Mengxuan Du, Binge Huang, Songlin Xin, Liqin Wu, Xiaojun He
{"title":"Atomic-engineered Ru single-atom-catalyst nanoplatforms with NIR-II-triggered oxidase-peroxidase cascades for bacterial pneumonia","authors":"Mengxuan Du, Binge Huang, Songlin Xin, Liqin Wu, Xiaojun He","doi":"10.1016/j.xcrp.2025.102870","DOIUrl":"https://doi.org/10.1016/j.xcrp.2025.102870","url":null,"abstract":"<h2>Summary</h2> Multidrug-resistant bacterial pneumonia (MDR-BP), particularly involving biofilm eradication, presents therapeutic challenges. While reactive oxygen species (ROS)-mediated chemodynamic therapy offers antibacterial potential, limitations in biocatalytic performance and nanotherapeutic efficacy hinder traditional approaches. We developed nitrogen-doped ruthenium single-atom catalysts (Ru-N-SACs) as a dual-functional nanotherapeutic platform. This nanozyme exhibits peroxidase-mimicking catalytic activity, generating ROS selectively. Near-infrared laser stimulation further enhances its activity and provides photothermal disruption of biofilms. The resulting synergistic action achieves complete biofilm eradication and improves survival in pneumonia models. Comprehensive multi-omics analyses elucidated the therapeutic effectiveness and regulatory mechanisms of Ru-N-SACs against MDR-BP pathogenesis. This work demonstrates a paradigm combining catalytic ROS generation and photothermal therapy for managing deep-tissue infections. It advances the design of precision-engineered nanozymes within antimicrobial nanomedicine, addressing the critical need for innovative strategies against MDR pathogens.","PeriodicalId":9703,"journal":{"name":"Cell Reports Physical Science","volume":"6 10","pages":"102870-102870"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147902278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcin Giza, Fraser J. Angus, Wai Kin Yiu, Madeleine McRoberts, Benjamin Vella, Jingbo Wang, Aleksandra B. Djurišić, Graeme Cooke, Elisabetta Arca, Pablo Docampo
{"title":"The case of the vanishing perovskite layer","authors":"Marcin Giza, Fraser J. Angus, Wai Kin Yiu, Madeleine McRoberts, Benjamin Vella, Jingbo Wang, Aleksandra B. Djurišić, Graeme Cooke, Elisabetta Arca, Pablo Docampo","doi":"10.1016/j.xcrp.2025.102890","DOIUrl":"https://doi.org/10.1016/j.xcrp.2025.102890","url":null,"abstract":"Publisher of over 50 scientific journals across the life, physical, earth, and health sciences, both independently and in partnership with scientific societies including Cell, Neuron, Immunity, Current Biology, AJHG, and the Trends Journals.","PeriodicalId":9703,"journal":{"name":"Cell Reports Physical Science","volume":"6 10","pages":"102890-102890"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147895869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Simultaneous dual-membrane protein degradation using bivalent aptamer-delivered lysosome-targeting chimeras","authors":"Xia Bai, Yuchun Wang, Xinyu Zhang, Chunxue Niu, Gang Yang, Deyu Yuan, Yun Wei, Lihua Zheng, Xu Song, Yongli Bao, Yongyun Zhao","doi":"10.1016/j.xcrp.2025.102866","DOIUrl":"https://doi.org/10.1016/j.xcrp.2025.102866","url":null,"abstract":"<h2>Summary</h2> Diseases often involve multiple abnormal proteins, and degrading them simultaneously is a promising therapeutic strategy. However, transitional lysosome-targeted chimeras (LYTACs) with dedicated delivery modules typically degrade only one protein. Adding more protein of interest (POI)-targeting modules to degrade multiple targets would increase the molecular weight, leading to higher doses and side effects. Here, we report a bivalent aptamer-based delivery system for LYTAC (BideTAC), which leverages the aptamer itself as a dual-function module for targeting and delivery, eliminating the need for a dedicated delivery module and effectively reducing the molecular weight. As a proof of concept, we designed a specific BideTAC (AptHP) to simultaneously degrade PD-L1 and HER2 by conjugating anti-PD-L1 antagonistic aptamer and anti-HER2 aptamer. AptHP effectively degrades two proteins simultaneously, enhancing the therapeutic effect. Therefore, BideTAC provides a potent tool for multiple protein degradation, opening an avenue to push aptamer-based LYTAC toward applications in synergistic therapy.","PeriodicalId":9703,"journal":{"name":"Cell Reports Physical Science","volume":"6 10","pages":"102866-102866"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.cell.com/cell-reports-physical-science/pdf/S2666-3864(25)00465-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147886902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guangjie Yan, Manhua Pan, Aaron M Keller, Ace George Santiago, Michael Lofgren, Ruma Banerjee, Peng Chen, Tai-Yen Chen
{"title":"Conformation-gated binding underlies kinetic asymmetry and negative cooperativity in ATP:cob(I)alamin adenosyltransferase.","authors":"Guangjie Yan, Manhua Pan, Aaron M Keller, Ace George Santiago, Michael Lofgren, Ruma Banerjee, Peng Chen, Tai-Yen Chen","doi":"10.1016/j.xcrp.2025.102768","DOIUrl":"10.1016/j.xcrp.2025.102768","url":null,"abstract":"<p><p>Vitamin B<sub>12</sub> (cobalamin) is a high-value yet scarce cofactor critical for metabolic homeostasis, necessitating efficient handling mechanisms. ATP:cob(I)alamin adenosyltransferase (MMAB) plays a central role in synthesizing, delivering, and repairing 5'-deoxyadenosylcobalamin (AdoCbl), but the kinetic mechanisms regulating this process, including negative cooperativity, remain unclear. Using single-molecule relative fluorescence spectroscopy, we reveal that conformation-gated binding mechanism, involving a required structural rearrangement prior to the first cofactor association, dictates MMAB's interaction kinetics. This mechanism slows the association of a second AdoCbl, resulting in strong negative cooperativity, favoring the singly bound state, and optimizing AdoCbl handling. This gating mechanism, supported by direct observation of a kinetic intermediate, also contributes to MMAB's preferential handling of AdoCbl over hydroxocobalamin, highlighting MMAB's effective cofactor utilization, supporting bacterial survival in nutrient-limited environments. Furthermore, our approach offers a platform to study cofactor interactions, including cobalamin sensing and gene regulation, shedding light on bacterial adaptation to nutrient fluctuations.</p>","PeriodicalId":9703,"journal":{"name":"Cell Reports Physical Science","volume":"6 8","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12431680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fathima Hameed Cherilakkudy, Midhun George Thomas, Ann Varghese, Sodiq O Waheed, Anandhu Krishnan, Vincenzo Venditti, Christopher J Schofield, Deyu Li, Christo Z Christov, Tatyana G Karabencheva-Christova
{"title":"Revealing the catalytic mechanism of the Fe(II)/2-oxoglutarate-dependent human epigenetic modifying enzyme ALKBH5.","authors":"Fathima Hameed Cherilakkudy, Midhun George Thomas, Ann Varghese, Sodiq O Waheed, Anandhu Krishnan, Vincenzo Venditti, Christopher J Schofield, Deyu Li, Christo Z Christov, Tatyana G Karabencheva-Christova","doi":"10.1016/j.xcrp.2025.102779","DOIUrl":"10.1016/j.xcrp.2025.102779","url":null,"abstract":"<p><p>ALKBH5 is one of only two known human non-heme Fe(II)/2-oxoglutarate-dependent oxygenases that catalyze the demethylation of N<sup>6</sup>-methyladenine (m<sup>6</sup>A) in single-stranded mRNA, underscoring its role in diverse cancers. Unlike its homolog, the fat mass and obesity-associated protein (FTO), which oxidizes m<sup>6</sup>A to a stable N<sup>6</sup>-hydroxymethyladenine (hm<sup>6</sup>A) intermediate, ALKBH5 demethylates m<sup>6</sup>A, yielding adenine and formaldehyde as products. Here, we integrate molecular dynamics simulations and quantum mechanics/molecular mechanics methods to elucidate ALKBH5's complete catalytic mechanism. Two post-hydroxylation pathways were evaluated: a proton transfer pathway and a Schiff base formation pathway, with the former emerging as the favored mechanism. We identify second-sphere residues Lys132 and Tyr139 as essential contributors to catalysis and demonstrate how Val191 and Tyr133 modulate activity. Dynamic analyses reveal that correlated motions of structural elements such as nucleotide recognition lids NRL1 and NRL2 and increased flexibility of the NRL2 loop in the hm<sup>6</sup>A intermediate may be critical for efficient demethylation.</p>","PeriodicalId":9703,"journal":{"name":"Cell Reports Physical Science","volume":"6 8","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenpeng Huang, Tianyao Wang, Yutong Liang, Fangfang Chao, Qi Yang, Todd E Barnhart, Jonathan W Engle, Liming Li, Lei Kang, Weibo Cai
{"title":"A zirconium-89-labeled antibody-drug conjugate PET probe for noninvasive monitoring of Nectin4 expression in breast cancer and lung cancer.","authors":"Wenpeng Huang, Tianyao Wang, Yutong Liang, Fangfang Chao, Qi Yang, Todd E Barnhart, Jonathan W Engle, Liming Li, Lei Kang, Weibo Cai","doi":"10.1016/j.xcrp.2025.102723","DOIUrl":"10.1016/j.xcrp.2025.102723","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) are aggressive solid tumors with limited treatment options. Nectin cell adhesion molecule 4 (Nectin4) is a tumor-associated antigen frequently overexpressed in these cancers, making it a promising therapeutic and imaging target. Here, we report the development and evaluation of [<sup>89</sup>Zr]Zr-desferrioxamine (DFO)-Padcev, a radiolabeled antibody-drug conjugate targeting Nectin4, for immuno-positron emission tomography (ImmunoPET) imaging. [<sup>89</sup>Zr]Zr-DFO-Padcev is synthesized with a radiochemical yield of 88.87% ± 2.59% and a radiochemical purity above 99%. ImmunoPET imaging successfully visualizes Nectin4-positive tumors in TNBC (MDA-MB-468) and NSCLC (H1975) models as early as 6 h post-injection, with uptake progressively increasing and peaking at 48 h (14.57 ± 1.94 and 9.50 ± 0.76 %ID/g, respectively). Minimal tumor uptake is observed in blocking and Nectin4-negative controls, confirming specificity. Complementary fluorescence imaging further reveals the <i>in vivo</i> distribution of Padcev, providing valuable insights into optimal therapeutic time windows.</p>","PeriodicalId":9703,"journal":{"name":"Cell Reports Physical Science","volume":"6 8","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12806174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subhechchha Paul, Brinthan Kanesalingam, Yan Ma, Julie Villanova, Guillermo Requena, Stanley Chidubem Akpu, Dierk Raabe, Ilenia Battiato, Leora Dresselhaus-Marais
{"title":"A percolating path to green iron.","authors":"Subhechchha Paul, Brinthan Kanesalingam, Yan Ma, Julie Villanova, Guillermo Requena, Stanley Chidubem Akpu, Dierk Raabe, Ilenia Battiato, Leora Dresselhaus-Marais","doi":"10.1016/j.xcrp.2025.102729","DOIUrl":"https://doi.org/10.1016/j.xcrp.2025.102729","url":null,"abstract":"<p><p>About 1.9 gigatons of steel is produced every year, emitting 8% (3.6 gigatons) of global CO<sub>2</sub> in the process. More than 50% of the CO<sub>2</sub> emissions come from a single step of steel production, known as ironmaking. Hydrogen-based direct reduction (HyDR) of iron oxide to iron has emerged as an emission-free ironmaking alternative. However, multiple physical and chemical phenomena ranging from nanometers to meters inside HyDR reactors alter the microstructure and pore networks in iron oxide pellets, in ways that resist gaseous transport of H<sub>2</sub>/H<sub>2</sub>O, slow reaction rates, and disrupt continuous reactor operation. Using synchrotron nano X-ray computed tomography and percolation theory, we quantify the evolution of pores in iron oxide pellets and demonstrate how nanoscale pore connectivity influences micro- and macroscale flow properties such as permeability, diffusivity, and tortuosity. Our modeling framework connects disparate scales and offers opportunities to accelerate HyDR.</p>","PeriodicalId":9703,"journal":{"name":"Cell Reports Physical Science","volume":"6 8","pages":"102729"},"PeriodicalIF":7.3,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhongzhe Wei, Xu Liu, Mingxuan Wang, Yao Lv, Songtao Huang, Jing Wang, Ming Jiang, Zhixiang Yang, Zihao Yao, Sheng Dai, Xiao‐Nian Li, Jianguo Wang
{"title":"Reaction-driven self-adapting Pd/Nb2O5 steering alkyne semi-hydrogenation","authors":"Zhongzhe Wei, Xu Liu, Mingxuan Wang, Yao Lv, Songtao Huang, Jing Wang, Ming Jiang, Zhixiang Yang, Zihao Yao, Sheng Dai, Xiao‐Nian Li, Jianguo Wang","doi":"10.1016/j.xcrp.2025.102770","DOIUrl":"https://doi.org/10.1016/j.xcrp.2025.102770","url":null,"abstract":"Publisher of over 50 scientific journals across the life, physical, earth, and health sciences, both independently and in partnership with scientific societies including Cell, Neuron, Immunity, Current Biology, AJHG, and the Trends Journals.","PeriodicalId":9703,"journal":{"name":"Cell Reports Physical Science","volume":"6 8","pages":"102770-102770"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147907434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}