Let G be a finite group, H ≤ G and R be a commutative ring with an identity 1R. Let CRG（H）={α ∈ RG｜αh = hα for all h ∈ H）, which is called the centralizer subalgebra of H in RG. Obviously, if H=G then CRG（H...Let G be a finite group, H ≤ G and R be a commutative ring with an identity 1R. Let CRG（H）={α ∈ RG｜αh = hα for all h ∈ H）, which is called the centralizer subalgebra of H in RG. Obviously, if H=G then CRG（H） is just the central subalgebra Z（RG） of RG. In this note, we show that the set of all H- conjugacy class sums of G forms an R-basis of CRG（H）. Furthermore, let N be a normal subgroup of G and γthe natural epimorphism from G to G to G/N. Then γ induces an epimorphism from RG to RG, also denoted by % We also show that if R is a field of characteristic zero, then γ induces an epimorphism from CRG（H） to CRG（H）, that is, 7（CRG（H）） = CRG（H）.展开更多
In this paper,we introduce a new concept of expansiveness,similar to the separating property.Specifically,we consider a compact Riemannian manifold M without boundary and a C^(1)vector field X on M,which generates a f...In this paper,we introduce a new concept of expansiveness,similar to the separating property.Specifically,we consider a compact Riemannian manifold M without boundary and a C^(1)vector field X on M,which generates a flowφ_(t)on M.We say that X is rescaling separating on a compact invariant setΛof X if there is a constantδ>0 such that,for any x,y∈Λ,if d(φ_(t)(x),φ_(t)(y))≤δ∥X(φ_(t)(x))∥for all t∈R,then y∈Orb(x).We prove that if X is rescaling separating onΛand every singularity of X inΛis hyperbolic,then any C^(1)vector field Y,whose flow commutes withφ_(t)onΛ,must be collinear to X onΛ.As applications of this result,we show that the centralizer of a rescaling separating C^(1)vector field without nonhyperbolic singularity is quasi-trivial.We also proved that there is an open and dense set u⊂χ^(1)(M)such that for any star vector fieldχ∈u,the centralizer of X is collinear to X on the chain recurrent set of X.展开更多
Let G be a group.The family of all sets which are closed in every Hausdorf group topology of G form the family of closed sets of a T_(1) topology M_(G) on G called the Markov topology.Similarly,the family of all algeb...Let G be a group.The family of all sets which are closed in every Hausdorf group topology of G form the family of closed sets of a T_(1) topology M_(G) on G called the Markov topology.Similarly,the family of all algebraic subsets of G forms a family of closed sets for another T_(1)topology Z_(G) on G called the Zarski topology.A subgroup H of G is said to be Markov(resp.Zarski)embedded if the equality M_(G|H)=M_(H)(resp.Z_(G|H)=Z_(H))holds.I's proved that an abirary subgroup of a free group is both Zariski and Markov embedded in it.展开更多
In this paper, the authors study the Cohen-Fischman-Westreich's double centralizer theorem for triangular Hopf algebras in the setting of almost-triangular Hopf algebras.
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
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
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
Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may de...Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.展开更多
Let U = Tri（fit, M, B） be a triangular ring, where A and B are unital rings, and M is a faithful （A, B）-bimodule. It is shown that an additive map φ on U is centralized at zero point （i.e., ,φ（A）B = A,φ（B）...Let U = Tri（fit, M, B） be a triangular ring, where A and B are unital rings, and M is a faithful （A, B）-bimodule. It is shown that an additive map φ on U is centralized at zero point （i.e., ,φ（A）B = A,φ（B） = 0 whenever AB = 0） if and only if it is a centralizer. Let 5 ： U →U be an additive map. It is also shown that the following four conditions are equivalent： （1） 5 is specially generalized derivable at zero point, i.e., 5（AB） = δ（A）B ＋ AS（B） - Aδ（I）B whenever AB = 0; （2） 5 is generalized derivable at zero point, i.e., there exist additive maps τ1 and τ2 on U derivable at zero point such that δ（AB） = δ（A）B ＋ Aτ1（B） = τ2（A）B ＋ Aδ（B） whenever AB = 0; （3） δ is a special generalized derivation; （4） δ is a generalized derivation. These results are then applied to nest algebras of Banach space展开更多
Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)re...Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.展开更多
Let H be a Hilbert space with dimH ≥2 and Z ∈ B（H） be an arbitrary but fixed operator. In this paper we show that an additive map （I） ： B（H）→ B（H） satisfies Ф（AB） = Ф（A）B = AФ（B） for any A, B ∈ ...Let H be a Hilbert space with dimH ≥2 and Z ∈ B（H） be an arbitrary but fixed operator. In this paper we show that an additive map （I） ： B（H）→ B（H） satisfies Ф（AB） = Ф（A）B = AФ（B） for any A, B ∈ B（H） with AB = Z if and only if Ф（AB） = Ф（A）B = AФ（B）, A, B ∈ B（H）, that is, （I） is a centralizer. Similar results are obtained for Hilbert space nest algebras. In addition, we show that Ф（A2） = AФ（A） = Ф（A）A for any A ∈ B（H） with A2 = 0 if and only if Ф（A） = AФ（I） = Ф（I）A, A ∈ B（H）, and generalize main results in Linear Algebra and its Application, 450, 243-249 （2014） to infinite dimensional case. New equivalent characterization of centralizers on B（H） is obtained.展开更多
The impact of heavy reduction on dendritic morphology was explored by combining experimental research and numerical simulation in metallurgy,including a detailed three-dimensional(3D)analysis and reconstruction of den...The impact of heavy reduction on dendritic morphology was explored by combining experimental research and numerical simulation in metallurgy,including a detailed three-dimensional(3D)analysis and reconstruction of dendritic solidification structures.Combining scanning electron microscopy and energy-dispersive scanning analysis and ANSYS simulation,the high-precision image processing software Mimics Research was utilized to conduct the extraction of dendritic morphologies.Reverse engineering software NX Imageware was employed for the 3D reconstruction of two-dimensional dendritic morphologies,restoring the dendritic characteristics in three-dimensional space.The results demonstrate that in a two-dimensional plane,dendrites connect with each other to form irregularly shaped“ring-like”structures.These dendrites have a thickness greater than 0.1 mm along the Z-axis direction,leading to the envelopment of molten steel by dendrites in a 3D space of at least 0.1 mm.This results in obstructed flow,confirming the“bridging”of dendrites in three-dimensional space,resulting in a tendency for central segregation.Dense and dispersed tiny dendrites,under the influence of heat flow direction,interconnect and continuously grow,gradually forming primary and secondary dendrites in three-dimensional space.After the completion of dendritic solidification and growth,these microdendrites appear dense and dispersed on the two-dimensional plane,providing the nuclei for the formation of new dendrites.When reduction occurs at a solid fraction of 0.46,there is a noticeable decrease in dendritic spacing,resulting in improved central segregation.展开更多
China has abundant resources of hot dry rocks.However,due to the fact that the evaluation methods for favorable areas are mainly qualitative,and the evaluation indicators and standards are inconsistent,which restrict ...China has abundant resources of hot dry rocks.However,due to the fact that the evaluation methods for favorable areas are mainly qualitative,and the evaluation indicators and standards are inconsistent,which restrict the evaluation efficiency and exploration process of dry hot rocks.This paper is based on the understanding of the geologic features and genesis mechanisms of hot dry rocks in China and abroad.By integrating the main controlling factors of hot dry rock formation,and using index grading and quantification,the fuzzy hierarchical comprehensive method is applied to establish an evaluation system and standards for favorable areas of hot dry rocks.The evaluation system is based on four indicators:heat source,thermal channel,thermal reservoir and cap rock.It includes 11 evaluation parameters,including time of magmatic/volcanic activity,depth of molten mass or magma chamber,distribution of discordogenic faults,burial depth of thermal reservoir,cap rock type and thickness,surface thermal anomaly,heat flow,geothermal gradient,Moho depth,Curie depth,Earthquake magnitude and focal depth.Each parameter is divided into 3 levels.Applying this evaluation system to assess hot dry rock in central Inner Mongolia revealed that Class I favorable zones cover approximately 494 km^(2),while Class II favorable zones span about 5.7×10^(4) km^(2).The Jirgalangtu Sag and Honghaershute Sag in the Erlian Basin,along with Reshuitang Town in Keshiketeng Banner,Reshui Town in Ningcheng County,and Reshuitang Town in Aohan Banner of Chifeng City,are identified as Class I favorable zones for hot dry rock resources.These areas are characterized by high-temperature subsurface molten bodies or magma chambers serving as high-quality heat sources,shallow thermal reservoir depths,and overlying thick sedimentary rock layers acting as caprock.The establishment and application of the evaluation system for favorable areas of hot dry rock are expected to provide new approaches and scientific basis for guiding the practice of selecting hot dry rock areas in China.展开更多
BACKGROUND Long-term chemotherapy for patients with gastric cancer(GC),facilitated by peripherally inserted central catheter(PICC)catheterization,reduces vascular damage and enhances drug delivery efficiency but carri...BACKGROUND Long-term chemotherapy for patients with gastric cancer(GC),facilitated by peripherally inserted central catheter(PICC)catheterization,reduces vascular damage and enhances drug delivery efficiency but carries risks of catheter-related complications.A combination of group psychological nursing and physical mo-vement care significantly mitigates the risk of venous thrombosis and improves psychological well-being,and enhances motor function,underscoring its clinical importance.AIM To assess group psychological and physical movement nursing in preventing venous thrombosis in patients with PICC GC.METHODS Sixty-five GC patients with PICC,admitted from January 2022 to January 2023,were randomly divided into two groups using the lottery method:A control group(n=35,routine nursing)and an observation group(n=30,routine nursing plus psychological nursing and physical movement nursing).Both groups re-ceived continuous care for 2 weeks.Pre-nursing and post-nursing data on psycho-logical state,physical function,chemotherapy-related thrombosis incidence,and cancer-related fatigue were analyzed using SPSS 26.0 and GraphPad Prism 8.0.RESULTS After nursing,both groups showed reduced Hamilton Anxiety Scale scores and increased General Perceived Self-Efficacy Scale scores,with the observation group performing better(P<0.05).The Functional Comprehensive Assessment score for the observation group after nursing was(65.42±2.35)points,lower than the control group’s(62.19±4.33)points(P<0.05).Although no significant difference was observed in the incidence of venous thrombosis between the two groups(χ2=0.815,P=0.367),the observation group had lower incidence.Both groups showed decreased Revised Piper Fatigue Scale scores,with the observation group scoring lower(P<0.05).CONCLUSION Group psychological and physical movement nursing for patients with PICC reduces venous thrombosis risk,improves psychological well-being,cancer-related fatigue,and physical function,making it highly promotable.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
Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central n...The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.展开更多
N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis a...N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.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
基金The NSF(11071155) of Chinathe NSF(2008A03) of Shandong Province
文摘Let G be a finite group, H ≤ G and R be a commutative ring with an identity 1R. Let CRG（H）={α ∈ RG｜αh = hα for all h ∈ H）, which is called the centralizer subalgebra of H in RG. Obviously, if H=G then CRG（H） is just the central subalgebra Z（RG） of RG. In this note, we show that the set of all H- conjugacy class sums of G forms an R-basis of CRG（H）. Furthermore, let N be a normal subgroup of G and γthe natural epimorphism from G to G to G/N. Then γ induces an epimorphism from RG to RG, also denoted by % We also show that if R is a field of characteristic zero, then γ induces an epimorphism from CRG（H） to CRG（H）, that is, 7（CRG（H）） = CRG（H）.
基金Supported by National Key R&D Program of China(Grant No.2022YFA1005801)National Natural Science Foundation of China(Grant No.12071018)the Fundamental Research Funds for the Central Universities。
文摘In this paper,we introduce a new concept of expansiveness,similar to the separating property.Specifically,we consider a compact Riemannian manifold M without boundary and a C^(1)vector field X on M,which generates a flowφ_(t)on M.We say that X is rescaling separating on a compact invariant setΛof X if there is a constantδ>0 such that,for any x,y∈Λ,if d(φ_(t)(x),φ_(t)(y))≤δ∥X(φ_(t)(x))∥for all t∈R,then y∈Orb(x).We prove that if X is rescaling separating onΛand every singularity of X inΛis hyperbolic,then any C^(1)vector field Y,whose flow commutes withφ_(t)onΛ,must be collinear to X onΛ.As applications of this result,we show that the centralizer of a rescaling separating C^(1)vector field without nonhyperbolic singularity is quasi-trivial.We also proved that there is an open and dense set u⊂χ^(1)(M)such that for any star vector fieldχ∈u,the centralizer of X is collinear to X on the chain recurrent set of X.
基金Supported by the Grant-in-Aid for Scientific Research(C)by the Japan Society for the Promotion of Science(20K03615)。
文摘Let G be a group.The family of all sets which are closed in every Hausdorf group topology of G form the family of closed sets of a T_(1) topology M_(G) on G called the Markov topology.Similarly,the family of all algebraic subsets of G forms a family of closed sets for another T_(1)topology Z_(G) on G called the Zarski topology.A subgroup H of G is said to be Markov(resp.Zarski)embedded if the equality M_(G|H)=M_(H)(resp.Z_(G|H)=Z_(H))holds.I's proved that an abirary subgroup of a free group is both Zariski and Markov embedded in it.
基金supported by the National Natural Science Foundation of China(No.11371088)the Natural Science Foundation of Jiangsu Province(No.BK2012736)
文摘In this paper, the authors study the Cohen-Fischman-Westreich's double centralizer theorem for triangular Hopf algebras in the setting of almost-triangular Hopf algebras.
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 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.
基金supported by the Natural Science Foundation of Guangdong Province,Nos.2019A1515010649(to WC),2022A1515012044(to JS)the China Postdoctoral Science Foundation,No.2018M633091(to JS).
文摘Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.
基金supported by National Natural Science Foundation of China (Grant No. 11101250)supported by National Natural Science Foundation of China (Grant No. 11171249)Youth Foundation of Shanxi Province (Grant No. 2012021004)
文摘Let U = Tri（fit, M, B） be a triangular ring, where A and B are unital rings, and M is a faithful （A, B）-bimodule. It is shown that an additive map φ on U is centralized at zero point （i.e., ,φ（A）B = A,φ（B） = 0 whenever AB = 0） if and only if it is a centralizer. Let 5 ： U →U be an additive map. It is also shown that the following four conditions are equivalent： （1） 5 is specially generalized derivable at zero point, i.e., 5（AB） = δ（A）B ＋ AS（B） - Aδ（I）B whenever AB = 0; （2） 5 is generalized derivable at zero point, i.e., there exist additive maps τ1 and τ2 on U derivable at zero point such that δ（AB） = δ（A）B ＋ Aτ1（B） = τ2（A）B ＋ Aδ（B） whenever AB = 0; （3） δ is a special generalized derivation; （4） δ is a generalized derivation. These results are then applied to nest algebras of Banach space
基金supported by the National Natural Science Foundation of China(82204634,82174047,81622051)the Zhejiang Provincial Natural Science Foundation of China(LQ22H280010)the Foundation of Zhejiang Chinese Medical University(2021ZR03).
文摘Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.
基金Supported by National Natural Foundation of China(Grant No.11001194)Provincial International Cooperation Project of Shanxi(Grant No.2014081027–2)
文摘Let H be a Hilbert space with dimH ≥2 and Z ∈ B（H） be an arbitrary but fixed operator. In this paper we show that an additive map （I） ： B（H）→ B（H） satisfies Ф（AB） = Ф（A）B = AФ（B） for any A, B ∈ B（H） with AB = Z if and only if Ф（AB） = Ф（A）B = AФ（B）, A, B ∈ B（H）, that is, （I） is a centralizer. Similar results are obtained for Hilbert space nest algebras. In addition, we show that Ф（A2） = AФ（A） = Ф（A）A for any A ∈ B（H） with A2 = 0 if and only if Ф（A） = AФ（I） = Ф（I）A, A ∈ B（H）, and generalize main results in Linear Algebra and its Application, 450, 243-249 （2014） to infinite dimensional case. New equivalent characterization of centralizers on B（H） is obtained.
基金supported by Open Foundation of the State Key Laboratory of Refractories and Metallurgy(No.G201711)the National Natural Science Foundation of China(Nos.52104317 and 51874001).
文摘The impact of heavy reduction on dendritic morphology was explored by combining experimental research and numerical simulation in metallurgy,including a detailed three-dimensional(3D)analysis and reconstruction of dendritic solidification structures.Combining scanning electron microscopy and energy-dispersive scanning analysis and ANSYS simulation,the high-precision image processing software Mimics Research was utilized to conduct the extraction of dendritic morphologies.Reverse engineering software NX Imageware was employed for the 3D reconstruction of two-dimensional dendritic morphologies,restoring the dendritic characteristics in three-dimensional space.The results demonstrate that in a two-dimensional plane,dendrites connect with each other to form irregularly shaped“ring-like”structures.These dendrites have a thickness greater than 0.1 mm along the Z-axis direction,leading to the envelopment of molten steel by dendrites in a 3D space of at least 0.1 mm.This results in obstructed flow,confirming the“bridging”of dendrites in three-dimensional space,resulting in a tendency for central segregation.Dense and dispersed tiny dendrites,under the influence of heat flow direction,interconnect and continuously grow,gradually forming primary and secondary dendrites in three-dimensional space.After the completion of dendritic solidification and growth,these microdendrites appear dense and dispersed on the two-dimensional plane,providing the nuclei for the formation of new dendrites.When reduction occurs at a solid fraction of 0.46,there is a noticeable decrease in dendritic spacing,resulting in improved central segregation.
基金Supported by PetroChina Prospective and Basic Technological Project(2022DJ5503).
文摘China has abundant resources of hot dry rocks.However,due to the fact that the evaluation methods for favorable areas are mainly qualitative,and the evaluation indicators and standards are inconsistent,which restrict the evaluation efficiency and exploration process of dry hot rocks.This paper is based on the understanding of the geologic features and genesis mechanisms of hot dry rocks in China and abroad.By integrating the main controlling factors of hot dry rock formation,and using index grading and quantification,the fuzzy hierarchical comprehensive method is applied to establish an evaluation system and standards for favorable areas of hot dry rocks.The evaluation system is based on four indicators:heat source,thermal channel,thermal reservoir and cap rock.It includes 11 evaluation parameters,including time of magmatic/volcanic activity,depth of molten mass or magma chamber,distribution of discordogenic faults,burial depth of thermal reservoir,cap rock type and thickness,surface thermal anomaly,heat flow,geothermal gradient,Moho depth,Curie depth,Earthquake magnitude and focal depth.Each parameter is divided into 3 levels.Applying this evaluation system to assess hot dry rock in central Inner Mongolia revealed that Class I favorable zones cover approximately 494 km^(2),while Class II favorable zones span about 5.7×10^(4) km^(2).The Jirgalangtu Sag and Honghaershute Sag in the Erlian Basin,along with Reshuitang Town in Keshiketeng Banner,Reshui Town in Ningcheng County,and Reshuitang Town in Aohan Banner of Chifeng City,are identified as Class I favorable zones for hot dry rock resources.These areas are characterized by high-temperature subsurface molten bodies or magma chambers serving as high-quality heat sources,shallow thermal reservoir depths,and overlying thick sedimentary rock layers acting as caprock.The establishment and application of the evaluation system for favorable areas of hot dry rock are expected to provide new approaches and scientific basis for guiding the practice of selecting hot dry rock areas in China.
文摘BACKGROUND Long-term chemotherapy for patients with gastric cancer(GC),facilitated by peripherally inserted central catheter(PICC)catheterization,reduces vascular damage and enhances drug delivery efficiency but carries risks of catheter-related complications.A combination of group psychological nursing and physical mo-vement care significantly mitigates the risk of venous thrombosis and improves psychological well-being,and enhances motor function,underscoring its clinical importance.AIM To assess group psychological and physical movement nursing in preventing venous thrombosis in patients with PICC GC.METHODS Sixty-five GC patients with PICC,admitted from January 2022 to January 2023,were randomly divided into two groups using the lottery method:A control group(n=35,routine nursing)and an observation group(n=30,routine nursing plus psychological nursing and physical movement nursing).Both groups re-ceived continuous care for 2 weeks.Pre-nursing and post-nursing data on psycho-logical state,physical function,chemotherapy-related thrombosis incidence,and cancer-related fatigue were analyzed using SPSS 26.0 and GraphPad Prism 8.0.RESULTS After nursing,both groups showed reduced Hamilton Anxiety Scale scores and increased General Perceived Self-Efficacy Scale scores,with the observation group performing better(P<0.05).The Functional Comprehensive Assessment score for the observation group after nursing was(65.42±2.35)points,lower than the control group’s(62.19±4.33)points(P<0.05).Although no significant difference was observed in the incidence of venous thrombosis between the two groups(χ2=0.815,P=0.367),the observation group had lower incidence.Both groups showed decreased Revised Piper Fatigue Scale scores,with the observation group scoring lower(P<0.05).CONCLUSION Group psychological and physical movement nursing for patients with PICC reduces venous thrombosis risk,improves psychological well-being,cancer-related fatigue,and physical function,making it highly promotable.
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 the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
基金supported by the National Natural Science Foundation of China,Nos.81901098(to TC),82201668(to HL)Fujian Provincial Health Technology Project,No.2021QNA072(to HL)。
文摘The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.
基金supported by the Natural Science Foundation of Heilongjiang Province of China,Outstanding Youth Foundation,No.YQ2022H003 (to DW)。
文摘N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.
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.
