Advanced Science最新文献

Correction to "Sequential Targeting Chondroitin Sulfate-Bilirubin Nanomedicine Attenuates Osteoarthritis via Reprogramming Lipid Metabolism in M1 Macrophages". 对“顺序靶向硫酸软骨素-胆红素纳米药物通过重编程M1巨噬细胞脂质代谢减轻骨关节炎”的修正。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-26 DOI: 10.1002/advs.202507227

引用次数: 0

Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids. 细胞内合成肽纳米结构的形成导致肿瘤球体的线粒体破坏和细胞死亡。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-26 DOI: 10.1002/advs.202412606

Sarah Chagri, Konrad Maxeiner, Maria J S A Silva, Lisa Förch, Julian Link, Patrick Roth, Raphael Meyer, Jana Fetzer, Anke Kaltbeitzel, Ingo Lieberwirth, Katharina Landfester, Manfred Wagner, David Y W Ng, Tanja Weil

{"title":"Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids.","authors":"Sarah Chagri, Konrad Maxeiner, Maria J S A Silva, Lisa Förch, Julian Link, Patrick Roth, Raphael Meyer, Jana Fetzer, Anke Kaltbeitzel, Ingo Lieberwirth, Katharina Landfester, Manfred Wagner, David Y W Ng, Tanja Weil","doi":"10.1002/advs.202412606","DOIUrl":"https://doi.org/10.1002/advs.202412606","url":null,"abstract":"Supramolecular assemblies found in nature demonstrate the concept of creating functionality through structure formation. In recent years, these complex natural architectures have inspired the development of materials for the formation of synthetic nanostructures within living cells. These intracellular assemblies have the potential to modulate cellular processes, yet their specific effects on cellular metabolism and 3D cell networks, such as tumor spheroids, still remain underexplored. Herein, the study correlates the glutathione-induced formation of synthetic nanostructures inside MDA-MB-231 triple-negative breast cancer cells to the metabolic disruption and mitochondrial degradation observed in 2D cell culture, as well as to cell death and size decrease in a 3D tumor spheroid model. In 2D cell culture, material-cell interactions are examined through live-cell imaging and by quantifying changes in mitochondrial respiration. By studying the interplay between glutathione-responsive cytosolic peptide assembly and the implications on the integrity of the mitochondrial network, as well as on 3D cell networks, the work advances the understanding of how synthetic intracellular nanofibers impact vital functions of living cells.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2412606"},"PeriodicalIF":14.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148866","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

deepTFBS: Improving within- and Cross-Species Prediction of Transcription Factor Binding Using Deep Multi-Task and Transfer Learning. deepTFBS：利用深度多任务和迁移学习改进转录因子结合的物种内和物种间预测。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-24 DOI: 10.1002/advs.202503135

Jingjing Zhai, Yuzhou Zhang, Chujun Zhang, Xiaotong Yin, Minggui Song, Chenglong Tang, Pengjun Ding, Zenglin Li, Chuang Ma

{"title":"deepTFBS: Improving within- and Cross-Species Prediction of Transcription Factor Binding Using Deep Multi-Task and Transfer Learning.","authors":"Jingjing Zhai, Yuzhou Zhang, Chujun Zhang, Xiaotong Yin, Minggui Song, Chenglong Tang, Pengjun Ding, Zenglin Li, Chuang Ma","doi":"10.1002/advs.202503135","DOIUrl":"https://doi.org/10.1002/advs.202503135","url":null,"abstract":"The precise prediction of transcription factor binding sites (TFBSs) is crucial in understanding gene regulation. In this study, deepTFBS, a comprehensive deep learning (DL) framework that builds a robust DNA language model of TF binding grammar for accurately predicting TFBSs within and across plant species is presented. Taking advantages of multi-task DL and transfer learning, deepTFBS is capable of leveraging the knowledge learned from large-scale TF binding profiles to enhance the prediction of TFBSs under small-sample training and cross-species prediction tasks. When tested using available information on 359 Arabidopsis TFs, deepTFBS outperformed previously described prediction strategies, including position weight matrix, deepSEA and DanQ, with a 244.49%, 49.15%, and 23.32% improvement of the area under the precision-recall curve (PRAUC), respectively. Further cross-species prediction of TFBS in wheat showed that deepTFBS yielded a significant PRAUC improvement of 30.6% over these three baseline models. deepTFBS can also utilize information from gene conservation and binding motifs, enabling efficient TFBS prediction in species where experimental data availability is limited. A case study, focusing on the WUSCHEL (WUS) transcription factor, illustrated the potential use of deepTFBS in cross-species applications, in our example between Arabidopsis and wheat. deepTFBS is publically available at https://github.com/cma2015/deepTFBS.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e03135"},"PeriodicalIF":14.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135998","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

Generation of Neural Organoids and Their Application in Disease Modeling and Regenerative Medicine. 神经类器官的生成及其在疾病建模和再生医学中的应用。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-24 DOI: 10.1002/advs.202501198

Ruiqi Huang, Feng Gao, Liqun Yu, Haokun Chen, Rongrong Zhu

{"title":"Generation of Neural Organoids and Their Application in Disease Modeling and Regenerative Medicine.","authors":"Ruiqi Huang, Feng Gao, Liqun Yu, Haokun Chen, Rongrong Zhu","doi":"10.1002/advs.202501198","DOIUrl":"https://doi.org/10.1002/advs.202501198","url":null,"abstract":"The complexity and precision of the human nervous system have posed significant challenges for researchers seeking suitable models to elucidate refractory neural disorders. Traditional approaches, including monolayer cell cultures and animal models, often fail to replicate the intricacies of human neural tissue. The advent of organoid technology derived from stem cells has addressed many of these limitations, providing highly representative platforms for studying the structure and function of the human embryonic brain and spinal cord. Researchers have induced neural organoids with regional characteristics by mimicking morphogen gradients in neural development. Recent advancements have demonstrated the utility of neural organoids in disease modeling, offering insights into the pathophysiology of various neural disorders, as well as in the field of neural regeneration. Developmental defects in neural organoids due to the lack of microglia or vascular systems are addressed. In addition to induction methods, microfluidics is used to simulate the dynamic physiological environment; bio-manufacturing technologies are employed to regulate physical signaling and shape the structure of complex organs. These technologies further expand the construction strategies and application scope of neural organoids. With the emergence of new material paradigms and advances in AI, new possibilities in the realm of neural organoids are witnessed.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e01198"},"PeriodicalIF":14.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136001","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

Heterojunction Derived Efficient Charge Separation for High Sensitivity Self-Powered Flexible Photodetectors toward Real-Time Heart Rate Monitoring. 用于实时心率监测的高灵敏度自供电柔性光电探测器的异质结衍生高效电荷分离。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-24 DOI: 10.1002/advs.202505945

Nan Ding, Ge Zhu, Xiaotao Zhang, Wen Xu, Hailong Liu, Yanan Ji, Yuanzheng Chen, Bin Dong

{"title":"Heterojunction Derived Efficient Charge Separation for High Sensitivity Self-Powered Flexible Photodetectors toward Real-Time Heart Rate Monitoring.","authors":"Nan Ding, Ge Zhu, Xiaotao Zhang, Wen Xu, Hailong Liu, Yanan Ji, Yuanzheng Chen, Bin Dong","doi":"10.1002/advs.202505945","DOIUrl":"https://doi.org/10.1002/advs.202505945","url":null,"abstract":"Real-time and accurate heart rate monitoring is crucial in the field of disease prevention and early diagnosis. Compared with the conventional rigid heart rate sensors, wearable flexible devices have unique advantages, such as convenient, high comfortable to the skin, and low data extraction errors. Currently, the available flexible electronic devices encounter with large power consumption, low detectivity, and slow response time, restricting their further commercial applications. Herein, flexible self-powered photodetectors (PDs) are developed by the synergistic strategy of engineering CsPbI3:Ho3+@SnS quantum dots (QDs) p-n heterojunctions and doping SnS QDs into spiro-OMeTAD hole transport layer (HTL). The designing CsPbI3:Ho3+@SnS QDs p-n heterojunctions as the photosensitive layer to effectively enhance the built-in field, reduce defect density, and boost the charge separation efficiency. Meanwhile, the high hole mobility and suitable energy band structure of p-type SnS QDs are doped into spiro-OMeTAD HTL, which can improve the hole extraction, and balance electron and hole mobilities. Such flexible self-powered PDs exhibit excellent sensitivity and stability with high responsivity (0.58 A W-1) and detectivity (1.13×1013 Jones), and fast response time (98.8 µs). The flexible self-powered PDs are further integrated with the light-emitting diodes (LEDs) as a photoplethysmography (PPG) system, realizing real-time and accurate heart rate monitoring.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2505945"},"PeriodicalIF":14.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136004","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

Multi-Omics and -Organ Insights into Energy Metabolic Adaptations in Early Sepsis Onset. 脓毒症早期发病的多组学和器官能量代谢适应研究。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-24 DOI: 10.1002/advs.202504418

Lin-Lin Xu, Zhengyuan Zhou, Sascha Schäuble, Wolfgang Vivas, Karen Dlubatz, Michael Bauer, Sebastian Weis, Mervyn Singer, Roman Lukaszewski, Gianni Panagiotou

{"title":"Multi-Omics and -Organ Insights into Energy Metabolic Adaptations in Early Sepsis Onset.","authors":"Lin-Lin Xu, Zhengyuan Zhou, Sascha Schäuble, Wolfgang Vivas, Karen Dlubatz, Michael Bauer, Sebastian Weis, Mervyn Singer, Roman Lukaszewski, Gianni Panagiotou","doi":"10.1002/advs.202504418","DOIUrl":"https://doi.org/10.1002/advs.202504418","url":null,"abstract":"Systemic metabolic dysregulation in sepsis critically impacts patient survival. To better understand its onset, untargeted serum metabolomics and lipidomics are analyzed from 152 presymptomatic patients undergoing major elective surgery, and identified key metabolites, including serine and aminoadipic acid, that differentiate postoperative uncomplicated infection from sepsis. Using single-nucleus RNA sequencing data from an in vivo mouse model of sepsis, tissue-independent down-regulation and tissue-specific differences of serine and energy-related genes including key module roles for the mitochondria-linked genes, Cox4i1, Cox8a, and Ndufa4 are identified. Finally, serine-dependent metabolic shifts, especially in the liver, are revealed by using 12C/13C murine data with labeled serine, and link altered activity of the serine hydroxymethyltransferase (SHMT) cycle with perturbed purine metabolism during sepsis. This study demonstrates the close interrelationship between early metabolite changes and mitochondrial dysfunction in sepsis, improves the understanding of the underlying pathophysiology, and highlights metabolic targets to prospectively treat presymptomatic, but at-risk, patients.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e04418"},"PeriodicalIF":14.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136018","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

2D Conductive MOFs Intercalated in MXene Interlayer for Fast and Trace Detection of Triethylamine at Room Temperature. MXene夹层中嵌入二维导电mof用于室温下快速痕量检测三乙胺。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-24 DOI: 10.1002/advs.202500786

Hao Zhang, Wei Cao, Jingfeng Wang, Lei Guo, Pu-Hong Wang, Zhi-Jun Ding, Lingmin Yu

{"title":"2D Conductive MOFs Intercalated in MXene Interlayer for Fast and Trace Detection of Triethylamine at Room Temperature.","authors":"Hao Zhang, Wei Cao, Jingfeng Wang, Lei Guo, Pu-Hong Wang, Zhi-Jun Ding, Lingmin Yu","doi":"10.1002/advs.202500786","DOIUrl":"https://doi.org/10.1002/advs.202500786","url":null,"abstract":"Metal-organic frameworks (MOFs) are newly developed materials for gas sensing applications currently. However, the prolonged response time limits their future applications because of their poor electrical conductivity. In this context, alternating stacked MXene@Cu-HHTP heterostructures characterized by a sandwich-type architecture comprised of Cu-HHTP (copper-catecholate frameworks), 2D conductive MOFs, and layered MXene achieve high-performance triethylamine (TEA) sensing. The unique interlayer pore architecture within the MXene@Cu-HHTP composites facilitates efficient mass transfer of gas molecules while retaining the large surface area and porosity characteristics of the MOFs, leading to rapid TEA response. MXene@Cu-HHTP composites respond to 50 ppm TEA in only 4 s and low detection limit (1 ppm). Demonstrated higher sensitivity compared to the original Cu-HHTP sensor (≈21 times at 200 ppm TEA). At room temperature and atmospheric conditions, the value of moisture resistance of MXene@Cu-HHTP composites can reach 80% through continuous real-time dynamic testing.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2500786"},"PeriodicalIF":14.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135944","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

Superior Capacitive Energy Storage of BaTiO₃-Based Polymorphic Relaxor Ferroelectrics Engineered by Mesoscopically Chemical Homogeneity. 介观化学均匀性设计的基于batio3的多晶弛豫铁电体的优越电容储能。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-24 DOI: 10.1002/advs.202502916

Aiwen Xie, Ziyi Yu, Junwei Lei, Yi Zhang, Ao Tian, Xuewen Jiang, Xinchun Xie, Yuewei Yin, Zhenqian Fu, Xiaoguang Li, Ruzhong Zuo

{"title":"Superior Capacitive Energy Storage of BaTiO3-Based Polymorphic Relaxor Ferroelectrics Engineered by Mesoscopically Chemical Homogeneity.","authors":"Aiwen Xie, Ziyi Yu, Junwei Lei, Yi Zhang, Ao Tian, Xuewen Jiang, Xinchun Xie, Yuewei Yin, Zhenqian Fu, Xiaoguang Li, Ruzhong Zuo","doi":"10.1002/advs.202502916","DOIUrl":"https://doi.org/10.1002/advs.202502916","url":null,"abstract":"Relaxor ferroelectrics exhibit giant potentials in capacitive energy storage, however, the scales of polar nanoregions determine the critical field values where the polarization saturation occurs. In this work, a mesoscopic structure engineered ergodic relaxor state is realized by adjusting submicron-grain scaled chemical homogenity, exhibiting polymorphic polar nanoregions of various scales in different grains. This produces a relatively continuous polarization switching with increasing the applied electric field from diverse grains, thus resulting in a linear-like polarization response feature. As a result, both a giant energy density (Wrec) ≈15.4 J cm-3 and a field-insensitive ultrahigh efficiency (η) ≈93.2% are simultaneously achieved at 78 kV mm-1 in (Ba, Ca)(Ti, Zr)O3-(Bi0.5Na0.5)SnO3 lead-free ceramics. Moreover, both the mesoscopic structure heterogeneity and complex high internal stresses in ultrafine grains decrease the temperature sensitivity of the nanodomain structural features. Together with the suppressed high-temperature defect motion from high ceramic density and submicron grain size, a record-high temperature stability with Wrec = 10.4±5% J cm-3 and η = 96±3% is obtained at 65 kV mm-1 and 0-250 °C, demonstrating great application potential of the studied ceramic in high-temperature energy storage capacitors. The proposed strategy in this work greatly expands the design mentality for next-generation high-performance energy-storage dielectrics.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2502916"},"PeriodicalIF":14.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136056","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

piR-RCC Suppresses Renal Cell Carcinoma Progression by Facilitating YBX-1 Cytoplasm Localization. piR-RCC通过促进YBX-1细胞质定位抑制肾癌进展。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-24 DOI: 10.1002/advs.202414398

Ruyue Wang, Fan Li, Yudong Lin, Zeyi Lu, Wenqin Luo, Zhehao Xu, Ziwei Zhu, Yi Lu, Xudong Mao, Yang Li, Zhinian Shen, Haohua Lu, Yining Chen, Liqun Xia, Mingchao Wang, Lifeng Ding, Gonghui Li

{"title":"piR-RCC Suppresses Renal Cell Carcinoma Progression by Facilitating YBX-1 Cytoplasm Localization.","authors":"Ruyue Wang, Fan Li, Yudong Lin, Zeyi Lu, Wenqin Luo, Zhehao Xu, Ziwei Zhu, Yi Lu, Xudong Mao, Yang Li, Zhinian Shen, Haohua Lu, Yining Chen, Liqun Xia, Mingchao Wang, Lifeng Ding, Gonghui Li","doi":"10.1002/advs.202414398","DOIUrl":"https://doi.org/10.1002/advs.202414398","url":null,"abstract":"PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, are widely expressed in eukaryotes and deregulated in several pathologies, including cancer. Little is known about their function and mechanism in renal cell carcinoma (RCC) progression. Herein, a down-regulated piRNA in RCC, termed piR-hsa-28489 (designated as piR-RCC), is identified to impede RCC progression both in vivo and in vitro. Mechanistically, piR-RCC directly interacts with Y-box binding protein 1 (YBX-1), thus impeding p-AKT-mediated YBX-1 phosphorylation and its subsequent nuclear translocation. Moreover, YBX-1 coordinates the transcription of ETS homologous factor (EHF) as a repressor factor. Consequently, piR-RCC enhances EHF expression, leading to the inhibition of RCC proliferation and metastasis. Based on these, a biomimetic nanoparticle platform is constructed to achieve RCC-specific targeted delivery of piR-RCC. The nanoparticles are fabricated using a cell membrane coating derived from cancer cells and used to encapsulate and deliver piR-RCC plasmids to renal orthotopic implantation in mice, hindering RCC progression. This study illustrates piR-RCC/YBX-1/EHF signaling axis in RCC, offering a promising therapeutic avenue for RCC.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e14398"},"PeriodicalIF":14.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136032","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

Small Extracellular Vesicles Orchestrate Cisplatin-Induced Ototoxicity: Potential Biomarker and Targets Discovery. 细胞外小泡协调顺铂诱导的耳毒性：潜在的生物标志物和靶点发现。

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-05-24 DOI: 10.1002/advs.202502627

Jingru Ai, Shasha Zhang, Mingchen Dai, Pei Jiang, Jingyuan Huang, Hairong Xiao, Yanqin Lin, Xujun Tang, Wei Tong, Jun He, Qiuyue Mao, Yintao Wang, Zixuan Ye, Tian Wang, Renjie Chai

{"title":"Small Extracellular Vesicles Orchestrate Cisplatin-Induced Ototoxicity: Potential Biomarker and Targets Discovery.","authors":"Jingru Ai, Shasha Zhang, Mingchen Dai, Pei Jiang, Jingyuan Huang, Hairong Xiao, Yanqin Lin, Xujun Tang, Wei Tong, Jun He, Qiuyue Mao, Yintao Wang, Zixuan Ye, Tian Wang, Renjie Chai","doi":"10.1002/advs.202502627","DOIUrl":"https://doi.org/10.1002/advs.202502627","url":null,"abstract":"Cisplatin-induced ototoxicity remains a clinical dilemma with limited mechanistic understanding and no food and drug administration (FDA)-approved therapies. Despite emerging roles of small extracellular vesicles (sEV) in drug ototoxicity, their molecular cargo profiles and causal roles to cisplatin-induced ototoxicity are unexplored. This study systematically investigates sEV derived from cochlear explants treated with cisplatin (Cis-sEV) and controls (Ctrl-sEV) using multi-omics profiling. Through small RNA sequencing, 83 differentially expressed microRNAs (miRNAs) are identified in Cis-sEV compared to Ctrl-sEV. Notably, mmu-miR-34a-5p, mmu-miR-140-5p, mmu-miR-15b-5p, mmu-miR-25-3p, and mmu-miR-339-5p are significantly upregulation in Cis-sEVs. Predicted target pathways of these differentially expressed miRNAs are enriched in apoptosis, inflammation, and cellular damage, indicating their potential involvement in cisplatin-induced cochlear damage. LC-MS/MS analysis reveals 90 upregulated and 150 downregulated proteins in Cis-sEV, with many involved in damage response. Specifically, CLTC, CCT2, ANXA6, and HSPA8 are uniquely upregulated proteins in Cis-sEV, and CLTC and ANXA6 are exclusively co-localized in hair cells (HCs) post-cisplatin exposure, suggesting that Cis-sEV originate primarily from damaged HCs. Moreover, CLTC in sEV may serve as a potential biomarker for cisplatin-induced ototoxicity as verified in both in vitro and in vivo models. This study provides novel insights into the molecular mechanisms of cisplatin-induced ototoxicity and identifies potential biomarker and therapeutic targets.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e02627"},"PeriodicalIF":14.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136051","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