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Single-cell RNA sequencing of the post-spinal cord injury dorsal root ganglia in cynomolgus monkeys:Elucidation of the cellular immune microenvironment of the central nervous system 认领 引用
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作者 Yiming Ren Bo Li +6 位作者 Bo Yang Baoyou Fan Shenghui Huang Guidong Shi Liang Liu Zhijian Wei Shiqing Feng 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第6期2506-2513,共8页
Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we use... Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we used a single-cell RNA sequencing dataset to create a comprehensive profile of the diverse cell types in the dorsal root ganglia and spinal cord of a mid-thoracic contusion injury model in cynomolgus monkeys.Cell communication analysis indicated that specific signaling events among various dorsal root ganglia cell types occur in response to spinal cord injury.Single-cell analysis using dimensionality reduction clustering identified distinct molecular signatures for nine cell types,including macrophage subpopulations,and differential gene expression profiles between dorsal root ganglia cells and spinal cord cells following spinal cord injury.The macrophage subpopulations were categorized into 11 clusters(MC0-MC10)based on differentially expressed genes,with the top 10 genes being ABCA6,RBMS3,EBF1,LAMA4,ANTXR2,LAMA2,SOX5,FOXP2,GHR,and APOD.MC0,MC1,and MC2 constituted the predominant macrophage populations.MC4,MC6,and MC9 were nearly absent in the spinal cord,but exhibited significant increases in the dorsal root ganglia post-spinal cord injury.Notably,these subpopulations possess a strong capacity for regulating axonal regeneration.The developmental progression of dorsal root ganglia macrophages after spinal cord injury was elucidated using cell trajectory and pseudo-time analyses.Genes such as EBF1(MC6 and MC9 marker),RBMS3(MC6 and MC9 marker),and ABCA6(MC6 marker)showed high expression levels in the critical pathways of macrophage function.Through ligand-receptor pair analysis,we determined that the effects of macrophages on microglia are predominantly mediated through interaction pairs(e.g.,SPP1-CD44,LAMC1-CD44,and FN1-CD44),potentially facilitating specific cellular communications within the immune microenvironment.The single-cell RNA sequencing dataset used in this study represents the first comprehensive transcriptional analysis of the dorsal root ganglia after spinal cord injury in cynomolgus monkeys,encompassing nearly all cell types within the dorsal root ganglia region.Using this dataset,we evaluated diverse subtypes of macrophages in the post-spinal cord injury dorsal root ganglia area and examined the signaling pathways that facilitate interactions among immune response-related macrophages in the dorsal root ganglia.Findings from this study provide a theoretical basis for understanding how the immune microenvironment influences the regenerative capacity of dorsal root ganglia neurons after spinal cord injury and offer novel insights into the complex processes underlying the pathobiology of spinal cord injury. 展开更多
关键词 cellular communication cellular microenvironment differentially expressed genes dorsal root ganglia immune cells macrophage microglia neurons single-cell sequence spinal cord injury
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Proteostasis decline and endoplasmic reticulum stress in aging:Implications for cellular senescence and senescence-associated secretory phenotype regulation 认领 引用
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作者 Philippe Pihán Lisa M.Ellerby Claudio Hetz 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第7期2934-2935,共2页
Aging is a universal biological process characterized by the progressive decline in cellular and tissue function,representing the main risk factor for the development of most chronic human diseases.At the cellular lev... Aging is a universal biological process characterized by the progressive decline in cellular and tissue function,representing the main risk factor for the development of most chronic human diseases.At the cellular level,one hallmark of aging is the accumulation of senescent cells—non-dividing yet metabolically active cells that adopt a unique phenotype,including the senescence-associated secretory phenotype(SASP)(Wang et al.,2024). 展开更多
关键词 proteostasis decline senescence associated secretory phenotype cellular tissue endoplasmic reticulum stress senescent cells non dividing cellular senescence aging
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Subcellular Organelles and Cellular Molecules:Localization,Detection,Prediction,and Diseases 认领 引用
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作者 Ye Zeng Bingmei M.Fu 《BIOCELL》 SCIE 2025年第6期925-930,共6页
1 Subcellular Organelle Dysfunction and Disease Progression The precise organization of subcellular organelles is important for maintaining cellular homeostasis.Compartmentalization orchestrates metabolic processes,si... 1 Subcellular Organelle Dysfunction and Disease Progression The precise organization of subcellular organelles is important for maintaining cellular homeostasis.Compartmentalization orchestrates metabolic processes,signal transductions,and stress responses.Disturbances in organelles,including the nucleus,mitochondria,lysosomes,and endoplasmic reticulum,can lead to widespread intracellular dysfunction and contribute to diverse pathologies.For example,mitochondrial reactive oxygen species(ROS)exacerbate endoplasmic reticulum(ER)stress,as demonstrated in studies linking ROS-mediated mitochondrial dysfunction to apoptosis in neurodegenerative diseases,cancer,and inflammatory diseases[1–4].ER stress has also been implicated in cardiac hypertrophy[5],lung fibrosis[6],liver fibrosis[7],and ulcerative colitis[8]. 展开更多
关键词 cellular homeostasiscompartmentalization localization reactive oxygen species ros exacerbate organization subcellular organelles subcellular organelle subcellular organelles intracellular dysfunction endoplasmic reticulumcan
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Post-translational modifications in hepatocellular carcinoma:Linking senescence,metabolic reprogramming,and immune evasion for therapeutic innovation 认领 引用
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作者 Tai-Xian Song Yao Rong +1 位作者 Hao-Min Ji Xing-Sheng Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2026年第6期35-60,共26页
Hepatocellular carcinoma remains a leading cause of cancer mortality.Although immune checkpoint inhibitors have improved outcomes for a subset of patients,primary and acquired resistance are common.Post-translational ... Hepatocellular carcinoma remains a leading cause of cancer mortality.Although immune checkpoint inhibitors have improved outcomes for a subset of patients,primary and acquired resistance are common.Post-translational modifications(PTMs)provide a rapid and reversible regulatory layer that links oncogenic signaling,metabolism,and chromatin state to cellular senescence and the tumor microenvironment.Here we synthesize evidence showing how ubiquitination,phosphorylation,acetylation,methylation,SUMOylation,O-GlcNAcylation,and lactylation modulate core senescence programs(p53etinoblastoma protein,DNA-damage response)and the senescence-associated secretory phenotype,thereby shaping myeloid recruitment,T-cell dysfunction,and immune evasion in hepatocellular carcinoma.We further discuss how metabolism-coupled PTMs rewire glycolysis-epigenetics crosstalk and generate spatially confined senescence-metabolic-immune niches that can be resolved by single-cell and spatial multi-omics.The current evidence base is dominated by mechanistic studies and correlative clinical datasets,underscoring the need for prospective validation and standardized PTM/senescence biomarkers.Finally,we propose a sequential“induce-remodel-clear”therapeutic concept in which senescence induction is paired with PTM-targeted modulation and immune or senolytic clearance to improve response durability. 展开更多
关键词 Hepatocellular carcinoma Post-translational modifications Cellular senescence Tumor immune microenvironment Metabolic reprogramming Immunotherapy Single-cell multi-omics Spatial transcriptomics Therapy resistance Precision medicine
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Epilepsy therapy beyond neurons: Unveiling astrocytes as cellular targets 认领 引用
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作者 Yuncan Chen Jiayi Hu +5 位作者 Ying Zhang Lulu Peng Xiaoyu Li Cong Li Xunyi Wu Cong Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第1期23-38,共16页
Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the ... Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction. 展开更多
关键词 astrocyte cellular microenvironment drug resistance epilepsy excitability homeostasis metabolism neural networks neuroinflammation neuron
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Achieving exceptional strength-ductility synergy in additively manufactured Hastelloy X superalloys by stabilizing cellular structures via Ta addition 认领 引用
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作者 Nan Chen Kefu Gan +4 位作者 Dan Zheng Pengda Niu Haoping Peng Tiechui Yuan Ruidi Li 《International Journal of Extreme Manufacturing》 SCIE EI CAS CSCD 2026年第2期591-619,共29页
Additive manufacturing of Hastelloy X superalloys remains challenges for practical aerospace applications due to the inadequate mechanical property at both ambient and high temperatures.To this end,this work proposes ... Additive manufacturing of Hastelloy X superalloys remains challenges for practical aerospace applications due to the inadequate mechanical property at both ambient and high temperatures.To this end,this work proposes a novel Ta-modified strategy manipulating elemental segregation to stabilize cellular structures,thereby obtaining an outstanding combination between strength and ductility across a wide temperature regime.In particular,the tensile strength and elongation of Ta-modified superalloys can reach up to 1214 MPa and 28.4%,respectively,highly increased by 47%and 10%compared to original Hastelloy X superalloys at 25℃.Meanwhile,the tensile strength and elongation at 650℃significantly increase to 843 MPa and 26.8%respectively,38%and 150%stronger than their counterparts of the original Ta-free Hastelloy X superalloys at identical conditions.Microstructural observations reveal that prominent local segregation of Ta/Mo elements and in situ MC precipitates along cellular boundaries synergistically enhanced the stability of cellular structures.The stabilized cellular structures serve as continuous and skeleton-like networks during deformation,synergistically contributing to outstanding ductility and enhanced mechanical strength,as well as sustained strain-hardening ability.The present work provides new insights into an efficient alloy design method for additively manufactured nickel-based superalloys with outstanding mechanical property within a wide temperature regime. 展开更多
关键词 additive manufacturing Hastelloy X superalloys cellular structures elemental segregation strength-ductility synergy
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RIS-assisted cellular networks with multiple D2D pairs:Outage and ergodic achievable rate 认领 引用
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作者 Yaxuan Liu Yiyang Ni +2 位作者 Haitao Zhao Yuxi Wang Yan Cai 《Digital Communications and Networks》 SCIE EI CSCD 2026年第1期52-65,共14页
Reconfigurable Intelligent Surface(RIS)is envisioned as a promising technology to improve the system capacity of 6G network,by controlling the electromagnetic wave propagation.Most existing works use the Central Limit... Reconfigurable Intelligent Surface(RIS)is envisioned as a promising technology to improve the system capacity of 6G network,by controlling the electromagnetic wave propagation.Most existing works use the Central Limit Theorem(CLT)to analyze the performance of RIS-assisted systems for large number of reflective elements.However,the assumption of extremely large number of elements may not be practical in the actual situation.In addition,the CLT-based approximation yields an inaccurate scaling law of the outage probability when the transmit Signal-to-Noise Ratio(SNR)tends to infinity.Motivated by these limitations,in this paper,we investigate the performance of RIS-assisted cellular networks with multiple Device-to-Device(D2D)users under the general fading channels,i.e.,Nakagami-m fading channels.We propose a tractable solution to evaluate the outage probability and the ergodic achievable rate,which is accurate for any number of reflective elements,any network topology,as well as any SNR.In addition,the accurate approximations for the high SNR case and the large number of reflective elements case are further derived in simpler closed form.Numerical results verify the accuracy of our analytical results and analyze the performance between CLT and the proposed method. 展开更多
关键词 Reconfigurable intelligent surface 6G cellular networks Device-to-device Outage probability Ergodic achievable rate Nakagami-fading
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Experimental study and 3D cellular automaton simulation of intergranular corrosion on laser-welded joints of Al-Cu-Li alloys under acidic conditions 认领 引用
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作者 Xinzhi Yang Gan Tian +4 位作者 Dejun Liu Biyun Ren Hui Cai Mengqing Liu Yan Zhang 《Defence Technology（防务技术）》 SCIE EI CAS CSCD 2026年第4期314-329,共16页
This study proposes a multi-scale research approach that integrates micro-characterization experiments and 3D cellular automata(CA)simulations to investigate the intergranular corrosion(IGC)behavior of equiaxed grains... This study proposes a multi-scale research approach that integrates micro-characterization experiments and 3D cellular automata(CA)simulations to investigate the intergranular corrosion(IGC)behavior of equiaxed grains in the fusion zone(FZ)of laser-welded joints of Al-Cu-Li alloys under acidic conditions.Combined with microscopic characterizations such as SEM and TEM,the significant segregation phe-nomenon of grain boundaries in the FZ of the laser welded joint of 2195-T8 aluminum-lithium alloy was revealed,and the typical morphologies of IGC in the FZ under two different concentrations of nitric acid were compared.Compared to the traditional CA model,the proposed approach uses the Voronoi method combined with experimental characterization data to reconstruct a polycrystalline micro-structural model.For the first time,the effects of grain boundary segregation and localized corrosion intensity on corrosion morphologies were incorporated.A CA model comprising seven cell types and five evolution rules was systematically developed,enabling the simulation of both overall uniform corrosion and localized grain boundary dissolution,as well as corrosion channel propagation in the FZ under acidic conditions.By employing neural network based parameter fitting,the model accurately captures the IGC depth evolution and the expansion characteristics of corrosion channels,thereby reproducing the local damage morphologies of the FZ after immersion corrosion.This study provides theoretical support for corrosion-resistant design of high-strength aluminum alloy welded joints and holds significant engineering value in enhancing the service life of aluminum components. 展开更多
关键词 Intergranular corrosion Cellular automata Simulation model Al-Cu-Li alloy
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Cellular Senescence in the Cardiovascular System:Molecular Mechanisms,Pathophysiology,and Senotherapeutic Interventions 认领 引用
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作者 Beata Franczyk Anna Bajer +10 位作者 Anna Bulicz Mikołaj Grabarczyk Paulina Jakubowska Katarzyna Krawiranda Natalia Kustosik Przemysław Kuzar Klaudia Leszto Maja Mejza Weronika Mstowska Jacek Rysz Ewelina Młynarska 《BIOCELL》 SCIE 2026年第7期1-40,共40页
Cellular senescence and the Senescence-Associated Secretory Phenotype(SASP)play both physiological and pathological roles in the cardiovascular system.While transient senescence aids regeneration,chronic accumulation ... Cellular senescence and the Senescence-Associated Secretory Phenotype(SASP)play both physiological and pathological roles in the cardiovascular system.While transient senescence aids regeneration,chronic accumulation of senescent cells promotes endothelial dysfunction,arterial stiffening,and maladaptive cardiac remodeling.This review elucidates the pivotal role of the immune system in senescent cell clearance and explores how immunosenescence drives systemic low-grade inflammation.Significant emphasis is placed on emerging pharmacological strategies,specifically senolytics and senomorphics,assessing their capacity to restore cardiac function and attenuate atherosclerosis.Additionally,the utility of molecular biomarkers and diverse in vitro and in vivo models is analyzed in the context of therapeutic efficacy.Ultimately,this article asserts that a comprehensive understanding of senescent-immune interactions is fundamental to the development of targeted,personalized interventions for age-related cardiovascular pathologies. 展开更多
关键词 Cellular senescence cardiovascular aging senolytics senomorphics cardiovascular system heart failure atherosclerosis endothelial dysfunction
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Optimal beamwidth design of periodic reference signals for integrated sensing and communications in cellular V2X networks 认领 引用
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作者 Chunlei Sun Xuqing Liu +3 位作者 Linpei Li Yuzheng Ren Dongzhe Li Haijun Zhang 《Digital Communications and Networks》 SCIE EI CSCD 2026年第3期550-559,共10页
Recently,the technique of Integrated Sensing and Communication(ISAC)has gained great attentions and is expected to enable more advanced applications in cellular Vehicle-to-Everything(V2X).We intend to use the periodic... Recently,the technique of Integrated Sensing and Communication(ISAC)has gained great attentions and is expected to enable more advanced applications in cellular Vehicle-to-Everything(V2X).We intend to use the periodical reference signals,such as the synchronization signals in 5G,to actively detect targets at different azimuths via beam scanning.This paper mainly aims to optimize the beamwidth of these reference signals in cellular-V2X to facilitate both sensing and communication functions.Firstly,to address the issue of insufficient beam duration for accurate estimation of Doppler and the corresponding velocity as well,we combine multi-ple beam scanning cycles to support improved sensing performance.In this context,an innovative beamwidth optimization algorithm is proposed.Specifically,we deduce the Fisher Information Matrix(FIM)of the suffi-cient statistic associated with target azimuths.Considering the randomness of the target position,we build the objective function based on the expected trace of the derived FIM.Additionally,we formulate the constraint of channel coherent time for efficient communications.It is worth noting that this is the first time to optimize the beamwidth of periodic reference signals for joint communication and sensing in cellular V2X.Experimental results show that the optimal beamwidth varies with the steering azimuth of antennas and reaches its maximum when the beam points at the direction perpendicular to the roadside. 展开更多
关键词 Integrated sensing and communications Cellular V2X Periodic reference signals Beamwidth optimization 5G
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β-Galactosidase Based Molecular Imaging for Visualization of Cellular Senescence 认领 引用
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作者 Jiani Huang Peili Cen +1 位作者 Hong Zhang Yan Zhong 《iRADIOLOGY》 CSCD 2026年第1期63-65,共3页
Cellular senescence is a distinct and irreversible biological process characterized by cell cycle arrest.It can be triggered by various stressors,including DNA damage,oxidative stress,telomere dysfunction,oncogenic ac... Cellular senescence is a distinct and irreversible biological process characterized by cell cycle arrest.It can be triggered by various stressors,including DNA damage,oxidative stress,telomere dysfunction,oncogenic activation,or extensive replication as well as by physiological stimuli such as developmental and repair signals[1]. 展开更多
关键词 cellular senescence molecular imaging senescence-associatedβ-galactosidase
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Constructing Tumor Cellular Cluster Models and Their Evolutionary Dynamics to Decode Tumor Evolution 认领 引用
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作者 Haili Qian Fei Ma 《Cancer Innovation》 CSCD 2026年第3期20-22,共3页
Tumor research has undergone a transition from a cancer cell-centered paradigm to a systematic evolutionary perspective.Can-cer is a highly complex disease,and tumor initiation and pro-gression have traditionally been... Tumor research has undergone a transition from a cancer cell-centered paradigm to a systematic evolutionary perspective.Can-cer is a highly complex disease,and tumor initiation and pro-gression have traditionally been interpreted primarily through genetic and molecular alterations within tumor cells.However,with the emergence of systems biology,this"cancer cell-centered"view has gradually evolved into a"systems evolutionary perspec-tive."The most recent theoretical framework in oncology em-phasizes that tumors are dynamic systems comprising multiple cell types and their interactions,highlighting that their evolution reflects system-level remodeling driven by multidimensional sig-naling networks[1].Within this framework,tumor cells,immune cells,stromal cells,and vascular-associated cells form highly in-terconnected regulatory networks through molecular interactions and cell-cell communication.These networks collectively shape tumor initiation,progression,and therapeutic response.Conse-quently,approaches focusing solely on single molecules or indi-vidual cells are unable to sufficiently account for the complexity and dynamic behavior of tumors. 展开更多
关键词 evolutionary dynamics systems biologythiscancer tumor evolution asystems evolutionary theoretical framework tumor cellular cluster models systematic evolutionary perspectivecan cer systems biology
Cellular homeostatic boundaries:The planetary boundaries of the cell 认领 引用
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作者 Qing-Hua Wu Jun-Yao Li 《Life Research》 2026年第3期78-80,共3页
In the intricate tapestry of life,the cell stands as the fundamental unit,orchestrating its survival and functionality through a symphony of meticulously regulated biochemical processes.However,just as the Earth’s ec... In the intricate tapestry of life,the cell stands as the fundamental unit,orchestrating its survival and functionality through a symphony of meticulously regulated biochemical processes.However,just as the Earth’s ecosystem has a carrying capacity,cells also face their own“survival limits”in maintaining normal function.Although the concept has not yet been clearly articulated by researchers,the survival limit of a cell implies the threshold of extreme conditions or parameters that a cell can withstand in order to maintain normal function and survival.These conditions include,but are not limited to,extreme ranges of key parameters such as energy metabolism,redox balance,molecular crowding,and signaling.Breaching these limits may lead to cellular dysfunction,senescence or even death. 展开更多
关键词 cellular homeostatic boundaries signaling planetary boundaries cell survival limits biochemical processes molecular crowding redox balance survival limit
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Letter to the Editor:Mesenchymal stromal cell-derived extracellular vesicles as a promising therapeutic candidate for attenuating cellular senescence 认领 引用
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作者 Wei Zhang Jing-Long Luo +1 位作者 Li Xiao Jian-Guang Zhang 《World Journal of Stem Cells》 SCIE 2026年第6期182-185,共4页
Cellular senescence,characterized by an irreversible growth arrest,plays a pivotal role in aging and age-related pathologies.The study published in the World Journal of Stem Cells by Yang et al investigated the therap... Cellular senescence,characterized by an irreversible growth arrest,plays a pivotal role in aging and age-related pathologies.The study published in the World Journal of Stem Cells by Yang et al investigated the therapeutic potential of mesenchymal stromal cell-derived extracellular vesicles(MSC-EVs)in mitigating cellular senescence,providing comprehensive evidence from both in vitro and in vivo experiments.A clinical-grade production process for MSC-EVs was established,along with defined release criteria for human application.Functional assays revealed that MSC-EVs significantly reduced senescence-associated markers,includingβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1β,while enhancing collagen I expression in aged human dermal fibroblasts.In a D-gal-induced aging mouse model,MSC-EVs ameliorated histopathological alterations,oxidative stress,and aging-related gene expression.Collectively,these findings underscore MSC-EVs as a promising anti-aging therapeutic strategy.Future research should focus on identifying the critical quality attributes of anti-senescent MSC-EVs and validating their efficacy in large animal models and clinical trials. 展开更多
关键词 Mesenchymal stromal cells Extracellular vesicles Exosomes Cellular senescence Aging
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Real-time visualization of drug-target interactions in native subcellular microenvironments for lysosome-targeted drug discovery 认领 引用 被引量：1
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作者 Ran Wang Yatong Yuan +9 位作者 Huarong Shao Yuehao Sun Changcheng Lai Mengrui Zhang Wenjing Song Tao Zhang Fengfeng Zhuang Qixin Chen Peixue Ling Xintian Shao 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2026年第2期544-553,共10页
Conventional ex vivo drug screening platforms struggle to recapitulate native subcellular microenvironments,leading to high off-target rates and compromised discovery of bioactive compounds.To address this,we develope... Conventional ex vivo drug screening platforms struggle to recapitulate native subcellular microenvironments,leading to high off-target rates and compromised discovery of bioactive compounds.To address this,we developed subcellular target-tracking fluorescent-visualization-based interaction screening(SubTrack-FVIS),a platform combining super-resolution imaging with target-specific fluorescent tagging.SubTrack-FVIS first maps nanoscale spatial distributions of drug targets within living cells,then screens compound libraries to identify molecules specifically binding to target-enriched domains,and finally quantifies drug-target interactions through super-resolution imaging tracking.Compared to traditional toolbox,SubTrack-FVIS reduces off-target effects by evaluating compound binding within native subcellular architectures.When applied to the lysosomal vacuolar H+-ATPases(V-ATPase)subunit,ATP6V1A,a validated anti-cancer target,this approach identified for lysosomal alkalization fluorescent drug(LAFD)as a potent inhibitor.Super-resolution imaging revealed LAFD's dynamic binding to ATP6V1A clusters,enabling real-time visualization of V-ATPase inhibition and subsequent lysosomal destabilization.Crucially,SubTrack-FVIS uncovered LAFD's unique mechanism of blocking autophagosome-lysosome fusion,resolving autophagic flux obstruction at sub-100 nm resolution.This platform establishes a visualization framework for discovering drugs within physiological subcellular contexts while simultaneously decoding their mechanistic impacts,offering application potential for target-centric drug development. 展开更多
关键词 Drug screening Cellular imaging Fluorescence labeling Lysosomal V-ATPase
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Integrating bulk and single-cell sequencing reveals cellular heterogeneity between lung adenocarcinoma in smokers and never-smokers 认领 引用 被引量：1
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作者 Zihuan Zhao Pan Yang +10 位作者 Yuhan Liu Kai Wang Xianfeng Xu Yuzhuo Wang Meng Zhu Na Qin Cheng Wang Weimin Li Hongxia Ma Zhoufeng Wang Hongbing Shen 《Journal of Biomedical Research》 CAS CSCD 2026年第3期247-265,共19页
Lung cancer in smokers(LCIS)and lung cancer in never-smokers(LCINS)are different entities with distinct molecular features.However,their cellular heterogeneity still requires further investigation.Through an integrate... Lung cancer in smokers(LCIS)and lung cancer in never-smokers(LCINS)are different entities with distinct molecular features.However,their cellular heterogeneity still requires further investigation.Through an integrated analysis of single-cell RNA sequencing and bulk sequencing data,we identified cell subpopulations associated with smoking and non-smoking patients.Subsequent transcriptomic analyses were performed to elucidate differences in cellular functions and the tumor microenvironment.We observed that smoking-associated cancer cells exhibited a higher degree of aggressiveness,which may correlate with an adverse prognosis in smoking patients.Additionally,immunosuppressive CXCL10+macrophages may contribute to tumorigenesis in smokers,and the immunoregulatory LGALS9-HAVCR2 axis could be a potential immunotherapeutic target.In nonsmokers,the inflammatory microenvironment may be involved in tumor development.Moreover,the reduced anti-tumor cytotoxicity may be associated with their suboptimal immunotherapeutic response.Our study uncovered differences in oncogenic and immune escape mechanisms between LCIS and LCINS patients and suggests potential immunotherapeutic strategies. 展开更多
关键词 lung cancer in smokers lung cancer in never-smokers single-cell RNA sequencing cellular heterogeneity
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Constructing porosity database for Al-Si alloy castings through 3D cellular automata model and machine learning 认领 引用
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作者 Qing-huai HOU Xue-long WU +10 位作者 De-cai KONG Hai-bo QIAO Xiao-ying MA Xiang CI Wen-bo WANG Yu-ling LANG Shi-wen XU Zhong-yao LI Yi-sheng MIAO Xing-xing LI Jun-sheng WANG 《Transactions of Nonferrous Metals Society of China》 SCIE EI CAS CSCD 2026年第6期1712-1728,共17页
A coupled three-dimensional cellular automata(CA)model has been used to predict the hydrogen porosity in an Al-Si alloy as a function of thermal boundary conditions.By quantifying the porosity distribution from simula... A coupled three-dimensional cellular automata(CA)model has been used to predict the hydrogen porosity in an Al-Si alloy as a function of thermal boundary conditions.By quantifying the porosity distribution from simulations,a porosity defect database was established,representing a cooling rate ranging from 0.25 to 50℃/s at an initial hydrogen content of 3.0×10-3 mL/g.Based on the database,four machine learning algorithms including support vector machine(SVM),random forest(RF),K-nearest neighbors(KNN),and gradient boosting machine(GBM)were trained and compared for each porosity characteristic to identify the optimal model.For the prediction of porosity percentage,the determination coefficient(R2)and the root mean square error(RMSE)on the test set reached 0.95 and 0.042,respectively.The predicted porosity distribution agreed well with experiments,indicating that the model can be used to map the porosity size in large casting components. 展开更多
关键词 Al-Si alloy porosity casting cellular automata machine learning database
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A data-driven integrated optimization method of macroscopic topology and microscopic configuration for the graded functional cellular structures 认领 引用
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作者 Yu Guo Yijie Lu +2 位作者 Zhengwei Zhang Yanguo Zhou Hui Liu 《Acta Mechanica Sinica》 SCIE EI CAS CSCD 2026年第2期473-495,共23页
In the topology optimization of the multiscale structure,how to ensure the connectivity between adjacent microstructures,how to control the design space of microstructures,and how to reduce the amount of calculation a... In the topology optimization of the multiscale structure,how to ensure the connectivity between adjacent microstructures,how to control the design space of microstructures,and how to reduce the amount of calculation and improve calculation efficiency are three basic challenging issues currently faced.To this end,this paper proposes a data-driven approach to achieve the integrated optimization of macroscopic topology and microscopic configuration of the graded functional cellular structures.At the macro level,a topological description function is introduced to realize the topological control of the macrostructure.At the micro level,several cutting functions are used to realize the control of the configuration and size of the microstructure.The integrated optimization design of macro and micro cellular structures can be realized.Based on the computational homogenization method and numerical integration technology,an optimization problem independent offline microstructure database is established at the microscopic scale,where the relationship between the equivalent elastic parameters,relative pseudo-density,and design variables of the microstructure is stored.Based on this offline database,the entire topology optimization process is completed only on a macro scale,which greatly reduces the amount of calculation and improves calculation efficiency.In addition,implicit geometric modeling of full-scale cellular structures can be achieved using the reconstruction technique introduced in this work,which ensures smooth connection between adjacent microstructures.Finally,numerical examples are used to verify the effectiveness of the algorithm and the superiority of gradient cellular structures compared with single-scale structures. 展开更多
关键词 Graded cellular structure Integrated optimization Data-driven Computational homogenization M-VCUT Level set method
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Advanced drug delivery platforms targeting cellular senescence:A promising strategy for cancer therapy 认领 引用
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作者 Xue Zhang Lingxiao Yang +5 位作者 Xiaopeng He Min Zhao Zaixiang Fang Gang Xu Zhenyu Duan Kui Luo 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2026年第6期3473-3505,共33页
Cellular senescence is a state of cell cycle arrest caused by various types of stress,and it is characterized by morphological changes,metabolic reprogramming,and the release of the senescence-associated secretory phe... Cellular senescence is a state of cell cycle arrest caused by various types of stress,and it is characterized by morphological changes,metabolic reprogramming,and the release of the senescence-associated secretory phenotype(SASP).In cancer therapy,senescence plays a complex role by inhibiting cancer progression,mediating metabolic imbalance,modulating local immune responses,and restructuring the cancer microenvironment.These mechanisms have been harnessed to develop nano-drug delivery systems(Nano-DDSs)-based combination therapies for cancer.We systematically explain key biological features of cellular senescence and detail recent advances in creating drug delivery systems aimed at targeting cancer senescence through these four mechanisms.Additionally,we discuss the clinical challenges in translating senescence-targeting strategies with Nano-DDSs and propose future directions within an interdisciplinary framework.This review offers valuable insights into designing advanced Nano-DDSs based on the multidimensional regulatory mechanisms of cellular senescence and their application in cancer treatment. 展开更多
关键词 Cellular senescence Cancer therapy Drug delivery systems Senescence-associated secretory phenotype Nanoplatforms Tumor microenvironment Senotherapy Senolytics
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Insights into microstructural variations in GH4169 thin-walled parts by laser powder bed fusion:a coupling finite-element/cellular-automaton study 认领 引用
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作者 Peng-Hang Ling Wu-Gui Jiang +3 位作者 Zhan-Cai Zhan Tao Chen Qing-Hua Qin Long-Hui Mao 《Acta Mechanica Sinica》 SCIE EI CAS CSCD 2026年第7期188-204,共17页
The complex characteristics of thin-walled parts fabricated by laser powder bed fusion(LPBF),particularly the dependence of their microstructures on wall thickness and scanning strategies,pose significant challenges f... The complex characteristics of thin-walled parts fabricated by laser powder bed fusion(LPBF),particularly the dependence of their microstructures on wall thickness and scanning strategies,pose significant challenges for this technology.This paper presents a predictive model for microstructural evolution of LPBF-fabricated thin-walled components,integrating three-dimensional cellular automaton(CA)with finite element(FE)analysis.The FE method is employed to solve the temperature field of thin-walled components during LPBF,and the resulting temperature history is used to predict micro-structural evolution in the CA model.Experimental validation via electron back scatter diffraction(EBSD)on a 4 mm-thick specimen confirms a high degree of agreement between model predictions and experimental results.The study reveals that when the thickness of samples prepared by LPBF is reduced from 4 mm to 0.4 mm,there is a significant coarsening of grain size.Additionally,grains at the bottom are observed to be coarser compared to those at the top,which is attributed to epitaxial growth and remelting.Furthermore,the study explores microstructural changes induced by manipulating laser power and scanning speed,while maintaining constant energy density.The findings indicate that grain morphology and size remain consistent across varying parameters,emphasizing the dominant influence of energy density.Within a predefined scanning strategy,an upsurge in laser energy density leads to an enlargement of the average grain size.Notably,the implementation of a cross-scanning strategy alters the melt pool orientation,disrupting the directional grain growth and fostering the formation of finer grains.This underscores the crucial significance of processing techniques in LPBF. 展开更多
关键词 Laser powder bed fusion Thin-walled components Cellular automaton Finite element Microstructural evolution
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