Science Advances最新文献_第2页

AI-driven universal lower-limb exoskeleton system for community ambulation 用于社区行走的人工智能驱动通用下肢外骨骼系统

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adq0288

Dawit Lee, Sanghyub Lee, Aaron J. Young

{"title":"AI-driven universal lower-limb exoskeleton system for community ambulation","authors":"Dawit Lee, Sanghyub Lee, Aaron J. Young","doi":"10.1126/sciadv.adq0288","DOIUrl":"https://doi.org/10.1126/sciadv.adq0288","url":null,"abstract":"Exoskeletons offer promising solutions for improving human mobility, but a key challenge is ensuring the controller adapts to changing walking conditions. We present an artificial intelligence (AI)–driven universal exoskeleton system that dynamically switches assistance types between walking modes, modulates assistance levels corresponding to the ground slope, and delivers assistance timely based on the current gait phase in real-time. During treadmill validation, AI-based assistance reduced metabolic cost by 6.5% compared to 3.5% for conventional assistance. We expanded testing the controller in real-world walking, where AI-based assistance showed effective modulation and higher user preference compared to conventional assistance. Leveraging the AI-based approach and a comprehensive dataset, the controller achieved superior performance in environment- and user-state estimations. This approach does not require a separate mode classifier and operates on a user-independent basis, enabling immediate deployment across diverse conditions. This study highlights the potential of AI-driven exoskeletons in facilitating human locomotion in real-world ambulation.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"20 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841858","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

Designing microplastic-binding peptides with a variational quantum circuit–based hybrid quantum-classical approach 用基于变分量子电路的量子-经典混合方法设计微塑料结合肽

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adq8492

Raul Conchello Vendrell, Akshay Ajagekar, Michael T. Bergman, Carol K. Hall, Fengqi You

{"title":"Designing microplastic-binding peptides with a variational quantum circuit–based hybrid quantum-classical approach","authors":"Raul Conchello Vendrell, Akshay Ajagekar, Michael T. Bergman, Carol K. Hall, Fengqi You","doi":"10.1126/sciadv.adq8492","DOIUrl":"https://doi.org/10.1126/sciadv.adq8492","url":null,"abstract":"De novo peptide design exhibits great potential in materials engineering, particularly for the use of plastic-binding peptides to help remediate microplastic pollution. There are no known peptide binders for many plastics—a gap that can be filled with de novo design. Current computational methods for peptide design exhibit limitations in sampling and scaling that could be addressed with quantum computing. Hybrid quantum-classical methods can leverage complementary strengths of near-term quantum algorithms and classical techniques for complex tasks like peptide design. This work introduces a hybrid quantum-classical generative framework for designing plastic-binding peptides combining variational quantum circuits with a variational autoencoder network. We demonstrate the framework’s effectiveness in generating peptide candidates, evaluate its efficiency for property-oriented design, and validate the candidates with molecular dynamics simulations. This quantum computing–based approach could accelerate the development of biomolecular tools for environmental and biomedical applications while advancing the study of biomolecular systems through quantum technologies.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"86 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841867","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

Metformin targets mitochondrial complex I to lower blood glucose levels 二甲双胍靶向线粒体复合物 I 降低血糖水平

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.ads5466

Colleen R. Reczek, Ram P. Chakrabarty, Karis B. D’Alessandro, Zachary L. Sebo, Rogan A. Grant, Peng Gao, G. R. Budinger, Navdeep S. Chandel

{"title":"Metformin targets mitochondrial complex I to lower blood glucose levels","authors":"Colleen R. Reczek, Ram P. Chakrabarty, Karis B. D’Alessandro, Zachary L. Sebo, Rogan A. Grant, Peng Gao, G. R. Budinger, Navdeep S. Chandel","doi":"10.1126/sciadv.ads5466","DOIUrl":"https://doi.org/10.1126/sciadv.ads5466","url":null,"abstract":"Metformin is among the most prescribed antidiabetic drugs, but the primary molecular mechanism by which metformin lowers blood glucose levels is unknown. Previous studies have proposed numerous mechanisms by which acute metformin lowers blood glucose, including the inhibition of mitochondrial complex I of the electron transport chain (ETC). Here, we used transgenic mice that globally express the Saccharomyces cerevisiae internal alternative NADH dehydrogenase (NDI1) protein to determine whether the glucose-lowering effect of acute oral administration of metformin requires inhibition of mitochondrial complex I of the ETC in vivo. NDI1 is a yeast NADH dehydrogenase enzyme that complements the loss of mammalian mitochondrial complex I electron transport function and is insensitive to pharmacologic mitochondrial complex I inhibitors including metformin. We demonstrate that NDI1 expression attenuates metformin’s ability to lower blood glucose levels under standard chow and high-fat diet conditions. Our results indicate that acute oral administration of metformin targets mitochondrial complex I to lower blood glucose.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"158 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841890","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

Dynamic responses of striatal cholinergic interneurons control behavioral flexibility

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adn2446

Zhenbo Huang, Ruifeng Chen, Matthew Ho, Xueyi Xie, Himanshu Gangal, Xuehua Wang, Jun Wang

{"title":"Dynamic responses of striatal cholinergic interneurons control behavioral flexibility","authors":"Zhenbo Huang, Ruifeng Chen, Matthew Ho, Xueyi Xie, Himanshu Gangal, Xuehua Wang, Jun Wang","doi":"10.1126/sciadv.adn2446","DOIUrl":"https://doi.org/10.1126/sciadv.adn2446","url":null,"abstract":"Striatal cholinergic interneurons (CINs) are key to regulating behavioral flexibility, involving both extinguishing learned actions and adopting new ones. However, the mechanisms driving these processes remain elusive. In this study, we initially demonstrate that chronic alcohol consumption disrupts the burst-pause dynamics of CINs and impairs behavioral flexibility. We next aimed to elucidate the mechanisms by which CIN dynamics control behavioral flexibility. We found that extinction learning enhances acetylcholine (ACh) release and that mimicking this enhancement through optogenetic induction of CIN burst firing accelerates the extinction process. In addition, we demonstrate that disrupting CIN pauses via continuous optogenetic stimulation reversibly impairs the updating of goal-directed behaviors. Overall, we demonstrate that CIN burst firing, which increases ACh release, promotes extinction learning, aiding the extinguishment of learned behaviors. Conversely, CIN firing pauses, which lead to ACh dips, are crucial for reversal learning, facilitating the adaptation of new actions. These findings shed light on how CIN dynamics regulate behavioral flexibility.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"256 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841873","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

Biologically inspired bioactive hydrogels for scarless corneal repair 用于无疤痕角膜修复的生物灵感生物活性水凝胶

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adt1643

Jianan Huang, Tuoying Jiang, Jiqiao Qie, Xiaoyu Cheng, Yiyao Wang, Yang Ye, Zhuoheng Yang, Hongji Yan, Ke Yao, Haijie Han

{"title":"Biologically inspired bioactive hydrogels for scarless corneal repair","authors":"Jianan Huang, Tuoying Jiang, Jiqiao Qie, Xiaoyu Cheng, Yiyao Wang, Yang Ye, Zhuoheng Yang, Hongji Yan, Ke Yao, Haijie Han","doi":"10.1126/sciadv.adt1643","DOIUrl":"https://doi.org/10.1126/sciadv.adt1643","url":null,"abstract":"Corneal injury–induced fibrosis occurs because of corneal epithelial basement membrane (EBM) injury and defective regeneration. Corneal fibrosis inhibition and transparency restoration depend on reestablished EBM, where the collagen network provides structural stability and heparan sulfate binds corneal epithelium–derived cytokines to regulate homeostasis. Inspired by this, bioactive hydrogels (Hep@Gel) composed of collagen-derived gelatins and highly anionic heparin were constructed for scarless corneal repair. Hep@Gel resembled the barrier function of the EBM regarding surface-confined binding, long-time sequestration, and progressive degradation of IL-1, TGF-β, and PDGF-BB, which robustly inhibited the apoptosis and myofibroblast transition of keratocytes. Animal models of rabbits and nonhuman primates confirmed that Hep@Gel effectively limited the influx of inflammatory and fibrotic cytokines from the epithelium into the stroma to down-regulate the wound healing cascade, contributing to better vision quality with 73% reduced fibrosis. Hep@Gel offers a solution for preventing corneal injury–induced scarring and substituting for lamellar keratoplasty to remove scarring.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"256 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841840","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

The three-dimensional genome drives the evolution of asymmetric gene duplicates via enhancer capture-divergence 三维基因组通过增强子捕获-分化推动非对称基因重复的进化

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adn6625

UnJin Lee, Deanna Arsala, Shengqian Xia, Cong Li, Mujahid Ali, Nicolas Svetec, Christopher B. Langer, Débora R. Sobreira, Ittai Eres, Dylan Sosa, Jianhai Chen, Li Zhang, Patrick Reilly, Alexander Guzzetta, J.J. Emerson, Peter Andolfatto, Qi Zhou, Li Zhao, Manyuan Long

{"title":"The three-dimensional genome drives the evolution of asymmetric gene duplicates via enhancer capture-divergence","authors":"UnJin Lee, Deanna Arsala, Shengqian Xia, Cong Li, Mujahid Ali, Nicolas Svetec, Christopher B. Langer, Débora R. Sobreira, Ittai Eres, Dylan Sosa, Jianhai Chen, Li Zhang, Patrick Reilly, Alexander Guzzetta, J.J. Emerson, Peter Andolfatto, Qi Zhou, Li Zhao, Manyuan Long","doi":"10.1126/sciadv.adn6625","DOIUrl":"https://doi.org/10.1126/sciadv.adn6625","url":null,"abstract":"Previous evolutionary models of duplicate gene evolution have overlooked the pivotal role of genome architecture. Here, we show that proximity-based regulatory recruitment by distally duplicated genes is an efficient mechanism for modulating tissue-specific production of preexisting proteins. By leveraging genomic asymmetries, we performed a coexpression analysis on Drosophila melanogaster tissue data to show the generality of enhancer capture-divergence (ECD) as a significant evolutionary driver of asymmetric, distally duplicated genes. We use the recently evolved gene HP6 / Umbrea as an example of the ECD process. By assaying genome-wide chromosomal conformations in multiple Drosophila species, we show that HP6/Umbrea was inserted near a preexisting, long-distance three-dimensional genomic interaction. We then use this data to identify a newly found enhancer ( FLEE1 ), buried within the coding region of the highly conserved, essential gene MFS18 , that likely neofunctionalized HP6/Umbrea . Last, we demonstrate ancestral transcriptional coregulation of HP6/Umbrea ’s future insertion site, illustrating how enhancer capture provides a highly evolvable, one-step solution to Ohno’s dilemma.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"23 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841868","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

Principles of CRISPR-Cas13 mismatch intolerance enable selective silencing of point-mutated oncogenic RNA with single-base precision CRISPR-Cas13错配不耐受原理可实现单碱基精确选择性沉默点突变致癌RNA

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adl0731

Carolyn Shembrey, Ray Yang, Joshua Casan, Wenxin Hu, Honglin Chen, Gurjeet J. Singh, Teresa Sadras, Krishneel Prasad, Jake Shortt, Ricky W. Johnstone, Joseph A. Trapani, Paul G. Ekert, Mohamed Fareh

{"title":"Principles of CRISPR-Cas13 mismatch intolerance enable selective silencing of point-mutated oncogenic RNA with single-base precision","authors":"Carolyn Shembrey, Ray Yang, Joshua Casan, Wenxin Hu, Honglin Chen, Gurjeet J. Singh, Teresa Sadras, Krishneel Prasad, Jake Shortt, Ricky W. Johnstone, Joseph A. Trapani, Paul G. Ekert, Mohamed Fareh","doi":"10.1126/sciadv.adl0731","DOIUrl":"https://doi.org/10.1126/sciadv.adl0731","url":null,"abstract":"Single-nucleotide variants (SNVs) are extremely prevalent in human cancers, although most of these remain clinically unactionable. The programmable RNA nuclease CRISPR-Cas13 has been deployed to specifically target oncogenic RNAs. However, silencing oncogenic SNVs with single-base precision remains extremely challenging due to the intrinsic mismatch tolerance of Cas13. Here, we show that introducing synthetic mismatches at precise positions of the spacer sequence enables de novo design of guide RNAs [CRISPR RNAs (crRNAs)] with strong preferential silencing of point-mutated transcripts. We applied these design principles to effectively silence the oncogenic KRAS G12 hotspot, NRAS G12D and BRAF V600E transcripts with minimal off-target silencing of the wild-type transcripts, underscoring the adaptability of this platform to silence various SNVs. Unexpectedly, the SNV-selective crRNAs harboring mismatched nucleotides reduce the promiscuous collateral activity of the Rfx Cas13d ortholog. These findings demonstrate that the CRISPR-Cas13 system can be reprogrammed to target mutant transcripts with single-base precision, showcasing the tremendous potential of this tool in personalized transcriptome editing.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"55 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841891","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

Ancient genomes reveal Avar-Hungarian transformations in the 9th-10th centuries CE Carpathian Basin 古代基因组揭示了公元 9-10 世纪喀尔巴阡山盆地的阿瓦尔-匈牙利变革

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adq5864

Dániel Gerber, Veronika Csáky, Bea Szeifert, Noémi Borbély, Kristóf Jakab, György Mező, Zsolt Petkes, Frigyes Szücsi, Sándor Évinger, Csilla Líbor, Piroska Rácz, Krisztián Kiss, Balázs Gusztáv Mende, Béla Miklós Szőke, Anna Szécsényi-Nagy

{"title":"Ancient genomes reveal Avar-Hungarian transformations in the 9th-10th centuries CE Carpathian Basin","authors":"Dániel Gerber, Veronika Csáky, Bea Szeifert, Noémi Borbély, Kristóf Jakab, György Mező, Zsolt Petkes, Frigyes Szücsi, Sándor Évinger, Csilla Líbor, Piroska Rácz, Krisztián Kiss, Balázs Gusztáv Mende, Béla Miklós Szőke, Anna Szécsényi-Nagy","doi":"10.1126/sciadv.adq5864","DOIUrl":"https://doi.org/10.1126/sciadv.adq5864","url":null,"abstract":"During the Early Medieval period, the Carpathian Basin witnessed substantial demographic shifts, notably under the Avar dominance for ~250 years, followed by the settlement of early Hungarians in the region during the late 9th century CE. This study presents the genetic analysis of 296 ancient samples, including 103 shotgun-sequenced genomes, from present-day Western Hungary. By using identity-by-descent segment sharing networks, this research offers detailed insights into the population structure and dynamics of the region from the 5th to 11th centuries CE, with specific focus on certain microregions. Our evaluations reveal spatially different histories in Transdanubia even between communities in close geographical proximity, highlighting the importance of dense sampling and analyses. Our findings highlight extensive homogenization and reorganization processes, as well as discontinuities between Hun, Avar, and Hungarian conquest period immigrant groups, alongside the spread and integration of ancestry related to the Hungarian conquerors.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"23 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841892","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

Regional differences in three-dimensional fiber organization, smooth muscle cell phenotype, and contractility in the pregnant mouse cervix

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adr3530

Christopher J. Hansen, Jackson H. Rogers, Alexus J. Brown, Naoko Boatwright, Shajila Siricilla, Christine M. O’Brien, Sourav Panja, Cameron M. Nichols, Kanchana Devanathan, Benjamin M. Hardy, Mark D. Does, Adam W. Anderson, Bibhash C. Paria, Anita Mahadevan-Jansen, Jeff Reese, Jennifer L. Herington

{"title":"Regional differences in three-dimensional fiber organization, smooth muscle cell phenotype, and contractility in the pregnant mouse cervix","authors":"Christopher J. Hansen, Jackson H. Rogers, Alexus J. Brown, Naoko Boatwright, Shajila Siricilla, Christine M. O’Brien, Sourav Panja, Cameron M. Nichols, Kanchana Devanathan, Benjamin M. Hardy, Mark D. Does, Adam W. Anderson, Bibhash C. Paria, Anita Mahadevan-Jansen, Jeff Reese, Jennifer L. Herington","doi":"10.1126/sciadv.adr3530","DOIUrl":"https://doi.org/10.1126/sciadv.adr3530","url":null,"abstract":"The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous contractions, distension had a minimal effect on contractility, and the upper cervix had forceful contractions in response to labor-inducing agents (oxytocin and prostaglandin E 2 ). These findings identify regional differences in cervix contractility related to contractile SMC content and fiber organization, which could be targeted with diagnostic technologies and for therapeutic intervention.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"30 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841831","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

Structural basis for membrane association and catalysis by phosphatidylserine synthase in Escherichia coli 大肠杆菌磷脂酰丝氨酸合成酶与膜结合和催化的结构基础

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adq4624

Eunju Lee, Gyuhyeok Cho, Jungwook Kim

引用次数: 0