Science Advances最新文献_第4页

Spatiotemporal toughness modulation in hydrogels through on-demand cross-linking 通过按需交联调节水凝胶的时空韧性

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adz0440

Jihun Lee, Rogerio M. Castilho, Sungmin Nam

{"title":"Spatiotemporal toughness modulation in hydrogels through on-demand cross-linking","authors":"Jihun Lee, Rogerio M. Castilho, Sungmin Nam","doi":"10.1126/sciadv.adz0440","DOIUrl":"10.1126/sciadv.adz0440","url":null,"abstract":"<div >Tough hydrogels are promising for soft robotics, bioelectronics, and tissue adhesives due to their exceptional resilience and biocompatibility, yet precise spatiotemporal control of their mechanics remains challenging. Here, we present a hydrogel platform that enables spatiotemporal modulation of toughness through a latent ionic cross-linking mechanism. By embedding calcium carbonate (CaCO<sub>3</sub>) microparticles in alginate/polyacrylamide double-network hydrogels, we create a system where localized calcium release and thus ionic cross-linking can be programmed in both space and time. Spatial control is achieved by direct ink writing of CaCO<sub>3</sub>, while temporal activation is triggered by glucono-δ-lactone, a biocompatible acidifier that releases calcium on demand. This strategy allows user-defined tuning of stiffness and toughness, enabling fabrication of three-dimensional (3D) hydrogels with tailored mechanical profiles. The resulting materials offer a versatile platform for anisotropic impact shielding, directional strain sensing, and 3D-printed tissue adhesives, representing a paradigm shift for adaptive, reconfigurable, and multifunctional soft materials.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 41","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adz0440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255790","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}

引用次数: 0

Hyperactive 20S proteasome enhances proteostasis and ERAD in C. elegans via degradation of intrinsically disordered proteins 过度活跃的20s蛋白酶体通过降解内在紊乱的蛋白质增强秀丽隐杆线虫的蛋白质稳态和ERAD

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adx3014

David Salcedo-Tacuma, Nadeem Asad, Md Qamrul Islam, Raymond Anderson, David M. Smith

{"title":"Hyperactive 20S proteasome enhances proteostasis and ERAD in C. elegans via degradation of intrinsically disordered proteins","authors":"David Salcedo-Tacuma, Nadeem Asad, Md Qamrul Islam, Raymond Anderson, David M. Smith","doi":"10.1126/sciadv.adx3014","DOIUrl":"10.1126/sciadv.adx3014","url":null,"abstract":"<div >Age-related proteinopathies, including Alzheimer’s and Parkinson’s disease, are driven by toxic accumulation of misfolded and intrinsically disordered proteins (IDPs) that overwhelm cellular proteostasis. The proteasome clears these proteins, but its failure in disease remains unclear. We engineered a <i>Caenorhabditis elegans</i> model with a hyperactive 20<i>S</i> proteasome (α3ΔN) for selective 20<i>S</i> activation. α3ΔN markedly enhanced IDP and misfolded protein degradation, reduced oxidative damage, and improved endoplasmic reticulum–associated degradation (ERAD). Aggregation-prone substrates such as vitellogenins and human alpha-1 antitrypsin (ATZ) were efficiently cleared. Integrated proteomic and transcriptomic analyses reveal systemic adaptations featuring increased protein turnover and oxidative stress resistance independent of superoxide dismutases (SODs). Notably, α3ΔN extended life span and stress resistance independently of canonical unfolded protein response (UPR) signaling via <i>xbp-1</i>. These findings substantiate a “20<i>S</i> pathway” of proteostasis that directly alleviates protein aggregation and oxidative stress, offering a promising therapeutic angle for neurodegenerative diseases.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 41","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx3014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255792","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}

引用次数: 0

Erratum for the Research Article “Ultrafast infrared nano-imaging of local electron-hole dynamics in CVD-grown single-walled carbon nanotubes” by J. Nishida et al. J. Nishida等人的研究论文“cvd生长的单壁碳纳米管中局部电子-空穴动力学的超快红外纳米成像”的勘误。

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.aec3197

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A unique mechanism involving cocatalysis of enzyme and nonenzyme to form β-carboline and spirotryprostatins in Aspergillus fumigatus 烟曲霉中酶和非酶共催化形成β-碳碱和螺旋体前列腺素的独特机制

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adz2319

Hai Gao, Deng Yu, Qiao Luo, Yanan Wang, Ling Lu, Weiming Zhu, Yi Wang

{"title":"A unique mechanism involving cocatalysis of enzyme and nonenzyme to form β-carboline and spirotryprostatins in Aspergillus fumigatus","authors":"Hai Gao, Deng Yu, Qiao Luo, Yanan Wang, Ling Lu, Weiming Zhu, Yi Wang","doi":"10.1126/sciadv.adz2319","DOIUrl":"10.1126/sciadv.adz2319","url":null,"abstract":"<div >Environmental stress represents an effective strategy for discovering natural products from microorganisms, but the processes involved remain unclear. Under acidic conditions, a previously unidentified class of β-carbolines (βCs), termed secofumitremorgins (SFs), with potent antiangiogenic activity in zebrafish models was found and identified via nuclear magnetic resonance, Marfey’s analysis, and quantum calculations. Using gene knockout, heterologous expression, precursor feeding, isotope tracing, molecular docking, and site-directed mutagenesis, a unique biosynthetic pathway for SFs was characterized, beyond the Pictet-Spenglerase–mediated biosynthetic process. Furthermore, an unreported pH-regulated mechanism was unveiled, where P450 (FtmG) facilitated new fumitremorgin intermediate formation, enabling spontaneous, nonenzymatic generation of βCs and spirotryprostatins under distinct pH conditions. Notably, this work provides detailed experimental evidence and reaction mechanisms for synergistic enzymatic and nonenzymatic catalysis driving metabolite diversification under pH stress. The findings expand biosynthetic paradigms for indole alkaloids and highlight the therapeutic potential of pH-elicited βCs, advancing strategies for natural product discovery.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 41","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adz2319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255679","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}

引用次数: 0

Concise network models of memory dynamics reveal explainable patterns in path data 记忆动力学的简明网络模型揭示了路径数据中可解释的模式

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adw4544

Rohit Sahasrabuddhe, Renaud Lambiotte, Martin Rosvall

引用次数: 0

Structural insights into the progressive recovery of α7 nicotinic acetylcholine receptor from nicotine-induced desensitization 尼古丁诱导脱敏后α - 7烟碱乙酰胆碱受体逐渐恢复的结构研究

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adx4432

Sanling Liu, Haopeng Chen, Xiaohong Zhu, Fei Ye, Yue Zhao, Junlin Qin, Yining Zheng, Xudong Wang, Longhua Zhang, Huan Chen, Xin Li, Wenjun Mu, Yaning Fu, Cheng Luo, Hongwei Hou, Chen Bai, Lei Liu, Changlin Tian

{"title":"Structural insights into the progressive recovery of α7 nicotinic acetylcholine receptor from nicotine-induced desensitization","authors":"Sanling Liu, Haopeng Chen, Xiaohong Zhu, Fei Ye, Yue Zhao, Junlin Qin, Yining Zheng, Xudong Wang, Longhua Zhang, Huan Chen, Xin Li, Wenjun Mu, Yaning Fu, Cheng Luo, Hongwei Hou, Chen Bai, Lei Liu, Changlin Tian","doi":"10.1126/sciadv.adx4432","DOIUrl":"10.1126/sciadv.adx4432","url":null,"abstract":"<div >Nicotine is the predominant alkaloid in tobacco leaves and affects the human nervous system by interacting with nicotinic acetylcholine receptors (nAChRs). Chronic nicotine exposure leads to nAChR desensitization, while nicotine withdrawal leads to nAChR recovery. However, detailed molecular mechanisms underlying nicotine-induced nAChR desensitization and its recovery remain elusive. Here, we present cryo-EM structures of the α7 nAChR in complex with nicotine in both an open state and multiple desensitized states. Comparative analyses reveal progressive conformational changes during recovery from nicotine-induced desensitization and show that asymmetric nicotine binding disrupts the symmetry of the channel pore at the 16′ and 17′ sites. Integrating these findings with patch-clamp recordings and computational simulations, we identify an agonist-free structure that represents an atypical desensitized state closely resembling the resting conformation of α7 nAChR. These detailed mechanistic studies enhance our understanding of nicotine’s effects on α7 nAChRs.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 41","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx4432","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255676","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}

引用次数: 0

Plasmonic pathway to hybrid nanomaterials through energy transfer 通过能量转移的等离子体路径到杂化纳米材料

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.ady7016

Hyuncheol Oh, Subhojyoti Chatterjee, Zhenyang Jia, Eric Gomez, Stephen A. Lee, Jiamu Lin, Ojasvi Verma, Stephan Link, Christy F. Landes

{"title":"Plasmonic pathway to hybrid nanomaterials through energy transfer","authors":"Hyuncheol Oh, Subhojyoti Chatterjee, Zhenyang Jia, Eric Gomez, Stephen A. Lee, Jiamu Lin, Ojasvi Verma, Stephan Link, Christy F. Landes","doi":"10.1126/sciadv.ady7016","DOIUrl":"10.1126/sciadv.ady7016","url":null,"abstract":"<div >Plasmon-induced resonance energy transfer (PIRET) is a promising approach for plasmonic photocatalysis and energy conversion, but challenges include elucidating the mechanism and maximizing its efficiency, both of which are hampered by competing processes. Another challenge is demonstrating that PIRET can photoinitiate reactions that follow efficient pathways compared to bulk processes. We report a plasmon-induced route to plasmonic-polymer hybrid nanomaterials using in operando single-particle spectroelectrochemistry. An energy transfer efficiency of 40% is achievable when the spectral overlap between gold nanorod scattering and polymer absorption is maximized. We also show that PIRET-initiated polymerization proceeds through a different mechanism than bulk polymerization, supported by spectroscopic evidence and density functional theory calculations, highlighting efficient energy cascading from photon to plasmon to exciton and, lastly, to unconventional light-initiated chemistry.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 41","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ady7016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255794","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}

引用次数: 0

Soma-derived 30-nt small RNAs are coupled with chromosome breakage and precisely target nontransposon DNA against elimination in Euplotes vannus soma来源的30-nt小rna与染色体断裂偶联，并精确靶向非转座子DNA以防止消除

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adx3690

Liping Lyu, Bijia Ding, Jinyu Fu, Iwona Rzeszutek, Estienne C. Swart, Mariusz Nowacki, Feng Gao

{"title":"Soma-derived 30-nt small RNAs are coupled with chromosome breakage and precisely target nontransposon DNA against elimination in Euplotes vannus","authors":"Liping Lyu, Bijia Ding, Jinyu Fu, Iwona Rzeszutek, Estienne C. Swart, Mariusz Nowacki, Feng Gao","doi":"10.1126/sciadv.adx3690","DOIUrl":"10.1126/sciadv.adx3690","url":null,"abstract":"<div >Metazoans suppress transposons via small RNA–mediated silencing, but ciliates physically eliminate transposons from somatic genomes. Here, we report the high-quality germline genome assembly of a marine ciliate <i>Euplotes vannus</i>, where ~80% are transposons and other germline-specific DNA that has to be precisely eliminated during soma development. We demonstrate that a class of soma-derived 30-nucleotide small RNAs precisely targets nontransposon DNA against elimination during this process. Small RNA–mediated targeting remains functional across varying small RNA lengths and is compatible with heterozygous sites. These small RNAs are cleaved by Dicer-like ribonuclease from long noncoding RNAs, which are bidirectionally transcribed of somatic chromosomes, initiated at subtelomeric chromosome breakage sequences (5′-TTGAA-3′). On the basis of these findings and time-course transcriptomic profiling, we propose a model elucidating the molecular mechanism of DNA elimination in <i>Euplotes</i>. These findings provide insights into the role of small RNAs in transmitting genetic information across generations and maintaining genome stability.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 41","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx3690","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255655","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}

引用次数: 0

Mechanism of USP21 autoinhibition and histone H2AK119 deubiquitination USP21自身抑制和组蛋白H2AK119去泛素化的机制

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.ady2604

Sanim Rahman, Chad W. Hicks, Alexander Gwizdala, Cynthia Wolberger

{"title":"Mechanism of USP21 autoinhibition and histone H2AK119 deubiquitination","authors":"Sanim Rahman, Chad W. Hicks, Alexander Gwizdala, Cynthia Wolberger","doi":"10.1126/sciadv.ady2604","DOIUrl":"10.1126/sciadv.ady2604","url":null,"abstract":"<div >Monoubiquitinated histone H2A lysine 119 (H2AK119ub) is a modification associated with transcriptional silencing and heterochromatin formation. Ubiquitin-specific protease 21 (USP21), one of four major H2AK119-specific deubiquitinating enzymes (DUBs), plays critical roles in diverse cellular processes. However, the mechanisms by which USP21 specifically deubiquitinates H2AK119ub and is regulated are unknown. We determined the cryo-EM structure of the USP21 catalytic domain bound to an H2AK119ub nucleosome, which revealed a recognition mode that differs from that of other H2AK119-specific DUBs. We unexpectedly found that the N-terminal IDR of USP21 inhibits the enzyme’s activity. Using AlphaFold-Multimer to perform a virtual screen of USP21 interactors, we identified kinases that phosphorylate the USP21 IDR and thereby relieve autoinhibition. AlphaFold3 modeling of USP21 suggests a structural model for autoinhibition. AlphaFold analysis suggests that phosphorylation-regulated autoinhibition may be a feature of various USP enzymes. These findings shed light on the mechanisms of H2AK119 deubiquitination and reveal a previously unexplored mode of phosphorylation-dependent DUB autoregulation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 41","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ady2604","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255787","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}

引用次数: 0

Erratum for the Research Article “ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner” by X. Xu et al. X. Xu等人的研究文章“ACTR5以ino80独立的方式控制CDKN2A和肿瘤进展”的勘误。

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.aec5118

引用次数: 0