Science AdvancesPub Date : 2025-04-23DOI: 10.1126/sciadv.ado6847
Emanuel J. Novais, Olivia K. Ottone, Eric V. Brown, Vedavathi Madhu, Victoria A. Tran, Pranay Ramteke, Abhijit S. Dighe, Michael D. Solga, Alexandra Manchel, Angelo C. Lepore, Makarand V. Risbud
{"title":"Genetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice","authors":"Emanuel J. Novais, Olivia K. Ottone, Eric V. Brown, Vedavathi Madhu, Victoria A. Tran, Pranay Ramteke, Abhijit S. Dighe, Michael D. Solga, Alexandra Manchel, Angelo C. Lepore, Makarand V. Risbud","doi":"10.1126/sciadv.ado6847","DOIUrl":"10.1126/sciadv.ado6847","url":null,"abstract":"<div >There are no appropriate mouse models to study the pathophysiology of spontaneous disc herniations in a wild-type setting. SM/J mice, a poor healer inbred strain, presented a high incidence of age-associated lumbar disc herniations with neurovascular innervations. Transcriptomic comparisons of the SM/J annulus fibrosus with human tissues showed shared pathways related to immune cell activation and inflammation. Notably, aged SM/J mice showed increased pain sensitization and neuroinflammation with altered extracellular matrix regulation in the dorsal root ganglia and spinal cord. There were increased T cells in the vertebral marrow, and cytometry by time-of-flight analysis showed increased splenic CD8+ T cells, nonspecific activation of CD8+ memory T cells, and enhanced interferon-γ production in the myeloid compartment. Single-cell RNA sequencing of peripheral blood mononuclear cells showed more B cells, with lower proportions of T cells, monocytes, and granulocytes. This study highlights the contribution of genetic background and aging to increased susceptibility of spontaneous intervertebral disc herniations in a clinically relevant murine model.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado6847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866092","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 : 2025-04-23DOI: 10.1126/sciadv.adp7075
Jonathan Oesterle, Yanli Ran, Paul Stahr, Jason N. D. Kerr, Timm Schubert, Philipp Berens, Thomas Euler
{"title":"Task-specific regional circuit adaptations in distinct mouse retinal ganglion cells","authors":"Jonathan Oesterle, Yanli Ran, Paul Stahr, Jason N. D. Kerr, Timm Schubert, Philipp Berens, Thomas Euler","doi":"10.1126/sciadv.adp7075","DOIUrl":"10.1126/sciadv.adp7075","url":null,"abstract":"<div >In the mouse retina, sustained ON alpha (sONα) retinal ganglion cells (RGCs) have different dendritic and receptive field sizes along the nasotemporal axis, with temporal sONα RGCs likely playing a role in visually guided hunting. Thus, we hypothesized that this cell type also exhibits regional adaptations in dendritic signal processing and that these adaptations are advantageous for prey capture. Here, we measured dendritic signals from individual sONα RGCs at different retinal locations. We measured both postsynaptic Ca<sup>2+</sup> signals at dendrites and presynaptic glutamate signals from bipolar cells (BCs). We found that temporal sONα RGCs exhibit, in addition to sustained-ON signals with only weak surrounds, signals with strong surround suppression, which were not present in nasal sONα RGCs. This difference was also present in the presynaptic inputs from BCs. Last, using population models in an encoder-decoder paradigm, we showed that these adaptations might be beneficial for detecting crickets in hunting behavior.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp7075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866062","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 : 2025-04-23DOI: 10.1126/sciadv.ads9481
Yang Li, Li-Guang Wu, Yan Yu, Lan Yang, David Selby, Xian-Hua Li
{"title":"Paleozoic carbonatites controlled rare-earth-elements mineralization at Bayan Obo","authors":"Yang Li, Li-Guang Wu, Yan Yu, Lan Yang, David Selby, Xian-Hua Li","doi":"10.1126/sciadv.ads9481","DOIUrl":"10.1126/sciadv.ads9481","url":null,"abstract":"<div >The net-zero emission race drives the consumption of rare-earth-elements (REE) at an accelerated rate. With the demand of REE being met by a few giant deposits such as Bayan Obo, decoding controls of ore formation is vital. Yet, after nearly a century of study, the genesis of Bayan Obo remains debated. Here, we demonstrate that two stages of carbonatites emplaced at Bayan Obo at 1320 and 430 million years ago (Ma). The effusive nature of the 1320 Ma carbonatite suppressed brine/fluid exsolution; hence, mineralization at this stage is limited, but its subsequent deformation created an ideal environment for water-rock interaction induced mineralization. The 430 Ma carbonatites exsolved voluminous brine/alkaline fluids rich in REE, with mineralization being promoted as veins and along beddings of the deformed Mesoproterozoic carbonatites via metasomatism. This stage contributed >70% REE. Our study highlights that multistage carbonatites emplaced at one locality could be a controlling factor for REE mineralization and explains the scarcity of giant deposits.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads9481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866063","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 : 2025-04-23DOI: 10.1126/sciadv.adn5409
Varun Arvind, Giulia Crosio, Kristen Howell, Hui Zhang, Angela Montero, Alice H. Huang
{"title":"Functional tendon regeneration is driven by regulatory T cells and IL-33 signaling","authors":"Varun Arvind, Giulia Crosio, Kristen Howell, Hui Zhang, Angela Montero, Alice H. Huang","doi":"10.1126/sciadv.adn5409","DOIUrl":"10.1126/sciadv.adn5409","url":null,"abstract":"<div >Tendon injuries heal by scar, leading to poor function. To date, the role of immune cells remains underexplored. Using a neonatal mouse model of functional tendon healing compared to adult scar–mediated healing, we identified a regenerative immune profile that is associated with type 1 inflammation followed by rapid polarization to type 2, driven by macrophages and regulatory T cells (T<sub>reg</sub> cells). Single-cell and bulk RNA sequencing also revealed neonatal T<sub>reg</sub> cells with an immunomodulatory signature distinct from adult. Neonatal T<sub>reg</sub> cell ablation resulted in a dysregulated immune response, failed tenocyte recruitment, and impaired regeneration. Adoptive transfer further confirmed the unique capacity of neonatal T<sub>reg</sub> cells to rescue functional regeneration. We showed that neonatal T<sub>reg</sub> cells mitigate interleukin-33 (IL-33) to enable tenocyte recruitment and structural restoration, and that adult IL-33 deletion improves functional healing. Collectively, these findings demonstrate that T<sub>reg</sub> cells and IL-33 immune dysfunction are critical components of failed tendon healing and identify potential targets to drive tendon regeneration.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adn5409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866074","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":"Neural representations of noncentral events during narrative encoding predict subsequent story ending originality","authors":"Xueyang Wang, Wei Liu, Kaixiang Zhuang, Cheng Liu, Jingyi Zhang, Li Fan, Qunlin Chen, Jiang Qiu","doi":"10.1126/sciadv.adu5251","DOIUrl":"10.1126/sciadv.adu5251","url":null,"abstract":"<div >On the basis of the confluence theories of creativity, creative ideation depends on forging links between existing memory traces. The synergy between memory and creative thought is well-established, but neural dynamics of memory integration for creativity are understudied. Here, we extended the traditional memory paradigm. Participants read, recalled narratives, and wrote endings. Computational linguistic analysis showed that those integrating more noncentral events—those less semantically connected to other events within the narrative—wrote more original endings. Analyzing fMRI data captured during narrative encoding, we discovered that story ending originality can be predicted by shared event representation across participants in the right Brodmann area 25 (BA25) and stronger hippocampal event segmentation signal during noncentral event encoding. These results held across different narrative types (i.e., crime, romance, and fantasy stories). Overall, these results offer notable insights, from the perspective of network structure into how humans encode and retrieve complex real-world experiences to enhance creativity.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu5251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866079","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 : 2025-04-23DOI: 10.1126/sciadv.adv2052
Rui Wu, Luca Girardi, Stefano Mintchev
{"title":"Encoding mechanical intelligence using ultraprogrammable joints","authors":"Rui Wu, Luca Girardi, Stefano Mintchev","doi":"10.1126/sciadv.adv2052","DOIUrl":"10.1126/sciadv.adv2052","url":null,"abstract":"<div >Animal bodies act as physical controllers, with their finely tuned passive mechanical responses physically “encoding” complex movements and environmental interactions. This capability allows animals to perform challenging tasks with minimal muscular or neural activities, a phenomenon known as embodied intelligence. However, realizing such robots remains challenging due to the lack of mechanically intelligent bodies with abundant tunable parameters—such as tunable stiffness—which is a critical factor akin to the programmable parameters of a neural network. We introduce an elastic rolling cam (ERC) with accurately inverse-designable rotational stiffness. The ERC can closely replicate 100,000 randomly generated stiffness profiles in simulation. Prototypes ranging from millimeters to centimeters were manufactured. To illustrate the mechanical intelligence encoded by programming the ERC’s stiffness response, we designed a bipedal robot with optimized ERC passive knees, achieving energy-efficient, open-loop stable walking across uneven terrain. We also demonstrated a quadcopter drone with ERC joints encoding an impact-activated, dual-state morphing.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv2052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866083","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":"Biomimetic rigid-soft finger design for highly dexterous and adaptive robotic hands","authors":"Ningbin Zhang, Peiwei Zhou, Xinyu Yang, Fengjie Shen, Jieji Ren, Tengyu Hou, Le Dong, Rong Bian, Dong Wang, Guoying Gu, Xiangyang Zhu","doi":"10.1126/sciadv.adu2018","DOIUrl":"10.1126/sciadv.adu2018","url":null,"abstract":"<div >In dexterous robotic hand design, achieving high mobility and adaptability comparable to human hands remains an ongoing challenge. Biomimetic designs mimicking the musculoskeletal structure have shown promise yet face difficulties in preserving key kinematic and mechanical principles while reducing system complexity. Here, we present a biomimetic finger design that preserves these principles through coordinated rigid-soft interplay, achieving structural and control simplicity for constructing dexterous robotic hands. Our design distills complex anatomical structures into skeletal mechanisms with regular geometrics, strategically deployed soft ligaments, and elastic tendon actuation, enabling controllable multi–degree-of-freedom dexterity while providing resilience and compliance. We establish mathematical models to analyze finger kinematics, rigid-soft interplay principles, and controllable actuation. Building on these models, we integrate biomimetic fingers with a thumb to develop an anthropomorphic robotic hand. Our robotic hand experimentally demonstrates remarkable dexterity and versatility across various tasks, including piano playing, power and pinch grasping, and in-hand manipulation, confirming the design effectiveness.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu2018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866059","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 : 2025-04-23DOI: 10.1126/sciadv.adt1736
Ning Wang, Ping Ding, Xingfang Ding, Yongqiang Zong, Weidong Sun
{"title":"Collapse of fragile Chinese Swamp Cypress forest","authors":"Ning Wang, Ping Ding, Xingfang Ding, Yongqiang Zong, Weidong Sun","doi":"10.1126/sciadv.adt1736","DOIUrl":"10.1126/sciadv.adt1736","url":null,"abstract":"<div >The tertiary relict species <i>Glyptostrobus pensilis</i>, formerly widespread in the Pearl River Delta, experienced a sudden decline and was on the brink of extinction in the late Holocene. The mechanism behind is still in debate. Here, using palynological records and principal components analysis, we show that <i>Glyptostrobus pensilis</i> is sensitive to anthropogenic disturbance. Elaborate <sup>14</sup>C results reveal that the forests ended around 2.1 thousand years before the present, with mild contemporaneous climate changes. The presence of burned marks on buried standing stumps suggests that the forests were destroyed by fire, consistent with fire attacks by the Han army during the conquest of the Nanyue Realm in 111 BCE. The swamp preserved the stumps underwater from the fire. Meanwhile, the increases in Poaceae and pioneer plants indicate a boost of human activity after the two conquests during 221 to 111 BCE, as supported by the increases in anthropogenic metal concentrations and population records.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt1736","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866070","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 : 2025-04-23DOI: 10.1126/sciadv.ads7876
Yao Yu, Xufen Yu, Bo Pan, Ho Man Chan, H. Ümit Kaniskan, Jian Jin, Ling Cai, Gang Greg Wang
{"title":"Pharmacologic degradation of WDR5 suppresses oncogenic activities of SS18::SSX and provides a therapeutic of synovial sarcoma","authors":"Yao Yu, Xufen Yu, Bo Pan, Ho Man Chan, H. Ümit Kaniskan, Jian Jin, Ling Cai, Gang Greg Wang","doi":"10.1126/sciadv.ads7876","DOIUrl":"10.1126/sciadv.ads7876","url":null,"abstract":"<div >Cancer-causing aberrations recurrently target the chromatic-regulatory factors, leading to epigenetic dysregulation. Almost all patients with synovial sarcoma (SS) carry a characteristic gene fusion, SS18::SSX, which produces a disease-specific oncoprotein that is incorporated into the switch/sucrose non-fermentable (SWI/SNF) chromatin-remodeling complexes and profoundly alters their functionalities. Targeting epigenetic dependency in cancers holds promise for improving current treatment. Leveraging on cancer cell dependency dataset, pharmacological tools, and genomic profiling, we find WDR5, a factor critical for depositing histone H3 lysine 4 (H3K4) methylation, to be an unexplored vulnerability in SS. Mechanistically, WDR5 and SS18::SSX interact and colocalize at oncogenes where WDR5 promotes H3K4 methylation and the chromatin association of SS18::SSX-containing chromatin-remodeling complexes. WDR5 degradation by proteolysis-targeting chimera (PROTAC) not only suppresses the SS18::SSX-related oncogenic programs but additionally causes the ribosomal protein deregulations leading to p53 activation. WDR5-targeted PROTAC suppresses SS growth in vitro and in vivo, providing a promising strategy for the SS treatment.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads7876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866086","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":"Giant switchable ferroelectric photovoltage in double-perovskite epitaxial films through chemical negative strain","authors":"Jie Tu, Hangren Li, Xudong Liu, Guoqiang Xi, Xiuqiao Liu, Mengqi Zhang, Rong Wu, Siyuan Du, Dongfei Lu, Longyuan Shi, Jing Xia, Yue-Wen Fang, Jiaqi Ding, Yuzhuo Liu, Yueyang Jia, Meng Yuan, Rui Yang, Xiaolong Li, Xiangmin Meng, Jianjun Tian, Linxing Zhang, Xianran Xing","doi":"10.1126/sciadv.ads4925","DOIUrl":"10.1126/sciadv.ads4925","url":null,"abstract":"<div >Double-perovskite films have been extensively studied in multifunctional fields due to their modifiability. Here, a controlled process strategy to induce chemical strain and anomalous Poisson deformation is proposed for perovskite-based films. The chemical negative strain in the local-ordering BiSmFe<sub>2</sub>O<sub>6</sub> double-perovskite films can be regulated by oxygen engineering to cause the effectively tunable bandgap. We markedly increased the switchable open-circuit voltage to ~1.56 V from ~0.50 V for Pt/BiSmFe<sub>2</sub>O<sub>6</sub>/Nb-SrTiO<sub>3</sub> devices, which is the highest in single-layer perovskite-based ferroelectric photovoltaic perpendicular devices under white light-emitting diode irradiation. The multifield composite action mechanism reveals the electrical cause of the large open-circuit voltage. The synergy of the optical fields and ferroelectric fields provides the possibility of multilevel storage. Structural characterizations indicate that the chemical strain offers a dual role of lattice distortion and vacancy migration. The strategy of controllable chemical strain facilitates further exploration of the application potential of ferroelectric materials for multifunctional electronic devices.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 17","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads4925","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866087","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}