Advanced SciencePub Date : 2025-06-16DOI: 10.1002/advs.202501916
Yuan Gao, Jiawei Zhou, Chen-Chen Wang, Zong-Hao Wang, Nian-Dong Mao, Meng-Lan He, Peng-Peng Zhang, Ping Huang, Guo-Wei Ye, Yu-Qing Zhang, Feng-Hui Tang, Hang Zhang, Tian Xie, Xiang-Yang Ye
{"title":"Novel ATR/PARP1 Dual Inhibitors Demonstrate Synergistic Antitumor Efficacy in Triple-Negative Breast Cancer Models.","authors":"Yuan Gao, Jiawei Zhou, Chen-Chen Wang, Zong-Hao Wang, Nian-Dong Mao, Meng-Lan He, Peng-Peng Zhang, Ping Huang, Guo-Wei Ye, Yu-Qing Zhang, Feng-Hui Tang, Hang Zhang, Tian Xie, Xiang-Yang Ye","doi":"10.1002/advs.202501916","DOIUrl":"https://doi.org/10.1002/advs.202501916","url":null,"abstract":"<p><p>Concomitant inhibition of ataxia telangiectasia and Rad3-related protein (ATR) and poly ADP-ribose Polymerase (PARP) pathways is a promising strategy in cancer therapy, potentially expanding the clinical utility of ATR inhibitor (ATRi) and PARP inhibitor (PARPi). A novel series of ATR/PARP1 dual inhibitors is developed through the pharmacophore fusion of AZD6738 and Olaparib. Among them, B8 emerges as the most promising candidate, exhibiting potent ATR (IC<sub>50</sub>: 17.3 nM) and PARP1 (IC<sub>50</sub>: 0.38 nM) inhibition. B8 effectively reduced cell viability, induced apoptosis, and caused G2/M cell cycle arrest in TNBC cells. Additionally, B8 significantly impaired TNBC colony formation, migration, and invasion. Mechanistically, B8 induces DNA damage, evidenced by increased γH2AX levels. In in vivo studies, B8 suppressed tumor growth more effectively than the combination in MDA-MB-468 xenografted mice, with no significant body weight loss. B8 also enhanced γH2AX expression in tumor tissues. These findings confirm the synergistic effects of ATR/PARP1 co-inhibition and highlight the potential of this novel inhibitor class for TNBC therapy.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e01916"},"PeriodicalIF":14.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300772","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 : 2025-06-16DOI: 10.1002/advs.202410945
Lu Xia, Jichuan Wang, Hui Xue, Haimeng Li, Qinghua Li, Sen Qin, Chunyu Yu, Yanhua Liu, Yu Gao, Lingyun Li, Sudun Guan, Enrun Zheng, Feiya Suo, Lin He, Yongsheng Wang, Wenling Han, Yongfeng Shang, Yong Geng, Luyang Sun
{"title":"A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer.","authors":"Lu Xia, Jichuan Wang, Hui Xue, Haimeng Li, Qinghua Li, Sen Qin, Chunyu Yu, Yanhua Liu, Yu Gao, Lingyun Li, Sudun Guan, Enrun Zheng, Feiya Suo, Lin He, Yongsheng Wang, Wenling Han, Yongfeng Shang, Yong Geng, Luyang Sun","doi":"10.1002/advs.202410945","DOIUrl":"https://doi.org/10.1002/advs.202410945","url":null,"abstract":"<p><p>Aberrant EGFR signaling drives non-small cell lung cancer (NSCLC) development, and despite the success of tyrosine kinase inhibitor (TKI) therapies in treating NSCLC, TKI resistance remains a major obstacle. Here, we report that the chemokine-like transmembrane protein CMTM6 is physically associated with EGFR. CMTM6 is shown to be co-localized with EGFR in recycling endosomes that are marked by RAB11, thereby preventing EGFR from lysosome-mediated degradation in NSCLC cells. The level of CMTM6 is elevated in NSCLC, and high expression of CMTM6 is associated with enhanced colocalization of CMTM6 with EGFR and RAB11 in NSCLC tumors and correlated with a poor prognosis in NSCLC patients. A CMTM6-targeting nanobody is developed and administration of this agent leads to blocking of the CMTM6-EGFR interaction, reduction of the EGFR protein level, and inhibition of the proliferation of TKI-resistant NSCLC cells in vitro and suppression of the growth of EGFR-TKI-resistant NSCLC in both cell line-derived xenografts and patient-derived xenograft models. The study indicates that CMTM6 is a stabilizer of EGFR in endocytic trafficking and provides evidence to support targeting CMTM6 as a potential therapeutic strategy to overcome TKI resistance in NSCLC treatment.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2410945"},"PeriodicalIF":14.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300770","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 : 2025-06-16DOI: 10.1002/advs.202505121
Bao Xue, Mao-Xing Zhang, Xiao-Chen Bi, Shou-Peng Lai, Xin-Tian Bie, Yuan Dong, Jian-Feng Li, Fang Gao, Xia Zhang, Ying Wang
{"title":"An Amygdala-hippocampus Circuit for Endocannabinoid Modulation of Anxiety Avoidance.","authors":"Bao Xue, Mao-Xing Zhang, Xiao-Chen Bi, Shou-Peng Lai, Xin-Tian Bie, Yuan Dong, Jian-Feng Li, Fang Gao, Xia Zhang, Ying Wang","doi":"10.1002/advs.202505121","DOIUrl":"https://doi.org/10.1002/advs.202505121","url":null,"abstract":"<p><p>Recent studies indicate a therapeutic potential of increased brain endocannabinoids (eCBs) in anxiety disorders, but the underlying brain circuits are still elusive. Here, it is observed that optogenetic inhibition and activation of anterior basolateral amygdala (aBLA) - ventral hippocampus (vHPC) glutamatergic projections respectively decrease and increase anxiety avoidance behaviors. Then, the contributions of eCBs in aBLA-vHPC projections to anxiety avoidance are investigated by employing three newly developed synapse- and circuit-specific eCB-targeted viral strategies to achieve real-time monitoring of eCB release, in vivo optogenetic activation of CB1 receptors, and CRISPR-Cas9 gene knockdown of eCB biosynthesis enzymes. Prominent eCB release are surprisingly found at aBLA-vHPC glutamatergic synapses during anxiety avoidance, suggesting inhibitory effects of increased eCBs in aBLA-vHPC projections on anxiety avoidance. This idea is further supported by findings that specific activation of CB1 receptors at aBLA-vHPC synapses inhibit presynaptic glutamate release and reduce anxiety avoidance. In contrast, specific knockdown of eCB biosynthesis enzymes at aBLA-vHPC synapses reduce eCB levels at aBLA-vHPC glutamatergic synapses and increase anxiety avoidance. Additionally, inhibition of aBLA-innervated vHPC glutamatergic neurons alleviates anxiety avoidance. Together, these findings reveal counteracting effects of increased eCB signaling in aBLA-vHPC circuits on anxiety avoidance.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e05121"},"PeriodicalIF":14.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300771","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 : 2025-06-12DOI: 10.1002/advs.202570172
Qilu Wu, Yuxiao Feng, Mathilde Lepoitevin, Meng Yu, Christian Serre, Jun Ge, Yuan Huang
{"title":"Metal–Organic Frameworks: Unlocking New Frontiers in Cardiovascular Diagnosis and Therapy (Adv. Sci. 22/2025)","authors":"Qilu Wu, Yuxiao Feng, Mathilde Lepoitevin, Meng Yu, Christian Serre, Jun Ge, Yuan Huang","doi":"10.1002/advs.202570172","DOIUrl":"https://doi.org/10.1002/advs.202570172","url":null,"abstract":"<p><b>Metal–Organic Frameworks</b></p><p>This image highlights the transformative potential of metal–organic frameworks (MOFs) in redefining the diagnosis and treatment of cardiovascular diseases. By harnessing their structural versatility and functional tunability, MOFs facilitate innovative approaches such as multimodal cardiovascular imaging and targeted drug delivery—bridging the gap between nanotechnology and clinical translation to address pressing challenges in cardiovascular care. More details can be found in article number 2416302 by Meng Yu, Christian Serre, Jun Ge, Yuan Huang, and co-workers.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":"12 22","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202570172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264445","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}
{"title":"Correlation Between Fecal Microbiota and Corticosteroid Responsiveness in Primary Immune Thrombocytopenia: an Exploratory Study (Adv. Sci. 22/2025)","authors":"Feng-Qi Liu, Zhuo-Yu An, Li-Juan Cui, Meng-Yu Xiao, Ye-Jun Wu, Wei Li, Bang-Shuo Zhang, Li Yu, Jia Feng, Zhuo-Gang Liu, Ru Feng, Zhong-Xing Jiang, Rui-Bin Huang, Hong-Mei Jing, Jin-Hai Ren, Xiao-Yu Zhu, Yun-Feng Cheng, Yu-Hua Li, He-Bing Zhou, Da Gao, Yi Liu, Fan Yu, Xin Wang, Jian-Lin Qiao, Dai-Hong Hu, Lu-Lu Wang, Meng-Tong Zang, Qi Chen, Qing-Yuan Qu, Jian-Ying Zhou, Meng-Lin Li, Yu-Xiu Chen, Qiu-Sha Huang, Hai-Xia Fu, Yue-Ying Li, Qian-Fei Wang, Xiao-Jun Huang, Xiao-hui Zhang, the Cooperative ITP Working Group","doi":"10.1002/advs.202570168","DOIUrl":"https://doi.org/10.1002/advs.202570168","url":null,"abstract":"<p><b>Immune Thrombocytopenia</b></p><p>Immune thrombocytopenia (ITP) is characterized by splenic platelet destruction and dysfunctional megakaryocyte maturation. Emerging research demonstrates that machine learning frameworks analyzing gut microbiome profiles and clinical parameters can reliably forecast treatment responses to corticosteroids through microbiota-immune axis modulation. This predictive modeling approach enables personalized therapeutic strategies in ITP care, advancing precision hematology through computational biomarker integration. More details can be found in article number 2410417 by Xiao-hui Zhang and co-worders.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":"12 22","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202570168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264555","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}
{"title":"Origins, Dispersal, and Impact: Bidirectional Introgression Between Chinese and European Pig Populations (Adv. Sci. 22/2025)","authors":"Yibin Qiu, Langqing Liu, Min Huang, Donglin Ruan, Rongrong Ding, Zebin Zhang, Enqin Zheng, Shiyuan Wang, Shaoxiong Deng, Xianglun Meng, Xinyan Cheng, Jiaxin Shi, Yingshan Yang, Fuchen Zhou, Sixiu Huang, Huaqiang Yang, Zicong Li, Gengyuan Cai, Zhenfang Wu, Jie Yang","doi":"10.1002/advs.202570167","DOIUrl":"https://doi.org/10.1002/advs.202570167","url":null,"abstract":"<p><b>Bidirectional Introgression</b></p><p>This cover depicts bidirectional genetic exchange between Asian and European pig populations. A DNA double helix bridging Asia (upper) and Europe (lower) symbolizes bidirectional gene flow driven by human-mediated activities, particularly intra-continental trade between China and Europe via shipping routes. This design highlights the role of human-mediated introgression in shaping the genetic and phenotypic constitution of modern pig breeds. More details can be found in article number 2416573 by Jie Yang, Zhenfang Wu, Langqing Liu, and co-workers.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":"12 22","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202570167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264473","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}
Advanced SciencePub Date : 2025-06-12DOI: 10.1002/advs.202570175
Zhibin Dong, Pei Li, Yi Jiang, Zhihan Wang, Shihui Fu, Hebin Che, Meng Liu, Xiaojing Zhao, Chunlei Liu, Chenghui Zhao, Qin Zhong, Chongyou Rao, Siwei Wang, Suyuan Liu, Dayu Hu, Dongjin Wang, Juntao Gao, Kai Guo, Xinwang Liu, En Zhu, Kunlun He
{"title":"Integrative Multi-Omics and Routine Blood Analysis Using Deep Learning: Cost-Effective Early Prediction of Chronic Disease Risks (Adv. Sci. 22/2025)","authors":"Zhibin Dong, Pei Li, Yi Jiang, Zhihan Wang, Shihui Fu, Hebin Che, Meng Liu, Xiaojing Zhao, Chunlei Liu, Chenghui Zhao, Qin Zhong, Chongyou Rao, Siwei Wang, Suyuan Liu, Dayu Hu, Dongjin Wang, Juntao Gao, Kai Guo, Xinwang Liu, En Zhu, Kunlun He","doi":"10.1002/advs.202570175","DOIUrl":"https://doi.org/10.1002/advs.202570175","url":null,"abstract":"<p><b>Early Prediction of Chronic Disease Risks</b></p><p>In article number 2412775, Zhibin Dong, Pei Li, Zhihan Wang, Kai Guo, Kunlun He, and co-workers developed a deep learning model called Omicsformer for detailed analysis and classification of routine blood samples. Omicsformer adeptly identified potential risks for nine diseases including cancer, cardiovascular conditions, and psychiatric conditions. Analysis of risk trajectories from 20 years of large clinical patients confirmed the validity of the group in preclinical risk assessment, revealing trends in increased disease risk at the time of onset.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":"12 22","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202570175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264474","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}
{"title":"Apoptotic Vesicles Derived from Mesenchymal Stem Cells Ameliorate Hypersensitivity Responses via Inducing CD8+ T Cells Apoptosis with Calcium Overload and Mitochondrial Dysfunction (Adv. Sci. 22/2025)","authors":"Anqi Liu, Peng Peng, Changze Wei, Fanhui Meng, Xiaoyao Huang, Peisheng Liu, Siyuan Fan, Xinyue Cai, Meiling Wu, Zilin Xuan, Qing Liu, Xinyu Qiu, Zhenlai Zhu, Hao Guo","doi":"10.1002/advs.202570169","DOIUrl":"https://doi.org/10.1002/advs.202570169","url":null,"abstract":"<p><b>Apoptotic Vesicles-Based Cell-free Therapy</b></p><p>In article number 2407446, Hao Guo, Zhenlai Zhu, Xinyu Qiu, and colleagues introduce a novel therapeutic potential of apoptotic vesicles (ApoVs) for ameliorating hypersensitivity reactions through the induction of CD8<sup>+</sup> T cell apoptosis. The cover illustrates that ApoVs derived from mesenchymal stem cells interact with CD8<sup>+</sup> T cells via membrane fusion, triggering calcium influx, mitochondrial dysfunction, and ultimately apoptosis in CD8<sup>+</sup> T cells. This study highlights the potential of products derived from apoptotic cells as a promising strategy for therapeutic applications in diseases involving CD8<sup>+</sup> T cell-mediated pathologies. \u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":"12 22","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202570169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264442","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}
Advanced SciencePub Date : 2025-06-12DOI: 10.1002/advs.202570174
Rahul Sheshanarayana, Fengqi You
{"title":"Knowledge Distillation for Molecular Property Prediction: A Scalability Analysis (Adv. Sci. 22/2025)","authors":"Rahul Sheshanarayana, Fengqi You","doi":"10.1002/advs.202570174","DOIUrl":"https://doi.org/10.1002/advs.202570174","url":null,"abstract":"<p><b>Knowledge Distillation for Molecular Property Prediction</b></p><p>This illustration shows how AI distills rich molecular insights from complex teacher models into compact student models, enabling accurate, scalable prediction of both experimental and quantum mechanical properties—advancing molecular design and discovery across domains. More details can be found in article number 2503271 by Rahul Sheshanarayana and Fengqi You.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":"12 22","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202570174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264674","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}
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