Research最新文献

{"title":"A Bioinspired Cellulosic Elastomer with Ultrahigh Robustness Enabled by Structure-Induced Reconstruction for Impact Protection.","authors":"Geyuan Jiang, Minxin Wang, Guangwen Xu, Dawei Zhao, Haipeng Yu","doi":"10.34133/research.1460","DOIUrl":"10.34133/research.1460","url":null,"abstract":"<p><p>Elastomers that combine high strength, exceptional toughness, self-healing capability, and scalable processability remain difficult to achieve. Here, we report a leech-inspired cellulosic elastomer constructed from cellulose, diatomite, and polyacrylamide through ethanol-induced structural reconstruction. The resulting bioinspired elastomer exhibits enhanced mechanical performance and efficient energy dissipation, with nearly complete compressive recoverability, a compressive strength above 90 MPa, and a load-bearing capacity exceeding 160,000 times its own weight. The elastomer further demonstrates high resistance to static puncture and dynamic impact, with a puncture resistance energy of 304.22 mJ and an impact toughness of 28.62 MJ m^-3, while maintaining self-healing capability without thermal treatment and tolerance to ultralow temperatures down to -196 °C. In addition, the elastomer is compatible with roll-to-roll manufacturing and can be produced at the meter scale at a low cost. This work offers a scalable strategy for fabricating robust elastomers with potential applications in advanced impact protection and emerging soft technologies.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1460"},"PeriodicalIF":10.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ratio of Silicon to Chitin in Diatom Cell Walls Influences Their Resilience to Environmental Stress.","authors":"Mengyuan Hao, Runyu You, Zhouyi Jiang, Linwei Liu, Lu Huang, Thomas Mock, Naikun Shen, Junrong Liang","doi":"10.34133/research.1452","DOIUrl":"10.34133/research.1452","url":null,"abstract":"<p><p>The diatom cell wall is a critically protective barrier against biotic and abiotic stress, yet the mechanisms by which its individual components confer resilience remain elusive. Using the model diatom <i>Thalassiosira pseudonana</i>, we show that resting cells chemically remodel their cell wall by increasing the ratio of silicon to chitin. Our integrative approach, based on a combination of transcriptomics, cell biology, and reverse genetics, reveals that the girdle-band-associated protein cingulin W2 (CinW2) directly regulates the biochemical cell wall composition, driving a \"high silicon-low chitin\" phenotype under abiotic and biotic stress. The regulation of the gene encoding CinW2 is controlled by an AP2-family transcription factor (AP2-1) that also modulates a chitinase, thereby orchestrating the compositional shift. This shift supporting a silicon-rich frustule provides enhanced structural reinforcement, substantially improving the resilience of <i>T. pseudonana</i> under biotic and abiotic stress. Tara Oceans metatranscriptome data suggest that genes involved in adjusting the ratio of silicon to chitin are widespread across diatom lineages and their expression appears to be responsive to changing environmental conditions in surface oceans. Although the CinW2-mediated regulatory mechanism has been identified only in the genus <i>Thalassiosira</i>, we have identified coregulated homologs in diverse diatom lineages. Collectively, our data therefore suggest that the molecular mechanism by which <i>T. pseudonana</i> modulates key cell wall components might represent a common strategy to cope with challenging environmental conditions.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1452"},"PeriodicalIF":10.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"940-nm Photobiomodulation Enhances ADSC-Mediated Tracheal Cartilage Repair through TRPV1-Associated Calcium Signaling and Mitochondrial Redox Remodeling.","authors":"Yong Xu, Erji Gao, Zhe-Sheng Chen, Bo Tao","doi":"10.34133/research.1440","DOIUrl":"10.34133/research.1440","url":null,"abstract":"<p><p>Tracheal cartilage repair requires simultaneous restoration of a stable cartilage matrix, airway patency, and mechanical support, yet the regenerative state of implanted stem cells remains difficult to control. Here, we show that 940-nm photobiomodulation (PBM) enhances the chondrogenic competence of adipose-derived stem cells (ADSCs) within a defined dose window. Among the radiant exposures tested, 50 J/cm² most effectively promoted cell-cycle progression, cartilage-matrix formation and expression of SRY-box transcription factor 9, type II collagen, and aggrecan, while suppressing fibrotic, hypertrophic, and catabolic markers. These effects were not reproduced by a temperature-matched heat control. In 3-dimensional porous scaffolds, preconditioned ADSCs exhibited improved survival, spreading, matrix deposition, and mechanical performance. Mechanistically, 940-nm PBM remodeled mitochondrial architecture, membrane potential, respiration, cellular adenosine triphosphate content and redox status. Pathway perturbation implicated transient receptor potential vanilloid 1-associated Ca²⁺ signaling, a redox-dependent component of Akt/glycogen synthase kinase 3β activation and SRY-box transcription factor 9 nuclear localization in the chondrogenic response. Preconditioning also preserved cartilage-associated gene expression under inflammatory challenge and altered macrophage-associated inflammatory marker profiles. In a rabbit tracheal cartilage defect model, constructs preconditioned at 50 J/cm² improved cartilage-like tissue formation, epithelial repopulation, lumen patency, and mechanical function. These findings support repeated 940-nm PBM conditioning as a controllable ex vivo strategy for enhancing ADSC chondrogenic competence and improving early tracheal cartilage repair across cellular and tissue scales.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1440"},"PeriodicalIF":10.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated CT Foundation Model and Radiomic Features Define Clinically and Biologically Distinct Colorectal Cancer Subtypes.","authors":"Du Cai, Haoning Qi, Qiuxia Yang, Yibin Zhao, Chenghang Li, Chuling Hu, Yinmeng Zhang, Rende Huang, Wenjun Mao, Xiaojian Wu, Yize Mao, Feng Gao","doi":"10.34133/research.1435","DOIUrl":"10.34133/research.1435","url":null,"abstract":"<p><p>Colorectal cancer is clinically heterogeneous, and current risk stratification does not fully capture differences in recurrence, survival, or treatment response. Molecular subtyping has improved biological classification, but sequencing-based workflows are not always available before treatment or at the population scale. We developed a survival-informed computed tomography (CT) phenotyping framework that combines CT foundation-model representations with PyRadiomics descriptors of tumor shape, intensity, and texture. Across 4 nonoverlapping cohorts, including SYSU6H cohort 1 (<i>N</i> = 902), SYSU6H cohort 2 (<i>N</i> = 3,267), external Ningbo cohort 1 (<i>N</i> = 509), and SYSU6HNAT neoadjuvant-treatment cohort (<i>N</i> = 709), fused CT features were selected and integrated to derive survival-informed CT imaging phenotypes, followed by evaluation of survival, adjusted prognostic associations, molecular correlates, phenotype assignment, and treatment response. The fused representation identified 2 survival-informed imaging phenotypes with marked survival differences. Compared with CT-S1, CT-S2 was associated with worse disease-free survival and overall survival (disease-free survival hazard ratio = 11.16, 95% confidence interval 9.19 to 13.55; overall survival hazard ratio = 14.29, 95% confidence interval 10.83 to 18.85; both <i>P</i> < 0.0001) and remained associated with outcomes after adjustment for clinicopathologic variables and measured tumor size. CT-S2 was enriched for consensus molecular subtype 4-like composition and stromal/extracellular matrix programs, suggesting transcriptomic and microenvironment-associated correlates linked to the adverse imaging phenotype. A flexible phenotype-assignment model reproduced prognostic separation in internal and external cohorts, and assigned phenotypes were associated with survival and pathological response in SYSU6HNAT. These findings suggest that integrated CT phenotyping may provide a noninvasive approach for identifying survival-informed colorectal cancer imaging phenotypes with exploratory molecular correlates, supporting further independent validation.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1435"},"PeriodicalIF":10.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microenvironment-Driven 3-Dimensional Biofabrication Enables Sequential Maturation of the Blood-Brain Barrier.","authors":"Sen Wang, Xinggang Mao, Chengyao Wang, Yingjie Liu, Chenrui Zhang, Siqi Yao, Luge Bai, Joaquim Miguel Oliveira, Rui L Reis, Ya Bai, Jiankang He, Zhilu Yang, Dichen Li, Ling Wang","doi":"10.34133/research.1408","DOIUrl":"https://doi.org/10.34133/research.1408","url":null,"abstract":"<p><p>Three-dimensional (3D) in vitro blood-brain barrier (BBB) models are essential for studying neurovascular development, drug permeability, and disease mechanisms, yet most fail to recapitulate the temporal sequence of cellular maturation. Here, we present a spatiotemporally organized 3D BBB model engineered via dynamic microenvironmental regulation. Temporally controlled enzymatic modulation of an alginate/collagen dual-network hydrogel enabled transition in matrix properties from strong to weak mechanical confinement, thereby triggering the embedded cells to shift from a quiescent to an active state and further enabling the construction of a BBB model with sequential endothelial and supporting cell development. The resulting 3D BBB model exhibits improved barrier integrity, reduced macromolecular leakage, and physiologically relevant drug-selective permeability. This strategy demonstrates that temporally controlled microenvironmental cues can guide multicellular tissue development, providing a versatile platform for neurovascular research and central-nervous-system-targeted drug evaluation.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1408"},"PeriodicalIF":10.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13636311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pH-Responsive Polysaccharide Hydrogel Modulates Oxygen Delivery and Immunometabolic Remodeling for Diabetic Bone Regeneration.","authors":"Haifu Sun, Nanning Lv, He Dong, Wei Geng, Jing Shi, Xinhui Wu, Yonggang Li, Yu Chen, Haowen Lu, Jun Dai, Longpo Zheng, Yusen Qiao","doi":"10.34133/research.1428","DOIUrl":"https://doi.org/10.34133/research.1428","url":null,"abstract":"<p><p>Diabetic bone defects are difficult to repair because chronic hypoxia, oxidative stress, persistent inflammation, and impaired osteoangiogenic coupling disrupt the healing cascade. Here, we report a pH-responsive polysaccharide hydrogel, GOZ6, for spatiotemporally coordinated diabetic bone regeneration. GOZ6 is formed by dynamic Schiff base crosslinking between gelatin and oxidized konjac glucomannan and co-delivers ZIF-8@CaO₂ and 6-gingerol, integrating gated oxygen release, calcium ion delivery, antioxidative protection, and immunomodulation. The hydrogel exhibited rapid gelation within approximately 67 s, a porous architecture with a porosity of 75.78%, pH-responsive degradation, and sustained oxygen release for up to 14 d under physiological conditions. Under mildly acidic conditions, approximately 60% of 6-gingerol was released within the first 3 d, supporting early anti-inflammatory and antioxidative intervention. In vitro, GOZ6 maintained cell viability above 90%, promoted macrophage polarization toward a reparative phenotype, suppressed pro-inflammatory cytokine production, and restored oxidative metabolism. Transcriptomic and protein analyses find that JAK1-STAT3 and PI3K-AKT may serve as central pathways involved in these effects. Moreover, the GOZ6-conditioned immune microenvironment enhanced endothelial migration and tube formation, alleviated oxidative stress in bone marrow mesenchymal stem cells, restored mitochondrial function, and promoted osteogenic differentiation. In a diabetic rat calvarial defect model, GOZ6 markedly enhanced vascularized bone regeneration, collagen deposition, and osteogenic marker expression while reducing local inflammation, without evident systemic toxicity. GOZ6 therefore provides a multifunctional strategy for converting diabetic bone defects into a repair-permissive microenvironment.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1428"},"PeriodicalIF":10.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13636438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis of Micro/Nanoplastics in Mammalian Systems: Gut to Systemic Multi-Organ Dysfunction.","authors":"Zhimin Xu, Runtong Huang, Lei Wang, Yi Zhang, Asmaa A Sharf-Eldin, Kui Xu, Mohamed G Moussa, Renqiang Yu, Heru Pramono, Leli Wang, Yulong Yin","doi":"10.34133/research.1439","DOIUrl":"https://doi.org/10.34133/research.1439","url":null,"abstract":"<p><p>Micro- and nanoplastics (MNPs) have emerged as widespread environmental contaminants with growing implications for human health. Growing evidence indicates that the gastrointestinal tract is not only the primary site of exposure but also a central regulator of systemic toxicity through interactions among the intestinal barrier, immune system, and gut microbiota. Consequently, research has shifted from describing tissue accumulation to elucidating how intestinal dysfunction drives multi-organ effects via the gut-organ axis. This review summarizes recent advances in mechanisms by which ingested MNPs disrupt intestinal homeostasis and subsequently affect extraintestinal organs. We first examine how particle size, morphology, surface properties, environmental weathering, and polymer chemistry shape intestinal responses. Particular attention is given to the emerging view that biodegradable plastics, despite lower environmental persistence, may produce bioactive degradation products in the gastrointestinal tract that alter host-microbiota metabolism. We then integrate current evidence on how barrier disruption, microbial dysbiosis, altered microbial metabolites, and immune signaling mediate communication along the gut-liver, gut-brain, gut-lung, and gut-endocrine axes. In addition, we compare commonly used experimental models, highlighting their respective strengths and limitations for mechanistic studies and translational research. Finally, we discuss intervention strategies and key challenges, including environmentally realistic exposure assessment, methodological standardization, long-term biological adaptation, and the development of human-relevant models. Overall, MNP toxicity arises from dynamic interactions between particle properties and host responses rather than burden alone. Ultimately, MNP risk assessment should move beyond the \"particle-accumulation\" paradigm toward a \"systemic-disruption\" framework, where the gut is recognized as a biological amplifier of exposure and functional homeostasis takes precedence over particle burden.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1439"},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytic Sirt2-Mediated Delactylation Limits Blood-Spinal Cord Barrier Reconstruction after Spinal Cord Injury.","authors":"Yixue Hu, Hao Hu, Zhonghan Wu, Yiyang Mu, Zeqiang Chen, Linhan Yang, Mengdi Zhang, Zihao Chen, Zhenyu Zhang, Ziyu Li, Fei Yao, Shuisheng Yu, Dasheng Tian, Li Cheng","doi":"10.34133/research.1447","DOIUrl":"https://doi.org/10.34133/research.1447","url":null,"abstract":"<p><p>Restoration of the blood-spinal cord barrier (BSCB) is required for substantial neurological improvement after spinal cord injury (SCI). Astrocytes are integral to this barrier and, after injury, undergo glycolytic adaptation accompanied by lactate accumulation. Whether a lactate-linked modification program in astrocytes participates in BSCB repair has remained unresolved. Here, we identify astrocytic delactylation as a brake on BSCB repair. Sirtuin2 (Sirt2), a delactylase, was strongly induced in astrocytes at the lesion border, and its expression paralleled the pathological expansion of microvessels. Selective deletion of <i>Sirt2</i> in astrocytes increased lactylation, produced a lactate-rich metabolic state, attenuated inflammatory astrocyte programs, enhanced repair-associated features, and reinforced BSCB repair. These changes further reduced inflammatory infiltration and promoted neuronal retention, increased 5-hydroxytryptamine-positive fiber density, and improved locomotor recovery. Pharmacological Sirt2 inhibition produced similar vascular and locomotor benefits. Mechanistically, <i>Sirt2</i> loss elevated H4K8la occupancy at the hepatocyte growth factor (<i>Hgf</i>) locus and promoted <i>Hgf</i> transcription, thereby facilitating BSCB repair. Astrocyte-specific <i>Sirt2</i> ablation also weakened CD8⁺ T-cell-related inflammatory activity after SCI. Collectively, our findings position astrocytic <i>Sirt2</i>-dependent delactylation as a negative epigenetic-metabolic regulator of BSCB reconstruction and support astrocytic delactylation as a therapeutic target for SCI.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1447"},"PeriodicalIF":10.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scoparone-Induced Phase Separation of ZDHHC12 Drives Ferroptosis via ATG12 S-palmitoylation and Ferritinophagy in Liver Fibrosis.","authors":"Yuyao Wei, Junli Xu, Jumei Tang, Jiaxin Zuo, Kaiwen Cheng, Chunbo Jiang, Yanshuang Zhuang, Mei Guo, Zili Zhang","doi":"10.34133/research.1450","DOIUrl":"https://doi.org/10.34133/research.1450","url":null,"abstract":"<p><p>Activated hepatic stellate cells (HSCs) are central effectors of liver fibrogenesis, and their selective elimination is critical for fibrosis regression. Although ferroptotic clearance of HSCs has emerged as a promising antifibrotic strategy, the upstream mechanisms coupling metabolic remodeling to ferroptosis susceptibility remain unclear. This study investigated whether scoparone (SCO) suppresses liver fibrosis through zinc finger DHHC-type palmitoyltransferase 12 (ZDHHC12) condensate formation, leading to enhanced autophagy-related protein 12 (ATG12) S-palmitoylation, induction of autophagy, and increased ferroptosis susceptibility in HSCs. We found that SCO restrained cell proliferation, migration, and fibrogenic activation while inducing iron overload, lipid peroxidation, glutathione depletion, and ferroptosis-like mitochondrial remodeling. Metabolomic and S-palmitoylation analyses linked these effects to increased palmitic acid levels and enhanced global protein S-palmitoylation. ZDHHC12 emerged as a SCO-responsive palmitoyltransferase associated with autophagy activation, ferritin turnover, ferroptosis induction, and repression of fibrogenic markers. Mechanistically, SCO promoted the formation of liquid-like ZDHHC12 condensates, which enhanced its interaction with ATG12 and facilitated ATG12 S-palmitoylation at the conserved Cys134 residue. This modification was associated with increased ATG12 stability through reduced ubiquitin-dependent proteasomal degradation, thereby promoting autophagy activation and increasing ferroptosis susceptibility in HSCs. Mutation of ATG12 at Cys134 attenuated these effects and diminished HSC ferroptosis. In cholestatic and toxic models of liver fibrosis, SCO alleviated liver injury and collagen deposition, whereas HSC-targeted silencing of ZDHHC12 or ATG12 attenuated these protective effects, supporting biological consistency in vivo. Integrated bioinformatic and clinical cohort analyses suggested that ZDHHC12 expression positively correlated with ATG12 expression and was associated with fibrosis progression in patients with liver fibrosis. Collectively, these findings support a ZDHHC12-dependent ATG12 S-palmitoylation pathway linking lipid metabolic remodeling to autophagy-mediated ferroptosis in HSCs and suggest phase-regulated S-palmitoylation as a potential antifibrotic target.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1450"},"PeriodicalIF":10.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Inflammation Supports Tumorigenesis: Activator Protein 1 Drives Stem Cell Memory to Augment Colitis and Cancer.","authors":"Lingyi Wu, Jingjing Chen, Hu Zhang, Min Wu","doi":"10.34133/research.1433","DOIUrl":"https://doi.org/10.34133/research.1433","url":null,"abstract":"<p><p>A recent study published in <i>Nature</i> reveals that colonic stem cells retain long-term memory via activator protein 1 transcription-factor-mediated epigenetic remodeling following the resolution of inflammation. Chronic inflammation is an established risk factor for cancer; however, the mechanisms through which tissues maintain a memory of inflammatory history to drive malignant transformation after resolution remain largely elusive. This primed state markedly accelerates tumorigenesis upon the acquisition of oncogenic mutations. Chronic inflammation, exemplified by ulcerative colitis, is a key driver of colorectal cancer. Contrary to the classical view that inflammation promotes tumorigenesis via DNA damage, Nagaraja et al. showed that inflammation leaves genomic imprints on colonic stem cells, lowering their threshold for malignant transformation upon subsequent oncogenic stimuli. First discovered in the innate immune system, inflammatory memory has since been confirmed in epithelial barrier cells and stem cells. Research indicates that following inflammatory exposure, cells retain lasting epigenetic imprints through the remodeling of chromatin, which is the complex interaction and also binding product of DNA and proteins. The specific mechanisms may involve alterations in chromatin accessibility and the modification of histones that are proteins that bind to DNA. This discovery provides a feasible approach to investigating the mechanisms underlying the interplay between inflammation, epigenetic memory, and tumorigenesis‌, deepening our understanding of tumor progression.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1433"},"PeriodicalIF":10.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}