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...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.展开更多
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 (B3...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.展开更多
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...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.展开更多
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 exp...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.展开更多
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 t...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.展开更多
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moti...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。展开更多
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)....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.展开更多
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 impor...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.展开更多
基金supported by the National Natural Science Foundation of China(Key Program),No.11932013the National Natural Science Foundation of China(General Program),No.82272255+2 种基金Armed Police Force High-Level Science and Technology Personnel ProjectThe Armed Police Force Focuses on Supporting Scientific and Technological Innovation TeamsKey Project of Tianjin Science and Technology Plan,No.20JCZDJC00570(all to XC)。
文摘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.
文摘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.
基金supported by National Natural Science Foundation of China(62101088,61801076,61971336)Natural Science Foundation of Liaoning Province(2022-MS-157,2023-MS-108)+1 种基金Key Laboratory of Big Data Intelligent Computing Funds for Chongqing University of Posts and Telecommunications(BDIC-2023-A-003)Fundamental Research Funds for the Central Universities(3132022230).
文摘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.
文摘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.
文摘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.
文摘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。
基金Project supported by the National Natural Science Foundation of China (Grant Nos.12175087 and 12105117)。
文摘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.
基金supported by the National Natural Science Foundation of China,Nos. 82071304 (to QXZ), 81671149 (to QXZ),and 81971179 (to XML)the Natural Science Foundation of Jiangsu Province,Nos. BK20191463 (to XML) and BK20161167 (to QXZ)。
文摘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.
