NaturePub Date : 2025-08-06DOI: 10.1038/d41586-025-02462-5
{"title":"Is your AI benchmark lying to you?","authors":"","doi":"10.1038/d41586-025-02462-5","DOIUrl":"https://doi.org/10.1038/d41586-025-02462-5","url":null,"abstract":"Artificial intelligence models are too often assessed against flawed goals — a stumbling block for progress.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"31 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786469","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}
Christopher A. Thomas, Henry Brinkerhoff, Jonathan M. Craig, Shuichi Hoshika, Desislava Mihaylova, Akira M. Pfeffer, Michaela C. Franzi, Sarah J. Abell, Jessica D. Carrasco, Jens H. Gundlach, Steven A. Benner, Andrew H. Laszlo
{"title":"Sequencing a DNA analog composed of artificial bases","authors":"Christopher A. Thomas, Henry Brinkerhoff, Jonathan M. Craig, Shuichi Hoshika, Desislava Mihaylova, Akira M. Pfeffer, Michaela C. Franzi, Sarah J. Abell, Jessica D. Carrasco, Jens H. Gundlach, Steven A. Benner, Andrew H. Laszlo","doi":"10.1038/s41467-025-61991-9","DOIUrl":"https://doi.org/10.1038/s41467-025-61991-9","url":null,"abstract":"<p>“ALternative Isoinformational ENgineered” (ALIEN) DNA is a biomimetic polymer composed of four entirely anthropogenic nucleotides. These alternative nucleosides form base pairs orthogonal to canonical bases and fold into the familiar B-form DNA double-helix, endowing ALIEN DNA with valuable biotechnological applications. The ability to sequence ALIEN DNA is essential for its continued development. However traditional sequencing approaches rely on chemical recognition of ACGT-DNA and cannot be easily adapted to ALIEN DNA. Here we demonstrate de novo nanopore sequencing of DNA comprised entirely of the four anthropogenic DNA bases. We show direct, label-free, single-molecule sequencing of such nucleic acids without the requirements of fluorescent labels, transliteration, amplification, or enzymatic synthesis. This paves the way for routine, accessible, and high-accuracy sequencing of DNA beyond A, C, G, and T.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"30 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787291","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}
Science AdvancesPub Date : 2025-08-06DOI: 10.1126/sciadv.adu3308
Yang Wang, Jingyu Li, Andrew A. Malcolm, William Mansfield, Stephen J. Clark, Ricard Argelaguet, Laura Biggins, Richard J. Acton, Simon Andrews, Wolf Reik, Gavin Kelsey, Peter J. Rugg-Gunn
{"title":"Combinatorial profiling of multiple histone modifications and transcriptome in single cells using scMTR-seq","authors":"Yang Wang, Jingyu Li, Andrew A. Malcolm, William Mansfield, Stephen J. Clark, Ricard Argelaguet, Laura Biggins, Richard J. Acton, Simon Andrews, Wolf Reik, Gavin Kelsey, Peter J. Rugg-Gunn","doi":"10.1126/sciadv.adu3308","DOIUrl":"https://doi.org/10.1126/sciadv.adu3308","url":null,"abstract":"Profiling combinations of histone modifications identifies gene regulatory elements in different states and discovers features controlling transcriptional and epigenetic programs. However, efforts to map chromatin states in complex, heterogeneous samples are hindered by the lack of methods that can profile multiple histone modifications together with transcriptomes in individual cells. Here, we describe single-cell multitargets and mRNA sequencing (scMTR-seq), a high-throughput method that enables simultaneous profiling of six histone modifications and transcriptome in single cells. We apply scMTR-seq to uncover dynamic and coordinated changes in chromatin states and transcriptomes during human endoderm differentiation. We also use scMTR-seq to produce lineage-resolved chromatin maps and gene regulatory networks in mouse blastocysts, revealing epigenetic asymmetries at gene regulatory regions between the three embryo lineages and identifying Trps1 as a potential repressor in epiblast cells of trophectoderm-associated enhancer networks and their target genes. Together, scMTR-seq enables investigation of combinatorial chromatin landscapes in a broad range of heterogeneous samples, providing insights into epigenetic regulatory systems.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"27 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787601","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}
Science AdvancesPub Date : 2025-08-06DOI: 10.1126/sciadv.adx8711
Kathryn H. Gunn, Anna Wheless, Thomas Calcraft, Mark Kreutzberger, Kareem El-Houshy, Edward H. Egelman, Peter B. Rosenthal, Saskia B. Neher
{"title":"Cryogenic electron tomography reveals helical organization of lipoprotein lipase in storage vesicles","authors":"Kathryn H. Gunn, Anna Wheless, Thomas Calcraft, Mark Kreutzberger, Kareem El-Houshy, Edward H. Egelman, Peter B. Rosenthal, Saskia B. Neher","doi":"10.1126/sciadv.adx8711","DOIUrl":"https://doi.org/10.1126/sciadv.adx8711","url":null,"abstract":"Lipoprotein lipase (LPL) is a triglyceride lipase that is contained in intracellular vesicles in an inactive storage form before secretion, but the precise structural details have not yet been resolved. Using cryo–electron tomography (cryo-ET), we observe that LPL exists inside of storage vesicles as a filament with an 11-nanometer diameter and is packed in these vesicles in two distinct patterns. Next, we solved a 4.2-Å resolution cryo–electron microscopy (cryo-EM) structure of this 11-nanometer LPL filament using purified protein. The filament is made of repeating pairs of LPL molecules with occluded active sites, rendering the LPL inactive. The comparison of the in situ subtomogram average and the in vitro cryo-EM structure indicates that the previously uncharacterized physiological storage form of LPL is an inactive filament.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"152 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787679","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}
Yousif A Lucinian, Christine Gagnon, Élise Latour, Virginie Hamel, Josep Iglesies-Grau, Anil Nigam, Francois Harel, Anna Nozza, Martin Juneau, Jean-Claude Moubarac, Louis Bherer, Matthieu Pelletier-Galarneau
{"title":"Effect of a single ultra processed meal on myocardial endothelial function, adenosine mediated effects and cognitive performances.","authors":"Yousif A Lucinian, Christine Gagnon, Élise Latour, Virginie Hamel, Josep Iglesies-Grau, Anil Nigam, Francois Harel, Anna Nozza, Martin Juneau, Jean-Claude Moubarac, Louis Bherer, Matthieu Pelletier-Galarneau","doi":"10.1038/s41598-025-11734-z","DOIUrl":"https://doi.org/10.1038/s41598-025-11734-z","url":null,"abstract":"<p><p>Consumption of ultra-processed foods has been linked to various adverse health effects; however, the mechanisms underlying these effects remain poorly understood. This study aimed to evaluate the impact of a single ultra-processed meal on myocardial blood flow (MBF), measured using positron emission tomography/computed tomography (PET/CT), and its effects on cognitive performance. Fourteen healthy adult males were enrolled in a randomized crossover trial, receiving either a non-ultra-processed meal (comprising foods from NOVA groups 1 to 3) or an ultra-processed meal (comprising foods from NOVA groups 1 to 4) before crossing over to the alternate meal. After each meal, rubidium-chloride PET/CT scans were conducted at baseline and during intermediate (80 µg/kg/min) and high-dose adenosine (140 µg/kg/min). Neuropsychological testing followed each meal. MBF and MFR at intermediate-dose adenosine was significantly higher after the ultra-processed meal compared to the non-ultra-processed meal (1.62 vs. 1.22 mL/min/g, p = 0.015, and 2.43 vs. 1.88, p = 0.012, respectively), with a mean relative difference of 40.7%. No significant differences were observed between the meals at baseline or high-dose adenosine for both MBF and MFR. When considering carry-over and learning effects, overall performance on neuropsychological testing was worse following the ultra-processed meal during the first period. In healthy adult males, a single ultra-processed meal enhanced adenosine-mediated MBF and MFR at intermediate-dose adenosine and was associated with potentially reduced cognitive performance compared to a non-ultra-processed meal.Trial registration number: NCT06353009 (ClinicalTrials.gov ID). Trial registration Date: 08/04/2024 https://clinicaltrials.gov/study/NCT06353009 .</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28671"},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Youna Paik, You-Min Kim, Youn-Kyung Choi, Sung-Hun Kim, Seong-Sik Kim, Wooil Kim, Yong-Il Kim
{"title":"Enhanced anti-microbial properties of clear aligner resin containing zwitterionic material.","authors":"Youna Paik, You-Min Kim, Youn-Kyung Choi, Sung-Hun Kim, Seong-Sik Kim, Wooil Kim, Yong-Il Kim","doi":"10.1038/s41598-025-14004-0","DOIUrl":"https://doi.org/10.1038/s41598-025-14004-0","url":null,"abstract":"<p><p>This study evaluated the mechanical and anti-bacterial properties of photocurable clear aligner resin (TC-85) incorporated with zwitterionic material, 2-methacryloyloxyethyl phosphorylcholine (MPC). Three experimental solutions were synthesized using 2-methacryloyloxyethyl phosphorylcholine (MPC) and clear aligner resin (TC-85). A group without any experimental solution served as a control. Specimens were fabricated by adding mixture of solutions to customized mold followed by post-curing procedure. Mechanical properties of the experimental groups were evaluated by tensile strength test, three-point flexural test, stress relaxation and creep test. Biological properties were evaluated through colony forming unit assay, MTT assay, and protein adsorption test. Incorporation of MPC into clear aligner resin achieved protein repellent and anti-microbial capabilities without compromising the mechanical properties. Tensile strength and three-point flexural test along with creep, stress relaxation test did not show significant difference in the mechanical properties. Addition of 1%, 2%, or 3% MPC into clear aligner resin significantly reduced the amount of bovine serum albumin adsorbed and proteins adsorbed from brain heart infusion medium by 1/3 ~ 1/4 that of a control (p < 0.001). The mixture of clear aligner resin with 3% MPC inhibited biofilm growth, reducing CFU counts by 40% compared to that of a control. Incorporating zwitterionic material with clear aligner resin TC-85 demonstrated an anti-biofouling activity while preserving its original mechanical properties, which may be a promising strategy to overcome the limitation of current clear aligner treatment.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28664"},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine learning approaches for predicting the structural number of flexible pavements based on subgrade soil properties.","authors":"Asadullah Ziar","doi":"10.1038/s41598-025-13852-0","DOIUrl":"https://doi.org/10.1038/s41598-025-13852-0","url":null,"abstract":"<p><p>This study presents a machine learning approach to predict the structural number of flexible pavements using subgrade soil properties and environmental conditions. Four algorithms were evaluated, including random forest, extreme gradient boosting, gradient boosting, and K nearest neighbors. The dataset was prepared by converting resilient modulus values into structural numbers using the bisection method applied to the American Association of State Highway and Transportation Officials 1993 design equation. Input variables included moisture content, dry unit weight, weighted plasticity index, and the number of freeze and thaw cycles. Each model was trained and tested using standard performance metrics. Gradient boosting achieved the highest accuracy with a determination coefficient of 0.917. Moisture content was identified as the most significant predictor in most models. The findings demonstrate that machine learning models can accurately predict pavement thickness requirements based on readily available soil and environmental data. This approach reduces reliance on expensive and time-consuming laboratory tests and provides a practical and efficient tool for pavement design. This study highlights the potential of machine learning models in enhancing pavement design by accurately predicting structural performance parameters based on soil and environmental factors.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28658"},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wiesława Radmacher, Igor Niezgodzki, Vicente Gilabert, Gregor Knorr, David M. Buchs, José A. Arz, Ignacio Arenillas, Martin A. Pearce, Jarosław Tyszka, Mateusz Mikołajczak, Osmín J. Vásquez, Sarit Ashckenazi-Polivoda, Sigal Abramovich, Mariusz Niechwedowicz, Gunn Mangerud
{"title":"Ocean freshening near the end of the Mesozoic","authors":"Wiesława Radmacher, Igor Niezgodzki, Vicente Gilabert, Gregor Knorr, David M. Buchs, José A. Arz, Ignacio Arenillas, Martin A. Pearce, Jarosław Tyszka, Mateusz Mikołajczak, Osmín J. Vásquez, Sarit Ashckenazi-Polivoda, Sigal Abramovich, Mariusz Niechwedowicz, Gunn Mangerud","doi":"10.1038/s41467-025-62189-9","DOIUrl":"https://doi.org/10.1038/s41467-025-62189-9","url":null,"abstract":"<p>Paleogeographic changes have significantly shaped ocean circulation and climate dynamics throughout Earth’s history. This study integrates geological proxies with climate simulations to assess how ocean gateway evolution influenced ocean salinity near the end of the Mesozoic (~66 Ma). Our modeling results demonstrate that 1) Central American Seaway shoaling reorganizes ocean currents, and 2) Arctic marine gateway restrictions, confining Arctic–Global Ocean exchange exclusively to the Greenland–Norwegian Seaway, drive Arctic Ocean surface freshening and southward outflow of buoyant, low-salinity waters. However, only the combined effect of these two factors leads to both Arctic freshening and increased water mass stratification in the Greenland–Norwegian Seaway, proto-North Atlantic, and the Western Tethys. This scenario aligns with Maastrichtian palynological, micropaleontological, and geochemical records from high- and low-latitude sites. Our findings highlight the profound impact of these latest Cretaceous paleogeographic reconfigurations in altering global salinity patterns, underscoring their role as key drivers of global climate dynamics.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"6 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786995","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}
Science AdvancesPub Date : 2025-08-06DOI: 10.1126/sciadv.adx1680
Yessenbek K. Aldakul, Marcus Schewe, Carlos Coll-Diez, Songhwan Hwang, Thomas Baukrowitz, Han Sun
{"title":"Atomistic mechanism of noncanonical voltage gating in K 2P channels","authors":"Yessenbek K. Aldakul, Marcus Schewe, Carlos Coll-Diez, Songhwan Hwang, Thomas Baukrowitz, Han Sun","doi":"10.1126/sciadv.adx1680","DOIUrl":"https://doi.org/10.1126/sciadv.adx1680","url":null,"abstract":"In classical voltage-gated cation channels, the movement of a voltage-sensing domain (VSD) opens a gate in the pore domain. However, two-pore domain K <jats:sup>+</jats:sup> (K <jats:sub>2P</jats:sub> ) channels lack a VSD and instead rely on K <jats:sup>+</jats:sup> movement within the selectivity filter (SF) to convert voltage changes into pore opening. To uncover the atomistic basis of voltage gating in TREK K <jats:sub>2P</jats:sub> channels, we integrated large-scale atomistic molecular dynamics simulations with extensive mutagenesis and patch-clamp electrophysiology, including sucrose-based experiments. Simulations revealed an asymmetric stability difference along the SF that results in a water-permeable extracellular side and a watertight intracellular side. Inactivation during inward flux occurs when water penetrates into the inner binding site and halts ion permeation, followed by the unbinding of three K <jats:sup>+</jats:sup> ions, consistent with gating charge analysis. Our findings provide unprecedented atomistic insights into the C-type inactivation of TREK K <jats:sub>2P</jats:sub> channels and establish a framework for investigating noncanonical voltage gating mechanisms in other ion channels.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"69 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787547","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}
Science AdvancesPub Date : 2025-08-06DOI: 10.1126/sciadv.adw7205
Michele Diego, Jade Hardouin, Gabrielle Mazevet-Schargrod, Matteo Pirro, Byunggi Kim, Roman Anufriev, Masahiro Nomura
{"title":"Hypersonic acoustic wave control via stealthy hyperuniform phononic nanostructures","authors":"Michele Diego, Jade Hardouin, Gabrielle Mazevet-Schargrod, Matteo Pirro, Byunggi Kim, Roman Anufriev, Masahiro Nomura","doi":"10.1126/sciadv.adw7205","DOIUrl":"https://doi.org/10.1126/sciadv.adw7205","url":null,"abstract":"Controlling hypersonic surface acoustic waves is crucial for advanced phononic devices such as high-frequency filters, sensors, and quantum computing components. While periodic phononic crystals enable precise bandgap engineering, their ability to suppress acoustic waves is limited to specific frequency ranges. Here, we experimentally demonstrate surface acoustic wave control using a hyperuniform arrangement of gold nanopillars on a lithium niobate layer. The hyperuniform structure, exhibiting characteristics of both random and ordered systems, leads to broad-range acoustic transmission reduction and bandgap-like regions of particularly strong suppression. By integrating linear and S-shaped waveguides into the hyperuniform pattern, we achieve efficient waveguiding at frequencies within these bandgaps. Both simulations and experiments confirm high transmission through the waveguides, demonstrating the flexibility of hyperuniform structures to support complex waveguide shapes. These findings provide an alternative approach to overcome limitations of traditional phononic crystals and advance acoustic technologies such as mechanical quantum computing and smartphone filters.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"9 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787558","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}