ACS Publications最新文献

{"title":"How to Train a Postprocessor for Tandem Mass Spectrometry Proteomics Database Search While Maintaining Control of the False Discovery Rate.","authors":"Jack Freestone, Lukas Käll, William Stafford Noble, Uri Keich","doi":"10.1021/acs.jproteome.4c00742","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00742","url":null,"abstract":"<p><p>Decoy-based methods are a popular choice for the statistical validation of peptide detection in tandem mass spectrometry and proteomics data. Such methods can achieve a substantial boost in statistical power when coupled with postprocessors such as Percolator that use auxiliary features to learn a better-discriminating scoring function. However, we recently showed that Percolator can struggle to control the false discovery rate (FDR) when reporting the list of discovered peptides. To address this problem, we introduce Percolator-RESET, which is an adaptation of our recently developed RESET meta-procedure to the peptide detection problem. Specifically, Percolator-RESET fuses Percolator's iterative SVM training procedure with RESET's general framework to provide valid false discovery rate control. Percolator-RESET operates in both a standard single-decoy mode and a two-decoy mode, with the latter requiring the generation of two decoys per target. We demonstrate that Percolator-RESET controls the FDR in both modes, both theoretically and empirically, while typically reporting only a marginally smaller number of discoveries than Percolator in the single-decoy mode. The two-decoy mode is marginally more powerful than both Percolator and the single-decoy mode and exhibits less variability than the latter.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750274","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}

{"title":"Design and Fabrication of Bioactive and Antibacterial LIPSS Surfaces on Titanium Alloy by Femtosecond Laser.","authors":"Yanping Yuan, Kun Zhou, Yang Wang","doi":"10.1021/acsabm.5c00064","DOIUrl":"https://doi.org/10.1021/acsabm.5c00064","url":null,"abstract":"<p><p>A titanium alloy is widely used in implants for its excellent mechanical properties and corrosion resistance. However, the bonding strength between a titanium alloy and bone tissue is low, and the bacterial adhesion is easily triggered on the implant surface, which may cause the failure of implants. Therefore, surface modification is necessary to improve the biological activity and antibacterial properties. In this work, four different types of laser-induced periodic surface structure (LIPSS) surfaces are designed and fabricated on the TiNi alloy by a femtosecond laser according to the size of MC3T3-E1 mouse embryonic osteoblasts. The in vitro osteogenic activity of the LIPSS surface is investigated. It is found that the LIPSS helps improve the in vitro osteogenic activity, and bonelike apatite tends to deposit and distribute on the LIPSS. The biological activity and antibacterial activity of the LIPSS surface are evaluated through cell culture experiments and <i>Escherichia coli</i> culture experiments. It is demonstrated that the horizontal LIPSS sample with a width of 30 μm has the highest cell proliferation rate (142.5% after 1 day, 132.3% after 3 days) and a good antibacterial rate (50.2%). These results provide guidance for the application of the LIPSS in biocompatibility and antibacterial aspects.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750117","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}

{"title":"Copper Nanoparticle Decorated Multilayer Nanocoatings for Controlled Nitric Oxide Release and Antimicrobial Performance with Biosafety.","authors":"Hyejoong Jeong, Jiwoong Heo, Moonhyun Choi, Jinkee Hong","doi":"10.1021/acs.biomac.4c01798","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01798","url":null,"abstract":"<p><p>Biomedical device-related bacterial infections are a leading cause of mortality, and traditional antibiotics contribute to resistance. Various surface modification strategies have been explored, but effective clinical solutions remain limited. This study introduces a novel antibacterial nanocoating with copper nanoparticles (CuNPs) that triggers localized nitric oxide (NO) release. The multilayered nanocoating is created using branched polyethylenimine (BPEI) and poly(acrylic acid) (PAA) via a Layer-by-Layer assembly method. CuNP-decorated nanocoatings are formed by reducing copper ions coordinated with amine/carboxylic acid groups. In a physiological environment, CuNPs oxidize to Cu(I), promoting NO release from endogenous NO donors. The nanocoating's thickness is adjustable to regulate amount of CuNPs and NO flux. The optimal thickness for effective NO release against <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> is identified, preventing microbial adhesion and biofilm formation. Importantly, the coating remains cytocompatible due to minimal CuNPs, physiological NO levels, and stable coating properties under physiological conditions.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750155","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}

{"title":"Synthesis of a New Purine Analogue Class with Antifungal Activity and Improved Potency against Fungal IP_3-4K.","authors":"Desmarini Desmarini, Daniel Truong, Pooja Sethiya, Guizhen Liu, Bethany Bowring, Henning Jessen, Hue Dinh, Amy K Cain, Philip E Thompson, Julianne T Djordjevic","doi":"10.1021/acsinfecdis.4c00975","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00975","url":null,"abstract":"<p><p>New antifungals are urgently needed to treat deadly fungal infections. Targeting the fungal inositol polyphosphate kinases IP_3-4K (Arg1) and IP₆K (Kcs1) is a promising strategy as it has been validated genetically to be crucial for fungal virulence but never pharmacologically. We now report the synthesis of <b>DT-23</b>, an analogue of <i>N</i>2-(<i>m</i>-trifluorobenzylamino)-<i>N</i>6-(<i>p</i>-nitrobenzylamino)purine (<b>TNP</b>), and demonstrate that it more potently inhibits recombinant Arg1 from the priority pathogen <i>Cryptococcus neoformans</i> (<i>Cn</i>) (IC₅₀ = 0.6 μM) than previous analogues (IC₅₀ = 10-30 μM). <b>DT-23</b> also inhibits recombinant Kcs1 with similar potency (IC₅₀ = 0.68 μM) and Arg1 and Kcs1 activity <i>in vivo</i>. Unlike previous analogues, <b>DT-23</b> inhibits fungal growth (MIC₅₀ = 15 μg/mL) and only 1.5 μg/mL synergizes with Amphotericin B to kill <i>Cn in vitro</i>. <b>DT-23</b>/Amphotericin B is also more protective against <i>Cn</i> infection in an insect model compared to each drug alone. Transcription profiling shows that <b>DT-23</b> impacts early stages in IP synthesis and cellular functions impacted by IPK gene deletion, consistent with its targeted effect. This study establishes the first pharmacological link between inhibiting IPK activity and antifungal activity, providing tools for studying IPK function and a foundation to potentially develop a new class of antifungal drug.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750249","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}

{"title":"Strong Coupling Møller-Plesset Perturbation Theory.","authors":"Yassir El Moutaoukal, Rosario R Riso, Matteo Castagnola, Enrico Ronca, Henrik Koch","doi":"10.1021/acs.jctc.5c00055","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c00055","url":null,"abstract":"<p><p>Perturbative approaches are methods to efficiently tackle many-body problems, offering both intuitive insights and analysis of correlation effects. However, their application to systems where light and matter are strongly coupled is nontrivial. Specifically, the definition of suitable orbitals for the zeroth-order Hamiltonian represents a significant theoretical challenge. While reviewing previously investigated orbital choices, this work presents an alternative polaritonic orbital basis suitable for the strong coupling regime. We develop a quantum electrodynamical (QED) Møller-Plesset perturbation theory using orbitals obtained from the strong coupling QED Hartree-Fock. We assess the strengths and limitations of the different approaches with emphasis on frequency and coupling strength dispersions, intermolecular interactions and polarization orientational effects. The results show the essential role of using a consistent molecular orbital framework in order to achieve an accurate description of cavity-induced electron-photon correlation effects.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750262","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}

{"title":"Studies Related to the Proposed Biotransformation of Bohemamine D into the Co-occurring Marine Natural Product Spinoxazine B.","authors":"Liangguang Yi, Chan Guo, Qiao Yan, Martin G Banwell, Yu-Tao He, Ya-Jian Hu, Michelle L Coote, Zhipeng Pei, Li-Juan Yu, Jas S Ward, Steven E Bottle","doi":"10.1021/acs.jnatprod.5c00109","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00109","url":null,"abstract":"<p><p>The 1,3-oxazin-6-one-containing spinoxazines A and B (<b>2</b> and <b>3</b>, respectively) have been isolated from the marine-derived <i>Streptomyces spinoverrucosus</i> strain SNB-048 and, by another group, from the Solar Saltern-derived <i>Streptomyces</i> sp. KMF-004. Two distinct pathways have been proposed for the conversion of the co-occurring pyrrolizidine alkaloid bohemamine D (<b>1</b>) into compound <b>3</b>. Here, we report that the readily prepared compound <b>10</b>, which embodies the 2-hydroxy-1,2-dihydro-3<i>H</i>-pyrrol-3-one core of bohemamine D (<b>1</b>) and is the bis-<i>O</i>-methyl ether of the alkaloid discoipyrrole C, is converted into 1,3-oxazin-6-one <b>11</b> on heating at elevated temperatures in air. The mechanism of this conversion was studied using density functional theory and the biosynthetic implications of it are discussed. The photochemical reaction of compound <b>10</b> in the presence of oxygen is also detailed and, again, the possible biosynthetic implications of the resulting conversion are considered.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750267","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}

{"title":"Encapsulation of a Probiotic Bacterial Strain in a Biocompatible Iron(III) Fumarate Matrix.","authors":"Laura I FitzGerald, Ashley L Sutton, Cara M Doherty","doi":"10.1021/acsabm.4c01398","DOIUrl":"https://doi.org/10.1021/acsabm.4c01398","url":null,"abstract":"<p><p>The encapsulation of bacteria in metal-organic frameworks (MOFs) is being studied for use in biomedicine and bioremediation. However, biocompatibility could be improved, as much of the research focuses on ZIF-8 and <i>Escherichia coli</i>. MIL-88A, composed of fumaric acid and iron, offers a safer alternative. This study investigates encapsulation of the probiotic strain <i>Lactiplantibacillus plantarum</i> 299v in a nanocrystalline matrix via a simple one-pot synthesis. The encapsulated bacteria show improved stability in saline, lysozyme and pepsin compared to uncoated cells. These findings highlight the potential of the iron(III) fumarate matrix for bacterial protection and controlled release for biological applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750129","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}

{"title":"Development of Thermostable and Immunogenic Block Copolymer Nanoparticles (BNPs) for mRNA Delivery.","authors":"Jian Hang Lam, Gaurav Sinsinbar, Ser Yue Loo, Teck Wan Chia, Yan Jun Lee, Jing Yi Fong, Yoong Eng Chia, Rocco Roberto Penna, Shaoqiong Liu, Steve Pascolo, Katherine Schultheis, Madhavan Nallani","doi":"10.1021/acs.biomac.4c01820","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01820","url":null,"abstract":"<p><p>Combining an amphiphilic block copolymer polybutadiene-<i>b</i>-poly(ethylene glycol) (PBD-<i>b</i>-PEO), an ionizable lipid, a helper lipid, and cholesterol produces thermostable BNPs. Luciferase mRNA-BNPs can be stored for over 1 year at 4 °C with no evidence of degradation to the mRNA or nanocarrier. In vivo, mRNA-BNPs exhibit a greater affinity for secondary lymphoid organs than mRNA-lipid nanoparticles (LNPs) and are efficiently taken up by macrophages and dendritic cells. Freshly fabricated ovalbumin (OVA) mRNA-BNPs elicit robust OVA-specific IgG and functional memory CD8⁺ T cells that persist for at least 5 months. Immunogenicity remains intact after 24 weeks of storage at 4 °C. Anti-PEG antibodies are not boosted by the repeated administration of mRNA-BNPs, unlike mRNA-LNPs. Syrian hamsters vaccinated with SARS-CoV-2 spike mRNA-BNPs are protected against weight loss associated with infection and potently suppress pulmonary viral loads. Protective efficacy is comparable to that conferred by a Comirnaty biosimilar. Cumulatively, mRNA-BNPs are thermostable, immunogenic and possess the potential for clinical application.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750167","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}

{"title":"Photodynamic Inactivation of <i>Staphylococcus aureus</i> and Biomolecules by Free and Encapsulated Indium(III) Phthalocyanines in PHB Nanoparticles: The Influence of the Position of the Coumarin Group.","authors":"Julyana Noval de Souza Ferreira, Barbara Silva Figueiredo, Vannyla Viktória Viana Vasconcelos, Antony Luca Luna Vieira de Abreu, Sheila Souza da Silva Ribeiro, Esra Nur Kaya, Mustafa Bulut, Joselito Nardy Ribeiro, Mahmut Durmuş, André Romero da Silva","doi":"10.1021/acs.biomac.4c00862","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c00862","url":null,"abstract":"<p><p>Antimicrobial photodynamic therapy (APDT) is a promising alternative to inactivating resistant microorganisms. Metallic phthalocyanines (Pc) substituted with coumarin groups exhibit favorable photophysical properties for APDT; however, their hydrophobicity limits administration. This study investigates indium(III) Pc substituted with 7-oxy-3-(3',4',5'-trimethoxyphenyl)coumarin at nonperipheral (<b>3nInOAc</b>) and peripheral (<b>4nInOAc</b>) positions, both in their free form and encapsulated in polyhydroxybutyrate nanoparticles, for the photodynamic inactivation of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and methicillin-susceptible <i>Staphylococcus aureus</i> (MSSA) bacteria. The photodynamic activity was also assessed through the photooxidation of tryptophan and bovine serum albumin. Theoretical calculations and molecular docking were performed to corroborate the experimental results, investigating the influence of molecular structure on the photodynamic and antimicrobial performance of Pc-loaded nanoparticles as well as their nanoparticulate properties. Overall, both free and encapsulated Pc were capable of photooxidizing biomolecules and exhibited moderate antimicrobial activity, with <b>4nInOAc</b> demonstrating superior efficacy, achieving an average reduction of 2 logs (99%) in MSSA and MRSA colonies.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750175","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}

{"title":"Investigation of a Palbociclib and Naringin Co-Amorphous System to Ameliorate Anticancer Potential: Insights on <i>In Silico Modeling,</i> Physicochemical Characterization, <i>Ex Vivo</i> Permeation, and <i>In Vitro</i> Efficacy.","authors":"Tanmoy Kanp, Anish Dhuri, Mayur Aalhate, Bharath Manoharan, Khushi Rode, Sharon Munagalasetty, Akella V S Sarma, Prasad Kshirsagar, Nagula Shankaraiah, Vasundhara Bhandari, Bhagwati Sharma, Pankaj Kumar Singh","doi":"10.1021/acs.molpharmaceut.4c01224","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01224","url":null,"abstract":"<p><p>Palbociclib (PCB), categorized as a BCS class II drug, is characterized by low aqueous solubility. The drug's limited aqueous solubility and poor dissolution rate pose significant challenges, potentially affecting its absorption and overall therapeutic efficacy. Co-amorphous (CAM) systems have been extensively investigated as a potential solution to overcome the issue of poor water solubility in numerous active pharmaceutical ingredients. This research study hypothesized that the coamorphization process involving the compounds PCB and naringin (NG) would lead to an increase in the aqueous solubility of PCB. Additionally, it was proposed that this process would also enhance the anticancer impact of PCB since NG is recognized for its pharmacological impact on breast cancer cells. <i>In silico</i> studies, it was revealed that PCB could interact with NG via hydrogen bonding. Furthermore, the prepared CAM (PCB-NG-CAM) system using PCB and NG was characterized by PXRD, DSC, FTIR, Raman spectroscopy, solid-state ¹³C nuclear magnetic resonance, and SEM. PCB-NG-CAM exhibited a significant increase in solubility, dissolution rate, and intestinal permeation compared to crystalline PCB. Furthermore, PCB-NG-CAM exhibited excellent physical stability at 40 °C/75% RH for up to 3 months. In addition, PCB-NG-CAM showed superior <i>in vitro</i> efficacy on MDA-MB-231 triple-negative breast cancer cell lines. PCB-NG-CAM resulted in a 2.24 times higher apoptosis rate and a 1.6 times greater ROS production than free PCB. Additionally, the inhibitory effect on cell migration and alterations in MMP was more pronounced in cells treated with PCB-NG-CAM. Therefore, this study indicated that PCB-NG-CAM has the potential to significantly improve the oral administration, solubility, and therapeutic efficacy of PCB.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750283","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}