Objective To investigate lateralization and Coherence analysis of blood perfusion in bilateral Neiguan （内关 PC 6） in different ages. Methods Healthy volunteers （n=30） were placed in a temperature-controlled room ...Objective To investigate lateralization and Coherence analysis of blood perfusion in bilateral Neiguan （内关 PC 6） in different ages. Methods Healthy volunteers （n=30） were placed in a temperature-controlled room as a resting state for 40 min. Then the blood perfusion of bilateral PC 6 were carried out using PeriFlux System 5000 for 25 minutes. Mean blood flux of every 5 minutes was calculated. Then the participants were divided into groups of young （n=18） and the old （n=12） as the boundary of 40 years, the asymmetry index and coherence value of bilateral PC 6 were analyzed in different group. Results The mean blood flow of the right PC 6 was significantly higher than the left PC 6 in three different epochs, the mean blood flow of right PC 6 vs left PC 6 is 9.74±3.36 vs 6.73±2.22 （t=5.9, P〈0.001）, 9.83±3.63 vs 6.99±2.37 （t=5.11, P〈0.001） and 9.69±3.40 vs 6.77±2.32 （t=5.99, P〈0.001）, respectively. Although the asymmetry index is higher in old group than in young group, there is no statistically significant age-related differences. Coherence analysis suggest that there is significant difference in frequency value corresponding to peak crest between young and old group. Conclusion The blood perfusion in right PC 6 is higher than left PC 6. Coherence analysis of laser Doppler flowmetry signals in bilateral PC 6 might provide a potential non-invasive method to assess microcirculatory changes in different ages.展开更多
BACKGROUND Caloric stimulation of the vestibular system is associated with autonomic response.The lateralization in the nervous system activities also involves the autonomic nervous system.AIM To compare the effect of...BACKGROUND Caloric stimulation of the vestibular system is associated with autonomic response.The lateralization in the nervous system activities also involves the autonomic nervous system.AIM To compare the effect of the right and left ear caloric test on the cardiac sympathovagal tone in healthy persons.METHODS This self-control study was conducted on 12 healthy male volunteers.The minimal ice water caloric test was applied for vestibular stimulation.This was done by irrigating 1 milliliter of 4±2°C ice water into the external ear canal in 1 s.In each experiment,only one ear was stimulated.For each ear,the pessimum position was considered as sham control and the optimum position was set as caloric vestibular stimulation of horizontal semicircular channel.The order of right or left caloric vestibular stimulation and the sequence of optimum or pessimum head position in each set were random.The recovery time between each calorie test was 5 min.The short-term heart rate variability(HRV)was used for cardiac sympathovagal tone metrics.All variables were compared using the analysis of variance.RESULTS After caloric vestibular stimulation,the short-term time-domain and frequencydomain HRV indices as well as,the systolic and the diastolic arterial blood pressure,the respiratory rate and the respiratory amplitude,had no significant changes.These negative results were similar in the right and the left sides.Nystagmus duration of left caloric vestibular stimulations in the optimum and the pessimum positions had significant differences(e.g.,72.14±39.06 vs 45.35±35.65,P<0.01).Nystagmus duration of right caloric vestibular stimulations in the optimum and the pessimum positions had also significant differences(e.g.,86.42±67.20 vs 50.71±29.73,P<0.01).The time of the start of the nystagmus following caloric vestibular stimulation had no differences in both sides and both positions.CONCLUSION Minimal ice water caloric stimulation of the right and left vestibular system did not affect the cardiac sympathovagal balance according to HRV indices.展开更多
We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate （TRUSBX） and radical prostatectomy （RP）. Some factors that could cause a discrepancy in results b...We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate （TRUSBX） and radical prostatectomy （RP）. Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative Study, We divided the patients into two groups using the Gleason score： an intermediate/high-grade group （≥7） and a low-grade group （〈6）. Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality （P〈 0.05）, and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation （P 〉 0.05）. Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer （PCa）. The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in Pca.展开更多
Background: Most orthopedists are right-handed. However, osteoarthritis occurs with equal frequency over both sides. Does perfect and effective arthroplasty surgery require ambidextrous motor skills? Objectives: In th...Background: Most orthopedists are right-handed. However, osteoarthritis occurs with equal frequency over both sides. Does perfect and effective arthroplasty surgery require ambidextrous motor skills? Objectives: In this study, we aimed to investigate the clinical features of arthroplasty for hip and knee joints (THR and TKR) on different sides affected by orthopedist laterality. Patients and Methods: All right-handed orthopedists performed 64 right and 52 left primary THR among 100 patients, and 115 right and 118 left primary TKR among 192 patients. Clinical and surgical features were retrospectively reviewed and analyzed. The body mass index (BMI), inner diameter of acetabular cup liners (ACD), diameter of the femoral head (FHD), diameter of the femoral stem (FSD), and the femoral neck length (FNL) were included in THR-receiving patients. The BMI, femoral component (FC) size, tibial plate (TP) size, and thickness of articular surface inserts (ASI) were included in TKR-receiving patients. Results: No significant differences were observed in ACD, FHD and FSD between patients receiving right and left THR groups (p = 0.16, 0.11, and 0.05, respectively). Similarly, there were no significant differences in FC, TP, and ASI between patients receiving right and left TKR groups (p = 0.06, 0.80, and 0.46, respectively). However, FNL in left THR group was significantly longer than that in right THR group (p = 0.01). Conclusion: This study showed that dexterity or proprioception in handedness had no affect on bone resection and thicknesses of the polyethylene in TKR and acetabular reaming and femoral canal rasping in THR. However, it did lead to differences in femoral neck resection. Right-handed orthopedists significantly tend to perform excessive femoral neck cutting or prefer the larger size of FNL when performing left side THR, while no differences occur when performing TKR.展开更多
BACKGROUND： Previous studies have demonstrated the relationship of lower limb dominance with left- and right-handedness, supporting findings suggest that there is a role for peripheral factors in the neural control o...BACKGROUND： Previous studies have demonstrated the relationship of lower limb dominance with left- and right-handedness, supporting findings suggest that there is a role for peripheral factors in the neural control of movement. OBJECTIVE： To investigate the effect of laterality pattern on the neural mechanisms of motor control at the peripheral level. DESIGN, TIME AND SETTING： A controlled observation experiment was performed at the Motor Diagnostics Laboratory of the Academy of Physical Education in Katowice, Poland, in June 2009. PARTICIPANTS： Twenty young male adults aged 21-23 years and presenting two laterality patterns in hand-foot combination （right handed-right footed and left handed-left footed groups） took part in the experiment. All participants were carefully screened to eliminate any neurological or muscle disease or trauma. METHODS： The experiment included a laterality evaluation and the motor evoked potentials of dominant and non-dominant limbs. Measures were done through the use of the Hoffmann-reflex （H-reflex） circuitry. The soleus H-reflex parameters elicited at rest in lower extremities were compared. The soleus H-reflex and the direct motor response were elicited in lower extremities of each participant in the same laboratory session. MAIN OUTCOME MEASURES： Onset latencies and min-max amplitudes of the direct motor response and the H-reflex; the motor and sensory conduction velocities; and symmetry coefficients of response parameters. RESULTS： The analysis of symmetry coefficients of direct and late motor responses confirmed differences between two laterality patterns in amplitude and latency of the H-reflex as well as in a sensory conduction velocity （P 〈 0.05）, but not in direct motor response parameters. The amplitude of the H-reflex and the calculated sensory la afferent conduction velocity in the dominant lower extremity were significantly depressed in the right-sided group in comparison to the left-sided group （P = 0.001）. The right-sided group presented significantly higher motor fiber conduction velocity in the dominant leg than in the non-dominant leg （P = 0.006）, with no similar effect in the left-sided group. CONCLUSION： The neural control of the H-reflex elicited at rest is related to the laterality pattern in hand-foot combination in healthy adults. This result strongly suggests the possible existence of intrinsic control mechanisms of afferent feedback related to functional dominance in human limbs.展开更多
Mechanical allodynia(MA),including punctate and dynamic forms,is a common and debilitating symptom suffered by millions of chronic pain patients.Some peripheral injuries result in the development of bilateral MA,while...Mechanical allodynia(MA),including punctate and dynamic forms,is a common and debilitating symptom suffered by millions of chronic pain patients.Some peripheral injuries result in the development of bilateral MA,while most injuries usually led to unilateral MA.To date,the control of such laterality remains poorly understood.Here,to study the role of microglia in the control of MA laterality,we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice.Surprisingly,the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA.Moreover,in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons.Consistent with behavioral results,microglial depletion did not prevent the opening of bilateral gates for Aβpathways in the superficial dorsal horn.This study challenges the role of microglia in the control of MA laterality in mice.Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.展开更多
Competitive swimmers may gain a specific training effect as the result of long term exercise in the water. This study aimed to compare isometric, non-isokinetic and isokinetic muscle strengths in competitive swimmers ...Competitive swimmers may gain a specific training effect as the result of long term exercise in the water. This study aimed to compare isometric, non-isokinetic and isokinetic muscle strengths in competitive swimmers and untrained persons. Twelve young male adults without exercise experience for over three years and twelve swimmers with over 10 years of competitive swimming experience performed various strength tests. Non-isokinetic tests were evaluated using one repetition of maximum half squat, vertical jump, and drop jump. Isometric and isokinetic (60 and 180 deg/s) muscle strengths were measured by both legs in knee extension and flexion. There were no significant differences between non-isokinetic and isometric muscle strengths of both groups. On the other hand, all isokinetic parameters in both angular velocities were significantly larger in competitive swimmers. There was significant laterality of isokinetic strength in untrained persons, but not in competitive swimmers. In addition, right and left differences of isokinetic strength tended to be smaller in competitive swimmers. In conclusion, competitive swimmers tended to be superior only in isokinetic strength, which is a similar muscle contraction in the water, and have less right and left differences.展开更多
Animal individuality is challenging to explain because individual differences are regulated by multiple selective forces that lead to unique combinations of characteristics.For instance,the study of personality,a core...Animal individuality is challenging to explain because individual differences are regulated by multiple selective forces that lead to unique combinations of characteristics.For instance,the study of personality,a core aspect of individuality,may benefit from integrating other factors underlying individual differences,such as lateralized cerebral processing.Indeed,the approach-withdrawal hypothesis(the left hemisphere controls approach behavior,the right hemisphere controls withdrawal behavior),may account for differences in boldness or exploration between left and right hemispheric dominant individuals.To analyze the relationships between personality and laterality we tested 80 male piglets with established laterality patterns for 2 motor functions(tail curling direction and the side of the snout used for manipulation)and a combined classification integrating both motor functions using cluster analysis.We analyzed basal salivary testosterone and cortisol along with their behavior in standardized tests as pre-established indicators of different personality traits(Boldness,Exploration,Activity,Sociability,and Coping).We found that the direction of the single motor biases showed significant associations with few personality traits.However,the combined laterality classification showed more,and more robust,significant associations with different personality traits compared with the single motor biases.These results supported the approachwithdrawal hypothesis because right-biased pigs were bolder and more explorative in a context of novelty.Additionally,right-biased pigs were more sociable than left-biased pigs.Therefore,the present study indicates that personality is indeed related to lateralized cerebral processing and provides insight into the multifactorial nature of individuality.展开更多
The establishment of left–right asymmetry is a fundamental process in animal development.Interference with this process leads to a range of disorders collectively known as laterality defects,which manifest as abnorma...The establishment of left–right asymmetry is a fundamental process in animal development.Interference with this process leads to a range of disorders collectively known as laterality defects,which manifest as abnormal arrangements of visceral organs.Among patients with laterality defects,congenital heart diseases(CHD)are prevalent.Through multiple model organisms,extant research has established that myosin-Id(MYO1D)deficiency causes laterality defects.This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D(NM_015194:c.1531G>A;p.D511N)in a consanguineous family with complex CHD and laterality defects.Further examination of the proband revealed asthenoteratozoospermia and shortened sperm.Afterward,the effects of the D511N variant and another known MYO1D variant(NM_015194:c.2293C>T;p.P765S)were assessed.The assessment showed that both enhance the interaction withβ-actin and SPAG6.Overall,this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans.Furthermore,this research established a connection between sperm defects and MYO1D variants.It offers guidance for exploring infertility and reproductive health concerns.The findings provide a critical basis for advancing personalized medicine and genetic counseling.展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
Background Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions: arithmetic calculation may be one of these phenomena. In this study, first, laterality of brain...Background Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions: arithmetic calculation may be one of these phenomena. In this study, first, laterality of brain areas associated with arithmetic calculations was revealed by functional magnetic resonance imaging (fMRI). Second, the relationship among laterality, handedness, and types of arithmetic task was assessed. Third, we postulate possible reasons for laterality. Methods Using a block-designed experiment, twenty-five right-handed and seven left-handed healthy volunteers carried out simple calculations, complex calculations and proximity judgments. T 1WI and GRE-EPI fMRI were performed with a GE 1.5T whole body MRI scanner. Statistical parametric mapping (SPM99) was used to process data and localize functional areas. Numbers of activated voxels were recorded to calculate laterality index for evaluating the laterality of functional brain areas. Results For both groups, the activation of functional areas in the frontal lobe showed a tendency towards the nonpredominant hand side, but the functional areas in the inferior parietal lobule had left laterality. During simple and complex calculations, the laterality indices of the prefrontal cortex and premotor area were higher in the right-handed group than that in the left-handed group, whereas the laterality of the inferior parietal lobule had no such significant difference. In both groups, when the difficulty of the task increased, the laterality of the prefrontal cortex, premotor area, and inferior parietal lobule decreased, but the laterality of posterior part of the inferior frontal gyrus increased. Conclusions The laterality of the functional brain areas associated with arithmetic calculations can be detected with fMRI. The laterality of the functional areas was related to handedness and task difficulty.展开更多
The muscular system plays a critical role in the human body by governing skeletal movement,cardiovascular function,and the activities of digestive organs.Additionally,muscle tissues serve an endocrine function by secr...The muscular system plays a critical role in the human body by governing skeletal movement,cardiovascular function,and the activities of digestive organs.Additionally,muscle tissues serve an endocrine function by secreting myogenic cytokines,thereby regulating metabolism throughout the entire body.Maintaining muscle function requires iron homeostasis.Recent studies suggest that disruptions in iron metabolism and ferroptosis,a form of iron-dependent cell death,are essential contributors to the progression of a wide range of muscle diseases and disorders,including sarcopenia,cardiomyopathy,and amyotrophic lateral sclerosis.Thus,a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention.This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury,as well as associated muscle diseases and disorders.Moreover,we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders.Finally,we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.展开更多
BACKGROUND:Tracheal intubation(TI)is a fundamental procedure for securing the airway or assisting ventilation in emergency medicine.Tracheal intubation in the lateral position(TILP)has been utilized in clinical practi...BACKGROUND:Tracheal intubation(TI)is a fundamental procedure for securing the airway or assisting ventilation in emergency medicine.Tracheal intubation in the lateral position(TILP)has been utilized in clinical practice,demonstrating potential advantages in specific scenarios,including emergency settings.However,there is a lack of comprehensive reviews and practical protocols on TILP application.To address this gap,we performed a narrative review,and provided evidence-based recommendations to formulate a practice protocol,to assist clinicians to effectively apply TILP.METHODS:We conducted a narrative review of TILP applications and developed recommendations based on clinical research evidence and clinical experience.Delphi method was used among the TILP consortium to grade the strength of the recommendations and to help reach consensus.The practice protocols were formulated as warranted by advancements in medical knowledge,technology,and practice.RESULTS:This narrative review summarized the current evidence on TILP application,highlighting its safety,efficacy,challenges,and potential complications.In total,24 recommendations and a clinical protocol for TILP application in emergency patients were established.CONCLUSION:TILP is a valuable technique in emergency medicine.We reviewed its application in emergency settings and formulated recommendations along with a clinical practice protocol.Future studies are needed to evaluate the safety and efficacy of TILP,broaden its scope of application,and explore effective training protocols.展开更多
The models constructed by particle flow simulation method can effectively simulate the heterogeneous substance characteristics and failure behaviors of rocks.However,existing contact models overlook the rock cracks,an...The models constructed by particle flow simulation method can effectively simulate the heterogeneous substance characteristics and failure behaviors of rocks.However,existing contact models overlook the rock cracks,and the various simulation methods that do consider cracks still exhibit certain limitations.In this paper,based on Flat-Joint model and Linear Parallel Bond model,a crack contact model considering linked substance in the crack is proposed by splitting the crack contact into two portions:linked portion and unlinked portion for calculation.The new contact model considers the influence of crack closure on the contact force-displacement law.And a better compressive tensile strength ratio(UCS/T)was obtained by limiting the failure of the contact bond to be solely controlled by the contact force and moment of the linked portion.Then,by employing the FISH Model tool within the Particle Flow Code,the contact model was constructed and verified through contact force–displacement experiments and loading-unloading tests with cracked model.Finally,the contact model was tested through simulations of rock mechanics experiments.The results indicate that the contact model can effectively simulate the axial and lateral strain laws of rocks simultaneously and has a relatively good reproduction of the bi-modularity of rocks.展开更多
Mountainous areas are the priority for forest restoration in semiarid regions,with hillslopes serving as the basic units of mountains.Precipitation is the only water source in these regions,and the uneven distribution...Mountainous areas are the priority for forest restoration in semiarid regions,with hillslopes serving as the basic units of mountains.Precipitation is the only water source in these regions,and the uneven distribution of hillslope soil moisture replenishment after precipitation determines vegetation survival and growth.Therefore,in this study experiments were performed on a hillslope in the Liupan Mountains,Ningxia Hui Autonomous Region,China,to quantify the unevenness of soil moisture replenishment.Soil water content(SWC)in the 0–60 cm layer and precipitation were monitored throughout the growing season in 2020 and 2021.The results showed that(1)Annual soil moisture replenishment was the highest at the mid-slope position,with an average of 309.9 mm,especially under moderate and heavy rain grade conditions,reaching 38.7% and 30.8% of the total replenishment,respectively;(2)Vertical replenishment played a dominant role in the total replenishment,accounting for 82.8%;lateral replenishment played an important but lesser role,accounting for up to 17.2% of the total replenishment;(3)Based on a soil moisture replenishment model established in this study,the maximal replenishment occurred at 90 m from the top of the slope;(4)The dominant factors contributing to the soil moisture replenishment were rainfall amount and saturated hydraulic conductivity(Ks).These findings suggest that attention should be given to both vertical and lateral soil moisture replenishment,and the mid-slope position could be preferred for site selection to achieve precise and integrated forest-water management on hillslopes in semi-arid mountainous regions.展开更多
This paper presents the design of an asymmetrically variable wingtip anhedral angles morphing aircraft,inspired by biomimetic mechanisms,to enhance lateral maneuver capability.Firstly,we establish a lateral dynamic mo...This paper presents the design of an asymmetrically variable wingtip anhedral angles morphing aircraft,inspired by biomimetic mechanisms,to enhance lateral maneuver capability.Firstly,we establish a lateral dynamic model considering additional forces and moments resulting during the morphing process,and convert it into a Multiple Input Multiple Output(MIMO)virtual control system by importing virtual inputs.Secondly,a classical dynamics inversion controller is designed for the outer-loop system.A new Global Fast Terminal Incremental Sliding Mode Controller(NDO-GFTISMC)is proposed for the inner-loop system,in which an adaptive law is implemented to weaken control surface chattering,and a Nonlinear Disturbance Observer(NDO)is integrated to compensate for unknown disturbances.The whole control system is proven semiglobally uniformly ultimately bounded based on the multi-Lyapunov function method.Furthermore,we consider tracking errors and self-characteristics of actuators,a quadratic programmingbased dynamic control allocation law is designed,which allocates virtual control inputs to the asymmetrically deformed wingtip and rudder.Actuator dynamic models are incorporated to ensure physical realizability of designed allocation law.Finally,comparative experimental results validate the effectiveness of the designed control system and control allocation law.The NDO-GFTISMC features faster convergence,stronger robustness,and 81.25%and 75.0%reduction in maximum state tracking error under uncertainty compared to the Incremental Nonlinear Dynamic Inversion Controller based on NDO(NDO-INDI)and Incremental Sliding Mode Controller based on NDO(NDO-ISMC),respectively.The design of the morphing aircraft significantly enhances lateral maneuver capability,maintaining a substantial control margin during lateral maneuvering,reducing the burden of the rudder surface,and effectively solving the actuator saturation problem of traditional aircraft during lateral maneuvering.展开更多
Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann c...Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.展开更多
BACKGROUND A case study of multiple distinct levels of skipped thoracolumbar spine infection was reported in which 13 successful vacuum sealing drainage(VSD)surgeries were treated.CASE SUMMARY The patient underwent a ...BACKGROUND A case study of multiple distinct levels of skipped thoracolumbar spine infection was reported in which 13 successful vacuum sealing drainage(VSD)surgeries were treated.CASE SUMMARY The patient underwent a total of 13 procedures within our medical facility,including five performed under local anesthesia and eight performed under general anesthesia.The source of the ailment was ultimately identified as Enterobacter cloacae.After the last procedure,the patient's symptoms were alleviated,and the recovery process was satisfactory.Three months post-operation,the Japanese Orthopaedic Association scores had improved to 100%.Imageological examination revealed a satisfactory position of internal fixation,and the abnormal signals in the vertebral body and intervertebral space had been eliminated when compared to the pre-operative results.CONCLUSION The study demonstrates that the extreme lateral approach debridement combined with multiple VSD operations is a secure and successful method of treatment for recurrent spinal infection,providing an alternative to traditional surgery.展开更多
Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is...Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.展开更多
Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understan...Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.展开更多
基金Supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes:ZZ070806National Natural Science Foundation of China:81001553National Basic Research Program of China:2015CB554502
文摘Objective To investigate lateralization and Coherence analysis of blood perfusion in bilateral Neiguan （内关 PC 6） in different ages. Methods Healthy volunteers （n=30） were placed in a temperature-controlled room as a resting state for 40 min. Then the blood perfusion of bilateral PC 6 were carried out using PeriFlux System 5000 for 25 minutes. Mean blood flux of every 5 minutes was calculated. Then the participants were divided into groups of young （n=18） and the old （n=12） as the boundary of 40 years, the asymmetry index and coherence value of bilateral PC 6 were analyzed in different group. Results The mean blood flow of the right PC 6 was significantly higher than the left PC 6 in three different epochs, the mean blood flow of right PC 6 vs left PC 6 is 9.74±3.36 vs 6.73±2.22 （t=5.9, P〈0.001）, 9.83±3.63 vs 6.99±2.37 （t=5.11, P〈0.001） and 9.69±3.40 vs 6.77±2.32 （t=5.99, P〈0.001）, respectively. Although the asymmetry index is higher in old group than in young group, there is no statistically significant age-related differences. Coherence analysis suggest that there is significant difference in frequency value corresponding to peak crest between young and old group. Conclusion The blood perfusion in right PC 6 is higher than left PC 6. Coherence analysis of laser Doppler flowmetry signals in bilateral PC 6 might provide a potential non-invasive method to assess microcirculatory changes in different ages.
文摘BACKGROUND Caloric stimulation of the vestibular system is associated with autonomic response.The lateralization in the nervous system activities also involves the autonomic nervous system.AIM To compare the effect of the right and left ear caloric test on the cardiac sympathovagal tone in healthy persons.METHODS This self-control study was conducted on 12 healthy male volunteers.The minimal ice water caloric test was applied for vestibular stimulation.This was done by irrigating 1 milliliter of 4±2°C ice water into the external ear canal in 1 s.In each experiment,only one ear was stimulated.For each ear,the pessimum position was considered as sham control and the optimum position was set as caloric vestibular stimulation of horizontal semicircular channel.The order of right or left caloric vestibular stimulation and the sequence of optimum or pessimum head position in each set were random.The recovery time between each calorie test was 5 min.The short-term heart rate variability(HRV)was used for cardiac sympathovagal tone metrics.All variables were compared using the analysis of variance.RESULTS After caloric vestibular stimulation,the short-term time-domain and frequencydomain HRV indices as well as,the systolic and the diastolic arterial blood pressure,the respiratory rate and the respiratory amplitude,had no significant changes.These negative results were similar in the right and the left sides.Nystagmus duration of left caloric vestibular stimulations in the optimum and the pessimum positions had significant differences(e.g.,72.14±39.06 vs 45.35±35.65,P<0.01).Nystagmus duration of right caloric vestibular stimulations in the optimum and the pessimum positions had also significant differences(e.g.,86.42±67.20 vs 50.71±29.73,P<0.01).The time of the start of the nystagmus following caloric vestibular stimulation had no differences in both sides and both positions.CONCLUSION Minimal ice water caloric stimulation of the right and left vestibular system did not affect the cardiac sympathovagal balance according to HRV indices.
文摘We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate （TRUSBX） and radical prostatectomy （RP）. Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative Study, We divided the patients into two groups using the Gleason score： an intermediate/high-grade group （≥7） and a low-grade group （〈6）. Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality （P〈 0.05）, and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation （P 〉 0.05）. Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer （PCa）. The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in Pca.
文摘Background: Most orthopedists are right-handed. However, osteoarthritis occurs with equal frequency over both sides. Does perfect and effective arthroplasty surgery require ambidextrous motor skills? Objectives: In this study, we aimed to investigate the clinical features of arthroplasty for hip and knee joints (THR and TKR) on different sides affected by orthopedist laterality. Patients and Methods: All right-handed orthopedists performed 64 right and 52 left primary THR among 100 patients, and 115 right and 118 left primary TKR among 192 patients. Clinical and surgical features were retrospectively reviewed and analyzed. The body mass index (BMI), inner diameter of acetabular cup liners (ACD), diameter of the femoral head (FHD), diameter of the femoral stem (FSD), and the femoral neck length (FNL) were included in THR-receiving patients. The BMI, femoral component (FC) size, tibial plate (TP) size, and thickness of articular surface inserts (ASI) were included in TKR-receiving patients. Results: No significant differences were observed in ACD, FHD and FSD between patients receiving right and left THR groups (p = 0.16, 0.11, and 0.05, respectively). Similarly, there were no significant differences in FC, TP, and ASI between patients receiving right and left TKR groups (p = 0.06, 0.80, and 0.46, respectively). However, FNL in left THR group was significantly longer than that in right THR group (p = 0.01). Conclusion: This study showed that dexterity or proprioception in handedness had no affect on bone resection and thicknesses of the polyethylene in TKR and acetabular reaming and femoral canal rasping in THR. However, it did lead to differences in femoral neck resection. Right-handed orthopedists significantly tend to perform excessive femoral neck cutting or prefer the larger size of FNL when performing left side THR, while no differences occur when performing TKR.
基金a Grant from the Ministry of Science and Higher Education of Poland, No. N 404 045 31/2332
文摘BACKGROUND： Previous studies have demonstrated the relationship of lower limb dominance with left- and right-handedness, supporting findings suggest that there is a role for peripheral factors in the neural control of movement. OBJECTIVE： To investigate the effect of laterality pattern on the neural mechanisms of motor control at the peripheral level. DESIGN, TIME AND SETTING： A controlled observation experiment was performed at the Motor Diagnostics Laboratory of the Academy of Physical Education in Katowice, Poland, in June 2009. PARTICIPANTS： Twenty young male adults aged 21-23 years and presenting two laterality patterns in hand-foot combination （right handed-right footed and left handed-left footed groups） took part in the experiment. All participants were carefully screened to eliminate any neurological or muscle disease or trauma. METHODS： The experiment included a laterality evaluation and the motor evoked potentials of dominant and non-dominant limbs. Measures were done through the use of the Hoffmann-reflex （H-reflex） circuitry. The soleus H-reflex parameters elicited at rest in lower extremities were compared. The soleus H-reflex and the direct motor response were elicited in lower extremities of each participant in the same laboratory session. MAIN OUTCOME MEASURES： Onset latencies and min-max amplitudes of the direct motor response and the H-reflex; the motor and sensory conduction velocities; and symmetry coefficients of response parameters. RESULTS： The analysis of symmetry coefficients of direct and late motor responses confirmed differences between two laterality patterns in amplitude and latency of the H-reflex as well as in a sensory conduction velocity （P 〈 0.05）, but not in direct motor response parameters. The amplitude of the H-reflex and the calculated sensory la afferent conduction velocity in the dominant lower extremity were significantly depressed in the right-sided group in comparison to the left-sided group （P = 0.001）. The right-sided group presented significantly higher motor fiber conduction velocity in the dominant leg than in the non-dominant leg （P = 0.006）, with no similar effect in the left-sided group. CONCLUSION： The neural control of the H-reflex elicited at rest is related to the laterality pattern in hand-foot combination in healthy adults. This result strongly suggests the possible existence of intrinsic control mechanisms of afferent feedback related to functional dominance in human limbs.
基金supported by grants from the Ministry of Science and Technology of China(2021ZD0203302)the National Natural Science Foundation of China(32170996,32060199)+3 种基金the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(2021SHIBS0002)the Guangdong Science and Technology Committee(2019A1515010041,A2021319)the Shenzhen Innovation Committee of Science and Technology(ZDSYS20200811144002008)the Shenzhen Science and Technology Innovation Committee(JCYJ20180302174233348).
文摘Mechanical allodynia(MA),including punctate and dynamic forms,is a common and debilitating symptom suffered by millions of chronic pain patients.Some peripheral injuries result in the development of bilateral MA,while most injuries usually led to unilateral MA.To date,the control of such laterality remains poorly understood.Here,to study the role of microglia in the control of MA laterality,we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice.Surprisingly,the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA.Moreover,in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons.Consistent with behavioral results,microglial depletion did not prevent the opening of bilateral gates for Aβpathways in the superficial dorsal horn.This study challenges the role of microglia in the control of MA laterality in mice.Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.
文摘Competitive swimmers may gain a specific training effect as the result of long term exercise in the water. This study aimed to compare isometric, non-isokinetic and isokinetic muscle strengths in competitive swimmers and untrained persons. Twelve young male adults without exercise experience for over three years and twelve swimmers with over 10 years of competitive swimming experience performed various strength tests. Non-isokinetic tests were evaluated using one repetition of maximum half squat, vertical jump, and drop jump. Isometric and isokinetic (60 and 180 deg/s) muscle strengths were measured by both legs in knee extension and flexion. There were no significant differences between non-isokinetic and isometric muscle strengths of both groups. On the other hand, all isokinetic parameters in both angular velocities were significantly larger in competitive swimmers. There was significant laterality of isokinetic strength in untrained persons, but not in competitive swimmers. In addition, right and left differences of isokinetic strength tended to be smaller in competitive swimmers. In conclusion, competitive swimmers tended to be superior only in isokinetic strength, which is a similar muscle contraction in the water, and have less right and left differences.
文摘Animal individuality is challenging to explain because individual differences are regulated by multiple selective forces that lead to unique combinations of characteristics.For instance,the study of personality,a core aspect of individuality,may benefit from integrating other factors underlying individual differences,such as lateralized cerebral processing.Indeed,the approach-withdrawal hypothesis(the left hemisphere controls approach behavior,the right hemisphere controls withdrawal behavior),may account for differences in boldness or exploration between left and right hemispheric dominant individuals.To analyze the relationships between personality and laterality we tested 80 male piglets with established laterality patterns for 2 motor functions(tail curling direction and the side of the snout used for manipulation)and a combined classification integrating both motor functions using cluster analysis.We analyzed basal salivary testosterone and cortisol along with their behavior in standardized tests as pre-established indicators of different personality traits(Boldness,Exploration,Activity,Sociability,and Coping).We found that the direction of the single motor biases showed significant associations with few personality traits.However,the combined laterality classification showed more,and more robust,significant associations with different personality traits compared with the single motor biases.These results supported the approachwithdrawal hypothesis because right-biased pigs were bolder and more explorative in a context of novelty.Additionally,right-biased pigs were more sociable than left-biased pigs.Therefore,the present study indicates that personality is indeed related to lateralized cerebral processing and provides insight into the multifactorial nature of individuality.
基金supported by the National Natural Science Foundation of China(No.81970268)the Natural Science Foundation of Hunan Province(No.2023JJ30781)the Graduate Student Scientific Research Innovation Project of Hunan Province(No.CX20220315).
文摘The establishment of left–right asymmetry is a fundamental process in animal development.Interference with this process leads to a range of disorders collectively known as laterality defects,which manifest as abnormal arrangements of visceral organs.Among patients with laterality defects,congenital heart diseases(CHD)are prevalent.Through multiple model organisms,extant research has established that myosin-Id(MYO1D)deficiency causes laterality defects.This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D(NM_015194:c.1531G>A;p.D511N)in a consanguineous family with complex CHD and laterality defects.Further examination of the proband revealed asthenoteratozoospermia and shortened sperm.Afterward,the effects of the D511N variant and another known MYO1D variant(NM_015194:c.2293C>T;p.P765S)were assessed.The assessment showed that both enhance the interaction withβ-actin and SPAG6.Overall,this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans.Furthermore,this research established a connection between sperm defects and MYO1D variants.It offers guidance for exploring infertility and reproductive health concerns.The findings provide a critical basis for advancing personalized medicine and genetic counseling.
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
文摘Background Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions: arithmetic calculation may be one of these phenomena. In this study, first, laterality of brain areas associated with arithmetic calculations was revealed by functional magnetic resonance imaging (fMRI). Second, the relationship among laterality, handedness, and types of arithmetic task was assessed. Third, we postulate possible reasons for laterality. Methods Using a block-designed experiment, twenty-five right-handed and seven left-handed healthy volunteers carried out simple calculations, complex calculations and proximity judgments. T 1WI and GRE-EPI fMRI were performed with a GE 1.5T whole body MRI scanner. Statistical parametric mapping (SPM99) was used to process data and localize functional areas. Numbers of activated voxels were recorded to calculate laterality index for evaluating the laterality of functional brain areas. Results For both groups, the activation of functional areas in the frontal lobe showed a tendency towards the nonpredominant hand side, but the functional areas in the inferior parietal lobule had left laterality. During simple and complex calculations, the laterality indices of the prefrontal cortex and premotor area were higher in the right-handed group than that in the left-handed group, whereas the laterality of the inferior parietal lobule had no such significant difference. In both groups, when the difficulty of the task increased, the laterality of the prefrontal cortex, premotor area, and inferior parietal lobule decreased, but the laterality of posterior part of the inferior frontal gyrus increased. Conclusions The laterality of the functional brain areas associated with arithmetic calculations can be detected with fMRI. The laterality of the functional areas was related to handedness and task difficulty.
基金the National Natural Science Foundation of China(82471593 to J.M.32330047 and 31930057 to F.W.+2 种基金and 82071970 to Y.W.and 82072506 to Y.L.)the Science Fund for Distinguished Young Scholars of Hubei Province(2023AFA109 to Y.W.)Hubei Provincial Natural Science Foundation of China(2024AFB963 to Q.R.).
文摘The muscular system plays a critical role in the human body by governing skeletal movement,cardiovascular function,and the activities of digestive organs.Additionally,muscle tissues serve an endocrine function by secreting myogenic cytokines,thereby regulating metabolism throughout the entire body.Maintaining muscle function requires iron homeostasis.Recent studies suggest that disruptions in iron metabolism and ferroptosis,a form of iron-dependent cell death,are essential contributors to the progression of a wide range of muscle diseases and disorders,including sarcopenia,cardiomyopathy,and amyotrophic lateral sclerosis.Thus,a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention.This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury,as well as associated muscle diseases and disorders.Moreover,we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders.Finally,we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.
基金National Natural Science Foundation of China(U24A20714 to XMF and 82102238 to PC)。
文摘BACKGROUND:Tracheal intubation(TI)is a fundamental procedure for securing the airway or assisting ventilation in emergency medicine.Tracheal intubation in the lateral position(TILP)has been utilized in clinical practice,demonstrating potential advantages in specific scenarios,including emergency settings.However,there is a lack of comprehensive reviews and practical protocols on TILP application.To address this gap,we performed a narrative review,and provided evidence-based recommendations to formulate a practice protocol,to assist clinicians to effectively apply TILP.METHODS:We conducted a narrative review of TILP applications and developed recommendations based on clinical research evidence and clinical experience.Delphi method was used among the TILP consortium to grade the strength of the recommendations and to help reach consensus.The practice protocols were formulated as warranted by advancements in medical knowledge,technology,and practice.RESULTS:This narrative review summarized the current evidence on TILP application,highlighting its safety,efficacy,challenges,and potential complications.In total,24 recommendations and a clinical protocol for TILP application in emergency patients were established.CONCLUSION:TILP is a valuable technique in emergency medicine.We reviewed its application in emergency settings and formulated recommendations along with a clinical practice protocol.Future studies are needed to evaluate the safety and efficacy of TILP,broaden its scope of application,and explore effective training protocols.
基金supported by the Natural Science Foundation of Heilongjiang Province(No.ZD2021E006)the National Natural Science Foundation of China(Nos.52174075 and 52074110).
文摘The models constructed by particle flow simulation method can effectively simulate the heterogeneous substance characteristics and failure behaviors of rocks.However,existing contact models overlook the rock cracks,and the various simulation methods that do consider cracks still exhibit certain limitations.In this paper,based on Flat-Joint model and Linear Parallel Bond model,a crack contact model considering linked substance in the crack is proposed by splitting the crack contact into two portions:linked portion and unlinked portion for calculation.The new contact model considers the influence of crack closure on the contact force-displacement law.And a better compressive tensile strength ratio(UCS/T)was obtained by limiting the failure of the contact bond to be solely controlled by the contact force and moment of the linked portion.Then,by employing the FISH Model tool within the Particle Flow Code,the contact model was constructed and verified through contact force–displacement experiments and loading-unloading tests with cracked model.Finally,the contact model was tested through simulations of rock mechanics experiments.The results indicate that the contact model can effectively simulate the axial and lateral strain laws of rocks simultaneously and has a relatively good reproduction of the bi-modularity of rocks.
基金financially supported by the Central Public-Interest Scientific Institution Basal Research Fund of Chinese Academy of Forestry(CAFYBB2021ZW002)the National Key Research and Development Program of China(2022YFF1300404)the National Natural Science Foundation of China(U21A2005)。
文摘Mountainous areas are the priority for forest restoration in semiarid regions,with hillslopes serving as the basic units of mountains.Precipitation is the only water source in these regions,and the uneven distribution of hillslope soil moisture replenishment after precipitation determines vegetation survival and growth.Therefore,in this study experiments were performed on a hillslope in the Liupan Mountains,Ningxia Hui Autonomous Region,China,to quantify the unevenness of soil moisture replenishment.Soil water content(SWC)in the 0–60 cm layer and precipitation were monitored throughout the growing season in 2020 and 2021.The results showed that(1)Annual soil moisture replenishment was the highest at the mid-slope position,with an average of 309.9 mm,especially under moderate and heavy rain grade conditions,reaching 38.7% and 30.8% of the total replenishment,respectively;(2)Vertical replenishment played a dominant role in the total replenishment,accounting for 82.8%;lateral replenishment played an important but lesser role,accounting for up to 17.2% of the total replenishment;(3)Based on a soil moisture replenishment model established in this study,the maximal replenishment occurred at 90 m from the top of the slope;(4)The dominant factors contributing to the soil moisture replenishment were rainfall amount and saturated hydraulic conductivity(Ks).These findings suggest that attention should be given to both vertical and lateral soil moisture replenishment,and the mid-slope position could be preferred for site selection to achieve precise and integrated forest-water management on hillslopes in semi-arid mountainous regions.
基金supported by the National Natural Science Foundation of China(Nos.62103052 and No.52175214)。
文摘This paper presents the design of an asymmetrically variable wingtip anhedral angles morphing aircraft,inspired by biomimetic mechanisms,to enhance lateral maneuver capability.Firstly,we establish a lateral dynamic model considering additional forces and moments resulting during the morphing process,and convert it into a Multiple Input Multiple Output(MIMO)virtual control system by importing virtual inputs.Secondly,a classical dynamics inversion controller is designed for the outer-loop system.A new Global Fast Terminal Incremental Sliding Mode Controller(NDO-GFTISMC)is proposed for the inner-loop system,in which an adaptive law is implemented to weaken control surface chattering,and a Nonlinear Disturbance Observer(NDO)is integrated to compensate for unknown disturbances.The whole control system is proven semiglobally uniformly ultimately bounded based on the multi-Lyapunov function method.Furthermore,we consider tracking errors and self-characteristics of actuators,a quadratic programmingbased dynamic control allocation law is designed,which allocates virtual control inputs to the asymmetrically deformed wingtip and rudder.Actuator dynamic models are incorporated to ensure physical realizability of designed allocation law.Finally,comparative experimental results validate the effectiveness of the designed control system and control allocation law.The NDO-GFTISMC features faster convergence,stronger robustness,and 81.25%and 75.0%reduction in maximum state tracking error under uncertainty compared to the Incremental Nonlinear Dynamic Inversion Controller based on NDO(NDO-INDI)and Incremental Sliding Mode Controller based on NDO(NDO-ISMC),respectively.The design of the morphing aircraft significantly enhances lateral maneuver capability,maintaining a substantial control margin during lateral maneuvering,reducing the burden of the rudder surface,and effectively solving the actuator saturation problem of traditional aircraft during lateral maneuvering.
基金support from the Miami Project to Cure Paralysis,the Buoniconti Fund,and the Interdisciplinary Stem Cell Institute(to AK,WDD,JDG,and ADL)the unconditional support of Dean Henri Ford of the Leonard M.Miller School of Medicine at the University of Miami.
文摘Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.
基金Supported by Natural Science Foundation of Shandong Province,No.ZR2023MH331.
文摘BACKGROUND A case study of multiple distinct levels of skipped thoracolumbar spine infection was reported in which 13 successful vacuum sealing drainage(VSD)surgeries were treated.CASE SUMMARY The patient underwent a total of 13 procedures within our medical facility,including five performed under local anesthesia and eight performed under general anesthesia.The source of the ailment was ultimately identified as Enterobacter cloacae.After the last procedure,the patient's symptoms were alleviated,and the recovery process was satisfactory.Three months post-operation,the Japanese Orthopaedic Association scores had improved to 100%.Imageological examination revealed a satisfactory position of internal fixation,and the abnormal signals in the vertebral body and intervertebral space had been eliminated when compared to the pre-operative results.CONCLUSION The study demonstrates that the extreme lateral approach debridement combined with multiple VSD operations is a secure and successful method of treatment for recurrent spinal infection,providing an alternative to traditional surgery.
基金supported by the Notional Natural Science Foundation of Chino,No.82160690Colloborotive Innovation Center of Chinese Ministry of Education,No.2020-39Science and Technology Foundation of Guizhou Province,No.ZK[2021]-014(all to FZ)。
文摘Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.
基金funded by NIH-NIA R01AG061708 (to PHO)Patrick Grange Memorial Foundation (to PHO)+1 种基金A Long Swim (to PHO)CureSPG4 Foundation (to PHO)。
文摘Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.
