{"title":"Interpretable Active Learning Identifies Iron-Doped Carbon Dots With High Photothermal Conversion Efficiency for Antitumor Synergistic Therapy","authors":"Tianliang Li, Bin Cao, Yitong Wang, Lixing Lin, Lifei Chen, Tianhao Su, Haicheng Song, Yuze Ren, Longhan Zhang, Yingying Chen, Zhenzhen Li, Lingyan Feng, Tong-yi Zhang","doi":"10.1002/agt2.70060","DOIUrl":"https://doi.org/10.1002/agt2.70060","url":null,"abstract":"<p>Active learning (AL) is a powerful method for accelerating novel materials discovery but faces huge challenges for extracting physical meaning. Herein, we novelly apply an interpretable AL strategy to efficiently optimize the photothermal conversion efficiency (PCE) of carbon dots (CDs) in photothermal therapy (PTT). An equivalent value (SHapley Additive exPlanations equivalent value [SHAP-EV]) is proposed which explicitly quantifies the linear contributions of experimental variables to the PCE, derived from the joint SHAP values. The SHAP-EV, with an <i>R</i><sup>2</sup> of 0.960 correlated to feature's joint SHAP, is integrated into the AL utility functions to enhance evaluation efficiency during optimization. Using this approach, we successfully synthesized iron-doped CDs (Fe-CDs) with PCE exceeding 78.7% after only 16 experimental trials over four iterations. This achievement significantly advances the previously low PCE values typically reported for CDs. Furthermore, Fe-CDs demonstrated multienzyme-like activities, which could respond to the tumor microenvironment (TME). In vitro and in vivo experiments demonstrate that Fe-CDs could enhance ferroptosis through synergistic PTT and chemodynamic therapy (CDT), thereby achieving remarkable antitumor efficacy. Our interpretable AL strategy offers new insights for accelerating bio-functional materials development in antitumor treatments.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"m6A Modulates RAN Translation From CAG Repeat Expansion RNA","authors":"Yuxiang Sun, Zhouxian Li, Hui Dai, Yinsheng Wang","doi":"10.1002/agt2.70072","DOIUrl":"https://doi.org/10.1002/agt2.70072","url":null,"abstract":"<p>Nucleotide repeat expansions contribute to the development of a number of neurodegenerative diseases. Recent studies revealed that DNA sequences with CAG and other nucleotide repeat expansions can undergo bidirectional transcription, and the ensuing transcripts could be translated into proteins through repeat-associated non-AUG (RAN) translation; however, not much is known about the precise mechanisms underlying RAN translation. Here, we demonstrated that m<sup>6</sup>A, installed by METTL3 and removed by FTO, promotes RAN translation in all three reading frames from the expanded CAG repeat RNA derived from the human <i>ATXN3</i> gene, in which repeat expansion contributes to spinocerebellar ataxia type 3 (SCA3). Genetic depletion and pharmacological inhibition of METTL3 result in significantly diminished levels of RAN translation products from all three reading frames, which could be restored by ectopic expression of wildtype METTL3, but not its catalytically inactive mutant. Conversely, genetic ablation of FTO led to augmented RAN translation in all three reading frames. Moreover, one of the RAN translation products, poly(serine), exhibits gel-like aggregates in cells. Together, our study unveiled a crucial role of m<sup>6</sup>A in modulating RAN translation from expanded CAG repeat RNA transcribed from the human <i>ATXN3</i> gene, and documented new biophysical properties of the poly(serine) RAN translation product.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaofei Niu, Xinwen Ou, Shizhe Ren, Ke Wang, Fengyan Song, Xiaobin Dong, Wu-Jie Guo, Hui-Qing Peng, Zujin Zhao, Jacky W. Y. Lam, Yong Sheng Zhao, Fei Li, Shu-Yan Yu, Ben Zhong Tang
{"title":"Inside Front Cover: Circularly Polarized Luminescence Inversion in AIE-Active Crystal Enabled by Solvent-Induced Transition Dipole Moment Regulation","authors":"Xiaofei Niu, Xinwen Ou, Shizhe Ren, Ke Wang, Fengyan Song, Xiaobin Dong, Wu-Jie Guo, Hui-Qing Peng, Zujin Zhao, Jacky W. Y. Lam, Yong Sheng Zhao, Fei Li, Shu-Yan Yu, Ben Zhong Tang","doi":"10.1002/agt2.70065","DOIUrl":"https://doi.org/10.1002/agt2.70065","url":null,"abstract":"<p>This study elucidates a novel phenomenon in chiral AIEgens crystalline materials, demonstrating solvent-induced circularly polarized luminescence (CPL) sign inversion while maintaining identical helical configuration and molecular chirality in the crystalline state. The observed CPL reversal originates from non-bonding interactions between co-crystallized solvent molecules and AIEgens, which modulate the <i>θ</i><sub>μ,m</sub> (S<sub>1</sub>→S<sub>0</sub>) of electric and magnetic transition dipole moments within the unit cell. The findings establish a unique mechanism for chiroptical property manipulation through supramolecular engineering of non-covalent interactions in crystalline systems (e70003).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 5","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lihan Lai, Yun Su, Cong Hu, Zehong Peng, Wei Xue, Liang Dong, Tony Y. Hu
{"title":"Back Cover: Integrating Aggregate Materials and Machine Learning Algorithms: Advancing Detection of Pathogen-Derived Extracellular Vesicles","authors":"Lihan Lai, Yun Su, Cong Hu, Zehong Peng, Wei Xue, Liang Dong, Tony Y. Hu","doi":"10.1002/agt2.70064","DOIUrl":"https://doi.org/10.1002/agt2.70064","url":null,"abstract":"<p>This review highlights cutting-edge strategies for enhancing the detection of pathogen-derived extracellular vesicles, including novel aggregate materials and machine learning approaches. Pathogen-derived vesicles are pivotal in host-pathogen interactions and possess significant diagnostic promise, as their unique cargo offers a rich repository of potential biomarkers. Enhancing vesicle detection may ultimately pave the way for transformative clinical applications (e70018).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 5","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Solid-Phase Upcycling Toward the Production of Ultrahigh-Loading Single-Atom Catalysts","authors":"Guanwu Lian, Zefan Du, Yifan Wang, Yelan Xiao, Mengyao Su, Chao Wu, Yucong Huang, Yuansheng Lin, Jingjing Xiong, Yichen Chen, Shibo Xi, Wenguang Tu, Zhigang Zou, Zhongxin Chen","doi":"10.1002/agt2.70052","DOIUrl":"https://doi.org/10.1002/agt2.70052","url":null,"abstract":"<p>The recovery of valuable transition metals from deactivated catalysts is crucial for alleviating the challenges of resource scarcity and environmental pollution. Guided by AI-powered big data analysis, we identified an important research gap in the sustainable recovery of early transition metals and proposed a solid-phase upcycling strategy to transform waste catalysts into highly valuable single-atom catalysts (SACs). This involves a heat-induced redispersion of metal aggregates into single atoms on the polycrystalline carbon nitride (PCN) support, producing highly active M<sub>1</sub>-PCN SACs up to 20 wt% (M = Cu, Fe, Co, and Ni). Subsequent techno-economic analysis confirms a two-thirds reduction in production cost and greenhouse gas emissions compared to conventional hydrometallurgical and pyrometallurgical processes, thus paving a new path in the development of sustainable technologies for metal recovery.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 8","pages":""},"PeriodicalIF":13.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucas S. Ribeiro, João Rocha Maia, Vítor M. Gaspar, Catarina A. Custódio, Emerson R. Camargo, Rita Sobreiro-Almeida, João F. Mano
{"title":"Nozzle Jamming Granularized Blood-Derived Proteins for Bioprinting Cell-Instructive Architectures","authors":"Lucas S. Ribeiro, João Rocha Maia, Vítor M. Gaspar, Catarina A. Custódio, Emerson R. Camargo, Rita Sobreiro-Almeida, João F. Mano","doi":"10.1002/agt2.70041","DOIUrl":"https://doi.org/10.1002/agt2.70041","url":null,"abstract":"<p>Exploring the natural availability and intrinsic bioactivity of blood-derived proteins opens new avenues for fabricating bioactive and patient-specific solutions for biomedical applications. Despite their several advantages, their use as inks for 3D printing is limited due to suboptimal rheological properties. To address this, we propose a dual-step strategy based on the initial generation of blood protein-based bulk hydrogels encompassing pristine and photo-responsive protein mixtures to allow their mechanical granularization followed by jamming, establishing injectable and printable granular inks. In this study, two globular-based protein matrices—human platelet lysates (PL) and bovine serum albumin (BSA)—were used as granular inks for 3D printing. We hypothesize that nozzle jamming—in contrast to the typically employed centrifugal jamming—would render optimized results for the granular protein inks’ processability. Printability was evaluated in filaments, scaffold grids, and convoluted structures. Taking advantage of the previously introduced photocurable moieties, post-printing photocrosslinking was used for the annealing of the microgels, leading to increased scaffold mechanical stability and robustness. The nozzle jamming methodology imparted the best print performance and reproducibility, where PLMA-based inks outperformed the BSAMA-based. In addition, the microgel granular constructs allowed primary human-derived adipose stem cells to adhere and proliferate, whereas the PLMA-based ink demonstrated higher cell affinity and enhanced biological performance. We further demonstrated that bioinks could be developed from PLMA-based inks, showcasing high viability without compromising 3D printing performance. Overall, this study gives clear insights into the importance of the jamming process as well as the granularization outcome requirements for the obtention of highly reproducible granular inks for 3D printing.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Wei, Xiangzhou Zhang, Xiaojia Wang, Yeqi Liu, Yuhai Zhang
{"title":"Inside Back Cover: New Transparent Rare-Earth-Based Hybrid Glasses: Synthesis, Luminescence, and X-Ray Imaging Application","authors":"Jun Wei, Xiangzhou Zhang, Xiaojia Wang, Yeqi Liu, Yuhai Zhang","doi":"10.1002/agt2.70066","DOIUrl":"https://doi.org/10.1002/agt2.70066","url":null,"abstract":"<p>A desolvation method below 140 °C was reported for a rapid synthesis of RE(NO<sub>3</sub>)<sub>3</sub>(C<sub>5</sub>H<sub>2</sub>N<sub>4</sub>)<sub>2</sub> hybrid glasses within an hour. The glasses containing the whole library of rare-earth ions exhibited a high transparency, which opened up a pathway to explore the elusive interactions between metals and organic linker, providing new insights for the design of rare-earth glasses (e70021).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 5","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yicheng Zhao, Jingyi Si, Shisong Jing, Bingmei Wang, Yueshan Xu, Jiyu Guan, Quan Liu, Jianlei Shen, Min Lv, Li Wang, Changfeng Zhu
{"title":"Multifunctional Framework Nucleic Acid Vehicle for Antibiotic Sensitization and Treatment of Methicillin-Resistant Staphylococcus aureus","authors":"Yicheng Zhao, Jingyi Si, Shisong Jing, Bingmei Wang, Yueshan Xu, Jiyu Guan, Quan Liu, Jianlei Shen, Min Lv, Li Wang, Changfeng Zhu","doi":"10.1002/agt2.70059","DOIUrl":"https://doi.org/10.1002/agt2.70059","url":null,"abstract":"<p>The increasing prevalence of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) due to antibiotic misuse necessitates novel therapeutic strategies to counter multidrug-resistant infections. Here, we introduce a self-assembling, aggregation-enhanced tetrahedral DNA nanostructure (tFNA) platform that achieves targeted drug delivery through controlled aggregation and sustained release, effectively restoring MRSA susceptibility to β-lactam antibiotics. These tetrahedral frameworks, termed tFNAs-ASOs-ceftriaxone sodium (TACs), serve as a dual-functional system that co-encapsulates antisense oligonucleotides (ASOs) targeting the <i>mecA</i> gene and the β-lactam antibiotic ceftriaxone sodium (Cef). Aggregation of TACs plays a pivotal role in maximizing drug retention and stability, prolonging the localized release of both ASOs and antibiotics while maintaining high bioavailability at the infection site. Characterization studies, including size distribution, zeta potential, and fluorescence quenching assays, confirm their robust aggregation stability and encapsulation efficiency, ensuring controlled drug kinetics and prolonged therapeutic effects. Upon interaction with bacterial cells, the locally concentrated TACs facilitate efficient ASO-mediated <i>mecA</i> silencing, thereby disrupting PBP2a expression and re-sensitizing MRSA to β-lactams. Simultaneously, the aggregated ceftriaxone sodium reservoir ensures sustained inhibition of bacterial cell wall synthesis, leading to effective bacterial clearance. In addition, TACs display potent antibiofilm activity by penetrating the biofilm matrix and delivering therapeutics directly to the embedded bacterial population, thereby overcoming the diffusion barriers. In vivo, TACs exhibit superior therapeutic efficacy in an MRSA-induced pneumonia mouse model, significantly improving survival rates, reducing bacterial burden, and mitigating lung tissue damage. These findings highlight the transformative potential of tFNAs as an intelligent drug aggregation and release system, offering a novel paradigm for optimizing antibiotic therapy against multidrug-resistant pathogens.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interfacial Engineering of Pillararene-Modified Ceria Nanoparticles for Regulable Enhanced Sonodynamic Therapy","authors":"Congcong Wang, Yanan Guo, Guoying Tan, Wanrong Kang, Wenjia Guo, Nan Song, Yu Tang","doi":"10.1002/agt2.70062","DOIUrl":"https://doi.org/10.1002/agt2.70062","url":null,"abstract":"<p>Sonodynamic therapy (SDT) has emerged as an advanced technology for treatment of malignant tumors. Many organic and inorganic sonosensitizers have been reported but they still have the respective limitations. Constructing the materials to integrate the superiorities of organic and inorganic sonosensitizers is expected to be a good method to enhance the efficiency of SDT. Herein, we report an intelligent sonosensitizer (TPA–OS⊂CP5@CeO<i><sub>x</sub></i>), integrating the organic (TPA–OS) and inorganic sonosensitizers (CP5@CeO<i><sub>x</sub></i>) via host–guest interaction. The modification of carboxyl-pillar[5]arene (CP5) on CeO<i><sub>x</sub></i> constructs the supramolecular interface by coupling of CP5 and oxygen vacancies. The band gap of CeO<i><sub>x</sub></i> is reduced and the ratio of Ce<sup>4+</sup>/Ce<sup>3+</sup> is increased to regulate tumor microenvironment. Thus, the SDT performance of CP5@CeO<sub><i>x</i></sub> can be improved. Furthermore, the synergistic effect of TPA–OS with aggregation-induced emission can further regulate and enhance the SDT efficiency. The cellular experiments demonstrate that TPA–OS⊂CP5@CeO<i><sub>x</sub></i> exhibits the synergistic therapeutic effect in double organelle of lysosome and mitochondria. The in vivo experiments suggest TPA–OS⊂CP5@CeO<i><sub>x</sub></i> has imaging-guided enhanced SDT performance to achieve tumor inhibition. This study contributes to the construction of novel intelligent sonosensitizers, indicating that supramolecular interface engineering is promising to realize the customized treatments with minimal side effects.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}