Nearly all real-world networks are complex networks and usually are in danger of collapse.Therefore,it is crucial to exploit and understand the mechanisms of network attacks and provide better protection for network f...Nearly all real-world networks are complex networks and usually are in danger of collapse.Therefore,it is crucial to exploit and understand the mechanisms of network attacks and provide better protection for network functionalities.Network dismantling aims to find the smallest set of nodes such that after their removal the network is broken into connected components of sub-extensive size.To overcome the limitations and drawbacks of existing network dismantling methods,this paper focuses on network dismantling problem and proposes a neighbor-loop structure based centrality metric,NL,which achieves a balance between computational efficiency and evaluation accuracy.In addition,we design a novel method combining NL-based nodes-removing,greedy tree-breaking and reinsertion.Moreover,we compare five baseline methods with our algorithm on ten widely used real-world networks and three types of model networks including Erd€os-Renyi random networks,Watts-Strogatz smallworld networks and Barabasi-Albert scale-free networks with different network generation parameters.Experimental results demonstrate that our proposed method outperforms most peer methods by obtaining a minimal set of targeted attack nodes.Furthermore,the insights gained from this study may be of assistance to future practical research into real-world networks.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.展开更多
Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central ne...Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the c...In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.展开更多
Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functio...Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.展开更多
Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these...Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.展开更多
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
In this paper, we propose a new centrality algorithm that can simultaneously rank the nodes and layers of multilayer networks, referred to as the MRFNL centrality. The centrality of nodes and layers are obtained by de...In this paper, we propose a new centrality algorithm that can simultaneously rank the nodes and layers of multilayer networks, referred to as the MRFNL centrality. The centrality of nodes and layers are obtained by developing a novel iterative algorithm for computing a set of tensor equations. Under some conditions, the existence and uniqueness of this centrality were proven by applying the Brouwer fixed point theorem. Furthermore, the convergence of the proposed iterative algorithm was established. Finally, numerical experiments on a simple multilayer network and two real-world multilayer networks(i.e., Pierre Auger Collaboration and European Air Transportation Networks) are proposed to illustrate the effectiveness of the proposed algorithm and to compare it to other existing centrality measures.展开更多
In this work we propose a centrality measure for networks, which we refer to as Laplacian centrality, that provides a general framework for the centrality of a vertex based on the idea that the importance (or centrali...In this work we propose a centrality measure for networks, which we refer to as Laplacian centrality, that provides a general framework for the centrality of a vertex based on the idea that the importance (or centrality) of a vertex is related to the ability of the network to respond to the deactivation or removal of that vertex from the network. In particular, the Laplacian centrality of a vertex is defined as the relative drop of Laplacian energy caused by the deactivation of this vertex. The Laplacian energy of network G with?n?vertices is defined as , where ?is the eigenvalue of the Laplacian matrix of G. Other dynamics based measures such as that of Masuda and Kori and PageRank compute the importance of a node by analyzing the way paths pass through a node while our measure captures this information as well as the way these paths are “redistributed” when the node is deleted. The validity and robustness of this new measure are illustrated on two different terrorist social network data sets and 84 networks in James Moody’s Add Health in school friendship nomination data, and is compared with other standard centrality measures.展开更多
AIM: To investigate the functional networks underlying the brain-activity changes of patients with high myopia using the voxel-wise degree centrality(DC) method.METHODS: In total, 38 patients with high myopia(HM...AIM: To investigate the functional networks underlying the brain-activity changes of patients with high myopia using the voxel-wise degree centrality(DC) method.METHODS: In total, 38 patients with high myopia(HM)(17 males and 21 females), whose binocular refractive diopter were-6.00 to-7.00 D, and 38 healthy controls(17 males and 21 females), closely matched in age, sex, and education levels, participated in the study. Spontaneous brain activities were evaluated using the voxel-wise DC method. The receiver operating characteristic curve was measured to distinguish patients with HM from healthy controls. Correlation analysis was used to explore the relationship between the observed mean DC values of the different brain areas and the behavioral performance.RESULTS: Compared with healthy controls, HM patients had significantly decreased DC values in the right inferior frontal gyrus/insula, right middle frontal gyrus, and right supramarginal/inferior parietal lobule(P〈0.05). In contrast, HM patients had significantly increased DC values in the right cerebellum posterior lobe, left precentral gyrus/postcentral gyrus, and right middle cingulate gyrus(P〈0.05). However, no relationship was found between the observed mean DC values of the different brain areas and the behavioral performance(P〉0.05).CONCLUSION: HM is associated with abnormalities in many brain regions, which may indicate the neural mechanisms of HM. The altered DC values may be used as a useful biomarker for the brain activity changes in HM patients.展开更多
In many cases randomness in community detection algorithms has been avoided due to issues with stability. Indeed replacing random ordering with centrality rankings has improved the performance of some techniques such ...In many cases randomness in community detection algorithms has been avoided due to issues with stability. Indeed replacing random ordering with centrality rankings has improved the performance of some techniques such as Label Propagation Algorithms. This study evaluates the effects of such orderings on the Speaker-listener Label Propagation Algorithm or SLPA, a modification of LPA which has already been stabilized through alternate means. This study demonstrates that in cases where stability has been achieved without eliminating randomness, the result of removing random ordering is over fitting and bias. The results of testing seven various measures of centrality in conjunction with SLPA across five social network graphs indicate that while certain measures outperform random orderings on certain graphs, random orderings have the highest overall accuracy. This is particularly true when strict orderings are used in each run. These results indicate that the more evenly distributed solution space which results from complete random ordering is more valuable than the more targeted search that results from centrality orderings.展开更多
The zero-degree calorimeter(ZDC)plays a crucial role toward determining the centrality in the Cooling-Storage-Ring External-target Experiment(CEE)at the Heavy Ion Research Facility in Lanzhou.A boosted decision tree(B...The zero-degree calorimeter(ZDC)plays a crucial role toward determining the centrality in the Cooling-Storage-Ring External-target Experiment(CEE)at the Heavy Ion Research Facility in Lanzhou.A boosted decision tree(BDT)multi-classification algorithm was employed to classify the centrality of the collision events based on the raw features from ZDC such as the number of fired channels and deposited energy.The data from simulated^(238)U+^(238)U collisions at 500 MeV∕u,generated by the IQMD event generator and subsequently modeled using the GEANT4 package,were employed to train and test the BDT model.The results showed the high accuracy of the multi-classification model adopted in ZDC for centrality determination,which is robust against variations in different factors of detector geometry and response.This study demon-strates the good performance of CEE-ZDC in determining the centrality in nucleus-nucleus collisions.展开更多
Road network is a corridor system that interacts with surrounding landscapes,and understanding their interaction helps to develop an optimal plan for sustainable transportation and land use.This study investigates the...Road network is a corridor system that interacts with surrounding landscapes,and understanding their interaction helps to develop an optimal plan for sustainable transportation and land use.This study investigates the relationships between road centrality and landscape patterns in the Wuhan Metropolitan Area,China.The densities of centrality measures,including closeness,betweenness,and straightness,are calculated by kernel density estimation(KDE).The landscape patterns are characterized by four landscape metrics,including percentage of landscape(PLAND),Shannon′s diversity index(SHDI),mean patch size(MPS),and mean shape index(MSI).Spearman rank correlation analysis is then used to quantify their relationships at both landscape and class levels.The results show that the centrality measures can reflect the hierarchy of road network as they associate with road grade.Further analysis exhibit that as centrality densities increase,the whole landscape becomes more fragmented and regular.At the class level,the forest gradually decreases and becomes fragmented,while the construction land increases and turns to more compact.Therefore,these findings indicate that the ability and potential applications of centrality densities estimated by KDE in quantifying the relationships between roads and landscapes,can provide detailed information and valuable guidance for transportation and land-use planning as well as a new insight into ecological effects of roads.展开更多
AIM:To explore the intrinsic brain activity variations in retinal vein occlusion(RVO)subjects by using the voxel-wise degree centrality(DC)technique.METHODS:Twenty-one subjects with RVO and twentyone healthy controls(...AIM:To explore the intrinsic brain activity variations in retinal vein occlusion(RVO)subjects by using the voxel-wise degree centrality(DC)technique.METHODS:Twenty-one subjects with RVO and twentyone healthy controls(HCs)were enlisted and underwent the resting-state functional magnetic resonance imaging(rs-f MRI)examination.The spontaneous cerebrum activity variations were inspected using the DC technology.The receiver operating characteristic(ROC)curve was implemented to distinguish the DC values of RVOs from HCs.The relationships between DC signal of definite regions of interest and the clinical characteristics in RVO group were evaluated by Pearson’s correlation analysis.RESULTS:RVOs showed notably higher DC signals in right superior parietal lobule,middle frontal gyrus and left precuneus,but decreased DC signals in left middle temporal gyrus and bilateral anterior cingulated(BAC)when comparing with HCs.The mean DC value of RVOs in the BAC were negatively correlated with the anxiety and depression scale.CONCLUSION:RVO is associated aberrant intrinsic brain activity patterns in several brain areas including painrelated as well as visual-related regions,which might assist to reveal the latent neural mechanisms.展开更多
A new centrality measure for complex networks, called resource flow centrality, is pro- posed in this paper. This centrality measure is based on the concept of the resource flow in net- works. It not only can be appli...A new centrality measure for complex networks, called resource flow centrality, is pro- posed in this paper. This centrality measure is based on the concept of the resource flow in net- works. It not only can be applied to the connected networks, but also the disconnected networks. Moreover, it overcomes some disadvantages of several common centrality measures. The perform- ance of the proposed measure is compared with some standard centrality measures using a classic dataset and the results indicate the proposed measure performs more reasonably. The statistical dis- tribution of the proposed centrality is investigated by experiments on large scale computer generated graphs and two networks from the real world.展开更多
We present an energy-based method to estimate centrality in electrical networks. Here the energy between a pair of vertices denotes by the effective resistance between them. If there is only one generation and one loa...We present an energy-based method to estimate centrality in electrical networks. Here the energy between a pair of vertices denotes by the effective resistance between them. If there is only one generation and one load, then the centrality of an edge in our method is the difference between the energy of network after deleting the edge and that of the original network. Compared with the local current-flow betweenness on the IEEE 14-bus system, we have an interesting discovery that our proposed centrality is closely related to it in the sense of that the significance of edges under the two measures are very similar.展开更多
Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,...Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.展开更多
基金the National Natural Science Foundation of China under Grants 61871209 and 61901210,in part by Artificial Intelligence and Intelligent Transportation Joint Technical Center of HUST and Hubei Chutian Intelligent Transportation Co.,LTD under project”Intelligent Transportation Operation Monitoring Network and System”.
文摘Nearly all real-world networks are complex networks and usually are in danger of collapse.Therefore,it is crucial to exploit and understand the mechanisms of network attacks and provide better protection for network functionalities.Network dismantling aims to find the smallest set of nodes such that after their removal the network is broken into connected components of sub-extensive size.To overcome the limitations and drawbacks of existing network dismantling methods,this paper focuses on network dismantling problem and proposes a neighbor-loop structure based centrality metric,NL,which achieves a balance between computational efficiency and evaluation accuracy.In addition,we design a novel method combining NL-based nodes-removing,greedy tree-breaking and reinsertion.Moreover,we compare five baseline methods with our algorithm on ten widely used real-world networks and three types of model networks including Erd€os-Renyi random networks,Watts-Strogatz smallworld networks and Barabasi-Albert scale-free networks with different network generation parameters.Experimental results demonstrate that our proposed method outperforms most peer methods by obtaining a minimal set of targeted attack nodes.Furthermore,the insights gained from this study may be of assistance to future practical research into real-world networks.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
文摘Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by Ohio State Start Up FundNational Institutes of Health(NIH)+12 种基金Department of Defense(DoD)Wings for Life Spinal Cord Research Foundation,Wings for Life Spinal Cord Research Foundation(Austria)California Institute of Regenerative Medicine(CIRM)International Spinal Research Trust(United Kingdom)Stanford University Bio-X Program Interdisciplinary Initiatives Seed Grant IIP-7Dennis Chan FoundationKlein Family FundLucile Packard Foundation for Children's HealthStanford Institute for Neuro-Innovation and Translational Neurosciences(SINTN)Saunders Family Neuroscience FundJames Doty Neurosurgery FundHearst Neuroscience FundEileen Bond Research Fund(to GP)。
文摘In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.
基金supported by a grant from the Progressive MS Alliance(BRAVE in MS)Le Grand Portage Fund。
文摘Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
基金supported by the National Natural Science Foundation of China, Nos. 82271411 (to RG), 51803072 (to WLiu)grants from the Department of Finance of Jilin Province, Nos. 2022SCZ25 (to RG), 2022SCZ10 (to WLiu), 2021SCZ07 (to RG)+2 种基金Jilin Provincial Science and Technology Program, No. YDZJ202201ZYTS038 (to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University, No. 2022qnpy11 (to WLuo)The Project of China-Japan Union Hospital of Jilin University, No. XHQMX20233 (to RG)
文摘Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
基金Project supported by the Postgraduate Research and Practice Innovation Program of Jiangsu Province,China(Grant No.AE91313/001/016)the National Natural Science Foundation of China(Grant No.11701097)the Natural Science Foundation of Jiangxi Province,China(Grant No.20161BAB212055)
文摘In this paper, we propose a new centrality algorithm that can simultaneously rank the nodes and layers of multilayer networks, referred to as the MRFNL centrality. The centrality of nodes and layers are obtained by developing a novel iterative algorithm for computing a set of tensor equations. Under some conditions, the existence and uniqueness of this centrality were proven by applying the Brouwer fixed point theorem. Furthermore, the convergence of the proposed iterative algorithm was established. Finally, numerical experiments on a simple multilayer network and two real-world multilayer networks(i.e., Pierre Auger Collaboration and European Air Transportation Networks) are proposed to illustrate the effectiveness of the proposed algorithm and to compare it to other existing centrality measures.
文摘In this work we propose a centrality measure for networks, which we refer to as Laplacian centrality, that provides a general framework for the centrality of a vertex based on the idea that the importance (or centrality) of a vertex is related to the ability of the network to respond to the deactivation or removal of that vertex from the network. In particular, the Laplacian centrality of a vertex is defined as the relative drop of Laplacian energy caused by the deactivation of this vertex. The Laplacian energy of network G with?n?vertices is defined as , where ?is the eigenvalue of the Laplacian matrix of G. Other dynamics based measures such as that of Masuda and Kori and PageRank compute the importance of a node by analyzing the way paths pass through a node while our measure captures this information as well as the way these paths are “redistributed” when the node is deleted. The validity and robustness of this new measure are illustrated on two different terrorist social network data sets and 84 networks in James Moody’s Add Health in school friendship nomination data, and is compared with other standard centrality measures.
基金Supported by National Natural Science Foundation of China (No.81760179 No.81360151)+2 种基金Natural Science Foundation of Jiangxi Province (No.20171BAB205046)Jiangxi Province Education Department Key Foundation (No. GJJ160033)Health Development Planning Commission Science Foundation of Jiangxi Province (No.20185118)
文摘AIM: To investigate the functional networks underlying the brain-activity changes of patients with high myopia using the voxel-wise degree centrality(DC) method.METHODS: In total, 38 patients with high myopia(HM)(17 males and 21 females), whose binocular refractive diopter were-6.00 to-7.00 D, and 38 healthy controls(17 males and 21 females), closely matched in age, sex, and education levels, participated in the study. Spontaneous brain activities were evaluated using the voxel-wise DC method. The receiver operating characteristic curve was measured to distinguish patients with HM from healthy controls. Correlation analysis was used to explore the relationship between the observed mean DC values of the different brain areas and the behavioral performance.RESULTS: Compared with healthy controls, HM patients had significantly decreased DC values in the right inferior frontal gyrus/insula, right middle frontal gyrus, and right supramarginal/inferior parietal lobule(P〈0.05). In contrast, HM patients had significantly increased DC values in the right cerebellum posterior lobe, left precentral gyrus/postcentral gyrus, and right middle cingulate gyrus(P〈0.05). However, no relationship was found between the observed mean DC values of the different brain areas and the behavioral performance(P〉0.05).CONCLUSION: HM is associated with abnormalities in many brain regions, which may indicate the neural mechanisms of HM. The altered DC values may be used as a useful biomarker for the brain activity changes in HM patients.
文摘In many cases randomness in community detection algorithms has been avoided due to issues with stability. Indeed replacing random ordering with centrality rankings has improved the performance of some techniques such as Label Propagation Algorithms. This study evaluates the effects of such orderings on the Speaker-listener Label Propagation Algorithm or SLPA, a modification of LPA which has already been stabilized through alternate means. This study demonstrates that in cases where stability has been achieved without eliminating randomness, the result of removing random ordering is over fitting and bias. The results of testing seven various measures of centrality in conjunction with SLPA across five social network graphs indicate that while certain measures outperform random orderings on certain graphs, random orderings have the highest overall accuracy. This is particularly true when strict orderings are used in each run. These results indicate that the more evenly distributed solution space which results from complete random ordering is more valuable than the more targeted search that results from centrality orderings.
基金This work was supported in part by the National Nature Science Foundation of China(NSFC)(Nos.11927901 and 12175084)the National Key Research and Development Program of China(Nos.2020YFE0202002 and 2022YFA1604900)the Fundamental Research Funds for the Central Universities(No.CCNU22QN005).
文摘The zero-degree calorimeter(ZDC)plays a crucial role toward determining the centrality in the Cooling-Storage-Ring External-target Experiment(CEE)at the Heavy Ion Research Facility in Lanzhou.A boosted decision tree(BDT)multi-classification algorithm was employed to classify the centrality of the collision events based on the raw features from ZDC such as the number of fired channels and deposited energy.The data from simulated^(238)U+^(238)U collisions at 500 MeV∕u,generated by the IQMD event generator and subsequently modeled using the GEANT4 package,were employed to train and test the BDT model.The results showed the high accuracy of the multi-classification model adopted in ZDC for centrality determination,which is robust against variations in different factors of detector geometry and response.This study demon-strates the good performance of CEE-ZDC in determining the centrality in nucleus-nucleus collisions.
基金Under the auspices of National Key Technology Research and Development Program of China(No.2012BAH28B02)
文摘Road network is a corridor system that interacts with surrounding landscapes,and understanding their interaction helps to develop an optimal plan for sustainable transportation and land use.This study investigates the relationships between road centrality and landscape patterns in the Wuhan Metropolitan Area,China.The densities of centrality measures,including closeness,betweenness,and straightness,are calculated by kernel density estimation(KDE).The landscape patterns are characterized by four landscape metrics,including percentage of landscape(PLAND),Shannon′s diversity index(SHDI),mean patch size(MPS),and mean shape index(MSI).Spearman rank correlation analysis is then used to quantify their relationships at both landscape and class levels.The results show that the centrality measures can reflect the hierarchy of road network as they associate with road grade.Further analysis exhibit that as centrality densities increase,the whole landscape becomes more fragmented and regular.At the class level,the forest gradually decreases and becomes fragmented,while the construction land increases and turns to more compact.Therefore,these findings indicate that the ability and potential applications of centrality densities estimated by KDE in quantifying the relationships between roads and landscapes,can provide detailed information and valuable guidance for transportation and land-use planning as well as a new insight into ecological effects of roads.
文摘AIM:To explore the intrinsic brain activity variations in retinal vein occlusion(RVO)subjects by using the voxel-wise degree centrality(DC)technique.METHODS:Twenty-one subjects with RVO and twentyone healthy controls(HCs)were enlisted and underwent the resting-state functional magnetic resonance imaging(rs-f MRI)examination.The spontaneous cerebrum activity variations were inspected using the DC technology.The receiver operating characteristic(ROC)curve was implemented to distinguish the DC values of RVOs from HCs.The relationships between DC signal of definite regions of interest and the clinical characteristics in RVO group were evaluated by Pearson’s correlation analysis.RESULTS:RVOs showed notably higher DC signals in right superior parietal lobule,middle frontal gyrus and left precuneus,but decreased DC signals in left middle temporal gyrus and bilateral anterior cingulated(BAC)when comparing with HCs.The mean DC value of RVOs in the BAC were negatively correlated with the anxiety and depression scale.CONCLUSION:RVO is associated aberrant intrinsic brain activity patterns in several brain areas including painrelated as well as visual-related regions,which might assist to reveal the latent neural mechanisms.
基金Supported by the National Natural Science Foundation of China(61272119,61203372)
文摘A new centrality measure for complex networks, called resource flow centrality, is pro- posed in this paper. This centrality measure is based on the concept of the resource flow in net- works. It not only can be applied to the connected networks, but also the disconnected networks. Moreover, it overcomes some disadvantages of several common centrality measures. The perform- ance of the proposed measure is compared with some standard centrality measures using a classic dataset and the results indicate the proposed measure performs more reasonably. The statistical dis- tribution of the proposed centrality is investigated by experiments on large scale computer generated graphs and two networks from the real world.
文摘We present an energy-based method to estimate centrality in electrical networks. Here the energy between a pair of vertices denotes by the effective resistance between them. If there is only one generation and one load, then the centrality of an edge in our method is the difference between the energy of network after deleting the edge and that of the original network. Compared with the local current-flow betweenness on the IEEE 14-bus system, we have an interesting discovery that our proposed centrality is closely related to it in the sense of that the significance of edges under the two measures are very similar.
基金supported by KAKENHI under grant number 23K08535,22K09274(to MK)。
文摘Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.