Research最新文献

{"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}

{"title":"Geometry-Mechanics Compatibility Enables Interpretable Inverse Design of Non-Rigid Origami.","authors":"Yucong Sun, Keyao Song, Yiqiu Wang, Wenshi Xue, Yang Li, Xiang Zhou","doi":"10.34133/research.1443","DOIUrl":"10.34133/research.1443","url":null,"abstract":"<p><p>Non-rigid origami offers a geometric route to programmable mechanical and kinematic functions in metamaterials, deployable structures, and robotic mechanisms. Yet, its inverse design remains constrained by a fundamental modeling dilemma: High-fidelity nonlinear simulations become prohibitively expensive when repeatedly applied across large design spaces, whereas reduced models are efficient but often rely on pattern-specific assumptions whose validity is difficult to assess across crease patterns. Here, we introduce a compatibility-guided inverse-design framework that uses a geometry-mechanics test to determine when a parameterized design family can be reliably represented by a single-degree-of-freedom (1-DOF) kinematic model. Once qualified, the reduced model enables rapid and interpretable exploration of the admissible design space, while incompatible cases remain evaluated using high-fidelity analysis. We demonstrate the framework by designing origami metamaterials with programmable multistability and multi-plateau mechanical responses, enabled by the identification and removal of key geometric constraints. Its broader applicability is further illustrated through target-shape morphing and task-specific robotic motion programming. By turning model reduction from an assumed approximation into an explicit design decision, this framework provides a geometry-driven route from target functions to manufacturable non-rigid origami while reducing reliance on simulation-intensive search.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1443"},"PeriodicalIF":10.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076029","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":"Beyond Seed and Soil: A Bacterial-Passenger Framework for Organ-Tropic Breast Cancer Metastasis.","authors":"Yumian Huang, Zhiwei Li, Fu Gao, Lei Huang, Gang Sun","doi":"10.34133/research.1429","DOIUrl":"10.34133/research.1429","url":null,"abstract":"<p><p>Breast cancer metastasis reflects both tumor cell heterogeneity and compatibility with distant organ microenvironments. Tumor-resident bacteria add a potential nongenetic layer to this process, but the strength of evidence varies substantially across proposed mechanisms. Here, we introduce the concept of a \"bacterial passenger\", which is operationally defined as a viable bacterium localized within, rather than merely adherent to, a tumor cell or circulating tumor cell during dissemination. Passenger status must be distinguished from nonviable microbial DNA, extracellular signals, and environmental or reagent contamination through viability-aware imaging, culture or functional assays, and matched strain-level evidence across primary tumors, circulating tumor cells, and metastases. The term describes physical codissemination and does not itself imply a causal effect. Breast cancer models show that intracellular bacteria can increase survival under fluid shear stress and metastatic colonization, yet direct evidence that they determine organ tropism, brain metastasis, or treatment resistance remains limited. We therefore present the seed-soil-passenger triad as a bacteria-centered, falsifiable extension of the seed-soil framework rather than a replacement. Its value lies in testable predictions about codissemination, organ-dependent effects, and stage-specific bacterial perturbation, coupled to rigorous low-biomass controls. Fungi and viruses are outside the present operational framework because comparable evidence for viable codissemination with breast cancer cells is not available.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"1429"},"PeriodicalIF":10.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040443","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}