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Emergent Rashba spin-orbit coupling in bulk gold with buried network of nanoscale interfaces 具有纳米级界面埋藏网络的大块金中的新兴Rashba自旋轨道耦合
IF 12.5 1区 综合性期刊
Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adz1680
Shreya Kumbhakar, Banashree Debnath, Tuhin Kumar Maji, Binita Tongbram, Shinjan Mandal, T. Phanindra Sai, T. V. Ramakrishnan, Manish Jain, H. R. Krishnamurthy, Anshu Pandey, Arindam Ghosh
{"title":"Emergent Rashba spin-orbit coupling in bulk gold with buried network of nanoscale interfaces","authors":"Shreya Kumbhakar,&nbsp;Banashree Debnath,&nbsp;Tuhin Kumar Maji,&nbsp;Binita Tongbram,&nbsp;Shinjan Mandal,&nbsp;T. Phanindra Sai,&nbsp;T. V. Ramakrishnan,&nbsp;Manish Jain,&nbsp;H. R. Krishnamurthy,&nbsp;Anshu Pandey,&nbsp;Arindam Ghosh","doi":"10.1126/sciadv.adz1680","DOIUrl":"10.1126/sciadv.adz1680","url":null,"abstract":"<div >The Rashba effect, which plays a crucial role in fundamental materials physics and potential spintronics applications, has been engineered in diverse systems, including semiconductor quantum wells, oxide heterostructures, metallic surfaces, topological insulators, ferroelectrics, etc. However, generating it in systems that preserve bulk inversion symmetry (BIS), for example, in bulk metals, has not been possible so far. We demonstrate a strategy to introduce and tune Rashba spin-orbit interaction (SOI) to unprecedented magnitudes in inversion-symmetric solids by incorporating ultrasmall silver nanoparticles in bulk gold. The near-identical lattice constants of Ag and Au allow dense packing of the Ag/Au hetero-interfaces without compromising the global BIS. By varying the density of embedded nanoparticles, we generate Rashba SOI in a bulk metal with coupling strength ~15 meV∙Å, higher than any known system preserving BIS globally, and show up to ~20 times increase in the spin-orbit scattering rate. We argue that the combined effect of charge transfer at the interfaces and polaronic localization enhances the SOI.</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.adz1680","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255785","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
A DNA-containing phase-separated compartment links the nuclear envelope to chromosome axes to promote homolog pairing in C. elegans 在秀丽隐杆线虫中,一个含有dna的相分离室将核膜与染色体轴连接起来,以促进同源配对
IF 12.5 1区 综合性期刊
Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adw5764
Ruoxi Wang, Yuqi Tian, Libo Liu, Jian-Hua Wang, Li Zhao, Yuanyuan Liu, Feifei Qi, Liangran Zhang, Jun Zhou, Meng-Qiu Dong, Jinmin Gao
{"title":"A DNA-containing phase-separated compartment links the nuclear envelope to chromosome axes to promote homolog pairing in C. elegans","authors":"Ruoxi Wang,&nbsp;Yuqi Tian,&nbsp;Libo Liu,&nbsp;Jian-Hua Wang,&nbsp;Li Zhao,&nbsp;Yuanyuan Liu,&nbsp;Feifei Qi,&nbsp;Liangran Zhang,&nbsp;Jun Zhou,&nbsp;Meng-Qiu Dong,&nbsp;Jinmin Gao","doi":"10.1126/sciadv.adw5764","DOIUrl":"10.1126/sciadv.adw5764","url":null,"abstract":"<div >Homologous chromosome pairing is a critical prerequisite for successful meiosis, yet the molecular mechanisms underlying this process remain elusive. In <i>Caenorhabditis elegans</i>, chromosome pairing centers (PCs) and PC-recruited proteins mediate homolog recognition and pairing. Here, we further dissect the molecular characteristics of this system and reveal the involvement of a phase-separated compartment in pairing. Focusing on the PC protein HIM-8, we explored its functional domains in vivo and its self-multimerizing properties in vitro. We find that the amino-terminal domain facilitates PC chromatin binding of the carboxyl-terminal domain, whereas the middle unstructured region is essential for PC association with the nuclear envelop (NE). Integrated analyses suggest that PC-NE association is mediated by a DNA-containing phase-separated compartment that is spatially distinct from, but connected to, the chromosome axis—likely through flexible linkages. We propose that homology evaluation occurs within this compartment, where direct DNA-DNA interactions could play a role.</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.adw5764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255793","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
Plasticity of the cytotoxic Nep1-like protein enables promiscuity in binding to its lipid receptor glycosylinositol phosphorylceramides 细胞毒性nep1样蛋白的可塑性使其与脂质受体糖酰肌醇磷酸化神经酰胺的结合具有混杂性
IF 12.5 1区 综合性期刊
Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adw6401
Nika Žibrat Kalanj, Andreja Prešern, Katerina Naumoska, Tina Snoj, Jana Aupič, Vesna Glavnik, Alen Albreht, Mojca Mally, Jure Derganc, Peter Greimel, Alessandra Magistrato, Gregor Anderluh
{"title":"Plasticity of the cytotoxic Nep1-like protein enables promiscuity in binding to its lipid receptor glycosylinositol phosphorylceramides","authors":"Nika Žibrat Kalanj,&nbsp;Andreja Prešern,&nbsp;Katerina Naumoska,&nbsp;Tina Snoj,&nbsp;Jana Aupič,&nbsp;Vesna Glavnik,&nbsp;Alen Albreht,&nbsp;Mojca Mally,&nbsp;Jure Derganc,&nbsp;Peter Greimel,&nbsp;Alessandra Magistrato,&nbsp;Gregor Anderluh","doi":"10.1126/sciadv.adw6401","DOIUrl":"10.1126/sciadv.adw6401","url":null,"abstract":"<div >Interactions between plants and pathogens pose a major challenge for plant health and agriculture. One type of threat comes from widespread cytolysins necrosis- and ethylene-inducing peptide 1–like proteins (NLPs) secreted by microbial pathogens. NLPs disrupt plant membranes through interactions with glycosylinositol phosphorylceramides (GIPCs), but the specificity of these interactions remains unclear. We studied binding and pore formation of NLPs in model membranes with GIPCs derived from dicotyledonous or monocotyledonous plants. Using the cytotoxic NLP 2 from fungus <i>Moniliophthora perniciosa</i> (MpNEP2), we show that membrane binding and damage extend beyond previously studied oomycetal NLPs. Furthermore, NLP<sub>Pya</sub> from the oomycete <i>Pythium aphanidermatum</i> exhibits promiscuous binding with a marked preference for branched GIPC series B lipids. Molecular dynamics simulations demonstrated that the structural plasticity of NLP<sub>Pya</sub> provides a rational basis for its interaction with a variety of GIPC headgroups. These results clarify the molecular basis of NLP cytotoxicity and emphasize their role in broad-spectrum pathogenicity.</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.adw6401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255659","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
Genome-wide CRISPR screen identifies splicing factor SF3B4 in driving hepatocellular carcinoma 全基因组CRISPR筛选发现剪接因子SF3B4驱动肝细胞癌
IF 12.5 1区 综合性期刊
Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adw7181
Yue Guo, Mingjing Xu, Hua Xue, Xiaofan Ding, Alissa M. Wong, Na Lin, Dandan Pu, Aikha M. Wong, Xin Wang, Hui Zhao, Nathalie Wong
{"title":"Genome-wide CRISPR screen identifies splicing factor SF3B4 in driving hepatocellular carcinoma","authors":"Yue Guo,&nbsp;Mingjing Xu,&nbsp;Hua Xue,&nbsp;Xiaofan Ding,&nbsp;Alissa M. Wong,&nbsp;Na Lin,&nbsp;Dandan Pu,&nbsp;Aikha M. Wong,&nbsp;Xin Wang,&nbsp;Hui Zhao,&nbsp;Nathalie Wong","doi":"10.1126/sciadv.adw7181","DOIUrl":"10.1126/sciadv.adw7181","url":null,"abstract":"<div >Although genome sequencings have recognized many cancer-associated genes in hepatocellular carcinoma (HCC), distinguishing their functional effect remains challenging. Leveraging on a genome-wide CRISPR knockout (KO) screening, we uncovered spliceosome factors as major survival essential genes in HCC and up-regulations of ferroptosis suppressors [particularly glutamate-cysteine ligase catalytic subunit (GCLC)] in lenvatinib resistance. Our KO screen in patient-derived HCC organoid showed splicing factor 3b subunit 4 (SF3B4) to be top-ranked, conferring prosurvival signal in HCC organoid and driving tumorigenic potentials in both hepatic progenitor organoids and hydrodynamic tail vein injection HCC murine model. The combined RNA immunoprecipitation sequencing, long-read isoform sequencing, and transcriptome revealed characteristic splicing landscape regulated by SF3B4 and identified T-box transcription factor 3 (TBX3) variant TBX3+2a as a potent downstream effector. Our findings highlighted vital roles of SF3B4 in HCC cell survival and tumor progression, and the phenomenon of ferroptosis resistance in patients unresponsive to first-line agent lenvatinib.</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.adw7181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255675","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
Uncovering the regulatory landscape of early human B cell lymphopoiesis and its implications in the pathogenesis of B-ALL 揭示早期人类B细胞淋巴生成的调控景观及其在B- all发病机制中的意义
IF 12.5 1区 综合性期刊
Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adw3110
Núria Planell, Xabier Martínez-de-Morentin, Daniel Mouzo, David Lara-Astiaso, Amaia Vilas-Zornoza, Patxi San Martín-Uriz, Diego Alignani, Bruno Paiva, Alberto Maillo, Aleksandra Kurowska, Nerea Berastegui, Paula Garcia-Olloqui, Arantxa Urdangarin, Peri Noori, Asier Ortega-Legarreta, Mikel Hernaez, Vincenzo Lagani, Narsis Kiani, Matthias Merkenschlager, Teresa Ezponda, José I. Martín-Subero, Ricardo N. Ramírez, Jesper Tegner, Felipe Prosper, David Gomez-Cabrero
{"title":"Uncovering the regulatory landscape of early human B cell lymphopoiesis and its implications in the pathogenesis of B-ALL","authors":"Núria Planell,&nbsp;Xabier Martínez-de-Morentin,&nbsp;Daniel Mouzo,&nbsp;David Lara-Astiaso,&nbsp;Amaia Vilas-Zornoza,&nbsp;Patxi San Martín-Uriz,&nbsp;Diego Alignani,&nbsp;Bruno Paiva,&nbsp;Alberto Maillo,&nbsp;Aleksandra Kurowska,&nbsp;Nerea Berastegui,&nbsp;Paula Garcia-Olloqui,&nbsp;Arantxa Urdangarin,&nbsp;Peri Noori,&nbsp;Asier Ortega-Legarreta,&nbsp;Mikel Hernaez,&nbsp;Vincenzo Lagani,&nbsp;Narsis Kiani,&nbsp;Matthias Merkenschlager,&nbsp;Teresa Ezponda,&nbsp;José I. Martín-Subero,&nbsp;Ricardo N. Ramírez,&nbsp;Jesper Tegner,&nbsp;Felipe Prosper,&nbsp;David Gomez-Cabrero","doi":"10.1126/sciadv.adw3110","DOIUrl":"10.1126/sciadv.adw3110","url":null,"abstract":"<div >Dysregulation of early B cell lymphopoiesis—the process guiding cellular immunity development—can lead to malignancy, making it crucial to understand its regulatory mechanisms. We generated a multiomics resource comprising paired chromatin accessibility and gene expression profiles across eight human B cell precursor populations, providing a detailed characterization of early human B cell development. Integrative analysis revealed highly cell type–specific regulatory elements and enabled the reconstruction of the gene regulatory network governing differentiation. We identified putative candidate regulons, such as ELK3, enriched in pro–B cells and potentially involved in cell cycle progression. Regulons from bulk data were projected onto single-cell data, validating their activity and refining the regulatory landscape. This resource enabled identification of active regulatory programs and transformation-associated states in B cell acute lymphoblastic leukemia. The publicly available atlas provides a valuable resource for understanding B cell development and disease, supporting future efforts to decode regulatory programs in immunity and hematologic malignancies.</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.adw3110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255791","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
Digital twin enables radiosensitive organic speciation in 3D 数字孪生使辐射敏感的有机物种在三维
IF 12.5 1区 综合性期刊
Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.adw5444
Laure Cazals, Agnès Desolneux, Simo Huotari, Lauren Dalecky, Christoph Sahle, Alessandro Mirone, Serge X. Cohen, Loïc Bertrand
{"title":"Digital twin enables radiosensitive organic speciation in 3D","authors":"Laure Cazals,&nbsp;Agnès Desolneux,&nbsp;Simo Huotari,&nbsp;Lauren Dalecky,&nbsp;Christoph Sahle,&nbsp;Alessandro Mirone,&nbsp;Serge X. Cohen,&nbsp;Loïc Bertrand","doi":"10.1126/sciadv.adw5444","DOIUrl":"10.1126/sciadv.adw5444","url":null,"abstract":"<div >State-of-the-art spectral imaging techniques using high-brilliance sources face an inherent trade-off between signal intensity and sample integrity, particularly in hyperspectral and multispectral imaging. Traditionally, optimizing acquisition parameters, such as source wavelength, intensity, and exposure time, relies on empirical adjustments to enhance image contrast. Here, we introduce a digital twin methodology to overcome these limitations. Focusing on x-ray Raman imaging, a powerful yet underutilized speciation probe constrained by low quantum efficiency, we demonstrate its application to sensitive organic samples. Our approach enabled a 10-fold reduction in acquisition time while maintaining operation below the damage threshold, paving the way for high-fidelity spectral imaging with minimal sample degradation.</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.adw5444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255678","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
Focused thermal energy at atomic microwave antenna sites for ecocatalysis 在原子微波天线上聚焦热能用于生态催化
IF 12.5 1区 综合性期刊
Science Advances Pub Date : 2025-10-10 DOI: 10.1126/sciadv.ady4043
Ryo Ishibashi, Fuminao Kishimoto, Tatsushi Yoshioka, Hiroki Yamada, Koki Muraoka, Toshiaki Ina, Hiroki Taniguchi, Akira Nakayama, Toru Wakihara, Kazuhiro Takanabe
{"title":"Focused thermal energy at atomic microwave antenna sites for ecocatalysis","authors":"Ryo Ishibashi,&nbsp;Fuminao Kishimoto,&nbsp;Tatsushi Yoshioka,&nbsp;Hiroki Yamada,&nbsp;Koki Muraoka,&nbsp;Toshiaki Ina,&nbsp;Hiroki Taniguchi,&nbsp;Akira Nakayama,&nbsp;Toru Wakihara,&nbsp;Kazuhiro Takanabe","doi":"10.1126/sciadv.ady4043","DOIUrl":"10.1126/sciadv.ady4043","url":null,"abstract":"<div >Green transformation demands efficient protocols to convert renewable energy into usable forms. Microwave (MW)–driven catalytic systems offer a promising electrification strategy for chemical processes by enabling targeted, energy-efficient reactions. Unlike conventional heating, MW irradiation can localize energy at catalytic active sites. A major breakthrough is the selective MW heating of isolated metal ions or nanoparticles. This study presents a general catalyst design strategy to control MW-induced heating of single metal ions by tuning the zeolite framework and electrostatic interactions. Key structural and electronic factors governing atomic-scale energy localization are identified. Applying this approach to the reverse water-gas shift reaction results in energy efficiency improvements via targeted heating of single-ion sites. These findings mark a milestone in MW-assisted catalysis, establishing a framework for using MW energy in heterogeneous systems. The work introduces design principles for single-atom-antenna MW catalysts, advancing the development of next-generation catalytic reactors driven by electromagnetic energy.</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.ady4043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255788","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
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,&nbsp;Rogerio M. Castilho,&nbsp;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,&nbsp;Nadeem Asad,&nbsp;Md Qamrul Islam,&nbsp;Raymond Anderson,&nbsp;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
{"title":"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.","authors":"","doi":"10.1126/sciadv.aec3197","DOIUrl":"10.1126/sciadv.aec3197","url":null,"abstract":"","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256881","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
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