Entering the 21st century, China’s economic development has reached new heights and the country has ascended to the world’s second largest economy. The 20 year unrelenting development in China also stimulates income...Entering the 21st century, China’s economic development has reached new heights and the country has ascended to the world’s second largest economy. The 20 year unrelenting development in China also stimulates income growth. The increased disposable income enables an ordinary Chinese family vehicle ownership which was unthinkable two decades ago. The most populous country has started a love affair with automobile just like in the United States. Annual automobile sales in China rose from 2.1 million in 2000 to 18.1 million in 2010 with a yearly growth rate of 24.3%, which spurs the vehicle ownership increase from 18.1 million in 2000 to 78.8 million in 2010, a growth rate of 15.9% The unprecedented motorization development in China is making a huge impact on all aspects of society, including negative consequences that cannot be ignored. Traffic congestion, air pollution, and dependency on imported oil are huge emerging problems threatening Chinese sustainable development. Although these problems occurred and still exist in many other developed and developing countries, they are more acute in China today. By collecting and analyzing the massive data from various sources, this paper explores the relationship between economic development and level of mobility by studying the historical developments from several developed counties and discusses the key issues in Chinese motorization development. The objective of the study is to predict the future level of motorization and its potential impacts.展开更多
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 disea...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.展开更多
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 disabi...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.展开更多
The performance characteristics,particularly the starting performance of direct line-fed induction motors,which are mainly influenced by the design of the rotor,are crucial considerations for end-users.It is quite a c...The performance characteristics,particularly the starting performance of direct line-fed induction motors,which are mainly influenced by the design of the rotor,are crucial considerations for end-users.It is quite a challenging issue for motor manufacturers to enhance the starting performance of existing mass-produced motors with minimal modifications and expenses.In this paper,a simple and cost-effective method to improve the starting performance of a commercial squirrel-cage induction motor(SCIM)is proposed.The influence of geometric parameters of the end-ring on the performance characteristics,including starting(locked rotor)torque,pull-up and break down torque,starting current,rotor electric parameters,current density,power losses,and efficiency have been comprehensively investigated.It has been revealed that among the other end-ring design parameters,the ring thickness has a significant effect on the performance characteristics.An optimal end-ring thickness is determined,and its performance characteristics have been compared to those of its initial counterpart.Numeric and parametric analyses have been conducted using a 2D time-stepping finite element method(FEM).The FEM results were validated using experimental measurements obtained from an 11 kW SCIM prototype.展开更多
The harmonics that appear in the squirrel cage asynchronous machine have been discussed in great detail in the literature for a long time. However, the systematization of the phenomenon is still pending, so we made an...The harmonics that appear in the squirrel cage asynchronous machine have been discussed in great detail in the literature for a long time. However, the systematization of the phenomenon is still pending, so we made an attempt to fill this gap in the previous parts of our study by elaborating formulas for calculation of parasitic torques. It was a general demand among those who work in this field towards the author to verify his formulas with measurements. In the literature, it seems,only one detailed, purposeful series of measurements has been published so far, the purpose of which was to investigate the effect of the number of rotor slots on the torque-speed characteristic curve of the machine. The main goal of this study is to verify the correctness of the formulas by comparing them with the referred series of measurements. Relying on this, the expected synchronous parasitic torques were developed for the frequently used rotor slot numbers-as a design guide for the engineer.Thus, together with our complete table for radial magnetic pull published in our previous work, the designer has all the principles, data and formulas available for the right number of rotor slots for his given machine and for the drive system. This brings this series of papers to an end.展开更多
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 stres...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.展开更多
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 ...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.展开更多
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 generat...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.展开更多
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 v...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.展开更多
Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The functio...Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The function of this neck hinge for controlling processive movement,however,remains unclear.Methods We made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay.Results In KIF13B,the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity,while the removal of this proline increases the both.In KIF1A,the deletion of entire flexible neck hinge merely enhances the processivity.The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1.Conclusion The neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility,which provides a novel strategy to reshape the processive movement of kinesin motors.展开更多
Currently,deep drilling operates under extreme conditions of high temperature and high pressure,demanding more from subterranean power motors.The all-metal positive displacement motor,known for its robust performance,...Currently,deep drilling operates under extreme conditions of high temperature and high pressure,demanding more from subterranean power motors.The all-metal positive displacement motor,known for its robust performance,is a critical choice for such drilling.The dimensions of the PDM are crucial for its performance output.To enhance this,optimization of the motor's profile using a genetic algorithm has been undertaken.The design process begins with the computation of the initial stator and rotor curves based on the equations for a screw cycloid.These curves are then refined using the least squares method for a precise fit.Following this,the PDM's mathematical model is optimized,and motor friction is assessed.The genetic algorithm process involves encoding variations and managing crossovers to optimize objective functions,including the isometric radius coefficient,eccentricity distance parameter,overflow area,and maximum slip speed.This optimization yields the ideal profile parameters that enhance the motor's output.Comparative analyses of the initial and optimized output characteristics were conducted,focusing on the effects of the isometric radius coefficient and overflow area on the motor's performance.Results indicate that the optimized motor's overflow area increased by 6.9%,while its rotational speed reduced by 6.58%.The torque,as tested by Infocus,saw substantial improvements of38.8%.This optimization provides a theoretical foundation for improving the output characteristics of allmetal PDMs and supports the ongoing development and research of PDM technology.展开更多
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 amy...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.展开更多
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 ...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.展开更多
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,...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.展开更多
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...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
文摘Entering the 21st century, China’s economic development has reached new heights and the country has ascended to the world’s second largest economy. The 20 year unrelenting development in China also stimulates income growth. The increased disposable income enables an ordinary Chinese family vehicle ownership which was unthinkable two decades ago. The most populous country has started a love affair with automobile just like in the United States. Annual automobile sales in China rose from 2.1 million in 2000 to 18.1 million in 2010 with a yearly growth rate of 24.3%, which spurs the vehicle ownership increase from 18.1 million in 2000 to 78.8 million in 2010, a growth rate of 15.9% The unprecedented motorization development in China is making a huge impact on all aspects of society, including negative consequences that cannot be ignored. Traffic congestion, air pollution, and dependency on imported oil are huge emerging problems threatening Chinese sustainable development. Although these problems occurred and still exist in many other developed and developing countries, they are more acute in China today. By collecting and analyzing the massive data from various sources, this paper explores the relationship between economic development and level of mobility by studying the historical developments from several developed counties and discusses the key issues in Chinese motorization development. The objective of the study is to predict the future level of motorization and its potential impacts.
基金supported by National Natural Science Foundation of China,No.32102745(to XL).
文摘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.
基金supported by a grant from the National Research Foundation(NRF)of Korea funded by the Korean Government,No.NRF-2022R1A2C1004022(to CM)。
文摘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.
文摘The performance characteristics,particularly the starting performance of direct line-fed induction motors,which are mainly influenced by the design of the rotor,are crucial considerations for end-users.It is quite a challenging issue for motor manufacturers to enhance the starting performance of existing mass-produced motors with minimal modifications and expenses.In this paper,a simple and cost-effective method to improve the starting performance of a commercial squirrel-cage induction motor(SCIM)is proposed.The influence of geometric parameters of the end-ring on the performance characteristics,including starting(locked rotor)torque,pull-up and break down torque,starting current,rotor electric parameters,current density,power losses,and efficiency have been comprehensively investigated.It has been revealed that among the other end-ring design parameters,the ring thickness has a significant effect on the performance characteristics.An optimal end-ring thickness is determined,and its performance characteristics have been compared to those of its initial counterpart.Numeric and parametric analyses have been conducted using a 2D time-stepping finite element method(FEM).The FEM results were validated using experimental measurements obtained from an 11 kW SCIM prototype.
文摘The harmonics that appear in the squirrel cage asynchronous machine have been discussed in great detail in the literature for a long time. However, the systematization of the phenomenon is still pending, so we made an attempt to fill this gap in the previous parts of our study by elaborating formulas for calculation of parasitic torques. It was a general demand among those who work in this field towards the author to verify his formulas with measurements. In the literature, it seems,only one detailed, purposeful series of measurements has been published so far, the purpose of which was to investigate the effect of the number of rotor slots on the torque-speed characteristic curve of the machine. The main goal of this study is to verify the correctness of the formulas by comparing them with the referred series of measurements. Relying on this, the expected synchronous parasitic torques were developed for the frequently used rotor slot numbers-as a design guide for the engineer.Thus, together with our complete table for radial magnetic pull published in our previous work, the designer has all the principles, data and formulas available for the right number of rotor slots for his given machine and for the drive system. This brings this series of papers to an end.
基金supported by Defence Innovative Research Program(DIRP)Grant(PA No.9015102335)from Defence Research&Technology Office,Ministry of Defence,Singapore。
文摘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.
文摘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.
基金supported by National Key R&D Program of China(2018YFA0901700)National Natural Science Foundation of China(22278241)+1 种基金a grant from the Institute Guo Qiang,Tsinghua University(2021GQG1016)Department of Chemical Engineering-iBHE Joint Cooperation Fund.
文摘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.
基金supported in part by the Science Foundation of the Chinese Academy of Railway Sciences under Grant Number:2023QT001。
文摘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.
文摘Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The function of this neck hinge for controlling processive movement,however,remains unclear.Methods We made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay.Results In KIF13B,the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity,while the removal of this proline increases the both.In KIF1A,the deletion of entire flexible neck hinge merely enhances the processivity.The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1.Conclusion The neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility,which provides a novel strategy to reshape the processive movement of kinesin motors.
基金supported by the National Natural Science Foundation of China (No.42172343)。
文摘Currently,deep drilling operates under extreme conditions of high temperature and high pressure,demanding more from subterranean power motors.The all-metal positive displacement motor,known for its robust performance,is a critical choice for such drilling.The dimensions of the PDM are crucial for its performance output.To enhance this,optimization of the motor's profile using a genetic algorithm has been undertaken.The design process begins with the computation of the initial stator and rotor curves based on the equations for a screw cycloid.These curves are then refined using the least squares method for a precise fit.Following this,the PDM's mathematical model is optimized,and motor friction is assessed.The genetic algorithm process involves encoding variations and managing crossovers to optimize objective functions,including the isometric radius coefficient,eccentricity distance parameter,overflow area,and maximum slip speed.This optimization yields the ideal profile parameters that enhance the motor's output.Comparative analyses of the initial and optimized output characteristics were conducted,focusing on the effects of the isometric radius coefficient and overflow area on the motor's performance.Results indicate that the optimized motor's overflow area increased by 6.9%,while its rotational speed reduced by 6.58%.The torque,as tested by Infocus,saw substantial improvements of38.8%.This optimization provides a theoretical foundation for improving the output characteristics of allmetal PDMs and supports the ongoing development and research of PDM technology.
基金supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX).
文摘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.
基金supported by the National Natural Science Foundation of China,No.81971177(to YK)the Natural Science Foundation of Beijing,No.7222198(to NH)the Peking University People's Hospital Research and Development Fund,No.RDX2021-01(to YK)。
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China,Nos.62027812(to HS),81771470(to HS),and 82101608(to YL)Tianjin Postgraduate Research and Innovation Project,No.2020YJSS122(to XD)。
文摘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.
基金Project supported by the Research Group of Nonequilibrium Statistics(Grant No.14078206)Kunming University of Science and Technology,China.
文摘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.
文摘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.
基金supported by the NIH (R01NS103481, R01NS111776, and R01NS131489)Indiana Department of Health (ISDH58180)(all to WW)。
文摘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.