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Lab to Fab Process Using Ablation Lasers: A Lightweight, Flexible, and Biocompatible Microheater for Wearable Therapy Applications. 使用烧蚀激光的实验室到Fab工艺:用于可穿戴治疗应用的轻质、柔性和生物相容性微加热器。
IF 4.7
ACS Applied Bio Materials Pub Date : 2025-10-17 DOI: 10.1021/acsabm.5c01263
Bhavani Prasad Yalagala, Tahereh Masalehdan, Changhao Ge, Mahmut Talha Kirimi, John Mercer, Morteza Amjadi Kolour, Hadi Heidari
{"title":"Lab to Fab Process Using Ablation Lasers: A Lightweight, Flexible, and Biocompatible Microheater for Wearable Therapy Applications.","authors":"Bhavani Prasad Yalagala, Tahereh Masalehdan, Changhao Ge, Mahmut Talha Kirimi, John Mercer, Morteza Amjadi Kolour, Hadi Heidari","doi":"10.1021/acsabm.5c01263","DOIUrl":"https://doi.org/10.1021/acsabm.5c01263","url":null,"abstract":"<p><p>Wearable thermal therapy has attained significant attention owing to its potential in various wearable and biomedical applications specifically targeted for accelerated wound healing using smart bandages. Here, in the current work, a large area, precision, and scalable fabrication methodology is proposed using an ultraviolet (UV)-based ablation laser as compared to conventional fabrication methods such as photolithography or printing. This laser-based approach is unique and offers rapid prototyping, superior material versatility, design flexibility, and minimal thermal damage to the emerging biocompatible polymer-based flexible substrates. A thin, flexible, and biocompatible microheater and an array (4 × 4) of diverse designs, including circular, hexagonal, and planar, were designed and fabricated on a gold-coated PAC substrate using the proposed ablation laser-based approach. Multiple heater sizes varying from small to extra-large were fabricated and are tailored for the targeted temperatures ranging from 30 °C to 100 °C for biomedical applications, especially wearable wound healing applications. Electrical and electrothermal characteristics revealed that the sheet resistance, thermal response, and response time vary with the structure and size of the microheaters. Further, mechanical flexibility and biocompatibility studies on the PAC, patterned gold electrodes, and polyimide substrate demonstrated excellent mechanical robustness and biocompatibility, clearly demonstrating its efficacy and ability for wearable and implantable applications. Finally, the proposed research paves the pathway for the fabrication of next-generation wearable and implantable biointegrated flexible microheater devices toward advanced thermal therapy solutions.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advanced Large DNA Manipulation Technologies for Constructing Microbial Cell Factories. 构建微生物细胞工厂的先进大型DNA操作技术。
IF 3.9 2区 生物学
ACS Synthetic Biology Pub Date : 2025-10-17 DOI: 10.1021/acssynbio.5c00539
Zubin Pan, Yi Wu
{"title":"Advanced Large DNA Manipulation Technologies for Constructing Microbial Cell Factories.","authors":"Zubin Pan, Yi Wu","doi":"10.1021/acssynbio.5c00539","DOIUrl":"https://doi.org/10.1021/acssynbio.5c00539","url":null,"abstract":"<p><p>Microbial cell factories play a pivotal role in the field of biomanufacturing. Enhancing their construction efficiency and product yield is essential for advancing synthetic biology and its industrial implementation. In recent years, the rapid development of large DNA manipulation technologies provided powerful support for cloning, assembling, delivering, and rearranging large DNA. This review hence systematically summarizes the core principles and recent advances in four categories of large DNA manipulation techniques. It highlights their key roles in access to complex biosynthetic gene clusters, constructing multigene biosynthetic pathways, introducing complex genetic modules into microbial chassis, structural rewiring, and modular reconstruction for metabolic network optimization. Furthermore, this review explores the emerging trend of large DNA manipulation technologies to advance microbial cell factories. This review is expected to serve as a technical reference for advancing large DNA manipulation technologies and extending their applications toward the construction of high-performance microbial cell factories.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Duplex Enzymatic Recombinase Amplification Assay Coupled with Lateral Flow Dipstick for Rapid Identification of Methicillin-Resistant Staphylococcus aureus. 双酶重组酶扩增法联合侧流试纸快速鉴定耐甲氧西林金黄色葡萄球菌。
IF 3.8 2区 医学
ACS Infectious Diseases Pub Date : 2025-10-17 DOI: 10.1021/acsinfecdis.5c00576
Arpasiri Srisrattakarn, Aroonwadee Chanawong, Orapan Sripichai, Jenjira Rujidamp, Neeranuch Maneenet, Nannapat Onsapiw, Thiwawan Bunleuhan, Aroonlug Lulitanond
{"title":"Duplex Enzymatic Recombinase Amplification Assay Coupled with Lateral Flow Dipstick for Rapid Identification of Methicillin-Resistant <i>Staphylococcus aureus</i>.","authors":"Arpasiri Srisrattakarn, Aroonwadee Chanawong, Orapan Sripichai, Jenjira Rujidamp, Neeranuch Maneenet, Nannapat Onsapiw, Thiwawan Bunleuhan, Aroonlug Lulitanond","doi":"10.1021/acsinfecdis.5c00576","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00576","url":null,"abstract":"<p><p>46 clinical isolates, 28 <i>nuc</i>-carrying and 18 <i>nuc</i>-negative isolates, and 23 <i>mecA</i>-carrying and 23 <i>mecA</i>-negative isolates were subjected to a developed duplex isothermal enzymatic recombinase amplification assay accompanied by a lateral flow assay (ERA-LFA) method for methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) detection. Additionally, 57 positive blood culture samples from patients were evaluated for preliminary testing. The sensitivity and specificity among the 46 clinical samples were 100% (28/28) and 88.9% (16/18), respectively, for <i>nuc</i> detection, and 100.0% (23/23 and 23/23) for <i>mecA</i> detection. For the 57 positive blood culture bottles, the ERA-LFA provided 100.0% (34/34) sensitivity and 95.7% (22/23) specificity for <i>nuc</i> detection and 96.5% specificity (55/57) for <i>mecA</i> detection. The detection limits of the ERA-LFA for the <i>nuc</i> and <i>mecA</i> genes were 1 and 10 CFU/reaction, respectively.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Improved Nucleoside (2'-Deoxy)Ribosyltransferases Maximize Enzyme Promiscuity while Maintaining Catalytic Efficiency. 改进的核苷(2'-脱氧)核糖基转移酶在保持催化效率的同时最大限度地提高酶的混杂性。
IF 3.8 2区 生物学
ACS Chemical Biology Pub Date : 2025-10-17 DOI: 10.1021/acschembio.5c00120
Peijun Tang, Greice M Zickuhr, Alison L Dickson, Christopher J Harding, Suneeta Devi, Tomas Lebl, David J Harrison, Rafael G da Silva, Clarissa M Czekster
{"title":"Improved Nucleoside (2'-Deoxy)Ribosyltransferases Maximize Enzyme Promiscuity while Maintaining Catalytic Efficiency.","authors":"Peijun Tang, Greice M Zickuhr, Alison L Dickson, Christopher J Harding, Suneeta Devi, Tomas Lebl, David J Harrison, Rafael G da Silva, Clarissa M Czekster","doi":"10.1021/acschembio.5c00120","DOIUrl":"https://doi.org/10.1021/acschembio.5c00120","url":null,"abstract":"<p><p>Nucleoside analogues have been extensively used to treat viral and bacterial infections and cancer for more than 60 years. However, their chemical synthesis is complex and often requires multiple steps and a dedicated synthetic route for every new nucleoside to be produced. Wild type nucleoside 2'-deoxyribosyltransferase enzymes are promising for biocatalysis. Guided by the structure of the enzyme from the thermophilic organism <i>Chroococcidiopsis thermalis</i> PCC 7203 (<i>Ct</i>NDT) bound to the ribonucleoside analogue Immucillin-H, we designed mutants of <i>Ct</i>NDT and the psychrotolerant <i>Bacillus psychrosaccharolyticus</i> (<i>Bp</i>NDT) to improve catalytic efficiency with 3'-deoxynucleosides and ribonucleosides, while maintaining nucleobase promiscuity to generate over 100 distinct nucleoside products. Enhanced catalytic efficiency toward ribonucleosides and 3'-deoxyribonucleosides occurred via gains in turnover rate, rather than improved substrate binding. We determined the crystal structures of two engineered variants as well as kinetic parameters with different substrates, unveiling molecular details underlying their expanded substrate scope. Our rational approach generated robust enzymes and a roadmap for reaction conditions applicable to a wide variety of substrates.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Using Topology to Predict Electrides in the Solid State. 利用拓扑学预测固态中的电子。
IF 2.8 2区 化学
The Journal of Physical Chemistry A Pub Date : 2025-10-17 DOI: 10.1021/acs.jpca.5c05317
Stefano Racioppi, Eva Zurek
{"title":"Using Topology to Predict Electrides in the Solid State.","authors":"Stefano Racioppi, Eva Zurek","doi":"10.1021/acs.jpca.5c05317","DOIUrl":"https://doi.org/10.1021/acs.jpca.5c05317","url":null,"abstract":"<p><p>Electrides are characterized by electron density highly localized in interstitial sites, which do not coincide with direct interatomic contacts. The rigorous quantum mechanical definition of electrides is based upon topological criteria derived from the electron density, and in particular the presence of non-nuclear attractors (NNAs). We employ these topological criteria in combination with crystal structure prediction methods (the XtalOpt evolutionary algorithm), to accelerate the discovery of crystalline electrides at ambient and nonambient pressures. The localization and quantification of NNAs is used as the primary discriminator for the electride character of a solid within a multiobjective evolutionary structure search. We demonstrate the reliability of this approach through a comprehensive crystal structure prediction study of Ca<sub>5</sub>Pb<sub>3</sub> at 20 GPa, a system previously theorized to exhibit electride character under compression. Our strategy could predict, and sort on-the-fly, several unknown low-enthalpy phases that possess NNAs in interstitial loci, such as the newly discovered <i>P</i>4/<i>mmm</i> structure. These results demonstrate how evolutionary algorithms, guided by rigorous topological descriptors, can be relied upon to effectively survey complex phases to find new electride candidates.</p>","PeriodicalId":59,"journal":{"name":"The Journal of Physical Chemistry A","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cryo-EM Structure of the Cyclase Domain and Evaluation of Substrate Channeling in a Bifunctional Class II Terpene Synthase. 双功能II类萜烯合成酶环化酶域的低温电镜结构和底物通道的评价。
IF 3 3区 生物学
Biochemistry Biochemistry Pub Date : 2025-10-17 DOI: 10.1021/acs.biochem.5c00509
Matthew N Gaynes, Kollin Schultz, Eliott S Wenger, Trey A Ronnebaum, Ronen Marmorstein, David W Christianson
{"title":"Cryo-EM Structure of the Cyclase Domain and Evaluation of Substrate Channeling in a Bifunctional Class II Terpene Synthase.","authors":"Matthew N Gaynes, Kollin Schultz, Eliott S Wenger, Trey A Ronnebaum, Ronen Marmorstein, David W Christianson","doi":"10.1021/acs.biochem.5c00509","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00509","url":null,"abstract":"<p><p>Copalyl diphosphate synthase from <i>Penicillium verruculosum</i> (PvCPS) is a bifunctional class II terpene synthase containing a prenyltransferase that produces geranylgeranyl diphosphate (GGPP) and a class II cyclase that utilizes GGPP as a substrate to generate the bicyclic diterpene copalyl diphosphate. Various stereoisomers of copalyl diphosphate establish the greater family of labdane natural products, many of which have environmental and medicinal impact. Understanding structure-function relationships in class II diterpene synthases is crucial for guiding protein engineering campaigns aimed at the generation of diverse bicyclic diterpene scaffolds. However, only a limited number of structures are available for class II cyclases from bacteria, plants, and humans, and no structures are available for a class II cyclase from a fungus. Further, bifunctional class II terpene synthases have not been investigated with regard to substrate channeling between the prenyltransferase and the cyclase. Here, we report the 2.9 Å-resolution cryo-EM structure of the 63-kD class II cyclase domain from PvCPS. Comparisons with bacterial and plant copalyl diphosphate synthases reveal conserved residues that likely guide the formation of the bicyclic labdane core but divergent catalytic dyads that mediate the final deprotonation step of catalysis. Substrate competition experiments reveal preferential GGPP transit from the PvCPS prenyltransferase to the cyclase, even when the enzymes are prepared as separate constructs. These results are consistent with a model in which transient prenyltransferase-cyclase association facilitates substrate channeling due to active-site proximity.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ultrathin Graphene Oxide Sheets Wrapped MoO2 Nanoparticles with Molecule Enrichment Function for Sensitive SERS Detection. 具有分子富集功能的超薄氧化石墨烯包裹MoO2纳米颗粒用于灵敏的SERS检测。
IF 6.7 1区 化学
Analytical Chemistry Pub Date : 2025-10-17 DOI: 10.1021/acs.analchem.5c04809
Na Li, Jiajia Song, Penghui Wei, Muhammad Usman Amin, Haibin Tang, Ganhong Zheng, Meiling Wang, Yongqing Ma, Yupeng Yuan, Chuhong Zhu
{"title":"Ultrathin Graphene Oxide Sheets Wrapped MoO<sub>2</sub> Nanoparticles with Molecule Enrichment Function for Sensitive SERS Detection.","authors":"Na Li, Jiajia Song, Penghui Wei, Muhammad Usman Amin, Haibin Tang, Ganhong Zheng, Meiling Wang, Yongqing Ma, Yupeng Yuan, Chuhong Zhu","doi":"10.1021/acs.analchem.5c04809","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c04809","url":null,"abstract":"<p><p>Benefiting from their low price, high performance stability, and moderate-to-high detection sensitivity, surface-enhanced Raman scattering (SERS) substrates made of noble metal-free materials have received much attention in the past few years. Improving the SERS sensitivity of non-noble metal materials is of great significance. Here, we propose a strategy of combining ultrathin graphene oxide (GO) sheets with plasmonic non-noble metal materials to enhance SERS sensitivity. By leveraging the adsorption property of GO and plasmonic hotspots of MoO<sub>2</sub> nanoparticles (MoO<sub>2</sub>-NPs), the enrichment of target molecules around hotspots can be realized, thereby achieving high detection sensitivity. Highly surface-roughened plasmonic MoO<sub>2</sub> nanospheres are wrapped by ultrathin-GO sheets, forming an ultrathin-GO/MoO<sub>2</sub>-NP hybrid. GO sheets with a huge specific surface area and high adsorption ability can trap analyte molecules in the locations near or in hotspots of MoO<sub>2</sub>-NPs. A uniform film of ultrathin-GO-wrapped MoO<sub>2</sub>-NPs shows a high enhancement factor of ∼1.12 × 10<sup>8</sup> and good spectral homogeneity (relative standard deviation, RSD = 9.7%). The detectable concentration limit for rhodamine 6G molecules is ∼10 pM, demonstrating high SERS sensitivity. In addition, the ultrathin-GO/MoO<sub>2</sub>-NP hybrid also exhibits excellent structural and chemical stabilities. The fabricated GO/MoO<sub>2</sub>-NP hybrid has promising applications in the SERS-based detection of trace chemical molecules.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiplexed Nanoparticle Protein Corona Enables Accurate and Precise Deep Plasma Proteomics. 复用纳米粒子蛋白电晕使准确和精确的深度血浆蛋白质组学。
IF 3.6 2区 生物学
Journal of Proteome Research Pub Date : 2025-10-17 DOI: 10.1021/acs.jproteome.5c00729
Ting Huang, Jian Wang, Alexey Stukalov, Simion Kreimer, Xiaoyan Zhao, Lee S Cantrell, Xiaoyuan Zhou, Adam Brewer, Giang Ho, Fredric Murolo, Kevin Quach, Mike Figa, Seth Just, Gabriel Castro, Eltaher Elgierari, Ryan W Benz, Khatereh Motamedchaboki, Serafim Batzoglou, Omid C Farokhzad, Jennifer E Van Eyk, Asim Siddiqui
{"title":"Multiplexed Nanoparticle Protein Corona Enables Accurate and Precise Deep Plasma Proteomics.","authors":"Ting Huang, Jian Wang, Alexey Stukalov, Simion Kreimer, Xiaoyan Zhao, Lee S Cantrell, Xiaoyuan Zhou, Adam Brewer, Giang Ho, Fredric Murolo, Kevin Quach, Mike Figa, Seth Just, Gabriel Castro, Eltaher Elgierari, Ryan W Benz, Khatereh Motamedchaboki, Serafim Batzoglou, Omid C Farokhzad, Jennifer E Van Eyk, Asim Siddiqui","doi":"10.1021/acs.jproteome.5c00729","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00729","url":null,"abstract":"<p><p>The Proteograph Product Suite, a multiplexed nanoparticle (NP) protein corona-based workflow, substantially improves the depth of detection of proteins by mass spectrometry (MS) by compressing the dynamic range of protein abundances. Here, we evaluate its quantitative performance and suitability for large-scale studies. Using multispecies spike-in experiments, we assessed fold change accuracy, linearity, precision, and the lower limit of quantification (LLOQ) across multiple MS platforms. Combined with the Orbitrap Astral MS, the Proteograph XT assay enabled identification of more than 7,000 plasma proteins. In mixed-species dilution experiments, fold change accuracy was preserved, with Proteograph quantifying 3.5 times more proteins than the Neat plasma workflow at the same fold change error threshold. Similar accuracy was observed with the Orbitrap Exploris 480 MS, and we also demonstrate that different proteome backgrounds do not impact the accuracy. Data produced with NPs from the four distinct NP batches (each supporting >100,000 assays) showed only a 4% increase in protein intensity CV across batches. Together, these results demonstrate that the Proteograph Product Suite provides depth as well as quantitative accuracy and precision to power new biomarker discovery and biological understanding in population-scale plasma proteomics cohorts.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of β-Carboline Derivatives Reveals a High Barrier to Resistance and Potent Activity against Ring-Stage and DHA-Induced Dormant Plasmodium falciparum. β-卡波林衍生物的特性揭示了对环期和dha诱导的休眠恶性疟原虫的高抗性屏障和有效活性。
IF 3.8 2区 医学
ACS Infectious Diseases Pub Date : 2025-10-17 DOI: 10.1021/acsinfecdis.5c00714
Reagan S Haney, Joshua H Butler, Lyric A Wardlaw, Emilio F Merino, Victoria Mendiola, Caitlin A Cooper, Jopaul Mathew, Patrick K Tumwebaze, Philip J Rosenthal, Roland A Cooper, Dennis E Kyle, Zaira Rizopoulos, Delphine Baud, Stephen Brand, Maxim Totrov, Paul R Carlier, Maria Belen Cassera
{"title":"Characterization of β-Carboline Derivatives Reveals a High Barrier to Resistance and Potent Activity against Ring-Stage and DHA-Induced Dormant <i>Plasmodium falciparum</i>.","authors":"Reagan S Haney, Joshua H Butler, Lyric A Wardlaw, Emilio F Merino, Victoria Mendiola, Caitlin A Cooper, Jopaul Mathew, Patrick K Tumwebaze, Philip J Rosenthal, Roland A Cooper, Dennis E Kyle, Zaira Rizopoulos, Delphine Baud, Stephen Brand, Maxim Totrov, Paul R Carlier, Maria Belen Cassera","doi":"10.1021/acsinfecdis.5c00714","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00714","url":null,"abstract":"<p><p>Malaria, caused by <i>Plasmodium falciparum</i>, remains a major global health challenge, with an estimated 263 million new infections and 597,000 deaths annually. Increasing resistance to current antimalarial drugs underscores the urgent need for new therapeutics that target novel pathways in the parasite. We previously reported a novel class of β-carboline antimalarials, exemplified by PRC1584, which demonstrated a favorable oral pharmacokinetic profile, <i>in vivo</i> efficacy in <i>Plasmodium berghei</i>-infected mice, and no cross-resistance with other antimalarials in various <i>P. falciparum</i> strains. In this study, we demonstrate that PRC1584 exhibits a high resistance barrier and retains potent activity against fresh Ugandan <i>P. falciparum</i> isolates. PRC1584, along with its more potent analog PRC1697, demonstrated strong <i>in vitro</i> potency against both actively proliferating ring stages and dihydroartemisinin-induced dormant stages. Additionally, our study demonstrated that PfKelch13-C580Y mutation was associated with an increased susceptibility to PRC1584, whereas PfKelch13-R549T and Pfcoronin-R100 K-E107V mutations were not associated with this effect. These findings underscore the therapeutic potential of this new \"irresistible\" compound class, support a possible novel mechanism of action, and suggest the future development of novel ACTs active against resistant parasites by targeting DHA dormancy, an essential survival mechanism of <i>P. falciparum</i>.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to "Quantitative Proteomics Combined with Phosphoproteome Reveal the Mechanism of the Density Sensing Regulator QseC in the Pathogenesis of Glaesserella parasuis". 修正“定量蛋白质组学联合磷酸化蛋白质组学揭示密度感应调节剂QseC在副猪小绿杆菌发病机制”。
IF 3.6 2区 生物学
Journal of Proteome Research Pub Date : 2025-10-17 DOI: 10.1021/acs.jproteome.5c00940
Xuefeng Yan, Yuhong Zhou, Xinyi Xiang, Congwei Gu, Mingde Zhao, Zehui Yu, Lvqin He
{"title":"Correction to \"Quantitative Proteomics Combined with Phosphoproteome Reveal the Mechanism of the Density Sensing Regulator QseC in the Pathogenesis of <i>Glaesserella parasuis</i>\".","authors":"Xuefeng Yan, Yuhong Zhou, Xinyi Xiang, Congwei Gu, Mingde Zhao, Zehui Yu, Lvqin He","doi":"10.1021/acs.jproteome.5c00940","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00940","url":null,"abstract":"","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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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