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Break the vicious cycle and remodel the malignant inflammatory microenvironment in ARDS with efferocytosis-informed nanodrugs 认领 引用
1
作者 Yikun Chen Wenling Li +8 位作者 Juan Cao Yongjun Wang Yufang Guo Liu Qing Li Wang Sisi Yu Lei Xing Hulin Jiang Bing Wan 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第7期583-590,共8页
Acute respiratory distress syndrome(ARDS)is one of the diseases with a significant mortality rate due to respiratory failure.Yet,malignant microenvironment(MM)composed mainly of inflammatory cytokines(IC)and reactive ... Acute respiratory distress syndrome(ARDS)is one of the diseases with a significant mortality rate due to respiratory failure.Yet,malignant microenvironment(MM)composed mainly of inflammatory cytokines(IC)and reactive oxygen species(ROS)limit the therapeutic effect.Herein we construct the nanoparticles(NPs)BSA-MnO2@Tan-ⅡA/PSLs(BMTPLs)to disrupt the vicious cycle between IC and ROS by suppressing IC production and scavenging ROS,which effectively remodels the MM of ARDS.The BMTPLs composed of the water-dispersible BSA-MnO2(BM)and phosphatidylserine(PS)-consisting lipid shell containing lipophilic tanshinoneⅡA(Tan-ⅡA).After phagocytosed by activated macrophages(M1)in an efferocytosis-like manner originating from the PS effect,the released Tan-ⅡA inhibit NF-κB pathway and further suppresses the secretion of IC.Concurrently,BM scavenging ROS alleviates the oxidative stress microenvironment,which deeply enhances the anti-inflammation effect of Tan-ⅡA.Moreover,the low-level ROS and down-regulation IC promote the transformation from pro-inflammatory M1 to anti-inflammatory M2 contributing to restoring tissue homeostasis.The results in vitro and in vivo indicate that the MM of ARDS can be effectively remodeled by BMTPLs,which holds great potential for ARDS treatment. 展开更多
关键词 ARDS Vicious cycle Malignant microenvironment Inflammation Efferocytosis Tan-IIA
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Tumor Microenvironment-responsive Self-immolative Polymers for Cancer Imaging and Therapy 认领 引用
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作者 Ihsan Ullah Wen-Jun Yang +2 位作者 Ye Liu Ci-Long Chu Youyong Yuan 《Chinese Journal of Polymer Science》 SCIE EI CAS CSCD 2026年第7期2112-2135,共24页
Self-immolative polymers(SIPs)have recently emerged as a distinct class of stimuli-responsive materials that undergo programmed domino-like degradation in response to specific biochemical triggers.The unique biochemic... Self-immolative polymers(SIPs)have recently emerged as a distinct class of stimuli-responsive materials that undergo programmed domino-like degradation in response to specific biochemical triggers.The unique biochemical characteristics of the tumor microenvironment(TME)include acidic pH,elevated glutathione(GSH)levels,excessive reactive oxygen species(ROS),dysregulated enzymes,and hypoxia.TMEresponsive SIPs have attracted significant attention for precise cancer imaging and therapy.By integrating labile linkages and modular structural design,these polymers can amplify weak biochemical signals into robust responses,enabling controlled drug release,signal amplification in imaging,and multifunctional theranostics.Compared with conventional responsive systems,SIP-based nanoplatforms offer enhanced sensitivity,tunable degradation kinetics,and the potential for sequential or cascade activation.In this review,we provide a comprehensive overview of the design principles,activation mechanisms,and functional applications of TME-responsive SIPs.We highlight representative strategies for their use in targeted drug delivery,tumor imaging,and synergistic therapeutic approaches and discuss the incorporation of emerging modalities such as near-infrared II(NIR-II)imaging and combination immunotherapy.Finally,we outline the major challenges and opportunities for advancing SIP-based nanomedicines for clinical translation and offer perspectives on how this rapidly evolving field may reshape the future of precision cancer diagnosis and treatment. 展开更多
关键词 Tumor microenvironment Self-immolative polymers Stimuli-responsive polymers Drug delivery systems Theranostics Cancer therapy
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In situ carrier-free nanovaccines reversing the immunosuppressive microenvironment for boosting tumor immunotherapy 认领 引用
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作者 Yilei Zhao Guoxin Zhu +7 位作者 Xuechun Wang Zilin Ma Jie Yan Songyan Li Wen Zhao Qingbin He Jianwei Jiao Guiqiang Zhang 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第2期325-330,共6页
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(Al3+),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
关键词 In situ vaccines Immunosuppressive microenvironment Self-assembly Photothermal therapy Macrophage polarization
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Pulsed Dynamic Water Electrolysis:Mass Transfer Enhancement,Microenvironment Regulation,and Hydrogen Production Optimization 认领 引用
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作者 Xuewei Zhang Wei Zhou +7 位作者 Xiaoxiao Meng Yuming Huang Yang Yu Haiqian Zhao Lijie Wang Fei Sun Jihui Gao Guangbo Zhao 《Nano-Micro Letters》 SCIE EI CAS CSCD 2026年第3期807-859,共53页
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
关键词 Pulsed dynamic electrolysis Water electrolysis Energy and mass transfer Microenvironment System stability
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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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Exercise suppresses breast cancer and reprograms the immune tumor microenvironment,cancer cell intrinsic features,and their interaction 认领 引用
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作者 Graeme J.Koelwyn Sayyed Hamed Shahoei +11 位作者 Courtenay Graham Geoffrey M.Nonis Milad Vahedi Puneet Sidhu Emily J.Brown Alireza Khodadadi-Jamayran Juan Liu Elisa De Stanchina Kathryn J.Moore Jason W.Locasale Erik R.Nelson Lee W.Jones 《Journal of Sport and Health Science》 SCIE CAS CSCD 2026年第6期38-48,F0003,共11页
Background:Exercise links with improved cancer outcomes following a diagnosis of primary breast cancer but experimental evidence and molecular mechanistic interrogation from preclinical studies are limited.The purpose... Background:Exercise links with improved cancer outcomes following a diagnosis of primary breast cancer but experimental evidence and molecular mechanistic interrogation from preclinical studies are limited.The purpose of this study was to evaluate the effects,and dose-response,of exercise in mouse models of breast cancer,as well as elucidate cancer cell extrinsic and intrinsic responses.Methods:Independent in vivo modeling was used to investigate the effects of exercise across distinct breast cancer models.Unbiased transcriptomic and metabolomic analyses,alongside cellular and proteomic interrogation,were used to determine tumor microenvironment(TME)-and cancer cell-specific effects.Results:Exercise inhibited breast cancer growth and metastasis across multiple syngeneic mouse models compared to sham control.Tumor growth inhibition was independent of estrogen receptor status,and in the 4T1 model,exercise exerted non-dose-dependent effects.In the Metl model,exercise decreased TME immune cell content,particularly tumor-associated macrophages,while promoting an activated anticancer innate immune cell gene signature.Concurrent in vivo cancer cell-intrinsic effects were characterized by broad transcriptomic reprogramming including downregulation of metabolic pathways and upregulation of pathways regulating proliferation and apoptosis.Whole tumor metabolomic analyses unveiled broad shifts including decreased nicotinamide adenine dinucleotide(NAD+)and lactate,as well as availability of biosynthetic precursors.Finally,in silico analyses identified TME ligands,such as High Mobility Group Box 2(HMGB2)and Cardiotrophin-1(CTF1)as candidate drivers of downstream gene expression changes in cancer cells.Conclusion:Exercise suppresses breast cancer progression,which occurs in conjunction with broad reprogramming of immune TME-cancer processes and their interaction. 展开更多
关键词 Exercise Breast cancer Tumor microenvironment Cancer cell phenotypes
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Applying microfluidic technology to interpret the tumor immune microenvironment and cancer immunotherapy 认领 引用
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作者 Xuhong Chen Dongxian Tan +5 位作者 Shuaiting Liu Ruolin Luo Yang Liu Miaomiao Zhang Siqi Li Jing Xu 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第2期169-185,共17页
In the past decade,cancer immunotherapy has emerged as a transformative treatment modality for diverse malignancies.Although impressive clinical efficacy has been demonstrated in some cancer patients,most patients res... In the past decade,cancer immunotherapy has emerged as a transformative treatment modality for diverse malignancies.Although impressive clinical efficacy has been demonstrated in some cancer patients,most patients respond poorly to immunotherapies.The complicated architecture and cellular composition of the tumor immune microenvironment(TIME)have substantial roles in the clinical outcomes of immunotherapies.Therefore,employing optimal in vitro models recapitulating the in vivo TIME characteristics is particularly important for interpreting the dynamic complexity of the TIME,evaluating drug efficacy,and developing novel immunotherapeutics.In recent years,microfluidic technology has been shown to be a valuable tool for mimicking dynamic crosstalk among the TIME in vitro through the manipulation of microscale fluids in an integrated device.Cellular behaviors,function and signal transduction,and tumor-immune interactions can be monitored in real time and analyzed in microfluidic chips by combining visualization technologies.Numerous recent studies have shown how to design and fabricate microfluidic chips for reproducing the complex three-dimensional architecture and dynamic changes in the TIME.This review comprehensively examines the application of innovative microfluidic technology in the field of cancer immunology research,focusing on interpreting dynamic crosstalk inside the TIME from bulk-cell to single-cell analyses,evaluating the efficacy of novel immunotherapies and preparing immunotherapeutic agents,and analyzes current limitations.This work aimed to propose a translational roadmap for leveraging microfluidics in elucidating mechanisms,biomarker discovery,high-throughput drug screening,and personalized immunotherapy development. 展开更多
关键词 Microfluidic chip tumor immune microenvironment immunotherapy cell‒cell interactions cancer immunology
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SARS-CoV-2 infection in brain tumors and the association with alterations in the tumor immune microenvironment 认领 引用
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作者 Weikang Chen Haojie Bai +9 位作者 Maoling Tian Yanxia Huang Depei Li Luyao Wu Wei Li Lei Zhou Wange Lu Xiaoxing Li Linyi Liu Xiaobing Jiang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第5期769-784,共16页
Objective:Recent clinical evidence indicates that persistent reservoirs of SARS-CoV-2 in human brain tissue are associated with various neurologic symptoms.While brain tumors have unique vascular abnormalities and imm... Objective:Recent clinical evidence indicates that persistent reservoirs of SARS-CoV-2 in human brain tissue are associated with various neurologic symptoms.While brain tumors have unique vascular abnormalities and immunosuppressive environments,it is unclear whether SARS-CoV-2 can infect brain tumors.Methods:Brain tumor samples were collected from a cohort of 72 COVID-19 patients during the SARS-CoV-2 BA.5 wave in Guangzhou.SARS-CoV-2 infection was confirmed by quantitative reverse-transcription polymerase chain reaction(qRT-PCR)and immunohistochemical(IHC)staining.Immune cell infiltration within the tumor tissues was assessed using IHC.RNA-sequencing was performed to investigate virus-host interactions in the brain tumors.Results:Brain tumor samples from 72 COVID-19 patients were examined and SARS-CoV-2 RNA was detected in 11%of the samples,which included samples from craniopharyngiomas,pituitary neuroendocrine tumors(PitNETs),meningiomas,and gliomas.SARS-CoV-2 infection was present in tumor and endothelial cells within these brain tumors.SARS-CoV-2-positive tumors had greater immune cell infiltration,particularly an increase in CD8+T cells in gliomas and pituitary PitNETs,along with the activation of innate signaling pathways.The transcriptomic analysis revealed that activation of the complement cascade within tumors may drive changes in the immune microenvironment of SARS-CoV-2-positive tumors.Conclusions:These findings provided evidence of SARS-CoV-2 infection in brain tumors and suggested a role in altering the tumor immunosuppressive microenvironment. 展开更多
关键词 SARS-CoV-2 brain tumors immune microenvironment innate immune complement activation
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Cancer cell membrane-biomimetic metallacycles for tumor microenvironment-responsive ferroptosis/apoptosis therapy with low systemic toxicity 认领 引用
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作者 Shao-Qi Guan Chen-Hui Liu +3 位作者 Ya-Ping Wang Xiao-Dong Zhang Zhong-Min Cao Mei Pan 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第7期564-571,共8页
Ferroptosis,a form of programmed cell death driven by iron-dependent lipid peroxidation(LPO),has emerged as a promising therapeutic strategy for cancer.However,challenges such as uncontrolled iron delivery,insufficien... Ferroptosis,a form of programmed cell death driven by iron-dependent lipid peroxidation(LPO),has emerged as a promising therapeutic strategy for cancer.However,challenges such as uncontrolled iron delivery,insufficient ferroptosis induction efficiency,and off-target drug leakage limit its applications.To address these limitations,we developed a biomimetic nanoplatform(Fe-DTX@M)integrating cancer cell membrane-camouflaged Fe-based metallacycles with the chemotherapeutic drug docetaxel(DTX),which synergistically amplifies ferroptosis and apoptosis for precise and effective cervical cancer therapy.The membrane camouflage enabled highly efficient tumor-specific accumulation,achieving a 5.4-fold increase compared to non-targeted controls,and reduced systemic toxicity.Within tumors,Fe2+/Fe3+cycles attributed to Fe-based metallacycle drove Fenton reactions to convert H2O2 into·OH,inducing LPO,while Fe3+-mediated glutathione depletion inhibited GPX4,amplifying ferroptosis with 2.4-fold malondialdehyde(MDA)increase.Acid-triggered DTX release of nanoplatform further promoted apoptosis,thereby enhancing therapeutic efficacy.Furthermore,Fe-DTX@M exhibited excellent long-term biocompatibility and safety in normal mice over 30 days post-intravenous injection.This combination of biomimetic metallacycles-induced ferroptosis and chemotherapy-induced apoptosis may provide a new paradigm for achieving effective cancer therapy. 展开更多
关键词 Metallacycles Cancer cell membrane Homologous targeting Ferroptosis Tumor microenvironment
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Microenvironment accessibility enables rare oxidation type of triterpenoids by plant P450 认领 引用
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作者 Wentao Sun Lin Xiang +4 位作者 Runming Wang Meilan Huang Bo Lv Youcai Hu Chun Li 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第2期297-302,共6页
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
关键词 Microenvironment accessibility P450 Triterpenoid Enzyme engineering Remote oxidation
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Cationic covalent framework microenvironment steering CuPt alloy toward record-breaking photoelectrochemical ethane synthesis from CO2 认领 引用
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作者 Fentahun Wondu Dagnaw Karim Harrath +9 位作者 Tao Zheng Yu-Ze Liu Huiwen Xue Wei Li Ze-Yu Zhang Zhen Li Xu-Bing Li Huaping Wang Qing-Xiao Tong Jing-Xin Jian 《Journal of Energy Chemistry》 SCIE EI CAS CSCD 2026年第1期339-349,I0009,共11页
Photoelectrochemical CO2reduction 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 CO2reduction 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 CO2enrichment from proton exclusion,the COF+/CuPt interface simultaneously facilitates CO2accessibility 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 CO2reduction 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 CO2conversion into value-added hydrocarbons. 展开更多
关键词 Photoelectrochemical CO2reduction COFs Reaction microenvironment C2product
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Modulation of the regenerative microenvironment within acellular nerve allografts using tacrolimus improves nerve regeneration 认领 引用
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作者 Jesús A.Acevedo Cintrón Jonathon Blake Schofield +5 位作者 Daniel A.Hunter Pranay Singh Alexa M.Negrón Morales Lauren Schellhardt Susan E.Mackinnon Matthew D.Wood 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第10期4978-4988,共11页
Acellular nerve allografts have been used as an alternative to reconstruct nerve gaps.However,regeneration and recovery using long acellular nerve allografts(>3 cm)is poor in comparison to short acellular nerve all... Acellular nerve allografts have been used as an alternative to reconstruct nerve gaps.However,regeneration and recovery using long acellular nerve allografts(>3 cm)is poor in comparison to short acellular nerve allografts(<3 cm).To understand why long acellular nerve allografts have limited regeneration,we focused on identifying differences in the microenvironment of short(2 cm)and long(4 cm)acellular nerve allografts by comparing the transcriptional profile of these acellular nerve allografts.After repairing the sciatic nerve of Lewis rats using either short or long acellular nerve allografts,we found that the proximal and mid-distal graft regions of long acellular nerve allografts are characterized by an upregulation of metabolic and immune pathways and downregulation of regenerative processes in comparison to the short acellular nerve allografts.Based on these results,we modulated the regenerative and immune microenvironment of long acellular nerve allografts using tacrolimus(FK506).Histomorphometric and muscle force analysis revealed that FK506 increases the number of axons and improves recovery of motor function across long acellular nerve allografts.Transcriptome analysis of the mid-distal graft region of long acellular nerve allografts from animals treated with FK506 revealed upregulation of regenerative pathways and downregulation of immune processes,specifically related to T cell activity.Additionally,FK506 altered the number of macrophages and Schwann cells in the long acellular nerve allografts.From the transcriptome analysis,we identified FK506 upregulates expression of Spp1(osteopontin)which promotes regeneration of motor neurons after injury.Experiments on cultured Schwann cells revealed that FK506 increases m RNA expression of Spp1.Our data show the development of a degenerative and immune microenvironment within long acellular nerve allografts and demonstrate that FK506 can modulate this microenvironment to improve nerve regeneration across these long acellular nerve allografts. 展开更多
关键词 acellular nerve allograft immunosuppression macrophages microenvironment nerve gap osteopontin(SPP1) peripheral nerve regeneration Schwann cells tacrolimus(FK506) transcriptome analysis
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An integrated cartilage-on-a-chip recapitulating the bio-chemo-mechanical microenvironment in osteoarthritic joints 认领 引用
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作者 Hongxing Jia Shaohua Yang +7 位作者 Lamei Du Han Gao Kaiqiang Sun Fanrui Kong Tan Tang Qiuting Zhang Tujun Weng Ye Xu 《Bio-Design and Manufacturing》 SCIE EI CAS CSCD 2026年第2期357-378,I0069-I0077,共22页
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
关键词 Osteoarthritis(OA) Bio-chemo-mechanical coupled microenvironment Cartilage-on-a-chip Mechanical stimulation Intercellular communications
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Coordinated DNA methyltransferase 3A and methyltransferase-like 7A activity reprograms the tumor microenvironment through discoidin domain receptor 1 signaling 认领 引用
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作者 Zhengyang Bai Dan Yang +3 位作者 Jiayi Li Yaobang Liu Bin Lian Jinping Li 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第1期107-132,共26页
Objective:Breast cancer is the most common malignancy in women and is characterized by a high recurrence rate that severely impacts patient survival.Regulatory T cells(Tregs)in the tumor microenvironment(TME)promote i... Objective:Breast cancer is the most common malignancy in women and is characterized by a high recurrence rate that severely impacts patient survival.Regulatory T cells(Tregs)in the tumor microenvironment(TME)promote immune evasion and metastasis,increasing recurrence risk.This study determined how the epigenetic regulators,DNMT3A and METTL7A,modulate Treg infiltration via the DDR1/STAT3/CXCL5 axis and influence breast cancer recurrence and prognosis.Methods:RNA sequencing(RNA-seq)was used to identify differentially expressed genes(DEGs),followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO),supported vector machine-recursive feature elimination(SVM-RFE)and ElasticNet identified DDR1 as a key gene.Validation included RT-qPCR,western blot,MSP,MeRIP-qPCR,and Co-IP to assess epigenetic regulation.Functional assays(CCK-8,Transwell,and Treg differentiation/chemotaxis)and xenograft models evaluated the role of DDR1 in tumor progression and recurrence.Results:DNMT3A upregulated DDR1 via DNA methylation,while METTL7A enhanced DDR1 mRNA stability via m6A modification.Co-regulation activated the DDR1/STAT3/CXCL5 axis,which boosted cancer cell proliferation,migration,and invasion.CXCL5 secretion increased Treg infiltration and accelerated tumor growth in vivo.DDR1 silencing reversed these effects,confirming that DDR1 has a pivotal role in breast cancer recurrence.Conclusion:DNMT3A and METTL7A were shown to cooperatively regulate DDR1 via DNA/m6A methylation,which drives Tregmediated immune suppression and recurrence.This study provided novel insights and therapeutic targets for breast cancer prognosis and treatment. 展开更多
关键词 Tumor microenvironment DNMT3A METTL7A DDR1/STAT3/CXCL5 axis Discoidin domain receptor 1
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Gastric microenvironment and gastric cancer:Interplay of acid,microbiota,and inflammation 认领 引用
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作者 Hao-Cheng Zheng Ting Zhou +1 位作者 Lei Sun Xia Ding 《World Journal of Gastroenterology》 SCIE CAS 2026年第20期13-24,共12页
Gastric cancer arises within a complex and dynamic microenvironment shaped by gastric acid secretion,microbial communities,and chronic inflammation.While Helicobacter pylori(H.pylori)remains the primary etiological fa... Gastric cancer arises within a complex and dynamic microenvironment shaped by gastric acid secretion,microbial communities,and chronic inflammation.While Helicobacter pylori(H.pylori)remains the primary etiological factor,recent studies have highlighted the contribution of non-H.pylori microbiota and their interactions with host factors in the progression of gastric carcinogenesis.This review explores the bidirectional interplay among hypochlorhydria,microbial dysbiosis,and mucosal immune responses,emphasizing how this triad drives the transition from chronic gastritis to metaplasia and malignancy.We detail the ecological and functional properties of key gastric microbial taxa,examine the regulatory roles of acid and parietal cells,and discuss inflammation-mediated epithelial remodeling.In addition,we summarize advances in multi-omics technologies-including 16S rRNA sequencing,metagenomics,spatial transcriptomics,and single-cell RNAseq-that are uncovering new dimensions of host-microbe interactions in the gastric niche.Collectively,these findings expand the classical Correa cascade into a more integrative ecosystem-based model of gastric cancer pathogenesis.While most studies remain preclinical or observational,the emerging insights provide a foundation for future investigations into risk stratification and gastric ecosystemmodulating strategies with potential relevance for prevention,early detection,and adjunctive intervention. 展开更多
关键词 Gastric microenvironment Gastric acid Parietal cells Helicobacter pylori Gastric microbiota
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Role of nanotechnology in modulating the tumor microenvironment to enhance immunotherapy efficacy 认领 引用
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作者 Ayushi Jain Saloni Verma +2 位作者 Alisha Jadhav Sharon John Shalini Gupta 《World Journal of Clinical Oncology》 2026年第1期8-21,共14页
The immunosuppressive tumor microenvironment(TME)of oral squamous cell carcinoma(OSCC)is marked by hypoxia,acidity,and abundant stromal cells,such as cancer-associated fibroblasts,tumor-associated macrophages,and myel... The immunosuppressive tumor microenvironment(TME)of oral squamous cell carcinoma(OSCC)is marked by hypoxia,acidity,and abundant stromal cells,such as cancer-associated fibroblasts,tumor-associated macrophages,and myeloid-derived suppressor cells,along with factors such as tobacco and alcohol exposure,human papillomavirus infection,and microbial imbalance that drive immune evasion and poor immunotherapy responses.This review critically evaluated nanotechnology-driven strategies for reprogramming the OSCC TME,focusing on overcoming immunosuppression,hypoxia,stromal barriers,and OSCC-specific challenges to enhance immunotherapy outcomes.Personalized nanotherapies guided by TME profiling,combination with radiotherapy/chemotherapy,and theranostic nanoparticles show promise despite manufacturingegulatory challenges.Nanotechnology enables transformative TME reprogramming to potentiate OSCC immunotherapy,necessitating interdisciplinary research and clinical validation. 展开更多
关键词 Immunotherapy Oral squamous cell carcinoma Nanomedicine Tumor microenvironment Tumor associated macrophages Hypoxia Nanoparticles
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Acupuncture improves transplanted neural stem cells in dementia mice by modulating hippocampal microenvironment via microRNA-124 mediated Notch and Wnt pathways 认领 引用
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作者 Yu-Jiao Li Xi Chen +9 位作者 Yong-Yin Luo Jun Chang Shu-Zhen Liu Xiao-Qian Shan Jing-Jing Song Nan Hao Xu-He Yan Wei-Li Gao Jian-Wei Liu Lan Zhao 《World Journal of Stem Cells》 SCIE 2026年第3期93-115,共23页
BACKGROUND Neural stem cells(NSCs)transplantation is a promising clinical therapy for Alzheimer’s disease(AD).The Notch and Wnt signaling pathways play important roles in the biological functions of NSCs,and microRNA... BACKGROUND Neural stem cells(NSCs)transplantation is a promising clinical therapy for Alzheimer’s disease(AD).The Notch and Wnt signaling pathways play important roles in the biological functions of NSCs,and microRNA-124(miR-124)regulates these pathways through its regulatory effects.AIM To explore the mechanism of acupuncture in enhancing the function of transplanted NSCs and their therapeutic potential in AD.METHODS This study utilized enzyme-linked immunosorbent assay,western blotting,and real-time fluorescent quantitative polymerase chain reaction,to investigate the effects of acupuncture on the role of miR-124 in regulating the Notch and Wnt signaling pathways,in NSCs transplantation therapy in a mouse model of AD-senescence-accelerated mouse prone 8 mice.An in vitro coculture model of mouse hippocampal brain slices and NSCs was established,and flow cytometry was used to examine the effects of acupuncture on the regulation of cyclin D1,an interactive protein in the Notch and Wnt signaling pathways,and on NSCs proliferation and differentiation.RESULTS Acupuncture significantly improved cognitive impairment in AD mice after NSCs transplantation(P<0.05);inhibited expression of characteristic pathological biomarkers of AD(P<0.05);and upregulated expression of NSCs-specific neuroproliferation and differentiation biomarkers(P<0.05).Upregulation of miR-124 modulated the key target genes Notch homolog 1,hairy and enhancer of split 5,and glycogen synthase kinase 3βin the Notch and Wnt signaling pathways(P<0.05);regulated the Notch and Wnt dual signaling pathways and achieved interaction(P<0.05);promoted NSCs proliferation and differentiation(P<0.05);restored damaged cells;and slowed the progression of AD.CONCLUSION Acupuncture may improve the hippocampal microenvironment by upregulating miR-124 to regulate the Notch and Wnt dual signaling pathways,promote NSCs proliferation and differentiation,facilitate the repair of damaged neurons,integrate neural circuits,restore biological functions,and improve cognitive impairment in AD mice. 展开更多
关键词 Neural stem cells Hippocampal microenvironment Acupuncture MicroRNA-124 Notch signaling pathway Wnt signaling pathway Alzheimer’s disease
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Evolving landscape of the gastric cancer immune microenvironment:From spatial architecture to precision biomarkers 认领 引用
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作者 Zhi-Yuan Yao Li-Jie Ma +1 位作者 Zheng-Xiang Han Gui-Juan Ji 《World Journal of Gastrointestinal Oncology》 SCIE 2026年第6期85-101,共17页
Gastric cancer remains a paradigm of therapeutic recalcitrance,driven by a complex ecosystem where therapeutic efficacy is dictated by the dynamic interplay between genomic instability and the tumor immune microenviro... Gastric cancer remains a paradigm of therapeutic recalcitrance,driven by a complex ecosystem where therapeutic efficacy is dictated by the dynamic interplay between genomic instability and the tumor immune microenvironment.While biomarkers such as programmed death-ligand 1 expression and microsatellite instability currently guide therapeutic decisions,they offer only a static glimpse into a spatially and temporally evolving landscape.In this mini-review,we systematically delineate the co-evolution of spatial architecture,metabolic rewiring,and microbial interactions that orchestrate immune evasion in gastric cancer.We dissect how specific“cellular neighborhoods”–governed by the interplay between myofibroblastic cancer-associated fibroblasts and intratumoral microbiota like Fusobacterium nucleatum–construct physical and biological barriers to T-cell infiltration.Furthermore,we explore“invisible”drivers of resistance,highlighting the synergistic potential of ferroptosis and pyroptosis in reshaping immunogenicity and the emerging role of the neuro-immune axis.Finally,we evaluate the clinical utility of next-generation biomarkers,ranging from tertiary lymphoid structure maturity and circulating tumor DNA molecular kinetics to artificial intelligence-driven“digital twins”.By integrating these multidimensional insights,we propose a strategic framework for precision immunooncology,transitioning from static profiling to holistic ecosystem engineering. 展开更多
关键词 Gastric cancer Biomarkers Tumor immune microenvironment Tertiary lymphoid structures Immune checkpoint inhibitors
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Fabricating engineered tissues with spatially varied microenvironments via embedded 3D printing in a cell-dense suspension 认领 引用
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作者 Min Ye Jie Gao +9 位作者 Zhiyuan Zheng Di Xin Zhe Zhang Shilu Zhu Qingdong Zhang Yang Zhang Liang Xu Shuwei Shen Mingzhai Sun Ronald X Xu 《International Journal of Extreme Manufacturing》 SCIE EI CAS CSCD 2026年第3期595-615,共21页
The long-term goal of bioengineered tissues is to achieve precise cell type distribution,physiological cell density,perfusable vascular channels,and mature functionality.However,fabricating engineered tissue with the ... The long-term goal of bioengineered tissues is to achieve precise cell type distribution,physiological cell density,perfusable vascular channels,and mature functionality.However,fabricating engineered tissue with the microenvironmental features of organs with physiological cell density remains a significant challenge in this field.To address this,several key obstacles must be overcome.First,vascularization is indispensable for engineered tissues;however,disturbances may occur when introducing vascular channels within pre-fabricated tissues.Second,maintaining fabrication precision becomes increasingly difficult during high-cell-density embedded printing.Third,the suspension bath used for embedded printing often fails to provide a suitable growth environment.Herein,we modified the rheological properties of the bioactive hydrogel by incorporating a thixotropic laponite nanoclay(LPN)and demonstrated that an optimized ratio of collagen methacrylate(ColMA)to LPN forms a self-healing suspension bath,which is enhanced by hydrogen bonding interactions and is capable of in situ crosslinking.This printing strategy was generalized as the embedded 3D printing in cell-dense suspension(EPICS).The self-healing properties of the EPICS remain unaffected even when encapsulating a near-physiological cell density of 108 cells·mL-1,and it provides precise control of the printing resolution from 1 mm to 100μm.Compared with the model containing 106 cells·mL-1,the use of EPICS could create a robust hepatic model with mature liver markers and reduced apoptosis gene expression.Moreover,EPICS can efficiently fabricate spatially controlled perfusable channels,thereby mimicking the spatially varied microenvironments of hepatocellular carcinoma,highlighting its broad applications in therapeutics involving tissue and organ constructs. 展开更多
关键词 embedded 3D printing cell-dense suspension spatially varied microenvironments tissue and organ constructs
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Essential genetic mutations impair DNA damage repair and modulate tumor immune microenvironment in ccRCC 认领 引用
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作者 Hongchao He Xian-De Liu Eric Jonasch 《MedScience》 SCIE CAS CSCD 2026年第2期231-246,共16页
Targeting DNA repair defects has shown therapeutic benefits in solid tumors with genetic mutations that disrupt DNA damage repair(DDR)pathways.Clear cell renal cell carcinoma(ccRCC)demonstrates an intermediate level o... Targeting DNA repair defects has shown therapeutic benefits in solid tumors with genetic mutations that disrupt DNA damage repair(DDR)pathways.Clear cell renal cell carcinoma(ccRCC)demonstrates an intermediate level of genomic instability,while it rarely carries mutations in these genes.Instead,it is characterized by the loss of chromosome 3p,the von Hippel‑Lindau(VHL)tumor suppressor gene inactivation,and secondary mutations in Polybromo‑1(PBRM1),SET domain‑containing 2(SETD2),and BRCA‑associated protein 1(BAP1).Here,we summarize and discuss how these essential mutations impair the DDR,activate the cytosolic DNA sensing pathway,alter the tumor immune microenvironment,and offer promising therapeutic targets. 展开更多
关键词 DNA damage repair defect tumor immune microenvironment clear cell renal cell carcinoma
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