A 3D crustal model was constructed using a combination of cutting-edge techniques,which were integrated to provide a density model for Egypt and address the sporadic distribution of seismic data.These techniques inclu...A 3D crustal model was constructed using a combination of cutting-edge techniques,which were integrated to provide a density model for Egypt and address the sporadic distribution of seismic data.These techniques include obtaining gravity data from the Gravity Field and Steady-State Ocean Circulation Explorer(GOCE),creating seismic profiles,analyzing the receiver functions of seismic data,obtaining information from boreholes,and providing geological interpretations.GOCE satellite gravity data were processed to construct a preliminary model based on nonlinear inversions of the data.A regional crustal thickness model was developed using receiver functions,seismic refraction profiles,and geological insights.The inverted model was validated using borehole data and compared with seismic estimates.The model exhibited strong consistency and revealed a correlation between crustal thickness,geology,and tectonics of Egypt.It showed that the shallowest depths of the Moho are located in the north along the Mediterranean Sea and in the eastern part along the Red Sea,reflecting an oceanic plate with a thin,high-density crust.The deepest Moho depths are located in the southwestern part of Egypt,Red Sea coastal mountains,and Sinai Peninsula.The obtained 3D model of crustal thickness provided finely detailed Moho depth estimates that aligned closely with geology and tectonic characteristics of Egypt,contributing valuable insights into the subsurface structure and tectonic processes of region.展开更多
Unsteady aerodynamic characteristics at high angles of attack are of great importance to the design and development of advanced fighter aircraft, which are characterized by post-stall maneuverability with multiple Deg...Unsteady aerodynamic characteristics at high angles of attack are of great importance to the design and development of advanced fighter aircraft, which are characterized by post-stall maneuverability with multiple Degrees-of-Freedom(multi-DOF) and complex flow field structure.In this paper, a special kind of cable-driven parallel mechanism is firstly utilized as a new suspension method to conduct unsteady dynamic wind tunnel tests at high angles of attack, thereby providing experimental aerodynamic data. These tests include a wide range of multi-DOF coupled oscillatory motions with various amplitudes and frequencies. Then, for aerodynamic modeling and analysis, a novel data-driven Feature-Level Attention Recurrent neural network(FLAR) is proposed. This model incorporates a specially designed feature-level attention module that focuses on the state variables affecting the aerodynamic coefficients, thereby enhancing the physical interpretability of the aerodynamic model. Subsequently, spin maneuver simulations, using a mathematical model as the baseline, are conducted to validate the effectiveness of the FLAR. Finally, the results on wind tunnel data reveal that the FLAR accurately predicts aerodynamic coefficients, and observations through the visualization of attention scores identify the key state variables that affect the aerodynamic coefficients. It is concluded that the proposed FLAR enhances the interpretability of the aerodynamic model while achieving good prediction accuracy and generalization capability for multi-DOF coupling motion at high angles of attack.展开更多
Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesi...Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesics,including opioids and nonsteroidal anti-inflammatory drugs,are often limited by their insufficient efficacy,tolerance,and risk of dependence.Traditional Chinese Medicine(TCM),characterized by its multi-component,multi-target,and systemic regulatory properties,has shown promising potential in cancer pain management.This review provides a comprehensive overview of the clinical classification and underlying mechanisms of cancer pain(including nerve infiltration,dysregulation of inflammatory mediators and ion channels,central sensitization,neuro-immune crosstalk,metabolic reprogramming,and gut-brain axis impairment),as well as the analgesic effects of representative TCM agents in cancer pain management.For example,bioactive components such as tetrahydroberberine,levo-tetrahydropalmatine,and piperine exert analgesic effects,thereby improving the quality of life of patients by inhibiting inflammatory cascades,regulating neurotransmitter systems,and preserving neural integrity.Commonly used preclinical models,including bone cancer pain,pancreatic cancer pain,and chemotherapy-induced peripheral neuropathy models,are summarized for their utility in mechanistic studies and efficacy evaluations.This review also discusses the current limitations of clinical evidence,such as small sample sizes,short follow-up periods,and limited translation from animal models,alongside major challenges in standardization,mechanistic elucidation,and clinical trial design.Future directions should focus on precise pain phenotyping,integrated multi-target interventions,rigorous efficacy safety validation,and innovations in drug delivery to facilitate the standardization and global adoption of TCM in cancer pain management.展开更多
The average stiffness performance indices throughout the workspace are commonly used as global stiffness performance indices to evaluate the overall stiffness performance of parallel mechanisms,which involves an analy...The average stiffness performance indices throughout the workspace are commonly used as global stiffness performance indices to evaluate the overall stiffness performance of parallel mechanisms,which involves an analysis of the stiffness performance of numerous discrete points in the workspace.This necessitates time-consuming and inefficient calculation,which is particularly pronounced in the optimization design stage of the mechanism,where the variations in the global stiffness performance indices versus various dimensional and structural parameters need to be analyzed.This paper presents a semi-analytical approach for stiffness modeling of the novel(R(RPS&RP))&2-UPS parallel mechanism(referred to as the Trifree mechanism)and proposes“local”stiffness performance indices as alternatives to global indices.Drawing on the screw theory,the Cartesian stiffness matrix of the Trifree mechanism is formulated explicitly by considering the compliances of all elastic elements and the over-constraint characteristics inherent in the mechanism.Based on the spherical motion pattern of the Trifree mechanism,four special reference configurations are extracted within the workspace.This yields“local”stiffness performance indices capable of accurately evaluating the overall stiffness performance of the mechanism and effectively improving the computational efficiency.The variations in global and“local”stiffness performance indices versus key design parameters are investigated.Furthermore,the proposed indices are applied to the Tricept and Trimule mechanisms.The results demonstrate that the proposed indices exhibit excellent computational accuracy and efficiency in evaluating the overall stiffness performance of these spherical parallel mechanisms.Moreover,the stiffness performance of the novel parallel mechanism investigated in this study closely resembles that of the well-known Tricept and Trimule mechanisms.This research proposes a semi-analytic stiffness model of the Trifree mechanism and“local”stiffness performance indices to evaluate the overall stiffness performance,thereby substantially improving the computational efficiency without sacrificing accuracy.展开更多
Embedding optical fiber sensors into composite materials offers the advantage of real-time structural monitoring.However,there is an order-of-magnitude difference in diameter between optical fibers and reinforcing fib...Embedding optical fiber sensors into composite materials offers the advantage of real-time structural monitoring.However,there is an order-of-magnitude difference in diameter between optical fibers and reinforcing fibers,and the detailed mechanism of how embedded optical fibers affect the micromechanical behavior and damage failure processes within composite materials remains unclear.This paper presents a micromechanical simulation analysis of composite materials embedded with optical fibers.By constructing representative volume elements(RVEs)with randomly distributed reinforcing fibers,the optical fiber,the matrix,and the interface phase,the micromechanical behavior and damage evolution under transverse tensile and compressive loads are explored.The study finds that the presence of embedded optical fibers significantly influences the initiation and propagation of microscopic damage within the composites.Under transverse tension,the fiber-matrix interface cracks first,followed by plastic cracking in the matrix surrounding the fibers,forming micro-cracks.Eventually,these cracks connect with the debonded areas at the fiber-matrix interface to form a dominant crack that spans the entire model.Under transverse compression,plastic cracking first occurs in the resin surrounding the optical fibers,connecting with the interface debonding areas between the optical fibers and the matrix to form two parallel shear bands.Additionally,it is observed that the strength of the interface between the optical fiber and the matrix critically affects the simulation results.The simulated damage morphologies align closely with those observed using scanning electron microscopy(SEM).These findings offer theoretical insights that can inform the design and fabrication of smart composite materials with embedded optical fiber sensors for advanced structural health monitoring.展开更多
The acetylpolyamine oxidase(APAO),spermine oxidase(SMO),and spermidine/spermine N1-acetyltransferase(SSAT)are pivotal enzymes in polyamine metabolism,exerting direct influence on polyamine homeostasis regulation.Dysfu...The acetylpolyamine oxidase(APAO),spermine oxidase(SMO),and spermidine/spermine N1-acetyltransferase(SSAT)are pivotal enzymes in polyamine metabolism,exerting direct influence on polyamine homeostasis regulation.Dysfunctions in these enzymes are intricately linked to inflammatory diseases and cancers.Establishing their three-dimensional structures is essential for exploring enzymatic catalytic mechanisms and designing inhibitors at the atomic level.This article primarily assesses the precision of AlphaFold2 and molecular dynamics simulations in determining the three-dimensional structures of these enzymes,utilizing protein conformation rationality assessment,residue correlation matrix,and other techniques.This provides robust models for subsequent polyamine catabolic metabolism calculations and offers valuable insights for modeling proteins that have yet to acquire crystal structures.展开更多
BACKGROUND Colorectal cancer(CRC)remains a major global health burden due to its high incidence and mortality,with treatment efficacy often hindered by tumor hetero-geneity,drug resistance,and a complex tumor microenv...BACKGROUND Colorectal cancer(CRC)remains a major global health burden due to its high incidence and mortality,with treatment efficacy often hindered by tumor hetero-geneity,drug resistance,and a complex tumor microenvironment(TME).Lactate metabolism plays a pivotal role in reshaping the TME,promoting immune eva-sion and epithelial-mesenchymal transition,making it a promising target for novel therapeutic strategies and prognostic modeling in CRC.AIM To offer an in-depth analysis of the role of lactate metabolism in CRC,high-lighting its significance in the TME and therapeutic response.METHODS Utilizing single-cell and transcriptomic data from the Gene Expression Omnibus and The Cancer Genome Atlas,we identified key lactate metabolic activities,particularly in the monocyte/macrophage subpopulation.RESULTS Seven lactate metabolism-associated genes were significantly linked to CRC prognosis and used to construct a predictive model.This model accurately forecasts patient outcomes and reveals notable distinct patterns of immune infiltration and transcriptomic profiles mutation profiles between high-and low-risk groups.High-risk patients demonstrated elevated immune cell infiltration,increased mutation frequencies,and heightened sensitivity to specific drugs(AZD6482,tozasertib,and SB216763),providing a foundation for personalized treatment approaches.Additionally,a nomogram integrating clinical and metabolic data effectively predicted 1-,3-,and 5-year survival rates.CONCLUSION This report underscored the pivotal mechanism of lactate metabolism in CRC prognosis and suggest novel avenues for therapeutic intervention.展开更多
Thermal Protection System(TPS)with thick tiles,low thermal conductivity,and a short re-entry stage stands as a critical element within reusable aircraft,whose reliability is related to the function and changes with th...Thermal Protection System(TPS)with thick tiles,low thermal conductivity,and a short re-entry stage stands as a critical element within reusable aircraft,whose reliability is related to the function and changes with their physical properties,external conditions,and degradation.Meanwhile,due to the limitation of testing resources,epistemic uncertainties stemming from the small samples are present in TPS reliability modeling.However,current TPS reliability modeling methods face challenges in characterizing the relationships among reliability and physical properties,external conditions,degradation,and epistemic uncertainties.Therefore,under the framework of belief reliability theory,a TPS reliability model is constructed,which takes into account the physical principle,external conditions,performance degradation,and epistemic uncertainties.A reliability simulation algorithm is proposed to calculate TPS reliability.Through a case study and comparison analysis,the proposed method is validated as more effective than the existing method.Additionally,reliability sensitivity analysis is conducted to identify the sensitive factors of reliability under the condition of small samples,through which suggestions are provided for TPS functional design and improvement.展开更多
文摘A 3D crustal model was constructed using a combination of cutting-edge techniques,which were integrated to provide a density model for Egypt and address the sporadic distribution of seismic data.These techniques include obtaining gravity data from the Gravity Field and Steady-State Ocean Circulation Explorer(GOCE),creating seismic profiles,analyzing the receiver functions of seismic data,obtaining information from boreholes,and providing geological interpretations.GOCE satellite gravity data were processed to construct a preliminary model based on nonlinear inversions of the data.A regional crustal thickness model was developed using receiver functions,seismic refraction profiles,and geological insights.The inverted model was validated using borehole data and compared with seismic estimates.The model exhibited strong consistency and revealed a correlation between crustal thickness,geology,and tectonics of Egypt.It showed that the shallowest depths of the Moho are located in the north along the Mediterranean Sea and in the eastern part along the Red Sea,reflecting an oceanic plate with a thin,high-density crust.The deepest Moho depths are located in the southwestern part of Egypt,Red Sea coastal mountains,and Sinai Peninsula.The obtained 3D model of crustal thickness provided finely detailed Moho depth estimates that aligned closely with geology and tectonic characteristics of Egypt,contributing valuable insights into the subsurface structure and tectonic processes of region.
基金supported by the National Natural Science Foundation of China(Nos.12172315,12072304,11702232)the Fujian Provincial Natural Science Foundation,China(No.2021J01050)the Aeronautical Science Foundation of China(No.20220013068002).
文摘Unsteady aerodynamic characteristics at high angles of attack are of great importance to the design and development of advanced fighter aircraft, which are characterized by post-stall maneuverability with multiple Degrees-of-Freedom(multi-DOF) and complex flow field structure.In this paper, a special kind of cable-driven parallel mechanism is firstly utilized as a new suspension method to conduct unsteady dynamic wind tunnel tests at high angles of attack, thereby providing experimental aerodynamic data. These tests include a wide range of multi-DOF coupled oscillatory motions with various amplitudes and frequencies. Then, for aerodynamic modeling and analysis, a novel data-driven Feature-Level Attention Recurrent neural network(FLAR) is proposed. This model incorporates a specially designed feature-level attention module that focuses on the state variables affecting the aerodynamic coefficients, thereby enhancing the physical interpretability of the aerodynamic model. Subsequently, spin maneuver simulations, using a mathematical model as the baseline, are conducted to validate the effectiveness of the FLAR. Finally, the results on wind tunnel data reveal that the FLAR accurately predicts aerodynamic coefficients, and observations through the visualization of attention scores identify the key state variables that affect the aerodynamic coefficients. It is concluded that the proposed FLAR enhances the interpretability of the aerodynamic model while achieving good prediction accuracy and generalization capability for multi-DOF coupling motion at high angles of attack.
基金supported by the National Natural Science Foundation of China(No.82360238,82071245)。
文摘Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesics,including opioids and nonsteroidal anti-inflammatory drugs,are often limited by their insufficient efficacy,tolerance,and risk of dependence.Traditional Chinese Medicine(TCM),characterized by its multi-component,multi-target,and systemic regulatory properties,has shown promising potential in cancer pain management.This review provides a comprehensive overview of the clinical classification and underlying mechanisms of cancer pain(including nerve infiltration,dysregulation of inflammatory mediators and ion channels,central sensitization,neuro-immune crosstalk,metabolic reprogramming,and gut-brain axis impairment),as well as the analgesic effects of representative TCM agents in cancer pain management.For example,bioactive components such as tetrahydroberberine,levo-tetrahydropalmatine,and piperine exert analgesic effects,thereby improving the quality of life of patients by inhibiting inflammatory cascades,regulating neurotransmitter systems,and preserving neural integrity.Commonly used preclinical models,including bone cancer pain,pancreatic cancer pain,and chemotherapy-induced peripheral neuropathy models,are summarized for their utility in mechanistic studies and efficacy evaluations.This review also discusses the current limitations of clinical evidence,such as small sample sizes,short follow-up periods,and limited translation from animal models,alongside major challenges in standardization,mechanistic elucidation,and clinical trial design.Future directions should focus on precise pain phenotyping,integrated multi-target interventions,rigorous efficacy safety validation,and innovations in drug delivery to facilitate the standardization and global adoption of TCM in cancer pain management.
基金Supported by National High-quality Development Project of China(Grant No.2340STCZB193).
文摘The average stiffness performance indices throughout the workspace are commonly used as global stiffness performance indices to evaluate the overall stiffness performance of parallel mechanisms,which involves an analysis of the stiffness performance of numerous discrete points in the workspace.This necessitates time-consuming and inefficient calculation,which is particularly pronounced in the optimization design stage of the mechanism,where the variations in the global stiffness performance indices versus various dimensional and structural parameters need to be analyzed.This paper presents a semi-analytical approach for stiffness modeling of the novel(R(RPS&RP))&2-UPS parallel mechanism(referred to as the Trifree mechanism)and proposes“local”stiffness performance indices as alternatives to global indices.Drawing on the screw theory,the Cartesian stiffness matrix of the Trifree mechanism is formulated explicitly by considering the compliances of all elastic elements and the over-constraint characteristics inherent in the mechanism.Based on the spherical motion pattern of the Trifree mechanism,four special reference configurations are extracted within the workspace.This yields“local”stiffness performance indices capable of accurately evaluating the overall stiffness performance of the mechanism and effectively improving the computational efficiency.The variations in global and“local”stiffness performance indices versus key design parameters are investigated.Furthermore,the proposed indices are applied to the Tricept and Trimule mechanisms.The results demonstrate that the proposed indices exhibit excellent computational accuracy and efficiency in evaluating the overall stiffness performance of these spherical parallel mechanisms.Moreover,the stiffness performance of the novel parallel mechanism investigated in this study closely resembles that of the well-known Tricept and Trimule mechanisms.This research proposes a semi-analytic stiffness model of the Trifree mechanism and“local”stiffness performance indices to evaluate the overall stiffness performance,thereby substantially improving the computational efficiency without sacrificing accuracy.
基金funded by the National Key Research and Development Program of China(Grant No.2022YFB3402500)the National Natural Science Foundation of China(Grant No.12372129).
文摘Embedding optical fiber sensors into composite materials offers the advantage of real-time structural monitoring.However,there is an order-of-magnitude difference in diameter between optical fibers and reinforcing fibers,and the detailed mechanism of how embedded optical fibers affect the micromechanical behavior and damage failure processes within composite materials remains unclear.This paper presents a micromechanical simulation analysis of composite materials embedded with optical fibers.By constructing representative volume elements(RVEs)with randomly distributed reinforcing fibers,the optical fiber,the matrix,and the interface phase,the micromechanical behavior and damage evolution under transverse tensile and compressive loads are explored.The study finds that the presence of embedded optical fibers significantly influences the initiation and propagation of microscopic damage within the composites.Under transverse tension,the fiber-matrix interface cracks first,followed by plastic cracking in the matrix surrounding the fibers,forming micro-cracks.Eventually,these cracks connect with the debonded areas at the fiber-matrix interface to form a dominant crack that spans the entire model.Under transverse compression,plastic cracking first occurs in the resin surrounding the optical fibers,connecting with the interface debonding areas between the optical fibers and the matrix to form two parallel shear bands.Additionally,it is observed that the strength of the interface between the optical fiber and the matrix critically affects the simulation results.The simulated damage morphologies align closely with those observed using scanning electron microscopy(SEM).These findings offer theoretical insights that can inform the design and fabrication of smart composite materials with embedded optical fiber sensors for advanced structural health monitoring.
基金National Natural Science Foundation of China(22073023)Natural Science Foundation of Henan Province(242300421134)+1 种基金the Young Backbone Teacher in Colleges and Universities of Henan Province(2021GGJS020)Foundation of State Key Laboratory of Antiviral Drugs。
文摘The acetylpolyamine oxidase(APAO),spermine oxidase(SMO),and spermidine/spermine N1-acetyltransferase(SSAT)are pivotal enzymes in polyamine metabolism,exerting direct influence on polyamine homeostasis regulation.Dysfunctions in these enzymes are intricately linked to inflammatory diseases and cancers.Establishing their three-dimensional structures is essential for exploring enzymatic catalytic mechanisms and designing inhibitors at the atomic level.This article primarily assesses the precision of AlphaFold2 and molecular dynamics simulations in determining the three-dimensional structures of these enzymes,utilizing protein conformation rationality assessment,residue correlation matrix,and other techniques.This provides robust models for subsequent polyamine catabolic metabolism calculations and offers valuable insights for modeling proteins that have yet to acquire crystal structures.
基金Supported by Henan Province Science and Technology Research Project,No.232102310043Henan Provincial Science and Technology Research and Development Plan Joint Fund,No.222103810047Key Scientific Research Project Plan of Colleges and Universities in Henan Province,No.22A320033.
文摘BACKGROUND Colorectal cancer(CRC)remains a major global health burden due to its high incidence and mortality,with treatment efficacy often hindered by tumor hetero-geneity,drug resistance,and a complex tumor microenvironment(TME).Lactate metabolism plays a pivotal role in reshaping the TME,promoting immune eva-sion and epithelial-mesenchymal transition,making it a promising target for novel therapeutic strategies and prognostic modeling in CRC.AIM To offer an in-depth analysis of the role of lactate metabolism in CRC,high-lighting its significance in the TME and therapeutic response.METHODS Utilizing single-cell and transcriptomic data from the Gene Expression Omnibus and The Cancer Genome Atlas,we identified key lactate metabolic activities,particularly in the monocyte/macrophage subpopulation.RESULTS Seven lactate metabolism-associated genes were significantly linked to CRC prognosis and used to construct a predictive model.This model accurately forecasts patient outcomes and reveals notable distinct patterns of immune infiltration and transcriptomic profiles mutation profiles between high-and low-risk groups.High-risk patients demonstrated elevated immune cell infiltration,increased mutation frequencies,and heightened sensitivity to specific drugs(AZD6482,tozasertib,and SB216763),providing a foundation for personalized treatment approaches.Additionally,a nomogram integrating clinical and metabolic data effectively predicted 1-,3-,and 5-year survival rates.CONCLUSION This report underscored the pivotal mechanism of lactate metabolism in CRC prognosis and suggest novel avenues for therapeutic intervention.
基金supported by the steady supports scientific research of Key Laboratory of Defense Science and Technology,China(No.WDZC20220105)the National Natural Science Foundation of China(Nos.51775020,62073009,U20B2002)the Science Challenge Project,China(No.TZ2018007)。
文摘Thermal Protection System(TPS)with thick tiles,low thermal conductivity,and a short re-entry stage stands as a critical element within reusable aircraft,whose reliability is related to the function and changes with their physical properties,external conditions,and degradation.Meanwhile,due to the limitation of testing resources,epistemic uncertainties stemming from the small samples are present in TPS reliability modeling.However,current TPS reliability modeling methods face challenges in characterizing the relationships among reliability and physical properties,external conditions,degradation,and epistemic uncertainties.Therefore,under the framework of belief reliability theory,a TPS reliability model is constructed,which takes into account the physical principle,external conditions,performance degradation,and epistemic uncertainties.A reliability simulation algorithm is proposed to calculate TPS reliability.Through a case study and comparison analysis,the proposed method is validated as more effective than the existing method.Additionally,reliability sensitivity analysis is conducted to identify the sensitive factors of reliability under the condition of small samples,through which suggestions are provided for TPS functional design and improvement.
