Advanced Science最新文献

3D Self-Supported Visible Light Photochemical Nanocatalysts.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202502981

Fateh Mikaeili, Mohammad Mahafuzur Rahaman, Pelagia-Irene Perena Gouma

{"title":"3D Self-Supported Visible Light Photochemical Nanocatalysts.","authors":"Fateh Mikaeili, Mohammad Mahafuzur Rahaman, Pelagia-Irene Perena Gouma","doi":"10.1002/advs.202502981","DOIUrl":"https://doi.org/10.1002/advs.202502981","url":null,"abstract":"This work focuses on 3D, self-supported, nanofibrous TiO2 structures (nanogrids) prepared using blend electrospinning. The presence of anatase and brookite phases in Cu-doped TiO2 nanogrids significantly enhances the photocatalytic properties of the titania system. The absorption edge in Cu-doped TiO2 shifts to the visible due to the narrowed bandgap and efficient separation of photogenerated charge carriers facilitated by Cu doping. The presence of the brookite phase further contributes to the enhanced performance, by reducing electron-hole recombination. A wide range of characterization techniques, including cyclic voltammetry and chronoamperometry studies which show that the Cu doped TiO₂ sample generates a significant photocurrent under visible light, are employed to elucidate the role of Cu doping in enhancing the visible light photocatalytic efficiency of TiO2 nanogrids, offering valuable insights for developing advanced photochemical catalysts for environmental and energy applications. The nanogrids studied here are far superior to P25 Degussa and are activated by natural sunlight and do not require a filtration system to remove nanoparticles from the water. These self-supported nanofibrous photochemical catalysts offer all the benefits of nanomaterials while suffering from none of their drawbacks.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2502981"},"PeriodicalIF":14.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rotation-Based Snap-Fit Mechanical Metamaterials.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202501749

Rui Xu, Yulong He, Chuanqing Chen, Jiapeng Sun, Xin Li, Ming-Hui Lu, Yan-Feng Chen

引用次数: 0

Development of MDM2-Targeting PROTAC for Advancing Bone Regeneration.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202415626

Sol Jeong, Jae-Kook Cha, Wasim Ahmed, Jaewan Kim, Minsup Kim, Kyung Tae Hong, Wonji Choi, Sunjoo Choi, Tae Hyeon Yoo, Hyun-Ju An, Seung Chan An, Jaemin Lee, Jimin Choi, Sun-Young Kim, Jun-Seok Lee, Soonchul Lee, Junwon Choi, Jin Man Kim

{"title":"Development of MDM2-Targeting PROTAC for Advancing Bone Regeneration.","authors":"Sol Jeong, Jae-Kook Cha, Wasim Ahmed, Jaewan Kim, Minsup Kim, Kyung Tae Hong, Wonji Choi, Sunjoo Choi, Tae Hyeon Yoo, Hyun-Ju An, Seung Chan An, Jaemin Lee, Jimin Choi, Sun-Young Kim, Jun-Seok Lee, Soonchul Lee, Junwon Choi, Jin Man Kim","doi":"10.1002/advs.202415626","DOIUrl":"https://doi.org/10.1002/advs.202415626","url":null,"abstract":"Proteolysis-targeting chimeras (PROTACs) degrade target proteins through the ubiquitin-proteasome system. To date, PROTACs are primarily used to treat various diseases; however, they have not been applied in regenerative therapy. Herein, this work introduces MDM2-targeting PROTACs customized for application in bone regeneration. An MDM2-PROTAC library is constructed by combining Nutlin-3 and CRBN ligands with various linker designs. Through a multistep validation process, this work develops MDM2-PROTACs (CL144 and CL174) that presented potent degradation efficiency and a robust inductive effect on the biomineralization. Next, this work performs whole-transcriptome analysis to dissect the biological effects of the CL144, and reveals the upregulation of osteogenic marker genes. Furthermore, CL144 effectively induced bone regeneration in bone graft and ovariectomy (OVX) models after local and systemic administration, respectively. In the OVX model, the combination treatment with CL144 and alendronate induced a synergistic effect. Overall, this study demonstrates the promising role of MDM2-PROTAC in promoting bone regeneration, marking the first step toward expanding the application of the PROTAC technology.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2415626"},"PeriodicalIF":14.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RACK7 Interacts with PRC2 Complex to Regulate Astrocyte Development.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202416350

Fangfang Jiao, Tianxiang Tang, Bowen Wang, Shengfei He, Yue Zhang, Li Dong, Bo Xu, Ying Liu, Ping Zhu, Rui Guo

{"title":"RACK7 Interacts with PRC2 Complex to Regulate Astrocyte Development.","authors":"Fangfang Jiao, Tianxiang Tang, Bowen Wang, Shengfei He, Yue Zhang, Li Dong, Bo Xu, Ying Liu, Ping Zhu, Rui Guo","doi":"10.1002/advs.202416350","DOIUrl":"https://doi.org/10.1002/advs.202416350","url":null,"abstract":"Dysregulation of epigenetic mechanisms plays a crucial role in brain development and disease. Emerging largely evidence suggests that Receptor for Activated C-kinase 7 (RACK7), an epigenetic reader protein, may play a role in brain development and neural developmental disease, but in vivo explorations are still lacking. Here, a Rack7 conditional knock-out mouse model is established and shows that Rack7-deficient mice exhibit overt developmental defects associated with aberrant astrocyte development. Mechanistically, it is found that RACK7 interacts with the histone H3 lysine 27 (H3K27) methyltransferase, i.e., the Polycomb Repressive Complex 2 (PRC2) complex, to establish the genomic locations of Suppressor of Zeste 12 homolog (SUZ12) and H3K27 methylation. Deletion of Rack7 in astrocytes leads to a remarkable decrease of H3K27me3 chromatin localization genome-wide. Furthermore, RACK7 works together with H3K27me3 to prevent overactivation of the Wnt signaling pathway and other astrocyte differentiation genes are found. Collectively, this study provides new insights into the cellular and molecular mechanisms underlying brain development regulated by RACK7.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2416350"},"PeriodicalIF":14.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202415459

Yu-Xuan Ma, Chen Lei, Tao Ye, Qian-Qian Wan, Kai-Yan Wang, Yi-Na Zhu, Ling Li, Xu-Fang Liu, Long-Zhang Niu, Franklin R Tay, Zhao Mu, Kai Jiao, Li-Na Niu

{"title":"Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration.","authors":"Yu-Xuan Ma, Chen Lei, Tao Ye, Qian-Qian Wan, Kai-Yan Wang, Yi-Na Zhu, Ling Li, Xu-Fang Liu, Long-Zhang Niu, Franklin R Tay, Zhao Mu, Kai Jiao, Li-Na Niu","doi":"10.1002/advs.202415459","DOIUrl":"https://doi.org/10.1002/advs.202415459","url":null,"abstract":"Diabetes mellitus is a metabolic disorder associated with an increased risk of fractures and delayed fracture healing, leading to a higher prevalence of bone defects. Recent advancements in strategies aim at regulating immune responses and enhancing neurovascularization have not met expectations. This study demonstrates that a silicon-based strategy significantly enhances vascularization and innervation, thereby optimizing the repair of diabetic bone defects. Silicon improves mitochondrial function and modulates mitochondrial fission dynamics in macrophages via the Drp1-Mff signaling pathway. Subsequently, functional mitochondria are transferred from macrophages to endothelial and neuronal cells through microvesicles, providing a protective mechanism for blood vessels and peripheral nerves during early wound healing. On this basis, an optimized strategy combining a silicified collagen scaffold with a Drp1-Fis1 interaction inhibitor is used to further regulate mitochondrial fission in macrophages and enhance the trafficking of functional mitochondria into stressed receptor cells. In diabetic mice with critical-sized calvarial defects, the silicon-based treatment significantly promotes vessel formation, nerve growth, and mineralized tissue development. These findings provide therapeutic insights into the role of silicon in promoting diabetic bone regeneration and highlight the importance of intercellular communication in diabetic conditions.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2415459"},"PeriodicalIF":14.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced Broadband Acoustic Absorption in Commercial Foam via Multiwall Carbon Nanotube-Induced Pore Reconstruction.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202501898

Jinkui Xiong, Jinlong Liu, Wengui Lin, Yifei Li, Longchao Liao, Mingfu Wen, Guisheng Zhong, Xiaodong Niu, Longshi Rao, Quan Wang, Bin Bao, Qingxian Liu

{"title":"Enhanced Broadband Acoustic Absorption in Commercial Foam via Multiwall Carbon Nanotube-Induced Pore Reconstruction.","authors":"Jinkui Xiong, Jinlong Liu, Wengui Lin, Yifei Li, Longchao Liao, Mingfu Wen, Guisheng Zhong, Xiaodong Niu, Longshi Rao, Quan Wang, Bin Bao, Qingxian Liu","doi":"10.1002/advs.202501898","DOIUrl":"https://doi.org/10.1002/advs.202501898","url":null,"abstract":"Noise pollution is an urgent environmental issue that leads to a series of adverse effects on human physical and mental health. Porous materials with rationally designed micropores or channels can effectively absorb noise across wide frequency ranges, making them a well-established candidate for mitigating acoustic propagation. However, common porous materials with a singular pore structure face a trade-off between acoustic absorption efficiency and thickness. Herein, this challenge is significantly mitigated by reconstructing the pore structure of commercial melamine foam using multiwall carbon nanotubes (MWCNTs). The melamine/MWCNTs foam exhibits multiscale composite pores, high porosity, and increased specific surface area while preserving the shape and thickness of the initial melamine foam. Due to increased energy dissipation from the porous structure and the resonance effect of MWCNTs, the 10 mm thick composite porous absorber exhibits an average absorption coefficient of ≈70% from 1300 to 6000 Hz, representing a 196.5% increase compared with that of initial melamine foam. The reconstructing pore structure by loading MWCNTs is a simple and general method for improving the acoustic absorption coefficient. It can be extended to other complex morphologies or material systems, offering significant application potential in noise control, acoustic instruments, and architectural design.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2501898"},"PeriodicalIF":14.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Eosinophils-Induced Lumican Secretion by Synovial Fibroblasts Alleviates Cartilage Degradation via the TGF-β Pathway Mediated by Anxa1 Binding.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202416030

Wenqian Chen, Yuwei Zhou, Wenxiu Yuan, Yanjing Ou, Hanyu Lin, Kaixun He, Xueshen Qian, Huachen Chen, Chengchaozi Wang, Jie Lu, Weiping Chen, Dexiong Li, Jiang Chen

{"title":"Eosinophils-Induced Lumican Secretion by Synovial Fibroblasts Alleviates Cartilage Degradation via the TGF-β Pathway Mediated by Anxa1 Binding.","authors":"Wenqian Chen, Yuwei Zhou, Wenxiu Yuan, Yanjing Ou, Hanyu Lin, Kaixun He, Xueshen Qian, Huachen Chen, Chengchaozi Wang, Jie Lu, Weiping Chen, Dexiong Li, Jiang Chen","doi":"10.1002/advs.202416030","DOIUrl":"https://doi.org/10.1002/advs.202416030","url":null,"abstract":"The innate immune response is crucial in the progression of temporomandibular joint osteoarthritis (TMJOA). Yet, the roles of eosinophils in TMJOA remain unclear, underscoring the need for further investigation into their potential impact and mechanism. Addressing the clinical observation that eosinophil numbers in synovial fluid are higher in healthy individuals than in those with TMJOA, the vital regulation of this cell population in TMJOA by using an ovalbumin (OVA)-induced hyper-eosinophilia asthma rats is explored and a rat model of antibody-mediated eosinophil depletion in vivo, and co-culture system of synovial fibroblasts, chondrocytes, and eosinophils in vitro. The abnormal synovial proliferation, cartilage degradation, and subchondral bone erosion are effectively inhibited in OVA-induced asthmatic rats appearing in the local accumulation of eosinophils in the synovium. Conversely, the reduction in synovial eosinophils exacerbated TMJOA in rats treated with TRFK. Mechanistically, the protective effect of eosinophils against TMJOA is attributed to their promotion of Lumican secretion in the synovium, where Lumican binds to Annexin A1 in chondrocytes, inhibits transforming growth factor β2 Annexin A1 and Smad2/3 phosphorylation. These results illustrate OVA/IL-5-induced eosinophils' crucial role in TMJOA, identifying Lumican as a key anti-TMJOA target. Collectively, these findings revealed the signature and mechanism in eosinophils that stimulate TMJOA resolution.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2416030"},"PeriodicalIF":14.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Universal and Versatile Zwitterionic Coating for Blood-Contacting Catheters with Long Lengths and Complex Geometries.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202502411

Tong Zhang, Tian Liang, Qichao Pan, Shouyan Zhang, Shuhua Zhang, Zhi Geng, Bo Zhu

{"title":"A Universal and Versatile Zwitterionic Coating for Blood-Contacting Catheters with Long Lengths and Complex Geometries.","authors":"Tong Zhang, Tian Liang, Qichao Pan, Shouyan Zhang, Shuhua Zhang, Zhi Geng, Bo Zhu","doi":"10.1002/advs.202502411","DOIUrl":"https://doi.org/10.1002/advs.202502411","url":null,"abstract":"Blood-contacting catheters are highly susceptible to thrombus formation, making heparin coating essential for reducing clinical complications. However, the limitations of heparin coatings have spurred significant efforts to develop alternative strategies. This study demonstrates a cost-efficient, mechanically viable, and universal zwitterion coating approach for long and complex catheters with near-zero fouling, super anticoagulation, and selective biocapturing. Leveraging the synergistic action of side groups, a wet-adhesive initiator-bearing polymer rapidly assembles on catheter surfaces in aqueous environments, facilitating the grafting of superhydrophilic and zwitterionic polymers onto catheter inner walls. This strategy demonstrates broad adaptability, successfully applying to ten substrates and showing exceptional versatility in modifying catheters and joints of various shapes and sizes. These coatings exhibit near-zero protein fouling across a broad pH range, and superior resistance to blood cells and bacteria. Furthermore, they maintain excellent stability under simulated bloodstream without compromising anticoagulant performance. Beyond antifouling properties, this method enables the construction of highly selective bio-interaction networks on catheter inner walls, allowing precise capture of circulating tumor cells from blood. This zwitterion coating technique, with its rapid modification, robust anticoagulant properties, and customizable bio-functionality, provides an attractive solution for, beyond catheters, a wide range of medical devices that must perform in challenging biological environments.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2502411"},"PeriodicalIF":14.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autocrine GDF10 Inhibits Hepatic Stellate Cell Activation via BMPR2/ALK3 Receptor to Prevent Liver Fibrosis.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202500616

Yinliang Zhang, Xiaochen Gai, Yuhui Li, Zuoyu Chen, Xi Zhang, Wei Qiao, Ping Qiu, Chunyuan Du, Sufang Sheng, Jingran Hao, Yujie Zhang, Heng Fan, Xiaorong Li, Ming Liu, Jun Zhang, Zhe Pan, Yongsheng Chang

{"title":"Autocrine GDF10 Inhibits Hepatic Stellate Cell Activation via BMPR2/ALK3 Receptor to Prevent Liver Fibrosis.","authors":"Yinliang Zhang, Xiaochen Gai, Yuhui Li, Zuoyu Chen, Xi Zhang, Wei Qiao, Ping Qiu, Chunyuan Du, Sufang Sheng, Jingran Hao, Yujie Zhang, Heng Fan, Xiaorong Li, Ming Liu, Jun Zhang, Zhe Pan, Yongsheng Chang","doi":"10.1002/advs.202500616","DOIUrl":"https://doi.org/10.1002/advs.202500616","url":null,"abstract":"Hepatic stellate cells (HSCs) play a central role in the development of liver fibrosis, and their activation is controlled by a complex interplay of autocrine/paracrine signals within the liver microenvironment. Here, we show that growth differentiation factor 10 (GDF10) is specifically expressed by HSCs in both mouse and human livers, and its expression is reduced in activated HSCs. Loss of GDF10 function promotes HSC activation and exacerbates liver fibrosis in mice, while gain of GDF10 function alleviates this pathological condition. Mechanistically, autocrine GDF10 binds to BMPR2/ALK3 receptor to elicit SMAD1/5/8-SMAD7 signaling pathway in HSCs. Activated SMAD1/5/8-SMAD7 signaling pathway then inhibits the TGF-β-SMAD2/3 signaling transduction, which is essential for HSC activation. Moreover, recombinant GDF10 protein treatment suppresses HSC activation and alleviates liver fibrosis in mice. In conclusion, GDF10 is an autocrine suppressor of HSC activation and a potential therapeutic target for the treatment of liver fibrosis.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2500616"},"PeriodicalIF":14.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide Attenuates Colon Cancer Development by Regulating Glucose Metabolism.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-24 DOI: 10.1002/advs.202411980

Yikai Zhang, Yi Xie, Shenglong Xia, Xinnuo Ge, Jiaying Li, Fang Liu, Fan Jia, Shengyao Wang, Qiao Zhou, Menghan Gao, Weihuan Fang, Chao Zheng

{"title":"The Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide Attenuates Colon Cancer Development by Regulating Glucose Metabolism.","authors":"Yikai Zhang, Yi Xie, Shenglong Xia, Xinnuo Ge, Jiaying Li, Fang Liu, Fan Jia, Shengyao Wang, Qiao Zhou, Menghan Gao, Weihuan Fang, Chao Zheng","doi":"10.1002/advs.202411980","DOIUrl":"https://doi.org/10.1002/advs.202411980","url":null,"abstract":"Colorectal cancer (CRC) is a leading cause of cancer mortality while diabetes is a recognized risk factor for CRC. Here we report that tirzepatide (TZP), a novel polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist for the treatment of diabetes, has a role in attenuating CRC growth. TZP significantly inhibited colon cancer cell proliferation promoted apoptosis in vitro and induced durable tumor regression in vivo under hyperglycemic and nonhyperglycemic conditions across multiple murine cancer models. As glucose metabolism is known to critically regulate colon cancer progression, spatial metabolomics results revealed that glucose metabolites are robustly reduced in the colon cancer regions of the TZP-treated mice. TZP inhibited glucose uptake and destabilized hypoxia-inducible factor-1 alpha (HIF-1α) with reduced expression and activity of the rate-limiting enzymes 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) and phosphofructokinase 1 (PFK-1). These effects contributed to the downregulation of glycolysis and the tricarboxylic acid (TCA) cycle. TZP also delayed tumor development in a patient-derived xenograft (PDX) mouse model accompanied by HIF-1α mediated PFKFB3-PFK-1 inhibition. Therefore, the study provides strong evidence that glycolysis-blocking TZP, besides its application in treating type 2 diabetes, has the potential for preclinical studies as a therapy for colorectal cancer used either as monotherapy or in combination with other anticancer therapies.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2411980"},"PeriodicalIF":14.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0