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Multi-component Microcapsules Derived Spatiotemporal Sonodynamic Reinforcing Therapy against Rheumatoid Arthritis. 多组分微胶囊衍生时空声动力强化治疗类风湿关节炎。
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-18 eCollection Date: 2025-01-01 DOI: 10.34133/research.0844
Danqing Huang, Min Nie, Rui Liu, Chang Xu, Jingjing Gan, Yuanjin Zhao, Lingyun Sun
{"title":"Multi-component Microcapsules Derived Spatiotemporal Sonodynamic Reinforcing Therapy against Rheumatoid Arthritis.","authors":"Danqing Huang, Min Nie, Rui Liu, Chang Xu, Jingjing Gan, Yuanjin Zhao, Lingyun Sun","doi":"10.34133/research.0844","DOIUrl":"10.34133/research.0844","url":null,"abstract":"<p><p>Microcarriers have demonstrated substantial potential in therapeutic delivery for rheumatoid arthritis (RA) treatment. Herein, we propose a novel spatiotemporal ultrasound-responsive microcapsule carrier to reinforce curcumin-based sonodynamic therapy in treating RA. Based on microfluidic technology, microcapsules with a hydrogel shell loaded with curcumin and a perfluorocarbon core enriched with oxygen (CUR/O<sub>2</sub>-MCs) can be obtained. Ascribed to the liquid-to-gas transition property of perfluorocarbon and the sonosensitivity of curcumin, ultrasound stimulation can realize controlled oxygen release followed by sonodynamic reactive oxygen species production. We have demonstrated that the ultrasound-activated CUR/O<sub>2</sub>-MCs can elevate reactive oxygen species amounts in overproliferating fibroblast-like synoviocytes, subsequently inducing fibroblast-like synoviocyte apoptosis. In addition, the released curcumin and oxygen can bring about macrophage repolarization, antiangiogenesis, and hypoxia alleviation, which are also important in blocking RA progression. Thus, in collagen-induced arthritis rats, our spatiotemporal sonodynamic microcapsules can attenuate symptoms and reduce joint damage. These results indicate that our ultrasound-responsive multifunctional microcapsule is an ideal candidate for sonodynamic therapy enhancement and RA treatment.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0844"},"PeriodicalIF":10.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114204","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}
引用次数: 0
Breaking the Barrier in Conversion of Methane to Ethanol: A Molecular Junction Photocatalyst. 突破甲烷转化为乙醇的障碍:一种分子结光催化剂。
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-16 eCollection Date: 2025-01-01 DOI: 10.34133/research.0890
Lingyi Li, Yingkui Yang, Xueiqn Liu
{"title":"Breaking the Barrier in Conversion of Methane to Ethanol: A Molecular Junction Photocatalyst.","authors":"Lingyi Li, Yingkui Yang, Xueiqn Liu","doi":"10.34133/research.0890","DOIUrl":"10.34133/research.0890","url":null,"abstract":"","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0890"},"PeriodicalIF":10.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12437095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081406","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}
引用次数: 0
Anisotropic Micro/Nanotopography Regulating Mitochondrial Dynamics in Cardiomyocytes. 各向异性微纳米形貌调节心肌细胞线粒体动力学。
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-16 eCollection Date: 2025-01-01 DOI: 10.34133/research.0891
Yan Liu, Bingcheng Yi, Liangliang Yang, Yanyan Yang, Tianxiang Li, Xiaolu Li, Jae Youl Cho, Dengshen Zhang, Qihui Zhou, Tao Yu
{"title":"Anisotropic Micro/Nanotopography Regulating Mitochondrial Dynamics in Cardiomyocytes.","authors":"Yan Liu, Bingcheng Yi, Liangliang Yang, Yanyan Yang, Tianxiang Li, Xiaolu Li, Jae Youl Cho, Dengshen Zhang, Qihui Zhou, Tao Yu","doi":"10.34133/research.0891","DOIUrl":"10.34133/research.0891","url":null,"abstract":"<p><p><b>Introduction:</b> Topographical cues of biomaterial scaffolds directly guide cell behaviors by determining integrin ligation and subsequent mechanotransducive pathways, but their influence on organelle (e.g., mitochondrion) behaviors remains unclear. <b>Objectives:</b> Considering the high sensitivity of mitochondria in cardiomyocytes to topographical signals, this study focused on investigating the impact of oriented micro/nano-wrinkled surfaces with varying wavelengths (0.5 to 25.0 μm) and amplitudes (0.05 to 4.30 μm) on the mitochondrial functions of rat embryonic myocardial cell line H9c2. <b>Methods and Results:</b> The results uncover a nonlinear response of cardiomyocyte behavior and mitochondrial homeostasis to these surface features. Notably, surfaces with a 3-μm wavelength and 0.7-μm amplitude (W3) promoted substantial cell elongation and orientation, whereas surfaces with a 0.5-μm wavelength and 0.05-μm amplitude (W0.5) triggered pronounced mitochondrial division. Remarkably, W0.5 topography facilitated mitochondrial division via cytoskeletal remodeling, involving vinculin and tubulin, which disrupted mitochondrial energy metabolism, enhanced reactive oxygen species (ROS)-mediated oxidative stress, and perturbed mitochondrial homeostasis by stimulating the adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway. The transcriptomic analysis identifies the pivotal involvement of the p53, FoxO, mTOR, HIF-1, and AMPK signaling pathways in regulating mitochondrial dynamics in myocardial cells induced by W0.5, confirming the essential role of the polyadenylation signal (AATAAA) in modulating transcript splicing processes. <b>Conclusion:</b> Overall, this study offers important insights into the regulatory mechanisms by which aligned micro/nano topographical stimuli impact mitochondrial responses in cardiomyocytes, which hold potential for the development of novel biomaterial-focused approaches for diagnosing and treating cardiovascular diseases.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"2025 ","pages":"0891"},"PeriodicalIF":10.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081421","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}
引用次数: 0
Large-Scale Facile Synthesis of Biomass Fibers and High-Entropy Metal Hierarchical Porous Carbon toward Enhanced Electromagnetic Absorption. 面向增强电磁吸收的生物质纤维和高熵金属分级多孔碳的大规模简易合成。
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-16 eCollection Date: 2025-01-01 DOI: 10.34133/research.0868
Peiyu Cui, Pengbo Zou, Yifan Kang, Xiang Yan, Xin Zhou, BoKun Wang, Fan Wu, Shibing Pan, Jiacheng Ma, Wenhuan Huang
{"title":"Large-Scale Facile Synthesis of Biomass Fibers and High-Entropy Metal Hierarchical Porous Carbon toward Enhanced Electromagnetic Absorption.","authors":"Peiyu Cui, Pengbo Zou, Yifan Kang, Xiang Yan, Xin Zhou, BoKun Wang, Fan Wu, Shibing Pan, Jiacheng Ma, Wenhuan Huang","doi":"10.34133/research.0868","DOIUrl":"10.34133/research.0868","url":null,"abstract":"<p><p>The elevated dielectric properties of carbonized cotton fibers with refined conductive networks result in substantial impedance mismatch, severely compromising their electromagnetic wave (EMW) absorption performance. Using cotton fibers and [Zn(pz)<sub>2</sub>] <i><sub>n</sub></i> complexes as easily prepared and low-cost raw materials, nano-hierarchically porous MnFeCuCe@C composites were constructed efficiently through optimization of the dynamic balance of element content and carbonization temperature. The results show that MnFeCuCe@C-20% exhibited a minimum reflection loss (RL<sub>min</sub>) of -81.44 dB with a thickness of only 1.52 mm at an ultralow loading of 20 wt%, and the effective absorption bandwidth of MnFeCuCe@C-900 °C was also remarkably enlarged to 5.13 GHz at a thickness of 1.6 mm. Modifying only the metal content of the precursor and carbonization temperature can effectively reinforce the magnetic-dielectric synergy and impedance matching. The augmented EMW attenuation primarily stems from the inherent hierarchical porous structure of the MnFeCuCe@C nanocomposite and the rapid electron migration within its high-entropy metal particles. Furthermore, its excellent dissipation capability in practical application scenarios was demonstrated further through radar cross-section simulations. This work comprehensively delineates the optimization strategies for material dielectric properties as well as the convenient and environmental synthesis method.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0868"},"PeriodicalIF":10.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12437104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081448","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}
引用次数: 0
Highly Selective Exogenous Neutrophils Effectively Inhibit Growth of Colon Cancer under the Guidance of Precision Navigation. 高选择性外源性中性粒细胞在精确导航引导下有效抑制结肠癌生长
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-16 eCollection Date: 2025-01-01 DOI: 10.34133/research.0894
Yunxi Yang, Chuyu Li, Yiming Shao, Xiao Wen, Cheng Lu, Xi Gao, Yiwen Mei, Bingwei Sun
{"title":"Highly Selective Exogenous Neutrophils Effectively Inhibit Growth of Colon Cancer under the Guidance of Precision Navigation.","authors":"Yunxi Yang, Chuyu Li, Yiming Shao, Xiao Wen, Cheng Lu, Xi Gao, Yiwen Mei, Bingwei Sun","doi":"10.34133/research.0894","DOIUrl":"10.34133/research.0894","url":null,"abstract":"<p><p>The diversity of neutrophils' subtypes and functions in the tumor microenvironmentunderlies their contributions to both pro- and anti-tumorigenic activities. How to elucidate the antitumor mechanisms of neutrophil and effectively utilize it still needs to be studied. In this study, neutrophil stimulus reaction index (NSRI) was established for high selectivity of neutrophils. Sufficient and highly selective exogenous neutrophils were used to infuse into tumor-bearing mice. Navigation technique was used to make neutrophils rapidly infiltrate into the tumor tissue, which played a key role in inhibiting tumor growth. We found that tumor cells were efficiently killed in direct coculture with sufficient neutrophils by promoting a multimodal death primarily dominated by apoptosis. Interestingly, colon cancer organoid diameters were decreased markedly cocultured with neutrophils, and were more remarkable in the application of organoid microinjection of neutrophils. Consistent with the 3D-printed model, in vivo model indicated that neutrophils meaningfully inhibited the tumor growth by formation of neutrophil extracellular traps (NETs) with neutrophil elastase (NE) payload. This study not only unveils the crucial anticancer effects of neutrophils but also sets out an innovative strategy of aggressive dose exogenous neutrophils with precise navigation, which provided the basis for advancements in neutrophil-based immunotherapy for colon cancer treatment.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0894"},"PeriodicalIF":10.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12437111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081377","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}
引用次数: 0
Cortical Single-Cell Primers of Abnormal Brain Activity in Parkinson's Disease. 帕金森病异常脑活动的皮质单细胞引物。
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.34133/research.0863
Daniela Mirzac, Martin B Glaser, Svenja L Kreis, Florian Ringel, Manuel Bange, Damian M Herz, StanislavA Groppa, Lilia Rotaru, Viviane Almeida, Jenny Blech, Mohammadsaleh Oshaghi, Sebastian Kunz, Matthias Klein, Jonas Paulsen, Heiko J Luhmann, Tobias Bopp, Philip L de Jager, Sergiu Groppa, Gabriel Gonzalez-Escamilla
{"title":"Cortical Single-Cell Primers of Abnormal Brain Activity in Parkinson's Disease.","authors":"Daniela Mirzac, Martin B Glaser, Svenja L Kreis, Florian Ringel, Manuel Bange, Damian M Herz, StanislavA Groppa, Lilia Rotaru, Viviane Almeida, Jenny Blech, Mohammadsaleh Oshaghi, Sebastian Kunz, Matthias Klein, Jonas Paulsen, Heiko J Luhmann, Tobias Bopp, Philip L de Jager, Sergiu Groppa, Gabriel Gonzalez-Escamilla","doi":"10.34133/research.0863","DOIUrl":"10.34133/research.0863","url":null,"abstract":"<p><p>Abnormal brain oscillatory activity is a well-established hallmark of bradykinesia and motor impairment in Parkinson's disease (PD), yet its molecular underpinnings remain unclear. To address this gap, we analyzed over 100,000 single-cell RNA transcriptomes from fresh dorsolateral prefrontal cortex tissue of individuals with PD and non-PD controls, undergoing deep brain stimulation-2 cohorts, which open up an unprecedent window to the characterization of human cortical brain tissue, aiming to uncover the molecular mechanisms of abnormal brain oscillatory activity in PD. Fresh brain tissue samples offer a unique opportunity to precisely elucidate the molecular underpinnings of known, clinically relevant electrophysiological hallmarks of neurodegeneration, which can be used to inform targeted therapeutic strategies. We depicted in microglia and astrocytes enrichment of mitochondrial electron transport and oxidative phosphorylation pathways, which were directly linked to the increase of pathological brain activity and the decrease of prokinetic brain activity. Additionally, the abnormal phase-amplitude coupling of beta-gamma brain activity was related to the dysfunction of oligodendrocyte precursor cells and inflammasome activation mediated by lymphocyte-driven adaptive immunity. We identified a distinct set of dysregulated genes from the mitogen-activated protein kinase phosphorylation pathways, mitochondrial electron transport at the intersection of neuroinflammation and neurodegeneration, suggesting pivotal roles in PD pathology. This unique dataset provides unprecedented insights into the immune and metabolic dysregulation underlying PD, offering a mechanistic framework for understanding invasive transcriptomic biomarkers related to prokinetic and pathologic brain activity in PD.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0863"},"PeriodicalIF":10.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064815","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}
引用次数: 0
Gut-Brain-Microbiome Axis in the Regulation of Cancer Immune Escape and Immunotherapy in Tumors. 肠-脑-微生物轴在肿瘤免疫逃逸和免疫治疗中的调控作用。
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.34133/research.0885
Wangting Xu, Qifan Xu, Peng Luo, Xudong Qu, Dandan Guo, Zhao Xie, Na Hang, Minjie Kuang, Enguo Chen, Ling Wang, Zhiping Yan, Songhua Cai, Wenjun Mao, Bufu Tang
{"title":"Gut-Brain-Microbiome Axis in the Regulation of Cancer Immune Escape and Immunotherapy in Tumors.","authors":"Wangting Xu, Qifan Xu, Peng Luo, Xudong Qu, Dandan Guo, Zhao Xie, Na Hang, Minjie Kuang, Enguo Chen, Ling Wang, Zhiping Yan, Songhua Cai, Wenjun Mao, Bufu Tang","doi":"10.34133/research.0885","DOIUrl":"10.34133/research.0885","url":null,"abstract":"<p><p>Accumulating evidence demonstrates crosstalk involving the intestine and the brain, with the gut microbiota serving as a critical mediator of this interaction. The gut microbiota, along with its derived metabolites and bioactive compounds, modulates the immune microenvironment of brain tumors via the gut-brain axis, thereby influencing tumor initiation, progression, invasion, and metastasis. This review systematically summarizes the pathophysiological mechanisms underlying gut-brain axis modulation of brain tumors and examines emerging therapeutic approaches, including advances in immunotherapy and targeted therapy, that hold promise for future brain tumor treatment strategies.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0885"},"PeriodicalIF":10.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065059","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}
引用次数: 0
Zhuque Base for Martian Habitation: Conceptual Design and Performance Analysis of Cave Dwellings and In Situ Construction. 朱雀火星居住基地:穴居与原位施工的概念设计与性能分析。
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.34133/research.0849
Cheng Zhou, Shanshan Cheng, Yuyue Gao, Jiannan Zhao, Long Xiao, Lieyun Ding
{"title":"Zhuque Base for Martian Habitation: Conceptual Design and Performance Analysis of Cave Dwellings and In Situ Construction.","authors":"Cheng Zhou, Shanshan Cheng, Yuyue Gao, Jiannan Zhao, Long Xiao, Lieyun Ding","doi":"10.34133/research.0849","DOIUrl":"10.34133/research.0849","url":null,"abstract":"<p><p>Sustainable habitation systems are critical to enabling deep-space exploration on Mars, where challenges such as low gravity, extreme thermal fluctuations, and resource constraints demand advanced structural innovations. This study introduces Zhuque Base, a habitat concept inspired by terrestrial cave-dwelling principles, optimized through finite element analysis via COMSOL Multiphysics. Three arch-based configurations-the eggshell, catenary, and 2-centered arch-were systematically evaluated by parameterizing geometric variables. The study demonstrated that eggshell arches significantly outperformed 2-centered and catenary arches in mechanical properties, reducing vertical displacement of critical points such as sidewalls by 53% and 44%, respectively. In terms of thermal efficiency, the optimal catenary arch showed 5.5% and 6.7% lower heat loss than eggshell and 2-centered arches. Furthermore, the implementation of optimal parameters (span: 3.2 m, height: 1.25 or 1.45 m) limits the peak compressive stress to 195.72 to 203.38 kPa, while the cross-sectional area can be increased by 14% to maximize the available internal space. These findings establish a parameter-driven framework for in situ Mars habitat optimization, emphasizing the trade-off between mechanical robustness and thermal efficiency in extraterrestrial structural design.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0849"},"PeriodicalIF":10.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065121","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}
引用次数: 0
Lactylation in Tumor Immune Escape and Immunotherapy: Multifaceted Functions and Therapeutic Strategies. 肿瘤免疫逃逸和免疫治疗中的乳酸化:多方面的功能和治疗策略。
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.34133/research.0793
Qing Li, Runkang Zhao, Yang Shen, Dandan Guo, Lvdan Deng, Rongbing Cai, Zhijun Shen, Zhao Xie, Na Hang, Sentao Fu, Dehuan Zhang, Yihang Xu, Zhao Huang, Bufu Tang, Ling Wang
{"title":"Lactylation in Tumor Immune Escape and Immunotherapy: Multifaceted Functions and Therapeutic Strategies.","authors":"Qing Li, Runkang Zhao, Yang Shen, Dandan Guo, Lvdan Deng, Rongbing Cai, Zhijun Shen, Zhao Xie, Na Hang, Sentao Fu, Dehuan Zhang, Yihang Xu, Zhao Huang, Bufu Tang, Ling Wang","doi":"10.34133/research.0793","DOIUrl":"10.34133/research.0793","url":null,"abstract":"<p><p>Since its initial identification in 2019, lactylation has emerged as a critical posttranslation modification, attracting substantial research interest due to its diverse roles in biological processes. Lysine lactylation represents a recently characterized posttranslational modification wherein lactate moieties are covalently attached to protein lysine residues through both enzymatic and nonenzymatic pathways. Lactate, a primary glycolytic product, suggests a link between cell metabolism and protein function regulation. In neoplastic tissues, the Warburg effect induces preferential glucose-to-lactate metabolism in cancer cells, establishing hypoxic conditions and elevated lactate concentrations as defining characteristics of the tumor microenvironment. Extensive research has demonstrated lactate's pivotal role in tumor metastasis and patient outcomes, particularly through its influence on tumor immune microenvironment remodeling, although the precise molecular mechanisms remain under investigation. The characterization of lysine lactylation provides a novel framework for understanding these mechanisms and presents innovative opportunities for therapeutic intervention. This review examines the influence of lactylation on the tumor microenvironment and its effect in various malignancies and explores emerging therapeutic strategies, including genetic manipulation, small-molecule inhibitors, clinical pharmaceuticals, and nanoparticle-based approaches, offering new perspectives in cancer treatment.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0793"},"PeriodicalIF":10.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065008","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}
引用次数: 0
Gut Commensal Antibiotic-Resistant Parabacteroides goldsteinii Ameliorates Mouse Colitis through Valine-Isobutyrate Metabolism. 肠道共生耐药金斯坦副杆菌通过缬氨酸-异丁酸盐代谢改善小鼠结肠炎。
IF 10.7 1区 综合性期刊
Research Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.34133/research.0867
Ningning He, Mengjie Mu, Xiaofang Li, Qingyuan Hao, Kaiwei Chen, Xinnan Zhao, Yang Sun, Haoyu Wang, Zhinan Wu, Hewei Liang, Mengmeng Wang, Liang Xiao, Tao Yu, Zhi-Peng Wang, Jixing Peng, Yuanqiang Zou, Shangyong Li
{"title":"Gut Commensal Antibiotic-Resistant <i>Parabacteroides goldsteinii</i> Ameliorates Mouse Colitis through Valine-Isobutyrate Metabolism.","authors":"Ningning He, Mengjie Mu, Xiaofang Li, Qingyuan Hao, Kaiwei Chen, Xinnan Zhao, Yang Sun, Haoyu Wang, Zhinan Wu, Hewei Liang, Mengmeng Wang, Liang Xiao, Tao Yu, Zhi-Peng Wang, Jixing Peng, Yuanqiang Zou, Shangyong Li","doi":"10.34133/research.0867","DOIUrl":"10.34133/research.0867","url":null,"abstract":"<p><p>Antibiotic cocktails (ABX) serve as potent therapeutic interventions for refractory ulcerative colitis (UC), yet invariably induce gut dysbiosis. This study demonstrates that pectin oligosaccharides synergistically enhance ABX efficacy by restoring gut microbiota balance and selectively enriched antibiotic-resistant <i>Parabacteroides goldsteinii</i> in a colitis mouse model. Our results further indicate that the gavage administration of <i>P. goldsteinii</i> AM58-2XD markedly alleviated colitis via enhancing the branched-chain amino acid metabolic pathway, particularly by facilitating valine metabolism. Notably, these anticolitis effects were partially attenuated in <i>P. goldsteinii</i> <sup>ΔilvE</sup> mutants, which are defective in valine-derived isobutyrate (IBN) biosynthesis. We further demonstrated that exogenous IBN supplementation effectively alleviated colitis symptoms in mice and enhanced gut barrier function via activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway. Conditional knockout of PPARγ in Caco-2 intestinal epithelial cells markedly abrogated the IBN-induced enhancement of tight junctions, thereby substantiating the critical role of the IBN-PPARγ pathway in metabolite-mediated mucosal repair. Collectively, we delineate a prebiotic/probiotic-metabolite axis wherein <i>P. goldsteinii</i> facilitates mucosal repair via IBN/PPARγ-dependent epithelial metabolic reprogramming. This insight redefines antibiotic-resistant commensals as precise biotherapeutics for microbiota restoration in refractory UC management.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0867"},"PeriodicalIF":10.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065036","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}
引用次数: 0
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