Heejong Kim, Batuhan K Karaman, Qingyu Zhao, Alan Q Wang, Mert R Sabuncu
{"title":"Learning-based inference of longitudinal image changes: Applications in embryo development, wound healing, and aging brain.","authors":"Heejong Kim, Batuhan K Karaman, Qingyu Zhao, Alan Q Wang, Mert R Sabuncu","doi":"10.1073/pnas.2411492122","DOIUrl":"https://doi.org/10.1073/pnas.2411492122","url":null,"abstract":"<p><p>Longitudinal imaging data are routinely acquired for health studies and patient monitoring. A central goal in longitudinal studies is tracking relevant change over time. Traditional methods remove nuisance variation with custom pipelines to focus on significant changes. In this work, we present a machine learning-based method that automatically ignores irrelevant changes and extracts the time-varying signal of interest. Our method, called Learning-based Inference of Longitudinal imAge Changes (LILAC), performs a pairwise comparison of longitudinal images in order to make a temporal difference prediction. LILAC employs a convolutional Siamese architecture to extract feature pairs, followed by subtraction and a bias-free fully connected layer to learn meaningful temporal image differences. We first showcase LILAC's ability to capture key longitudinal changes by simply training it to predict the temporal ordering of images. In our experiments, temporal ordering accuracy exceeded 0.98, and predicted time differences were strongly correlated with actual changes in relevant variables (Pearson Correlation Coefficient <i>r</i> = 0.911 with embryo phase change, and r = 0.875 with time interval in wound healing). Next, we trained LILAC to explicitly predict specific targets, such as the change in clinical scores in patients with mild cognitive impairment. LILAC models achieved over a 40% reduction in root mean square error compared to baseline methods. Our empirical results demonstrate that LILAC effectively localizes and quantifies relevant individual-level changes in longitudinal imaging data, offering valuable insights for studying temporal mechanisms or guiding clinical decisions.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 8","pages":"e2411492122"},"PeriodicalIF":9.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468535","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}
Andrew I. Perault, Amelia St. John, Ashley L. DuMont, Bo Shopsin, Alejandro Pironti, Victor J. Torres
{"title":"Enterobacter hormaechei replaces virulence with carbapenem resistance via porin loss","authors":"Andrew I. Perault, Amelia St. John, Ashley L. DuMont, Bo Shopsin, Alejandro Pironti, Victor J. Torres","doi":"10.1073/pnas.2414315122","DOIUrl":"https://doi.org/10.1073/pnas.2414315122","url":null,"abstract":"Pathogenic <jats:italic>Enterobacter</jats:italic> species are of increasing clinical concern due to the multidrug-resistant nature of these bacteria, including resistance to carbapenem antibiotics. Our understanding of <jats:italic>Enterobacter</jats:italic> virulence is limited, hindering the development of new prophylactics and therapeutics targeting infections caused by <jats:italic>Enterobacter</jats:italic> species. In this study, we assessed the virulence of contemporary clinical <jats:italic>Enterobacter hormaechei</jats:italic> isolates in a mouse model of intraperitoneal infection and used comparative genomics to identify genes promoting virulence. Through mutagenesis and complementation studies, we found two porin-encoding genes, <jats:italic>ompC</jats:italic> and <jats:italic>ompD</jats:italic> , to be required for <jats:italic>E. hormaechei</jats:italic> virulence. These porins imported clinically relevant carbapenems into the bacteria, and thus loss of OmpC and OmpD desensitized <jats:italic>E. hormaechei</jats:italic> to the antibiotics. Our genomic analyses suggest porin-related genes are frequently mutated in <jats:italic>E. hormaechei</jats:italic> , perhaps due to the selective pressure of antibiotic therapy during infection. Despite the importance of OmpC and OmpD during infection of immunocompetent hosts, we found the two porins to be dispensable for virulence in a neutropenic mouse model. Moreover, porin loss provided a fitness advantage during carbapenem treatment in an ex vivo human whole blood model of bacteremia. Our data provide experimental evidence of pathogenic <jats:italic>Enterobacter</jats:italic> species gaining antibiotic resistance via loss of porins and argue antibiotic therapy during infection of immunocompromised patients is a conducive environment for the selection of porin mutations enhancing the multidrug-resistant profile of these pathogens.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"21 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462632","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}
James E. Gonzales, Iktae Kim, Abhishek Bastiray, Wonmuk Hwang, Jae-Hyun Cho
{"title":"Evolutionary rewiring of the dynamic network underpinning allosteric epistasis in NS1 of the influenza A virus","authors":"James E. Gonzales, Iktae Kim, Abhishek Bastiray, Wonmuk Hwang, Jae-Hyun Cho","doi":"10.1073/pnas.2410813122","DOIUrl":"https://doi.org/10.1073/pnas.2410813122","url":null,"abstract":"Viral proteins frequently mutate to evade host innate immune responses, yet the impact of these mutations on the molecular energy landscape remains unclear. Epistasis, the intramolecular communications between mutations, often renders the combined mutational effects unpredictable. Nonstructural protein 1 (NS1) is a major virulence factor of the influenza A virus (IAV) that activates host PI3K by binding to its p85β subunit. Here, we present a deep analysis of the impact of evolutionary mutations in NS1 that emerged between the 1918 pandemic IAV strain and its descendant PR8 strain. Our analysis reveals how the mutations rewired interresidue communications, which underlie long-range allosteric and epistatic networks in NS1. Our findings show that PR8 NS1 binds to p85β with approximately 10-fold greater affinity than 1918 NS1 due to allosteric mutational effects, which are further tuned by epistasis. NMR chemical shift perturbation and methyl-axis order parameter analyses revealed that the mutations induced long-range structural and dynamic changes in PR8 NS1, relative to 1918 NS1, enhancing its affinity to p85β. Complementary molecular dynamics simulations and graph theory-based network analysis for conformational dynamics on the submicrosecond timescales uncover how these mutations rewire the dynamic network, which underlies the allosteric epistasis. Significantly, we find that conformational dynamics of residues with high betweenness centrality play a crucial role in communications between network communities and are highly conserved across influenza A virus evolution. These findings advance our mechanistic understanding of the allosteric and epistatic communications between distant residues and provide insight into their role in the molecular evolution of NS1.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"50 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462627","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}
Felix J. Elling, Fabien Pierrel, Sophie-Carole Chobert, Sophie S. Abby, Thomas W. Evans, Arthur Reveillard, Ludovic Pelosi, Juliette Schnoebelen, Jordon D. Hemingway, Ahcène Boumendjel, Kevin W. Becker, Pieter Blom, Julia Cordes, Vinitra Nathan, Frauke Baymann, Sebastian Lücker, Eva Spieck, Jared R. Leadbetter, Kai-Uwe Hinrichs, Roger E. Summons, Ann Pearson
{"title":"A novel quinone biosynthetic pathway illuminates the evolution of aerobic metabolism","authors":"Felix J. Elling, Fabien Pierrel, Sophie-Carole Chobert, Sophie S. Abby, Thomas W. Evans, Arthur Reveillard, Ludovic Pelosi, Juliette Schnoebelen, Jordon D. Hemingway, Ahcène Boumendjel, Kevin W. Becker, Pieter Blom, Julia Cordes, Vinitra Nathan, Frauke Baymann, Sebastian Lücker, Eva Spieck, Jared R. Leadbetter, Kai-Uwe Hinrichs, Roger E. Summons, Ann Pearson","doi":"10.1073/pnas.2421994122","DOIUrl":"https://doi.org/10.1073/pnas.2421994122","url":null,"abstract":"The dominant organisms in modern oxic ecosystems rely on respiratory quinones with high redox potential (HPQs) for electron transport in aerobic respiration and photosynthesis. The diversification of quinones, from low redox potential (LPQ) in anaerobes to HPQs in aerobes, is assumed to have followed Earth’s surface oxygenation ~2.3 billion years ago. However, the evolutionary origins of HPQs remain unresolved. Here, we characterize the structure and biosynthetic pathway of an ancestral HPQ, methyl-plastoquinone (mPQ), that is unique to bacteria of the phylum <jats:italic>Nitrospirota</jats:italic> . mPQ is structurally related to the two previously known HPQs, plastoquinone from <jats:italic>Cyanobacteriota</jats:italic> /chloroplasts and ubiquinone from <jats:italic>Pseudomonadota</jats:italic> /mitochondria, respectively. We demonstrate a common origin of the three HPQ biosynthetic pathways that predates the emergence of <jats:italic>Nitrospirota</jats:italic> , <jats:italic>Cyanobacteriota</jats:italic> , and <jats:italic>Pseudomonadota</jats:italic> . An ancestral HPQ biosynthetic pathway evolved ≥ 3.4 billion years ago in an extinct lineage and was laterally transferred to these three phyla ~2.5 to 3.2 billion years ago. We show that <jats:italic>Cyanobacteriota</jats:italic> and <jats:italic>Pseudomonadota</jats:italic> were ancestrally aerobic and thus propose that aerobic metabolism using HPQs significantly predates Earth’s surface oxygenation. Two of the three HPQ pathways were later obtained by eukaryotes through endosymbiosis forming chloroplasts and mitochondria, enabling their rise to dominance in modern oxic ecosystems.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"6 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462630","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}
{"title":"Structural requirements of KAI2 ligands for activation of signal transduction","authors":"Rito Kushihara, Akihiko Nakamura, Katsuki Takegami, Yoshiya Seto, Yusuke Kato, Hideo Dohra, Toshiyuki Ohnishi, Yasushi Todoroki, Jun Takeuchi","doi":"10.1073/pnas.2414779122","DOIUrl":"https://doi.org/10.1073/pnas.2414779122","url":null,"abstract":"Karrikin Insensitive 2 (KAI2), identified as the receptor protein for karrikins (KARs), which are smoke-derived seed germination stimulants, belongs to the same α/β-hydrolase family as D14, the receptor for strigolactones (SLs). KAI2 is believed to recognize an endogenous butenolide (KAI2 ligand; KL), but the identity of this compound remains unknown. Recent studies have suggested that ligand hydrolysis by KAI2 is a prerequisite for receptor activation to induce interaction with the target proteins, similar to the situation with D14. However, direct experimental evidence has been lacking. Here, we designed KAI2 ligands (carba-dMGers) whose butenolide rings were modified so that they cannot be hydrolyzed or dissociated from the original ligand molecule by KAI2, by structurally modifying dMGer, a potent and selective KAI2 agonist. Using these dMGer analogs, we found that the strongly bioactive ligand, (+)-dMGer, was hydrolyzed by KAI2 at a lower enzymatic rate compared with the weakly bioactive ligand, (+)-1′-carba-dMGer, and the hydrolyzed butenolide ring of (+)-dMGer was transiently trapped in the catalytic pocket of KAI2. Additionally, structural analysis revealed that (+)-6′-carba-dMGer bound to the catalytic pocket of KAI2 in the unhydrolyzed state. However, this binding did not induce the interaction between KAI2 and SMAX1, indicating that ligand binding to the receptor alone was not sufficient for KAI2 signaling. This study showed experimental data from a ligand structure–activity study that ligand hydrolysis and subsequent covalent adduct formation with the catalytic triad plays a key role in KAI2 activation, providing insight into the chemical structure of the <jats:italic>Arabidopsis</jats:italic> KL.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"65 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462634","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}
Santiago Priego-Cubero, Eva Knoch, Zhidan Wang, Saleh Alseekh, Karl-Heinz Braun, Philipp Chapman, Alisdair R. Fernie, Chang Liu, Claude Becker
{"title":"Subfunctionalization and epigenetic regulation of a biosynthetic gene cluster in Solanaceae","authors":"Santiago Priego-Cubero, Eva Knoch, Zhidan Wang, Saleh Alseekh, Karl-Heinz Braun, Philipp Chapman, Alisdair R. Fernie, Chang Liu, Claude Becker","doi":"10.1073/pnas.2420164122","DOIUrl":"https://doi.org/10.1073/pnas.2420164122","url":null,"abstract":"Biosynthetic gene clusters (BGCs) are sets of often heterologous genes that are genetically and functionally linked. Among eukaryotes, BGCs are most common in plants and fungi and ensure the coexpression of the different enzymes coordinating the biosynthesis of specialized metabolites. Here, we report the identification of a withanolide BGC in <jats:italic>Physalis grisea</jats:italic> (ground-cherry), a member of the nightshade family ( <jats:italic>Solanaceae</jats:italic> ). A combination of transcriptomic, epigenomic, and metabolic analyses revealed that, following a duplication event, this BGC evolved two tissue-specifically expressed subclusters, containing several pairs of paralogs that contribute to related but distinct biochemical processes; this subfunctionalization is tightly associated with epigenetic features and the local chromatin environment. The two subclusters appear strictly isolated from each other at the structural chromatin level, each forming a highly self-interacting chromatin domain with tissue-dependent levels of condensation. This correlates with gene expression in either above- or below-ground tissue, thus spatially separating the production of different withanolide compounds. By comparative phylogenomics, we show that the withanolide BGC most likely evolved before the diversification of the <jats:italic>Solanaceae</jats:italic> family and underwent lineage-specific diversifications and losses. The tissue-specific subfunctionalization is common to species of the <jats:italic>Physalideae</jats:italic> tribe but distinct from other, independent duplication events outside of this clade. In sum, our study reports on an instance of an epigenetically modulated subfunctionalization within a BGC and sheds light on the biosynthesis of withanolides, a highly diverse group of steroidal triterpenoids important in plant defense and amenable to pharmaceutical applications due to their anti-inflammatory, antibiotic, and anticancer properties.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"47 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462625","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}
{"title":"Planar device–enabled speckle illumination for dark-field label-free imaging beyond the diffraction limit","authors":"Zetao Fan, Xinxiang You, Douguo Zhang","doi":"10.1073/pnas.2423223122","DOIUrl":"https://doi.org/10.1073/pnas.2423223122","url":null,"abstract":"Dark-field microscopy is a technique used in optical microscopy to increase the contrast in unstained samples, making it possible to observe details that would otherwise be difficult to see under bright-field microscopy; thus, it has been widely employed in biological research, material science, and medical diagnostics. However, most dark-field microscopy methods cannot overcome the optical diffraction limit and require a bulky dark-field condenser and precise alignment of each optical element. In this study, we introduce a planar photonic device that can produce random speckles for dark-field illumination and improve the optical resolution. This planar device is made of random distribution fibers for injection of a laser beam, a scattering layer to produce random speckles, a one-dimensional photonic crystal (1DPC) to produce a hollow cone of light, and a metallic film to increase the energy efficiency. This planar device can work as a substrate for conventional microscopy. Taking advantage of the hollow cone of light with random speckles generated by the proposed planar device, we achieve a high-contrast, label-free image with a 1.55-fold improvement in spatial resolution. Furthermore, random evanescent speckles can be generated on the 1DPC just through tuning the incident wavelength, which demonstrates the ability for optical surface imaging beyond the diffraction limit. The advantage of this technique is that it does not require complex optical system or precise knowledge of the illumination pattern. This study will expand the potential applications of dark-field microscopy and provide insights into samples that might otherwise be invisible under traditional dark-field microscopy.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"10 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462598","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}
Xuechunzi Bai, Angelina Wang, Ilia Sucholutsky, Thomas L. Griffiths
{"title":"Explicitly unbiased large language models still form biased associations","authors":"Xuechunzi Bai, Angelina Wang, Ilia Sucholutsky, Thomas L. Griffiths","doi":"10.1073/pnas.2416228122","DOIUrl":"https://doi.org/10.1073/pnas.2416228122","url":null,"abstract":"Large language models (LLMs) can pass explicit social bias tests but still harbor implicit biases, similar to humans who endorse egalitarian beliefs yet exhibit subtle biases. Measuring such implicit biases can be a challenge: As LLMs become increasingly proprietary, it may not be possible to access their embeddings and apply existing bias measures; furthermore, implicit biases are primarily a concern if they affect the actual decisions that these systems make. We address both challenges by introducing two measures: LLM Word Association Test, a prompt-based method for revealing implicit bias; and LLM Relative Decision Test, a strategy to detect subtle discrimination in contextual decisions. Both measures are based on psychological research: LLM Word Association Test adapts the Implicit Association Test, widely used to study the automatic associations between concepts held in human minds; and LLM Relative Decision Test operationalizes psychological results indicating that relative evaluations between two candidates, not absolute evaluations assessing each independently, are more diagnostic of implicit biases. Using these measures, we found pervasive stereotype biases mirroring those in society in 8 value-aligned models across 4 social categories (race, gender, religion, health) in 21 stereotypes (such as race and criminality, race and weapons, gender and science, age and negativity). These prompt-based measures draw from psychology’s long history of research into measuring stereotypes based on purely observable behavior; they expose nuanced biases in proprietary value-aligned LLMs that appear unbiased according to standard benchmarks.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"16 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462638","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}
Emily J. Wu, Ankita T. Kandalkar, Julian F. Ehrmann, Alexander B. Tong, Jing Zhang, Qian Cong, Hao Wu
{"title":"A structural atlas of death domain fold proteins reveals their versatile roles in biology and function","authors":"Emily J. Wu, Ankita T. Kandalkar, Julian F. Ehrmann, Alexander B. Tong, Jing Zhang, Qian Cong, Hao Wu","doi":"10.1073/pnas.2426986122","DOIUrl":"https://doi.org/10.1073/pnas.2426986122","url":null,"abstract":"Death domain fold (DDF) superfamily proteins are critically important players in pathways of cell death and inflammation. DDFs are often essential scaffolding domains in receptors, adaptors, or effectors of these pathways by mediating homo- and hetero-oligomerization including helical filament assembly. At the downstream ends of these pathways, effector oligomerization by DDFs brings the enzyme domains into proximity for their dimerization and activation. Hundreds of structures of these domains have been solved. However, a comprehensive understanding of DDFs is lacking. In this article, we report the curation of a DDF structural atlas as a public website (deathdomain.org) and deduce the common and distinct principles of DDF-mediated oligomerization among the four families (death domain or DD, death effector domain or DED, caspase recruitment domain or CARD, and pyrin domain or PYD). We further annotate DDFs genome-wide based on AlphaFold-predicted models and protein sequences. These studies reveal mechanistic rules for this widely distributed domain superfamily.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"13 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462633","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}
{"title":"Manipulating hydrogenation pathways enables economically viable electrocatalytic aldehyde-to-alcohol valorization","authors":"Ze-Cheng Yao, Jing Chai, Tang Tang, Liang Ding, Zhe Jiang, Jiaju Fu, Xiaoxia Chang, Bingjun Xu, Liang Zhang, Jin-Song Hu, Li-Jun Wan","doi":"10.1073/pnas.2423542122","DOIUrl":"https://doi.org/10.1073/pnas.2423542122","url":null,"abstract":"Electrocatalytic reduction (ECR) of furfural represents a sustainable route for biomass valorization. Unfortunately, traditional Cu-catalyzed ECR suffers from diversified product distribution and industrial-incompatible production rates, mainly caused by the intricate mechanism−performance relationship. Here, we manipulate hydrogenation pathways on Cu by introducing ceria as an auxiliary component, which enables the mechanism switching from proton-coupled electron transfer to electrochemical hydrogen-atom transfer (HAT) and thus high-speed furfural-to-furfuryl alcohol electroconversion. Theoretical and kinetic analyses show that oxygen-vacancy-rich ceria delivers an efficient formation−diffusion−hydrogenation chain of H* by diminishing H* adsorption. Spectroscopic characterizations indicate that Cu/ceria interfacial perimeter enriches the local furfural, synergistically lowering the barrier of the rate-determining HAT step across the perimeter. Our Cu/ceria catalyst realizes high-rate HAT-dominated ECR for electrosynthesis of single-product furfuryl alcohol, achieving a high production rate of 19.1 ± 0.4 mol h <jats:sup>−1</jats:sup> m <jats:sup>−2</jats:sup> and a Faradaic efficiency of 97 ± 1% at an economically viable partial current density of over 0.1 A cm <jats:sup>−2</jats:sup> . Our results demonstrate a highly efficient route for biofeedstock valorization with enhanced techno-economic feasibility.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"21 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462636","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}