Understanding the spectrum of non-motor symptoms in multiple sclerosis:insights from animal models

Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic,physically debilitating neurological disorder.In addition to experiencing motor disability,patients with multiple sclerosis also experience a variety of nonmotor symptoms,including cognitive deficits,anxiety,depression,sensory impairments,and pain.However,the pathogenesis and treatment of such non-motor symptoms in multiple scle rosis are still under research.Preclinical studies for multiple sclerosis benefit from the use of disease-appropriate animal models,including experimental autoimmune encephalomyelitis.Prior to understanding the pathophysiology and developing treatments for non-motor symptoms,it is critical to chara cterize the animal model in terms of its ability to replicate certain non-motor features of multiple sclerosis.As such,no single animal model can mimic the entire spectrum of symptoms.This review focuses on the non-motor symptoms that have been investigated in animal models of multiple sclerosis as well as possible underlying mechanisms.Further,we highlighted gaps in the literature to explain the nonmotor aspects of multiple sclerosis in expe rimental animal models,which will serve as the basis for future studies.

P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis

Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

基于Ansys的笼型感应电动机优化设计

针对感应电动机设计过程中需要解决降低电机损耗高、工作效率低、功率因数小和操作特性差等问题,设计了一台额定功率20 kW,额定转速3000 r/min的笼型感应电动机,该设计采用Ansys EM中的RMxprt模块对感应电机进行快速建模和有限元分析,优化电机参数后利用Ansys Motor Cad对所设计的感应电机进行电磁场和温度场的耦合仿真.仿真结果表明,和国内外相同类型的感应电机相比,本文设计的感应电动机具有更高的效率,同时损耗和铁心温度也得到降低.

Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive function.While heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and function.Methods:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,respectively.In a separate trial,blended ice was ingested before and during exercise as a cooling strategy.Data were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging techniques.Results:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia.Executive function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex.Conversely,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural perturbations.Conclusion:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.

Origin of tradeoff between movement velocity and attachment duration of kinesin motor on a microtubule

Kinesin-1 motor protein is a homodimer containing two identical motor domains connected by a common long coiledcoil stalk via two flexible neck linkers. The motor can step on a microtubule with a velocity of about 1 μm·s-1and an attachment duration of about 1 s under physiological conditions. The available experimental data indicate a tradeoff between velocity and attachment duration under various experimental conditions, such as variation of the solution temperature,variation of the strain between the two motor domains, and so on. However, the underlying mechanism of the tradeoff is unknown. Here, the mechanism is explained by a theoretical study of the dynamics of the motor under various experimental conditions, reproducing quantitatively the available experimental data and providing additional predictions. How the various experimental conditions lead to different decreasing rates of attachment duration versus velocity is also explained.

Collective Molecular Machines: Multidimensionality and Reconfigurability

Molecular machines are key to cellular activity where they are involved in converting chemical and light energy into efficient mechanical work.During the last 60 years,designing molecular structures capable of generating unidirectional mechanical motion at the nanoscale has been the topic of intense research.Effective progress has been made,attributed to advances in various fields such as supramolecular chemistry,biology and nanotechnology,and informatics.However,individual molecular machines are only capable of producing nanometer work and generally have only a single functionality.In order to address these problems,collective behaviors realized by integrating several or more of these individual mechanical units in space and time have become a new paradigm.In this review,we comprehensively discuss recent developments in the collective behaviors of molecular machines.In particular,collective behavior is divided into two paradigms.One is the appropriate integration of molecular machines to efficiently amplify molecular motions and deformations to construct novel functional materials.The other is the construction of swarming modes at the supramolecular level to perform nanoscale or microscale operations.We discuss design strategies for both modes and focus on the modulation of features and properties.Subsequently,in order to address existing challenges,the idea of transferring experience gained in the field of micro/nano robotics is presented,offering prospects for future developments in the collective behavior of molecular machines.

A Loss-model-based Efficiency Optimization Control Method for Induction Traction System of High-speed Train under Emergency Self-propelled Mode

Increasing attention has been paid to the efficiency improvement of the induction traction system of high-speed trains due to the high demand for energy saving. In emergency self-propelled mode, however, the dc-link voltage and the traction power of the motor are significantly reduced, resulting in decreased traction efficiency due to the low load and low speed operations. Aiming to tackle this problem, a novel efficiency improved control method is introduced to the emergency mode of high-speed train traction system in this paper. In the proposed method, a total loss model of induction motor considering the behaviors of both iron and copper loss is established. An improved iterative algorithm with decreased computational burden is then introduced, resulting in a fast solving of the optimal flux reference for loss minimization at each control period. In addition, considering the parameter variation problem due to the low load and low speed operations, a parameter estimation method is integrated to improve the controller's robustness. The effectiveness of the proposed method on efficiency improvement at low voltage and low load conditions is demonstrated by simulated and experimental results.

Pathological mechanisms of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amyotrophic lateral sclerosis is still a long one.According to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways.The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis.Here,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis.In addition,we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis.Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.

FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.

Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Symmetric Brownian motor subjected to Lévy noise

In the past few years,attention has mainly been focused on the symmetric Brownian motor(BM)with Gaussian noises,whose current and energy conversion efficiency are very low.Here,we investigate the operating performance of the symmetric BM subjected to Lévy noise.Through numerical simulations,it is found that the operating performance of the motor can be greatly improved in asymmetric Lévy noise.Without any load,the Lévy noises with smaller stable indexes can let the motor give rise to a much greater current.With a load,the energy conversion efficiency of the motor can be enhanced by adjusting the stable indexes of the Lévy noises with symmetry breaking.The results of this research are of great significance for opening up BM’s intrinsic physical mechanism and promoting the development of nanotechnology.

Device-assisted enteroscopy: Are we ready to dismiss the spiral?

Motorized spiral enteroscopy(MSE)is the latest advance in device-assisted enteroscopy.Adverse events related to MSE were discussed in a recent large systematic review and meta-analysis and were directly compared with those of balloon enteroscopy in a case-matched study and a randomized controlled trial.Following the real-life application of MSE,an unexpected safety issue emerged regarding esophageal injury and the technique has been withdrawn from the global market,despite encouraging results in terms of diagnostic and therapeutic yield.We conducted an Italian multicenter real-life prospective study,which was prematurely terminated after the withdrawal of MSE from the market.The primary goals were the evaluation of MSE performance(both diagnostic and therapeutic)and its safety in routine endoscopic practice,particularly in the early phase of introduction in the endoscopic unit.A subanalysis,which involved patients who underwent MSE after unsuccessful balloon enteroscopy,demonstrated,for the first time,the promising performance of MSE as a rescue procedure.Given its remarkable performance in clinical practice and its potential role as a backup technique following a previously failed enteroscopy,it may be more appropriate to refine and enhance MSE in the future rather than completely abandoning it.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Integration of bio-inspired limb-like structure damping into motor suspension of high-speed trains to enhance bogie hunting stability

Hunting stability is an important performance criterion in railway vehicles.This study proposes an incorporation of a bio-inspired limb-like structure(LLS)-based nonlinear damping into the motor suspension system for traction units to improve the nonlinear critical speed and hunting stability of high-speed trains(HSTs).Initially,a vibration transmission analysis is conducted on a HST vehicle and a metro vehicle that suffered from hunting motion to explore the effect of different motor suspension systems from on-track tests.Subsequently,a simplified lateral dynamics model of an HST bogie is established to investigate the influence of the motor suspension on the bogie hunting behavior.The bifurcation analysis is applied to optimize the motor suspension parameters for high critical speed.Then,the nonlinear damping of the bio-inspired LLS,which has a positive correlation with the relative displacement,can further improve the modal damping of hunting motion and nonlinear critical speed compared with the linear motor suspension system.Furthermore,a comprehensive numerical model of a high-speed train,considering all nonlinearities,is established to investigate the influence of different types of motor suspension.The simulation results are well consistent with the theoretical analysis.The benefits of employing nonlinear damping of the bio-inspired LLS into the motor suspension of HSTs to enhance bogie hunting stability are thoroughly validated.

Insights into spinal muscular atrophy from molecular biomarkers

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

Exploring Motor Imagery EEG: Enhanced EEG Microstate Analysis with GMD-Driven Density Canopy Method

The analysis of microstates in EEG signals is a crucial technique for understanding the spatiotemporal dynamics of brain electrical activity.Traditional methods such as Atomic Agglomerative Hierarchical Clustering(AAHC),K-means clustering,Principal Component Analysis(PCA),and Independent Component Analysis(ICA)are limited by a fixed number of microstate maps and insufficient capability in cross-task feature extraction.Tackling these limitations,this study introduces a Global Map Dissimilarity(GMD)-driven density canopy K-means clustering algorithm.This innovative approach autonomously determines the optimal number of EEG microstate topographies and employs Gaussian kernel density estimation alongside the GMD index for dynamic modeling of EEG data.Utilizing this advanced algorithm,the study analyzes the Motor Imagery(MI)dataset from the GigaScience database,GigaDB.The findings reveal six distinct microstates during actual right-hand movement and five microstates across other task conditions,with microstate C showing superior performance in all task states.During imagined movement,microstate A was significantly enhanced.Comparison with existing algorithms indicates a significant improvement in clustering performance by the refined method,with an average Calinski-Harabasz Index(CHI)of 35517.29 and a Davis-Bouldin Index(DBI)average of 2.57.Furthermore,an information-theoretical analysis of the microstate sequences suggests that imagined movement exhibits higher complexity and disorder than actual movement.By utilizing the extracted microstate sequence parameters as features,the improved algorithm achieved a classification accuracy of 98.41%in EEG signal categorization for motor imagery.A performance of 78.183%accuracy was achieved in a four-class motor imagery task on the BCI-IV-2a dataset.These results demonstrate the potential of the advanced algorithm in microstate analysis,offering a more effective tool for a deeper understanding of the spatiotemporal features of EEG signals.

Review of Fault-tolerant Control for Motor Inverter Failure with Operational Quality Considered

In recent years,motor drive systems have garnered increasing attention due to their high efficiency and superior control performance.This is especially apparent in aerospace,marine propulsion,and electric vehicles,where high performance,efficiency,and reliability are crucial.The ability of the drive system to maintain long-term fault-tolerant control(FTC)operation after a failure is essential.The likelihood of inverter failures surpasses that of other components in the drive system,highlighting its critical importance.Long-term FTC operation ensures the system retains its fundamental functions until safe repairs or replacements can be made.The focus of developing a FTC strategy has shifted from basic FTC operations to enhancing the post-fault quality to accommodate the realities of prolonged operation post-failure.This paper primarily investigates FTC strategies for inverter failures in various motor drive systems over the past decade.These strategies are categorized into three types based on post-fault operational quality:rescue,remedy,and reestablishment.The paper discusses each typical control strategy and its research focus,the strengths and weaknesses of various algorithms,and recent advancements in FTC.Finally,this review summarizes effective FTC techniques for inverter failures in motor drive systems and suggests directions for future research.

Cortical activity in patients with high-functioning ischemic stroke during the Purdue Pegboard Test:insights into bimanual coordinated fine motor skills with functional near-infrared spectroscopy

After stroke,even high-functioning individuals may experience compromised bimanual coordination and fine motor dexterity,leading to reduced functional independence.Bilateral arm training has been proposed as a promising intervention to address these deficits.However,the neural basis of the impairment of functional fine motor skills and their relationship to bimanual coordination performance in stroke patients remains unclear,limiting the development of more targeted interventions.To address this gap,our study employed functional near-infrared spectroscopy to investigate cortical responses in patients after stroke as they perform functional tasks that engage fine motor control and coordination.Twenty-four high-functioning patients with ischemic stroke(7 women,17 men;mean age 64.75±10.84 years)participated in this cross-sectional observational study and completed four subtasks from the Purdue Pegboard Test,which measures unimanual and bimanual finger and hand dexterity.We found significant bilateral activation of the sensorimotor cortices during all Purdue Pegboard Test subtasks,with bimanual tasks inducing higher cortical activation than the assembly subtask.Importantly,patients with better bimanual coordination exhibited lower cortical activation during the other three Purdue Pegboard Test subtasks.Notably,the observed neural response patterns varied depending on the specific subtask.In the unaffected hand task,the differences were primarily observed in the ipsilesional hemisphere.In contrast,the bilateral sensorimotor cortices and the contralesional hemisphere played a more prominent role in the bimanual task and assembly task,respectively.While significant correlations were found between cortical activation and unimanual tasks,no significant correlations were observed with bimanual tasks.This study provides insights into the neural basis of bimanual coordination and fine motor skills in high-functioning patients after stroke,highlighting task-dependent neural responses.The findings also suggest that patients who exhibit better bimanual performance demonstrate more efficient cortical activation.Therefore,incorporating bilateral arm training in post-stroke rehabilitation is important for better outcomes.The combination of functional near-infrared spectroscopy with functional motor paradigms is valuable for assessing skills and developing targeted interventions in stroke rehabilitation.

A Stable Fuzzy-Based Computational Model and Control for Inductions Motors

In this paper,a stable and adaptive sliding mode control(SMC)method for induction motors is introduced.Determining the parameters of this system has been one of the existing challenges.To solve this challenge,a new self-tuning type-2 fuzzy neural network calculates and updates the control system parameters with a fast mechanism.According to the dynamic changes of the system,in addition to the parameters of the SMC,the parameters of the type-2 fuzzy neural network are also updated online.The conditions for guaranteeing the convergence and stability of the control system are provided.In the simulation part,in order to test the proposed method,several uncertain models and load torque have been applied.Also,the results have been compared to the SMC based on the type-1 fuzzy system,the traditional SMC,and the PI controller.The average RMSE in different scenarios,for type-2 fuzzy SMC,is 0.0311,for type-1 fuzzy SMC is 0.0497,for traditional SMC is 0.0778,and finally for PI controller is 0.0997.