Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal deg...Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.展开更多
The multi-satellite electromagnetic formation flight system is nonlinear and strongly coupled,which makes modeling and optimization challenging.To simplify electromagnetic force evaluation and dynamics modeling,we int...The multi-satellite electromagnetic formation flight system is nonlinear and strongly coupled,which makes modeling and optimization challenging.To simplify electromagnetic force evaluation and dynamics modeling,we introduce a reference frame consistent with each satellite body frame,in which the electromagnetic dipoles and electromagnetic forces are represented as two-dimensional vectors.Then,the maneuver time is divided into time intervals,and different satellite sets are activated in each interval,converting the multi-satellite formation reconfiguration problem into an optimal trajectory problem of each two-satellite subsystem.To this end,a token-based dynamic programming method with a switching penalty of active satellite sets is proposed to determine the sequence of satellite sets participating in each time interval,thereby enabling all satellites to reach their desired states.For the two-satellite subsystem with the objectives of minimizing maneuver time and energy consumption,the Gauss pseudo-spectral method is employed to generate the optimal reconfiguration trajectory.Numerical simulations verify the effectiveness of the proposed optimization method.展开更多
Online programming platforms are popular in programming education.However,there has been no research investigating students’real opinions and expectations of the error feedback mechanisms,leaving educators without a ...Online programming platforms are popular in programming education.However,there has been no research investigating students’real opinions and expectations of the error feedback mechanisms,leaving educators without a solid data foundation when attempting to improve the error feedback mechanisms.This paper makes a survey of 834 students across various programming courses and investigates student perceptions of error feedback mechanisms on online programming platforms.It explores the effectiveness of existing feedback,student satisfaction,and preferences for potential improvements,focusing on automatic error localization and program repair mechanisms.Results reveal a significant portion of students are dissatisfied with current feedback due to its limited informativeness.Students also express a clear demand for stronger feedback mechanisms,such as error localization and repair hints.Nevertheless,they prefer feedback that subtly guides them toward solutions,rather than providing direct and explicit answers,valuing the opportunity to enhance their debugging skills.The findings suggest a need for balanced,educational-focused feedback mechanisms that aid learning while promoting independent problem-solving.展开更多
In this paper,we consider a robust semi-infinite interval-valued optimization problem with inequality constraints having an uncertain parameter.The parametric representation of the aforesaid problem is also considered...In this paper,we consider a robust semi-infinite interval-valued optimization problem with inequality constraints having an uncertain parameter.The parametric representation of the aforesaid problem is also considered in order to derive the necessary and sufficient optimality conditions.Furthermore,we formulate a mixed-type dual problem and derive duality results which associate the robust weak efficient solution of the primal and its dual problems.Several examples are given to illustrate the results in the manuscript.展开更多
With a collection of more than 360,000 artifacts,the Sichuan Museum showcases the civilization of Sichuan while actively bringing cultural relics to life through a wide range of educational programs.
Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),whic...Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),which have revolutionized the treatment of several solid tumors,have shown limited efficacy inGBMowing to the highly immunosuppressive and heterogeneousmicroenvironment of the tumor.The unique immune landscape of the central nervous system(CNS),characterized by low immunogenicity,restricted T-cell infiltration,and an abundance of regulatory and myeloid-derived suppressor cells,poses considerable barriers to effective immune reactivation.This review provides a comprehensive synthesis of the mechanistic barriers undermining ICI efficacy in GBM,including the blood-brain barrier,low tumor mutational burden,adaptive immune resistance,and iatrogenic immunosuppression.It also explores emerging predictive and prognostic biomarkers,such as programmed death-ligand 1(PD-L1)expression,immune gene signatures,tumor-infiltrating lymphocyte profiles,and circulating markers in cerebrospinal fluid and plasma,which hold promise for guiding patient selection and therapeutic monitoring.Importantly,recent breakthroughs in combinatorial immunotherapy strategies are highlighted,including the integration of ICIs with radiotherapy,anti-angiogenic agents,oncolytic viruses,personalized neoantigen vaccines,and tumor microenvironment reprogramming approaches.Innovative delivery platforms,such as nanoparticles,focused ultrasound,and convection-enhanced delivery,are also discussed for their potential to improve drug bioavailability and local immune activation in the CNS.This review hypothesizes that the therapeutic efficacy of ICIs in GBM can be considerably enhanced by disrupting immune exclusion and reversing immunosuppression through integrated,multimodal strategies guided by dynamic biomarker profiling and spatially resolved immunemapping.This hypothesisdriven approach aims to bridge translational gaps and inform next-generation clinical trial designs that may unlock the potential of immunotherapy for GBM.展开更多
I was 26 the first time I travelled to China,and even now,it feels like an unexpected chapter in my life.The opportunity came out of the blue.I learned,just a month before departure,that I had been selected for a one-...I was 26 the first time I travelled to China,and even now,it feels like an unexpected chapter in my life.The opportunity came out of the blue.I learned,just a month before departure,that I had been selected for a one-month professional training programme.The news ignited a wave of excitement.For nearly two weeks,I stayed up late into the night,imagining a country I had never seen,trying to picture what China might really be like,beyond the images in books,films and media.展开更多
Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understoo...Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understood,in particular the influence on the hydrodynamic forces and moments of the distance of the foil to the free surface.Considering this,the present paper documents an experimental investigation in which forces and torque produced,under uniform flow,by a full-scale state-of-the-art hydrofoil(suitable both for kitesurf and windsurf)were measured.A range of velocities,angles of attack,and submergences were tested,leading to Froude numbers based on submergence with maximum values around five,a typical range in actual sailing conditions.From these tests,formulae for the hydrodynamic coefficients have been proposed.They can be used for developing Velocity Prediction Programs(VPP)for this kind of craft,a necessary tool to plan racing configurations and to analyze their racing performance.With the aim of making the experimental data useful for benchmarking numerical models and for future research on related topics such as foil ventilation and transition to turbulence,the specimen’s 3D file is provided as supplementary material to this paper.展开更多
Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 str...Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 stroke survivors from two neurology wards into an intervention group(n=55)who received the stepped self-care program and a control group(n=55)who received usual care from June to December 2023.The Self-Care of Stroke Inventory,Stroke Self-Efficacy Questionnaire,and the short version of the Stroke Specific Quality of Life Scale were administered at baseline(T0),immediately post-intervention(T_(1)),and at 1-month(T_(2))and 3-month(T_(3))follow-ups.Data were analyzed using repeated measures analyses of variance,and generalized estimating equations.Results A total of 48 participants in the intervention group and 50 participants in the control group completed the study.No statistically significant differences were observed at T0 in any of the measured indicators(all P>0.05).The study showed significant group,time,and group×time interaction effects across the assessed outcomes(all P<0.05).Follow-up between-group comparisons at T_(1),T_(2),and T_(3) indicated that the intervention group had significantly higher scores in self-care maintenance,self-care monitoring,self-care management,self-efficacy,and quality of life than the control group(all P<0.001).Conclusions The stepped self-care program significantly improved self-care behaviors,self-efficacy,and quality of life among stroke survivors.These findings support the broader implementation of this approach in post-discharge home self-care.展开更多
Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disruptin...Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.展开更多
To systematically elucidate the central role of the cardiac autonomic nervous system(ANS)in maintaining cardiovascular homeostasis,analyze the pathological mechanisms underlying its dysregulation,integrate multidiscip...To systematically elucidate the central role of the cardiac autonomic nervous system(ANS)in maintaining cardiovascular homeostasis,analyze the pathological mechanisms underlying its dysregulation,integrate multidisciplinary research findings from the U.S.stimulating peripheral nerves to alleviate disease symptoms(SPARC)program,and evaluate the unique advantages and current limitations of acupuncture in modulating cardiac ANS function,ultimately proposing novel strategies for the prevention and treatment of cardiovascular diseases.A systematic literature review was conducted to synthesize current knowledge on the fundamental regulatory mechanisms of the cardiac ANS,the SPARC program's innovative contributions to neuroanatomy and neural pathway mapping,as well as clinical and experimental evidence supporting acupuncture's modulation of the ANS.The SPARC program has made significant progress in elucidating the anatomical organization and neural circuitry of the cardiac ANS through interdisciplinary collaboration,offering novel insights and methodological frameworks for studying cardiac autonomic regulation.Acupuncture,as a cornerstone of traditional medicine,has demonstrated both specificity and multi-target regulatory effects on the cardiac ANS through clinical and experimental studies.However,challenges remain,including an incomplete mechanistic understanding,technical limitations in research methodologies,and difficulties in translating findings into clinical practice.Future research on acupuncture should build upon its inherent strengths while advancing its integration with modern scientific and technological approaches.Strengthening interdisciplinary collaboration and leveraging artificial intelligence can open new frontiers in mechanistic exploration and technological innovation.These efforts will facilitate the internationalization of acupuncture research and contribute innovative perspectives and therapeutic strategies for cardiovascular disease prevention and treatment.展开更多
Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(P...Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.展开更多
Instrumental and expert assessments were used to assess the effect of massage on facial skin blood perfusion,as well as the effects of the long-term use of the two skin health programs on the water content of the stra...Instrumental and expert assessments were used to assess the effect of massage on facial skin blood perfusion,as well as the effects of the long-term use of the two skin health programs on the water content of the stratum corneum,F4,L^(*),dermal and epidermal thickness and density,facial wrinkles,and so on.Sixty healthy Chinese women were selected as the study subjects,which were subsequently divided into G1 non-massage group and G2 massage group.The results show that massage can increase the blood perfusion of facial skin.Group G2 solution is found to be more effective in improving the skin structural barrier(epidermal density),skin elasticity,firmness(dermal thickness)and forehead wrinkles.展开更多
During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive...During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive distance)to a moving target as quickly as possible,resulting in the extended minimum-time intercept problem(EMTIP).Existing research has primarily focused on the zero-distance intercept problem,MTIP,establishing the necessary or sufficient conditions for MTIP optimality,and utilizing analytic algorithms,such as root-finding algorithms,to calculate the optimal solutions.However,these approaches depend heavily on the properties of the analytic algorithm,making them inapplicable when problem settings change,such as in the case of a positive effective range or complicated target motions outside uniform rectilinear motion.In this study,an approach employing a high-accuracy and quality-guaranteed mixed-integer piecewise-linear program(QG-PWL)is proposed for the EMTIP.This program can accommodate different effective interception ranges and complicated target motions(variable velocity or complicated trajectories).The high accuracy and quality guarantees of QG-PWL originate from elegant strategies such as piecewise linearization and other developed operation strategies.The approximate error in the intercept path length is proved to be bounded to h^(2)/(4√2),where h is the piecewise length.展开更多
Message structure reconstruction is a critical task in protocol reverse engineering,aiming to recover protocol field structures without access to source code.It enables important applications in network security,inclu...Message structure reconstruction is a critical task in protocol reverse engineering,aiming to recover protocol field structures without access to source code.It enables important applications in network security,including malware analysis and protocol fuzzing.However,existing methods suffer from inaccurate field boundary delineation and lack hierarchical relationship recovery,resulting in imprecise and incomplete reconstructions.In this paper,we propose ProRE,a novel method for reconstructing protocol field structures based on program execution slice embedding.ProRE extracts code slices from protocol parsing at runtime,converts them into embedding vectors using a data flow-sensitive assembly language model,and performs hierarchical clustering to recover complete protocol field structures.Evaluation on two datasets containing 12 protocols shows that ProRE achieves an average F1 score of 0.85 and a cophenetic correlation coefficient of 0.189,improving by 19%and 0.126%respectively over state-of-the-art methods(including BinPRE,Tupni,Netlifter,and QwQ-32B-preview),demonstrating significant superiority in both accuracy and completeness of field structure recovery.Case studies further validate the effectiveness of ProRE in practical malware analysis scenarios.展开更多
The operational demands of a wide range significantly exacerbate combustion instability issues within ramjet combustor.To suppress combustion oscillations,an open-loop control system utilizing Linear Genetic Programmi...The operational demands of a wide range significantly exacerbate combustion instability issues within ramjet combustor.To suppress combustion oscillations,an open-loop control system utilizing Linear Genetic Programming(LGP)has been developed for a full-scale annular ramjet combustor.The LGP is used to generate control laws that include multi-frequency forcing.These laws are then transformed into square waves to actuate the solenoid valve,which modulates the kerosene supply for open-loop control.The results show that the duty cycle has little effect on instability amplitude,whereas an increase in frequency leads to a remarked reduction in combustion amplitude.After five generations evolvements,the pressure amplitude is reduced by 40.6% under the optimal control law generated by LGP.Furthermore,the machine learning process is depicted using a proximity map of control law similarity,with the search pathway visualized by the steepest descent.All individuals go forward to the upper left corner of the map with the evolution process,terminating at the optimal individual of the fifth generation.展开更多
LargeLanguageModels(LLMs)are increasingly appliedinthe fieldof code translation.However,existing evaluation methodologies suffer from two major limitations:(1)the high overlap between test data and pretraining corpora...LargeLanguageModels(LLMs)are increasingly appliedinthe fieldof code translation.However,existing evaluation methodologies suffer from two major limitations:(1)the high overlap between test data and pretraining corpora,which introduces significant bias in performance evaluation;and(2)mainstream metrics focus primarily on surface-level accuracy,failing to uncover the underlying factors that constrain model capabilities.To address these issues,this paper presents TCode(Translation-Oriented Code Evaluation benchmark)—a complexity-controllable,contamination-free benchmark dataset for code translation—alongside a dedicated static feature sensitivity evaluation framework.The dataset is carefully designed to control complexity along multiple dimensions—including syntactic nesting and expression intricacy—enabling both broad coverage and fine-grained differentiation of sample difficulty.This design supports precise evaluation of model capabilities across a wide spectrum of translation challenges.The proposed evaluation framework introduces a correlation-driven analysis mechanism based on static program features,enabling predictive modeling of translation success from two perspectives:Code Form Complexity(e.g.,code length and character density)and Semantic Modeling Complexity(e.g.,syntactic depth,control-flow nesting,and type system complexity).Empirical evaluations across representative LLMs—including Qwen2.5-72B and Llama3.3-70B—demonstrate that even state-of-the-art models achieve over 80% compilation success on simple samples,but their accuracy drops sharply below 40% on complex cases.Further correlation analysis indicates that Semantic Modeling Complexity alone is correlated with up to 60% of the variance in translation success,with static program features exhibiting nonlinear threshold effects that highlight clear capability boundaries.This study departs fromthe traditional accuracy-centric evaluation paradigm and,for the first time,systematically characterizes the capabilities of large languagemodels in translation tasks through the lens of programstatic features.The findings provide actionable insights for model refinement and training strategy development.展开更多
The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD...The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171076(to XS)and U22A20311(to XS),82101168(to TL)Shanghai Science and technology Innovation Action Plan,No.23Y11901300(to JS)+1 种基金Science and Technology Commission of Shanghai Municipality,No.21ZR1451500(to TL)Shanghai Pujiang Program,No.22PJ1412200(to BY)。
文摘Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.
文摘The multi-satellite electromagnetic formation flight system is nonlinear and strongly coupled,which makes modeling and optimization challenging.To simplify electromagnetic force evaluation and dynamics modeling,we introduce a reference frame consistent with each satellite body frame,in which the electromagnetic dipoles and electromagnetic forces are represented as two-dimensional vectors.Then,the maneuver time is divided into time intervals,and different satellite sets are activated in each interval,converting the multi-satellite formation reconfiguration problem into an optimal trajectory problem of each two-satellite subsystem.To this end,a token-based dynamic programming method with a switching penalty of active satellite sets is proposed to determine the sequence of satellite sets participating in each time interval,thereby enabling all satellites to reach their desired states.For the two-satellite subsystem with the objectives of minimizing maneuver time and energy consumption,the Gauss pseudo-spectral method is employed to generate the optimal reconfiguration trajectory.Numerical simulations verify the effectiveness of the proposed optimization method.
基金supported by the National Natural Science Foundation of China under Grant No.92582204,No.62577007,and No.62177003the Fundamental Research Funds for the Central Universities under Grant No.JKF-2025011975129.
文摘Online programming platforms are popular in programming education.However,there has been no research investigating students’real opinions and expectations of the error feedback mechanisms,leaving educators without a solid data foundation when attempting to improve the error feedback mechanisms.This paper makes a survey of 834 students across various programming courses and investigates student perceptions of error feedback mechanisms on online programming platforms.It explores the effectiveness of existing feedback,student satisfaction,and preferences for potential improvements,focusing on automatic error localization and program repair mechanisms.Results reveal a significant portion of students are dissatisfied with current feedback due to its limited informativeness.Students also express a clear demand for stronger feedback mechanisms,such as error localization and repair hints.Nevertheless,they prefer feedback that subtly guides them toward solutions,rather than providing direct and explicit answers,valuing the opportunity to enhance their debugging skills.The findings suggest a need for balanced,educational-focused feedback mechanisms that aid learning while promoting independent problem-solving.
基金supported by the MATRICES,SERB-DST,New Delhi,India(No.MTR/2021/000002).
文摘In this paper,we consider a robust semi-infinite interval-valued optimization problem with inequality constraints having an uncertain parameter.The parametric representation of the aforesaid problem is also considered in order to derive the necessary and sufficient optimality conditions.Furthermore,we formulate a mixed-type dual problem and derive duality results which associate the robust weak efficient solution of the primal and its dual problems.Several examples are given to illustrate the results in the manuscript.
文摘With a collection of more than 360,000 artifacts,the Sichuan Museum showcases the civilization of Sichuan while actively bringing cultural relics to life through a wide range of educational programs.
文摘Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),which have revolutionized the treatment of several solid tumors,have shown limited efficacy inGBMowing to the highly immunosuppressive and heterogeneousmicroenvironment of the tumor.The unique immune landscape of the central nervous system(CNS),characterized by low immunogenicity,restricted T-cell infiltration,and an abundance of regulatory and myeloid-derived suppressor cells,poses considerable barriers to effective immune reactivation.This review provides a comprehensive synthesis of the mechanistic barriers undermining ICI efficacy in GBM,including the blood-brain barrier,low tumor mutational burden,adaptive immune resistance,and iatrogenic immunosuppression.It also explores emerging predictive and prognostic biomarkers,such as programmed death-ligand 1(PD-L1)expression,immune gene signatures,tumor-infiltrating lymphocyte profiles,and circulating markers in cerebrospinal fluid and plasma,which hold promise for guiding patient selection and therapeutic monitoring.Importantly,recent breakthroughs in combinatorial immunotherapy strategies are highlighted,including the integration of ICIs with radiotherapy,anti-angiogenic agents,oncolytic viruses,personalized neoantigen vaccines,and tumor microenvironment reprogramming approaches.Innovative delivery platforms,such as nanoparticles,focused ultrasound,and convection-enhanced delivery,are also discussed for their potential to improve drug bioavailability and local immune activation in the CNS.This review hypothesizes that the therapeutic efficacy of ICIs in GBM can be considerably enhanced by disrupting immune exclusion and reversing immunosuppression through integrated,multimodal strategies guided by dynamic biomarker profiling and spatially resolved immunemapping.This hypothesisdriven approach aims to bridge translational gaps and inform next-generation clinical trial designs that may unlock the potential of immunotherapy for GBM.
文摘I was 26 the first time I travelled to China,and even now,it feels like an unexpected chapter in my life.The opportunity came out of the blue.I learned,just a month before departure,that I had been selected for a one-month professional training programme.The news ignited a wave of excitement.For nearly two weeks,I stayed up late into the night,imagining a country I had never seen,trying to picture what China might really be like,beyond the images in books,films and media.
文摘Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understood,in particular the influence on the hydrodynamic forces and moments of the distance of the foil to the free surface.Considering this,the present paper documents an experimental investigation in which forces and torque produced,under uniform flow,by a full-scale state-of-the-art hydrofoil(suitable both for kitesurf and windsurf)were measured.A range of velocities,angles of attack,and submergences were tested,leading to Froude numbers based on submergence with maximum values around five,a typical range in actual sailing conditions.From these tests,formulae for the hydrodynamic coefficients have been proposed.They can be used for developing Velocity Prediction Programs(VPP)for this kind of craft,a necessary tool to plan racing configurations and to analyze their racing performance.With the aim of making the experimental data useful for benchmarking numerical models and for future research on related topics such as foil ventilation and transition to turbulence,the specimen’s 3D file is provided as supplementary material to this paper.
基金The National Natural Science Foundation of China[72174184]provided policy and financialsupport for this research.
文摘Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 stroke survivors from two neurology wards into an intervention group(n=55)who received the stepped self-care program and a control group(n=55)who received usual care from June to December 2023.The Self-Care of Stroke Inventory,Stroke Self-Efficacy Questionnaire,and the short version of the Stroke Specific Quality of Life Scale were administered at baseline(T0),immediately post-intervention(T_(1)),and at 1-month(T_(2))and 3-month(T_(3))follow-ups.Data were analyzed using repeated measures analyses of variance,and generalized estimating equations.Results A total of 48 participants in the intervention group and 50 participants in the control group completed the study.No statistically significant differences were observed at T0 in any of the measured indicators(all P>0.05).The study showed significant group,time,and group×time interaction effects across the assessed outcomes(all P<0.05).Follow-up between-group comparisons at T_(1),T_(2),and T_(3) indicated that the intervention group had significantly higher scores in self-care maintenance,self-care monitoring,self-care management,self-efficacy,and quality of life than the control group(all P<0.001).Conclusions The stepped self-care program significantly improved self-care behaviors,self-efficacy,and quality of life among stroke survivors.These findings support the broader implementation of this approach in post-discharge home self-care.
基金financially supported by Ministerio de Ciencia e Innovación projects SAF2017-82736-C2-1-R to MTMFin Universidad Autónoma de Madrid and by Fundación Universidad Francisco de Vitoria to JS+2 种基金a predoctoral scholarship from Fundación Universidad Francisco de Vitoriafinancial support from a 6-month contract from Universidad Autónoma de Madrida 3-month contract from the School of Medicine of Universidad Francisco de Vitoria。
文摘Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.
基金supported by the National Natural Science Foundation of China(82174513)Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ-JQ2023003).
文摘To systematically elucidate the central role of the cardiac autonomic nervous system(ANS)in maintaining cardiovascular homeostasis,analyze the pathological mechanisms underlying its dysregulation,integrate multidisciplinary research findings from the U.S.stimulating peripheral nerves to alleviate disease symptoms(SPARC)program,and evaluate the unique advantages and current limitations of acupuncture in modulating cardiac ANS function,ultimately proposing novel strategies for the prevention and treatment of cardiovascular diseases.A systematic literature review was conducted to synthesize current knowledge on the fundamental regulatory mechanisms of the cardiac ANS,the SPARC program's innovative contributions to neuroanatomy and neural pathway mapping,as well as clinical and experimental evidence supporting acupuncture's modulation of the ANS.The SPARC program has made significant progress in elucidating the anatomical organization and neural circuitry of the cardiac ANS through interdisciplinary collaboration,offering novel insights and methodological frameworks for studying cardiac autonomic regulation.Acupuncture,as a cornerstone of traditional medicine,has demonstrated both specificity and multi-target regulatory effects on the cardiac ANS through clinical and experimental studies.However,challenges remain,including an incomplete mechanistic understanding,technical limitations in research methodologies,and difficulties in translating findings into clinical practice.Future research on acupuncture should build upon its inherent strengths while advancing its integration with modern scientific and technological approaches.Strengthening interdisciplinary collaboration and leveraging artificial intelligence can open new frontiers in mechanistic exploration and technological innovation.These efforts will facilitate the internationalization of acupuncture research and contribute innovative perspectives and therapeutic strategies for cardiovascular disease prevention and treatment.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(Grant Number 242300421283)Major Science and Technology Project of Henan Province(221100310200)。
文摘Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.
文摘Instrumental and expert assessments were used to assess the effect of massage on facial skin blood perfusion,as well as the effects of the long-term use of the two skin health programs on the water content of the stratum corneum,F4,L^(*),dermal and epidermal thickness and density,facial wrinkles,and so on.Sixty healthy Chinese women were selected as the study subjects,which were subsequently divided into G1 non-massage group and G2 massage group.The results show that massage can increase the blood perfusion of facial skin.Group G2 solution is found to be more effective in improving the skin structural barrier(epidermal density),skin elasticity,firmness(dermal thickness)and forehead wrinkles.
基金supported by the National Natural Sci‐ence Foundation of China(Grant No.62306325)。
文摘During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive distance)to a moving target as quickly as possible,resulting in the extended minimum-time intercept problem(EMTIP).Existing research has primarily focused on the zero-distance intercept problem,MTIP,establishing the necessary or sufficient conditions for MTIP optimality,and utilizing analytic algorithms,such as root-finding algorithms,to calculate the optimal solutions.However,these approaches depend heavily on the properties of the analytic algorithm,making them inapplicable when problem settings change,such as in the case of a positive effective range or complicated target motions outside uniform rectilinear motion.In this study,an approach employing a high-accuracy and quality-guaranteed mixed-integer piecewise-linear program(QG-PWL)is proposed for the EMTIP.This program can accommodate different effective interception ranges and complicated target motions(variable velocity or complicated trajectories).The high accuracy and quality guarantees of QG-PWL originate from elegant strategies such as piecewise linearization and other developed operation strategies.The approximate error in the intercept path length is proved to be bounded to h^(2)/(4√2),where h is the piecewise length.
文摘Message structure reconstruction is a critical task in protocol reverse engineering,aiming to recover protocol field structures without access to source code.It enables important applications in network security,including malware analysis and protocol fuzzing.However,existing methods suffer from inaccurate field boundary delineation and lack hierarchical relationship recovery,resulting in imprecise and incomplete reconstructions.In this paper,we propose ProRE,a novel method for reconstructing protocol field structures based on program execution slice embedding.ProRE extracts code slices from protocol parsing at runtime,converts them into embedding vectors using a data flow-sensitive assembly language model,and performs hierarchical clustering to recover complete protocol field structures.Evaluation on two datasets containing 12 protocols shows that ProRE achieves an average F1 score of 0.85 and a cophenetic correlation coefficient of 0.189,improving by 19%and 0.126%respectively over state-of-the-art methods(including BinPRE,Tupni,Netlifter,and QwQ-32B-preview),demonstrating significant superiority in both accuracy and completeness of field structure recovery.Case studies further validate the effectiveness of ProRE in practical malware analysis scenarios.
基金support from the National Natural Science Foundation of China(No.12002372)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.2022QNRC001)the Natural Science Foundation of Hunan Province,China(No.2021JJ40674)。
文摘The operational demands of a wide range significantly exacerbate combustion instability issues within ramjet combustor.To suppress combustion oscillations,an open-loop control system utilizing Linear Genetic Programming(LGP)has been developed for a full-scale annular ramjet combustor.The LGP is used to generate control laws that include multi-frequency forcing.These laws are then transformed into square waves to actuate the solenoid valve,which modulates the kerosene supply for open-loop control.The results show that the duty cycle has little effect on instability amplitude,whereas an increase in frequency leads to a remarked reduction in combustion amplitude.After five generations evolvements,the pressure amplitude is reduced by 40.6% under the optimal control law generated by LGP.Furthermore,the machine learning process is depicted using a proximity map of control law similarity,with the search pathway visualized by the steepest descent.All individuals go forward to the upper left corner of the map with the evolution process,terminating at the optimal individual of the fifth generation.
文摘LargeLanguageModels(LLMs)are increasingly appliedinthe fieldof code translation.However,existing evaluation methodologies suffer from two major limitations:(1)the high overlap between test data and pretraining corpora,which introduces significant bias in performance evaluation;and(2)mainstream metrics focus primarily on surface-level accuracy,failing to uncover the underlying factors that constrain model capabilities.To address these issues,this paper presents TCode(Translation-Oriented Code Evaluation benchmark)—a complexity-controllable,contamination-free benchmark dataset for code translation—alongside a dedicated static feature sensitivity evaluation framework.The dataset is carefully designed to control complexity along multiple dimensions—including syntactic nesting and expression intricacy—enabling both broad coverage and fine-grained differentiation of sample difficulty.This design supports precise evaluation of model capabilities across a wide spectrum of translation challenges.The proposed evaluation framework introduces a correlation-driven analysis mechanism based on static program features,enabling predictive modeling of translation success from two perspectives:Code Form Complexity(e.g.,code length and character density)and Semantic Modeling Complexity(e.g.,syntactic depth,control-flow nesting,and type system complexity).Empirical evaluations across representative LLMs—including Qwen2.5-72B and Llama3.3-70B—demonstrate that even state-of-the-art models achieve over 80% compilation success on simple samples,but their accuracy drops sharply below 40% on complex cases.Further correlation analysis indicates that Semantic Modeling Complexity alone is correlated with up to 60% of the variance in translation success,with static program features exhibiting nonlinear threshold effects that highlight clear capability boundaries.This study departs fromthe traditional accuracy-centric evaluation paradigm and,for the first time,systematically characterizes the capabilities of large languagemodels in translation tasks through the lens of programstatic features.The findings provide actionable insights for model refinement and training strategy development.
基金financially supported by the Natural Science Foundation of Jiangsu Province (No.BK20200709)the Natural Science Foundation of China (Nos.62288102,32201127 and 82270113)+2 种基金the Natural Science Foundation of Guangdong Province (No.2023A1515011386)the Natural Science Foundation of the Jiangsu Higher Education Institutes (No.20KJB430031)the startup fund from Nanjing Tech University,and Disciplinary Fund of School of Pharmaceutical Sciences (2024)。
文摘The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.
