Science AdvancesPub Date : 2025-07-23DOI: 10.1126/sciadv.adu4875
Minsu Jeong, Jihae Lee, Seokwoo Kim, Xiangxin Gong, Rouli Fang, Yuhui Yang, Sang Hoon Chae, Junsuk Rho
{"title":"Obtuse-angled separation of chiral resonances with planar asymmetry–induced tunability of quality factors","authors":"Minsu Jeong, Jihae Lee, Seokwoo Kim, Xiangxin Gong, Rouli Fang, Yuhui Yang, Sang Hoon Chae, Junsuk Rho","doi":"10.1126/sciadv.adu4875","DOIUrl":"10.1126/sciadv.adu4875","url":null,"abstract":"<div >Photonic crystal (PhC) supports Bloch resonances that confine electromagnetic energy within the subwavelength thickness and enable polarization modulation through their intrinsic mode states. If a PhC generates chiral resonances, then it can selectively enhance or suppress specific circular polarizations, making it ideal for chiral optics. Here, we devise a design strategy to realize chiral resonant modes with large angular divergence and tunable quality factors (<i>Q</i> factors) by introducing planar structural perturbations. The <i>Q</i> factor exhibits an inverse-square dependence on perturbation strength, consistent with the behavior of quasi-bound states in the continuum. Theoretical and experimental results demonstrate chiral modes with high circular dichroism, large separation angles, and high-<i>Q</i> factors. We further couple 2D excitons to these resonant modes, achieving spatially separated chiral emission. Using Brillouin zone folding, we translate bound modes at high-symmetry points into the radiative region, suggesting a strategy to control polarization, group velocity, and topology in photonic systems.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu4875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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}
Science AdvancesPub Date : 2025-07-23DOI: 10.1126/sciadv.adv0618
Alexander Triccas, Daniel M. Chevrier, Mariana Verezhak, Johannes Ihli, Manuel Guizar-Sicairos, Mirko Holler, André Scheffel, Noriaki Ozaki, Virginie Chamard, Rachel Wood, Tilman A. Grünewald, Fabio Nudelman
{"title":"Dynamic change of calcium-rich compartments during coccolithophore biomineralization","authors":"Alexander Triccas, Daniel M. Chevrier, Mariana Verezhak, Johannes Ihli, Manuel Guizar-Sicairos, Mirko Holler, André Scheffel, Noriaki Ozaki, Virginie Chamard, Rachel Wood, Tilman A. Grünewald, Fabio Nudelman","doi":"10.1126/sciadv.adv0618","DOIUrl":"10.1126/sciadv.adv0618","url":null,"abstract":"<div >Coccolithophores are abundant marine phytoplankton that produce biomineralized calcite scales, called coccoliths, which sequester substantial amounts of carbon and play a substantial role in biogeochemical cycles. However, mechanisms underlying the storage and transport of ions essential for calcification remain unresolved. We used ptychographic x-ray computed tomography under cryogenic conditions to visualize intracellular calcium-rich structures involved in the storage of calcium ions in the coccolithophore species <i>Chrysotila carterae</i>. During calcification, we observed a range of structures, from small electron-dense bodies within larger compartments to denser and distributed globular compartments, before returning to small bodies once scale formation is complete. Nanobeam-scanning x-ray fluorescence measurements further revealed that these electron-dense bodies are rich in phosphorus and calcium (molar ratio of ~4:1). The dynamic nature of structures suggests that these bodies are part of the required cellular calcium ion transport pathways, a fundamental process critical for understanding the response of coccolithophores to climate change.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv0618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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}
Science AdvancesPub Date : 2025-07-23DOI: 10.1126/sciadv.adx1357
Wan-Ping Huang, Vedanth Kumar, Karen Yap, Haiyan An, Sabin J. John, Rachel E. Hodgson, Anna Sanchez Avila, Emily Day, Brittany C. S. Ellis, Tek Hong Chung, Jenny Lord, Michaela Müller-McNicoll, Eugene V. Makeyev, Tatyana A. Shelkovnikova
{"title":"M6A-dependent RNA condensation underlies FUS autoregulation and can be harnessed for ALS therapy development","authors":"Wan-Ping Huang, Vedanth Kumar, Karen Yap, Haiyan An, Sabin J. John, Rachel E. Hodgson, Anna Sanchez Avila, Emily Day, Brittany C. S. Ellis, Tek Hong Chung, Jenny Lord, Michaela Müller-McNicoll, Eugene V. Makeyev, Tatyana A. Shelkovnikova","doi":"10.1126/sciadv.adx1357","DOIUrl":"10.1126/sciadv.adx1357","url":null,"abstract":"<div >Mutations in the <i>FUS</i> gene cause aggressive amyotrophic lateral sclerosis (ALS-FUS). Beyond mRNA, <i>FUS</i> generates partially processed transcripts retaining introns 6 and 7. We demonstrate that these FUSint6&7-RNA molecules form nuclear condensates, scaffolded by the highly structured intron 7 and associated with nuclear speckles. Using hybridization-proximity labeling proteomics, we show that the FUSint6&7-RNA condensates are enriched for splicing factors and the N6-methyladenosine (m6A) reader YTHDC1. These ribonucleoprotein structures facilitate posttranscriptional FUS splicing and depend on m6A/YTHDC1 for integrity. In cells expressing mutant FUS, FUSint6&7-RNAs become hypermethylated, which in turn stimulates their condensation and splicing. We further show that FUS protein is repelled by m6A. Thus, ALS-FUS mutations may cause abnormal activation of FUS posttranscriptional splicing through altered RNA methylation. Notably, ectopic expression of FUS intron 7 sequences dissolves endogenous FUSint6&7-RNA condensates, down-regulating FUS mRNA and protein. Our findings reveal a condensation-dependent mechanism regulating FUS splicing, with possible therapeutic implications for ALS.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx1357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Targeting tumor-associated CCR2+ macrophages to inhibit pancreatic cancer recurrence following irreversible electroporation","authors":"Weichen Xu, Shaoyue Li, Xuexia Shan, Qiao Wang, Xinhua Chen, Shengbo Wu, Yincheng Gao, Dandan Shan, Shisi Ding, Weiwei Ren, Xiaodong Hou, Shuo Liu, Taixia Wang, Yuting Shen, Zhiyuan Niu, Huixiong Xu, Liping Sun, Wenwen Yue","doi":"10.1126/sciadv.adw2937","DOIUrl":"10.1126/sciadv.adw2937","url":null,"abstract":"<div >Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with pronounced resistance to conventional therapies. Irreversible electroporation (IRE) is a promising therapy for PDAC; however, its clinical efficacy is limited by a high recurrence rate. Here, using a preclinical PDAC model, we characterized the tumor immune microenvironment following insufficient IRE (iIRE) through single-cell RNA sequencing. We found that iIRE induces a CCR2<sup>+</sup> tumor-associated macrophage (CCR2<sup>+</sup> TAM)–mediated immunosuppressive microenvironment in residual tumors. Consequently, we developed a macrophage-based proteolipid vesicle (mPLV) coencapsulating the CCR2 antagonist PF-4136309 (PF) and gemcitabine (GEM), named PF/GEM@mPLV. Our findings suggest that PF/GEM@mPLV achieves high drug accumulation within tumors through iIRE-induced inflammation. Reduction of CCR2<sup>+</sup> TAMs enhances antitumor immunity and improves chemotherapeutic response. PF/GEM@mPLV markedly inhibits tumor recurrence following iIRE, diminishes hepatic metastases, and prolongs survival in preclinical PDAC models. These findings uncover the role of CCR2<sup>+</sup> TAMs in iIRE-induced immunosuppression, offering a promising strategy to enhance the clinical potential of IRE in PDAC.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adw2937","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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}
Science AdvancesPub Date : 2025-07-23DOI: 10.1126/sciadv.ado2837
Jessica A. Wojick, Alekh Paranjapye, Juliann K. Chiu, Corinna S. Oswell, Malaika Mahmood, Lisa M. Wooldridge, Blake A. Kimmey, Raquel Adaia Sandoval Ortega, Nora M. McCall, Seungmin Han, Jacqueline W. K. Wu, Maxx Yung, Lindsay L. Ejoh, Samar Nasser Chehimi, Richard C. Crist, Benjamin C. Reiner, Erica Korb, Gregory Corder
{"title":"A nociceptive amygdala-striatal pathway modulating affective-motivational pain","authors":"Jessica A. Wojick, Alekh Paranjapye, Juliann K. Chiu, Corinna S. Oswell, Malaika Mahmood, Lisa M. Wooldridge, Blake A. Kimmey, Raquel Adaia Sandoval Ortega, Nora M. McCall, Seungmin Han, Jacqueline W. K. Wu, Maxx Yung, Lindsay L. Ejoh, Samar Nasser Chehimi, Richard C. Crist, Benjamin C. Reiner, Erica Korb, Gregory Corder","doi":"10.1126/sciadv.ado2837","DOIUrl":"10.1126/sciadv.ado2837","url":null,"abstract":"<div >The basolateral amygdala (BLA) assigns valence to sensory stimuli, with a dedicated nociceptive ensemble encoding the negative valence of pain. However, the effects of chronic pain on the transcriptomic signatures and projection architecture of this BLA nociceptive ensemble are not well understood. Here, we show that optogenetic inhibition of the nociceptive BLA ensemble reduces affective-motivational behaviors in chronic neuropathic pain. Single-nucleus RNA sequencing revealed peripheral injury–induced changes in genetic pathways involved in axonal and presynaptic organization in nociceptive BLA neurons. Next, we identified a previously uncharacterized nociceptive hotspot in the nucleus accumbens shell that is innervated by BLA nociceptive neurons. Axonal calcium imaging of BLA projections to the accumbens and chemogenetic inhibition of this pathway revealed pain-related transmission from the amygdala to the medial nucleus accumbens, facilitating both acute and chronic pain affective-motivational behaviors. Together, this work defines a critical nociceptive amygdala-striatal circuit underlying pain unpleasantness across pain states.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado2837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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}
Science AdvancesPub Date : 2025-07-23DOI: 10.1126/sciadv.ady0183
Ziyang Lu, Luhe Qi, Junqing Chen, Cai Lu, Jing Huang, Lu Chen, Yuying Wu, Jiahao Feng, Jinyou Lin, Ze Liu, Erlantz Lizundia, Chaoji Chen
{"title":"A superstrong, decarbonizing structural material enabled by microbe-assisted cell wall engineering via a biomechanochemical process","authors":"Ziyang Lu, Luhe Qi, Junqing Chen, Cai Lu, Jing Huang, Lu Chen, Yuying Wu, Jiahao Feng, Jinyou Lin, Ze Liu, Erlantz Lizundia, Chaoji Chen","doi":"10.1126/sciadv.ady0183","DOIUrl":"10.1126/sciadv.ady0183","url":null,"abstract":"<div >Lightweight and high-strength structural materials promise exceptional applications in advanced engineering fields. As a productive and sustainable material, wood exhibits exceptional potential to be converted into high-performance structural materials. Inspired by ancient buried wood—a naturally formed material after wood endures in microbial-rich and high-pressure environments for thousands of years—here, we demonstrate a biomechanochemical process to rapidly transform natural wood into artificial ancient buried wood (named Bio-Strong-Wood). Biotreatment depolymerizes the lignin and softens the cell wall. Then, Bio-Strong-Wood components are linked via a strong network of hydrogen and covalent bonds through the mechanochemical treatment. This results in a substantially enhanced mechanical strength (539 ± 21.7 megapascals), which outperforms the SAE 304 stainless steel. In addition, life cycle and technoeconomic assessments reveal that the obtained material achieves negative carbon emissions of 1.17 kilograms of carbon dioxide equivalent per kilogram. Overall, our work provides an economically competitive, environmentally sustainable, and decarbonizing alternative to existing structural materials.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ady0183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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}
Science AdvancesPub Date : 2025-07-23DOI: 10.1126/sciadv.adv6990
Yongwei Gu, Aixue Li, Yuanye Zeng, Mengyuan He, Fu Qi, Rongmei Liu, Huanhuan Cai, Dan Li, Xiaomeng Tang, Zhiqin Fu, Xin Wu, Jiyong Liu
{"title":"Engineering hybrid nanoparticles for targeted codelivery of triptolide and CYP3A4-siRNA against pulmonary metastatic melanoma","authors":"Yongwei Gu, Aixue Li, Yuanye Zeng, Mengyuan He, Fu Qi, Rongmei Liu, Huanhuan Cai, Dan Li, Xiaomeng Tang, Zhiqin Fu, Xin Wu, Jiyong Liu","doi":"10.1126/sciadv.adv6990","DOIUrl":"10.1126/sciadv.adv6990","url":null,"abstract":"<div >Pulmonary metastatic melanoma (PMM) is an aggressive malignancy with limited response and rapid resistance to clinical chemotherapy, radiotherapy, immunotherapy, and biological therapies. Here, we developed a targeted biomimetic drug delivery system, TP-siRC@tHyNPs, by fusing exosomes derived from engineered cells overexpressing DR5 single-chain variable fragments (DR5-Exo) with liposomes coencapsulating triptolide (TP) and CYP3A4-siRNA (TP-siRC@Lip). DR5-Exo facilitated the targeted delivery of drug to tumor cells through DR5 receptor recognition and simultaneously activated apoptotic pathways. Moreover, CYP3A4-siRNA effectively prolonged the half-life of TP, thereby enhancing its antiproliferative and pro-apoptotic effects. Mechanistic studies revealed that TP-siRC@tHyNPs induced immunogenic cell death, reprogrammed macrophage polarization, arrested cell cycle progression, and triggered apoptotic pathways. In vivo experiments demonstrated that TP-siRC@tHyNPs specifically accumulated in lung tissue, notably inhibiting the growth of PMM while exhibiting negligible toxicity in tumor-bearing mice. Overall, this study provides a promising strategy for targeting PMM treatment, improving therapeutic efficacy while reducing off-target toxicity.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv6990","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Photoacoustic and fluorescence hybrid microscope for cortex-wide imaging of neurovascular dynamics with subcellular resolution","authors":"Liangjian Liu, Zhiqiang Xu, Zhenjie Lai, Bin Xu, Taofeng Wu, Guangying Ma, Hongdong Zhang, Jiahao Li, Weilei Ma, Tiancheng Lei, Xiufeng Li, Zeyi Guo, Zheng Song, Ningbo Chen, Shiwei Ye, Jing Meng, Puxiang Lai, Feng Shen, Junlei Chang, Yingjie Zhu, Hairong Zheng, Wei Zheng, Chengbo Liu","doi":"10.1126/sciadv.adw5275","DOIUrl":"10.1126/sciadv.adw5275","url":null,"abstract":"<div >Simultaneously monitoring cortex-wide microvascular dynamics, blood oxygenation metabolism, and neuronal activities with high spatiotemporal resolution is essential for understanding neurovascular coupling (NVC). However, it remains a challenge for existing neuroimaging tools. Here, we report a linear transducer array–based hybrid microscope (LiTA-HM) that integrates photoacoustic microscopy and confocal fluorescence microscopy to achieve simultaneous neurovascular imaging with a field of view (FOV) of 6 millimeters by 5 millimeters, a spatial resolution of ~6 micrometers, and a temporal resolution of 0.8 seconds. We design an array of eight miniature transducers to enlarge FOV and optimize a polygon mirror–based ultrafast scanner to achieve real-time imaging. Proof-of-concept imaging experiments were conducted on awake mice. Different couplings between thousands of neuron somas and vessel branches down to capillaries were observed in hypoxia and anesthesia experiments. Spatiotemporal correlations and functional connectivity in NVC were uncovered for spreading depolarization waves occurred in a drug-induced epilepsy experiment. We expect that LiTA-HM will enable broad applications of neuroimaging.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adw5275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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}
Science AdvancesPub Date : 2025-07-23DOI: 10.1126/sciadv.adx5922
Donghyeon Kang, Byung-Joon Park, Joon-Ha Hwang, Young-Jun Kim, So-Hee Kim, Hyun Woo Kim, Ki Jun Yu, Jinyoung Jeon, Hyeon Yeong Lee, Youngwook Chung, Soo Hyun Nam, Byung-Ok Choi, Sang-Woo Kim
{"title":"In-body current path manipulation with minimal attenuation","authors":"Donghyeon Kang, Byung-Joon Park, Joon-Ha Hwang, Young-Jun Kim, So-Hee Kim, Hyun Woo Kim, Ki Jun Yu, Jinyoung Jeon, Hyeon Yeong Lee, Youngwook Chung, Soo Hyun Nam, Byung-Ok Choi, Sang-Woo Kim","doi":"10.1126/sciadv.adx5922","DOIUrl":"10.1126/sciadv.adx5922","url":null,"abstract":"<div >Wireless power transfer–based neuromodulation has emerged as a promising alternative to battery-powered implants. However, its practical application is hindered by limited therapeutic efficacy resulting from low power transfer efficiency, shallow penetration depth, and safety concerns. In this study, we report an in-body current path manipulation and concentration for advanced targeted neuromodulation, overcoming the limitations of conventional technologies. By implanting a focusing electrode, we were able to direct the triboelectric current, which has a low frequency and high impedance generated by human movement, toward the target area, with the concentrated current exhibiting minimal attenuation regardless of the electrode size, implantation site, and depth. Applying our technology to modulate damaged neural systems confirmed therapeutic efficacy and validated safety, demonstrating its potential for next-generation targeted neuromodulation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx5922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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}
Science AdvancesPub Date : 2025-07-23DOI: 10.1126/sciadv.adq0011
Danai Riga, Karlijn L. Kooij, Kelly Rademakers, Inge G. Wolterink-Donselaar, Onur Basak, Frank J. Meye
{"title":"Neuropeptide Y neurons surrounding the locus coeruleus inhibit noradrenergic system activity to reduce anxiety","authors":"Danai Riga, Karlijn L. Kooij, Kelly Rademakers, Inge G. Wolterink-Donselaar, Onur Basak, Frank J. Meye","doi":"10.1126/sciadv.adq0011","DOIUrl":"10.1126/sciadv.adq0011","url":null,"abstract":"<div >Adaptive responses to challenging environments depend on optimal function of the locus coeruleus (LC), the brain’s main source of noradrenaline and primary mediator of the initial stress response. Combining functional circuit dissection and causal in vivo interventions in mice, we here investigate a built-in peptidergic regulatory system that restricts LC noradrenergic output. In particular, we characterize a population of neuropeptide Y (NPY)–expressing neurons surrounding LC noradrenergic cells. We show that this peri-LC<sub>NPY</sub> population exerts neuromodulatory inhibitory control over the LC via NPY-Y1R signaling. Under naïve conditions, this results in bidirectional control of anxiety-like behaviors. Stressful experiences recruit peri-LC<sub>NPY</sub> neurons, leading to local NPY release in vivo, whereas enhanced peri-LC<sub>NPY</sub> neuronal activity curbs anxiety after stress. Together, we establish a causal role for peri-LC<sub>NPY</sub>–mediated neuromodulation of the LC in the regulation of anxiety, providing mechanistic insights into the endogenous systems underlying adaptive responses to adversity.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 30","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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}
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