Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations...Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.展开更多
The sulfation and decomposition process has proven effective in selectively extracting lithium from lepidolite.It is essential to clarify the thermochemical behavior and kinetic parameters of decomposition reactions.A...The sulfation and decomposition process has proven effective in selectively extracting lithium from lepidolite.It is essential to clarify the thermochemical behavior and kinetic parameters of decomposition reactions.Accordingly,comprehensive kinetic study by employing thermalgravimetric analysis at various heating rates was presented in this paper.Two main weight loss regions were observed during heating.The initial region corresponded to the dehydration of crystal water,whereas the subsequent region with overlapping peaks involved complex decomposition reactions.The overlapping peaks were separated into two individual reaction peaks and the activation energy of each peak was calculated using isoconversional kinetics methods.The activation energy of peak 1 exhibited a continual increase as the reaction conversion progressed,while that of peak 2 steadily decreased.The optimal kinetic models,identified as belonging to the random nucleation and subsequent growth category,provided valuable insights into the mechanism of the decomposition reactions.Furthermore,the adjustment factor was introduced to reconstruct the kinetic mechanism models,and the reconstructed models described the kinetic mechanism model more accurately for the decomposition reactions.This study enhanced the understanding of the thermochemical behavior and kinetic parameters of the lepidolite sulfation product decomposition reactions,further providing theoretical basis for promoting the selective extraction of lithium.展开更多
This paper investigates the reliability of internal marine combustion engines using an integrated approach that combines Fault Tree Analysis(FTA)and Bayesian Networks(BN).FTA provides a structured,top-down method for ...This paper investigates the reliability of internal marine combustion engines using an integrated approach that combines Fault Tree Analysis(FTA)and Bayesian Networks(BN).FTA provides a structured,top-down method for identifying critical failure modes and their root causes,while BN introduces flexibility in probabilistic reasoning,enabling dynamic updates based on new evidence.This dual methodology overcomes the limitations of static FTA models,offering a comprehensive framework for system reliability analysis.Critical failures,including External Leakage(ELU),Failure to Start(FTS),and Overheating(OHE),were identified as key risks.By incorporating redundancy into high-risk components such as pumps and batteries,the likelihood of these failures was significantly reduced.For instance,redundant pumps reduced the probability of ELU by 31.88%,while additional batteries decreased the occurrence of FTS by 36.45%.The results underscore the practical benefits of combining FTA and BN for enhancing system reliability,particularly in maritime applications where operational safety and efficiency are critical.This research provides valuable insights for maintenance planning and highlights the importance of redundancy in critical systems,especially as the industry transitions toward more autonomous vessels.展开更多
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy...AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.展开更多
AIM:To summarize publication trends in the field of strabismus over the past 30y and predict future research hotspots.METHODS:A total of 2915 English-language articles and reviews on strabismus,published between 1993 ...AIM:To summarize publication trends in the field of strabismus over the past 30y and predict future research hotspots.METHODS:A total of 2915 English-language articles and reviews on strabismus,published between 1993 and 2022,were retrieved from the Web of Science Core Collection.Bibliometric analyses were performed using VOSviewer and CiteSpace software to explore publication trends,as well as the contributions and collaborative networks of countries/regions,authors,institutions,and journals.RESULTS:The annual number of publications on strabismus showed a consistent upward trend.The United States(USA)maintained a leading position in this research field while Republic of Korea and China emerged as rapidly advancing contributors over the last decade.The University of California,Los Angeles ranked as the most productive institution,and Jonathan M.Holmes from USA was the most productive author.Journal of AAPOS was the leading journal with the most strabismus publications,whereas the two most highly cited articles were both published in Ophthalmology.Co-occurrence analysis identified pivotal keywords and burst terms,including intermittent exotropia(IXT),acute acquired comitant esotropia(AACE),functional magnetic resonance imaging(fMRI),and surgical treatment,which were confirmed as predominant and frontier topics.CONCLUSION:This study provides a comprehensive bibliometric analysis of strabismus research,revealing the evolution of research hotspots over the past 30y and outlining several cutting-edge directions for future investigation.展开更多
It is important to determine the safety lifetime of Multi-mode Time-Dependent Structural System(MTDSS). However, there is still a lack of corresponding analysis methods.Therefore, this paper establishes MTDSS safety l...It is important to determine the safety lifetime of Multi-mode Time-Dependent Structural System(MTDSS). However, there is still a lack of corresponding analysis methods.Therefore, this paper establishes MTDSS safety lifetime model firstly, and then proposes a Kriging surrogate model based method to estimate safety lifetime. The first step of proposed method is to construct the Kriging model of MTDSS performance function by using extremum learning function. By identifying possible extremum mode of MTDSS, the performance function of MTDSS can be equivalently transformed into the one of Single-mode Time-Dependent Structure(STDS).The second step is to use the Advanced First Failure Instant Learning Function(AFFILF) to train the Kriging model constructed in the first step, so that the convergent Kriging model can identify the possible First Failure Instant(FFI) of STDS. Then safety lifetime can be searched quickly by dichotomy search. By using AFFILF, the minimum instant that the state is not accurately identified by the current Kriging model is selected as the training point, which avoids the unnecessary calculation which may be introduced into the existing First Failure Instant Learning Function(FFILF).In addition, the Candidate Sample Pool(CSP) reduction strategy is also adopted. By adaptively deleting the random candidate sample points whose FFI have been accurately identified by the current Kriging model, the training efficiency is further improved. Three cases show that the proposed method is accurate and efficient.展开更多
In practical engineering, many uncertain factors in loading or degradation of material properties may vary with time. Stochastic process modeling constitutes a suitable approach for describing these time-dependent unc...In practical engineering, many uncertain factors in loading or degradation of material properties may vary with time. Stochastic process modeling constitutes a suitable approach for describing these time-dependent uncertainties. By adopting this approach, however, the timedependent reliability calculation is a great challenge owing to the complexity and the huge computational burden. This paper presents a new instantaneous response surface method t-IRS for time-dependent reliability analysis. Different from the adaptive extreme response surface approach, the proposed method does not need to build and update surrogate models separately at each time node. It first uses the expansion optimal linear estimation method to discretize the stochastic processes into a set of independent standard normal variables together with some deterministic functions of time. Time is then treated as an independent one-dimensional variable. Next, initial samples are generated by Latin hypercube sampling, and the corresponding response values are calculated and utilized to construct an instantaneous response surrogate model of the Kriging type. The active learning method is applied to update the Kriging surrogate model until satisfactory accuracy is achieved. Finally, the instantaneous response surrogate model is used to compute the time-dependent reliability via Monte Carlo simulation. Four case studies are utilized to demonstrate the effectiveness of the ^-IRS method for time-dependent reliability analysis.展开更多
Diffusions of multiple components have numerous applications such as underground water flow, pollutant movement, stratospheric warming, and food processing. Particularly, liquid hydrogen is used in the cooling process...Diffusions of multiple components have numerous applications such as underground water flow, pollutant movement, stratospheric warming, and food processing. Particularly, liquid hydrogen is used in the cooling process of the aeroplane. Further, liquid nitrogen can find applications in cooling equipment or electronic devices, i.e., high temperature superconducting(HTS) cables. So, herein, we have analysed the entropy generation(EG), nonlinear thermal radiation and unsteady(time-dependent) nature of the flow on quadratic combined convective flow over a permeable slender cylinder with diffusions of liquid hydrogen and nitrogen. The governing equations for flow and heat transfer characteristics are expressed in terms of nonlinear coupled partial differential equations. The solutions of these equations are attempted numerically by employing the quasilinearization technique with the implicit finite difference approximation. It is found that EG is minimum for double diffusion(liquid hydrogen and heat diffusion)than triple diffusion(diffusion of liquid hydrogen, nitrogen and heat). The enhancing values of the radiation parameter R_(d) and temperature ratio θ_(w) augment the fluid temperature for steady and unsteady cases as well as the local Nusselt number. Because, the fluid absorbs the heat energy released due to radiation, and in turn releases the heat energy from the cylinder to the surrounding surface.展开更多
In this paper,we present a new method of intelligent back analysis(IBA)using grey Verhulst model(GVM)to identify geotechnical parameters of rock mass surrounding tunnel,and validate it via a test for a main openings o...In this paper,we present a new method of intelligent back analysis(IBA)using grey Verhulst model(GVM)to identify geotechnical parameters of rock mass surrounding tunnel,and validate it via a test for a main openings of−600 m level in Coal Mine“6.13”,Democratic People's Republic of Korea.The displacement components used for back analysis are the crown settlement and sidewalls convergence monitored at the end of the openings excavation,and the final closures predicted by GVM.The non-linear relation between displacements and back analysis parameters was obtained by artificial neural network(ANN)and Burger-creep viscoplastic(CVISC)model of FLAC3D.Then,the optimal parameters were determined for rock mass surrounding tunnel by genetic algorithm(GA)with both groups of measured displacements at the end of the final excavation and closures predicted by GVM.The maximum absolute error(MAE)and standard deviation(Std)between calculated displacements by numerical simulation with back analysis parameters and in situ ones were less than 6 and 2 mm,respectively.Therefore,it was found that the proposed method could be successfully applied to determining design parameters and stability for tunnels and underground cavities,as well as mine openings and stopes.展开更多
In order to consider the time-dependent characteristic of risk factors of hydropower project,the method of stochastic process simulating structure resistance and load effect is adopted.On the basis of analyzing the st...In order to consider the time-dependent characteristic of risk factors of hydropower project,the method of stochastic process simulating structure resistance and load effect is adopted.On the basis of analyzing the structure characteristics and mode of operation,the operation safety risk rate assessment model of hydropower project is established on the comprehensive application of the improved analytic hierarchy process,the time-dependent reliability theory and the risk rate threshold.A scheme to demonstrate the time-dependent risk rate assessment method for an example of the earth-rock dam is particularly implemented by the proposed approach.The example shows that operation safety risk rate is closely related to both the service period and design standard;considering the effect of time-dependent,the risk rate increases with time and the intersection of them reflects the technical service life of structures.It could provide scientific basis for the operation safety and risk decision of the hydropower project by predicting the trend of risk rate via this model.展开更多
Reliability is a crucial metric in aerospace engineering.The results of reliability assessments for components like aerospace electromagnetic relays directly impact the development and operational reliability of aeros...Reliability is a crucial metric in aerospace engineering.The results of reliability assessments for components like aerospace electromagnetic relays directly impact the development and operational reliability of aerospace engineering systems.Current methods for analyzing the reliability of aerospace electromagnetic relays have limitations,such as neglecting the combined effects of multiple uncertain factors,degradation of key component properties,and the influence of fluctuations in aerospace environments.Additionally,these methods often assume a single-type uncertainty in the manufacturing process,leading to significant deviations between the analysis results and actual measurement results.To address these issues,this study proposes an efficient timedependent reliability analysis method based on the HL-RF algorithm,considering a hybrid of probabilistic and interval uncertainty that accounts for degradation and environmental conditions.The proposed method is applied to the reliability analysis of actual aerospace electromagnetic relay products and compared with traditional methods,demonstrating significant advantages.The proposed method has been applied to the time-dependent reliability analysis of actual aerospace electromagnetic relay products under different environmental conditions.The analysis results exhibit an error margin within 5.12% compared to actual measurement results.Compared to analysis methods solely based on probabilistic uncertainty quantification or interval uncertainty quantification,this method reduces the analysis error by 52% and 67% respectively.When compared to two other state-of-the-art methods that integrate probabilistic and interval uncertainty quantification,the error reduction is 23%.These demonstrate the superiority of the proposed method and validates its effectiveness.The presented approach has the potential to be extended for reliability analysis in other aerospace electromechanical systems.展开更多
This study is devoted to the analysis of a one-dimensional time-dependent double-diffusive flow over a semi-infinite vertical plate, under a convective surface boundary condition. Using similarity variable, the govern...This study is devoted to the analysis of a one-dimensional time-dependent double-diffusive flow over a semi-infinite vertical plate, under a convective surface boundary condition. Using similarity variable, the governing nonlinear partial differential equations have been transformed into a set of coupled nonlinear ordinary differential equations, which are solved numerically by using shooting method alongside with Runge-Kutta integration scheme as embedded in Maple software programme. The numerical results of the skin-friction coefficient, the Nusselt and Sherwood numbers are discussed and depicted graphically.展开更多
The strategy on repair and strengthening of existing bridges based on time-dependent reliability was analyzed with the maximum expected benefit as the objective function. A sample of risk-ranking decision was illustra...The strategy on repair and strengthening of existing bridges based on time-dependent reliability was analyzed with the maximum expected benefit as the objective function. A sample of risk-ranking decision was illustrated based on updated inspection information with 35 survival age. The effect of improvement of live loads and difference of repair methods on time-dependent reliability of existing bridges are considered. The results show that the decision method can be used in real project, with the cost of failure consequence and the risk of failure considered.展开更多
During the life of an offshore structure, its structural strength declines due to various kinds of damages related to the time factor. In this paper, four major kinds of damages, including damages caused by fatigue, d...During the life of an offshore structure, its structural strength declines due to various kinds of damages related to the time factor. In this paper, four major kinds of damages, including damages caused by fatigue, dent, corrosion and marine life, are discussed. Based on these analyses, formulas for the evaluation of the damaged structure reliability are derived. Furthermore the computer program ISM for the analysis of structural reliability is developed by the use of Advanced First Order Second Moment method and Monte-Carlo Importance Sampling method. The reliability of a turbular joint and a beam are studied as numerical examples. The results show that the theory and the analysis method given in this paper are reasonable and effective.展开更多
In this paper, Homotopy Analysis method with Genetic Algorithm is presented and used to obtain an analytical solution for the time-dependent Emden-Fowler type of equations and wave-type equation with singular behavior...In this paper, Homotopy Analysis method with Genetic Algorithm is presented and used to obtain an analytical solution for the time-dependent Emden-Fowler type of equations and wave-type equation with singular behavior at x = 0. The advantage of this single global method employed to present a reliable framework is utilized to overcome the singularity behavior at the point x = 0 for both models. The method is demonstrated for a variety of problems in one and higher dimensional spaces where approximate-exact solutions are obtained. The results obtained in all cases show the reliability and the efficiency of this method.展开更多
Catastrophic failure in engineering structures of island reefs would occur when the tertiary creep initiates in coral reef limestone with a transition from short-to long-term load.Due to the complexity of biological s...Catastrophic failure in engineering structures of island reefs would occur when the tertiary creep initiates in coral reef limestone with a transition from short-to long-term load.Due to the complexity of biological structures,the underlying micro-behaviors involving time-dependent deformation are poorly understood.For this,an abnormal phenomenon was observed where the axial and lateral creep deformations were mutually independent by a series of triaxial tests under constant stress and strain rate conditions.The significantly large lateral creep deformation implies that the creep process cannot be described in continuum mechanics regime.Herein,it is hypothesized that sliding mechanism of crystal cleavages dominates the lateral creep deformation in coral reef limestone.Then,approaches of polarizing microscope(PM)and scanning electronic microscope(SEM)are utilized to validate the hypothesis.It shows that the sliding behavior of crystal cleavages combats with conventional creep micro-mechanisms at certain condition.The former is sensitive to time and strain rate,and is merely activated in the creep regime.展开更多
The growing need for sustainable energy solutions,driven by rising energy shortages,environmental concerns,and the depletion of conventional energy sources,has led to a significant focus on renewable energy.Solar ener...The growing need for sustainable energy solutions,driven by rising energy shortages,environmental concerns,and the depletion of conventional energy sources,has led to a significant focus on renewable energy.Solar energy,among the various renewable sources,is particularly appealing due to its abundant availability.However,the efficiency of commercial solar photovoltaic(PV)modules is hindered by several factors,notably their conversion efficiency,which averages around 19%.This efficiency can further decline to 10%–16%due to temperature increases during peak sunlight hours.This study investigates the cooling of PV modules by applying water to their front surface through Computational fluid dynamics(CFD).The study aimed to determine the optimal conditions for cooling the PV module by analyzing the interplay between water film thickness,Reynolds number,and their effects on temperature reduction and heat transfer.The CFD analysis revealed that the most effective cooling condition occurred with a 5 mm thick water film and a Reynolds number of 10.These specific parameters were found to maximize the heat transfer and temperature reduction efficiency.This finding is crucial for the development of practical and efficient cooling systems for PV modules,potentially leading to improved performance and longevity of solar panels.Alternative cooling fluids or advanced cooling techniques that might offer even better efficiency or practical benefits.展开更多
The SKP1 gene is an important component of the SCF(SKP1-Cullin1-F-box)complex and serves as a bridge connecting the F-box and Cullin1genes(F-box-SKP1-Cullin1).The pattern of S-RNase being ubiquitously labelled by the ...The SKP1 gene is an important component of the SCF(SKP1-Cullin1-F-box)complex and serves as a bridge connecting the F-box and Cullin1genes(F-box-SKP1-Cullin1).The pattern of S-RNase being ubiquitously labelled by the SCF complex and degraded by the 26S protease accounts for the bulk of the available self-incompatibility studies.In this study,15 ClSKP1s from the‘Xiangshui'lemon genome and ubiquitome exist in the same SKP1 conserved domain(CD)as SKP1s in other species.The q PCR results showed that SKP1-6 and SKP1-14 have tissue expression patterns specific for expression in pollen.In addition,SKP1-6 and SKP1-14 in the stigma,style and ovary were significantly upregulated after self-pollination compared to those after cross-pollination.A subcellular location showed that SKP1-6 and SKP1-14 were located in the nucleus.In addition,yeast two-hybrid(Y2H)assays,bimolecular fluorescence complementation(BiFC)and luciferase complementation imaging(LCI)assays showed that SKP1-6 interacted with F-box1,F-box33,F-box34,F-box17,F-box19,Cullin1-2 and 26S proteasome subunit 4 homolog A(26S PS4HA).SKP1-14 interacted with F-box17,F-box19,F-box35,Cullin1-2 and 26S PS4HA.The interaction of Cullin1-2 and the F-box with SKP1 as a bridge was verified by a yeast three-hybrid experiment.The ability of S3-RNase to inhibit pollen and pollen tube growth and development was assessed using in vitro pollen co-culture experiments with recombinant S3-RNase proteins.Overall,this study provides important experimental evidence and theoretical basis for understanding the mechanism of self-incompatibility in plants by revealing the key role of the SCF complex in‘Xiangshui'lemon,which is bridged by ClSKP1-6,in self-incompatibility.The results of this study are of great significance for the future indepth exploration of the molecular mechanism of the SCF complex and its wide application in the self-incompatibility of plants.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.展开更多
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.
基金financially supported by the National Natural Science Foundation of China(Nos.52034002 and U2202254)the Fundamental Research Funds for the Central Universities,China(No.FRF-TT-19-001)。
文摘The sulfation and decomposition process has proven effective in selectively extracting lithium from lepidolite.It is essential to clarify the thermochemical behavior and kinetic parameters of decomposition reactions.Accordingly,comprehensive kinetic study by employing thermalgravimetric analysis at various heating rates was presented in this paper.Two main weight loss regions were observed during heating.The initial region corresponded to the dehydration of crystal water,whereas the subsequent region with overlapping peaks involved complex decomposition reactions.The overlapping peaks were separated into two individual reaction peaks and the activation energy of each peak was calculated using isoconversional kinetics methods.The activation energy of peak 1 exhibited a continual increase as the reaction conversion progressed,while that of peak 2 steadily decreased.The optimal kinetic models,identified as belonging to the random nucleation and subsequent growth category,provided valuable insights into the mechanism of the decomposition reactions.Furthermore,the adjustment factor was introduced to reconstruct the kinetic mechanism models,and the reconstructed models described the kinetic mechanism model more accurately for the decomposition reactions.This study enhanced the understanding of the thermochemical behavior and kinetic parameters of the lepidolite sulfation product decomposition reactions,further providing theoretical basis for promoting the selective extraction of lithium.
基金supported by Istanbul Technical University(Project No.45698)supported through the“Young Researchers’Career Development Project-training of doctoral students”of the Croatian Science Foundation.
文摘This paper investigates the reliability of internal marine combustion engines using an integrated approach that combines Fault Tree Analysis(FTA)and Bayesian Networks(BN).FTA provides a structured,top-down method for identifying critical failure modes and their root causes,while BN introduces flexibility in probabilistic reasoning,enabling dynamic updates based on new evidence.This dual methodology overcomes the limitations of static FTA models,offering a comprehensive framework for system reliability analysis.Critical failures,including External Leakage(ELU),Failure to Start(FTS),and Overheating(OHE),were identified as key risks.By incorporating redundancy into high-risk components such as pumps and batteries,the likelihood of these failures was significantly reduced.For instance,redundant pumps reduced the probability of ELU by 31.88%,while additional batteries decreased the occurrence of FTS by 36.45%.The results underscore the practical benefits of combining FTA and BN for enhancing system reliability,particularly in maritime applications where operational safety and efficiency are critical.This research provides valuable insights for maintenance planning and highlights the importance of redundancy in critical systems,especially as the industry transitions toward more autonomous vessels.
基金Supported by the Central High Level Hospital Clinical Research Funding(No.BJ-2024-089).
文摘AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.
基金Supported by National Natural Science Foundation of China(No.82020108006,No.81730025).
文摘AIM:To summarize publication trends in the field of strabismus over the past 30y and predict future research hotspots.METHODS:A total of 2915 English-language articles and reviews on strabismus,published between 1993 and 2022,were retrieved from the Web of Science Core Collection.Bibliometric analyses were performed using VOSviewer and CiteSpace software to explore publication trends,as well as the contributions and collaborative networks of countries/regions,authors,institutions,and journals.RESULTS:The annual number of publications on strabismus showed a consistent upward trend.The United States(USA)maintained a leading position in this research field while Republic of Korea and China emerged as rapidly advancing contributors over the last decade.The University of California,Los Angeles ranked as the most productive institution,and Jonathan M.Holmes from USA was the most productive author.Journal of AAPOS was the leading journal with the most strabismus publications,whereas the two most highly cited articles were both published in Ophthalmology.Co-occurrence analysis identified pivotal keywords and burst terms,including intermittent exotropia(IXT),acute acquired comitant esotropia(AACE),functional magnetic resonance imaging(fMRI),and surgical treatment,which were confirmed as predominant and frontier topics.CONCLUSION:This study provides a comprehensive bibliometric analysis of strabismus research,revealing the evolution of research hotspots over the past 30y and outlining several cutting-edge directions for future investigation.
基金supported by the National Natural Science Foundation of China(No.52075442)the National Science and Technology Major Project(2017-Ⅳ-0009-0046)the National Natural Science Foundation of China(No.51975476)。
文摘It is important to determine the safety lifetime of Multi-mode Time-Dependent Structural System(MTDSS). However, there is still a lack of corresponding analysis methods.Therefore, this paper establishes MTDSS safety lifetime model firstly, and then proposes a Kriging surrogate model based method to estimate safety lifetime. The first step of proposed method is to construct the Kriging model of MTDSS performance function by using extremum learning function. By identifying possible extremum mode of MTDSS, the performance function of MTDSS can be equivalently transformed into the one of Single-mode Time-Dependent Structure(STDS).The second step is to use the Advanced First Failure Instant Learning Function(AFFILF) to train the Kriging model constructed in the first step, so that the convergent Kriging model can identify the possible First Failure Instant(FFI) of STDS. Then safety lifetime can be searched quickly by dichotomy search. By using AFFILF, the minimum instant that the state is not accurately identified by the current Kriging model is selected as the training point, which avoids the unnecessary calculation which may be introduced into the existing First Failure Instant Learning Function(FFILF).In addition, the Candidate Sample Pool(CSP) reduction strategy is also adopted. By adaptively deleting the random candidate sample points whose FFI have been accurately identified by the current Kriging model, the training efficiency is further improved. Three cases show that the proposed method is accurate and efficient.
基金supported by the National Natural Science Foundation of China (Nos.11572134 and 11832013).
文摘In practical engineering, many uncertain factors in loading or degradation of material properties may vary with time. Stochastic process modeling constitutes a suitable approach for describing these time-dependent uncertainties. By adopting this approach, however, the timedependent reliability calculation is a great challenge owing to the complexity and the huge computational burden. This paper presents a new instantaneous response surface method t-IRS for time-dependent reliability analysis. Different from the adaptive extreme response surface approach, the proposed method does not need to build and update surrogate models separately at each time node. It first uses the expansion optimal linear estimation method to discretize the stochastic processes into a set of independent standard normal variables together with some deterministic functions of time. Time is then treated as an independent one-dimensional variable. Next, initial samples are generated by Latin hypercube sampling, and the corresponding response values are calculated and utilized to construct an instantaneous response surrogate model of the Kriging type. The active learning method is applied to update the Kriging surrogate model until satisfactory accuracy is achieved. Finally, the instantaneous response surrogate model is used to compute the time-dependent reliability via Monte Carlo simulation. Four case studies are utilized to demonstrate the effectiveness of the ^-IRS method for time-dependent reliability analysis.
文摘Diffusions of multiple components have numerous applications such as underground water flow, pollutant movement, stratospheric warming, and food processing. Particularly, liquid hydrogen is used in the cooling process of the aeroplane. Further, liquid nitrogen can find applications in cooling equipment or electronic devices, i.e., high temperature superconducting(HTS) cables. So, herein, we have analysed the entropy generation(EG), nonlinear thermal radiation and unsteady(time-dependent) nature of the flow on quadratic combined convective flow over a permeable slender cylinder with diffusions of liquid hydrogen and nitrogen. The governing equations for flow and heat transfer characteristics are expressed in terms of nonlinear coupled partial differential equations. The solutions of these equations are attempted numerically by employing the quasilinearization technique with the implicit finite difference approximation. It is found that EG is minimum for double diffusion(liquid hydrogen and heat diffusion)than triple diffusion(diffusion of liquid hydrogen, nitrogen and heat). The enhancing values of the radiation parameter R_(d) and temperature ratio θ_(w) augment the fluid temperature for steady and unsteady cases as well as the local Nusselt number. Because, the fluid absorbs the heat energy released due to radiation, and in turn releases the heat energy from the cylinder to the surrounding surface.
基金Project(32-41)supported by the National Science and Technical Development Foundation of DPR of Korea。
文摘In this paper,we present a new method of intelligent back analysis(IBA)using grey Verhulst model(GVM)to identify geotechnical parameters of rock mass surrounding tunnel,and validate it via a test for a main openings of−600 m level in Coal Mine“6.13”,Democratic People's Republic of Korea.The displacement components used for back analysis are the crown settlement and sidewalls convergence monitored at the end of the openings excavation,and the final closures predicted by GVM.The non-linear relation between displacements and back analysis parameters was obtained by artificial neural network(ANN)and Burger-creep viscoplastic(CVISC)model of FLAC3D.Then,the optimal parameters were determined for rock mass surrounding tunnel by genetic algorithm(GA)with both groups of measured displacements at the end of the final excavation and closures predicted by GVM.The maximum absolute error(MAE)and standard deviation(Std)between calculated displacements by numerical simulation with back analysis parameters and in situ ones were less than 6 and 2 mm,respectively.Therefore,it was found that the proposed method could be successfully applied to determining design parameters and stability for tunnels and underground cavities,as well as mine openings and stopes.
基金Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No. 51021004)
文摘In order to consider the time-dependent characteristic of risk factors of hydropower project,the method of stochastic process simulating structure resistance and load effect is adopted.On the basis of analyzing the structure characteristics and mode of operation,the operation safety risk rate assessment model of hydropower project is established on the comprehensive application of the improved analytic hierarchy process,the time-dependent reliability theory and the risk rate threshold.A scheme to demonstrate the time-dependent risk rate assessment method for an example of the earth-rock dam is particularly implemented by the proposed approach.The example shows that operation safety risk rate is closely related to both the service period and design standard;considering the effect of time-dependent,the risk rate increases with time and the intersection of them reflects the technical service life of structures.It could provide scientific basis for the operation safety and risk decision of the hydropower project by predicting the trend of risk rate via this model.
基金supported by the National Natural Science Foundation of China(No.52277141).
文摘Reliability is a crucial metric in aerospace engineering.The results of reliability assessments for components like aerospace electromagnetic relays directly impact the development and operational reliability of aerospace engineering systems.Current methods for analyzing the reliability of aerospace electromagnetic relays have limitations,such as neglecting the combined effects of multiple uncertain factors,degradation of key component properties,and the influence of fluctuations in aerospace environments.Additionally,these methods often assume a single-type uncertainty in the manufacturing process,leading to significant deviations between the analysis results and actual measurement results.To address these issues,this study proposes an efficient timedependent reliability analysis method based on the HL-RF algorithm,considering a hybrid of probabilistic and interval uncertainty that accounts for degradation and environmental conditions.The proposed method is applied to the reliability analysis of actual aerospace electromagnetic relay products and compared with traditional methods,demonstrating significant advantages.The proposed method has been applied to the time-dependent reliability analysis of actual aerospace electromagnetic relay products under different environmental conditions.The analysis results exhibit an error margin within 5.12% compared to actual measurement results.Compared to analysis methods solely based on probabilistic uncertainty quantification or interval uncertainty quantification,this method reduces the analysis error by 52% and 67% respectively.When compared to two other state-of-the-art methods that integrate probabilistic and interval uncertainty quantification,the error reduction is 23%.These demonstrate the superiority of the proposed method and validates its effectiveness.The presented approach has the potential to be extended for reliability analysis in other aerospace electromechanical systems.
文摘This study is devoted to the analysis of a one-dimensional time-dependent double-diffusive flow over a semi-infinite vertical plate, under a convective surface boundary condition. Using similarity variable, the governing nonlinear partial differential equations have been transformed into a set of coupled nonlinear ordinary differential equations, which are solved numerically by using shooting method alongside with Runge-Kutta integration scheme as embedded in Maple software programme. The numerical results of the skin-friction coefficient, the Nusselt and Sherwood numbers are discussed and depicted graphically.
基金TheLiaoningProviceCommunicationDe partmentKeyScienceFoundation (No .0 10 1)
文摘The strategy on repair and strengthening of existing bridges based on time-dependent reliability was analyzed with the maximum expected benefit as the objective function. A sample of risk-ranking decision was illustrated based on updated inspection information with 35 survival age. The effect of improvement of live loads and difference of repair methods on time-dependent reliability of existing bridges are considered. The results show that the decision method can be used in real project, with the cost of failure consequence and the risk of failure considered.
文摘During the life of an offshore structure, its structural strength declines due to various kinds of damages related to the time factor. In this paper, four major kinds of damages, including damages caused by fatigue, dent, corrosion and marine life, are discussed. Based on these analyses, formulas for the evaluation of the damaged structure reliability are derived. Furthermore the computer program ISM for the analysis of structural reliability is developed by the use of Advanced First Order Second Moment method and Monte-Carlo Importance Sampling method. The reliability of a turbular joint and a beam are studied as numerical examples. The results show that the theory and the analysis method given in this paper are reasonable and effective.
文摘In this paper, Homotopy Analysis method with Genetic Algorithm is presented and used to obtain an analytical solution for the time-dependent Emden-Fowler type of equations and wave-type equation with singular behavior at x = 0. The advantage of this single global method employed to present a reliable framework is utilized to overcome the singularity behavior at the point x = 0 for both models. The method is demonstrated for a variety of problems in one and higher dimensional spaces where approximate-exact solutions are obtained. The results obtained in all cases show the reliability and the efficiency of this method.
基金supported by the National Natural Science Foundation of China(Grant Nos.41877267,41877260)the Priority Research Program of the Chinese Academy of Science(Grant No.XDA13010201).
文摘Catastrophic failure in engineering structures of island reefs would occur when the tertiary creep initiates in coral reef limestone with a transition from short-to long-term load.Due to the complexity of biological structures,the underlying micro-behaviors involving time-dependent deformation are poorly understood.For this,an abnormal phenomenon was observed where the axial and lateral creep deformations were mutually independent by a series of triaxial tests under constant stress and strain rate conditions.The significantly large lateral creep deformation implies that the creep process cannot be described in continuum mechanics regime.Herein,it is hypothesized that sliding mechanism of crystal cleavages dominates the lateral creep deformation in coral reef limestone.Then,approaches of polarizing microscope(PM)and scanning electronic microscope(SEM)are utilized to validate the hypothesis.It shows that the sliding behavior of crystal cleavages combats with conventional creep micro-mechanisms at certain condition.The former is sensitive to time and strain rate,and is merely activated in the creep regime.
文摘The growing need for sustainable energy solutions,driven by rising energy shortages,environmental concerns,and the depletion of conventional energy sources,has led to a significant focus on renewable energy.Solar energy,among the various renewable sources,is particularly appealing due to its abundant availability.However,the efficiency of commercial solar photovoltaic(PV)modules is hindered by several factors,notably their conversion efficiency,which averages around 19%.This efficiency can further decline to 10%–16%due to temperature increases during peak sunlight hours.This study investigates the cooling of PV modules by applying water to their front surface through Computational fluid dynamics(CFD).The study aimed to determine the optimal conditions for cooling the PV module by analyzing the interplay between water film thickness,Reynolds number,and their effects on temperature reduction and heat transfer.The CFD analysis revealed that the most effective cooling condition occurred with a 5 mm thick water film and a Reynolds number of 10.These specific parameters were found to maximize the heat transfer and temperature reduction efficiency.This finding is crucial for the development of practical and efficient cooling systems for PV modules,potentially leading to improved performance and longevity of solar panels.Alternative cooling fluids or advanced cooling techniques that might offer even better efficiency or practical benefits.
基金supported by grants from the National Natural Science Foundation of China(Grant No.31960585)Science and Technology Major Project of Guangxi(Grant No.Guike AA22068092)+1 种基金Guangxi Science and Technology Vanguard Special Action Project(Grant No.202204)State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources(Grant Nos.SKLCUSA-a201906,SKLCU-SA-c201901)。
文摘The SKP1 gene is an important component of the SCF(SKP1-Cullin1-F-box)complex and serves as a bridge connecting the F-box and Cullin1genes(F-box-SKP1-Cullin1).The pattern of S-RNase being ubiquitously labelled by the SCF complex and degraded by the 26S protease accounts for the bulk of the available self-incompatibility studies.In this study,15 ClSKP1s from the‘Xiangshui'lemon genome and ubiquitome exist in the same SKP1 conserved domain(CD)as SKP1s in other species.The q PCR results showed that SKP1-6 and SKP1-14 have tissue expression patterns specific for expression in pollen.In addition,SKP1-6 and SKP1-14 in the stigma,style and ovary were significantly upregulated after self-pollination compared to those after cross-pollination.A subcellular location showed that SKP1-6 and SKP1-14 were located in the nucleus.In addition,yeast two-hybrid(Y2H)assays,bimolecular fluorescence complementation(BiFC)and luciferase complementation imaging(LCI)assays showed that SKP1-6 interacted with F-box1,F-box33,F-box34,F-box17,F-box19,Cullin1-2 and 26S proteasome subunit 4 homolog A(26S PS4HA).SKP1-14 interacted with F-box17,F-box19,F-box35,Cullin1-2 and 26S PS4HA.The interaction of Cullin1-2 and the F-box with SKP1 as a bridge was verified by a yeast three-hybrid experiment.The ability of S3-RNase to inhibit pollen and pollen tube growth and development was assessed using in vitro pollen co-culture experiments with recombinant S3-RNase proteins.Overall,this study provides important experimental evidence and theoretical basis for understanding the mechanism of self-incompatibility in plants by revealing the key role of the SCF complex in‘Xiangshui'lemon,which is bridged by ClSKP1-6,in self-incompatibility.The results of this study are of great significance for the future indepth exploration of the molecular mechanism of the SCF complex and its wide application in the self-incompatibility of plants.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
