{"title":"Unveiling the Over-Lithiation Behavior of NCM523 Cathode Towards Long-Life Anode-Free Li Metal Batteries.","authors":"Ruimin Gao, Minzhi Zhan, Tingcan Li, Pei Xiong, Qian Zhang, Zhefeng Chen, Jike Wang, Xinping Ai, Feng Pan, Liumin Suo, Jiangfeng Qian","doi":"10.1002/advs.202503558","DOIUrl":"https://doi.org/10.1002/advs.202503558","url":null,"abstract":"<p><p>Anode-free lithium metal batteries (AFLMBs) offer the potential for significantly enhanced energy densities. However, their practical application is limited by a shortened cycling life due to inevitable Li loss from parasitic reactions. This study addresses this challenge by incorporating an over-lithiated Li<sub>1+</sub> <sub>x</sub>Ni<sub>0.5</sub>Co<sub>0.2</sub>Mn<sub>0.3</sub>O<sub>2</sub> (Li<sub>1+</sub> <sub>x</sub>NCM523) cathode as an internal Li reservoir to compensate for lithium loss during extended cycling. A rigorous investigation of the deep discharge behavior of the Li<sub>1+</sub> <sub>x</sub>NCM523 cathode reveals a critical over-lithiation threshold at x = 0.7. At this threshold, excess Li<sup>+</sup> ions are safely accommodated within the crystal structure by a transformation from the LiO<sub>4</sub> octahedron to two tetrahedral sites. Beyond this threshold (x ≥ 0.7), the structural stability of the cathode is significantly compromised due to the irreversible reduction of transition metal (TM) ions. The optimal Li-rich Li<sub>1.7</sub>NCM523 releases an additional charge capacity of ≈160 mAh g<sup>-1</sup> during the first charge. Consequently, the AFLMBs (Li<sub>1.7</sub>NCM523||Cu) achieve outstanding capacity retention of 93.3% after 100 cycles at 0.5 C and 78.5% after 200 cycles at 1 C. The findings establish a research paradigm for designing superior over-lithiated transition metal oxide cathode materials and underscore the critical role of the lithium reservoir in extending the cycle life of AFLMBs.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2503558"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668516","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}
{"title":"A Bio-Adaptive Janus-Adhesive Dressing with Dynamic Lubrication Overlayer for Prevention of Postoperative Infection and Adhesion.","authors":"Yuan Gao, Junchang Guo, Shuangyang Li, Liansong Ye, Binyang Lu, Jiaxin Liu, Jing Luo, Yijia Zhu, Liuxiang Chen, Tingfa Peng, Jinlong Yang, Dehui Wang, Chaoming Xie, Xu Deng, Bing Hu","doi":"10.1002/advs.202500138","DOIUrl":"https://doi.org/10.1002/advs.202500138","url":null,"abstract":"<p><p>Wound postoperative infection and adhesion are prevalent clinical conditions resulting from surgical trauma. However, integrating intraoperative repair and postoperative management into a dressing suitable for wounds with unpredictable surface shapes and surroundings remains a formidable challenge. Here, we attempt to introduce a dynamic antifouling surface as wound protective covering and report an in situ formation of slippery-adhesive Janus gel (SAJG) by assembling hydrogel (N-hydrosuccinimide ester-activated powders) and elastomer (Silicon oil-infused polydimethylsiloxane). First powders can rapidly absorb interfacial water to gel and bond to tissue based on network entanglement, forming a tough adhesive hydrogel. Then precured organosilicon is applied to hydrogel and bonded together, forming a slippery elastomer. Due to the molecular polarity difference between hydrogel and elastomer, SAJG exhibits anisotropic surface behavior as evidenced by liquid repellency (hydrophilic vs. hydrophobic), and adhesion performance (bioadhesion vs. antiadhesion). Further, in vivo models are constructed and results demonstrated that the SAJG can effectively prevent bacterial infection to promote wound healing and avoid postoperative adhesion. Predictably, the morphologically adaptive SAJG with slippery and adhesive properties will have tremendous potential in addressing complex wound infections and postoperative complications.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2500138"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668564","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}
Advanced SciencePub Date : 2025-03-20DOI: 10.1002/advs.202412498
Yu Cao, Qirong Xie, Qiang Zheng, Jingping Zhang, Mengyu Yao, Zhongyong Du, Lujun Zhang, Tianyang Hu, Yunli Zhao, Jianlin Du, Yongyong Li, Yuxing Feng, N D Melgiri, Xiaodong Zhao, Rongzhong Huang, Yang Sun
{"title":"Macrophage HM13/SPP Enhances Foamy Macrophage Formation and Atherogenesis.","authors":"Yu Cao, Qirong Xie, Qiang Zheng, Jingping Zhang, Mengyu Yao, Zhongyong Du, Lujun Zhang, Tianyang Hu, Yunli Zhao, Jianlin Du, Yongyong Li, Yuxing Feng, N D Melgiri, Xiaodong Zhao, Rongzhong Huang, Yang Sun","doi":"10.1002/advs.202412498","DOIUrl":"https://doi.org/10.1002/advs.202412498","url":null,"abstract":"<p><p>Aryl Hydrocarbon Receptor-Interacting Protein (AIP) reduces macrophage cholesterol-ester accumulation and may prevent atherogenic foamy macrophage formation. Analyzing AIP-associated regulatory gene networks can aid in identifying key regulatory mechanism(s) underlying foamy macrophage formation. A weighted gene co-expression network analysis on the Stockholm Atherosclerosis Gene Expression (STAGE) patient cohort identifies AIP as a negative correlate of Histocompatibility Minor 13 (HM13), which encodes the ER-associated degradation (ERAD) protein Signal Peptide Peptidase (HM13/SPP). The negative correlation between AIP and HM13/SPP on mRNA and protein levels is validated in oxLDL-stimulated macrophages and human plaque foamy macrophages. Mechanistically, AIP, via its chaperone interaction with Aryl Hydrocarbon Receptor (AHR), inhibits p38-c-JUN-mediated HM13 transactivation, thereby suppressing macrophage lipid accumulation. Myeloid HM13/SPP overexpression enhances oxLDL-induced foamy macrophage formation in vitro as well as atherogenesis and plaque foamy macrophage load in vivo, while myeloid HM13/SPP knockout produces the opposite effects. Mechanistically, myeloid HM13/SPP enhances oxLDL-induced foamy macrophage formation in vitro as well as atherogenesis and plaque foamy macrophage load in vivo via promoting ERAD-mediated proteasomal degradation of the metabolic regulator Heme Oxygenase-1 (HO-1). In conclusion, AIP downregulates macrophage HM13/SPP, a driver of oxLDL-induced lipid loading, foamy macrophage generation, and atherogenesis.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2412498"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668587","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}
Advanced SciencePub Date : 2025-03-20DOI: 10.1002/advs.202407349
Linfei Mao, Jiayu Lu, Quanjun Yang, Zhenqi Liu, Cuiping Wu, Bingbing Ke, Kaiyan Su, Haolin Yuan, Yaqi Cui, Yao Wang, Richard Salvi, Guang Yang, Shankai Yin, Feng Liu, Chunyan Li
{"title":"Bilirubin Targeting WNK1 to Alleviate NLRP3-Mediated Neuroinflammation.","authors":"Linfei Mao, Jiayu Lu, Quanjun Yang, Zhenqi Liu, Cuiping Wu, Bingbing Ke, Kaiyan Su, Haolin Yuan, Yaqi Cui, Yao Wang, Richard Salvi, Guang Yang, Shankai Yin, Feng Liu, Chunyan Li","doi":"10.1002/advs.202407349","DOIUrl":"https://doi.org/10.1002/advs.202407349","url":null,"abstract":"<p><p>Bilirubin, an endogenous metabolite with many significant physiological roles, particularly anti-inflammatory properties, shows great promise as a treatment for inflammatory diseases. However, the binding targets and downstream signaling mechanisms of bilirubin remain unclear. Here, by using quantitative phosphorylation proteomics and several powerful chemical biology techniques such as the Cellular Thermal Shift Assay (CETSA), molecular docking, and MicroScale Thermophoresis (MST), it is identified and confirmed that with-no-lysine (K) kinase 1 (WNK1) is the primary target of bilirubin at physiological concentrations. Bilirubin binds to the kinase domain of WNK1, activating its kinase activity and increasing the intracellular chloride ion concentration via the downstream SPAK/OSR1-KCC2 pathway in neurons. Manipulating endogenous bilirubin levels by deleting Blvra, the bilirubin synthesis enzyme, and Ugt1a1, its metabolic enzyme, significantly promotes and inhibits the activation of the lipopolysaccharide (LPS)-induced NLRP3 inflammasome, respectively, in mouse hippocampus. Similarly, exogenous bilirubin supplementation suppressed LPS-induced NLRP3 inflammasome activation in mouse hippocampus in a WNK1-dependent manner. Quantitative phosphoproteomic analysis of WNK1 downstream signaling elucidated the broad biological roles of WNK1, notably its function in suppressing inflammation. The findings clarify the direct targets and signaling mechanisms underlying the anti-inflammatory effects of bilirubin and pave the way for exploring its novel functions.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2407349"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668571","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}
Advanced SciencePub Date : 2025-03-20DOI: 10.1002/advs.202416688
Meiling Liu, Xiansheng Li, Wenshuo Zhang, Lanxin Li, Liang Li, Chengming Wang, Gang Pei, Bin Zhao, Chongwen Zou
{"title":"Three-State Thermochromic Smart Window for Building Energy-Saving.","authors":"Meiling Liu, Xiansheng Li, Wenshuo Zhang, Lanxin Li, Liang Li, Chengming Wang, Gang Pei, Bin Zhao, Chongwen Zou","doi":"10.1002/advs.202416688","DOIUrl":"https://doi.org/10.1002/advs.202416688","url":null,"abstract":"<p><p>Smart windows that dynamically regulate solar spectrum transmission to reduce energy consumption in heating, ventilation, and air conditioning systems are highly desirable. However, the limited amplitude of the regulation and narrow wavelength control often degrade the modulation performance of existing smart windows. To improve solar modulation and thermal management, here we propose a three-state thermochromic smart window (TSSW) capable of modulation across the entire solar spectrum. The TSSW is mainly based on the unique phase transition properties of tungsten-doped vanadium dioxide (W-VO₂) and perovskite films, which can stepwise control the visible light and near-infrared (NIR) transmittance separately, leading to the adaptive transitions between cold, warm, and hot states. Results indicate that the TSSW achieves a solar modulation rate of 23.5%, with indoor solar irradiance decreasing from 413.6 W/m<sup>2</sup> in the cold state to 374.5 W/m<sup>2</sup> in the warm state, and down to 189.1 W/m<sup>2</sup> in the hot state. The simulation results show that the annual total energy demand can be reduced by up to 102.09 WJ/m<sup>2</sup> in some typical regions. Compared to Low-E glass and ordinary glass, this TSSW offers superior energy-saving potential, making it an ideal solution for reducing building energy consumption.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2416688"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668682","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}
{"title":"Triple-Stimuli Responsive Soft Robots with Photo-Programmable Ferriferous Oxide Particle Patterns.","authors":"Siwei Hu, Kexing Li, Weijia Nong, Zhong-Wen Liu, Zhao-Tie Liu, Yanhu Zhan, Jinqiang Jiang, Peng Yang, Guo Li","doi":"10.1002/advs.202500669","DOIUrl":"https://doi.org/10.1002/advs.202500669","url":null,"abstract":"<p><p>Magneto-driven soft robots featuring remote and highly permeable controllability are considered promising, especially in biomedical and engineering applications. However, there is still lack of a high-precision method to regulate the distribution of magnetic fillers in polymer substrates, which severely limits the improvement of the actuating functionality. This work provides a photo-regulatable method to develop soft robots with locally distributed magnetic Fe<sub>3</sub>O<sub>4</sub> nanoparticles. Solvent-casted polyvinyl alcohol/sodium carboxymethyl cellulose film is prepared as the substrate, and Fe<sup>3+</sup> ions are introduced to coordinate with carboxylate groups by surface treatment. Two processes, photo-reduction of Fe<sup>3+</sup> to Fe<sup>2+</sup> ions and the hydrolytic reaction of the two ions, are sequentially combined to in situ generate magnetic Fe<sub>3</sub>O<sub>4</sub> particles. Spatiotemporal control of UV light irradiation determines the Fe<sup>3+</sup>/Fe<sup>2+</sup> ratio and, therefore the amount of generated Fe<sub>3</sub>O<sub>4</sub> nanoparticles that decide magnetic field, NIR light, and moisture responsive actuating functionalities. Moreover, the external geometry of the composite can be tuned by inducing the formation of Al<sup>3+</sup>-carboxylate coordinates for strain retention, which enables shape programming of the composite to exhibit complex 3D-3D actuating behaviors. The proposed method enables the design and preparation of soft robots with spatially tunable magnetism and more advanced actuating behaviors.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2500669"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668686","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}
Advanced SciencePub Date : 2025-03-20DOI: 10.1002/advs.202413456
Weiwei Wang, Yanting Liu, Jiayi Gu, Shaoya An, Cheng Ma, Haichun Gao, Nianzhi Jiao, Jian-Ren Shen, John Thomas Beatty, Michal Koblížek, Xing Zhang, Qiang Zheng, Jing-Hua Chen
{"title":"Cryo-EM Analysis of a Tri-Heme Cytochrome-Associated RC-LH1 Complex from the Marine Photoheterotrophic Bacterium Dinoroseobacter Shibae.","authors":"Weiwei Wang, Yanting Liu, Jiayi Gu, Shaoya An, Cheng Ma, Haichun Gao, Nianzhi Jiao, Jian-Ren Shen, John Thomas Beatty, Michal Koblížek, Xing Zhang, Qiang Zheng, Jing-Hua Chen","doi":"10.1002/advs.202413456","DOIUrl":"https://doi.org/10.1002/advs.202413456","url":null,"abstract":"<p><p>The reaction center-light harvesting 1 (RC-LH1) complex converts solar energy into electrical energy, driving the initiation of photosynthesis. The authors present a cryo-electron microscopy structure of the RC-LH1 isolated from a marine photoheterotrophic bacterium Dinoroseobacter shibae. The RC comprises four subunits, including a three-heme cytochrome (Cyt) c protein, and is surrounded by a closed LH ring composed of 17 pairs of antenna subunits. Notably, a novel subunit with an N-terminal \"helix-turn-helix\" motif embedded in the gap between the RC and the LH ring is identified. The purified RC-LH1 complex exhibits high stability in solutions containing Mg<sup>2+</sup> or Ca<sup>2+</sup>. The periplasmic Cyt c<sub>2</sub> is predicted to bind at the junction between the Cyt subunit and the membrane plane, enabling electron transfer from Cyt c<sub>2</sub> to the proximal heme of the tri-heme Cyt, and subsequently to the special pair of bacteriochlorophylls. These findings provide structural insights into the efficient energy and electron transfer processes within a distinct type of RC-LH1, and shed light on evolutionary adaptations of photosynthesis.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2413456"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668506","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}
{"title":"Imaging-Guided Microscale Photothermal Stereolithography Bioprinting.","authors":"Jingyu Sun, Tianqi Fang, Yuze Zhang, Jue Wang, Huan Han, Tsengming Chou, Junfeng Liang, Dilhan M Kalyon, Hongjun Wang, Shang Wang","doi":"10.1002/advs.202500640","DOIUrl":"https://doi.org/10.1002/advs.202500640","url":null,"abstract":"<p><p>Stereolithography bioprinting relies heavily on costly photoinitiators for polymerization, limiting its potential for further technical advancement to meet growing needs in tissue engineering and regenerative medicine. Thermal initiators, in contrast, are low cost, and rapid growth of the photothermal conversion field offers a wide range of materials and tools to convert light into heat. However, high-resolution photothermal stereolithography bioprinting remains unattainable due to the difficulty of confining heat in an aqueous environment. Here, this challenge has been fully addressed by establishing imaging-guided microscale photothermal stereolithography bioprinting (ImPSB). This technique is achieved through building a novel imaging-guided stereolithography system that provides depth-resolved visualization of the printing dynamics, creating a unique photothermal initiator in the second near-infrared window, and developing a new bioink by seeing and controlling the photothermal gelation process. ImPSB achieves a printing resolution of ≈47 µm and generates smooth lines of arbitrarily designed shapes with a cross-sectional diameter as small as ≈104 µm, representing an unprecedented scale from photothermal aqueous stereolithography. Its cellular biocompatibility in printing both bioscaffold and cell-laden hydrogel is demonstrated, and its feasibility of transdermal printing is also shown. This work sets a new path for high-resolution stereolithography bioprinting where the vast photothermal resources can be utilized.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2500640"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668582","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}
{"title":"Semaphorin 3E-Plexin D1 Axis Drives Lung Fibrosis through ErbB2-Mediated Fibroblast Activation.","authors":"Zhesong Deng, Jinkun Chen, Ruonan Yang, Yuan Zhan, Shanshan Chen, Jiaheng Zhang, Hao Fu, Yiya Gu, Qian Huang, Jixing Wu, Lianyu Shan, Abdelilah Soussi Gounni, Jungang Xie","doi":"10.1002/advs.202415007","DOIUrl":"https://doi.org/10.1002/advs.202415007","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is characterized by excessive fibroblast recruitment and persistent extracellular matrix deposition at sites of tissue injury, leading to severe morbidity and mortality. However, the precise mechanisms by which fibroblasts contribute to IPF pathogenesis remain poorly understood. The study reveals that Sema3E and its receptor Plexin D1 are significantly overexpressed in the lungs of IPF patients and bleomycin (BLM)-induced lung fibrotic mice. Elevated plasma levels of Sema3E in IPF patients are negatively correlated with lung function. Importantly, Sema3E in IPF lungs predominantly exists as the P61-Sema3E. The knockdown of Sema3E or Plexin D1 effectively inhibits fibroblast activation, proliferation, and migration. Mechanistically, Furin-mediated cleavage of P87-Sema3E into P61-Sema3E drives these pro-fibrotic activities, with P61-Sema3E-PlexinD1 axis promoting fibroblast activation, proliferation, and migration by affecting the phosphorylation of ErbB2, which subsequently activates the ErbB2 pathways. Additionally, Furin inhibition reduces fibroblast activity by decreasing P61-Sema3E production. In vivo, both whole-lung Sema3E knockdown and fibroblast-specific Sema3E knockout confer protection against BLM-induced lung fibrosis. These findings underscore the crucial role of the P61-Sema3E-Plexin D1 axis in IPF pathogenesis and suggest that targeting this pathway may hold promise for the development of novel therapeutic strategies for IPF treatment.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2415007"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668693","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}
{"title":"Targeting COPA to Enhance Erdafitinib Sensitivity in FGFR-Altered Bladder Cancer.","authors":"Huayuan Zhao, Xincheng Gao, Yangkai Jiang, Yanchao Yu, Liang Wang, Jiayin Sun, Miao Wang, Xing Xiong, Chao Huang, Hui Zhang, Guosong Jiang","doi":"10.1002/advs.202413209","DOIUrl":"https://doi.org/10.1002/advs.202413209","url":null,"abstract":"<p><p>Fibroblast growth factor receptor (FGFR) family aberrations are common in urothelial cancer. The FGFR tyrosine kinase inhibitor erdafitinib has been approved for locally advanced or metastatic urothelial cancer with FGFR2/3 alterations. Despite the initial efficacy of erdafitinib, resistance cannot be avoided. The molecular mechanisms underlying erdafitinib resistance have not been well investigated. Here, genome-wide CRISPR screen is performed and coatomer protein complex subunit α (COPA) is identified as a key target to enhance erdafitinib sensitivity. Functionally, the deficiency of COPA reduces the proliferation of FGFR-altered bladder cancer cells upon erdafitinib treatment. Mechanistically, COPA knockout increases the degradation of leucine-rich pentatricopeptide repeat containing (LRPPRC) protein, leading to reduced inhibitor of DNA binding 3 (ID3) mRNA stability in an m6A-dependent manner. Collectively, these findings reveal a novel mechanism of erdafitinib resistance, providing a potential therapeutic target for FGFR-altered bladder cancer.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2413209"},"PeriodicalIF":14.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668701","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}
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