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
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
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
Saltmarsh is one of the blue carbon ecosystems for the highest carbon burial efficiency.However,the buried carbon in saltmarsh may still be exported to coastal water through porewater exchange,a process that has often...Saltmarsh is one of the blue carbon ecosystems for the highest carbon burial efficiency.However,the buried carbon in saltmarsh may still be exported to coastal water through porewater exchange,a process that has often been overlooked in previous studies.A typical tidal creek of the Dongtan saltmarsh wetland in Chongming Island,Shanghai,China,was studied.The224Ra and223Ra activities were measured and the hydrological parameters such as water flow were determined,from which the porewater exchange rate in the tidal creek was estimated to be 1.78±1.73 cm/d.Meanwhile,the carbon concentrations in porewater were determined,based on which the fluxes of dissolved inorganic carbon(DIC),dissolved organic carbon(DOC),CH_(4),and CO_(2)exported from porewater exchange were derived to be 60±17,6.6±4.0,0.082±0.079,and 16±11 mmol/(m^(2)·d),respectively.In addition,analysis on different species of carbon in the creek water showed that,the fluxes of DIC,DOC,CH_(4),and CO_(2)exported laterally from tidal creek to coastal sea were 58±14,7.6±2.3,0.0011±0.00063,and 1.5±0.68 mmol/(m^(2)·d),respectively,indicating that the porewater exchange-derived carbon fluxes accounted for a large portion of the lateral carbon outwelling,and even much higher than those in CH_(4)and CO_(2)fluxes.Furthermore,the carbon exported from porewater exchange accounted for 50%of the carbon burial in the tidal creek system,of which DIC accounted for 73%of the total carbon flux transported by porewater exchange.Therefore,this study indicated that the porewater exchange-derived carbon fluxes to the tidal creek water may cause an overestimation in the carbon sequestration capacity of saltmarsh wetlands,and revealed the importance of porewater exchange for the carbon cycle of tidal creek system of saltmarsh wetlands.展开更多
The advancement of various types of fluorescent nanoparticles is crucial for enhancing the application of lateral flow immunoassays(LFIA)across multiple fields.Currently,the fluorescent nanoparticles utilized in LFIA ...The advancement of various types of fluorescent nanoparticles is crucial for enhancing the application of lateral flow immunoassays(LFIA)across multiple fields.Currently,the fluorescent nanoparticles utilized in LFIA predominantly consist of traditional dye-doped nanoparticles or aggregation-induced luminescence dye-doped nanoparticles.The reliance on specific types of nanoparticles limits the diversity of signal reporting groups available for LFIA.Herein,we developed a solid-state luminescent dye-doped nanoparticles(SLDNPs)-based LFIA system with exceptional stability for the detection of C-reactive protein(CRP)in serum.The synthesis of SLD_(520)NP_(S)was simplicity,efficient and eco-friendly,which was ideal for large-scale production of the LFIA test strip.And the SLD_(520)NP_(S)exhibits superior fluorescence quantum yield(49%),fully guarantees the performance of the LFIA test strip.The constructed SLD_(520)NPsm Ab1-based LFIA demonstrated a satisfactory linear relationship with CRP concentrations ranging from 0.5 ng/mL to 100 ng/mL,with limits of detection(LOD)of 0.78 ng/mL and a visible LOD of 1 ng/mL using a handheld 405 nm lamp.Furthermore,the developed LFIA exhibited excellent recoveries in serum,ranging from 94.45%to 102.5%.Overall,the outstanding performance of the SLD_(520)NPs-mAb1-based LFIA indicates that solid-state luminescent dyes have significant potential applications in the field of LFIA.展开更多
Lateral flow immunoassay(LFIA),a rapid detection technique noted for simplicity and economy,has showcased indispensable applicability in diverse domains such as disease screening,food safety,and environmental monitori...Lateral flow immunoassay(LFIA),a rapid detection technique noted for simplicity and economy,has showcased indispensable applicability in diverse domains such as disease screening,food safety,and environmental monitoring.Nevertheless,challenges still exist in detecting ultra-low concentration analytes due to the inherent sensitivity limitations of LFIA.Recently,significant advances have been achieved by integrating enzyme activity probes and transforming LFIA into a highly sensitive tool for rapidly detecting trace analyte concentrations.Specifically,modifying natural enzymes or engineered nanozymes allows them to function as immune probes,directly catalyzing the production of signal molecules or indirectly initiating enzyme activity.Therefore,the signal intensity and detection sensitivity of LFIA are markedly elevated.The present review undertakes a comprehensive examination of pertinent research literature,offering a systematic analysis of recently proposed enzyme-based signal amplification strategies.By way of comparative assessment,the merits and demerits of current approaches are delineated,along with the identification of research avenues that still need to be explored.It is anticipated that this critical overview will garner considerable attention within the biomedical and materials science communities,providing valuable direction and insight toward the advancement of high-performance LFIA technologies.展开更多
Chakouyi(CKY)horses from the Qinghai-Xizang Plateau are well known for their unique lateral gaits and high-altitude adaptation,but genetic mechanisms underlying these phenotypes remain unclear.This study presents a co...Chakouyi(CKY)horses from the Qinghai-Xizang Plateau are well known for their unique lateral gaits and high-altitude adaptation,but genetic mechanisms underlying these phenotypes remain unclear.This study presents a comparison of 60 newly resequenced genomes of gaited CKY horses with 139 public genomes from 19 horse breeds.Population structure analyses(admixture,PCA,and neighbor-joining tree)reveal a close genetic relationship between CKY and other highland breeds(Tibetan and Chaidamu horses).Compared with other Chinese breeds,CKY horses present reduced nucleotide diversity(θπ)and lower inbreeding(FROHcoefficient),suggesting possible selective pressures.A key region on chromosome 23(Chr23:22.3-22.6 Mb)is associated with the lateral gaits and harbors a highly prevalent nonsense mutation(Chr 23:22,391,254 C>A,Ser301STOP)in the DMRT3 gene,with an 88%homozygosity rate,which is strongly correlated with the distinctive gait of CKY horses.Furthermore,selection signals reveal that the EPAS1 gene is related to high-altitude adaptation,and the CAT gene contributes to altitude resilience in CKY horses.These findings suggest that preserving genetic diversity is essential for maintaining the unique gaits and high-altitude adaptations of CKY horses.展开更多
Columnar jointed rock mass(CJRM)combines and mosaic of slender rock columns with different height-to-width(H/W)ratios.Revealing the correlation of the mechanical behavior of individual rock columns with internal facto...Columnar jointed rock mass(CJRM)combines and mosaic of slender rock columns with different height-to-width(H/W)ratios.Revealing the correlation of the mechanical behavior of individual rock columns with internal factors(H/W ratio and material strength)and external factor(lateral pressure)is fundamental to understanding the deterioration of CJRM.We adopt a numerical scheme that combines a statistical meso-damage constitutive model with a finite element formulation based on finite deformation,which can simultaneously consider both material failure and structural instability of the rock columns.Compression tests of rock columns with different H/W ratios and material strengths under varying lateral pressures were conducted to analyze the macro-strength features and failure modes.The numerical results show that increasing the material strength can improve the macro-strength,while the effect of H/W ratio is the opposite.Both increases can promote the conversion of failure modes,and the evolution process is as follows:material failure-induced structural instability→synergy and competition between material failure and structural instability→structural instability-induced material failure.Notably,for the last failure mode,an increase in lateral pressure decreases the macro-strength of the rock column and heightens its instability risk.This finding provides new insights into the response of rocks with different H/W ratios under lateral pressure,extending beyond traditional material-based perspectives.According to the position of the failure mode demarcation line,the failure mode of the rock column can be regulated.展开更多
Leaves and glumes act as lateral organs and have essential effects on photosynthesis and seed morphology,thus affecting yield.However,the molecular mechanisms controlling their polarity development in rice still need ...Leaves and glumes act as lateral organs and have essential effects on photosynthesis and seed morphology,thus affecting yield.However,the molecular mechanisms controlling their polarity development in rice still need further study.Here,we isolated a polarity defect of lateral organs 1(pdl1)mutant in rice,which exhibits twisted/filamentous-shaped leaves and cracked/filamentous-shaped lemmas caused by defects in polarity development.PDL1 encodes a SUPPRESSOR OF GENE SILENCING 3 protein localized in the cytoplasmic granules.PDL1 is expressed in the shoot apical meristem,inflorescence meristem,floral meristem,and lateral organs including leaves and floral organs.PDL1 is involved in the synthesis of tasiR-ARF,which may subsequently modulate the expression of OsARFs.Meanwhile,the expression levels of abaxial miR165/166 and the adaxial identity genes OSHBs were respectively increased and reduced significantly.The results of this study clarify the molecular mechanism by which PDL1-mediated tasiR-ARF synthesis regulates the lateral organ polarity development in rice.展开更多
This paper aims to evaluate the stochastic response of steel columns subjected to blast loads using the modified single degree of freedom(MSDOF)method,which assessed towards the conventional single degree of freedom(S...This paper aims to evaluate the stochastic response of steel columns subjected to blast loads using the modified single degree of freedom(MSDOF)method,which assessed towards the conventional single degree of freedom(SDOF)and the experimentally validated Finite Element(FE)methods(LSDYNA).For this purpose,special atten-tion is given to calculating the response of H-shaped steel columns under blast.The damage amount is determined based on the support rotation criterion,which is expressed as a function of their maximum lateral mid-span dis-placement.To account for uncertainties in input parameters and obtain the failure probability,the Monte Carlo simulation(MCS)method is employed,complemented by the Latin Hypercube Sampling(LHS)method to reduce the number of simulations.A parametric analysis is hence performed to examine the effect of several input pa-rameters(including both deterministic and probabilistic parameters)on the probability of column damage as a function of support rotation.First,the MSDOF method confirms its higher accuracy in estimating the probability of column damage due to blast,compared to the conventional SDOF.The collected results also show that un-certainties of several input parameters have significant effects on the column behavior.In particular,geometric parameters(including cross-sectional characteristics,boundary conditions and column length)have major effect on the corresponding column response,in the same way of input blast load parameters and material properties.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
BACKGROUND To observe the endoscopic and pathological characteristics of laterally spreading tumors(LSTs)and explore the risk factors for carcinogenesis and submucosal infiltration.AIM To analyze the clinicopathologic...BACKGROUND To observe the endoscopic and pathological characteristics of laterally spreading tumors(LSTs)and explore the risk factors for carcinogenesis and submucosal infiltration.AIM To analyze the clinicopathological features of colorectal LSTs treated endoscopically and determine risk factors associated with carcinogenesis and submucosal invasion,providing evidence-based guidance for optimal treatment strategy selection.METHODS This study retrospectively analyzed the sex,age,and endoscopic and pathological features of patients who underwent endoscopic treatment for colorectal LSTs in our hospital from January 2021 to July 2024.Single-factor analysis was used to identify the risk factors for cancer and submucosal infiltration,and the factors with statistical significance were included in multivariate logistic regression analysis.RESULTS A total of 422 patients,including 224 males and 198 females,aged 63.45±9.23 years,were included.There were 456 LST lesions in total.The length of the endoscopically resected specimens was 3.01±0.48 cm,and the length of the lesions was 2.37±1.59 cm.It was located in 115 rectums(25.2%),40 sigmoid colon(8.8%),26 descending colon(5.7%),109 transverse colon(23.9%),112 ascending colon(24.6%),and 54 ileocecal regions(11.8%).Endoscopic submucosal dissection(ESD)was performed in 237 patients(52.0%),and endoscopic mucosal resection(EMR)was performed in 95 patients(20.8%).There were 113 EMR with precutting cases(24.8%),11 ESD with snare cases(2.4%),4 delayed bleeding cases and 5 intraoperative perforations.The pathological results revealed 119 cases of low-grade intraepithelial neoplasia(26.1%),221 cases of high-grade intraepithelial neoplasia(48.5%),82 cases of intramucosal carcinoma(18.0%),and 34 cases of submucous invasive carcinoma(7.5%).Multiple logistic regression analyses revealed that lesion size(>2 cm),lesion location(rectal)and endoscopic classification[false depressed tubulovillous adenoma(LST-NG pseudodepressed type,LST-NG-PD),type 1 particles(LST-G homogenous type),and LST-G nodular mixed type],accompanied by large nodules(with)were independent risk factors for carcinogenesis;endoscopic classification(LST-NG-PD)and the presence of large nodules were independent risk factors for submucosal infiltration.CONCLUSION These risk factors provide practical guidance for treatment selection:LST-NG-PD with large nodules should prioritize ESD,while high-risk rectal lesions>2 cm may require additional imaging evaluation before endoscopic resection.展开更多
Irregularities in the track and uneven forces acting on the train can cause shifts in the position of the superconducting magnetic levitation train relative to the track during operation.These shifts lead to asymmetri...Irregularities in the track and uneven forces acting on the train can cause shifts in the position of the superconducting magnetic levitation train relative to the track during operation.These shifts lead to asymmetries in the flow field structure on both sides of the narrow suspension gap,resulting in instability and deterioration of the train’s aerodynamic characteristics,significantly impacting its operational safety.In this study,we firstly validate the aerodynamic characteristics of the superconducting magnetic levitation system by developing a numerical simulation method based on wind tunnel test results.We then investigate the influence of lateral translation parameters on the train’s aerodynamic performance under conditions both with and without crosswinds.We aim to clarify the evolution mechanism of the flow field characteristics under the coupling effect between the train and the U-shaped track and to identify the most unfavorable operational parameters contributing to the deterioration of the train’s aerodynamic properties.The findings show that,without crosswinds,a lateral translation of 30 mm causes a synchronous resonance phenomenon at the side and bottom gaps of the train-track coupling,leading to the worst aerodynamic performance.Under crosswind conditions,a lateral translation of 40 mm maximizes peak pressure fluctuations and average turbulent kinetic energy around the train,resulting in the poorest aerodynamic performance.This research provides theoretical support for enhancing the operational stability of superconducting magnetic levitation trains.展开更多
Background:The extensor carpi radial muscle may become imbalanced compared to other muscles in the upper arm and can disrupt the overall muscle balance in the upper limb.This muscular imbalance may then cause inflamma...Background:The extensor carpi radial muscle may become imbalanced compared to other muscles in the upper arm and can disrupt the overall muscle balance in the upper limb.This muscular imbalance may then cause inflammation or irritation in the tendon.Regular physical activity is rarely used as the only treatment for lowering limb edema.Heavy slow resistance(HSR)training is effective compared to regular exercises.HSR affects functional abilities and physical refinement differently from conventional workouts.This study evaluated the effects of HSR and conventional exercise(CE)on subjects aged 45–65 years with unilateral elbow pain on,in Chennai city.Methods:Patient received conservative care in the Physiotherapy Department from January 2022 to April 2022.This study compares the pre-and posttypes.Tennis Elbow Evaluation(Patient-Rated Tennis Elbow Evaluation,PRTEE)questionnaires,a patient-specific functional scale,and grip strength tests were used in the study.Results from the study's treatment HSR group and treatment CE group are contrasted.Results:After 12 weeks of therapy,investigators reassessed grip strength,PRTEE scores,and functional scale responses.In the posttest results of the Patient-Rated Tennis Elbow Evaluation survey,there is a statistically significant difference between Group HSR and Group CE(p<0.001).The posttest outcomes from the patient-specific activity scoring scheme questionnaire revealed a statistically significant disparity between Groups HSR and CE(p<0.001).The mean values for both groups exhibited a noteworthy change,with Team HSR demonstrating higher values in contrast to the control treatment.Conclusion:HSR exercise demonstrates superior effectiveness over CEs for lateral epicondylitis(LE)management,emphasizing its significance in treatment.展开更多
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.
基金Supported by the National Key R&D Program of China(No.2022YFE0209300)the National Natural Science Foundation of China(Nos.42106043,42141016)。
文摘Saltmarsh is one of the blue carbon ecosystems for the highest carbon burial efficiency.However,the buried carbon in saltmarsh may still be exported to coastal water through porewater exchange,a process that has often been overlooked in previous studies.A typical tidal creek of the Dongtan saltmarsh wetland in Chongming Island,Shanghai,China,was studied.The224Ra and223Ra activities were measured and the hydrological parameters such as water flow were determined,from which the porewater exchange rate in the tidal creek was estimated to be 1.78±1.73 cm/d.Meanwhile,the carbon concentrations in porewater were determined,based on which the fluxes of dissolved inorganic carbon(DIC),dissolved organic carbon(DOC),CH_(4),and CO_(2)exported from porewater exchange were derived to be 60±17,6.6±4.0,0.082±0.079,and 16±11 mmol/(m^(2)·d),respectively.In addition,analysis on different species of carbon in the creek water showed that,the fluxes of DIC,DOC,CH_(4),and CO_(2)exported laterally from tidal creek to coastal sea were 58±14,7.6±2.3,0.0011±0.00063,and 1.5±0.68 mmol/(m^(2)·d),respectively,indicating that the porewater exchange-derived carbon fluxes accounted for a large portion of the lateral carbon outwelling,and even much higher than those in CH_(4)and CO_(2)fluxes.Furthermore,the carbon exported from porewater exchange accounted for 50%of the carbon burial in the tidal creek system,of which DIC accounted for 73%of the total carbon flux transported by porewater exchange.Therefore,this study indicated that the porewater exchange-derived carbon fluxes to the tidal creek water may cause an overestimation in the carbon sequestration capacity of saltmarsh wetlands,and revealed the importance of porewater exchange for the carbon cycle of tidal creek system of saltmarsh wetlands.
基金supported by the National Natural Science Foundation of China(Nos.22064014,21765013)the Science and Technology Development Plan Project of Lanzhou(No.20211-146)+3 种基金the Science and Technology Project of Gansu Province(Nos.21YF5FA071,21JR7RA538)the Industrial Support Programme for Higher Education Institutions Project(Nos.2023CYZC-69,2024CYCZ-05)the 2023 Gansu Provincial Key Talent Project(No.2023RCXM26)a Gansu province postdoctoral grant(No.00247)。
文摘The advancement of various types of fluorescent nanoparticles is crucial for enhancing the application of lateral flow immunoassays(LFIA)across multiple fields.Currently,the fluorescent nanoparticles utilized in LFIA predominantly consist of traditional dye-doped nanoparticles or aggregation-induced luminescence dye-doped nanoparticles.The reliance on specific types of nanoparticles limits the diversity of signal reporting groups available for LFIA.Herein,we developed a solid-state luminescent dye-doped nanoparticles(SLDNPs)-based LFIA system with exceptional stability for the detection of C-reactive protein(CRP)in serum.The synthesis of SLD_(520)NP_(S)was simplicity,efficient and eco-friendly,which was ideal for large-scale production of the LFIA test strip.And the SLD_(520)NP_(S)exhibits superior fluorescence quantum yield(49%),fully guarantees the performance of the LFIA test strip.The constructed SLD_(520)NPsm Ab1-based LFIA demonstrated a satisfactory linear relationship with CRP concentrations ranging from 0.5 ng/mL to 100 ng/mL,with limits of detection(LOD)of 0.78 ng/mL and a visible LOD of 1 ng/mL using a handheld 405 nm lamp.Furthermore,the developed LFIA exhibited excellent recoveries in serum,ranging from 94.45%to 102.5%.Overall,the outstanding performance of the SLD_(520)NPs-mAb1-based LFIA indicates that solid-state luminescent dyes have significant potential applications in the field of LFIA.
基金Financial supports from the National Natural Science Foundation of China(NSFC,Nos.52272144 and 22205048)Heilongjiang Provincial Natural Science Foundation of China(No.JQ2022E001)+3 种基金China Postdoctoral Science Foundation(Nos.2022M710931 and 2023T160154)Heilongjiang Postdoctoral Science Foundation(No.LBH-Z22010)Natural Science Foundation of Shandong Province(No.ZR2020ZD42)the Fundamental Research funds for the Central Universities are greatly acknowledged.
文摘Lateral flow immunoassay(LFIA),a rapid detection technique noted for simplicity and economy,has showcased indispensable applicability in diverse domains such as disease screening,food safety,and environmental monitoring.Nevertheless,challenges still exist in detecting ultra-low concentration analytes due to the inherent sensitivity limitations of LFIA.Recently,significant advances have been achieved by integrating enzyme activity probes and transforming LFIA into a highly sensitive tool for rapidly detecting trace analyte concentrations.Specifically,modifying natural enzymes or engineered nanozymes allows them to function as immune probes,directly catalyzing the production of signal molecules or indirectly initiating enzyme activity.Therefore,the signal intensity and detection sensitivity of LFIA are markedly elevated.The present review undertakes a comprehensive examination of pertinent research literature,offering a systematic analysis of recently proposed enzyme-based signal amplification strategies.By way of comparative assessment,the merits and demerits of current approaches are delineated,along with the identification of research avenues that still need to be explored.It is anticipated that this critical overview will garner considerable attention within the biomedical and materials science communities,providing valuable direction and insight toward the advancement of high-performance LFIA technologies.
基金the members of the Extending Station for Animal Husbandry and Veterinary Technology of Tianzhu Xizang Autonomous County for their help in sample collection and data acquisition.This research was supported by the Supercomputing Center of Lanzhou University and the Chakouyi horse conservation project from the Tianzhu Xizang Autonomous County Government([20]0097).
文摘Chakouyi(CKY)horses from the Qinghai-Xizang Plateau are well known for their unique lateral gaits and high-altitude adaptation,but genetic mechanisms underlying these phenotypes remain unclear.This study presents a comparison of 60 newly resequenced genomes of gaited CKY horses with 139 public genomes from 19 horse breeds.Population structure analyses(admixture,PCA,and neighbor-joining tree)reveal a close genetic relationship between CKY and other highland breeds(Tibetan and Chaidamu horses).Compared with other Chinese breeds,CKY horses present reduced nucleotide diversity(θπ)and lower inbreeding(FROHcoefficient),suggesting possible selective pressures.A key region on chromosome 23(Chr23:22.3-22.6 Mb)is associated with the lateral gaits and harbors a highly prevalent nonsense mutation(Chr 23:22,391,254 C>A,Ser301STOP)in the DMRT3 gene,with an 88%homozygosity rate,which is strongly correlated with the distinctive gait of CKY horses.Furthermore,selection signals reveal that the EPAS1 gene is related to high-altitude adaptation,and the CAT gene contributes to altitude resilience in CKY horses.These findings suggest that preserving genetic diversity is essential for maintaining the unique gaits and high-altitude adaptations of CKY horses.
基金supported in part by the National Natural Science Foundation of China(4227233052079019)+1 种基金the Liaoning Province Science and Technology Plan Joint Program(Applied Basic Research Project)(2023JH2/101700340)the Fundamental Research Funds for the Central Universities(DUT24ZD135).
文摘Columnar jointed rock mass(CJRM)combines and mosaic of slender rock columns with different height-to-width(H/W)ratios.Revealing the correlation of the mechanical behavior of individual rock columns with internal factors(H/W ratio and material strength)and external factor(lateral pressure)is fundamental to understanding the deterioration of CJRM.We adopt a numerical scheme that combines a statistical meso-damage constitutive model with a finite element formulation based on finite deformation,which can simultaneously consider both material failure and structural instability of the rock columns.Compression tests of rock columns with different H/W ratios and material strengths under varying lateral pressures were conducted to analyze the macro-strength features and failure modes.The numerical results show that increasing the material strength can improve the macro-strength,while the effect of H/W ratio is the opposite.Both increases can promote the conversion of failure modes,and the evolution process is as follows:material failure-induced structural instability→synergy and competition between material failure and structural instability→structural instability-induced material failure.Notably,for the last failure mode,an increase in lateral pressure decreases the macro-strength of the rock column and heightens its instability risk.This finding provides new insights into the response of rocks with different H/W ratios under lateral pressure,extending beyond traditional material-based perspectives.According to the position of the failure mode demarcation line,the failure mode of the rock column can be regulated.
基金supported by the National Natural Science Foundation of China(32470354,31900612,and 31971919)the Natural Science Foundation of Chongqing,China(cstc2020jcyj-jqX0020)+1 种基金the Foundation for Innovative Research Groups of the Natural Science Foundation of Chongqing,China(cstc2021jcyj-cxttX0004)the Chongqing Talent Program Foundation,China(cstc2024ycjhbgzxm0063)。
文摘Leaves and glumes act as lateral organs and have essential effects on photosynthesis and seed morphology,thus affecting yield.However,the molecular mechanisms controlling their polarity development in rice still need further study.Here,we isolated a polarity defect of lateral organs 1(pdl1)mutant in rice,which exhibits twisted/filamentous-shaped leaves and cracked/filamentous-shaped lemmas caused by defects in polarity development.PDL1 encodes a SUPPRESSOR OF GENE SILENCING 3 protein localized in the cytoplasmic granules.PDL1 is expressed in the shoot apical meristem,inflorescence meristem,floral meristem,and lateral organs including leaves and floral organs.PDL1 is involved in the synthesis of tasiR-ARF,which may subsequently modulate the expression of OsARFs.Meanwhile,the expression levels of abaxial miR165/166 and the adaxial identity genes OSHBs were respectively increased and reduced significantly.The results of this study clarify the molecular mechanism by which PDL1-mediated tasiR-ARF synthesis regulates the lateral organ polarity development in rice.
文摘This paper aims to evaluate the stochastic response of steel columns subjected to blast loads using the modified single degree of freedom(MSDOF)method,which assessed towards the conventional single degree of freedom(SDOF)and the experimentally validated Finite Element(FE)methods(LSDYNA).For this purpose,special atten-tion is given to calculating the response of H-shaped steel columns under blast.The damage amount is determined based on the support rotation criterion,which is expressed as a function of their maximum lateral mid-span dis-placement.To account for uncertainties in input parameters and obtain the failure probability,the Monte Carlo simulation(MCS)method is employed,complemented by the Latin Hypercube Sampling(LHS)method to reduce the number of simulations.A parametric analysis is hence performed to examine the effect of several input pa-rameters(including both deterministic and probabilistic parameters)on the probability of column damage as a function of support rotation.First,the MSDOF method confirms its higher accuracy in estimating the probability of column damage due to blast,compared to the conventional SDOF.The collected results also show that un-certainties of several input parameters have significant effects on the column behavior.In particular,geometric parameters(including cross-sectional characteristics,boundary conditions and column length)have major effect on the corresponding column response,in the same way of input blast load parameters and material properties.
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).
文摘BACKGROUND To observe the endoscopic and pathological characteristics of laterally spreading tumors(LSTs)and explore the risk factors for carcinogenesis and submucosal infiltration.AIM To analyze the clinicopathological features of colorectal LSTs treated endoscopically and determine risk factors associated with carcinogenesis and submucosal invasion,providing evidence-based guidance for optimal treatment strategy selection.METHODS This study retrospectively analyzed the sex,age,and endoscopic and pathological features of patients who underwent endoscopic treatment for colorectal LSTs in our hospital from January 2021 to July 2024.Single-factor analysis was used to identify the risk factors for cancer and submucosal infiltration,and the factors with statistical significance were included in multivariate logistic regression analysis.RESULTS A total of 422 patients,including 224 males and 198 females,aged 63.45±9.23 years,were included.There were 456 LST lesions in total.The length of the endoscopically resected specimens was 3.01±0.48 cm,and the length of the lesions was 2.37±1.59 cm.It was located in 115 rectums(25.2%),40 sigmoid colon(8.8%),26 descending colon(5.7%),109 transverse colon(23.9%),112 ascending colon(24.6%),and 54 ileocecal regions(11.8%).Endoscopic submucosal dissection(ESD)was performed in 237 patients(52.0%),and endoscopic mucosal resection(EMR)was performed in 95 patients(20.8%).There were 113 EMR with precutting cases(24.8%),11 ESD with snare cases(2.4%),4 delayed bleeding cases and 5 intraoperative perforations.The pathological results revealed 119 cases of low-grade intraepithelial neoplasia(26.1%),221 cases of high-grade intraepithelial neoplasia(48.5%),82 cases of intramucosal carcinoma(18.0%),and 34 cases of submucous invasive carcinoma(7.5%).Multiple logistic regression analyses revealed that lesion size(>2 cm),lesion location(rectal)and endoscopic classification[false depressed tubulovillous adenoma(LST-NG pseudodepressed type,LST-NG-PD),type 1 particles(LST-G homogenous type),and LST-G nodular mixed type],accompanied by large nodules(with)were independent risk factors for carcinogenesis;endoscopic classification(LST-NG-PD)and the presence of large nodules were independent risk factors for submucosal infiltration.CONCLUSION These risk factors provide practical guidance for treatment selection:LST-NG-PD with large nodules should prioritize ESD,while high-risk rectal lesions>2 cm may require additional imaging evaluation before endoscopic resection.
基金Projects(52372369,52302447,52388102)supported by the National Natural Science Foundation of ChinaProjects(2022YFB4301201-02,2023YFB4302502-02)supported by the National Key R&D Program of China。
文摘Irregularities in the track and uneven forces acting on the train can cause shifts in the position of the superconducting magnetic levitation train relative to the track during operation.These shifts lead to asymmetries in the flow field structure on both sides of the narrow suspension gap,resulting in instability and deterioration of the train’s aerodynamic characteristics,significantly impacting its operational safety.In this study,we firstly validate the aerodynamic characteristics of the superconducting magnetic levitation system by developing a numerical simulation method based on wind tunnel test results.We then investigate the influence of lateral translation parameters on the train’s aerodynamic performance under conditions both with and without crosswinds.We aim to clarify the evolution mechanism of the flow field characteristics under the coupling effect between the train and the U-shaped track and to identify the most unfavorable operational parameters contributing to the deterioration of the train’s aerodynamic properties.The findings show that,without crosswinds,a lateral translation of 30 mm causes a synchronous resonance phenomenon at the side and bottom gaps of the train-track coupling,leading to the worst aerodynamic performance.Under crosswind conditions,a lateral translation of 40 mm maximizes peak pressure fluctuations and average turbulent kinetic energy around the train,resulting in the poorest aerodynamic performance.This research provides theoretical support for enhancing the operational stability of superconducting magnetic levitation trains.
文摘Background:The extensor carpi radial muscle may become imbalanced compared to other muscles in the upper arm and can disrupt the overall muscle balance in the upper limb.This muscular imbalance may then cause inflammation or irritation in the tendon.Regular physical activity is rarely used as the only treatment for lowering limb edema.Heavy slow resistance(HSR)training is effective compared to regular exercises.HSR affects functional abilities and physical refinement differently from conventional workouts.This study evaluated the effects of HSR and conventional exercise(CE)on subjects aged 45–65 years with unilateral elbow pain on,in Chennai city.Methods:Patient received conservative care in the Physiotherapy Department from January 2022 to April 2022.This study compares the pre-and posttypes.Tennis Elbow Evaluation(Patient-Rated Tennis Elbow Evaluation,PRTEE)questionnaires,a patient-specific functional scale,and grip strength tests were used in the study.Results from the study's treatment HSR group and treatment CE group are contrasted.Results:After 12 weeks of therapy,investigators reassessed grip strength,PRTEE scores,and functional scale responses.In the posttest results of the Patient-Rated Tennis Elbow Evaluation survey,there is a statistically significant difference between Group HSR and Group CE(p<0.001).The posttest outcomes from the patient-specific activity scoring scheme questionnaire revealed a statistically significant disparity between Groups HSR and CE(p<0.001).The mean values for both groups exhibited a noteworthy change,with Team HSR demonstrating higher values in contrast to the control treatment.Conclusion:HSR exercise demonstrates superior effectiveness over CEs for lateral epicondylitis(LE)management,emphasizing its significance in treatment.
