(Motif-Processed Community Search)算法和基于MP-index的社区搜索算法。MCC模型可以协助用户自由指定社区的基础连通结构,MPCS算法可以用来解决MCC的搜索问题。此外,提出两个分别针对motif实例搜索过程及所属社区判断过程的剪枝优化技术。最后,设计了MP-index以避免社区搜索过程中的冗余遍历操作。在多个真实数据集上进行实验的结果表明:剪枝优化可以使MPCS算法的耗时减少60%~85%,而基于MP-index的社区搜索算法相较于加入剪枝优化的MPCS算法,效率提升普遍达到了2~3个数量级。可见,所提方法在商品推荐和社交网络等问题上有着实际应用价值。

Influence of coupling asymmetry on signal amplification in a three-node motif

The three-node feedforward motif has been revealed to function as a weak signal amplifier. In this motif, two nodes(input nodes) receive a weak input signal and send it unidirectionally to the third node(output node). Here, we change the motif's unidirectional couplings(feedforward) to bidirectional couplings(feedforward and feedback working together).We find that a small asymmetric coupling, in which the feedforward effect is stronger than the feedback effect, may enable the three-node motif to go through two distinct dynamic transitions, giving rise to a double resonant signal response. We present an analytical description of the double resonance, which agrees with the numerical findings.

人端粒i-motif:结构、识别和生物学功能

人端粒i-motif是由人端粒末端富含胞嘧啶(cytosine,C)的核酸序列形成的特殊高级结构,在端粒重复序列RNA(telomeric repeat-containing RNA,TERRA)转录调控、端粒功能维持和端粒酶活性抑制等方面发挥重要作用。端粒i-motif与多种癌症的发生密切相关,是癌症治疗的一个新靶点。相对于核酸G-四链体等高级结构,端粒i-motif稳定性较差,且受溶液pH、离子状态和拥挤环境等的影响,其在近中性的生理环境下能否稳定形成,长久以来存在争议。采用体外筛选的小分子配体特异性识别并稳定端粒i-motif,为探究该结构的生物学功能以及以端粒为靶点的癌症治疗提供了新策略,是目前的研究热点。但相对于其他核酸高级结构,目前所报道的端粒i-motif特异性配体分子仍较为匮乏。因此,本文将简要介绍i-motif结构的发现历程及其结构特征,并着重对体外环境下人端粒i-motif稳定性的影响因素,以及目前已报道的端粒i-motif配体分子及其生物学功能和调控机制等进行综述。文章内容将为近生理条件下端粒i-motif的结构研究和以其为靶点的特异性配体筛选提供基础,同时也为人端粒相关的癌症机制探究和治疗策略开发等提供思路与方向。

Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke

We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.

三维motif方法及其对微观形貌的表征

采用分水岭算法得到三维粗糙度motif.提出最小面积选择原则对粗糙度motif进行初始合并,去除被认为是噪音的非显著motif.通过溢出点面积阀值对粗糙度motif进行进一步的合并及多等级的分析,同时采用高度判断标准以防止对含有公共显著峰的2个motif进行合并.最后对扫描隧道显微镜所扫得的C(100)面进行分析,得到了该表面的motif参数,分析该表面的纹理,展示了该方法的独到之处,并对三维motif方法波动特性进行了分析.

表面形貌的Motif评定方法及其发展

Motif方法是一种新的表面形貌评定方法 ,通过设定不同的阈值 ,可以将波度和表面粗糙度分离开来 ,它强调大的轮廓峰和谷对功能的影响 ,在评定中选取了重要的轮廓特征 ,而忽略了不重要的特征。介绍了 2维 Mo-tif的参数和合并条件 ,然后对 3维 Motif方法的定义、评定参数及算法等进行了综述 ,并提出了推广这一评定方法需要注意的问题。

Motif识别算法简介及软件性能研究

Motif在转录和后转录水平的基因表达调控中起着重要的作用。目前,识别Motif的算法和相应的软件已有不少,但是却鲜有对各种算法及软件性能共同评测的研究和报告。介绍了算法的分类以及三种常见的Mo-tif识别算法W ordup,MM和G ibbs采样,并对A lignACE,MEME,MotifSampler,W eeder等13种Motif寻找软件进行性能比较分析。通过生物学意义的研究和性能比较结果可以得出:由于唯有W eeder算法考虑了Motif保守核心位置,因而它在各种软件中识别效果较好;大部分算法只考虑简单而且短的Motif,所以各种软件对酵母菌这种单细胞生物的Motif识别性能比多细胞生物要高。

基于邻域分析的3D-motif表面评定算法研究

对当前几种主要的3D-motif评定方法做出简述,分析了连续曲面离散化后的拓扑矛盾的解决方法,并基于邻域分析的算法编制程序,得到分割过程中的几个特征表面,实现对三维表面形貌的motif分割和参数提取,并讨论了表面形貌研究对微机械的摩擦润滑性能的重要性。

合金韧窝断口微观形貌的扫描白光干涉三维检测重构及Motif表征

针对30CrMnSiA合金韧窝断口复杂的表面特征,运用扫描白光干涉法检测微观形貌。系统采用Linnik结构,并通过空间频域分析算法重建断口表面三维形貌,试验中扫描行程达120μm,纵向检测精度优于5 nm,频域分析表现出很强的位相提取和噪声抑制能力。研究韧窝断口的三维Motif表征方法,提出包含深度、长度、宽度、面积、方向角和各向异性率等6参数的定义,以及基于面积和深度阈值的合并算法。考虑到韧窝三维形态的各向异性,对基于纵横比的表面微观粗糙度定义进行修正。采用3D-Motif法对试验获得的断口三维形貌进行表面纹理分割,提取韧窝个体特征参数和统计数据,其中测得断口表面微观粗糙度为0.15～0.70,从而为定量化研究材料的断裂机理提供客观依据。

基于嵌入式系统的Motif图形界面开发技术研究

针对应用于国防领域的国内某特种车辆对显控系统的具体功能需求,讨论了在嵌入式实时操作系统VxWorks的基础上利用Motif库作为工具开发图形用户界面的相关技术。从建立基于Tornado的嵌入式应用软件交叉开发环境入手,总结出了XWindow/Motif程序接口及其代码的调试框架,研究了在嵌入式图形用户界面实际开发过程中所遇到的具体技术难题,并通过解决这些技术问题,最终实现了对VxWorks在图形用户界面开发方面的功能扩展。

X-Windows/Motif下应用软件中文界面的实现技术

Ｘ－Ｗｉｎｄｏｗｓ／Ｍｏｔｉｆ是一个符合国际开放标准且应用非常广泛的图形开发环境。在其环境下实现应用程序人－机界面的中文化问题在国内已日趋重要。本文介绍了在Ｘ－Ｗｉｎｄｏｗｓ／Ｍｏｔｉｆ环境下开发应用程序中文界面的一些方法。

MOTIF合并算法研究

MOTIF合并算法本质上是一种递归算法,因此给程序的设计带来了一定的复杂性。文中详细分析了MOTIF合并算法的设计要点,给出了算法的伪代码,并通过具体的实例来演示了算法的评定结果。

Motif环境下的交互式监控图形生成技术

本文探讨了Motif环境下，监控图形交互生成与批量化生产的问题，阐述了开放环境下监控图形生成工具开发的必要性，分析了生成工具与实时系统的关系，从监视、控制两方面论述了生成工具的设计思想，并简要介绍了图形生成工具IPM的设计及功能。