Kaichun Yang, Ruoyu Zhong, Ke Li, John Mai, Pengzhan Liu, Ye He, Joseph Rich, Ying Chen, Janna Wang, Zhiteng Ma, Xianchen Xu, Qian Wu, Tony Jun Huang
Mechanomodulation, the process of altering cellular behavior through applied mechanical forces, plays a critical role in physiological processes and has substantial implications for cancer therapy, immunology, and drug development. However, precise and efficient stimulation of nonadherent cells remains a major challenge, limiting the investigation of mechanotransduction pathways and the development of targeted therapeutics. Here, we developed an acoustofluidic platform named Suspension-cell Targeted Response to Excitation via Acoustofluidic Mechanomodulation (STREAM) to enable precise, high-throughput stimulation of suspension cells. STREAM accomplishes this using 101.14-megahertz high-frequency surface acoustic waves to deliver controlled mechanical stimulation at a throughput of 500,000 cells per minute. STREAM modulates intracellular calcium ion (Ca2+) signaling by activating mechanosensitive ion channels, triggering mitochondrial membrane disruption and tunable K562 leukemia cell apoptosis rates from 5.15 to 47.1%. STREAM provides a scalable, precise tool for studying mechanotransduction in suspension cells, with broad applications in cancer research, immunotherapy, and high-throughput drug screening.
{"title":"Precision acoustofluidics for high-throughput mechanobiology in suspension cells","authors":"Kaichun Yang, Ruoyu Zhong, Ke Li, John Mai, Pengzhan Liu, Ye He, Joseph Rich, Ying Chen, Janna Wang, Zhiteng Ma, Xianchen Xu, Qian Wu, Tony Jun Huang","doi":"10.1126/sciadv.ady1136","DOIUrl":"10.1126/sciadv.ady1136","url":null,"abstract":"<div >Mechanomodulation, the process of altering cellular behavior through applied mechanical forces, plays a critical role in physiological processes and has substantial implications for cancer therapy, immunology, and drug development. However, precise and efficient stimulation of nonadherent cells remains a major challenge, limiting the investigation of mechanotransduction pathways and the development of targeted therapeutics. Here, we developed an acoustofluidic platform named Suspension-cell Targeted Response to Excitation via Acoustofluidic Mechanomodulation (STREAM) to enable precise, high-throughput stimulation of suspension cells. STREAM accomplishes this using 101.14-megahertz high-frequency surface acoustic waves to deliver controlled mechanical stimulation at a throughput of 500,000 cells per minute. STREAM modulates intracellular calcium ion (Ca<sup>2+</sup>) signaling by activating mechanosensitive ion channels, triggering mitochondrial membrane disruption and tunable K562 leukemia cell apoptosis rates from 5.15 to 47.1%. STREAM provides a scalable, precise tool for studying mechanotransduction in suspension cells, with broad applications in cancer research, immunotherapy, and high-throughput drug screening.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888036","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}
Activating the stimulator of interferon genes (STING) pathway in conventional type I dendritic cells (cDC1s) is crucial for inhibiting solid tumor metastasis. A major hurdle is the cell type–specific delivery of immune agonists. To overcome this, we created a DNA-scaffolded poly(lactic-co-glycolic acid) nanoparticle platform for precisely loading antibodies targeting cDC1 receptors, specifically DEC205 and Clec9A. Optimizing these targeting ligands revealed a 1:1 ratio as ideal for preferentially targeting splenic cDC1s in vivo. When the STING agonist MSA-2 was delivered via this platform, termed programmable and ratiometrically-engineered immunomodulatory nanoparticle (PRIME NP), its immunostimulatory activity significantly increased. In CT26 tumor–bearing mice, PRIME NP treatment triggered robust proinflammatory signaling and activated both innate and adaptive immune responses, leading to potent CD8+ T cell–driven tumor regression and long-term survival in preclinical models. This work provides a framework for designing actively targeted particles and emphasizes DNA-scaffolded nanoparticles as an effective strategy to enhance the STING-cDC1 pathway for solid tumor treatment.
{"title":"Dual-receptor targeting of type I dendritic cells with DNA-scaffolded nanoparticles enhances STING-licensed antitumor immunity","authors":"Deblin Jana, Emilia Herdes, Justin Moustouka, Kayla M. Mash, Jingge Chen, Kareem Ebeid, Marwa Sallam, Akram Abbasi, Tejal Desai","doi":"10.1126/sciadv.aeb0452","DOIUrl":"10.1126/sciadv.aeb0452","url":null,"abstract":"<div >Activating the stimulator of interferon genes (STING) pathway in conventional type I dendritic cells (cDC1s) is crucial for inhibiting solid tumor metastasis. A major hurdle is the cell type–specific delivery of immune agonists. To overcome this, we created a DNA-scaffolded poly(lactic-<i>co</i>-glycolic acid) nanoparticle platform for precisely loading antibodies targeting cDC1 receptors, specifically DEC205 and Clec9A. Optimizing these targeting ligands revealed a 1:1 ratio as ideal for preferentially targeting splenic cDC1s in vivo. When the STING agonist MSA-2 was delivered via this platform, termed programmable and ratiometrically-engineered immunomodulatory nanoparticle (PRIME NP), its immunostimulatory activity significantly increased. In CT26 tumor–bearing mice, PRIME NP treatment triggered robust proinflammatory signaling and activated both innate and adaptive immune responses, leading to potent CD8<sup>+</sup> T cell–driven tumor regression and long-term survival in preclinical models. This work provides a framework for designing actively targeted particles and emphasizes DNA-scaffolded nanoparticles as an effective strategy to enhance the STING-cDC1 pathway for solid tumor treatment.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888014","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}
Bo Wang, Lei Li, Mengfan Xu, Nannan Hu, Wenzhuo Gao, Jie Zhang, Bo Yin, Zhanhua Xin, Junzhi Yu
Fish swim with four main gaits—anguilliform, subcarangiform, carangiform, and thunniform—produced by waves along varying portions of the body. However, how muscle activation length influences swimming performance remains poorly understood. We present a reconfigurable robotic fish that replicates all four gaits in a single platform by rapidly tuning its body stiffness. Vacuum-driven layer jamming muscles in four tensegrity joints enable quick (≤1 s) stiffness modulation (stiffness ratio of 46.6) and gait switching. In thunniform gait, the robot reaches 1.24 body lengths per second, whereas in anguilliform gait, it achieves agile maneuvering with a turning radius of 0.26 body lengths. Fluid simulations show that the thunniform gait generates stronger vortices and 142% more thrust compared with anguilliform motion at 5 Hz, explaining its high-speed performance. The robot dynamically adapts gaits during locomotion—using thunniform for fast traversal and anguilliform for obstacle negotiation—demonstrating environmental adaptability. This work advances understanding of aquatic multimodal locomotion.
{"title":"Adaptive multimodal swimming gaits in a reconfigurable modular soft robotic fish","authors":"Bo Wang, Lei Li, Mengfan Xu, Nannan Hu, Wenzhuo Gao, Jie Zhang, Bo Yin, Zhanhua Xin, Junzhi Yu","doi":"10.1126/sciadv.aea1299","DOIUrl":"10.1126/sciadv.aea1299","url":null,"abstract":"<div >Fish swim with four main gaits—anguilliform, subcarangiform, carangiform, and thunniform—produced by waves along varying portions of the body. However, how muscle activation length influences swimming performance remains poorly understood. We present a reconfigurable robotic fish that replicates all four gaits in a single platform by rapidly tuning its body stiffness. Vacuum-driven layer jamming muscles in four tensegrity joints enable quick (≤1 s) stiffness modulation (stiffness ratio of 46.6) and gait switching. In thunniform gait, the robot reaches 1.24 body lengths per second, whereas in anguilliform gait, it achieves agile maneuvering with a turning radius of 0.26 body lengths. Fluid simulations show that the thunniform gait generates stronger vortices and 142% more thrust compared with anguilliform motion at 5 Hz, explaining its high-speed performance. The robot dynamically adapts gaits during locomotion—using thunniform for fast traversal and anguilliform for obstacle negotiation—demonstrating environmental adaptability. This work advances understanding of aquatic multimodal locomotion.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888021","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}
Inhalation therapy shows great potential for treating idiopathic pulmonary fibrosis (IPF), but airway mucus imposes strong adhesive and steric barriers to drug delivery. Compared with other types of micelles, our results demonstrated that amphiphilic micelles formed by DSPE-PCB [carboxybetaine polymer conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DB)] exhibited superior physicochemical properties for mucus penetration. Furthermore, we found that incorporating a conformationally adaptive azobenzene (Azo) intermediate into DB further enhanced this effect by modulating mechanical properties of micelle. By tuning DB/DAB ratios during self-assembly, we generated a micelle library with adjustable deformability (1- to 40-fold). The enhanced mucus penetration ability led to a nearly fourfold reduction in the retention time of DSPE-Azo-PCB (DAB) micelles in respiratory mucus, significantly increasing drug accumulation in lung tissue and reducing irritation to the respiratory tract. This study integrates both the physicochemical and mechanical properties of micelles to optimize mucus penetration, offering previously unidentified strategies for the development of inhalation formulations.
{"title":"A softness zwitterionic micelles efficiently deliver inhaled nintedanib by enhancing airway mucus penetration","authors":"Binghua Wang, Peibo Fan, Fanqi Guo, Zhihui Song, Zhenzhong Zhang, Xiang Lu, Jinjin Shi","doi":"10.1126/sciadv.ady1030","DOIUrl":"10.1126/sciadv.ady1030","url":null,"abstract":"<div >Inhalation therapy shows great potential for treating idiopathic pulmonary fibrosis (IPF), but airway mucus imposes strong adhesive and steric barriers to drug delivery. Compared with other types of micelles, our results demonstrated that amphiphilic micelles formed by DSPE-PCB [carboxybetaine polymer conjugated to 1,2-distearoyl-<i>sn</i>-glycero-3-phosphoethanolamine (DB)] exhibited superior physicochemical properties for mucus penetration. Furthermore, we found that incorporating a conformationally adaptive azobenzene (Azo) intermediate into DB further enhanced this effect by modulating mechanical properties of micelle. By tuning DB/DAB ratios during self-assembly, we generated a micelle library with adjustable deformability (1- to 40-fold). The enhanced mucus penetration ability led to a nearly fourfold reduction in the retention time of DSPE-Azo-PCB (DAB) micelles in respiratory mucus, significantly increasing drug accumulation in lung tissue and reducing irritation to the respiratory tract. This study integrates both the physicochemical and mechanical properties of micelles to optimize mucus penetration, offering previously unidentified strategies for the development of inhalation formulations.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888038","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}
Milena Stolz, Lukas Sušac, Amin Fahim, Rieke Keller, Lisa Saggau, Filippo Mancia, Simon Trowitzsch, Robert Tampé
Adaptive immunity depends on major histocompatibility complex class I (MHC I) presentation of peptides, a process orchestrated by the peptide-loading complex (PLC) in the endoplasmic reticulum (ER). The PLC ensures precise peptide selection and loading and is a major target of viral immune evasion, notably by human cytomegalovirus (HCMV). Here, we report the 2.59- to 2.88-Å cryo–electron microscopy structure of native human PLC bound to the HCMV immune evasin US6. US6 inhibits the transporter associated with antigen processing 1/2 (TAP1/2) by laterally attaching its transmembrane helix to TAP2 using a disulfide-rich domain to mimic a translocating peptide. This domain blocks the ER-lumenal exit and locks TAP in an outward-facing conformation with closed nucleotide-binding domains and asymmetric adenosine 5′-triphosphate/adenosine 5′-diphosphate occlusion. The structure also reveals how TAP’s amino-terminal transmembrane domains scaffold the MHC I chaperone tapasin. These findings elucidate the mechanism of US6-mediated immune evasion and highlight potential targets for therapeutic modulation of immune presentation in infection and cancer.
{"title":"Architectural principles of transporter-chaperone coupling within the native MHC I peptide-loading complex","authors":"Milena Stolz, Lukas Sušac, Amin Fahim, Rieke Keller, Lisa Saggau, Filippo Mancia, Simon Trowitzsch, Robert Tampé","doi":"10.1126/sciadv.aea7735","DOIUrl":"10.1126/sciadv.aea7735","url":null,"abstract":"<div >Adaptive immunity depends on major histocompatibility complex class I (MHC I) presentation of peptides, a process orchestrated by the peptide-loading complex (PLC) in the endoplasmic reticulum (ER). The PLC ensures precise peptide selection and loading and is a major target of viral immune evasion, notably by human cytomegalovirus (HCMV). Here, we report the 2.59- to 2.88-Å cryo–electron microscopy structure of native human PLC bound to the HCMV immune evasin US6. US6 inhibits the transporter associated with antigen processing 1/2 (TAP1/2) by laterally attaching its transmembrane helix to TAP2 using a disulfide-rich domain to mimic a translocating peptide. This domain blocks the ER-lumenal exit and locks TAP in an outward-facing conformation with closed nucleotide-binding domains and asymmetric adenosine 5′-triphosphate/adenosine 5′-diphosphate occlusion. The structure also reveals how TAP’s amino-terminal transmembrane domains scaffold the MHC I chaperone tapasin. These findings elucidate the mechanism of US6-mediated immune evasion and highlight potential targets for therapeutic modulation of immune presentation in infection and cancer.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888002","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}
Jonathan I. Kim, Zachary Ellsworth, Erin L. Dunnington, Brian S. Wong, Nidhi R. Mehta, Chisa Zensho, Dan Fu
Super-resolution fluorescence microscopy has transformed biological imaging beyond the diffraction limit. However, many biomolecules, nanostructures, drug molecules, and metabolites cannot be easily tagged, requiring a label-free imaging approach. Stimulated Raman scattering (SRS) microscopy is a powerful platform for super-resolution label-free imaging, yet current super-resolution SRS approaches rely on photoswitching, saturation, or sample expansion, which are limited by labeling, photodamage, or signal dilution, respectively. Here, we combine SRS with 4Pi interferometry to enhance axial resolution nearly sevenfold. We report on improvements in imaging sensitivity and axial resolution using 80-nanometer polystyrene beads. Harnessing the improved axial resolution, we demonstrate super-resolution 4Pi-SRS imaging in resolving small lipid droplet structures in mammalian cells and lipid membranes in Escherichia coli cells. Because 4Pi-SRS uses interferometry to improve axial resolution, it is orthogonal to all previous super-resolution SRS techniques; thus, it is straightforward to integrate it with existing methods to achieve much higher resolution chemical imaging than previously possible.
{"title":"4Pi stimulated Raman scattering for label-free super-resolution chemical imaging","authors":"Jonathan I. Kim, Zachary Ellsworth, Erin L. Dunnington, Brian S. Wong, Nidhi R. Mehta, Chisa Zensho, Dan Fu","doi":"10.1126/sciadv.aec0523","DOIUrl":"10.1126/sciadv.aec0523","url":null,"abstract":"<div >Super-resolution fluorescence microscopy has transformed biological imaging beyond the diffraction limit. However, many biomolecules, nanostructures, drug molecules, and metabolites cannot be easily tagged, requiring a label-free imaging approach. Stimulated Raman scattering (SRS) microscopy is a powerful platform for super-resolution label-free imaging, yet current super-resolution SRS approaches rely on photoswitching, saturation, or sample expansion, which are limited by labeling, photodamage, or signal dilution, respectively. Here, we combine SRS with 4Pi interferometry to enhance axial resolution nearly sevenfold. We report on improvements in imaging sensitivity and axial resolution using 80-nanometer polystyrene beads. Harnessing the improved axial resolution, we demonstrate super-resolution 4Pi-SRS imaging in resolving small lipid droplet structures in mammalian cells and lipid membranes in <i>Escherichia coli</i> cells. Because 4Pi-SRS uses interferometry to improve axial resolution, it is orthogonal to all previous super-resolution SRS techniques; thus, it is straightforward to integrate it with existing methods to achieve much higher resolution chemical imaging than previously possible.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888005","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}
Cross-electrophile coupling (XEC) has emerged as a powerful strategy for constructing carbon─carbon bonds. Here, we report the first transition-metal-free electrochemical XEC between readily available benzyl alcohol derivatives and primary alkyl bromides, enabling the efficient construction of C(sp3)─C(sp3) bonds to access valuable benzylic quaternary and tertiary carbon centers. This method expands the reaction profiles of both benzyl alcohols and electrochemistry. A key to unlocking this transformation is the identification of 4-tert-butylbenzoyl (TBBz) as an effective activating group for benzyl alcohols. This modular protocol features broad substrate scope, compatibility with CO2 and chlorosilanes as coupling partners, and is amenable to gram-scale synthesis. The synthetic utility of this method is exemplified by the simplified synthesis of high-value commercial building blocks and advanced intermediates for bioactive compounds, as well as the facile access to bioisosteric analogs of drug molecules.
{"title":"Transition-metal-free electrochemical cross-electrophile coupling of activated benzyl alcohols and primary alkyl bromides","authors":"Guang Chen, Changhao Huang, Like Luo, Dayu Tian, Xiaocheng Wang, Hai-Jun Zhang","doi":"10.1126/sciadv.aeb3720","DOIUrl":"10.1126/sciadv.aeb3720","url":null,"abstract":"<div >Cross-electrophile coupling (XEC) has emerged as a powerful strategy for constructing carbon─carbon bonds. Here, we report the first transition-metal-free electrochemical XEC between readily available benzyl alcohol derivatives and primary alkyl bromides, enabling the efficient construction of C(sp<sup>3</sup>)─C(sp<sup>3</sup>) bonds to access valuable benzylic quaternary and tertiary carbon centers. This method expands the reaction profiles of both benzyl alcohols and electrochemistry. A key to unlocking this transformation is the identification of 4-<i>tert</i>-butylbenzoyl (TBBz) as an effective activating group for benzyl alcohols. This modular protocol features broad substrate scope, compatibility with CO<sub>2</sub> and chlorosilanes as coupling partners, and is amenable to gram-scale synthesis. The synthetic utility of this method is exemplified by the simplified synthesis of high-value commercial building blocks and advanced intermediates for bioactive compounds, as well as the facile access to bioisosteric analogs of drug molecules.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888009","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}
Vortex beams carrying orbital angular momentum (OAM) have attracted growing attention across fields, including optics and acoustics, for potential applications in particle manipulation and high-speed communication. Intracavity generation of OAM beams, such as OAM lasers, efficiently produces high-power, high–beam-quality vortices. This scheme, however, remains rarely explored in acoustics. Here, we propose and demonstrate an acoustic intracavity OAM generation mechanism with tunable topological charges via a single nonreciprocal nonlinear boundary in a compact resonator ring. In the linear regime, the boundary creates non-Hermitian complex effective magnetic fields piercing the ring, leading to a non-Hermitian Zeeman-like effect that splits clockwise and counterclockwise eigenmodes. Upon incorporation of nonlinearity to the boundary, all resonators are mutually locked, producing a single-mode self-oscillatory OAM radiation exhibiting hysteresis and bistability. Moreover, the topological charge is tunable by manipulating the boundary. Our work reveals intriguing physics related to nonlinear, non-Hermitian boundaries and offers potentials in the next generation of acoustic self-oscillatory OAM sources, switchers, and memory devices.
{"title":"Hysteretic self-oscillatory acoustic radiation with tunable orbital angular momentum","authors":"Li Zhang, Hong-yu Zou, Yong Ge, Wenwen Liu, Hong-xiang Sun, Fujia Chen, Qiaolu Chen, Yuang Pan, Mingyu Tong, Yuze Hu, Ning Han, Bei Wu, Junyao Wu, Qingdong Yang, Shou-qi Yuan, Hongsheng Chen, Yihao Yang, Shuang Zhang","doi":"10.1126/sciadv.ady5416","DOIUrl":"10.1126/sciadv.ady5416","url":null,"abstract":"<div >Vortex beams carrying orbital angular momentum (OAM) have attracted growing attention across fields, including optics and acoustics, for potential applications in particle manipulation and high-speed communication. Intracavity generation of OAM beams, such as OAM lasers, efficiently produces high-power, high–beam-quality vortices. This scheme, however, remains rarely explored in acoustics. Here, we propose and demonstrate an acoustic intracavity OAM generation mechanism with tunable topological charges via a single nonreciprocal nonlinear boundary in a compact resonator ring. In the linear regime, the boundary creates non-Hermitian complex effective magnetic fields piercing the ring, leading to a non-Hermitian Zeeman-like effect that splits clockwise and counterclockwise eigenmodes. Upon incorporation of nonlinearity to the boundary, all resonators are mutually locked, producing a single-mode self-oscillatory OAM radiation exhibiting hysteresis and bistability. Moreover, the topological charge is tunable by manipulating the boundary. Our work reveals intriguing physics related to nonlinear, non-Hermitian boundaries and offers potentials in the next generation of acoustic self-oscillatory OAM sources, switchers, and memory devices.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888043","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}
Disordered microstructures are key to the distinct multifunctional properties of many natural materials. However, understanding the relationship between their microstructures and physical functions remains formidable, hindering engineering applications. Here, we introduce a physics-guided, self-supervised artificial intelligence (AI) framework called generative networks for disordered metamaterials (GNDM), trained on a progressively expanding dataset starting from a few initial samples. We integrate a formula writing module in the training process of neural networks to enforce the identification of the most selective set of hidden geometric invariants that dictate bulk properties. By inversely solving the formulae, GNDM manipulate disordered geometric features to extrapolate property space and design previously unknown structures via its generator module, validated by experiments. GNDM offers an all-in-one AI framework that closes the loop of feature extraction, property prediction, formula writing, and inverse design, unraveling the regulative role of disorder, a critical challenge in the study of metamaterials with complex microstructures.
{"title":"Self-supervised AI for decoding and designing disordered metamaterials","authors":"Min Shen, Ke Liu, Sheng Mao, Chiara Daraio","doi":"10.1126/sciadv.adx7389","DOIUrl":"10.1126/sciadv.adx7389","url":null,"abstract":"<div >Disordered microstructures are key to the distinct multifunctional properties of many natural materials. However, understanding the relationship between their microstructures and physical functions remains formidable, hindering engineering applications. Here, we introduce a physics-guided, self-supervised artificial intelligence (AI) framework called generative networks for disordered metamaterials (GNDM), trained on a progressively expanding dataset starting from a few initial samples. We integrate a formula writing module in the training process of neural networks to enforce the identification of the most selective set of hidden geometric invariants that dictate bulk properties. By inversely solving the formulae, GNDM manipulate disordered geometric features to extrapolate property space and design previously unknown structures via its generator module, validated by experiments. GNDM offers an all-in-one AI framework that closes the loop of feature extraction, property prediction, formula writing, and inverse design, unraveling the regulative role of disorder, a critical challenge in the study of metamaterials with complex microstructures.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888018","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}
Yu-Ying Chen, Karina Rodriguez, Adriana K. Alexander, Xin Xu, Brian Papas, Martin A. Estermann, Humphrey Hung-Chang Yao
Sex determination of mammalian gonads hinges upon sex-specific differentiation of gonadal supporting cells: Sertoli cells in the testis and granulosa cells in the ovary. To gain insights into how supporting cells acquire their identities, we performed joint single-nucleus transcriptomics and chromatin accessibility assays on murine gonadal cells during sex determination. By contrasting sex-specific gene expression and corresponding chromatin accessibility among progenitor and differentiated cells, we found that sex-specific chromatin regions in supporting cells are established shortly after sex determination, accompanied by the acquisition of active histone marks. The presence of potential transcription factor–binding motifs in the open chromatin regions revealed regulatory networks underlying ovary-enriched factors LEF1 and MSX1, which promote granulosa fate by inducing granulosa-specific genes such as Foxl2 and Fst. Our results not only identify the gene regulatory framework underlying supporting cell sex differentiation but also provide invaluable resources for the field.
{"title":"Single-nucleus multiomics of murine gonads reveals transcriptional regulatory network underlying supporting lineage differentiation","authors":"Yu-Ying Chen, Karina Rodriguez, Adriana K. Alexander, Xin Xu, Brian Papas, Martin A. Estermann, Humphrey Hung-Chang Yao","doi":"10.1126/sciadv.aea7403","DOIUrl":"10.1126/sciadv.aea7403","url":null,"abstract":"<div >Sex determination of mammalian gonads hinges upon sex-specific differentiation of gonadal supporting cells: Sertoli cells in the testis and granulosa cells in the ovary. To gain insights into how supporting cells acquire their identities, we performed joint single-nucleus transcriptomics and chromatin accessibility assays on murine gonadal cells during sex determination. By contrasting sex-specific gene expression and corresponding chromatin accessibility among progenitor and differentiated cells, we found that sex-specific chromatin regions in supporting cells are established shortly after sex determination, accompanied by the acquisition of active histone marks. The presence of potential transcription factor–binding motifs in the open chromatin regions revealed regulatory networks underlying ovary-enriched factors LEF1 and MSX1, which promote granulosa fate by inducing granulosa-specific genes such as <i>Foxl2</i> and <i>Fst</i>. Our results not only identify the gene regulatory framework underlying supporting cell sex differentiation but also provide invaluable resources for the field.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145887981","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}
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