Science Advances最新文献_第4页

Astrocytes-derived LCN2 triggers EV-A71–induced muscle soreness via accumulating lactate 星形胶质细胞衍生的LCN2通过积累乳酸触发ev - a71诱导的肌肉酸痛

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-16 DOI: 10.1126/sciadv.adt9837

Qiao You, Jing Wu, Chaoyong Wang, Deyan Chen, Shiji Deng, Yurong Cai, Nan Zhou, Ruining Lyu, Yajie Qian, Yi Xie, Miao He, Zhiwei Wu

{"title":"Astrocytes-derived LCN2 triggers EV-A71–induced muscle soreness via accumulating lactate","authors":"Qiao You, Jing Wu, Chaoyong Wang, Deyan Chen, Shiji Deng, Yurong Cai, Nan Zhou, Ruining Lyu, Yajie Qian, Yi Xie, Miao He, Zhiwei Wu","doi":"10.1126/sciadv.adt9837","DOIUrl":"10.1126/sciadv.adt9837","url":null,"abstract":"<div >Viral muscle soreness (VMS) is a common feature during acute viral infections, including those caused by enteroviruses, and it substantially diminishes patients’ quality of life. At present, we aim to establish the “brain-muscle” axis to explore the underlying mechanisms of VMS. We initially observed that diminished pain threshold occurred in enterovirus A71 (EV-A71)–infected C57BL/6J and AG6 mice. Subsequently, RNA sequencing data showed that lipocalin 2 (LCN2) was up-regulated during multiple viral infections, including EV-A71, Japanese encephalitis virus, vesicular stomatitis virus, and West Nile virus, which all caused VMS. As expected, <i>Lcn2</i>-deficient C57BL/6 J (<i>Lcn2</i><sup>−/−</sup>) mice exhibited greater pain tolerance, as shown by stronger grip force and stable motor function after EV-A71 infection. Mechanistically, EV-A71–induced high-mobility group 1 (HMGB1) stimulated astrocyte-derived LCN2 secreted into the circulatory system, which enhanced glycolysis and induced lactate buildup in muscle through increasing pyruvate dehydrogenase kinase 1 (PDK1) expression and decreasing pyruvate dehydrogenase (PDH) activity. Together, HMGB1/LCN2/PDK1/lactate pathway in the brain-muscle axis promoted VMS development.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt9837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074823","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}

引用次数: 0

Ancestral reconstruction of polyethylene terephthalate degrading cutinases reveals a rugged and unexplored sequence-fitness landscape 聚对苯二甲酸乙二醇酯降解角质酶的祖先重建揭示了一个崎岖和未探索的序列适应度景观

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-14 DOI: 10.1126/sciadv.ads8318

Vanessa Vongsouthi, Rosemary Georgelin, Dana S. Matthews, Jake Saunders, Brendon M. Lee, Jennifer Ton, Adam M. Damry, Rebecca L. Frkic, Matthew A. Spence, Colin J. Jackson

{"title":"Ancestral reconstruction of polyethylene terephthalate degrading cutinases reveals a rugged and unexplored sequence-fitness landscape","authors":"Vanessa Vongsouthi, Rosemary Georgelin, Dana S. Matthews, Jake Saunders, Brendon M. Lee, Jennifer Ton, Adam M. Damry, Rebecca L. Frkic, Matthew A. Spence, Colin J. Jackson","doi":"10.1126/sciadv.ads8318","DOIUrl":"10.1126/sciadv.ads8318","url":null,"abstract":"<div >The use of protein engineering to generate enzymes for the degradation of polyethylene terephthalate (PET) is a promising route for plastic recycling, yet traditional engineering approaches often fail to explore protein sequence space for optimal enzymes. In this work, we use multiplexed ancestral sequence reconstruction (mASR) to address this, exploring the evolutionary sequence space of PET-degrading cutinases. Using 20 statistically equivalent phylogenies of the bacterial cutinase family, we generated 48 ancestral sequences revealing a wide range of PETase activities, highlighting the value of mASR in uncovering functional variants. Our findings show PETase activity can evolve through multiple pathways involving mutations remote from the active site. Moreover, analyzing the PETase fitness landscape with local ancestral sequence embedding (LASE) revealed that LASE can capture sequence features linked to PETase activity. This work highlights mASR’s potential in exploration of sequence space and underscores the use of LASE in readily mapping the protein fitness landscapes.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads8318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950599","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}

引用次数: 0

Emergent social conventions and collective bias in LLM populations 新兴的社会习俗和法学硕士群体的集体偏见

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-14 DOI: 10.1126/sciadv.adu9368

Ariel Flint Ashery, Luca Maria Aiello, Andrea Baronchelli

引用次数: 0

The cost of clean air: Global disparities in reducing indoor wildfire-related PM2.5 exposure 清洁空气的成本：减少室内野火相关PM2.5暴露的全球差异

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-14 DOI: 10.1126/sciadv.ady0890

Jing Li, Yifang Zhu

引用次数: 0

State-dependent associative plasticity highlights function-specific premotor-motor pathways crucial for arbitrary visuomotor mapping 状态依赖的联想可塑性强调了对任意视觉运动映射至关重要的功能特异性前运动-运动通路

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-14 DOI: 10.1126/sciadv.adu4098

Sonia Turrini, Francesca Fiori, Giorgio Arcara, Vincenzo Romei, Giuseppe di Pellegrino, Alessio Avenanti

{"title":"State-dependent associative plasticity highlights function-specific premotor-motor pathways crucial for arbitrary visuomotor mapping","authors":"Sonia Turrini, Francesca Fiori, Giorgio Arcara, Vincenzo Romei, Giuseppe di Pellegrino, Alessio Avenanti","doi":"10.1126/sciadv.adu4098","DOIUrl":"10.1126/sciadv.adu4098","url":null,"abstract":"<div >Arbitrary visuomotor mapping (AVMM) showcases the brain’s ability to link sensory inputs with actions. The ventral premotor cortex (PMv) is proposed as central to sensorimotor transformations, relaying descending motor commands through the primary motor cortex (M1). However, direct evidence of this pathway’s involvement in AVMM remains elusive. In four experiments, we used cortico-cortical paired associative stimulation (ccPAS) to enhance (ccPAS<sub>PMv-M1</sub>) or inhibit (ccPAS<sub>M1-PMv</sub>) PMv-to-M1 connectivity via Hebbian plasticity. Leveraging state-dependent properties of transcranial magnetic stimulation, we targeted function-specific visuomotor neurons within the pathway, testing their physiological/behavioral relevance to AVMM. State-dependent ccPAS<sub>PMv-M1</sub>, applied during motor responses to target visual cues, enhanced neurophysiological and behavioral indices of AVMM, while ccPAS<sub>M1-PMv</sub> had an opposite influence, with the effects being more pronounced for target relative to control visual cues. These results highlight the plasticity and causal role of spatially overlapping but functionally specific neural populations within the PMv-M1 pathway in AVMM and suggest state-dependent ccPAS as a tool for targeted modulation of visuomotor pathways.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu4098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950623","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}

引用次数: 0

Phosphorylation by Aurora kinase A facilitates cortical-cytoplasmic dynamics of Par-3 in asymmetric division of radial glia progenitors 极光激酶A的磷酸化促进了Par-3在放射状胶质祖细胞不对称分裂中的皮质-细胞质动力学

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-14 DOI: 10.1126/sciadv.adq3858

Jason Q. Garcia, Vincent Mouilleau, Henry Ng, Xiang Zhao, David O. Morgan, Su Guo

{"title":"Phosphorylation by Aurora kinase A facilitates cortical-cytoplasmic dynamics of Par-3 in asymmetric division of radial glia progenitors","authors":"Jason Q. Garcia, Vincent Mouilleau, Henry Ng, Xiang Zhao, David O. Morgan, Su Guo","doi":"10.1126/sciadv.adq3858","DOIUrl":"10.1126/sciadv.adq3858","url":null,"abstract":"<div >During asymmetric cell division (ACD) of radial glia progenitors (RGPs), the cortical polarity regulator Par-3 is detected in the cytoplasm colocalizing with dynein and Notch ligand DeltaD (Dld). What drives Par-3 to the cytoplasm and its impact on RGP ACD remain unknown. Here, we visualize cytoplasmic Par-3 using in vivo time-lapse imaging and find that Ser<sup>954</sup> of zebrafish Par-3 is phosphorylated by Aurora kinase A (AurkA) in vitro. Expression of the nonphosphorylated mutant Par-3<sup>S954A</sup> dominant negatively affects embryonic development, reduces cytoplasmic Par-3, and disrupts the anteroposterior asymmetry of cortical Par-3 and Dld endosomes and, in turn, daughter cell fate. AurkA in mitotic RGPs shows dynamic pericentrosomal distribution that transiently colocalizes with cortical Par-3 preferentially on the posterior side. AurkA is both necessary and sufficient to increase cytoplasmic while decreasing cortical Par-3, disrupts Par-3 cortical asymmetry, and perturbs polarized Dld endosome dynamics. These findings suggest that AurkA regulates Par-3 cortical-cytoplasmic dynamics that is critical for ACD and daughter cell fate.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq3858","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950630","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}

引用次数: 0

Endogenous/exogenous dual-responsive nanozyme for photothermally enhanced ferroptosis-immune reciprocal synergistic tumor therapy 内源性/外源性双反应纳米酶用于光热增强铁中毒-免疫互惠协同肿瘤治疗

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-14 DOI: 10.1126/sciadv.adq3870

Hanxi Zhang, Jiazhen Lv, Hao Wu, Yuhan He, Mengyue Li, Chunhui Wu, Dong Lv, Yiyao Liu, Hong Yang

{"title":"Endogenous/exogenous dual-responsive nanozyme for photothermally enhanced ferroptosis-immune reciprocal synergistic tumor therapy","authors":"Hanxi Zhang, Jiazhen Lv, Hao Wu, Yuhan He, Mengyue Li, Chunhui Wu, Dong Lv, Yiyao Liu, Hong Yang","doi":"10.1126/sciadv.adq3870","DOIUrl":"10.1126/sciadv.adq3870","url":null,"abstract":"<div >Apoptosis resistance and immune evasion of tumor cells substantially increase the risk of cancer treatment failure. Here, a multifunctional nanozyme MET-CMS@FeTA (MCMSFT) formulated to induce nonapoptotic ferroptosis and boost immune recognition/attack, where compensatory mechanisms collectively overcome intrinsic tumor therapeutic limitations and improve medical intervention outcomes. Leveraging the multienzyme-like activity of MCMSFT to achieve oxygen generation, hydroxyl radical production, and glutathione depletion promotes hypoxia relief and triggers apoptosis/ferroptosis. Notably, MCMSFT-mediated photothermal therapy (PTT) facilitates direct tumor thermal ablation and offers exogenous heat to accelerate nanocatalytic reactions. Furthermore, PTT/ferroptosis-caused immunogenic cell death favors antitumor immunity initiation. Simultaneously, metformin administration and hypoxia amelioration down-regulate programmed death ligand 1 alleviating immune evasion. Interferon-γ secretion poses positive feedback to ferroptosis, thereby establishing a ferroptosis-immune mutual amplification loop. Antitumor performances illustrate that MCMSFT eliminates primary tumors and suppresses metastasis/rechallenge tumors. Collectively, MCMSFT surmounts the predicament of apoptosis resistance and immune evasion in cancer treatment to acquire more effective and comprehensive therapy efficacy.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq3870","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950606","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}

引用次数: 0

Observation of edge supercurrent in topological antiferromagnet MnBi2Te4-based Josephson junctions 拓扑反铁磁体mnbi2te4基Josephson结边缘超电流的观察

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-14 DOI: 10.1126/sciadv.ads8730

Enze Zhang, Zi-Ting Sun, Zehao Jia, Jinshan Yang, Jingyi Yan, Linfeng Ai, Ying-Ming Xie, Yuda Zhang, Xue-Jian Gao, Xian Xu, Shanshan Liu, Qiang Ma, Chaowei Hu, Xufeng Kou, Jin Zou, Ni Ni, Kam Tuen Law, Shaoming Dong, Faxian Xiu

{"title":"Observation of edge supercurrent in topological antiferromagnet MnBi2Te4-based Josephson junctions","authors":"Enze Zhang, Zi-Ting Sun, Zehao Jia, Jinshan Yang, Jingyi Yan, Linfeng Ai, Ying-Ming Xie, Yuda Zhang, Xue-Jian Gao, Xian Xu, Shanshan Liu, Qiang Ma, Chaowei Hu, Xufeng Kou, Jin Zou, Ni Ni, Kam Tuen Law, Shaoming Dong, Faxian Xiu","doi":"10.1126/sciadv.ads8730","DOIUrl":"10.1126/sciadv.ads8730","url":null,"abstract":"<div >Hybridizing superconductivity with topology and magnetism attracts growing interest in condensed matter physics. Here, we present our findings on the measurement of supercurrent induced in an intrinsic antiferromagnetic topological insulator MnBi<sub>2</sub>Te<sub>4</sub>. By constructing a MnBi<sub>2</sub>Te<sub>4</sub> proximity Josephson junction, we observed an anomalously large period of the Fraunhofer patterns, indicating a strong Josephson coupling state. As the MnBi<sub>2</sub>Te<sub>4</sub> thickness is reduced, a distinct asymmetric edge supercurrent emerges, aligning consistently with the observed oscillatory junction magnetoresistance. Leveraging this large asymmetric edge supercurrent, we have realized a nonvolatile Josephson diode device with programmable polarity, achieved through training with an out-of-plane magnetic field. Theoretical calculations substantiate that these behaviors are attributed to the interference between the highly asymmetric topological edge channel–mediated supercurrent induced in MnBi<sub>2</sub>Te<sub>4</sub>. Our study establishes this system as a promising avenue for investigating topological superconductivity, chiral Majorana edge modes, and advanced functionality device applications.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads8730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950616","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}

引用次数: 0

Self-positioning microdevices enable adaptable spatial displaying 自定位微设备使空间显示适应性强

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-14 DOI: 10.1126/sciadv.adv2721

Qi Guo, Zeyi Li, Yajie Zhou, Shanshan Zhao, Yaxin Wang, Mingjiang Zhang, Guangen Li, Zhi Tong, Taotao Zhuang, Shu-Hong Yu

{"title":"Self-positioning microdevices enable adaptable spatial displaying","authors":"Qi Guo, Zeyi Li, Yajie Zhou, Shanshan Zhao, Yaxin Wang, Mingjiang Zhang, Guangen Li, Zhi Tong, Taotao Zhuang, Shu-Hong Yu","doi":"10.1126/sciadv.adv2721","DOIUrl":"10.1126/sciadv.adv2721","url":null,"abstract":"<div >Adaptable display with spatial imaging, fostering advancements in extended reality with unconventional form requirements, is indispensable in scientific research, telemedicine, rescue, and space exploration. The adjustable photon spin angular momentum derived from chiral optical materials offer applicative lights for binocular stereo imaging displays, thus allowing an unimaginable immersive experience while maintaining awareness of surroundings. However, current chiral illuminant struggles to obtain adequate electroluminescence asymmetry during power-on display. Here, we present a designed self-positioning strategy to build new flexible spatial displays, integrating numerous multilayered circularly polarized electroluminescent microdevices, for real-time depth information control on the screen. With the devices’ luminescence asymmetry value of up to 1.0 under electro-excitation, we visualize third-dimensional information using our chiral material-integrated tablet. Afterward, combined with a robot, we realize a series of remote human-machine interaction operations based on extended reality conditions. Our adaptable spatial display bridges the gap between virtuality and reality, making pioneering explorations in chiral luminous fields for extended reality and beyond.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv2721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950618","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}

引用次数: 0

Fibronectin in the olfactory mucus increases sensitivity of olfactory receptor response to odorants 嗅觉粘液中的纤维连接蛋白增加了嗅觉受体对气味反应的敏感性

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-05-14 DOI: 10.1126/sciadv.adu7271

Stella Chapman, Kenji Kondo, Sayoko Ihara, Chiori Ijichi, Kazushige Touhara, Koji Sato

{"title":"Fibronectin in the olfactory mucus increases sensitivity of olfactory receptor response to odorants","authors":"Stella Chapman, Kenji Kondo, Sayoko Ihara, Chiori Ijichi, Kazushige Touhara, Koji Sato","doi":"10.1126/sciadv.adu7271","DOIUrl":"10.1126/sciadv.adu7271","url":null,"abstract":"<div >Olfaction is a highly sensitive chemical detection system, but the origins of this sensitivity remain poorly understood. In terrestrial vertebrates, inhaled odorants diffuse through olfactory epithelial mucus (OEM) before activating olfactory receptors (ORs) on olfactory sensory neurons and initiating adenosine 3′,5′-monophosphate (cAMP)–mediated signaling. Impaired OEM secretion is associated with impaired olfactory sensitivity in humans and mice, but it remains unclear whether OEM directly improves sensitivity and whether specific active factors exist. Here, using a cAMP imaging–based heterologous OR expression assay, we demonstrate that fibronectin from human OEM increases the sensitivity of OR response to odorant. Fibronectin application partially restores electrical olfactory response of the mouse olfactory epithelium after OEM removal. In humans, OEM fibronectin levels are significantly decreased in patients with idiopathic olfactory disorder. These findings shed light on the role of OEM fibronectin in olfaction and may lead to sensitivity-enhancing additives for odorant sensors and treatments for hyposmia.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 20","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu7271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950629","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}

引用次数: 0