Science Advances最新文献_第2页

LCE-integrated soft skin for millimeter-scale steerable soft everting robots 基于lce集成的毫米级可操纵软悬垂机器人软皮肤

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2025-10-15 DOI: 10.1126/sciadv.adw8636

Sukjun Kim, Gaoweiang Dong, Aedan Mangan, Devyansh Agrawal, Shengqiang Cai, Tania K. Morimoto

引用次数: 0

Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma 肼嗪抑制半胱胺双加氧酶治疗先兆子痫和老年性胶质母细胞瘤

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2025-10-15 DOI: 10.1126/sciadv.adx7687

Kyosuke Shishikura, Jiasong Li, Yiming Chen, Nate R. McKnight, Thomas P. Keeley, Katelyn A. Bustin, Eric W. Barr, Snehil R. Chilkamari, Mahaa Ayub, Sun Woo Kim, Zongtao Lin, Ren-Ming Hu, Kelly Hicks, Xie Wang, Donald M. O’Rourke, J. Martin Bollinger, Zev A. Binder, William H. Parsons, Kirill A. Martemyanov, Aimin Liu, Megan L. Matthews

{"title":"Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma","authors":"Kyosuke Shishikura, Jiasong Li, Yiming Chen, Nate R. McKnight, Thomas P. Keeley, Katelyn A. Bustin, Eric W. Barr, Snehil R. Chilkamari, Mahaa Ayub, Sun Woo Kim, Zongtao Lin, Ren-Ming Hu, Kelly Hicks, Xie Wang, Donald M. O’Rourke, J. Martin Bollinger, Zev A. Binder, William H. Parsons, Kirill A. Martemyanov, Aimin Liu, Megan L. Matthews","doi":"10.1126/sciadv.adx7687","DOIUrl":"https://doi.org/10.1126/sciadv.adx7687","url":null,"abstract":"Hydralazine (HYZ), a treatment for preeclampsia and hypertensive crisis, is listed by the World Health Organization as an essential medicine. Its mode of action has remained unknown through its seven decades of clinical use. Here, we identify 2-aminoethanethiol dioxygenase (ADO), a key mediator of targeted protein degradation, as a selective HYZ target. The drug chelates ADO’s metallocofactor and can alkylate one of its ligands. The resultant inactivation stabilizes regulators of G protein signaling (RGS4 and RGS5) that ADO normally marks for proteolysis, explaining the drug’s vasodilatory activity and comporting with observations of diminished RGS levels in both clinical preeclampsia and a mouse model thereof. Its inhibition of ADO suggested use of HYZ against glioblastoma (GBM); indeed, a single dose robustly senesces cultured GBM cells. By establishing ADO as a nexus for GBM and preeclampsia and connecting it to HYZ, the results create opportunities for directed tailoring of the old drug for new therapies.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"76 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145289322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure and function of otoferlin, a synaptic protein of sensory hair cells essential for hearing 耳铁蛋白的结构和功能，耳铁蛋白是听觉所必需的感觉毛细胞的突触蛋白

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2025-10-15 DOI: 10.1126/sciadv.ady8532

Han Chen, Constantin Cretu, Abigail Trebilcock, Natalia Evdokimova, Norbert Babai, Laura Feldmann, Florian Leidner, Fritz Benseler, Sophia Mutschall, Klara Esch, Csaba Zoltan Kibedi Szabo, Vladimir Pena, Constantin Pape, Helmut Grubmüller, Nicola Strenzke, Nils Brose, Carolin Wichmann, Julia Preobraschenski, Tobias Moser

{"title":"Structure and function of otoferlin, a synaptic protein of sensory hair cells essential for hearing","authors":"Han Chen, Constantin Cretu, Abigail Trebilcock, Natalia Evdokimova, Norbert Babai, Laura Feldmann, Florian Leidner, Fritz Benseler, Sophia Mutschall, Klara Esch, Csaba Zoltan Kibedi Szabo, Vladimir Pena, Constantin Pape, Helmut Grubmüller, Nicola Strenzke, Nils Brose, Carolin Wichmann, Julia Preobraschenski, Tobias Moser","doi":"10.1126/sciadv.ady8532","DOIUrl":"https://doi.org/10.1126/sciadv.ady8532","url":null,"abstract":"Hearing relies upon speedy synaptic transmission of sound information from inner hair cells (IHCs) to spiral ganglion neurons. To accomplish this, IHCs use a sophisticated presynaptic machinery including the multi-C 2 domain protein otoferlin that is affected by human deafness mutations. Otoferlin is essential for IHC exocytosis, but how it binds Ca 2+ and the target membrane to serve synaptic vesicle (SV) tethering, docking, and fusion remained unclear. Here, we obtained cryo–electron microscopy structures of otoferlin and employed molecular dynamics simulations of membrane binding. We show that membrane binding by otoferlin involves C 2 B-C 2 G domains and repositions C 2 F and C 2 G domains. Disruption of Ca 2+ -binding sites of the C 2 D domain in mice altered synaptic sound encoding and eliminated the Ca 2+ cooperativity of IHC exocytosis, indicating that it requires the binding of several Ca 2+ -ions by otoferlin. Together, our findings elucidate molecular mechanisms underlying otoferlin-mediated SV docking and support the role of otoferlin as Ca 2+ sensor of SV fusion in IHCs.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"28 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145289284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure and quenching of a bundle-shaped phycobilisome 束状藻胆体的结构与猝灭

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2025-10-15 DOI: 10.1126/sciadv.adz6774

Anna D. Burtseva, Yury B. Slonimskiy, Timur N. Baymukhametov, Maria A. Sinetova, Daniil A. Gvozdev, Georgy V. Tsoraev, Dmitry A. Cherepanov, Eugene G. Maksimov, Vladimir O. Popov, Konstantin M. Boyko, Nikolai N. Sluchanko

{"title":"Structure and quenching of a bundle-shaped phycobilisome","authors":"Anna D. Burtseva, Yury B. Slonimskiy, Timur N. Baymukhametov, Maria A. Sinetova, Daniil A. Gvozdev, Georgy V. Tsoraev, Dmitry A. Cherepanov, Eugene G. Maksimov, Vladimir O. Popov, Konstantin M. Boyko, Nikolai N. Sluchanko","doi":"10.1126/sciadv.adz6774","DOIUrl":"https://doi.org/10.1126/sciadv.adz6774","url":null,"abstract":"Cyanobacteria use soluble antenna megacomplexes, phycobilisomes (PBSs), to maximize light-harvesting efficiency and small photoswitchable orange carotenoid proteins (OCPs) to down-regulate PBSs in high light. Among known PBS morphologies, the one from the basal cyanobacterial genus Gloeobacter still lacks detailed structural characterization. Here, we reconstructed a cryo–electron microscopy structure of the >10-megadalton Gloeobacter violaceus PBS, with diverging, conformationally mobile bundles of rods composed of stacked phycoerythrin and phycocyanin hexamers, stemming from a pentacylindrical allophycocyanin core belted by auxiliary phycocyanin hexamers. We show how two Gloeobacter -specific multidomain linker proteins, Glr1262 and Glr2806, maintain this bundle-shaped architecture and reveal its differential regulation via nonphotochemical quenching by two OCP types of G. violaceus that recognize separate binding sites within the allophycocyanin core, including lateral cylinders absent in tricylindrical cores.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"199 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatiotemporally controlled delivery of biological effectors from nanofiber scaffolds accelerates skin wound healing in porcine models 纳米纤维支架的生物效应物的时空控制递送加速了猪模型的皮肤伤口愈合

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2025-10-15 DOI: 10.1126/sciadv.adz5302

Xindan Zhang, Bowen Gong, Feng Rao, Hongtao Hu, Feng Tian, Yonglai Lu, Liqun Zhang, Younan Xia, Jiajia Xue

{"title":"Spatiotemporally controlled delivery of biological effectors from nanofiber scaffolds accelerates skin wound healing in porcine models","authors":"Xindan Zhang, Bowen Gong, Feng Rao, Hongtao Hu, Feng Tian, Yonglai Lu, Liqun Zhang, Younan Xia, Jiajia Xue","doi":"10.1126/sciadv.adz5302","DOIUrl":"https://doi.org/10.1126/sciadv.adz5302","url":null,"abstract":"Skin wound healing is a dynamic process, yet scaffolds enabling stage-specific modulation remain limited. We fabricated a nanofiber scaffold from FDA-approved materials, consisting of two outer layers of radially aligned and random poly(ε-caprolactone) fibers and a middle layer of electrosprayed phase-change microparticles loaded with platelet-derived growth factor–BB (PDGF-BB)/vascular endothelial growth factor (VEGF) in the periphery and PDGF-BB/epidermal growth factor (EGF) in the center. Near-infrared irradiation through a photomask enabled spatiotemporal control of growth factor release, aligning PDGF-BB, VEGF, and EGF delivery with specific phases of wound healing to promote vascularization, cell proliferation, and tissue remodeling. In a preclinical porcine model, it enhanced closure and modulated the microenvironment by activating PI3K-Akt, MAPK, and immune pathways, up-regulating genes for survival and repair while down-regulating those linked to apoptosis and inflammation. With scalable manufacturing and large-animal efficacy, this scaffold holds translational potential for skin wound healing.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"54 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vector analog computing via on-demand metasurface dispersive polarization transformation 基于按需超表面色散偏振变换的矢量模拟计算

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2025-10-15 DOI: 10.1126/sciadv.adz5123

Hui Yang, Jie Xu, Meiyu Peng, Hairong He, Yuting Jiang, Dian Yu, Ruibo Jin, Yingjie Gu, Yueqiang Hu, Huigao Duan, Hui Jing

{"title":"Vector analog computing via on-demand metasurface dispersive polarization transformation","authors":"Hui Yang, Jie Xu, Meiyu Peng, Hairong He, Yuting Jiang, Dian Yu, Ruibo Jin, Yingjie Gu, Yueqiang Hu, Huigao Duan, Hui Jing","doi":"10.1126/sciadv.adz5123","DOIUrl":"https://doi.org/10.1126/sciadv.adz5123","url":null,"abstract":"Optical analog computing can potentially feature high-throughput parallel processing with ultralow power and high speed and is promising for efficient signal processing. Previous platforms have mainly focused on scalar computing with optical intensities, which is highly sensitive to environmental disturbance and has been primarily restricted to single or basic computations because of intrinsic fixed correlation between the input and output signals. To our knowledge, for the first time, we use polarization vectors for optical analog computing with a single-layered metasurface to overcome these restrictions. The underlying mechanism is on-demand polarization transformation on the dispersive Poincaré spheres, constructing intrinsic variable correlations between the incident polarization vectors and output signals. We choose the universal logical gates and mathematical function operations as two specific examples. Experimental results of our vector computing metadevices exhibit minimal errors relative to the target values. Our work opens up an avenue for advanced optical signal processing across both classical and quantum domains.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Developmental alterations in brain network asymmetry in 3- to 9-month infants with congenital sensorineural hearing loss 先天性感音神经性听力损失3 ~ 9个月婴儿脑网络不对称的发育改变

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2025-10-15 DOI: 10.1126/sciadv.adx1327

Guangfang Liu, Xin Zhou, Zhenyan Hu, Yidi Liu, Endi Huo, Heather Bortfeld, Qi Dong, Chunhui Chen, Haihong Liu, Haijing Niu

{"title":"Developmental alterations in brain network asymmetry in 3- to 9-month infants with congenital sensorineural hearing loss","authors":"Guangfang Liu, Xin Zhou, Zhenyan Hu, Yidi Liu, Endi Huo, Heather Bortfeld, Qi Dong, Chunhui Chen, Haihong Liu, Haijing Niu","doi":"10.1126/sciadv.adx1327","DOIUrl":"https://doi.org/10.1126/sciadv.adx1327","url":null,"abstract":"Auditory exposure plays a crucial role in shaping brain development, but little is known about whether and how an initial lack of auditory exposure might disrupt the development of functional network lateralization. We addressed this issue by acquiring functional near-infrared spectroscopy data from infants aged 3 to 9 months with congenital sensorineural hearing loss (SNHL). The SNHL infants showed efficient small-world characteristics within each hemisphere. However, unlike typically developing controls, who showed an age-related leftward lateralization of network efficiencies, SNHL infants did not exhibit the emergence of hemispheric asymmetry. Intriguingly, lateralization of frontal efficiency was preserved in SNHL infants with mild hearing loss but declined significantly with increasing severity of hearing impairment. These findings suggest that even SNHL infants with some residual hearing experience disruption in the development of functional lateralization. This underscores the importance of providing early auditory access to SNHL infants to support robust functional integration during early development.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"27 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rupture of solidified ancient magma that impeded preceding swarm migrations led to the 2024 Noto earthquake 凝固的古岩浆破裂阻碍了之前的蜂群迁移，导致了2024年诺托地震

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2025-10-15 DOI: 10.1126/sciadv.adv5938

Ryota Takagi, Keisuke Yoshida, Tomomi Okada

引用次数: 0

Bubble-driven cell detachment 气泡驱动细胞脱离

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2025-10-15 DOI: 10.1126/sciadv.adu3708

Bert Vandereydt, Baptiste Blanc, Kripa K. Varanasi

引用次数: 0

Tracing stratospheric transport using subannual plutonium-239 fallout in polar ice cores 利用极地冰芯中的次年钚-239沉降物追踪平流层运输