Science Advances最新文献

{"title":"Reprogrammable curved-straight origami: Multimorphability and volumetric tunability","authors":"Morad Mirzajanzadeh,&nbsp;Damiano Pasini","doi":"10.1126/sciadv.adu4678","DOIUrl":"10.1126/sciadv.adu4678","url":null,"abstract":"<div >Existing origami patterns can transform flat sheets into curved surfaces or be stacked into volumetric lattices with tunable properties. Their folded surfaces, however, cannot morph into other rigid states, and their three-dimensional (3D) tessellations allow stiffness tuning only through large size variations, causing abrupt shifts in stiffness and affecting other properties such as relative density. These limitations hinder their use as reprogrammable structural materials in real-life applications. Here, we introduce a reprogrammable origami integrating curved and straight bistable creases to address both challenges: attaining rigidity while allowing reversible remorphability into numerous load-bearing shapes and generating 3D curved-plate lattices, delivering in a prescribed configuration of fixed dimensions continuously tunable elastic moduli spanning two orders of magnitude. Leveraging curved origami theories, differential geometry, paperboard models, and experiments, we construct the folded pattern, formulate its geometric mechanics, and quantify its mechanical performance. Our approach provides a versatile platform for multifunctional metamaterials, enabling adaptive and resilient materials in aerospace, biomechanics, and soft robotics.</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.adu4678","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866089","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":"Reducing racial ingroup biases in empathy and altruistic decision-making by shifting racial identification","authors":"Shuting Mei,&nbsp;Yiwen Deng,&nbsp;Guo Zheng,&nbsp;Shihui Han","doi":"10.1126/sciadv.adt6207","DOIUrl":"10.1126/sciadv.adt6207","url":null,"abstract":"<div >Findings of racial ingroup biases in empathy and social behaviors require understanding of relevant psychological and brain mechanisms. Using self-report, behavioral, and neuroimaging measures, we tested the hypothesis that racial identification provides a cognitive basis for racial ingroup biases in empathy and altruistic decision-making. We showed that a mask training procedure using other-race facial disguises altered self-face perception and promoted identification with the other race. Shift in racial identification modulated the medial prefrontal activity, increased electrophysiological responses to pain expressions of other-race faces, enhanced the right premotor/frontal/insular activities in response to perceived painful stimulation to other-race individuals, and decreased own-race favoritism in altruistic decision-making. Furthermore, the medial prefrontal activity related to the shift in racial identification predicted greater neural responses to other-race pain after the training procedure. Our findings highlight the shift of racial identification as a psychological basis for reducing racial ingroup biases in social emotions and behaviors.</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.adt6207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866064","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":"Multidimensional multiplexing metalens for STED microscopy","authors":"Ziheng Ji,&nbsp;Qinmiao Chen,&nbsp;Xinbo Sha,&nbsp;Haili Wang,&nbsp;Xing Ma,&nbsp;Zhengtong Liu,&nbsp;Qinghai Song,&nbsp;Shumin Xiao","doi":"10.1126/sciadv.adt2807","DOIUrl":"10.1126/sciadv.adt2807","url":null,"abstract":"<div >Stimulated emission depletion (STED) microscopy is a versatile super-resolution imaging technique for life sciences and data storage. Despite continuous breakthroughs, modern STED microscopes are still relatively bulky and limited to laboratory setups. Here, we exploit the multidimensional multiplexing properties of metalenses and experimentally demonstrate the realization of a compact STED lens with a single metasurface. A 635-nm right-handed circularly polarized excitation laser is focused by the metalens into a diffraction-limited Gaussian beam, while a 780-nm depletion beam with opposite chirality is converted into a high-quality donut-shaped focus on the same plane. As a consequence, STED super-resolution imaging based on the metalens has been obtained by recording the unpolarized photoluminescence using the same metalens. The experimentally demonstrated resolution reaches 0.7× of the diffraction limit and can be further improved. This study represents a critical step toward the miniaturization and integration of STED microscope.</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.adt2807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866071","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":"A molecularly defined mPFC-BLA circuit specifically regulates social novelty preference","authors":"Yiqiong Liu,&nbsp;Ying Wang,&nbsp;Guoguang Xie,&nbsp;Qianying Yang,&nbsp;Aritra Bhattacherjee,&nbsp;Chao Zhang,&nbsp;Yi Zhang","doi":"10.1126/sciadv.adt9008","DOIUrl":"10.1126/sciadv.adt9008","url":null,"abstract":"<div >Social novelty preference is an important aspect of social interaction for evaluating new threats and opportunities for survival, but the underlying neuronal mechanism remains unclear. Here, we identify a molecularly defined medial prefrontal cortex (mPFC) excitatory neuron subtype, located in layer 5 expressing <i>Il1rapl2</i>, which is highly associated with social deficit disorders in genome-wide association studies and might be responsible for regulating social novelty preference. Using an <i>Il1rapl2</i>-Cre mouse line, we show that chemogenetic activation of the mPFC <i>Il1rapl2</i>-expressing neurons impairs social novelty preference but with little effect on sociability. In addition, fiber photometry recording indicates that this neuron subtype is inhibited when mice interact with novel but not with familiar mice. Furthermore, viral tracing and terminal manipulation reveal that basolateral amygdala (BLA)–projecting <i>Il1rapl2</i>⁺ neurons mediate the social novelty preference. Thus, our study uncovers a molecularly defined mPFC-BLA circuit that specifically regulates social novelty preference, highlighting that specific neuron subtypes and circuits could modulate distinct aspects of social behaviors.</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.adt9008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866068","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":"Synaptophysin accelerates synaptic vesicle fusion by expanding the membrane upon neurotransmitter loading","authors":"Julia Preobraschenski,&nbsp;Alex J. B. Kreutzberger,&nbsp;Marcelo Ganzella,&nbsp;Agnieszka Münster-Wandowski,&nbsp;Mark A. B. Kreutzberger,&nbsp;Linda H. M. Oolsthorn,&nbsp;Sascha Seibert,&nbsp;Volker Kiessling,&nbsp;Dietmar Riedel,&nbsp;Agata Witkowska,&nbsp;Gudrun Ahnert-Hilger,&nbsp;Lukas K. Tamm,&nbsp;Reinhard Jahn","doi":"10.1126/sciadv.ads4661","DOIUrl":"10.1126/sciadv.ads4661","url":null,"abstract":"<div >Synaptic transmission is mediated by the exocytotic release of neurotransmitters stored in synaptic vesicles (SVs). SVs filled with neurotransmitters preferentially undergo exocytosis, but it is unclear how this is achieved. Here, we show that during transmitter loading, SVs substantially increase in size, which is reversible and requires synaptophysin, an abundant membrane protein with an unclear function. SVs are larger when synaptophysin is knocked out, and conversely, liposomes are smaller when reconstituted with synaptophysin. Moreover, transmitter loading of SVs accelerates fusion in vitro, which is abolished when synaptophysin is lacking despite near normal transmitter uptake. We conclude that synaptophysin functions as a curvature-promoting entity in the SV membrane, allowing for major lateral expansion of the SV membrane during neurotransmitter filling, thus increasing their propensity for exocytosis.</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.ads4661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866078","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":"Structural dissection of ergosterol metabolism reveals a pathway optimized for membrane phase separation","authors":"Israel Juarez-Contreras,&nbsp;Laura J. S. Lopes,&nbsp;Jamie Holt,&nbsp;Lorena Yu-Liao,&nbsp;Katherine O’Shea,&nbsp;Jose Ruiz-Ruiz,&nbsp;Alexander Sodt,&nbsp;Itay Budin","doi":"10.1126/sciadv.adu7190","DOIUrl":"10.1126/sciadv.adu7190","url":null,"abstract":"<div >Sterols are among the most abundant lipids in eukaryotic cells yet are synthesized through notoriously long metabolic pathways. It has been proposed that the molecular evolution of such pathways must have required each step to increase the capacity of its product to condense and order phospholipids. Here, we carry out a systematic analysis of the ergosterol pathway that leverages the yeast vacuole’s capacity to phase separate into ordered membrane domains. In the post-synthetic steps specific to ergosterol biosynthesis, we find that successive modifications act to oscillate ordering capacity, settling on a level that supports phase separation while retaining fluidity of the resulting domains. Simulations carried out with each intermediate showed how conformers in the sterol’s alkyl tail are capable of modulating long-range ordering of phospholipids, which could underlie changes in phase behavior. Our results indicate that the complexity of sterol metabolism could have resulted from the need to balance lipid interactions required for membrane organization.</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.adu7190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866054","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":"Magnetically driven triboelectric nanogenerator for a wireless, versatile energy transfer system","authors":"Junyeop Kim,&nbsp;Jeongmin Yoo,&nbsp;Hantae Seo,&nbsp;Raudel Avila,&nbsp;Gooyoon Chung,&nbsp;Gyuri Shin,&nbsp;Sujeong Gwak,&nbsp;Yongbin Han,&nbsp;Ju-Hyuck Lee,&nbsp;Hong-Joon Yoon,&nbsp;Yoonseok Park","doi":"10.1126/sciadv.adu5919","DOIUrl":"10.1126/sciadv.adu5919","url":null,"abstract":"<div >The development of stable and multifunctional monitoring or actuating systems for implantable biomedical devices necessitates a high-capacity power supply. By using the oscillation of a magnetic field, energy can be transmitted through various media such as skin, fat, liquids, metals, and fabrics. We demonstrate a magnetically actuated implantable triboelectric generator that can effectively transfer energy independently of the surrounding media. The oscillation of the magnetic field enables contact of elastomeric magnets with the top and bottom electrodes of the generator, generating a path for electrical energy through contact electrification. The performance of the magnetically actuated triboelectric generator exhibits high tolerability for lateral and angular misalignment, transferring energy through different media including tissue, liquid, air, wood, metal, and fabrics. This addresses a critical issue present in ultrasound approaches. These findings suggest that a magnetically actuated triboelectric generator can be an alternative technology capable of overcoming the medium-related challenges of ultrasound, providing power to medical implants.</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.adu5919","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866095","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":"C. elegans transgenerational avoidance of P. fluorescens is mediated by the Pfs1 sRNA and vab-1","authors":"Renee J. Seto,&nbsp;Rachel Brown,&nbsp;Rachel Kaletsky,&nbsp;Lance R. Parsons,&nbsp;Rebecca S. Moore,&nbsp;Julia M. Balch,&nbsp;Zemer Gitai,&nbsp;Coleen T. Murphy","doi":"10.1126/sciadv.adt3850","DOIUrl":"10.1126/sciadv.adt3850","url":null,"abstract":"<div >In its natural habitat, <i>Caenorhabditis elegans</i> must distinguish friend from foe. <i>Pseudomonas</i> are abundant in the worm’s environment and can be nutritious or pathogenic. Previously, we found that worms learn to avoid <i>Pseudomonas aeruginosa</i> and <i>Pseudomonas vranovensis</i> through a small RNA (sRNA)–mediated pathway targeting the <i>C. elegans</i> gene <i>maco-1</i>, and this behavior is inherited for four generations. Here, we show that <i>C. elegans</i> learns to transgenerationally avoid another pathogenic bacteria <i>Pseudomonas fluorescens</i> 15 (PF15). The PF15 sRNA, Pfs1, targets the <i>VAB-1</i> ephrin receptor through 16 nt of perfect match, suggesting the evolution of a distinct bacterial sRNA/<i>C. elegans</i> gene target pair. Knockdown of both <i>maco-1 and vab-1</i> induce PF15 avoidance, and <i>vab-1</i> loss reduces <i>maco-1</i> expression, placing both genes in the sRNA-targeted pathogenic avoidance pathway. Thus, multiple genes in this avoidance pathway can act as targets for bacterial sRNAs, expanding the possibilities for evolution of trans-kingdom regulation of <i>C. elegans</i> 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.adt3850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866096","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":"Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MPro inhibitors with potent in vivo efficacy","authors":"Tyler C. Detomasi,&nbsp;Gilles Degotte,&nbsp;Sijie Huang,&nbsp;Rahul K. Suryawanshi,&nbsp;Amy Diallo,&nbsp;Luca Lizzadro,&nbsp;Francisco J. Zaptero-Belinchón,&nbsp;Taha Y. Taha,&nbsp;Jiapeng Li,&nbsp;Alicia L. Richards,&nbsp;Eric R. Hantz,&nbsp;Zain Alam,&nbsp;Mauricio Montano,&nbsp;Maria McCavitt-Malvido,&nbsp;Rajesh Gumpena,&nbsp;James R. Partridge,&nbsp;Galen J. Correy,&nbsp;Yusuke Matsui,&nbsp;Annemarie F. Charvat,&nbsp;Isabella S. Glenn,&nbsp;Julia Rosecrans,&nbsp;Jezrael L. Revalde,&nbsp;Dashiell Anderson,&nbsp;Judd F. Hultquist,&nbsp;Michelle R. Arkin,&nbsp;R. Jeffrey Neitz,&nbsp;Danielle L. Swaney,&nbsp;Nevan J. Krogan,&nbsp;Brian K. Shoichet,&nbsp;Kliment A. Verba,&nbsp;Melanie Ott,&nbsp;Adam R. Renslo,&nbsp;Charles S. Craik","doi":"10.1126/sciadv.adt7836","DOIUrl":"10.1126/sciadv.adt7836","url":null,"abstract":"<div >The main protease (M^Pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a validated drug target. Starting with a lead-like dihydrouracil chemotype identified in a large-library docking campaign, we improved M^Pro inhibition &gt;1000-fold by engaging additional M^Pro subsites and using a latent electrophile to engage Cys¹⁴⁵. Advanced leads from this series show pan-coronavirus antiviral activity, low clearance in mice, and for <b>AVI-4773</b>, a rapid reduction in viral titers &gt;1,000,000 after just three doses. Both compounds are well distributed in mouse tissues, including brain, where concentrations &gt;1000× the 90% effective concentration are observed 8 hours after oral dosing for <b>AVI-4773</b>. <b>AVI-4516</b> shows minimal inhibition of major cytochrome P450s and human proteases. <b>AVI-4516</b> also exhibits synergy with the RNA-dependent RNA polymerase inhibitor, molnupiravir, in cellular infection models. Related analogs strongly inhibit nirmatrelvir-resistant M^Pro mutant virus. The properties of this chemotype are differentiated from existing clinical and preclinical M^Pro inhibitors and will advance therapeutic development against emerging SARS-CoV-2 variants and other coronaviruses.</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.adt7836","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866052","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":"Conformational plasticity of mitochondrial VDAC2 controls the kinetics of its interaction with cytosolic proteins","authors":"William M. Rosencrans,&nbsp;Harisankar Khuntia,&nbsp;Motahareh Ghahari Larimi,&nbsp;Radhakrishnan Mahalakshmi,&nbsp;Tsyr-Yan Yu,&nbsp;Sergey M. Bezrukov,&nbsp;Tatiana K. Rostovtseva","doi":"10.1126/sciadv.adv4410","DOIUrl":"10.1126/sciadv.adv4410","url":null,"abstract":"<div >The voltage-dependent anion channel (VDAC) is a key conduit of the mitochondrial outer membrane for water-soluble metabolites and ions. Among the three mammalian isoforms, VDAC2 is unique because of its embryonic lethality upon knockout. Using single-molecule electrophysiology, we investigate the biophysical properties that distinguish VDAC2 from VDAC1 and VDAC3. Unlike the latter, VDAC2 exhibits dynamic switching between multiple high-conductance, anion-selective substates. Using α-synuclein (αSyn)—a known VDAC1 cytosolic regulator—we found that higher-conductance substates correlate with increased on-rates of αSyn-VDAC2 interaction but shorter blockage times, maintaining a consistent equilibrium constant across all substates. This suggests that αSyn detects VDAC2’s dynamic structural variations before final binding. We explored the dependence of VDAC2’s unique amino-terminal extension and cysteines on substate behavior, finding that both structural elements modulate substate occurrence. The discovered conformational flexibility enables VDAC2 recognition by diverse binding partners, explaining its critical physiological role via dynamical adaptation to mitochondrial metabolic conditions.</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.adv4410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866053","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}