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
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 cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.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
Based on the split hopkinson pressure bar(SHPB)tests results,the cubic specimens have been numerically modeled in this paper to investigate the impact of key factors,such as the rise time,duration,and incident pulse s...Based on the split hopkinson pressure bar(SHPB)tests results,the cubic specimens have been numerically modeled in this paper to investigate the impact of key factors,such as the rise time,duration,and incident pulse shape,on achieving stress uniformity.After analysis,the paper provides actionable methods aimed at optimizing the conditions for stress uniformity within the cubic specimen.Finally,the lateral inertia effect of cubic specimen has been scrutinized to address the existing gap in this academic area.展开更多
Non-right-handedness(NRH),encompassing left-handedness and mixed-handedness,has been frequently reported at elevated rates in individuals with various psychiatric disorders.The consistency of this association across m...Non-right-handedness(NRH),encompassing left-handedness and mixed-handedness,has been frequently reported at elevated rates in individuals with various psychiatric disorders.The consistency of this association across multiple conditions and its underlying mechanisms is the subject of ongoing investigation.This review synthesized current evidence to explore the association between NRH and psychiatric disorders from epidemiological,genetic,and neurobiological perspectives.We systematically identified and appraised relevant literature investigating NRH prevalence in psychiatric populations and potential explanatory mechanisms.Epidemiological evidence indicates an elevated prevalence of NRH,particularly within neurodevelopmental disorders.Potential contributing mechanisms identified include early developmental disruptions,shared genetic predispositions,and atypical patterns of brain lateralization.While the association between NRH and psychiatric conditions,especially neurodevelopmental disorders,is evident,the causal pathways and relative contributions of identified mechanisms are complex and debated.This review highlighted key areas requiring further research to elucidate these relationships.展开更多
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,para...Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).展开更多
Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute cour...Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.展开更多
Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address thes...Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address these challenges,we propose an Uncertainty-Driven Graph Embedding-Enhanced Lateral Movement Detection framework(UGEA-LMD).First,the framework employs event-level incremental encoding on a continuous-time graph to capture fine-grained behavioral evolution,enabling newly appearing nodes to retain temporal contextual awareness even in the absence of historical interactions and thereby fundamentally mitigating the cold-start problem.Second,in the embedding space,we model the dependency structure among feature dimensions using a Gaussian copula to quantify the uncertainty distribution,and generate augmented samples with consistent structural and semantic properties through adaptive sampling,thus expanding the representation space of sparse samples and enhancing the model’s generalization under sparse sample conditions.Unlike static graph methods that cannot model temporal dependencies or data augmentation techniques that depend on predefined structures,UGEA-LMD offers both superior temporaldynamic modeling and structural generalization.Experimental results on the large-scale LANL log dataset demonstrate that,under the transductive setting,UGEA-LMD achieves an AUC of 0.9254;even when 10%of nodes or edges are withheld during training,UGEA-LMD significantly outperforms baseline methods on metrics such as recall and AUC,confirming its robustness and generalization capability in sparse-sample and cold-start scenarios.展开更多
N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory lo...N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.展开更多
With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of th...With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of these biological processes do not fully explain the onset,progression,and development of these conditions.Therefore,exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research.This review summarizes the potential common pathogeneses of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Huntington’s disease,frontotemporal lobar dementia,and Lewy body disease.Research findings have indicated that several common biological processes,including aging,genetic factors,progressive neuronal dysfunction,neuronal death and apoptosis,protein misfolding and aggregation,neuroinflammation,mitochondrial dysfunction,axonal transport defects,and gut microbiota dysbiosis,are involved in the pathogenesis of these six neurodegenerative diseases.Based on current information derived from diverse areas of research,these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases.Furthermore,promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed.Hence,these potential common biological processes may represent only very small,limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases.In clinical treatment,interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases.Therefore,future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks,rather than isolating individual biological processes.Based on this,therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions,as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.展开更多
Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammati...Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammation plays a significant role in the progression of these diseases.However,there is limited research on therapeutic approaches to specifically target neuroinflammation.The role of T lymphocytes,which are crucial mediators of the adaptive immune response,in neurodegenerative diseases has been increasingly recognized.This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases.The pathogenesis of neurodegenerative diseases is complex,involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons,and T cells are a key component of these processes.One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells,including microglia,astrocytes,B cells,and natural killer cells.Different subsets of CD4~+T cells,such as Th1,Th2,Th17,and regulatory T cells,can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases.Additionally,CD8~+T cells,which can directly regulate immune responses and kill target cells,also play several important roles in neurodegenerative diseases.Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that,while some patients respond positively,others may not respond as well and may even experience adverse effects.Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system,which can lead to undesirable side effects.However,with new insights into the pathophysiology of neurodegenerative diseases,there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.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.
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partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
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.
基金Funded by the National Natural Science Foundation of China(Nos.52278518 and 51938011)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.24KJB560021)。
文摘Based on the split hopkinson pressure bar(SHPB)tests results,the cubic specimens have been numerically modeled in this paper to investigate the impact of key factors,such as the rise time,duration,and incident pulse shape,on achieving stress uniformity.After analysis,the paper provides actionable methods aimed at optimizing the conditions for stress uniformity within the cubic specimen.Finally,the lateral inertia effect of cubic specimen has been scrutinized to address the existing gap in this academic area.
基金supported by a grant from NIH(R01AI132695)to RM。
文摘Chronic wasting disease—a prion disease affecting cervids:Many neurological conditions,including Alzheimer's and Parkinson's diseases,amyotrophic lateral sclerosis,frontotemporal dementias,among others,are caused by the accumulation of misfolded proteins in the brain.These diseases affect not only humans,but also animals.
文摘Non-right-handedness(NRH),encompassing left-handedness and mixed-handedness,has been frequently reported at elevated rates in individuals with various psychiatric disorders.The consistency of this association across multiple conditions and its underlying mechanisms is the subject of ongoing investigation.This review synthesized current evidence to explore the association between NRH and psychiatric disorders from epidemiological,genetic,and neurobiological perspectives.We systematically identified and appraised relevant literature investigating NRH prevalence in psychiatric populations and potential explanatory mechanisms.Epidemiological evidence indicates an elevated prevalence of NRH,particularly within neurodevelopmental disorders.Potential contributing mechanisms identified include early developmental disruptions,shared genetic predispositions,and atypical patterns of brain lateralization.While the association between NRH and psychiatric conditions,especially neurodevelopmental disorders,is evident,the causal pathways and relative contributions of identified mechanisms are complex and debated.This review highlighted key areas requiring further research to elucidate these relationships.
文摘Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).
基金supported by the National Key Research and Development Program of China,No.2022YFC2703101(to YC)the National Natural Science Fundation of China,No.82371422(to YC)+1 种基金the National Innovation and Entrepreneurship Training Program for College Students,No.202310611408(to XW)the 1·3·5 Project for Disciplines of Excellence Clinical Research Fund,West China Hospital,Sichuan University,No.2023HXFH032(to YC)。
文摘Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.
基金supported by the Zhongyuan University of Technology Discipline Backbone Teacher Support Program Project(No.GG202417)the Key Research and Development Program of Henan under Grant 251111212000.
文摘Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address these challenges,we propose an Uncertainty-Driven Graph Embedding-Enhanced Lateral Movement Detection framework(UGEA-LMD).First,the framework employs event-level incremental encoding on a continuous-time graph to capture fine-grained behavioral evolution,enabling newly appearing nodes to retain temporal contextual awareness even in the absence of historical interactions and thereby fundamentally mitigating the cold-start problem.Second,in the embedding space,we model the dependency structure among feature dimensions using a Gaussian copula to quantify the uncertainty distribution,and generate augmented samples with consistent structural and semantic properties through adaptive sampling,thus expanding the representation space of sparse samples and enhancing the model’s generalization under sparse sample conditions.Unlike static graph methods that cannot model temporal dependencies or data augmentation techniques that depend on predefined structures,UGEA-LMD offers both superior temporaldynamic modeling and structural generalization.Experimental results on the large-scale LANL log dataset demonstrate that,under the transductive setting,UGEA-LMD achieves an AUC of 0.9254;even when 10%of nodes or edges are withheld during training,UGEA-LMD significantly outperforms baseline methods on metrics such as recall and AUC,confirming its robustness and generalization capability in sparse-sample and cold-start scenarios.
基金supported by the National Institute on Aging(Nos.AG000723 and AG000578)(to VAB)the Fondation Sante(No.19656),Greece 2.0+1 种基金the National Recovery and Resilience Plan’s flagship program TAEDR-0535850the European Research Council(No.101077374-Synapto Mitophagy)(to KP)。
文摘N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.
基金supported by the National Natural Science Foundation of China,No.82160255(to RX)the Natural Science Foundation of Jiangxi Province,No.20212BAB216026(to HL)+2 种基金Science and Technology Plan Project of Health Commission of Jiangxi Province,No.202110016(to HL)Science and Technology Plan Project of Jiangxi Provincial Administration of Traditional Chinese Medicine,No.2022B975(to HL)a grant from Jiangxi Province Key Laboratory of Neurology,No.2024SSY06081(to RX).
文摘With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of these biological processes do not fully explain the onset,progression,and development of these conditions.Therefore,exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research.This review summarizes the potential common pathogeneses of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Huntington’s disease,frontotemporal lobar dementia,and Lewy body disease.Research findings have indicated that several common biological processes,including aging,genetic factors,progressive neuronal dysfunction,neuronal death and apoptosis,protein misfolding and aggregation,neuroinflammation,mitochondrial dysfunction,axonal transport defects,and gut microbiota dysbiosis,are involved in the pathogenesis of these six neurodegenerative diseases.Based on current information derived from diverse areas of research,these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases.Furthermore,promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed.Hence,these potential common biological processes may represent only very small,limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases.In clinical treatment,interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases.Therefore,future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks,rather than isolating individual biological processes.Based on this,therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions,as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.
基金supported by Yunnan Provincial Science and Technology Department,Nos.202403AC100007(to NZ),202301AY070001-239(to JY)Yunnan Revitalization Talent Support Program,Nos.2019-069(to ZY)and 2019-300(to JY)+1 种基金the National Natural Science Foundation of China,Nos.32260196(to JY)a grant from Kunming Medical University,No.2024S085(to KL)。
文摘Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammation plays a significant role in the progression of these diseases.However,there is limited research on therapeutic approaches to specifically target neuroinflammation.The role of T lymphocytes,which are crucial mediators of the adaptive immune response,in neurodegenerative diseases has been increasingly recognized.This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases.The pathogenesis of neurodegenerative diseases is complex,involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons,and T cells are a key component of these processes.One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells,including microglia,astrocytes,B cells,and natural killer cells.Different subsets of CD4~+T cells,such as Th1,Th2,Th17,and regulatory T cells,can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases.Additionally,CD8~+T cells,which can directly regulate immune responses and kill target cells,also play several important roles in neurodegenerative diseases.Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that,while some patients respond positively,others may not respond as well and may even experience adverse effects.Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system,which can lead to undesirable side effects.However,with new insights into the pathophysiology of neurodegenerative diseases,there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.
