The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of famil...The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.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
Detecting biomarkers in body fluids by optical lateral flow immune assay(LFIA) technology provides rapid access to disease information for early diagnosis.LFIA is based on an antigen-antibody reaction and is rapidly b...Detecting biomarkers in body fluids by optical lateral flow immune assay(LFIA) technology provides rapid access to disease information for early diagnosis.LFIA is based on an antigen-antibody reaction and is rapidly becoming the preferred choice of physicians and patients for point-of-care testing due to its simplicity,cost-effectiveness,and rapid detection.Observing the optical signal change from the colloidal gold of the traditional LFIA strip has been widely applied for various biomarkers detection in body fluids.Despite the significant progress,rapid real-time detection of color changes in the colloidal gold by the naked eye still faces many limitations,such as large errors and the inability to quantify and accurately detect.New optical LFIA strip technology has emerged in recent years to extend its application scenarios for achieving quantitative detection such as fluorescence,afterglow,and chemiluminescence.Herein,we summarized the development of optical LFIA technology from single to hyphenated optical signals for biomarkers detection in body fluids from invasive and non-invasive sources.Moreover,the challenge and outlook of optical LFIA strip technology are highlighted to inspire the designing of next-generation diagnostic platforms.展开更多
Objective The associations of serum trace element levels with disease progression and survival duration were assessed in individuals diagnosed with sporadic amyotrophic lateral sclerosis(sALS)in China.Methods Clinical...Objective The associations of serum trace element levels with disease progression and survival duration were assessed in individuals diagnosed with sporadic amyotrophic lateral sclerosis(sALS)in China.Methods Clinical data,including diagnostic indicators,clinical characteristics,Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores,and serum concentrations of calcium(Ca),magnesium(Mg),iron(Fe),copper(Cu),and zinc(Zn),were collected for hospitalized patients with sALS between 2018 and 2021.Correlation analysis,random forest analysis,and the Gehan-Breslow-Wilcoxon test were used to evaluate the relations between serum trace element levels,disease progression,and survival duration.Results Lower serum Ca levels and higher Mg levels were observed in patients with ALSFRS-R scores<39.Serum Mg was significantly negatively correlated with ALSFRS-R,trunk,and respiratory scores.Serum Cu and Zn also showed significant negative correlations with the respiratory score,whereas Ca and Fe were not significantly correlated with the ALSFRS-R score.The serum levels of Ca,Mg,Cu,Zn,and Fe remained consistent regardless of the site of disease onset.ALSFRS-R analysis revealed that serum Ca and Mg had a substantial effect on the total ALSFRS-R score,with serum Mg significantly influencing the course of the disease.Notably,low serum Mg levels were associated with extended survival times in patients with sALS.Conclusion Serum levels of Ca and Mg play critical roles in the progression of sALS,and a reduced serum Mg level is related to an extended survival time.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
Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives ...Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.展开更多
Soft robots,as a modern gateway to unlocking the mysteries of underwater realms,present new complexities.Modeling their behavior when in contact with external forces,whether point-based or distributed,is a primary cha...Soft robots,as a modern gateway to unlocking the mysteries of underwater realms,present new complexities.Modeling their behavior when in contact with external forces,whether point-based or distributed,is a primary challenge due to the nature of soft bodies.To obtain a holistic view of the system’s behavior determining the governing dynamics is deemed necessary.This paper proposes a new technique to simulate the dynamic lateral undulation of a soft robotic fish with a cable-driven soft tail.By integrating the rigid finite element method with rigid-body robotics,the model represents the undulation of a finite number of rigid elements connected through a set of torsional spring and damper.Instead of directly modeling external forces,we substitute equivalent joint torques into the system dynamics,allowing us to consider external effects without complicating the model.The resulting model yields valuable insights into the system’s behavior,including propulsive and lateral forces.A comparison with experimental results shows strong agreement,with a tip amplitude error of 10% at 0.8 Hz,5.25% at 1.6 Hz and 2.54%at 2.2 Hz flapping frequency.These findings illuminate the influence of lateral undulation on the overall dynamics,paving the way for fully autonomous robotic fish.展开更多
BACKGROUND Ileocecal laterally spreading tumors(LSTs)complicated by appendiceal tubular adenoma are rare and challenging to diagnose because of the absence of typical symptoms and specific diagnostic signs.Traditional...BACKGROUND Ileocecal laterally spreading tumors(LSTs)complicated by appendiceal tubular adenoma are rare and challenging to diagnose because of the absence of typical symptoms and specific diagnostic signs.Traditionally,the primary treatment has been laparoscopic appendectomy(LA).CASE SUMMARY A 63-year-old female presented with changes in bowel habits.Colonoscopy revealed an ileocecal LST.The patient underwent endoscopic submucosal dissection.Postoperative follow-up colonoscopy revealed mucosal elevation at the appendiceal orifice,with pathology confirming tubular adenoma.Abdominal computed tomography indicated a suspicious appendiceal tumor,leading to LA with partial cecectomy.The postoperative recovery was uneventful.At the 1-year follow-up,colonoscopy revealed no evidence of tumor recurrence.CONCLUSION Ileocecal LSTs with appendiceal tubular adenomas are traditionally treated with LA.endoscopic submucosal dissection can also yield favorable outcomes.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
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
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
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
Fluorescence lateral flow immunoassay(LFA)has emerged as a powerful tool for rapid screening of various biomarkers owing to its simplicity,sensitivity and flexibility.It is noteworthy that fluorescent probe mainly det...Fluorescence lateral flow immunoassay(LFA)has emerged as a powerful tool for rapid screening of various biomarkers owing to its simplicity,sensitivity and flexibility.It is noteworthy that fluorescent probe mainly determines the analytical performance of LFA.Due to the emission and excitation wavelengths are located in the visible region,most fluorophores are inevitably subject to light scattering and background autofluorescence.Herein,we reported a novel LFA sensor based on the second near-infrared(NIR-Ⅱ)fluorescent probe with excellent anti-interference capability.The designed NIR-Ⅱprobe was the Nd^(3+)and Yb^(3+)doped rare earth nanoparticles(RENPs)by employing Nd^(3+)as energy donor and Yb^(3+)as energy acceptor,which of the donor-acceptor energy transfer(ET)efficiency reached up to 80.7%.Meanwhile,relying on the convenient and effective encapsulation strategy of poly(lactic-co-glycolic acid)(PLGA)microspheres to RENPs,the surface functionalized NIR-Ⅱprobe(RE@PLGA)was obtained for subsequent bioconjugation.Benefiting from the optical advantages of NIR-Ⅱprobe,this proposed NIR-ⅡLFA displayed a good linear relationship ranging from 7 ng/mL to 200 ng/mL for the detection ofα-fetoprotein(AFP),an important biomarker of hepatocellular carcinoma(HCC).The limit of detection(LOD)was determined as low as 3.0 ng/m L,which was of 8.3 times lower than clinical cutoff value.It is promising that LFA sensor based on this efficient RENPs probe provides new opportunities for high sensitive detection of various biomarkers in biological samples.展开更多
Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves ...Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.展开更多
Recent experiments have found that a liquid crystal elastomer(LCE)rod supported in the middle can rotate continuously under horizontal illumination due to the combined impacts of gravity and light-fueled lateral bend-...Recent experiments have found that a liquid crystal elastomer(LCE)rod supported in the middle can rotate continuously under horizontal illumination due to the combined impacts of gravity and light-fueled lateral bend-ing deformation.Similar to traditional gravity-driven systems,it is constrained by the direction of gravity and cannot be applied in microgravity environments.This study introduces a lateral constraint to a liquid crystal elastomer rod system,enabling self-rotation under lighting from any direction,including horizontal and vertical illumination.Through theoretical modeling,the results indicate that the system can steadily rotate under the combined impacts of lateral forces and vertical illumination.Factors like thermal energy flux,thermal conduc-tivity coefficient,the LCE rod length,contraction coefficient,and friction coefficient affect the angular velocity of the self-rotation.The numerical computations align closely with the experimental data.Our proposed steadily self-rotating system features a simple structure with constant self-rotation.It operates independently of gravity direction,making it an excellent choice for special environments,such as the microgravity conditions on the Moon.The lateral constraint strategy presented in this study offers a general approach to expanding the applica-tions of gravity-driven self-sustained motion,with promising potential,especially in microgravity settings,where its versatility under varying lighting conditions could yield valuable insights.展开更多
Amyotrophic lateral sclerosis(ALS),one of the most prevalent neurodegenerative disorders,is pathologically characterized by the progressive degeneration of both upper and lower motor neurons,leading to muscle weakness...Amyotrophic lateral sclerosis(ALS),one of the most prevalent neurodegenerative disorders,is pathologically characterized by the progressive degeneration of both upper and lower motor neurons,leading to muscle weakness,paralysis,and death within 2–4 years post-diagnosis.ALS is categorized into familial ALS(FALS)and sporadic ALS,with FALS accounting for approximately 10%of ALS cases.As a genetically heterogeneous disease,ALS exhibits diverse inheritance patterns,including autosomal dominant,autosomal recessive,and X-linked transmission,and genetic factors play pivotal roles in disease pathogenesis.To date,at least 34 disease-causing loci and 32 genes for ALS have been identified.The investigations of mutant protein products and the establishment of animal models have unraveled potential pathogenic pathways,offering insights into the mechanisms of neurodegeneration in ALS.This review focuses on ALS clinical characteristics,neuropathological features,causative loci/genes,genetic susceptibility factors,animal models,and pathogenic mechanisms,with particular attention to recent advances in genetic findings and pathogenic pathways of ALS.Elucidation of the genetic basis of ALS could provide the scientific foundation for personalized treatments to address this recalcitrant disease.展开更多
Dear Editor,Post-traumatic stress disorder(PTSD)is a chronic neuropsychiatric disorder triggered by severe traumatic events,characterized by persistent intrusive memories,emotional dysregulation,hyperarousal,and avoid...Dear Editor,Post-traumatic stress disorder(PTSD)is a chronic neuropsychiatric disorder triggered by severe traumatic events,characterized by persistent intrusive memories,emotional dysregulation,hyperarousal,and avoidance behaviors[1,2].PTSD is associated with significant gene expression changes in key brain regions,including the ventral tegmental area(VTA),which may underlie dysregulation of dopaminergic signaling and stress-related behaviors[3].展开更多
Monocot root systems comprise a large number of lateral roots to allow them to survive and colonize land.Auxin signaling pathways centered on Aux/IAA play a crucial role in lateral root development.However,in non-mode...Monocot root systems comprise a large number of lateral roots to allow them to survive and colonize land.Auxin signaling pathways centered on Aux/IAA play a crucial role in lateral root development.However,in non-model monocot plants,the effects of Aux/IAA on lateral root initiation and number remain largely unknown.The present study transformed PheIAA17,a member of the Aux/IAA family of Moso bamboo,into rice and found that it significantly drove plants to produce lateral roots and improved the rooting rate.Quantitative experiments showed that PheIAA17 overexpression significantly affected the expression of ARF family members.Phylogenetic and promoter analyses indicate that PheARF3-2 belongs to class B ARF,and the promoter region contains auxin response elements.The results of yeast one-hybrid and dual-luciferase reporter assays confirmed that PheIAA17 bound specific fragments of the PheARF3-2 promoter to repress its transcriptional activity.Y2H and BiFC assay have shown that PheIAA17 and PheIAA30-3 could physically interact in vitro and in vivo.Taken together,this study reports a new molecular module centered on PheIAA17,which directs plants to alter root morphology through an increase in lateral roots.展开更多
Background and objectives:Recent studies have highlighted a link between amyotrophic lateral sclerosis(ALS)and gut microbiota.This prospective study aimed to evaluate the effects of electroacupuncture combined with Ch...Background and objectives:Recent studies have highlighted a link between amyotrophic lateral sclerosis(ALS)and gut microbiota.This prospective study aimed to evaluate the effects of electroacupuncture combined with Chinese herbal medicine on gut microbiota and metabolomics in ALS patients.Methods:Ten ALS patients were randomly assigned to either a treatment group(electroacupuncture with Chinese herbal medicine,n=6)or a control group(waiting treatment,n=4).Healthy controls(age-and sex-matched,n=10)were also included.Data were collected after 12 sessions of electroacupuncture and follow-ups at three and six months.ALS functional rating scale scores were documented pre-and post-treatment.Stool samples were collected at two time points(T0 and T4 weeks)and analyzed,and metabolomic profiles from urine samples were analyzed post-treatment.Heatmap correlation analysis was used to explore relationships between microbiota,metabolomics,and clinical outcomes.Results:Treatment with electroacupuncture reduced Eisenbergiella abundance in the treatment group.A significant positive correlation was found between Lachnospiraceae and ALS functional rating scale scores(P<0.005 and P<0.001,respectively).Differential expression of purine metabolism was observed in ALS patients(P=0.0017).Conclusions:Imbalances in the gut microbiome and metabolic disorders have been found among patients with ALS.These imbalances appear to be partially mitigated by treatment with electroacupuncture combined with Chinese herbal medicine.Our research suggests that Eisenbergiella might be a diagnostic biomarker and a potential therapeutic target for ALS.展开更多
Subduction zones are major convergent boundaries,where the downgoing oceanic plates usually form continuous tabular slabs extending deep into the Earth’s interior.However,many subducting slabs especially those with y...Subduction zones are major convergent boundaries,where the downgoing oceanic plates usually form continuous tabular slabs extending deep into the Earth’s interior.However,many subducting slabs especially those with young ages,exhibit complex geometry,with varying degrees of influence on the overlying continent and surface environment.To better understand the mechanism of such slab deformation,we apply four-dimensional finite element geodynamic models with data assimilation to investigate the evolution of the Cocos subduction in Central America,where a double-slab configuration with complex tearing has recently been observed.We reproduce the subduction history of the Cocos slab since the Eocene.During this period,multiple episodes of tearing occurred within the Cocos slab,starting at 25 Ma.We find that the ancient Farallon slab,subducted during the Mesozoic,enhances the lateral pressure gradient across the slab hinge,promoting eastward mantle flow and tearing of the Cocos slab.The repeated tearing and subduction of the young Cocos plate have shaped the complex slab configuration in the region.展开更多
基金supported by the Natural Science Foundation of Beijing,Nos.7244428(to WZ)and 7222215(to JH)the Peking University Medicine Sailing Program forYoung Scholars’Scientific and Technological Innovation,No.BMU2023YFJHPY034(to WZ)+4 种基金the National Natural Science Foundation of China,Nos.81873784,82071426(to DF),and81974197(to JH)the Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(to DF)Beijing Physician-Scientist TrainingProgram,No.BJPSTP-2024-03(to JH)the China Postdoctoral Science Foundation,Nos.2022TQ0014(to LX),2022M720284(to LX)the E-Town Cooperation&Development Foundation,No.YCXJ-JZ-2023-017(to LX).
文摘The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.
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 Natural Science Foundation of China (Nos.22234005,22494632,22404081)the Natural Science Foundation of Jiangsu Province (Nos.BK20222015,BK20240534)。
文摘Detecting biomarkers in body fluids by optical lateral flow immune assay(LFIA) technology provides rapid access to disease information for early diagnosis.LFIA is based on an antigen-antibody reaction and is rapidly becoming the preferred choice of physicians and patients for point-of-care testing due to its simplicity,cost-effectiveness,and rapid detection.Observing the optical signal change from the colloidal gold of the traditional LFIA strip has been widely applied for various biomarkers detection in body fluids.Despite the significant progress,rapid real-time detection of color changes in the colloidal gold by the naked eye still faces many limitations,such as large errors and the inability to quantify and accurately detect.New optical LFIA strip technology has emerged in recent years to extend its application scenarios for achieving quantitative detection such as fluorescence,afterglow,and chemiluminescence.Herein,we summarized the development of optical LFIA technology from single to hyphenated optical signals for biomarkers detection in body fluids from invasive and non-invasive sources.Moreover,the challenge and outlook of optical LFIA strip technology are highlighted to inspire the designing of next-generation diagnostic platforms.
文摘Objective The associations of serum trace element levels with disease progression and survival duration were assessed in individuals diagnosed with sporadic amyotrophic lateral sclerosis(sALS)in China.Methods Clinical data,including diagnostic indicators,clinical characteristics,Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores,and serum concentrations of calcium(Ca),magnesium(Mg),iron(Fe),copper(Cu),and zinc(Zn),were collected for hospitalized patients with sALS between 2018 and 2021.Correlation analysis,random forest analysis,and the Gehan-Breslow-Wilcoxon test were used to evaluate the relations between serum trace element levels,disease progression,and survival duration.Results Lower serum Ca levels and higher Mg levels were observed in patients with ALSFRS-R scores<39.Serum Mg was significantly negatively correlated with ALSFRS-R,trunk,and respiratory scores.Serum Cu and Zn also showed significant negative correlations with the respiratory score,whereas Ca and Fe were not significantly correlated with the ALSFRS-R score.The serum levels of Ca,Mg,Cu,Zn,and Fe remained consistent regardless of the site of disease onset.ALSFRS-R analysis revealed that serum Ca and Mg had a substantial effect on the total ALSFRS-R score,with serum Mg significantly influencing the course of the disease.Notably,low serum Mg levels were associated with extended survival times in patients with sALS.Conclusion Serum levels of Ca and Mg play critical roles in the progression of sALS,and a reduced serum Mg level is related to an extended survival time.
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 Natural Science Foundation of China,Nos.82071426,81873784Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(all to DF)。
文摘Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.
文摘Soft robots,as a modern gateway to unlocking the mysteries of underwater realms,present new complexities.Modeling their behavior when in contact with external forces,whether point-based or distributed,is a primary challenge due to the nature of soft bodies.To obtain a holistic view of the system’s behavior determining the governing dynamics is deemed necessary.This paper proposes a new technique to simulate the dynamic lateral undulation of a soft robotic fish with a cable-driven soft tail.By integrating the rigid finite element method with rigid-body robotics,the model represents the undulation of a finite number of rigid elements connected through a set of torsional spring and damper.Instead of directly modeling external forces,we substitute equivalent joint torques into the system dynamics,allowing us to consider external effects without complicating the model.The resulting model yields valuable insights into the system’s behavior,including propulsive and lateral forces.A comparison with experimental results shows strong agreement,with a tip amplitude error of 10% at 0.8 Hz,5.25% at 1.6 Hz and 2.54%at 2.2 Hz flapping frequency.These findings illuminate the influence of lateral undulation on the overall dynamics,paving the way for fully autonomous robotic fish.
文摘BACKGROUND Ileocecal laterally spreading tumors(LSTs)complicated by appendiceal tubular adenoma are rare and challenging to diagnose because of the absence of typical symptoms and specific diagnostic signs.Traditionally,the primary treatment has been laparoscopic appendectomy(LA).CASE SUMMARY A 63-year-old female presented with changes in bowel habits.Colonoscopy revealed an ileocecal LST.The patient underwent endoscopic submucosal dissection.Postoperative follow-up colonoscopy revealed mucosal elevation at the appendiceal orifice,with pathology confirming tubular adenoma.Abdominal computed tomography indicated a suspicious appendiceal tumor,leading to LA with partial cecectomy.The postoperative recovery was uneventful.At the 1-year follow-up,colonoscopy revealed no evidence of tumor recurrence.CONCLUSION Ileocecal LSTs with appendiceal tubular adenomas are traditionally treated with LA.endoscopic submucosal dissection can also yield favorable outcomes.
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.
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 the National Natural Science Foundation of China(Nos.U2267221,22107029,22377135)the Bohai Rim Advanced Research Institute for Drug Discovery(No.LX215002)+5 种基金the Natural Science Foundation of Shandong Province(No.ZR2022QH212)the Taishan Scholars Program(No.tsqn202312305)the Young Elite Scientists Sponsorship Program by Chinese Chemical Societythe Fundamental Research Projects of Science&Technology Innovation and development Plan in Yantai City(No.2023JCYJ059)the Shandong Laboratory Program(No.SYS202205)the Shanghai Postdoctoral Excellence Program(No.2023704)。
文摘Fluorescence lateral flow immunoassay(LFA)has emerged as a powerful tool for rapid screening of various biomarkers owing to its simplicity,sensitivity and flexibility.It is noteworthy that fluorescent probe mainly determines the analytical performance of LFA.Due to the emission and excitation wavelengths are located in the visible region,most fluorophores are inevitably subject to light scattering and background autofluorescence.Herein,we reported a novel LFA sensor based on the second near-infrared(NIR-Ⅱ)fluorescent probe with excellent anti-interference capability.The designed NIR-Ⅱprobe was the Nd^(3+)and Yb^(3+)doped rare earth nanoparticles(RENPs)by employing Nd^(3+)as energy donor and Yb^(3+)as energy acceptor,which of the donor-acceptor energy transfer(ET)efficiency reached up to 80.7%.Meanwhile,relying on the convenient and effective encapsulation strategy of poly(lactic-co-glycolic acid)(PLGA)microspheres to RENPs,the surface functionalized NIR-Ⅱprobe(RE@PLGA)was obtained for subsequent bioconjugation.Benefiting from the optical advantages of NIR-Ⅱprobe,this proposed NIR-ⅡLFA displayed a good linear relationship ranging from 7 ng/mL to 200 ng/mL for the detection ofα-fetoprotein(AFP),an important biomarker of hepatocellular carcinoma(HCC).The limit of detection(LOD)was determined as low as 3.0 ng/m L,which was of 8.3 times lower than clinical cutoff value.It is promising that LFA sensor based on this efficient RENPs probe provides new opportunities for high sensitive detection of various biomarkers in biological samples.
文摘Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
基金supported by the University Natural Science Research Project of Anhui Province(Grant Nos.2022AH040042 and 2022AH020029)the National Natural Science Foundation of China(Grant No.12172001)+1 种基金Anhui Provincial Natural Science Foundation(Grant No.2208085Y01)the Housing and Urban-Rural Development Science and Technology Project of Anhui Province(Grant No.2022-YF069).
文摘Recent experiments have found that a liquid crystal elastomer(LCE)rod supported in the middle can rotate continuously under horizontal illumination due to the combined impacts of gravity and light-fueled lateral bend-ing deformation.Similar to traditional gravity-driven systems,it is constrained by the direction of gravity and cannot be applied in microgravity environments.This study introduces a lateral constraint to a liquid crystal elastomer rod system,enabling self-rotation under lighting from any direction,including horizontal and vertical illumination.Through theoretical modeling,the results indicate that the system can steadily rotate under the combined impacts of lateral forces and vertical illumination.Factors like thermal energy flux,thermal conduc-tivity coefficient,the LCE rod length,contraction coefficient,and friction coefficient affect the angular velocity of the self-rotation.The numerical computations align closely with the experimental data.Our proposed steadily self-rotating system features a simple structure with constant self-rotation.It operates independently of gravity direction,making it an excellent choice for special environments,such as the microgravity conditions on the Moon.The lateral constraint strategy presented in this study offers a general approach to expanding the applica-tions of gravity-driven self-sustained motion,with promising potential,especially in microgravity settings,where its versatility under varying lighting conditions could yield valuable insights.
基金funded by the National Natural Science Foundation of China(81800219)the Natural Science Foundation of Hunan Province(2023JJ30715)+5 种基金Scientific Research Project of Hunan Provincial Health Commission(A202303018385 and B202303078399)Health Research Project of Hunan Provincial Health Commission(W20243024)Province-level College Students'Innovative Training Plan Program(S202310533352)Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(YX202109)Sublimation Scholars Project of Central South UniversityDistinguished Professor of the Lotus Scholars Award Program of Hunan Province,China.
文摘Amyotrophic lateral sclerosis(ALS),one of the most prevalent neurodegenerative disorders,is pathologically characterized by the progressive degeneration of both upper and lower motor neurons,leading to muscle weakness,paralysis,and death within 2–4 years post-diagnosis.ALS is categorized into familial ALS(FALS)and sporadic ALS,with FALS accounting for approximately 10%of ALS cases.As a genetically heterogeneous disease,ALS exhibits diverse inheritance patterns,including autosomal dominant,autosomal recessive,and X-linked transmission,and genetic factors play pivotal roles in disease pathogenesis.To date,at least 34 disease-causing loci and 32 genes for ALS have been identified.The investigations of mutant protein products and the establishment of animal models have unraveled potential pathogenic pathways,offering insights into the mechanisms of neurodegeneration in ALS.This review focuses on ALS clinical characteristics,neuropathological features,causative loci/genes,genetic susceptibility factors,animal models,and pathogenic mechanisms,with particular attention to recent advances in genetic findings and pathogenic pathways of ALS.Elucidation of the genetic basis of ALS could provide the scientific foundation for personalized treatments to address this recalcitrant disease.
基金supported by grants from the National Natural Science Foundation of China(81871062)Guangdong Basic and Applied Basic Research Foundation(2024A1515012913)+1 种基金the Key Research Foundation of Guangdong Provincial Education Bureau(2023ZDZX2037)the Special Fund of Science and Technology Innovation Cultivation of Guangdong University Students(pdjh2024a238,pdjh2025ak133)。
文摘Dear Editor,Post-traumatic stress disorder(PTSD)is a chronic neuropsychiatric disorder triggered by severe traumatic events,characterized by persistent intrusive memories,emotional dysregulation,hyperarousal,and avoidance behaviors[1,2].PTSD is associated with significant gene expression changes in key brain regions,including the ventral tegmental area(VTA),which may underlie dysregulation of dopaminergic signaling and stress-related behaviors[3].
基金supported by the National Key Research and Development Program of China(2021YFD2200505)the National Natural Science Foundation of China(32071849)。
文摘Monocot root systems comprise a large number of lateral roots to allow them to survive and colonize land.Auxin signaling pathways centered on Aux/IAA play a crucial role in lateral root development.However,in non-model monocot plants,the effects of Aux/IAA on lateral root initiation and number remain largely unknown.The present study transformed PheIAA17,a member of the Aux/IAA family of Moso bamboo,into rice and found that it significantly drove plants to produce lateral roots and improved the rooting rate.Quantitative experiments showed that PheIAA17 overexpression significantly affected the expression of ARF family members.Phylogenetic and promoter analyses indicate that PheARF3-2 belongs to class B ARF,and the promoter region contains auxin response elements.The results of yeast one-hybrid and dual-luciferase reporter assays confirmed that PheIAA17 bound specific fragments of the PheARF3-2 promoter to repress its transcriptional activity.Y2H and BiFC assay have shown that PheIAA17 and PheIAA30-3 could physically interact in vitro and in vivo.Taken together,this study reports a new molecular module centered on PheIAA17,which directs plants to alter root morphology through an increase in lateral roots.
基金2023 Research and Cultivation Fund of Capital Medical University-Study on the correlation between intestinal flora and neurofilament light chain in mice with amyotrophic lateral sclerosis induced by acupuncture(PYZ23032)R&D Program of Beijing Municipal Education Commission 2024:Study on the improvement of clinical symptoms and mechanism of acupuncture in amyotrophic lateral sclerosis(KM202410025018)+1 种基金China National Natural Science Foundation of Youth Project(No.82405557)2024-2026 Chinese Association of Chinese Medicine Young Talent Lifting Project(2024-QNRC2-B08).
文摘Background and objectives:Recent studies have highlighted a link between amyotrophic lateral sclerosis(ALS)and gut microbiota.This prospective study aimed to evaluate the effects of electroacupuncture combined with Chinese herbal medicine on gut microbiota and metabolomics in ALS patients.Methods:Ten ALS patients were randomly assigned to either a treatment group(electroacupuncture with Chinese herbal medicine,n=6)or a control group(waiting treatment,n=4).Healthy controls(age-and sex-matched,n=10)were also included.Data were collected after 12 sessions of electroacupuncture and follow-ups at three and six months.ALS functional rating scale scores were documented pre-and post-treatment.Stool samples were collected at two time points(T0 and T4 weeks)and analyzed,and metabolomic profiles from urine samples were analyzed post-treatment.Heatmap correlation analysis was used to explore relationships between microbiota,metabolomics,and clinical outcomes.Results:Treatment with electroacupuncture reduced Eisenbergiella abundance in the treatment group.A significant positive correlation was found between Lachnospiraceae and ALS functional rating scale scores(P<0.005 and P<0.001,respectively).Differential expression of purine metabolism was observed in ALS patients(P=0.0017).Conclusions:Imbalances in the gut microbiome and metabolic disorders have been found among patients with ALS.These imbalances appear to be partially mitigated by treatment with electroacupuncture combined with Chinese herbal medicine.Our research suggests that Eisenbergiella might be a diagnostic biomarker and a potential therapeutic target for ALS.
基金supported by the Strategy Priority Research Program(Category B)of the Chinese Academy of Sciences(Grant No.XDB0710000)the National Natural Science Foundation of China(Grant No.92355302)supported by the National Supercomputer Center in Tianjin.
文摘Subduction zones are major convergent boundaries,where the downgoing oceanic plates usually form continuous tabular slabs extending deep into the Earth’s interior.However,many subducting slabs especially those with young ages,exhibit complex geometry,with varying degrees of influence on the overlying continent and surface environment.To better understand the mechanism of such slab deformation,we apply four-dimensional finite element geodynamic models with data assimilation to investigate the evolution of the Cocos subduction in Central America,where a double-slab configuration with complex tearing has recently been observed.We reproduce the subduction history of the Cocos slab since the Eocene.During this period,multiple episodes of tearing occurred within the Cocos slab,starting at 25 Ma.We find that the ancient Farallon slab,subducted during the Mesozoic,enhances the lateral pressure gradient across the slab hinge,promoting eastward mantle flow and tearing of the Cocos slab.The repeated tearing and subduction of the young Cocos plate have shaped the complex slab configuration in the region.
