Advanced Science最新文献_第10页

Entropy Decoding the Fundamental Law of Phase Competition in Glass Formation. 熵解码玻璃形成相竞争的基本规律。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 Epub Date: 2026-06-15 DOI: 10.1002/advs.75936

Benke Huo, Zhengqing Cai, Bingtao Wang, Zhenqiang Song, Shi-Dong Feng, Zijing Li, Xingjun Liu, Li-Min Wang

{"title":"Entropy Decoding the Fundamental Law of Phase Competition in Glass Formation.","authors":"Benke Huo, Zhengqing Cai, Bingtao Wang, Zhenqiang Song, Shi-Dong Feng, Zijing Li, Xingjun Liu, Li-Min Wang","doi":"10.1002/advs.75936","DOIUrl":"10.1002/advs.75936","url":null,"abstract":"The quest to understand the fundamentals of optimal glass-forming compositions in multi-component alloys has long been challenging. To gain insights into the mechanism, a systematic study of glass compositions is conducted using a new strategy of entropy engineering, imposed by the integration of eutectic or intermetallic phases featured by their low melting entropies, which can be determined experimentally and precisely. The optimal composition designed using entropy engineering is further compared with that derived from the conventional \"deep eutectic\" principle and empirical trial-and-error. For the ternary Cu-Zr-Ti alloys, a series of compositions are achieved, and the ranking of their glass-forming ability indicates a correlation with the melting entropies of initial phases. In particular, the optimal glass-forming composition of Cu59.99Zr28.75Ti11.26 is designed using two initial phases of intermetallic Cu50Zr50 and eutectic Cu73.5Ti26.5 with the lowest melting entropies. This designed composition is remarkably equivalent to the reported one, Cu60Zr30Ti10. It is more meaningful that this study uncovers the phase competition mechanism involved in glass formation in a quantitative way for the first time, emphasizing the importance of melting entropies in screening and balancing the competing phases upon glass formation.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e75936"},"PeriodicalIF":14.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Pollen-Enhanced Bionic Mechanoreceptor Induced by Asymmetric Ionic Convection in Hydrogel for Sensory-Augmented Prostheses. 非对称离子对流水凝胶诱导花粉增强仿生机械感受器用于感官增强假体。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 Epub Date: 2026-06-19 DOI: 10.1002/advs.202521235

Zi Hao Guo, Jingyu Deng, Yanzhang Xu, Chenchen Zhou, Yangshi Shao, Xiong Pu, Munho Kim, Namjoon Cho

{"title":"A Pollen-Enhanced Bionic Mechanoreceptor Induced by Asymmetric Ionic Convection in Hydrogel for Sensory-Augmented Prostheses.","authors":"Zi Hao Guo, Jingyu Deng, Yanzhang Xu, Chenchen Zhou, Yangshi Shao, Xiong Pu, Munho Kim, Namjoon Cho","doi":"10.1002/advs.202521235","DOIUrl":"10.1002/advs.202521235","url":null,"abstract":"The growing prevalence of age-related limb loss underscores the need for prosthetic technologies that restore not only motor function but also authentic sensory feedback. Current prosthetic systems largely depend on sensory substitution or signal remapping, which fall short of replicating natural somatosensory signals. In this work, we develop a plant-enhanced bionic mechanoreceptor that mimics biological touch by converting mechanical stimuli into ionic signals. Incorporating bio-derived pollen microgels into the hydrogel matrix introduces interfacial ion-anchoring sites that strengthen cation-matrix interactions, enhance ionic polarization, and significantly amplify the piezoionic output. This enhancement arises from pressure-driven asymmetric ion transport within the ionically conductive hydrogel. As a result, the output signal increases by up to 12-fold, providing a simple and accessible strategy to improve the sensitivity of piezoionic mechanoreceptors. Then, we demonstrate the integration of ten such mechanoreceptors into a robotic prosthetic arm and utilize a deep learning algorithm to interpret the complex signal patterns. The system achieves accurate recognition of object interaction, validating the potential for naturalistic tactile feedback. This platform offers a scalable, biomimetic solution for developing next-generation sensory-augmented prostheses and may inform future designs in neuroprosthetics and human-machine interfaces.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e21235"},"PeriodicalIF":14.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RBM10 Deficiency Promotes Anti-PD-1 Resistance in LUAD via STING Alternative Splicing-Driven CCL7 Signaling and Macrophage Polarization. RBM10缺乏通过STING选择性剪接驱动的CCL7信号和巨噬细胞极化促进LUAD抗pd -1抗性。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 Epub Date: 2026-06-22 DOI: 10.1002/advs.202522159

Weitong Gao, Ruqiong Wang, Bo An, Lishuang Qi, Zihan Jing, Xingmei Ren, Yang Zhou, Mingjun Xu, Jiaojiao Li, Jie Liu, Liying Wang, Gang Xu, Rou Li, Dexin Jia, Yan Yu

{"title":"RBM10 Deficiency Promotes Anti-PD-1 Resistance in LUAD via STING Alternative Splicing-Driven CCL7 Signaling and Macrophage Polarization.","authors":"Weitong Gao, Ruqiong Wang, Bo An, Lishuang Qi, Zihan Jing, Xingmei Ren, Yang Zhou, Mingjun Xu, Jiaojiao Li, Jie Liu, Liying Wang, Gang Xu, Rou Li, Dexin Jia, Yan Yu","doi":"10.1002/advs.202522159","DOIUrl":"10.1002/advs.202522159","url":null,"abstract":"Although immune checkpoint inhibitors have improved outcomes in lung adenocarcinoma (LUAD), many patients still exhibit inadequate responses. The immunomodulatory functions of RNA-binding motif (RBM) proteins remain poorly understood. Using in vivo and in vitro models of RBM10 deficiency combined with cytokine arrays, CLIP-seq, RIP, and proteomics, we found that RBM10 deficiency promotes an immunosuppressive microenvironment, and targeting key chemokines restored anti-PD-1 efficacy in RBM10-deficient LUAD models. RBM10 deficiency enhanced the polarization and recruitment of M2 tumor-associated macrophages (TAMs), both in vitro and in vivo. Mechanistically, RBM10 loss disrupted STING exon 3 exclusion via alternative splicing and impaired QKI-mediated stabilization of the STING-E3(-) isoform, shifting the splicing balance toward the STING-E3(+) isoform and promoting CCL7 secretion. CCL7 acted through its receptor CCR2 on macrophages, driving M2 polarization and recruitment. This central pathway was further reinforced by a positive feedback loop wherein M2-polarized TAMs transferred mitochondria to tumor cells, potentially contributing to mtDNA-cGAS-STING signaling and sustained CCL7 production. Therapeutically, CCL7/CCR2 blockade synergized with PD-1 inhibition to promote tumor regression in RBM10-deficient tumors. Collectively, RBM10 serves as a key immunoregulator in LUAD by modulating the STING-CCL7-CCR2 axis, and targeting the CCL7-CCR2 axis represents a promising strategy to overcome anti-PD-1 resistance.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e22159"},"PeriodicalIF":14.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148292787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ultrafast Hot-Carrier Cooling in CsPbBr₃ Supercrystals via Long-Range Electronic Coupling. 远距离电子耦合CsPbBr3超晶体的超快热载子冷却。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 Epub Date: 2026-06-09 DOI: 10.1002/advs.75913

Junhong Yu, Manoj Sharma, Yadong Han, Ke Wang, Zhenzhong Lian, Chang Cao, Lan Nguyen, Naufan Nurrosyid, Baiquan Liu, Jacek J Jasieniak

{"title":"Ultrafast Hot-Carrier Cooling in CsPbBr3 Supercrystals via Long-Range Electronic Coupling.","authors":"Junhong Yu, Manoj Sharma, Yadong Han, Ke Wang, Zhenzhong Lian, Chang Cao, Lan Nguyen, Naufan Nurrosyid, Baiquan Liu, Jacek J Jasieniak","doi":"10.1002/advs.75913","DOIUrl":"10.1002/advs.75913","url":null,"abstract":"Lead halide perovskite (LHP) nanocrystals (NCs) exhibit prolonged hot carrier (HC) cooling, which benefits photovoltaics but hinders light-emitting applications. Current strategies to modulate HC dynamics often compromise intrinsic material properties or introduce competing photophysical processes. Here, we demonstrate that long-range electronic coupling in CsPbBr3 supercrystals (SCs) efficiently accelerates HC cooling across different excitation regimes, enabling cooling dynamics approaching the prediction of the longitudinal optical phonon model. Owing to enhanced electronic density of states arising from cooperative interactions, transient absorption (TA) spectroscopy reveals SCs enable HC cooling that is twice as fast as isolated nanocrystals (NCs) at low carrier densities (2 × 1017 cm-3). Remarkably, under high excitation densities (4.3 × 1018 cm-3), carrier delocalization within the superlattices further weakens the spatial confinement-induced Auger heating, accelerating HC cooling by over an order of magnitude. This work establishes SCs as a fresh platform to manipulate HC cooling.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e75913"},"PeriodicalIF":14.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Al─N Co-Doped LLZO Solid Electrolytes via One-Step Sintering: Toward High Ionic Conductivity. 一步烧结Al─N共掺杂LLZO固体电解质：迈向高离子导电性。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 Epub Date: 2026-06-09 DOI: 10.1002/advs.75980

Hao Zhang, Yaocong Wang, Quande Che, Jiaming Wu, Yanzhu Zhang, Dongxu Mao, Xundao Liu, Jiajie Li, Zhengmao Ye, Dehua Dong

{"title":"Al─N Co-Doped LLZO Solid Electrolytes via One-Step Sintering: Toward High Ionic Conductivity.","authors":"Hao Zhang, Yaocong Wang, Quande Che, Jiaming Wu, Yanzhu Zhang, Dongxu Mao, Xundao Liu, Jiajie Li, Zhengmao Ye, Dehua Dong","doi":"10.1002/advs.75980","DOIUrl":"10.1002/advs.75980","url":null,"abstract":"Garnet-type Li7La3Zr2O12 (LLZO) is a promising solid electrolyte for solid-state lithium batteries owing to its relatively high ionic conductivity and wide electrochemical window. However, its conductivity still needs further improvement to meet practical application requirements. Herein, we propose for the first time a cation-anion co-doping strategy to synthesize Al─N co-doped LLZO via a one-step sintering process, achieving a high ionic conductivity of 2.19 × 10-3 S cm-1. Nudged elastic band (NEB) calculations reveal that Al─N co-doping reduces the energy barrier for Li+ migration, thereby enhancing ionic transport. Remarkably, the Li|LLZO-Al0.50N0.50|Li symmetric cell demonstrates stable lithium plating/stripping cycling over 600 h at 0.1 mA cm-2, and the LiFePO4| LLZO-Al0.50N0.50|Li full cell retains 82.6% of its initial capacity after 200 cycles at 0.3 C. This work confirms Al─N co-doping as an effective strategy for improving the ionic conductivity of LLZO, offering a viable route toward high-performance garnet-type solid electrolytes.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e75980"},"PeriodicalIF":14.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leonurine Ameliorates Doxorubicin-Induced Cardiotoxicity via STING/NF-κB/NLRP3 Inflammasome Signaling Pathway. 通过STING/NF-κB/NLRP3炎症小体信号通路改善阿霉素诱导的心脏毒性

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 Epub Date: 2026-06-12 DOI: 10.1002/advs.75912

Wang Jun, Chen Xiaoyang, Xu Jianglin, Yang Zhi, Tao Meijiao, He Jiale, Zhao Jiangfeng, Hei Xuanding, Xu Xuegong, Wang Wei, Li Chun

{"title":"Leonurine Ameliorates Doxorubicin-Induced Cardiotoxicity via STING/NF-κB/NLRP3 Inflammasome Signaling Pathway.","authors":"Wang Jun, Chen Xiaoyang, Xu Jianglin, Yang Zhi, Tao Meijiao, He Jiale, Zhao Jiangfeng, Hei Xuanding, Xu Xuegong, Wang Wei, Li Chun","doi":"10.1002/advs.75912","DOIUrl":"10.1002/advs.75912","url":null,"abstract":"Doxorubicin-induced cardiomyopathy (DIC) remains a dose-limiting clinical challenge. This study reveals that cardiac vascular endothelial cells (CVECs) act as initial sensors of doxorubicin cardiotoxicity: circulating doxorubicin activates the cGAS‑STING pathway in CVECs, triggering NLRP3 inflammasome‑mediated pyroptosis and release of pathogenic extracellular vesicles that induce mitochondrial dysfunction in neighboring cardiomyocytes, establishing a self‑perpetuating injury loop. Leonurine (LEO), a natural alkaloid, is identified as a direct STING inhibitor that specifically binds the TYR261 residue, blocking both STING oligomerization and STING‑TBK1 heterodimer formation-a mechanism distinct from known STING inhibitors. LEO exerts hierarchical dual protection: directly preserving cardiomyocyte mitochondria while primarily inhibiting endothelial STING to disrupt the pathogenic loop. This endothelial‑centric strategy shifts the therapeutic paradigm from direct cardiomyocyte protection to upstream endothelial intervention, establishing LEO as a promising candidate for DIC.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e75912"},"PeriodicalIF":14.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Personalized Network-Guided Neuromodulation Enhances Human Working Memory. 个性化网络引导神经调节增强人类工作记忆。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 Epub Date: 2026-06-12 DOI: 10.1002/advs.202523009

Ahsan Khan, Hongming Li, Camille Blaine, Julie Grier, Ethan Hammett, Almaris Figueroa-Gonzalez, Sarai Garcia, Romain Duprat, Justin Reber, Joseph Deluisi, Christos Davatzikos, Theodore D Satterthwaite, Yong Fan, Desmond J Oathes

{"title":"Personalized Network-Guided Neuromodulation Enhances Human Working Memory.","authors":"Ahsan Khan, Hongming Li, Camille Blaine, Julie Grier, Ethan Hammett, Almaris Figueroa-Gonzalez, Sarai Garcia, Romain Duprat, Justin Reber, Joseph Deluisi, Christos Davatzikos, Theodore D Satterthwaite, Yong Fan, Desmond J Oathes","doi":"10.1002/advs.202523009","DOIUrl":"10.1002/advs.202523009","url":null,"abstract":"The next frontier in cognitive neuromodulation is defined by personalized and adaptive protocols, necessitating approaches tailored to individual functional neuroanatomy and brain-state fluctuations. Here, we introduce an adaptive neuromodulation framework that integrates individualized network targeting with real-time decoding of brain states to precisely target working memory functional networks. Using concurrent transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI), we first mapped participant-specific networks and identified personalized targets. A real-time decoder then tracked stimulation-evoked neural dynamics to empirically determine the optimal frequency (i.e., the best-performing within a tested set of 5, 10, and 20 Hz) and a corresponding suboptimal frequency for each individual. In a multi-session crossover study, only the optimal-frequency stimulation significantly improved working memory, with the decoder's output predicting behavioral gains. A key finding is the substantial inter-individual variability in the optimal frequency, providing evidence against the notion of a universal \"best\" frequency. Our results demonstrate that cognitive enhancement is governed by the precise interaction between stimulation target and frequency. This work provides a causal demonstration of personalized, network-based neuromodulation and offers proof of concept for a generalizable, biomarker-driven framework, representing a step toward advancing cognitive therapeutics. Trial Registration: This study is registered at ClinicalTrials.gov (identifier: NCT04402294).","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e23009"},"PeriodicalIF":14.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pressure-Induced Drift Artifacts in Stretchable Liquid Metal ThinFilm Electrocardiogram Electrodes. 可拉伸液态金属薄膜心电图电极中的压力诱发漂移伪影。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 Epub Date: 2026-07-02 DOI: 10.1002/advs.76002

Ding Li, Zi-Gan Xu, Zhi-Kang Chen, Shuo-Yan Xu, Jia-Yi Cui, Si-Yuan Wo, Zi-Xu Wang, Yi-Kun Liu, Jia-Ju Yin, Hou-Fang Liu, Xiao-Ming Wu, Lu-Qi Tao, Yi Yang, Tian-Ling Ren

{"title":"Pressure-Induced Drift Artifacts in Stretchable Liquid Metal ThinFilm Electrocardiogram Electrodes.","authors":"Ding Li, Zi-Gan Xu, Zhi-Kang Chen, Shuo-Yan Xu, Jia-Yi Cui, Si-Yuan Wo, Zi-Xu Wang, Yi-Kun Liu, Jia-Ju Yin, Hou-Fang Liu, Xiao-Ming Wu, Lu-Qi Tao, Yi Yang, Tian-Ling Ren","doi":"10.1002/advs.76002","DOIUrl":"10.1002/advs.76002","url":null,"abstract":"Reliably monitoring epidermal electrophysiological signals with precision is essential for advanced healthcare systems and next-generation human-machine interfaces. Although stretchable thin-film electrodes have shown promise for accurate electrocardiogram signal acquisition, the issue of pressure-induced drift artifacts remains largely overlooked. We developed a stretchable LM thin-film electrode integrated with an LM strain sensor to quantitatively investigate the drift artifact alongside skin deformation simultaneously and in situ. While most existing research focuses on strain-induced drift, our findings reveal that the pressure-induced drift artifact is more significant in stretchable LM electrodes. This work further emphasizes the limitations of the skin-electrode impedance model in explaining the pressure-induced drift, and confirms that its primary origin lies in skin potential change. Based on this, we validated an adaptive filtering method using the noise signal reconstructed from strain sensor data to calibrate pressure-induced drifts. Compared to traditional static filtering methods, it demonstrates superior performance in suppressing irregular pressure-induced drift artifacts.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e76002"},"PeriodicalIF":14.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Near-Infrared Fluorescent PROTAC Enables Theranostic Imaging and Selective Tau Degradation in Alzheimer's Disease. 近红外荧光PROTAC支持阿尔茨海默病的治疗成像和选择性Tau降解。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 DOI: 10.1002/advs.77545

Ziwei Ren, Qian Yue, Ning Gao, Qiu-Lian Hao, Yan Huo, Chuchu Li, Xinyue Leng, Lu-Lu Sun, Maggie Pui Man Hoi, Hai-Hao Han, Mingliang Ma, Xu-Wen Li

{"title":"Near-Infrared Fluorescent PROTAC Enables Theranostic Imaging and Selective Tau Degradation in Alzheimer's Disease.","authors":"Ziwei Ren, Qian Yue, Ning Gao, Qiu-Lian Hao, Yan Huo, Chuchu Li, Xinyue Leng, Lu-Lu Sun, Maggie Pui Man Hoi, Hai-Hao Han, Mingliang Ma, Xu-Wen Li","doi":"10.1002/advs.77545","DOIUrl":"10.1002/advs.77545","url":null,"abstract":"The hyperphosphorylated Tau (p-Tau) protein plays a central role in the pathogenesis of Alzheimer's disease (AD) by driving neurofibrillary tangle formation and neuronal dysfunction. While proteolysis targeting chimeras (PROTACs) offer a promising approach for directly eliminating pathogenic proteins, their real-time visualization in living systems remains challenging. Here, we report the rational design and synthesis of a series of near-infrared (NIR) fluorescent Tau-targeting degraders that integrate theranostic imaging with targeted protein degradation. Among them, compound D9 emerges as a dual-functional degrader capable of both high-contrast fluorescence tracking and potent Tau clearance at 10 nM. Mechanistic investigations indicate that D9 induces Tau degradation through activation of the ubiquitin-proteasome system (UPS), as confirmed by inhibitor assays. Beyond Tau degradation, D9 also downregulates amyloid precursor protein (APP) and β-amyloid (Aβ) expression, suggesting broader neuroprotective effects. In in vivo studies, D9 significantly promotes p-Tau clearance and alleviates cognitive deficits in 3 ×Tg-AD mice. These findings demonstrate that D9 represents a first-in-class NIR fluorescent PROTAC for theranostic imaging and targeted degradation of Tau, providing a powerful platform for visualizing degradation dynamics and developing next-generation AD therapeutics.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e77545"},"PeriodicalIF":14.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Radiation-Triggered Chemokine-Secreting Probiotics for Boron Neutron Capture Therapy Based Radioimmunotherapy. 辐射触发的促趋化因子分泌益生菌用于基于放射免疫治疗的硼中子俘获治疗。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-09-01 DOI: 10.1002/advs.77542

Yang Liu, Yuzhong Qian, Shaobo Huang, Bingbing Li, Yue Yu, Xiang Cheng, Chang Chen, Jiheng Wang, Maosong Yang, Lizheng Liang, Xiancai Meng, Zhigang Liu

引用次数: 0