This study investigates prescribed-time position tracking control for electromagnetic satellite formations subject to model uncertainties and external disturbances.Using the Clohessy-Wiltshire equations as the relativ...This study investigates prescribed-time position tracking control for electromagnetic satellite formations subject to model uncertainties and external disturbances.Using the Clohessy-Wiltshire equations as the relative motion dynamics model,a prescribed time output feedback control strategy is proposed.A prescribed-time extended state observer is designed to estimate the relative velocity and external disturbances.The disturbance estimates are then used as the feedforward component of the controller.Building on this framework,a novel prescribed-time active disturbance rejection control strategy for position tracking is developed via a backstepping control design.The convergence of the extended state observer and the stability of the closed-loop system are rigorously analyzed using Lyapunov stability theory.Numerical simulations are performed to validate the effectiveness of the proposed controller.展开更多
Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent...Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent,and metastatic malignancies.Mechanistically,ferroptosis induction not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),eliciting damage-associated molecular patterns(DAMPs)release to activate partial antitumor immunity.However,standalone ferroptosis therapy fails to initiate robust systemic antitumor immune responses due to inherent limitations:low tumor immunogenicity,immunosuppressive microenvironment constraints,and tumor microenvironment(TME)-associated physiological barriers(e.g.,hypoxia,dense extracellular matrix).To address these challenges,synergistic approaches have been developed to enhance immune cell infiltration and reestablish immunosurveillance,encompassing(1)direct amplification of antitumor immunity,(2)disruption of immunosuppressive tumor niches,and(3)biophysical hallmark remodeling in TME.Rational nanocarrier design has emerged as a critical enabler for overcoming biological delivery barriers and optimizing therapeutic efficacy.Unlike prior studies solely addressing ferroptosis or nanotechnology in tumor therapy,this work first systematically outlines the synergistic potential of nanoparticles in combined ferroptosis-immunotherapy strategies.It advances multidimensional nanoplatform design principles for material selection,structural configuration,physicochemical modulation,multifunctional integration,and artificial intelligence-enabled design,providing a scientific basis for efficacy optimization.Moreover,it examines translational challenges of ferroptosis-immunotherapy nanoplatforms across preclinical and clinical stages,proposing actionable solutions while envisioning future onco-immunotherapy directions.Collectively,it provides systematic insights into advanced nanomaterial design principles and therapeutic optimization strategies,offering a roadmap for accelerating clinical translation in onco-immunotherapy research.展开更多
Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemot...Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.展开更多
Parasitic interface side reactions and uncontrollable Zn deposition seriously erode the cycling performance of aqueous zinc ion batteries,thus impeding the large-scale application.Herein,an organic acid molecule with ...Parasitic interface side reactions and uncontrollable Zn deposition seriously erode the cycling performance of aqueous zinc ion batteries,thus impeding the large-scale application.Herein,an organic acid molecule with a unique molecular structure,camphorsulfonic acid(CSA),is first proposed to remodel the interface microenvironment as an electrolyte additive.The proton provided by CSA can neutralize the hydroxide ions generated by side reactions and inhibit the accumulation of alkaline by-products.The sulfonic acid groups are firmly adsorbed on the Zn anode surface,thereby enabling the regulation of interfacial species.Specifically,oxygen-containing functional groups combined with hydrophobic rigid carbon rings achieve a water-poor interface environment and promote the transfer of Zn^(2+),providing a suitable environment for Zn deposition.As a result,Zn//Zn symmetrical battery can run for over 2800 h(2 mA cm^(-2)-2 mAh cm^(-2)),demonstrating 28-times lifespan compared to the battery without CSA.Furthermore,Zn//KVO full cell presents excellent performance of 800 cycles at 3 A g^(-1).Besides,the pouch cell with CSA can also operate a capacity of 153.8 mAh after 60 cycles at 0.5 A g^(-1) with96.5%capacity retention rate.This work provides an organism-inspired additive selection for stabilizing the interface chemistry of the Zn anode.展开更多
Triterpenoids are valuable medicinal scaffolds,characterized by excellent pharmacological properties and the presence of hydroxyl and carboxyl groups that allow for further structural modifications.Expanding the scope...Triterpenoids are valuable medicinal scaffolds,characterized by excellent pharmacological properties and the presence of hydroxyl and carboxyl groups that allow for further structural modifications.Expanding the scope of oxidative modifications on these molecules is crucial for increasing their synthetic structural diversity and unlocking new potential pharmacological activities.However,the progress has been limited by the scarcity of suitable tailoring enzymes.Here,we reported a break-through in achieving targeted and remote dual-site oxidation of licorice triterpenoids using a single P450 mutant.This approach successfully enabled the selective synthesis of the rare triterpenoid,liquiritic acid and 24-OH-liquiritic acid.Our findings demonstrate that microenvironmental accessibility engineering of triterpenoid substrates within the P450 enzyme is essential for continuous and regioselective oxidation.This study not only sheds light on the mechanistic aspects of P450 catalysis but also expands the enzymatic toolkit for selective oxidative modifications in triterpenoid biosynthesis.展开更多
In situ tumor vaccines,which leverage the antigenic profile of individual tumors,have demonstrated significant potential in tumor immunotherapy.However,their efficacy is often limited by the immunosuppressive tumor mi...In situ tumor vaccines,which leverage the antigenic profile of individual tumors,have demonstrated significant potential in tumor immunotherapy.However,their efficacy is often limited by the immunosuppressive tumor microenvironment(TME)and insufficient tumor targeting.To address these challenges,we engineered in situ nanovaccines through the self-assembly of the photosensitizer indocyanine green,immune adjuvant aluminum(Al^(3+)),and hydrophilic drug zoledronic acid(ZOL).Intravenous injection of these nanovaccines led to efficient tumor accumulation,enhancing drug bioavailability and enabling the release of tumor-associated antigens via photothermal therapy.Additionally,the built-in ZOL induces polarization of tumor-associated macrophages,reversing the immunosuppressive TME.The potent antitumor immune response triggered by these nanovaccines effectively suppresses tumor growth.This study,which integrates a straightforward assembly method,substantial drug loading capacity,and promising therapeutic outcomes,introduces a novel and effective paradigm for carrier-free in situ nanovaccines in cancer treatment.展开更多
Hard disk drives(HDDs)serve as the primary storage devices in modern data centers.Once a failure occurs,it often leads to severe data loss,significantly degrading the reliability of storage systems.Numerous studies ha...Hard disk drives(HDDs)serve as the primary storage devices in modern data centers.Once a failure occurs,it often leads to severe data loss,significantly degrading the reliability of storage systems.Numerous studies have proposed machine learning-based HDD failure prediction models.However,the Self-Monitoring,Analysis,and Reporting Technology(SMART)attributes differ across HDD manufacturers.We define hard drives of the same brand and model as homogeneous HDD groups,and those from different brands or models as heterogeneous HDD groups.In practical engineering scenarios,a data center is often composed of a heterogeneous population of HDDs,spanning multiple vendors and models.Existing research predominantly focuses on homogeneous datasets,ignoring the model’s generalization capability across heterogeneous HDDs.As a result,HDD models with limited samples often suffer from poor training effectiveness and prediction performance.To address this issue,we investigate generalizable SMART predictors across heterogeneous HDD groups.By extracting time-series features within a fixed sliding time window,we propose a Heterogeneous Disk Failure Prediction Method based on Time Series Features(HDFPM)framework.This method is adaptable to HDD models with limited sample sizes,thereby enhancing its applicability and robustness across diverse drive populations.Experimental results show that the proposed model achieves an F1-score of 0.9518 when applied to two different Seagate HDD models,while maintaining the False Positive Rate(FPR)below 1%.After incorporating the Complexity-Ratio Dynamic Time Warping(CDTW)based feature enhancement method,the best prediction model achieves a True Positive Rate(TPR)of up to 0.93 between the two models.For next-day failure prediction across various Seagate models,the model achieves an F1-score of up to 0.8792.Moreover,the experimental results also show that within the same brand,the higher the proportion of shared SMART attributes across different models,the better the prediction performance.In addition,HDFPMdemonstrates the best stability andmost significant performance in heterogeneous environments.展开更多
Osteoarthritis(OA),the most common chronic joint disease,leads to remarkable morbidity and disability.The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of ost...Osteoarthritis(OA),the most common chronic joint disease,leads to remarkable morbidity and disability.The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of osteoarthritic joints is crucial for elucidating OA pathogenesis and facilitating drug development.In this study,we present a microfluidics-based cartilage-on-a-chip model that integrates tunable mechanical stimulation and inter-tissue/cell communication,mimicking the key physiological characteristics of articular cartilage for organ-level OA research.By applying controllable mechanical compression,we established a model that captures healthy and injury hallmarks of the cartilage and directly observed the mechanotransduction responses in chondrocytes.We further demonstrated that mechanically damaged cartilage induces synovial abnormalities and immune dysregulation and explored the potential of our chip as a platform for screening therapeutic targets.This cartilage-on-a-chip offers an in vitro system with a close-to-in vivo microenvironment for investigating complex bio-chemo-mechanical interactions,paving the way for advanced studies on OA pathogenesis and drug screening.展开更多
Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immuno...Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immunosuppressive microenvironment,and contributes to therapeutic resistance.We synthesize current knowledge on how autonomic(sympathetic and parasympathetic)and sensory innervation regulate gastric cancer biology.These circuits act through neurotransmitters(catecholamines,acetylcholine)and neuropeptides(substance P[SP],calcitonin gene-related peptide[CGRP])to foster tumor growth and angiogenesis,facilitate perineural invasion,and enable immune evasion by recruiting suppressive myeloid and lymphoid populations and by inducing checkpoint molecule expression.We also examine how chronic stress and the microbiota-gut-brain axis intensify immunosuppression via glucocorticoid signaling and microbially derived metabolites.In parallel,we discuss why current immunotherapies achieve only modest response rates(approximately 10%-20%)in many settings,emphasizing neurally mediated mechanisms of resistance.We evaluate therapeutic strategies that target the neuro-immune axis-including pharmacological neuromodulation,selective neural ablation,and rational combination regimens-and outline how single-cell approaches and neural-tumor-microenvironment organoid models can accelerate mechanism-driven translation.This review aims to integrate current evidence from neuroscience and immuno-oncology to construct a conceptual framework for neuro-immune regulation in gastric cancer and to identify potential therapeutic strategies to overcome treatment resistance by targeting neural-tumor-immune crosstalk.展开更多
Pulsed dynamic electrolysis(PDE),driven by renewable energy,has emerged as an innovative electrocatalytic conversion method,demonstrating significant potential in addressing global energy challenges and promoting sust...Pulsed dynamic electrolysis(PDE),driven by renewable energy,has emerged as an innovative electrocatalytic conversion method,demonstrating significant potential in addressing global energy challenges and promoting sustainable development.Despite significant progress in various electrochemical systems,the regulatory mechanisms of PDE in energy and mass transfer and the lifespan extension of electrolysis systems,particularly in water electrolysis(WE)for hydrogen production,remain insufficiently explored.Therefore,there is an urgent need for a deeper understanding of the unique contributions of PDE in mass transfer enhancement,microenvironment regulation,and hydrogen production optimization,aiming to achieve low-energy consumption,high catalytic activity,and long-term stability in the generation of target products.Here,this review critically examines the microenvironmental effects of PDE on energy and mass transfer,the electrode degradation mechanisms in the lifespan extension of electrolysis systems,and the key factors in enhancing WE for hydrogen production,providing a comprehensive summary of current research progress.The review focuses on the complex regulatory mechanisms of frequency,duty cycle,amplitude,and other factors in hydrogen evolution reaction(HER)performance within PDE strategies,revealing the interrelationships among them.Finally,the potential future directions and challenges for transitioning from laboratory studies to industrial applications are proposed.展开更多
Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches ...Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.展开更多
Tumor survival,genomic stability,and therapy resistance are dictated by the DNA damage response(DDR).Although poly(ADP-ribose)polymerase(PARP)inhibitors have established the DDR as a therapeutic target,many tumors eva...Tumor survival,genomic stability,and therapy resistance are dictated by the DNA damage response(DDR).Although poly(ADP-ribose)polymerase(PARP)inhibitors have established the DDR as a therapeutic target,many tumors evade first-generation drugs by rewiring their adaptive repair pathways and imposing microenvironmental constraints.This review synthesizes recent discoveries in key DDR pathways,such as PARP,ataxia telangiectasia and Rad3-related kinase(ATR),ataxia telangiectasia mutated kinase(ATM),checkpoint kinase 1(CHK1),WEE1 G2 checkpoint kinase(WEE1),and DNA-dependent protein kinase(DNA-PK),and describes the next-generation inhibitors designed to increase selectivity and circumvent resistance.We also analyze the role of hypoxia,stromal remodeling,inflammatory cytokines,and immune-cell plasticity in the tumor microenvironment in determining DDR dependency and response.Special attention is paid to cGAS-STING,immunogenic signaling via damage-associated molecular patterns(DAMPs),and mechanisms that convert a cold tumor into a hot one.Lastly,we touch upon the new nanocarrier-based delivery approaches that enhance pharmacokinetics,target resistant tumor niches,and expand the possibilities for combinatorics with immunotherapy and radiotherapy.Collectively,these findings provide a guide to the implementation of next-generation DDR inhibitors and nanomedicines to deliver a more accurate,durable,and context-specific cancer therapy.展开更多
Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains...Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains unclear.This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach.Methods:Leveraging bulk datasets,single-cell RNA sequencing,and integrative spatial transcriptomics,we developed a prognostic model based on hypoxia-and fructose metabolism-related genes(HFGs)to delineate tumor cell subpopulations and their intercellular signaling networks.Results:We identified a specific subset of stanniocalcin-2 positive(STC2+)malignant cells spatially enriched within tumor regions and strongly associated with poor prognosis.This subset served as a key signaling hub in the TME,exhibiting increased epithelial–mesenchymal transition activity.STC2+cells engage in two spatially organized ligand–receptor interactions:the growth differentiation factor 15(GDF15)—transforming growth factor beta receptor 2(TGFBR2)pathway targeting endothelial cells and the migration inhibitory factor(MIF)—(cluster of differentiation 74[CD74]+C-X-C motif chemokine receptor 4[CXCR4])pathway targeting macrophages.Conclusion:This study identified a malignant cell state in CRC that is metabolically defined and spatially limited,including liver metastases,and is characterized by elevated STC2 expression and active immune-stromal interactions.Given the interplay between metabolic reprogramming and TME remodeling,STC2+malignant cells are a functionally significant subpopulation and a potential therapeutic target.展开更多
Photoelectrochemical CO_(2)reduction to multi-carbon products fuels remains challenged by inefficient C–C coupling and competing proton reduction reaction.Herein,we designed a cationic covalent organic framework(COF+...Photoelectrochemical CO_(2)reduction to multi-carbon products fuels remains challenged by inefficient C–C coupling and competing proton reduction reaction.Herein,we designed a cationic covalent organic framework(COF+)to create an electrostatic microenvironment that synergizes with CuPt alloy nanoparticles for selective ethylene/ethane production.By spatially decoupling CO_(2)enrichment from proton exclusion,the COF^(+)/CuPt interface simultaneously facilitates CO_(2)accessibility while impeding H+migration,suppressing the hydrogen evolution reaction(HER).This unique microenvironment stabilizes key anionic intermediates(*COO^(−),*OCCO^(−))and promotes*CO dimerization,steering electron transfer toward C–C coupling.The optimized system achieves a record-high Faradaic efficiency of 51.5%±5.3%for ethane and 10.6%±2.5%for ethylene with a total C2+yield exceeding 62%at−0.25 V vs.RHE and high stability(>300 min),representing the highest performance for photoelectrochemical CO_(2)reduction to ethane.The combined analyses of in situ spectroscopy and theoretical calculations reveal that electrostatic field effects lower the energy barrier for*OCCO formation while accelerating hydrogenation kinetics.Therefore,this work demonstrates that microenvironment modification of the active site by cationic covalent organic framework is a versatile strategy for solar-driven CO_(2)conversion into value-added hydrocarbons.展开更多
This research is focused on the calculation of a reasonable detonator delay time for realizing cut blast vibration control.First,the viscoelastic rock mass parameters corresponding to the engineering rock mass quality...This research is focused on the calculation of a reasonable detonator delay time for realizing cut blast vibration control.First,the viscoelastic rock mass parameters corresponding to the engineering rock mass quality classification were determined based on wave theory of Kelvin medium.Then,a calculation model was obtained for the millisecond-delay cut blast vibration in Kelvin media using the Starfield charge superposition principle.Further,the influence of the delay time on the cut blast vibration was quantitatively analyzed and a method for calculating the reasonable cut blasting millisecond delay time is proposed according to the principle of dimensional analysis.Finally,field tests were used to verify the applicability of the method.The results show that 5 ms to 20 ms is a better detonator delay time range and cut blasting vibration can be effectively controlled using the delay time calculated by the calculation model described in this paper.展开更多
Hydrogen peroxide(H_(2)O_(2))is a versatile oxidant with significant applications,particularly in regulating the microenvironment for healthcare purposes.Herein,a rational design of the photoanode is implemented to en...Hydrogen peroxide(H_(2)O_(2))is a versatile oxidant with significant applications,particularly in regulating the microenvironment for healthcare purposes.Herein,a rational design of the photoanode is implemented to enhance H_(2)O_(2) production by oxidizing H_(2)O in a portable photoelectrocatalysis(PEC)device.The obtained solution from this system is demonstrated for effective bactericidal activity against Staphylococcus aureus and Escherichia coli,while maintaining low toxicity toward hippocampal neuronal cells.The photoanode is achieved by Mo-doped BiVO4 films,which are subsequently loaded with cobalt-porphyrin(Co-py)molecules as a co-catalyst.As a result,the optimal performance for H_(2)O_(2) production rate was achieved at 8.4μmol h^(−1) cm^(−2),which is 1.8 times that of the pristine BiVO4 photoanode.Density functional theory(DFT)simulations reveal that the improved performance results from a 1.1 eV reduction in the energy of the rate-determining step of·OH adsorption by the optimal photoanode.This study demonstrates a PEC approach for promoting H_(2)O_(2) production by converting H_(2)O for antibacterial purposes,offering potential applications in conventionally controlling microenvironments for healthcare applications.展开更多
Flowering time is a critical agronomic trait with a profound effect on the productivity and adaptabillity of rapeseed(Brassica napus L.).Strategically advancing flowering time can reduce the risk of yield losses due t...Flowering time is a critical agronomic trait with a profound effect on the productivity and adaptabillity of rapeseed(Brassica napus L.).Strategically advancing flowering time can reduce the risk of yield losses due to extreme climatic conditions and facilitate the cultivation of subsequent crops on the same land,thereby enhancing overall agricultural efficiency.In this review,we synthesize current information on flowering time regulation in rapeseed through an integrated analysis of its genetic,hormonal,and environmental dimensions,emphasizing their crosstalk and implications for yield.We consolidate multi-omics evidence from population genetics,functional genomics,and systems biology to create a haplotype-based framework that overcomes the trade-off between flowering time and yield,providing support for the precision breeding of early-maturing cultivars.The insights presented here could inform future research on flowering time regulation and guide strategies for increasing rapeseed productivity.展开更多
Considering the impact of terminal impact time constraints and the state information of maneuvering targets on the guidance accuracy in multi-UAV cooperative guidance,this paper proposes an impact time cooperative con...Considering the impact of terminal impact time constraints and the state information of maneuvering targets on the guidance accuracy in multi-UAV cooperative guidance,this paper proposes an impact time cooperative control guidance law(ITCCG)that combines the optimal error dynamics with an improved adaptive cubature Kalman filter(IACKF)algorithm.First,a terminal impact time feedback term is introduced into proportional navigation guidance based on the relative virtual guidance model,and terminal time control is achieved through optimal error dynamics.Then,the Huber loss function is used to reduce the impact of measurement outliers,and the diagonal decomposition is applied to address the issue of non-positive definite matrices that cannot undergo Cholesky decomposition.Finally,the ITCCG and IACKF algorithms combined achieve multi-UAV time-cooperated guidance based on maneuvering target state estimation.Simulation results show that the proposed algorithm effectively reduces the target state estimation error and achieves cooperative guidance within the desired time frame.展开更多
文摘This study investigates prescribed-time position tracking control for electromagnetic satellite formations subject to model uncertainties and external disturbances.Using the Clohessy-Wiltshire equations as the relative motion dynamics model,a prescribed time output feedback control strategy is proposed.A prescribed-time extended state observer is designed to estimate the relative velocity and external disturbances.The disturbance estimates are then used as the feedforward component of the controller.Building on this framework,a novel prescribed-time active disturbance rejection control strategy for position tracking is developed via a backstepping control design.The convergence of the extended state observer and the stability of the closed-loop system are rigorously analyzed using Lyapunov stability theory.Numerical simulations are performed to validate the effectiveness of the proposed controller.
基金supported by the National Natural Science Foundation of China(Nos.82302373,81903846)Natural Science Foundation of Sichuan Province(No.2022NSFSC1925)+1 种基金Chengdu Technology Innovation Research and Development Project(No.2022-YF05-01546-SN)the Introduction of Talents Research Project of Chengdu University(No.2081921049)。
文摘Emerging ferroptosis-immunotherapy strategies,integrating functionalized nanoplatforms with ferroptosis-inducing agents and immunomodulatory therapeutics,demonstrate significant potential in managing primary,recurrent,and metastatic malignancies.Mechanistically,ferroptosis induction not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),eliciting damage-associated molecular patterns(DAMPs)release to activate partial antitumor immunity.However,standalone ferroptosis therapy fails to initiate robust systemic antitumor immune responses due to inherent limitations:low tumor immunogenicity,immunosuppressive microenvironment constraints,and tumor microenvironment(TME)-associated physiological barriers(e.g.,hypoxia,dense extracellular matrix).To address these challenges,synergistic approaches have been developed to enhance immune cell infiltration and reestablish immunosurveillance,encompassing(1)direct amplification of antitumor immunity,(2)disruption of immunosuppressive tumor niches,and(3)biophysical hallmark remodeling in TME.Rational nanocarrier design has emerged as a critical enabler for overcoming biological delivery barriers and optimizing therapeutic efficacy.Unlike prior studies solely addressing ferroptosis or nanotechnology in tumor therapy,this work first systematically outlines the synergistic potential of nanoparticles in combined ferroptosis-immunotherapy strategies.It advances multidimensional nanoplatform design principles for material selection,structural configuration,physicochemical modulation,multifunctional integration,and artificial intelligence-enabled design,providing a scientific basis for efficacy optimization.Moreover,it examines translational challenges of ferroptosis-immunotherapy nanoplatforms across preclinical and clinical stages,proposing actionable solutions while envisioning future onco-immunotherapy directions.Collectively,it provides systematic insights into advanced nanomaterial design principles and therapeutic optimization strategies,offering a roadmap for accelerating clinical translation in onco-immunotherapy research.
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
基金financially supported by The Excellent Youth Project of the Education Department of Hunan Province(No.24B0008)the National Natural Science Foundation of China(No.52377222)。
文摘Parasitic interface side reactions and uncontrollable Zn deposition seriously erode the cycling performance of aqueous zinc ion batteries,thus impeding the large-scale application.Herein,an organic acid molecule with a unique molecular structure,camphorsulfonic acid(CSA),is first proposed to remodel the interface microenvironment as an electrolyte additive.The proton provided by CSA can neutralize the hydroxide ions generated by side reactions and inhibit the accumulation of alkaline by-products.The sulfonic acid groups are firmly adsorbed on the Zn anode surface,thereby enabling the regulation of interfacial species.Specifically,oxygen-containing functional groups combined with hydrophobic rigid carbon rings achieve a water-poor interface environment and promote the transfer of Zn^(2+),providing a suitable environment for Zn deposition.As a result,Zn//Zn symmetrical battery can run for over 2800 h(2 mA cm^(-2)-2 mAh cm^(-2)),demonstrating 28-times lifespan compared to the battery without CSA.Furthermore,Zn//KVO full cell presents excellent performance of 800 cycles at 3 A g^(-1).Besides,the pouch cell with CSA can also operate a capacity of 153.8 mAh after 60 cycles at 0.5 A g^(-1) with96.5%capacity retention rate.This work provides an organism-inspired additive selection for stabilizing the interface chemistry of the Zn anode.
基金supported by grants from the National Natural Science Foundation of China(Nos.22108154,22138006,32171430).
文摘Triterpenoids are valuable medicinal scaffolds,characterized by excellent pharmacological properties and the presence of hydroxyl and carboxyl groups that allow for further structural modifications.Expanding the scope of oxidative modifications on these molecules is crucial for increasing their synthetic structural diversity and unlocking new potential pharmacological activities.However,the progress has been limited by the scarcity of suitable tailoring enzymes.Here,we reported a break-through in achieving targeted and remote dual-site oxidation of licorice triterpenoids using a single P450 mutant.This approach successfully enabled the selective synthesis of the rare triterpenoid,liquiritic acid and 24-OH-liquiritic acid.Our findings demonstrate that microenvironmental accessibility engineering of triterpenoid substrates within the P450 enzyme is essential for continuous and regioselective oxidation.This study not only sheds light on the mechanistic aspects of P450 catalysis but also expands the enzymatic toolkit for selective oxidative modifications in triterpenoid biosynthesis.
基金supported by Natural Science Foundation of Shandong Province(Nos.ZR2023MB081,ZR2024QB346)Shandong Traditional Chinese Medicine Technology Project(No.Q-2023127).
文摘In situ tumor vaccines,which leverage the antigenic profile of individual tumors,have demonstrated significant potential in tumor immunotherapy.However,their efficacy is often limited by the immunosuppressive tumor microenvironment(TME)and insufficient tumor targeting.To address these challenges,we engineered in situ nanovaccines through the self-assembly of the photosensitizer indocyanine green,immune adjuvant aluminum(Al^(3+)),and hydrophilic drug zoledronic acid(ZOL).Intravenous injection of these nanovaccines led to efficient tumor accumulation,enhancing drug bioavailability and enabling the release of tumor-associated antigens via photothermal therapy.Additionally,the built-in ZOL induces polarization of tumor-associated macrophages,reversing the immunosuppressive TME.The potent antitumor immune response triggered by these nanovaccines effectively suppresses tumor growth.This study,which integrates a straightforward assembly method,substantial drug loading capacity,and promising therapeutic outcomes,introduces a novel and effective paradigm for carrier-free in situ nanovaccines in cancer treatment.
基金supported by the Tianjin Manufacturing High Quality Development Special Foundation(No.20232185)the Roycom Foundation(No.70306901).
文摘Hard disk drives(HDDs)serve as the primary storage devices in modern data centers.Once a failure occurs,it often leads to severe data loss,significantly degrading the reliability of storage systems.Numerous studies have proposed machine learning-based HDD failure prediction models.However,the Self-Monitoring,Analysis,and Reporting Technology(SMART)attributes differ across HDD manufacturers.We define hard drives of the same brand and model as homogeneous HDD groups,and those from different brands or models as heterogeneous HDD groups.In practical engineering scenarios,a data center is often composed of a heterogeneous population of HDDs,spanning multiple vendors and models.Existing research predominantly focuses on homogeneous datasets,ignoring the model’s generalization capability across heterogeneous HDDs.As a result,HDD models with limited samples often suffer from poor training effectiveness and prediction performance.To address this issue,we investigate generalizable SMART predictors across heterogeneous HDD groups.By extracting time-series features within a fixed sliding time window,we propose a Heterogeneous Disk Failure Prediction Method based on Time Series Features(HDFPM)framework.This method is adaptable to HDD models with limited sample sizes,thereby enhancing its applicability and robustness across diverse drive populations.Experimental results show that the proposed model achieves an F1-score of 0.9518 when applied to two different Seagate HDD models,while maintaining the False Positive Rate(FPR)below 1%.After incorporating the Complexity-Ratio Dynamic Time Warping(CDTW)based feature enhancement method,the best prediction model achieves a True Positive Rate(TPR)of up to 0.93 between the two models.For next-day failure prediction across various Seagate models,the model achieves an F1-score of up to 0.8792.Moreover,the experimental results also show that within the same brand,the higher the proportion of shared SMART attributes across different models,the better the prediction performance.In addition,HDFPMdemonstrates the best stability andmost significant performance in heterogeneous environments.
基金supported by the National Natural Science Foundation of China(Nos.12072010 and 11674019)the Fundamental Research Funds for the Central Universities(No.YWF22-K-101)the National Key Research and Development Program of China(No.2022YFB3804300).
文摘Osteoarthritis(OA),the most common chronic joint disease,leads to remarkable morbidity and disability.The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of osteoarthritic joints is crucial for elucidating OA pathogenesis and facilitating drug development.In this study,we present a microfluidics-based cartilage-on-a-chip model that integrates tunable mechanical stimulation and inter-tissue/cell communication,mimicking the key physiological characteristics of articular cartilage for organ-level OA research.By applying controllable mechanical compression,we established a model that captures healthy and injury hallmarks of the cartilage and directly observed the mechanotransduction responses in chondrocytes.We further demonstrated that mechanically damaged cartilage induces synovial abnormalities and immune dysregulation and explored the potential of our chip as a platform for screening therapeutic targets.This cartilage-on-a-chip offers an in vitro system with a close-to-in vivo microenvironment for investigating complex bio-chemo-mechanical interactions,paving the way for advanced studies on OA pathogenesis and drug screening.
文摘Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immunosuppressive microenvironment,and contributes to therapeutic resistance.We synthesize current knowledge on how autonomic(sympathetic and parasympathetic)and sensory innervation regulate gastric cancer biology.These circuits act through neurotransmitters(catecholamines,acetylcholine)and neuropeptides(substance P[SP],calcitonin gene-related peptide[CGRP])to foster tumor growth and angiogenesis,facilitate perineural invasion,and enable immune evasion by recruiting suppressive myeloid and lymphoid populations and by inducing checkpoint molecule expression.We also examine how chronic stress and the microbiota-gut-brain axis intensify immunosuppression via glucocorticoid signaling and microbially derived metabolites.In parallel,we discuss why current immunotherapies achieve only modest response rates(approximately 10%-20%)in many settings,emphasizing neurally mediated mechanisms of resistance.We evaluate therapeutic strategies that target the neuro-immune axis-including pharmacological neuromodulation,selective neural ablation,and rational combination regimens-and outline how single-cell approaches and neural-tumor-microenvironment organoid models can accelerate mechanism-driven translation.This review aims to integrate current evidence from neuroscience and immuno-oncology to construct a conceptual framework for neuro-immune regulation in gastric cancer and to identify potential therapeutic strategies to overcome treatment resistance by targeting neural-tumor-immune crosstalk.
基金financially supported by the Key Research and Development Program of Heilongjiang Province(No.2024ZXJ03C06)National Natural Science Foundation of China(No.52476192,No.52106237)+1 种基金Natural Science Foundation of Heilongjiang Province(No.YQ2022E027)Technology Project of China Datang Technology Innovation Co.,Ltd(No.DTKC-2024-20610).
文摘Pulsed dynamic electrolysis(PDE),driven by renewable energy,has emerged as an innovative electrocatalytic conversion method,demonstrating significant potential in addressing global energy challenges and promoting sustainable development.Despite significant progress in various electrochemical systems,the regulatory mechanisms of PDE in energy and mass transfer and the lifespan extension of electrolysis systems,particularly in water electrolysis(WE)for hydrogen production,remain insufficiently explored.Therefore,there is an urgent need for a deeper understanding of the unique contributions of PDE in mass transfer enhancement,microenvironment regulation,and hydrogen production optimization,aiming to achieve low-energy consumption,high catalytic activity,and long-term stability in the generation of target products.Here,this review critically examines the microenvironmental effects of PDE on energy and mass transfer,the electrode degradation mechanisms in the lifespan extension of electrolysis systems,and the key factors in enhancing WE for hydrogen production,providing a comprehensive summary of current research progress.The review focuses on the complex regulatory mechanisms of frequency,duty cycle,amplitude,and other factors in hydrogen evolution reaction(HER)performance within PDE strategies,revealing the interrelationships among them.Finally,the potential future directions and challenges for transitioning from laboratory studies to industrial applications are proposed.
基金Supported by National Natural Science Foundation of China,No.82170638Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality,No.23ZR1458300+1 种基金Key Discipline Project of Shanghai Municipal Health System,No.2024ZDXK0004and Pujiang Project of Shanghai Magnolia Talent Plan,No.24PJD098.
文摘Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.
文摘Tumor survival,genomic stability,and therapy resistance are dictated by the DNA damage response(DDR).Although poly(ADP-ribose)polymerase(PARP)inhibitors have established the DDR as a therapeutic target,many tumors evade first-generation drugs by rewiring their adaptive repair pathways and imposing microenvironmental constraints.This review synthesizes recent discoveries in key DDR pathways,such as PARP,ataxia telangiectasia and Rad3-related kinase(ATR),ataxia telangiectasia mutated kinase(ATM),checkpoint kinase 1(CHK1),WEE1 G2 checkpoint kinase(WEE1),and DNA-dependent protein kinase(DNA-PK),and describes the next-generation inhibitors designed to increase selectivity and circumvent resistance.We also analyze the role of hypoxia,stromal remodeling,inflammatory cytokines,and immune-cell plasticity in the tumor microenvironment in determining DDR dependency and response.Special attention is paid to cGAS-STING,immunogenic signaling via damage-associated molecular patterns(DAMPs),and mechanisms that convert a cold tumor into a hot one.Lastly,we touch upon the new nanocarrier-based delivery approaches that enhance pharmacokinetics,target resistant tumor niches,and expand the possibilities for combinatorics with immunotherapy and radiotherapy.Collectively,these findings provide a guide to the implementation of next-generation DDR inhibitors and nanomedicines to deliver a more accurate,durable,and context-specific cancer therapy.
基金supported by the Joint Project of the Chongqing Science and Technology Commission(2025MSXM040).
文摘Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains unclear.This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach.Methods:Leveraging bulk datasets,single-cell RNA sequencing,and integrative spatial transcriptomics,we developed a prognostic model based on hypoxia-and fructose metabolism-related genes(HFGs)to delineate tumor cell subpopulations and their intercellular signaling networks.Results:We identified a specific subset of stanniocalcin-2 positive(STC2+)malignant cells spatially enriched within tumor regions and strongly associated with poor prognosis.This subset served as a key signaling hub in the TME,exhibiting increased epithelial–mesenchymal transition activity.STC2+cells engage in two spatially organized ligand–receptor interactions:the growth differentiation factor 15(GDF15)—transforming growth factor beta receptor 2(TGFBR2)pathway targeting endothelial cells and the migration inhibitory factor(MIF)—(cluster of differentiation 74[CD74]+C-X-C motif chemokine receptor 4[CXCR4])pathway targeting macrophages.Conclusion:This study identified a malignant cell state in CRC that is metabolically defined and spatially limited,including liver metastases,and is characterized by elevated STC2 expression and active immune-stromal interactions.Given the interplay between metabolic reprogramming and TME remodeling,STC2+malignant cells are a functionally significant subpopulation and a potential therapeutic target.
基金financial support from the National Natural Science Foundation of China(No.52273187)the Guangdong Basic and Applied Basic Research Foundation(2022A1515110372,2023A1515011306,2023A1515240077)+1 种基金the National Key Research and Development Program of China(2022YFA1502900)the Guangdong-Hong Kong Joint Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province(2023B1212120011).
文摘Photoelectrochemical CO_(2)reduction to multi-carbon products fuels remains challenged by inefficient C–C coupling and competing proton reduction reaction.Herein,we designed a cationic covalent organic framework(COF+)to create an electrostatic microenvironment that synergizes with CuPt alloy nanoparticles for selective ethylene/ethane production.By spatially decoupling CO_(2)enrichment from proton exclusion,the COF^(+)/CuPt interface simultaneously facilitates CO_(2)accessibility while impeding H+migration,suppressing the hydrogen evolution reaction(HER).This unique microenvironment stabilizes key anionic intermediates(*COO^(−),*OCCO^(−))and promotes*CO dimerization,steering electron transfer toward C–C coupling.The optimized system achieves a record-high Faradaic efficiency of 51.5%±5.3%for ethane and 10.6%±2.5%for ethylene with a total C2+yield exceeding 62%at−0.25 V vs.RHE and high stability(>300 min),representing the highest performance for photoelectrochemical CO_(2)reduction to ethane.The combined analyses of in situ spectroscopy and theoretical calculations reveal that electrostatic field effects lower the energy barrier for*OCCO formation while accelerating hydrogenation kinetics.Therefore,this work demonstrates that microenvironment modification of the active site by cationic covalent organic framework is a versatile strategy for solar-driven CO_(2)conversion into value-added hydrocarbons.
基金National Natural Science Foundation of China under Grant Nos.51979205 and 51939008。
文摘This research is focused on the calculation of a reasonable detonator delay time for realizing cut blast vibration control.First,the viscoelastic rock mass parameters corresponding to the engineering rock mass quality classification were determined based on wave theory of Kelvin medium.Then,a calculation model was obtained for the millisecond-delay cut blast vibration in Kelvin media using the Starfield charge superposition principle.Further,the influence of the delay time on the cut blast vibration was quantitatively analyzed and a method for calculating the reasonable cut blasting millisecond delay time is proposed according to the principle of dimensional analysis.Finally,field tests were used to verify the applicability of the method.The results show that 5 ms to 20 ms is a better detonator delay time range and cut blasting vibration can be effectively controlled using the delay time calculated by the calculation model described in this paper.
基金support from the National Key Technologies R&D Program of China(2022YFE0114800)National Natural Science Foundation of China(22075047),and the 111 Project(D16008)。
文摘Hydrogen peroxide(H_(2)O_(2))is a versatile oxidant with significant applications,particularly in regulating the microenvironment for healthcare purposes.Herein,a rational design of the photoanode is implemented to enhance H_(2)O_(2) production by oxidizing H_(2)O in a portable photoelectrocatalysis(PEC)device.The obtained solution from this system is demonstrated for effective bactericidal activity against Staphylococcus aureus and Escherichia coli,while maintaining low toxicity toward hippocampal neuronal cells.The photoanode is achieved by Mo-doped BiVO4 films,which are subsequently loaded with cobalt-porphyrin(Co-py)molecules as a co-catalyst.As a result,the optimal performance for H_(2)O_(2) production rate was achieved at 8.4μmol h^(−1) cm^(−2),which is 1.8 times that of the pristine BiVO4 photoanode.Density functional theory(DFT)simulations reveal that the improved performance results from a 1.1 eV reduction in the energy of the rate-determining step of·OH adsorption by the optimal photoanode.This study demonstrates a PEC approach for promoting H_(2)O_(2) production by converting H_(2)O for antibacterial purposes,offering potential applications in conventionally controlling microenvironments for healthcare applications.
基金supported by the National Key Research and Development Program of China(2022YFD1200400)the National Natural Science Foundation of China(32272111)+4 种基金Special fund for youth team of the Southwest Universities(SWU-XJPY202306)Chongqing Natural Science Foundation(CSTB2024NSCQLZX0012)Modern Agro-industry Technology Research System(CARS-12)Chongqing Modern Agricultural Industry Technology System(COMAITS202504)Biological Breeding-National Science and Technology Major Project(2022ZD04008).We sincerely appreciate the Plant Editors team for English language editing of the manuscript,which significantly improved its clarity and overall quality.
文摘Flowering time is a critical agronomic trait with a profound effect on the productivity and adaptabillity of rapeseed(Brassica napus L.).Strategically advancing flowering time can reduce the risk of yield losses due to extreme climatic conditions and facilitate the cultivation of subsequent crops on the same land,thereby enhancing overall agricultural efficiency.In this review,we synthesize current information on flowering time regulation in rapeseed through an integrated analysis of its genetic,hormonal,and environmental dimensions,emphasizing their crosstalk and implications for yield.We consolidate multi-omics evidence from population genetics,functional genomics,and systems biology to create a haplotype-based framework that overcomes the trade-off between flowering time and yield,providing support for the precision breeding of early-maturing cultivars.The insights presented here could inform future research on flowering time regulation and guide strategies for increasing rapeseed productivity.
基金supported by the Fundamental Research Funds for the Central Universities of China(FRF-TP-24-058A)with additional support from the National Key Laboratory of Helicopter Aeromechanics(2024-ZSJ-LB-02-02).
文摘Considering the impact of terminal impact time constraints and the state information of maneuvering targets on the guidance accuracy in multi-UAV cooperative guidance,this paper proposes an impact time cooperative control guidance law(ITCCG)that combines the optimal error dynamics with an improved adaptive cubature Kalman filter(IACKF)algorithm.First,a terminal impact time feedback term is introduced into proportional navigation guidance based on the relative virtual guidance model,and terminal time control is achieved through optimal error dynamics.Then,the Huber loss function is used to reduce the impact of measurement outliers,and the diagonal decomposition is applied to address the issue of non-positive definite matrices that cannot undergo Cholesky decomposition.Finally,the ITCCG and IACKF algorithms combined achieve multi-UAV time-cooperated guidance based on maneuvering target state estimation.Simulation results show that the proposed algorithm effectively reduces the target state estimation error and achieves cooperative guidance within the desired time frame.
