ACS Central Science最新文献

{"title":"The Martini 3 Lipidome: Expanded and Refined Parameters Improve Lipid Phase Behavior","authors":"Kasper B. Pedersen,&nbsp;, ,&nbsp;Helgi I. Ingólfsson,&nbsp;, ,&nbsp;Daniel P. Ramirez-Echemendia,&nbsp;, ,&nbsp;Luís Borges-Araújo,&nbsp;, ,&nbsp;Mikkel D. Andreasen,&nbsp;, ,&nbsp;Charly Empereur-mot,&nbsp;, ,&nbsp;Josef Melcr,&nbsp;, ,&nbsp;Tugba N. Ozturk,&nbsp;, ,&nbsp;W. F. Drew Bennett,&nbsp;, ,&nbsp;Lisbeth R. Kjølbye,&nbsp;, ,&nbsp;Christopher Brasnett,&nbsp;, ,&nbsp;Valentina Corradi,&nbsp;, ,&nbsp;Hanif M. Khan,&nbsp;, ,&nbsp;Elio A. Cino,&nbsp;, ,&nbsp;Jackson Crowley,&nbsp;, ,&nbsp;Hyuntae Kim,&nbsp;, ,&nbsp;Balázs Fábián,&nbsp;, ,&nbsp;Ana C. Borges-Araújo,&nbsp;, ,&nbsp;Giovanni M. Pavan,&nbsp;, ,&nbsp;Guillaume Launay,&nbsp;, ,&nbsp;Fabio Lolicato,&nbsp;, ,&nbsp;Tsjerk A. Wassenaar,&nbsp;, ,&nbsp;Manuel N. Melo,&nbsp;, ,&nbsp;Sebastian Thallmair,&nbsp;, ,&nbsp;Timothy S. Carpenter,&nbsp;, ,&nbsp;Luca Monticelli,&nbsp;, ,&nbsp;D. Peter Tieleman,&nbsp;, ,&nbsp;Birgit Schiøtt,&nbsp;, ,&nbsp;Paulo C. T. Souza*,&nbsp;, and ,&nbsp;Siewert J. Marrink*,&nbsp;","doi":"10.1021/acscentsci.5c00755","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00755","url":null,"abstract":"<p >Lipid membranes are central to cellular life. Complementing experiments, computational modeling has been essential in unraveling complex lipid-biomolecule interactions, crucial in both academia and industry. The Martini model, a coarse-grained force field for efficient molecular dynamics simulations, is widely used to study membrane phenomena but has faced limitations, particularly in capturing realistic lipid phase behavior. Here, we present refined Martini 3 lipid models with a mapping scheme that distinguishes lipid tails that differ by just two carbon atoms, enhancing the structural resolution and thermodynamic accuracy of model membrane systems including ternary mixtures. The expanded Martini lipid library includes thousands of models, enabling simulations of complex and biologically relevant systems. These advancements establish Martini as a robust platform for lipid-based simulations across diverse fields.</p><p >Expanded and reparameterized Martini 3 lipidome with refined mapping improves lipid phase behavior and enables accurate simulations of complex and biologically relevant membrane systems.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1598–1610"},"PeriodicalIF":10.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00755","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Synthetic Phage-Peptide Conjugate as a Potent Antibacterial Agent for Pseudomonas aeruginosa Infections","authors":"Yanxi Yang,&nbsp;, ,&nbsp;Shelby Vexler,&nbsp;, ,&nbsp;Maria C. Jordan,&nbsp;, ,&nbsp;Serena Abbondante,&nbsp;, ,&nbsp;Dayeon Kang,&nbsp;, ,&nbsp;Huan Peng,&nbsp;, ,&nbsp;Michaela Marshall,&nbsp;, ,&nbsp;Bita V. Naini,&nbsp;, ,&nbsp;Saumya Jain,&nbsp;, ,&nbsp;Yei-Chen Lai,&nbsp;, ,&nbsp;Nasim Annabi,&nbsp;, ,&nbsp;Kenneth P. Roos,&nbsp;, ,&nbsp;Eric Pearlman,&nbsp;, and ,&nbsp;Irene A. Chen*,&nbsp;","doi":"10.1021/acscentsci.5c00562","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00562","url":null,"abstract":"<p >Antibiotic resistance among Gram-negative organisms is a major challenge. Some molecules, including antimicrobial peptides such as polymyxin B (PMB), are antibacterial but toxic due to low specificity, causing poor clinical utility. Drug delivery to bacterial cells using a biocompatible nanomaterial is a possible approach to securing such drugs. We engineered a nonlytic phage to recognize the lipopolysaccharide of Gram-negative bacteria and cross-linked thousands of peptides per virion, making “PMB-M13^αLPS”. PMB-M13^αLPS reduced the minimum inhibitory concentration <i>in vitro</i> by ∼2 orders of magnitude across multiple pathogen strains. Immunocompetent mice with multidrug-resistant <i>P. aeruginosa</i> pneumonia or corneal infection were effectively treated by PMB-M13^αLPS, which showed potency ∼2 orders of magnitude greater <i>in vivo</i> compared to that of PMB. PMB-M13^αLPS was well-tolerated, with no toxic effects. Conjugates of antimicrobial peptides and synthetic phages combine engineerable targeting with large payload capacity, improving potency and therapeutic index for otherwise toxic molecules.</p><p >A phage-peptide conjugate delivers an effective but toxic peptide specifically to bacterial cells. The conjugate treated mouse models of infection safely, showing how to increase clinical utility.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1715–1735"},"PeriodicalIF":10.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00562","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precise and In Vivo-Compatible Spatial Proteomics via Bioluminescence-Triggered Photocatalytic Proximity Labeling","authors":"Xuege Sun,&nbsp;, ,&nbsp;Yanling Zhang,&nbsp;, ,&nbsp;Wenjie Lu,&nbsp;, ,&nbsp;Hongyang Guo,&nbsp;, ,&nbsp;Guodong He,&nbsp;, ,&nbsp;Siyuan Luo,&nbsp;, ,&nbsp;Haodong Guo,&nbsp;, ,&nbsp;Zijuan Zhang,&nbsp;, ,&nbsp;Wenjing Wang,&nbsp;, ,&nbsp;Ling Chu,&nbsp;, ,&nbsp;Xiangyu Liu,&nbsp;, and ,&nbsp;Wei Qin*,&nbsp;","doi":"10.1021/acscentsci.5c00520","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00520","url":null,"abstract":"<p >Protein function is closely tied to its localization and interactions, which can be mapped using proximity labeling (PL). Traditional PL methods, such as peroxidases and biotin ligases, suffer from toxicity or high background. While visible-light-triggered photocatalytic labeling offers great potential, it is limited by light-induced background and restricted <i>in vivo</i> applications. Here we present BRET-ID, an <i>in vivo</i>-compatible PL technology for precise mapping of membraneless organelles and transient protein–protein interactions with subminute temporal resolution. BRET-ID combines a genetically encoded photocatalyst and NanoLuc luciferase, locally generating blue light to activate the photocatalyst via bioluminescence resonance energy transfer (BRET). This activation produces singlet oxygen, which oxidizes nearby proteins for analysis with a streamlined chemoproteomic workflow. BRET-ID enables precise mapping of ER membrane proteins, exhibiting high spatial specificity. Leveraging its high temporal resolution, BRET-ID provides 1 min snapshots of dynamic GPCR interactions during ligand-induced endocytosis. Additionally, BRET-ID identifies G3BP1-interacting proteins in arsenite-stressed cells and tumor xenografts, uncovering novel stress granule components, including the mTORC2 subunit RICTOR. BRET-ID serves as a powerful genetically encoded tool for studying protein localization and molecular interactions in living organisms.</p><p >A genetically encoded BRET-activated proximity labeling tool enables high-resolution mapping of protein localizations and interactions in live cells and <i>in vivo</i>.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1611–1626"},"PeriodicalIF":10.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the Stabilization Mechanism of Electron-Enriched PtNiCo Catalysts in Practical Direct Methanol Fuel Cells","authors":"Min Chen,&nbsp;, ,&nbsp;Yichi Guan,&nbsp;, ,&nbsp;Zhengpei Miao*,&nbsp;, ,&nbsp;Shuo Zhang,&nbsp;, ,&nbsp;Chunxia Wu,&nbsp;, ,&nbsp;Yu Zhou,&nbsp;, ,&nbsp;Hongxian Luo,&nbsp;, ,&nbsp;Daoxiong Wu,&nbsp;, ,&nbsp;Ruisong Li,&nbsp;, ,&nbsp;Junming Luo,&nbsp;, and ,&nbsp;Xinlong Tian*,&nbsp;","doi":"10.1021/acscentsci.5c01144","DOIUrl":"https://doi.org/10.1021/acscentsci.5c01144","url":null,"abstract":"<p >The rational design of Pt-based alloy catalysts with dual resistance to CO poisoning and metal leaching, enabled by interfacial electronic modulation, remains a critical challenge for practical direct methanol fuel cells (DMFCs). Here, we report a highly stable catalyst comprising electron-enriched TiN-meditated PtNiCo (denoted as e-PtNiCo) for DMFCs, demonstrating stabilization mechanisms rooted in enhanced Pt-CO antibonding interactions and strengthened Pt–Co/Ni chemical bonds. The e-PtNiCo catalyst exhibits a voltage decay of 9.6% at 100 mA cm^–2 over 50 h under practical DMFC operating conditions─a 4-fold improvement compared with the benchmarked PtNiCo (37.7%). Density functional theory calculations and post-mortem elemental analysis reveal that the developed catalysts possess tailored *CO adsorption energetics (−1.62 eV vs −1.27 eV for carbon-supported counterparts) and a 2-fold reduction in Ni/Co dissolution, governed by robust metal–support electronic coupling. This work establishes a mechanistic framework linking support-induced electronic effects to the stability of Pt-based alloys, offering a generalizable strategy for designing structurally durable, high-performance electrocatalysts in energy conversion technologies.</p><p >A remarkably stable catalyst comprises electron-enriched TiN-meditated PtNiCo, exhibiting both excellent CO-tolerance and metal leaching resistance for practical direct methanol fuel cells.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 10","pages":"1862–1869"},"PeriodicalIF":10.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c01144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145332093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astragaloside IV Alleviates Fructose-Induced Intestinal Metabolic Senescence by Targeting Ketohexokinase Asn261/Ala226 to Preserve Intestinal Stem Cell Homeostasis","authors":"Qifang Wu,&nbsp;, ,&nbsp;Yingna Li,&nbsp;, ,&nbsp;Yunyun Zhao,&nbsp;, ,&nbsp;Ruifen Zhang,&nbsp;, ,&nbsp;Jingyang Tong,&nbsp;, ,&nbsp;Chunlei Ji,&nbsp;, ,&nbsp;Yiming Zhao,&nbsp;, ,&nbsp;Mingjiang Wu,&nbsp;, ,&nbsp;Xiaosheng Jin,&nbsp;, ,&nbsp;Dandan Wang*,&nbsp;, ,&nbsp;Haibin Tong*,&nbsp;, ,&nbsp;Liwei Sun*,&nbsp;, and ,&nbsp;Fangbing Liu*,&nbsp;","doi":"10.1021/acscentsci.5c00726","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00726","url":null,"abstract":"<p >Excessive fructose intake drives intestinal aging and impairs intestinal stem cell (ISC) function, yet effective therapeutic interventions remain elusive. Astragaloside IV (AS-IV), a natural saponin from <i>Astragalus membranaceus</i>, has been widely recognized for its antiaging, anti-inflammatory, and gut-protective properties. Here, we revealed that AS-IV alleviates fructose-induced intestinal metabolic senescence via direct inhibition of ketohexokinase (KHK), the key rate-limiting enzyme in fructose metabolism. Molecular docking and site-directed mutagenesis identified Asn261 and Ala226 as distinct binding sites for AS-IV on KHK, with Asn261 also serving as a critical catalytic residue that is essential for KHK activity. Mutation at Asn261 abolished KHK enzymatic function, reduced the accumulation of fructose-derived metabolites such as palmitic acid and ceramide, and thereby prevented fructose-induced ISC cycle arrest. AS-IV’s therapeutic efficacy was validated across <i>Drosophila</i>, murine intestinal organoids, and mice, where treatment consistently reversed high-fructose-induced intestinal metabolic senescence phenotypes, restored ISC proliferation, and preserved ISC homeostasis. These findings indicate that KHK is a previously unrecognized molecular target of AS-IV and reveal a conserved mechanism by which AS-IV modulates fructose metabolism to interfere with gut aging. Our results highlight its therapeutic potential in treating fructose-driven intestinal aging and associated metabolic disorders.</p><p >We discovered KHK as a novel target of Astragaloside IV, which alleviates fructose-induced intestinal metabolic senescence by binding to Asn261 and Ala226 residues in KHK.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1682–1699"},"PeriodicalIF":10.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective and Potent Peptide Binders of RNF43 for Wnt Signaling Inhibition","authors":"Sunhee Hwang,&nbsp;, ,&nbsp;Paula Flórez Salcedo,&nbsp;, ,&nbsp;Antonion Korcari,&nbsp;, ,&nbsp;John M. Nicoludis,&nbsp;, ,&nbsp;Estefania Martinez Valdivia,&nbsp;, ,&nbsp;Lingling Peng,&nbsp;, ,&nbsp;Aaron T. Balana,&nbsp;, ,&nbsp;Justin Mak,&nbsp;, ,&nbsp;Christopher M. Crittenden,&nbsp;, ,&nbsp;Amin Famili,&nbsp;, ,&nbsp;Peter Liu,&nbsp;, ,&nbsp;David Castillo-Azofeifa,&nbsp;, ,&nbsp;Rami N. Hannoush,&nbsp;, ,&nbsp;Stephen E. Miller,&nbsp;, ,&nbsp;Christina I. Schroeder,&nbsp;, and ,&nbsp;Xinxin Gao*,&nbsp;","doi":"10.1021/acscentsci.5c00744","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00744","url":null,"abstract":"<p >The Wnt/β-catenin pathway is critical in human tumor progression. Cell-surface transmembrane E3 ubiquitin ligase ring finger 43 negatively regulates Wnt signaling through ubiquitination of Wnt coreceptor Frizzled. Aberrant Wnt signaling through inactivating mutations of RNF43 has been identified in various forms of cancers, highlighting its significance in tumor biology. However, the precise mechanism underlying the function of RNF43 remains elusive, largely due to the absence of selective molecular tools allowing for detection or manipulation of endogenous RNF43. Here we present a series of disulfide-constrained peptides, including GUR-1.6.12.2, which exhibit high affinity and specificity against RNF43. GUR-1.6.12.2 can be used as a valuable research tool to delineate RNF43 activity in various contexts. We showcased its application in immunofluorescence, where RNF43 was detected in intestinal crypts using biotinylated GUR-1.6.12.2. We then combined experimental and computational structural approaches to propose a model of GUR-1.6.12.2 and its binding to RNF43. Importantly, we generated a functional RNF43-DCP by producing a hexavalent GUR-1.6.12.2 molecule, which exhibited inhibitory activity against Wnt signaling in cells by competing with R-spondin, a RNF43 ligand that potentiates signaling. The RNF43 binders presented here offer new opportunities for the research and development of anticancer therapies targeting Wnt signaling with improved selectivity.</p><p >Here we report the development of selective and potent disulfide-constrained peptide binders of RNF43. The functional hexavalent peptide inhibits Wnt signaling in cells by competing with R-spondin.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1670–1681"},"PeriodicalIF":10.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00744","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Illuminating Mitochondrial Dynamics: Ultrahigh Labeling Stability Probe for Long-Term SIM Super-Resolution Imaging of Mitochondria","authors":"Xiangpeng Lin,&nbsp;, ,&nbsp;Xuelei Pang,&nbsp;, ,&nbsp;Yue Huang,&nbsp;, ,&nbsp;Xinxin Duan,&nbsp;, ,&nbsp;Yunfei Wei,&nbsp;, ,&nbsp;Ning Jing,&nbsp;, ,&nbsp;Meng Zhang*,&nbsp;, and ,&nbsp;Yu-Hui Zhang*,&nbsp;","doi":"10.1021/acscentsci.5c00695","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00695","url":null,"abstract":"<p >Delineating intricate mitochondrial dynamic changes over extended time scales through combined fluorescent probes and super-resolution microscopy is pivotal for deciphering the pathogenesis of mitochondrial-related diseases. However, a major challenge lies in the scarcity of probes that simultaneously exhibit robust labeling stability, exceptional photostability, and minimal cytotoxicity. Herein, rational design and screening yielded a novel covalent mitochondrial probe, HZ Mito Red. Due to its exceptional covalent labeling efficiency, HZ Mito Red exhibits superior mitochondrial labeling stability, with a 10-fold improvement compared to Mito Tracker Red (MTR). Furthermore, it exhibits remarkable photostability, retaining over 80% fluorescence after 300 SIM images, and negligible phototoxicity, preserving mitochondrial integrity even after 400 SIM images of continuous imaging. These advantageous properties facilitated the pioneering of high signal-to-noise, long-term dynamic SIM super-resolution imaging of mitochondria during ferroptosis, apoptosis, and autophagy, achieving unprecedented detailed delineation of mitochondrial morphology. Additionally, engineered for multichannel mitochondrial imaging, HZ Mito Deep Red mirrors the exceptional labeling stability of HZ Mito Red, achieving near-phototoxicity-free dynamic tracking with 60% fluorescence retention after 300 SIM images. Significantly, both HZ Mito Red and HZ Mito Deep Red are compatible with cell immunofluorescence staining. This study provides a robust and versatile tool for the in-depth analysis of mitochondrial dynamics in disease states.</p><p >Novel covalent mitochondrial fluorescent probes with excellent labeling stability, high photostability, and low phototoxicity allow long-term SIM super-resolution dynamic imaging of mitochondria.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1700–1714"},"PeriodicalIF":10.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-Driven Prediction of Enantioselectivity for the Sharpless Asymmetric Dihydroxylation: Model Development and Experimental Validation","authors":"Blake E. Ocampo,&nbsp;, ,&nbsp;Bilal Altundas,&nbsp;, ,&nbsp;Matthew J. Bock,&nbsp;, ,&nbsp;Sara Feiz,&nbsp;, and ,&nbsp;Scott E. Denmark*,&nbsp;","doi":"10.1021/acscentsci.5c00900","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00900","url":null,"abstract":"<p >The Sharpless asymmetric dihydroxylation remains a key transformation in chemical synthesis, yet its success hides unexpected cases of lower selectivity. A chemoinformatic workflow was developed to allow data-driven analysis of the reaction. A database of 1007 reactions employing AD-mix α and β was curated from the literature, and an alignment-dependent, fragment-based featurization of alkenes was implemented for modeling. This platform converged on machine learning models capable of predicting the magnitude of enantioselectivity for multiple alkene classes, achieving <i>Q</i>²_F3 values ≥ 0.8, test <i>r</i>² values ≥ 0.7 and mean absolute errors (MAE) ≤ 0.3 kcal/mol. The features of alkenes contributing to model performance were assessed with SHapley Additive exPlanations (SHAP) analysis to gather insight into factors underlying predictions. Experimental validation demonstrated that the models could achieve meaningful predictions on out-of-sample alkenes.</p><p >A data-driven approach was designed to analyze the Sharpless Asymmetric Dihydroxylation for insight into factors driving enantioselectivity and high-performing models were experimentally validated</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1640–1650"},"PeriodicalIF":10.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recruitment of Aβ into α-Synuclein Condensates Catalyzes Primary Nucleation of α-Synuclein Aggregation","authors":"Owen M. Morris,&nbsp;Alexander Röntgen,&nbsp;Zenon Toprakcioglu*,&nbsp;Mariana Cali,&nbsp;Samuel Dada and Michele Vendruscolo*,&nbsp;","doi":"10.1021/acscentsci.5c00614","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00614","url":null,"abstract":"<p >The aggregation of amyloid-β (Aβ) and α-synuclein (αSyn) is linked to Alzheimer’s and Parkinson’s diseases, with growing evidence suggesting possible interactions between Aβ and αSyn in the pathology of these neurodegenerative conditions. In this context, the recent observation that protein aggregation into amyloid fibrils may take place within liquid condensates generated through liquid–liquid phase separation prompts the question of how amyloidogenic proteins interact with each other, and more specifically whether Aβ can influence the overall phase behavior of αSyn or vice versa. To address this question, we investigated the interplay between Aβ40, the most abundant form of Aβ, with αSyn. We found that monomeric Aβ40 is sequestered into αSyn condensates, where it enhances heterogeneous primary nucleation, and accelerates the aggregation of αSyn within the liquid condensates. Using a chemical kinetics framework, we further showed that this liquid-to-solid transition is not significantly affected by adding preformed Aβ40 fibrillar seeds, further indicating that monomeric Aβ40 specifically enhances the primary nucleation of αSyn within the condensed phase. These findings identify some of the key mechanistic processes underlying amyloid aggregation within liquid condensates, prompting further investigations into the possible role of Aβ and αSyn cocondensation interactions in the onset and progression of neurodegenerative disorders.</p><p >This study reports the effect of amyloid-β (Aβ) on the phase transitions of α-synuclein (αSyn), showing that Aβ40 is recruited into αSyn condensates where it accelerates αSyn amyloid aggregation.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1481–1491"},"PeriodicalIF":10.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesoporous Potassium-Based Metal–Organic Framework as a Drug Carrier","authors":"Bo Fang,&nbsp;, ,&nbsp;Tianyu Shan,&nbsp;, ,&nbsp;Sailing Chen,&nbsp;, ,&nbsp;Fei Pan,&nbsp;, ,&nbsp;Xue Yang,&nbsp;, ,&nbsp;Ding Xiao,&nbsp;, ,&nbsp;Feihe Huang*,&nbsp;, and ,&nbsp;Zhengwei Mao*,&nbsp;","doi":"10.1021/acscentsci.5c00904","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00904","url":null,"abstract":"<p >To date, the number of reported mesoporous metal–organic frameworks (MOFs) remains limited. Herein, we report a novel mesoporous potassium-based MOF (K-MOF), designated as <b>KMOF-1</b>, whose precise structure was determined by using single-crystal X-ray diffraction. <b>KMOF-1</b> used 18-crown-6 units as the organic linkers and potassium ions as the metal centers, forming a framework topological structure with interconnected four-membered rings. The specific surface area of the synthesized <b>KMOF-1</b> was determined by the Brunauer–Emmett–Teller method, which showed a high specific surface area of 1034 m²/g. <b>KMOF-1</b> was demonstrated to be a promising drug carrier, exhibiting encapsulation capabilities for various drugs and maintaining stability for a defined period under simulated physiological conditions. Using vascular endothelial growth factor (VEGF) aptamers as model drugs, we further confirmed the effective loading of VEGF aptamers in <b>KMOF-1</b> (<b>KMOF-1@VEGF</b>) and the ability of <b>KMOF-1@VEGF</b> to release VEGF aptamers responsively in acidic environments. Additionally, in vitro studies showed that <b>KMOF-1</b> protected VEGF aptamers from degradation by nucleases, allowing them to be effectively taken up by cells. This novel K-MOF, with its biocompatible metal centers, mesoporous channels, and demonstrated efficacy as a drug carrier, offers a significant advancement in developing MOF-based drug delivery systems.</p><p >The mesoporous structure, high drug loading capacity, and biocompatibility of <b>KMOF-1</b> make it a promising candidate for biomedical applications.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1651–1658"},"PeriodicalIF":10.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}