Cased explosives generate highly energetic fragments as their casing breaks up. Due to the complexity of casing fragment related behavior such as embedment, perforation and ricochet, it may be insufficient to use equi...Cased explosives generate highly energetic fragments as their casing breaks up. Due to the complexity of casing fragment related behavior such as embedment, perforation and ricochet, it may be insufficient to use equivalent triangular pressure loading in fragment impact simulations. This simplified method may over- or under-predict the target response. Recently, a procedure using contact techniques has been proposed to overcome such difficulties. It has been shown that the new method has the inherent capability in modeling the multi-piece and multi-hit fragment impact problems in a more realistic way. To investigate the applicability of the proposed method to simulations involving multi-layer penetration, the selected problems of fragment impact on multi-layer targets are described in this paper. It is demonstrated that this method is capable of predicting the complicated multi-layer structural response caused by fragment impact and penetration. Modeling procedures and some technical issues are also discussed.展开更多
The key parameters that characterize the morphological quality of multi-layer and multi-pass metal laser deposited parts are the surface roughness and the error between the actual printing height and the theoretical m...The key parameters that characterize the morphological quality of multi-layer and multi-pass metal laser deposited parts are the surface roughness and the error between the actual printing height and the theoretical model height.The Taguchi method was employed to establish the correlations between process parameter combinations and multi-objective characterization of metal deposition morphology(height error and roughness).Results show that using the signal-to-noise ratio and grey relational analysis,the optimal parameter combination for multi-layer and multi-pass deposition is determined as follows:laser power of 800 W,powder feeding rate of 0.3 r/min,step distance of 1.6 mm,and scanning speed of 20 mm/s.Subsequently,a Genetic Bayesian-back propagation(GB-BP)network is constructed to predict multi-objective responses.Compared with the traditional back propagation network,the GB-back propagation network improves the prediction accuracy of height error and surface roughness by 43.14%and 71.43%,respectively.This network can accurately predict the multi-objective characterization of morphological quality of multi-layer and multi-pass metal deposited parts.展开更多
At present,the emerging solid-phase friction-based additive manufacturing technology,including friction rolling additive man-ufacturing(FRAM),can only manufacture simple single-pass components.In this study,multi-laye...At present,the emerging solid-phase friction-based additive manufacturing technology,including friction rolling additive man-ufacturing(FRAM),can only manufacture simple single-pass components.In this study,multi-layer multi-pass FRAM-deposited alumin-um alloy samples were successfully prepared using a non-shoulder tool head.The material flow behavior and microstructure of the over-lapped zone between adjacent layers and passes during multi-layer multi-pass FRAM deposition were studied using the hybrid 6061 and 5052 aluminum alloys.The results showed that a mechanical interlocking structure was formed between the adjacent layers and the adja-cent passes in the overlapped center area.Repeated friction and rolling of the tool head led to different degrees of lateral flow and plastic deformation of the materials in the overlapped zone,which made the recrystallization degree in the left and right edge zones of the over-lapped zone the highest,followed by the overlapped center zone and the non-overlapped zone.The tensile strength of the overlapped zone exceeded 90%of that of the single-pass deposition sample.It is proved that although there are uneven grooves on the surface of the over-lapping area during multi-layer and multi-pass deposition,they can be filled by the flow of materials during the deposition of the next lay-er,thus ensuring the dense microstructure and excellent mechanical properties of the overlapping area.The multi-layer multi-pass FRAM deposition overcomes the limitation of deposition width and lays the foundation for the future deposition of large-scale high-performance components.展开更多
Three different kinds of PELE(the penetrator with lateral efficiency) were launched by ballistic artillery to impact the multi-layer spaced metal target plates.The lmpact velocities of the projectiles were measured by...Three different kinds of PELE(the penetrator with lateral efficiency) were launched by ballistic artillery to impact the multi-layer spaced metal target plates.The lmpact velocities of the projectiles were measured by the velocity measuring system.The damage degree and process of each laye r of target plate impacted by the three kinds of projectiles were analyzed.The experimental results show that all the three kinds of projectiles have the effect of expanding holes on the multi-layer spaced metal target plates.For the normal structure PELE(without layered) with tungsten alloy jacket and the radial layered PELE with tungsten alloy jacket,the diameters of holes on the seco nd layer of plates are 3.36 times and 3.76 times of the diameter of the projectile,re spectively.For radial layered PELE with W/Zr-based amorphous composite jacket,due to the large number of tungsten wires dispersed after the impact,the diameter of the holes on the four-layer spaced plates can reach 2.4 times,3.04 times,5.36 times and 2.68 times of the diameter of the projectile.Besides,the normal structure PELE with tungsten alloy jacket and the radial layered PELE whit tungsten alloy jacket formed a large number of fragments impact marks on the third target plate.Although the number of fragments penetrating the third target plate is not as large as that of the normal structure PELE,the area of dispersion of fragments impact craters on the third target plate is larger by the radial layered PELE.The radial layered PELE with W/Zr-based amorphous composite jacket released a lot of heat energy due to the impact of the matrix material,and formed a large area of ablation marks on the last three target plates.展开更多
Themain goal of this work is to study the ballistic performance ofmulti-layered moderately-thick metallic targets.Several target configurations have been considered in thiswork,with various types of interlayer connect...Themain goal of this work is to study the ballistic performance ofmulti-layered moderately-thick metallic targets.Several target configurations have been considered in thiswork,with various types of interlayer connection(spaced,contacted and adhesive)and the number of layers(four and eight),and the influence of target configurations on ballistic performance has been studied experimentally and numerically.In the experiments,the targets were impacted by 12.7-mm projectiles at a velocity around 820 m/s.The experimental results show that,with similar total thickness,the contacted and adhesive targets exhibit better ballistic performance than the monolithic targets,and the four-layered targets are better than the eight-layered targets with the same connection type.To explore the ballistic resistance mechanism,numerical method has been used to simulate the penetration process of each target.The numerical results indicate that petal formation and friction have significant influence on targets’ballistic performance.Friction has stronger influence on themulti-layered targets than on themonolithic ones.According to the numerical results,about 14%of projectile’s initial kinetic energy is dissipated by friction during penetrating the four-layered contacted target,which is proved to be the most effective type of target studied in thiswork.The results also indicate that,in contrast to common understanding,friction plays an important role even when the impact velocity is significantly higher than the ballistic limit.The outcome of this work may provide useful information for a better understanding of ballistic resistant mechanisms and more efficient utilization of multi-layered metallic targets in armor structural design.展开更多
This paper studies the target controllability of multilayer complex networked systems,in which the nodes are highdimensional linear time invariant(LTI)dynamical systems,and the network topology is directed and weighte...This paper studies the target controllability of multilayer complex networked systems,in which the nodes are highdimensional linear time invariant(LTI)dynamical systems,and the network topology is directed and weighted.The influence of inter-layer couplings on the target controllability of multi-layer networks is discussed.It is found that even if there exists a layer which is not target controllable,the entire multi-layer network can still be target controllable due to the inter-layer couplings.For the multi-layer networks with general structure,a necessary and sufficient condition for target controllability is given by establishing the relationship between uncontrollable subspace and output matrix.By the derived condition,it can be found that the system may be target controllable even if it is not state controllable.On this basis,two corollaries are derived,which clarify the relationship between target controllability,state controllability and output controllability.For the multi-layer networks where the inter-layer couplings are directed chains and directed stars,sufficient conditions for target controllability of networked systems are given,respectively.These conditions are easier to verify than the classic criterion.展开更多
In many engineering networks, only a part of target state variables are required to be estimated.On the other hand,multi-layer complex network exists widely in practical situations.In this paper, the state estimation ...In many engineering networks, only a part of target state variables are required to be estimated.On the other hand,multi-layer complex network exists widely in practical situations.In this paper, the state estimation of target state variables in multi-layer complex dynamical networks with nonlinear node dynamics is studied.A suitable functional state observer is constructed with the limited measurement.The parameters of the designed functional observer are obtained from the algebraic method and the stability of the functional observer is proven by the Lyapunov theorem.Some necessary conditions that need to be satisfied for the design of the functional state observer are obtained.Different from previous studies, in the multi-layer complex dynamical network with nonlinear node dynamics, the proposed method can estimate the state of target variables on some layers directly instead of estimating all the individual states.Thus, it can greatly reduce the placement of observers and computational cost.Numerical simulations with the three-layer complex dynamical network composed of three-dimensional nonlinear dynamical nodes are developed to verify the effectiveness of the method.展开更多
The huge impact kinetic energy cannot be quickly dissipated by the energy-absorbing structure and transferred to the other vehicle through the car body structure,which will cause structural damage and threaten the liv...The huge impact kinetic energy cannot be quickly dissipated by the energy-absorbing structure and transferred to the other vehicle through the car body structure,which will cause structural damage and threaten the lives of the occupants.Therefore,it is necessary to understand the laws of energy conversion,dissipation and transfer during train collisions.This study proposes a multi-layer progressive analysis method of energy flow during train collisions,considering the characteristics of the train.In this method,the train collision system is divided into conversion,dissipation,and transfer layers from the perspective of the train,collision interface,and car body structure to analyze the energy conversion,dissipation and transfer characteristics.Taking the collision process of a rail train as an example,a train collision energy transfer path analysis model was established based on power flow theory.The results show that when the maximum mean acceleration of the vehicle meets the standard requirements,the jerk may exceed the allowable limit of the human body,and there is a risk of injury to the occupants of a secondary collision.The decay rate of the collision energy along the direction of train operation reaches 79%.As the collision progresses,the collision energy gradually converges in the structure with holes,and the structure deforms when the gathered energy is greater than the maximum energy the structure can withstand.The proposed method helps to understand the train collision energy flow law and provides theoretical support for the train crashworthiness design in the future.展开更多
The growing incidence of cyberattacks necessitates a robust and effective Intrusion Detection Systems(IDS)for enhanced network security.While conventional IDSs can be unsuitable for detecting different and emerging at...The growing incidence of cyberattacks necessitates a robust and effective Intrusion Detection Systems(IDS)for enhanced network security.While conventional IDSs can be unsuitable for detecting different and emerging attacks,there is a demand for better techniques to improve detection reliability.This study introduces a new method,the Deep Adaptive Multi-Layer Attention Network(DAMLAN),to boost the result of intrusion detection on network data.Due to its multi-scale attention mechanisms and graph features,DAMLAN aims to address both known and unknown intrusions.The real-world NSL-KDD dataset,a popular choice among IDS researchers,is used to assess the proposed model.There are 67,343 normal samples and 58,630 intrusion attacks in the training set,12,833 normal samples,and 9711 intrusion attacks in the test set.Thus,the proposed DAMLAN method is more effective than the standard models due to the consideration of patterns by the attention layers.The experimental performance of the proposed model demonstrates that it achieves 99.26%training accuracy and 90.68%testing accuracy,with precision reaching 98.54%on the training set and 96.64%on the testing set.The recall and F1 scores again support the model with training set values of 99.90%and 99.21%and testing set values of 86.65%and 91.37%.These results provide a strong basis for the claims made regarding the model’s potential to identify intrusion attacks and affirm its relatively strong overall performance,irrespective of type.Future work would employ more attempts to extend the scalability and applicability of DAMLAN for real-time use in intrusion detection systems.展开更多
In practical engineering construction,multi-layered barriers containing geomembranes are extensively applied to retard the migration of pollutants.However,the associated analytical theory on pollutants diffusion still...In practical engineering construction,multi-layered barriers containing geomembranes are extensively applied to retard the migration of pollutants.However,the associated analytical theory on pollutants diffusion still needs to be further improved.In this work,general analytical solutions are derived for one-dimensional diffusion of degradable organic contaminant(DOC)in the multi-layered media containing geomembranes under a time-varying concentration boundary condition,where the variable substitution and separated variable approaches are employed.These analytical solutions with clear expressions can be used not only to study the diffusion behaviors of DOC in bottom and vertical composite barrier systems,but also to verify other complex numerical models.The proposed general analytical solutions are then fully validated via three comparative analyses,including comparisons with the experimental measurements,an existing analytical solution,and a finite-difference solution.Ultimately,the influences of different factors on the composite cutoff wall’s(CCW,which consists of two soil-bentonite layers and a geomembrane)service performance are investigated through a composite vertical barrier system as the application example.The findings obtained from this investigation can provide scientific guidance for the barrier performance evaluation and the engineering design of CCWs.This application example also exhibits the necessity and effectiveness of the developed analytical solutions.展开更多
Transportation structures such as composite pavements and railway foundations typically consist of multi-layered media designed to withstand high bearing capacity.A theoretical understanding of load transfer mechanism...Transportation structures such as composite pavements and railway foundations typically consist of multi-layered media designed to withstand high bearing capacity.A theoretical understanding of load transfer mechanisms in these multi-layer composites is essential,as it offers intuitive insights into parametric influences and facilitates enhanced structural performance.This paper employs an improved transfer matrix method to address the limitations of existing theoretical approaches for analyzing multi-layer composite structures.By establishing a twodimensional composite pavement model,it investigates load transfer characteristics and validates the accuracy through finite element simulation.The proposed method offers a straightforward analytical approach for examining internal interactions between structural layers.Case studies indicate that the concrete surface layer is the main load-bearing layer for most vertical normal and shear stresses.The soil base layer reduces the overall mechanical response of the substructure,while horizontal actions increase the risk of interfacial slip and cracking.Structural optimization analysis demonstrates that increasing the thickness of the concrete surface layer,enhancing the thickness and stiffness of the soil base layer,or incorporating gradient layers can significantly mitigate these risks of interfacial slip and cracking.The findings of this study can guide the optimization design,parameter analysis,and damage prevention of multi-layer composite structures.展开更多
This study proposes a general imperfect thermal contact model to predict the thermal contact resistance at the interface among multi-layered composite structures.Based on the Green-Lindsay(GL)thermoelastic theory,semi...This study proposes a general imperfect thermal contact model to predict the thermal contact resistance at the interface among multi-layered composite structures.Based on the Green-Lindsay(GL)thermoelastic theory,semi analytical solutions of temperature increment and displacement of multi-layered composite structures are obtained by using the Laplace transform method,upon which the effects of thermal resistance coefficient,partition coefficient,thermal conductivity ratio and heat capacity ratio on the responses are studied.The results show that the generalized imperfect thermal contact model can realistically describe the imperfect thermal contact problem.Accordingly,it may degenerate into other thermal contact models by adjusting the thermal resistance coefficient and partition coefficient.展开更多
Low Earth Orbit(LEO)mega-constellation networks,exemplified by Starlink,are poised to play a pivotal role in future mobile communication networks,due to their low latency and high capacity.With the massively deployed ...Low Earth Orbit(LEO)mega-constellation networks,exemplified by Starlink,are poised to play a pivotal role in future mobile communication networks,due to their low latency and high capacity.With the massively deployed satellites,ground users now can be covered by multiple visible satellites,but also face complex handover issues with such massive high-mobility satellites in multi-layer.The end-to-end routing is also affected by the handover behavior.In this paper,we propose an intelligent handover strategy dedicated to multi-layer LEO mega-constellation networks.Firstly,an analytic model is utilized to rapidly estimate the end-to-end propagation latency as a key handover factor to construct a multi-objective optimization model.Subsequently,an intelligent handover strategy is proposed by employing the Dueling Double Deep Q Network(D3QN)-based deep reinforcement learning algorithm for single-layer constellations.Moreover,an optimal crosslayer handover scheme is proposed by predicting the latency-jitter and minimizing the cross-layer overhead.Simulation results demonstrate the superior performance of the proposed method in the multi-layer LEO mega-constellation,showcasing reductions of up to 8.2%and 59.5%in end-to-end latency and jitter respectively,when compared to the existing handover strategies.展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
Stab-resistant textiles play a critical role in personal protection,necessitating a deeper understanding of how structural and layering factors influence their performance.The current study experimentally examines the...Stab-resistant textiles play a critical role in personal protection,necessitating a deeper understanding of how structural and layering factors influence their performance.The current study experimentally examines the effects of textile structure,layering,and ply orientation on the stab resistance of multi-layer textiles.Three 3D warp interlock(3DWI)structures({f1},{f2},{f3})and a 2D woven fabric({f4}),all made of high-performance p-aramid yarns,were engineered and manufactured.Multi-layer specimens were prepared and subjected to drop-weight stabbing tests following HOSBD standards.Stabbing performance metrics,including Depth of Trauma(DoT),Depth of Penetration(DoP),and trauma deformation(Ymax,Xmax),were investigated and analyzed.Statistical analyses(Two-and One-Way ANOVA)indicated that fabric type and layer number significantly impacted DoP(P<0.05),while ply orientation significantly affected DoP(P<0.05)but not DoT(P>0.05).Further detailed analysis revealed that 2D woven fabrics exhibited greater trauma deformation than 3D WIF structures.Increasing the number of layers reduced both DoP and DoT across all fabric structures,with f3 demonstrating the best performance in multi-layer configurations.Aligned ply orientations also enhanced stab resistance,underscoring the importance of alignment in dissipating impact energy.展开更多
The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integrat...The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies.Human epidermal growth factor receptor,hormone receptors,and angiogenesis factors are among the established therapies in tumor reduction and managing side effects.Novel targeted therapies like KRAS G12C,Claudin-18 isoform 2(CLDN18.2),Trophoblast cell-surface antigen 2(TROP2),and epigenetic regulators emphasize their promise in advancing precision medicine.However,in many cases,the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions.The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology.This review seeks to elucidate recent advancements,address persisting challenges,and explore opportunities for innovative developments in cancer target research.Additionally,it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research.In conclusion,innovative approaches in oncology,supported by pharmacological research,ongoing clinical trials,molecular biosciences,and artificial intelligence,are poised to significantly transform cancer treatment.展开更多
Diabetes involves multi-organ complications that seriously threaten human life and health,and has become a major public health problem of global concern.Unfortunately,clinical management strategies for diabetic compli...Diabetes involves multi-organ complications that seriously threaten human life and health,and has become a major public health problem of global concern.Unfortunately,clinical management strategies for diabetic complications are still in their“infancy”,restricted by a limited understanding of their complex pathological mechanism.As is well established,lipid metabolism disorder is the characteristic pathological factors of diabetes,but the detailed molecular mechanisms driving the progression of multi-organ complications remain obscure.Protein S-acylation(often referred to as S-palmitoylation)is a reversible lipid modification that reversibly binds fatty acids to protein-specific cysteine(Cys)residues through palmitoyl acyl transferases(PATs,also known as DHHCs)and deacylation enzymes,which is involved in the pathological progression of a variety of complex diseases such as cancer,neurological disorders and metabolic syndrome.Notably,recent studies have shown that protein S-acylation drives the progression of diabetes and its multiple complications,and targeted intervention in the protein S-acylation process significantly alleviates the progression of diabetes and its complications,suggesting that protein S-acylation may be a common pathological link and intervention target of diabetes complications.Therefore,this review systematically comprehends the contribution of protein S-acylation to the progression of diabetes and its complications,summarizes the influence of the diabetic environment on S-acylation related enzymes,as well as providing an in-depth analysis of current drugs,measures,and challenges in targeting S-acylation.Finally,the accessibility of targeting protein S-acylation to prevent diabetes and its complications and the focus of future in-depth studies are envisioned,with a view to providing comprehensive and in-depth references and rationale for future novel strategies targeting protein S-acylation to prevent and treat diabetes and its multi-organ complications.展开更多
In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquiti...In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.展开更多
Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis....Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.展开更多
文摘Cased explosives generate highly energetic fragments as their casing breaks up. Due to the complexity of casing fragment related behavior such as embedment, perforation and ricochet, it may be insufficient to use equivalent triangular pressure loading in fragment impact simulations. This simplified method may over- or under-predict the target response. Recently, a procedure using contact techniques has been proposed to overcome such difficulties. It has been shown that the new method has the inherent capability in modeling the multi-piece and multi-hit fragment impact problems in a more realistic way. To investigate the applicability of the proposed method to simulations involving multi-layer penetration, the selected problems of fragment impact on multi-layer targets are described in this paper. It is demonstrated that this method is capable of predicting the complicated multi-layer structural response caused by fragment impact and penetration. Modeling procedures and some technical issues are also discussed.
基金National Natural Science Foundation of China(52175237)。
文摘The key parameters that characterize the morphological quality of multi-layer and multi-pass metal laser deposited parts are the surface roughness and the error between the actual printing height and the theoretical model height.The Taguchi method was employed to establish the correlations between process parameter combinations and multi-objective characterization of metal deposition morphology(height error and roughness).Results show that using the signal-to-noise ratio and grey relational analysis,the optimal parameter combination for multi-layer and multi-pass deposition is determined as follows:laser power of 800 W,powder feeding rate of 0.3 r/min,step distance of 1.6 mm,and scanning speed of 20 mm/s.Subsequently,a Genetic Bayesian-back propagation(GB-BP)network is constructed to predict multi-objective responses.Compared with the traditional back propagation network,the GB-back propagation network improves the prediction accuracy of height error and surface roughness by 43.14%and 71.43%,respectively.This network can accurately predict the multi-objective characterization of morphological quality of multi-layer and multi-pass metal deposited parts.
基金supported by the National Key Research and Development Program of China(No.2022YFB3404700)the National Natural Science Foundation of China(Nos.52105313 and 52275299)+2 种基金the Research and Development Program of Beijing Municipal Education Commission,China(No.KM202210005036)the Natural Science Foundation of Chongqing,China(No.CSTB2023NSCQ-MSX0701)the National Defense Basic Research Projects of China(No.JCKY2022405C002).
文摘At present,the emerging solid-phase friction-based additive manufacturing technology,including friction rolling additive man-ufacturing(FRAM),can only manufacture simple single-pass components.In this study,multi-layer multi-pass FRAM-deposited alumin-um alloy samples were successfully prepared using a non-shoulder tool head.The material flow behavior and microstructure of the over-lapped zone between adjacent layers and passes during multi-layer multi-pass FRAM deposition were studied using the hybrid 6061 and 5052 aluminum alloys.The results showed that a mechanical interlocking structure was formed between the adjacent layers and the adja-cent passes in the overlapped center area.Repeated friction and rolling of the tool head led to different degrees of lateral flow and plastic deformation of the materials in the overlapped zone,which made the recrystallization degree in the left and right edge zones of the over-lapped zone the highest,followed by the overlapped center zone and the non-overlapped zone.The tensile strength of the overlapped zone exceeded 90%of that of the single-pass deposition sample.It is proved that although there are uneven grooves on the surface of the over-lapping area during multi-layer and multi-pass deposition,they can be filled by the flow of materials during the deposition of the next lay-er,thus ensuring the dense microstructure and excellent mechanical properties of the overlapping area.The multi-layer multi-pass FRAM deposition overcomes the limitation of deposition width and lays the foundation for the future deposition of large-scale high-performance components.
基金supported by National Natural Science Foundation of China(Grant No.11802141)Postgraduate Research&Practice Innovation Program of Jiangsu Province(Grant No.KYCX18_0465)。
文摘Three different kinds of PELE(the penetrator with lateral efficiency) were launched by ballistic artillery to impact the multi-layer spaced metal target plates.The lmpact velocities of the projectiles were measured by the velocity measuring system.The damage degree and process of each laye r of target plate impacted by the three kinds of projectiles were analyzed.The experimental results show that all the three kinds of projectiles have the effect of expanding holes on the multi-layer spaced metal target plates.For the normal structure PELE(without layered) with tungsten alloy jacket and the radial layered PELE with tungsten alloy jacket,the diameters of holes on the seco nd layer of plates are 3.36 times and 3.76 times of the diameter of the projectile,re spectively.For radial layered PELE with W/Zr-based amorphous composite jacket,due to the large number of tungsten wires dispersed after the impact,the diameter of the holes on the four-layer spaced plates can reach 2.4 times,3.04 times,5.36 times and 2.68 times of the diameter of the projectile.Besides,the normal structure PELE with tungsten alloy jacket and the radial layered PELE whit tungsten alloy jacket formed a large number of fragments impact marks on the third target plate.Although the number of fragments penetrating the third target plate is not as large as that of the normal structure PELE,the area of dispersion of fragments impact craters on the third target plate is larger by the radial layered PELE.The radial layered PELE with W/Zr-based amorphous composite jacket released a lot of heat energy due to the impact of the matrix material,and formed a large area of ablation marks on the last three target plates.
基金This work was supported by the National Natural Science Foundation of China[Grant Nos.12102023 and 12072011].
文摘Themain goal of this work is to study the ballistic performance ofmulti-layered moderately-thick metallic targets.Several target configurations have been considered in thiswork,with various types of interlayer connection(spaced,contacted and adhesive)and the number of layers(four and eight),and the influence of target configurations on ballistic performance has been studied experimentally and numerically.In the experiments,the targets were impacted by 12.7-mm projectiles at a velocity around 820 m/s.The experimental results show that,with similar total thickness,the contacted and adhesive targets exhibit better ballistic performance than the monolithic targets,and the four-layered targets are better than the eight-layered targets with the same connection type.To explore the ballistic resistance mechanism,numerical method has been used to simulate the penetration process of each target.The numerical results indicate that petal formation and friction have significant influence on targets’ballistic performance.Friction has stronger influence on themulti-layered targets than on themonolithic ones.According to the numerical results,about 14%of projectile’s initial kinetic energy is dissipated by friction during penetrating the four-layered contacted target,which is proved to be the most effective type of target studied in thiswork.The results also indicate that,in contrast to common understanding,friction plays an important role even when the impact velocity is significantly higher than the ballistic limit.The outcome of this work may provide useful information for a better understanding of ballistic resistant mechanisms and more efficient utilization of multi-layered metallic targets in armor structural design.
基金supported by the National Natural Science Foundation of China (U1808205)Hebei Natural Science Foundation (F2000501005)。
文摘This paper studies the target controllability of multilayer complex networked systems,in which the nodes are highdimensional linear time invariant(LTI)dynamical systems,and the network topology is directed and weighted.The influence of inter-layer couplings on the target controllability of multi-layer networks is discussed.It is found that even if there exists a layer which is not target controllable,the entire multi-layer network can still be target controllable due to the inter-layer couplings.For the multi-layer networks with general structure,a necessary and sufficient condition for target controllability is given by establishing the relationship between uncontrollable subspace and output matrix.By the derived condition,it can be found that the system may be target controllable even if it is not state controllable.On this basis,two corollaries are derived,which clarify the relationship between target controllability,state controllability and output controllability.For the multi-layer networks where the inter-layer couplings are directed chains and directed stars,sufficient conditions for target controllability of networked systems are given,respectively.These conditions are easier to verify than the classic criterion.
基金Project supported by the National Natural Science Foundation of China (Grant Nos.62373197 and 61873326)。
文摘In many engineering networks, only a part of target state variables are required to be estimated.On the other hand,multi-layer complex network exists widely in practical situations.In this paper, the state estimation of target state variables in multi-layer complex dynamical networks with nonlinear node dynamics is studied.A suitable functional state observer is constructed with the limited measurement.The parameters of the designed functional observer are obtained from the algebraic method and the stability of the functional observer is proven by the Lyapunov theorem.Some necessary conditions that need to be satisfied for the design of the functional state observer are obtained.Different from previous studies, in the multi-layer complex dynamical network with nonlinear node dynamics, the proposed method can estimate the state of target variables on some layers directly instead of estimating all the individual states.Thus, it can greatly reduce the placement of observers and computational cost.Numerical simulations with the three-layer complex dynamical network composed of three-dimensional nonlinear dynamical nodes are developed to verify the effectiveness of the method.
基金Supported by the National Natural Science Foundation of China(Grant No.52172409)Postdoctoral Innovation Talents Support Program(Grant No.BX20240298)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.2682024GF023)Heilongjiang Province Postdoctoral Foundation Project(Grant No.LBH-Z23041).
文摘The huge impact kinetic energy cannot be quickly dissipated by the energy-absorbing structure and transferred to the other vehicle through the car body structure,which will cause structural damage and threaten the lives of the occupants.Therefore,it is necessary to understand the laws of energy conversion,dissipation and transfer during train collisions.This study proposes a multi-layer progressive analysis method of energy flow during train collisions,considering the characteristics of the train.In this method,the train collision system is divided into conversion,dissipation,and transfer layers from the perspective of the train,collision interface,and car body structure to analyze the energy conversion,dissipation and transfer characteristics.Taking the collision process of a rail train as an example,a train collision energy transfer path analysis model was established based on power flow theory.The results show that when the maximum mean acceleration of the vehicle meets the standard requirements,the jerk may exceed the allowable limit of the human body,and there is a risk of injury to the occupants of a secondary collision.The decay rate of the collision energy along the direction of train operation reaches 79%.As the collision progresses,the collision energy gradually converges in the structure with holes,and the structure deforms when the gathered energy is greater than the maximum energy the structure can withstand.The proposed method helps to understand the train collision energy flow law and provides theoretical support for the train crashworthiness design in the future.
基金Nourah bint Abdulrahman University for funding this project through the Researchers Supporting Project(PNURSP2025R319)Riyadh,Saudi Arabia and Prince Sultan University for covering the article processing charges(APC)associated with this publication.Special acknowledgement to Automated Systems&Soft Computing Lab(ASSCL),Prince Sultan University,Riyadh,Saudi Arabia.
文摘The growing incidence of cyberattacks necessitates a robust and effective Intrusion Detection Systems(IDS)for enhanced network security.While conventional IDSs can be unsuitable for detecting different and emerging attacks,there is a demand for better techniques to improve detection reliability.This study introduces a new method,the Deep Adaptive Multi-Layer Attention Network(DAMLAN),to boost the result of intrusion detection on network data.Due to its multi-scale attention mechanisms and graph features,DAMLAN aims to address both known and unknown intrusions.The real-world NSL-KDD dataset,a popular choice among IDS researchers,is used to assess the proposed model.There are 67,343 normal samples and 58,630 intrusion attacks in the training set,12,833 normal samples,and 9711 intrusion attacks in the test set.Thus,the proposed DAMLAN method is more effective than the standard models due to the consideration of patterns by the attention layers.The experimental performance of the proposed model demonstrates that it achieves 99.26%training accuracy and 90.68%testing accuracy,with precision reaching 98.54%on the training set and 96.64%on the testing set.The recall and F1 scores again support the model with training set values of 99.90%and 99.21%and testing set values of 86.65%and 91.37%.These results provide a strong basis for the claims made regarding the model’s potential to identify intrusion attacks and affirm its relatively strong overall performance,irrespective of type.Future work would employ more attempts to extend the scalability and applicability of DAMLAN for real-time use in intrusion detection systems.
基金Project(2023YFC3707800)supported by the National Key Research and Development Program of China。
文摘In practical engineering construction,multi-layered barriers containing geomembranes are extensively applied to retard the migration of pollutants.However,the associated analytical theory on pollutants diffusion still needs to be further improved.In this work,general analytical solutions are derived for one-dimensional diffusion of degradable organic contaminant(DOC)in the multi-layered media containing geomembranes under a time-varying concentration boundary condition,where the variable substitution and separated variable approaches are employed.These analytical solutions with clear expressions can be used not only to study the diffusion behaviors of DOC in bottom and vertical composite barrier systems,but also to verify other complex numerical models.The proposed general analytical solutions are then fully validated via three comparative analyses,including comparisons with the experimental measurements,an existing analytical solution,and a finite-difference solution.Ultimately,the influences of different factors on the composite cutoff wall’s(CCW,which consists of two soil-bentonite layers and a geomembrane)service performance are investigated through a composite vertical barrier system as the application example.The findings obtained from this investigation can provide scientific guidance for the barrier performance evaluation and the engineering design of CCWs.This application example also exhibits the necessity and effectiveness of the developed analytical solutions.
基金supported by Fundamental Research Funds for the Central Universities(No.lzujbky-2024-05)Innovation Foundation of Provincial Education Department of Gansu(2024B-005)+2 种基金Scientific Department of Gansu(24CXGA083,24CXGA024,JK2024-28,JK2024-32 and 23CXJA0007)Industrial Support Plan Project of Provincial Education Department of Gansu(2025CYZC-003 and CYZC-2024-10)the Hunan Natural Science Foundation Science and Education Joint Fund Project(2022JJ60109).
文摘Transportation structures such as composite pavements and railway foundations typically consist of multi-layered media designed to withstand high bearing capacity.A theoretical understanding of load transfer mechanisms in these multi-layer composites is essential,as it offers intuitive insights into parametric influences and facilitates enhanced structural performance.This paper employs an improved transfer matrix method to address the limitations of existing theoretical approaches for analyzing multi-layer composite structures.By establishing a twodimensional composite pavement model,it investigates load transfer characteristics and validates the accuracy through finite element simulation.The proposed method offers a straightforward analytical approach for examining internal interactions between structural layers.Case studies indicate that the concrete surface layer is the main load-bearing layer for most vertical normal and shear stresses.The soil base layer reduces the overall mechanical response of the substructure,while horizontal actions increase the risk of interfacial slip and cracking.Structural optimization analysis demonstrates that increasing the thickness of the concrete surface layer,enhancing the thickness and stiffness of the soil base layer,or incorporating gradient layers can significantly mitigate these risks of interfacial slip and cracking.The findings of this study can guide the optimization design,parameter analysis,and damage prevention of multi-layer composite structures.
基金Projects(42477162,52108347,52178371,52168046,52178321,52308383)supported by the National Natural Science Foundation of ChinaProjects(2023C03143,2022C01099,2024C01219,2022C03151)supported by the Zhejiang Key Research and Development Plan,China+6 种基金Project(LQ22E080010)supported by the Exploring Youth Project of Zhejiang Natural Science Foundation,ChinaProject(LR21E080005)supported by the Outstanding Youth Project of Natural Science Foundation of Zhejiang Province,ChinaProject(2022M712964)supported by the Postdoctoral Science Foundation of ChinaProject(2023AFB008)supported by the Natural Science Foundation of Hubei Province for Youth,ChinaProject(202203)supported by Engineering Research Centre of Rock-Soil Drilling&Excavation and Protection,Ministry of Education,ChinaProject(202305-2)supported by the Science and Technology Project of Zhejiang Provincial Communication Department,ChinaProject(2021K256)supported by the Construction Research Founds of Department of Housing and Urban-Rural Development of Zhejiang Province,China。
文摘This study proposes a general imperfect thermal contact model to predict the thermal contact resistance at the interface among multi-layered composite structures.Based on the Green-Lindsay(GL)thermoelastic theory,semi analytical solutions of temperature increment and displacement of multi-layered composite structures are obtained by using the Laplace transform method,upon which the effects of thermal resistance coefficient,partition coefficient,thermal conductivity ratio and heat capacity ratio on the responses are studied.The results show that the generalized imperfect thermal contact model can realistically describe the imperfect thermal contact problem.Accordingly,it may degenerate into other thermal contact models by adjusting the thermal resistance coefficient and partition coefficient.
基金supported by the National Natural Science Foundation of China(No.62401597)Natural Science Foundation of Hunan Province,China(No.2024JJ6469)the Research Project of National University of Defense Technology,China(No.ZK22-02).
文摘Low Earth Orbit(LEO)mega-constellation networks,exemplified by Starlink,are poised to play a pivotal role in future mobile communication networks,due to their low latency and high capacity.With the massively deployed satellites,ground users now can be covered by multiple visible satellites,but also face complex handover issues with such massive high-mobility satellites in multi-layer.The end-to-end routing is also affected by the handover behavior.In this paper,we propose an intelligent handover strategy dedicated to multi-layer LEO mega-constellation networks.Firstly,an analytic model is utilized to rapidly estimate the end-to-end propagation latency as a key handover factor to construct a multi-objective optimization model.Subsequently,an intelligent handover strategy is proposed by employing the Dueling Double Deep Q Network(D3QN)-based deep reinforcement learning algorithm for single-layer constellations.Moreover,an optimal crosslayer handover scheme is proposed by predicting the latency-jitter and minimizing the cross-layer overhead.Simulation results demonstrate the superior performance of the proposed method in the multi-layer LEO mega-constellation,showcasing reductions of up to 8.2%and 59.5%in end-to-end latency and jitter respectively,when compared to the existing handover strategies.
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
文摘Stab-resistant textiles play a critical role in personal protection,necessitating a deeper understanding of how structural and layering factors influence their performance.The current study experimentally examines the effects of textile structure,layering,and ply orientation on the stab resistance of multi-layer textiles.Three 3D warp interlock(3DWI)structures({f1},{f2},{f3})and a 2D woven fabric({f4}),all made of high-performance p-aramid yarns,were engineered and manufactured.Multi-layer specimens were prepared and subjected to drop-weight stabbing tests following HOSBD standards.Stabbing performance metrics,including Depth of Trauma(DoT),Depth of Penetration(DoP),and trauma deformation(Ymax,Xmax),were investigated and analyzed.Statistical analyses(Two-and One-Way ANOVA)indicated that fabric type and layer number significantly impacted DoP(P<0.05),while ply orientation significantly affected DoP(P<0.05)but not DoT(P>0.05).Further detailed analysis revealed that 2D woven fabrics exhibited greater trauma deformation than 3D WIF structures.Increasing the number of layers reduced both DoP and DoT across all fabric structures,with f3 demonstrating the best performance in multi-layer configurations.Aligned ply orientations also enhanced stab resistance,underscoring the importance of alignment in dissipating impact energy.
文摘The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies.Human epidermal growth factor receptor,hormone receptors,and angiogenesis factors are among the established therapies in tumor reduction and managing side effects.Novel targeted therapies like KRAS G12C,Claudin-18 isoform 2(CLDN18.2),Trophoblast cell-surface antigen 2(TROP2),and epigenetic regulators emphasize their promise in advancing precision medicine.However,in many cases,the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions.The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology.This review seeks to elucidate recent advancements,address persisting challenges,and explore opportunities for innovative developments in cancer target research.Additionally,it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research.In conclusion,innovative approaches in oncology,supported by pharmacological research,ongoing clinical trials,molecular biosciences,and artificial intelligence,are poised to significantly transform cancer treatment.
基金supported by National Natural Science Foundation of China(No.82304909)National Natural Science Foundation of China(No.82174112)Tianjin Science and Technology Innovation Base Construction(No.24ZYJDSY00280).
文摘Diabetes involves multi-organ complications that seriously threaten human life and health,and has become a major public health problem of global concern.Unfortunately,clinical management strategies for diabetic complications are still in their“infancy”,restricted by a limited understanding of their complex pathological mechanism.As is well established,lipid metabolism disorder is the characteristic pathological factors of diabetes,but the detailed molecular mechanisms driving the progression of multi-organ complications remain obscure.Protein S-acylation(often referred to as S-palmitoylation)is a reversible lipid modification that reversibly binds fatty acids to protein-specific cysteine(Cys)residues through palmitoyl acyl transferases(PATs,also known as DHHCs)and deacylation enzymes,which is involved in the pathological progression of a variety of complex diseases such as cancer,neurological disorders and metabolic syndrome.Notably,recent studies have shown that protein S-acylation drives the progression of diabetes and its multiple complications,and targeted intervention in the protein S-acylation process significantly alleviates the progression of diabetes and its complications,suggesting that protein S-acylation may be a common pathological link and intervention target of diabetes complications.Therefore,this review systematically comprehends the contribution of protein S-acylation to the progression of diabetes and its complications,summarizes the influence of the diabetic environment on S-acylation related enzymes,as well as providing an in-depth analysis of current drugs,measures,and challenges in targeting S-acylation.Finally,the accessibility of targeting protein S-acylation to prevent diabetes and its complications and the focus of future in-depth studies are envisioned,with a view to providing comprehensive and in-depth references and rationale for future novel strategies targeting protein S-acylation to prevent and treat diabetes and its multi-organ complications.
文摘In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
基金supported by the Natural Science Foundation of Jilin Province(No.SKL202302002).
文摘Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.
