ACS Publications最新文献

{"title":"Voices in <i>Molecular Pharmaceutics</i>: Meet Dr. Wei Shao, Who Designs and Synthesizes Organic Functional Materials for Phototheranostics.","authors":"Wei Shao","doi":"10.1021/acs.molpharmaceut.5c01291","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c01291","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032441","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":"The Accommodation of Excess Charge in Binary Particle Lattices: A Many-Body Electrostatic Study.","authors":"Holly Avis, Eric B Lindgren, Benjamin Stamm, Elena Besley, Anthony J Stace","doi":"10.1021/acs.jpcb.5c04192","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c04192","url":null,"abstract":"<p><p>Many binary particle lattices are fabricated from charged particles on the assumption that the resultant structure is overall charge neutral. Results presented here from calculations on nine separate particle lattice types show that when both Coulomb and many-body multipole electrostatic interactions are taken into account, a lattice can actually gain stability by accommodating a small excess charge, either positive or negative. This effect arises from an increase in stability due to charge-induced multipole interactions, which serve to counteract destabilizing interactions that arise from repulsive Coulomb forces. It is shown that most of the lattice types considered could accommodate over 20% excess charge before becoming completely destabilized.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032485","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":"Correction to \"Self-Assembly of Accumulated Sphingolipids into Cytotoxic Fibrils in Globoid Cell Leukodystrophy and Their Inhibition by Small Molecules in Vitro\".","authors":"Sourav Kumar, Evelina Nikelshparg, Jana Pilátová, Ashim Paul, Vijay Kumar, Gil Koren, Dana Laor Bar-Yosef, Roy Beck, Henrik H Jensen, Daniel Segal","doi":"10.1021/acsnano.5c14040","DOIUrl":"https://doi.org/10.1021/acsnano.5c14040","url":null,"abstract":"","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":" ","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability Testing Reveals Photoselective Clipping of Heavy Chain C-Terminal Amino Acids That Leads to Fragmentation and Aggregation of an Antibody Fab Fragment.","authors":"Arka Mukhopadhyay, Kersti Karu, Paul A Dalby","doi":"10.1021/acs.molpharmaceut.5c00592","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00592","url":null,"abstract":"<p><p>We built a custom device to subject an antibody fragment A33 Fab to controlled stress conditions that combined pH, temperature, agitation, and LED-based light exposure in polypropylene microplates; to simulate the real-world challenges it may encounter during storage and transportation and to evaluate the key degradation routes in Fab formulations. We also explored the addition of Tween 80 as a surfactant and the impact of plate surface siliconisation. Monomer loss and fragmentation was monitored by size-exclusion chromatography, aggregate formation determined by changes in hydrodynamic radius in DLS, and chemical modifications identified through intact mass analysis by LC-MS, and N-terminal sequencing. The findings indicated that the light exposure conditions often interacted with other factors. In particular, light exposure in the UV to blue range led to chemical degradations that led to greater susceptibility to aggregation, particularly at elevated temperatures. Interestingly, while Tween 80 provided stabilization, particularly within siliconized plates, the presence of Tween 80 also promoted losses due to light exposure, consistent with previous findings that Tween 80 could act as a photosensitizer. Exposure of A33 Fab to light led to sequential losses of amino acids selectively from only the heavy chain C-terminus, indicating a photosensitive hotspot in that region of the Fab structure. These also suggested that photoinduced clipping of the heavy chain C-terminus increased the susceptibility of A33 Fab to fragmentation into heavy and light chains and aggregation, consistent with previous work in which flexibility-suppressing mutations of the hinge region decreased the aggregation kinetics.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032430","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":"Plasma Proteomic High-Performance Biomarkers for Early Diagnosis of Colorectal Cancer.","authors":"Haoran Jin, Kai Deng, Shaochong Qi, Zhaomin Deng, Lu Pu, Dongqin Xu, Weina Jing, Jin Wang, Zhiliang Zuo, Jinlin Yang, Hao Jiang","doi":"10.1021/acs.jproteome.5c00483","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00483","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a major global health challenge due to its high incidence, mortality, and low rate of early detection. Early diagnosis, targeting precancerous lesions (advanced adenomas) and early stage CRC (Tis and T1), is critical for improving patient survival. Given the limitations of current detection methods for advanced adenomas, developing high-performance early diagnostic strategies is essential for effective prevention. In this study, we employed the proximity extension assay using the Olink Explore 384 Cardiometabolic panel to identify 15 protein biomarkers, of which 8 proteins (MMP7, GDF15, REG1B, RNASE3, REG1A, TFF3, MFAP5, and TGM2) were incorporated into multiple machine learning models to diagnose colorectal advanced neoplasia (AN) in the discovery cohort (<i>n</i> = 80), achieving AUC values above 0.90. These models also demonstrated significant diagnostic performance, with AUCs greater than 0.88, for patients with AN or advanced adenomas in the validation cohort (<i>n</i> = 69). Furthermore, hub biomarkers (MMP7 and GDF15) were identified and subsequently validated along with an analysis of their clinical significance. Thus, our study identifies multiprotein signatures validated in two cohorts with high diagnostic performance for colorectal AN, contributing to the development of the clinical detection kit for noninvasive early diagnosis of CRC.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028554","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":"A Novel Lipid Microbubble Targeting E-Selectin for Ultrasound Molecular Imaging of Acute Kidney Injury in Rats.","authors":"Ruoyan Si, Changan Zhao, Liping Mo, Zeyu Xu, Yujin Zong, Ziyan Jia, Wenbao Zhao, Jiamei Lu, Xiaodong Xue, Lina Chen, Rongguo Fu, Shuting Ren","doi":"10.1021/acs.molpharmaceut.5c00883","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00883","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a common clinical syndrome characterized by abnormal renal function and structure. Microcirculatory perfusion disorders and inflammatory responses are critical pathophysiologies of AKI. Recently, ultrasound molecular imaging has been considered a valuable tool for preclinical and clinical diagnostics that can sensitively target histological structures of interest, particularly in evaluating renal microcirculation. The purpose of this study was to explore a lipid microbubble (MB_E-selectin) that targets E-selectin molecules expressed on the activated endothelium and to perform ultrasound molecular imaging for the kidney in cisplatin-induced AKI in rats. Using freeze-drying methods, three formular nontargeted microbubbles (NMBs-1, NMBs-2, NMBs-3) were prepared, and three corresponding MB_E-selectin suspensions (MB_E-selectin-1, MB_E-selectin-2, MB_E-selectin-3) were constructed via maleimide-thiol conjugation chemistry. The results revealed that the physicochemical characteristics of three NMBs and MB_E-selectin suspensions were usable for intravenous injection as ultrasound contrast agents (UCAs), and the anti-E-selectin antibody successfully conjugated to the lipid shell surface of the bubbles in three MB_E-selectin suspensions, which could bind specifically to E-selectin molecules expressed on human umbilical vein endothelial cells (HUVECs) treated with tumor necrosis factor-alpha (TNF-α). During ultrasound imaging for the kidney in the cisplatin-induced AKI model, the time-to-peak (TTP) and area under the curve (AUC) of the MB_E-selectin-2 suspension significantly increased, but the wash-in rate (WIR) and wash-out rate (WOR) significantly decreased compared with those of the NMBs-2 suspension or the control group. The normalized differential targeted enhancement (NdTE) of the MB_E-selectin-2 suspension was significantly greater than that of the NMBs-2 suspension in the model group, as was the residual-to-saturation ratio (RSR) at 8 min. In conclusion, we successfully prepared a novel MB_E-selectin suspension carrying an anti-E-selectin antibody that can be used for intravenous injection and can enhance ultrasound imaging of the kidney as a UCA, particularly in a cisplatin-induced AKI model. Ultrasound molecular imaging of the MB_E-selectin suspension may be helpful for evaluating renal microcirculation or injury in AKI diseases.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028526","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":"Development and Validation of a Novel LC-MS/MS-Based Proteomics Method for Quantitation of Retinol Binding Protein 4 (RBP4) and Transthyretin (TTR).","authors":"Aprajita S Yadav, Katya B Rubinow, Alex Zelter, Aurora K Authement, Bryan R Kestenbaum, John K Amory, Nina Isoherranen","doi":"10.1021/acs.jproteome.5c00679","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00679","url":null,"abstract":"<p><p>Retinol binding protein 4 (RBP4), the circulating carrier of retinol, complexes with transthyretin (TTR) and is a potential biomarker of cardiometabolic disease. However, RBP4 quantitation relies on immunoassays and Western blots without retinol and TTR measurement. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous absolute quantitation of circulating RBP4 and TTR is critical to establishing their biomarker potential. Surrogate peptides with reproducible, linear LC-MS/MS response were selected. Purified proteins were used as quantitation standards and heavy-labeled peptides as internal standards. Matrix effects were evaluated. The validated method was applied to measure inter- and intraindividual variability in RBP4 and TTR concentrations in healthy individuals and patients with diabetic kidney disease. Quantitation was linear for the clinically relevant concentration ranges of RBP4 (0.5-6 μM) and TTR (5.8-69 μM). Assay interday variability was <12% and precision within 5%. The interindividual variability for RBP4 and TTR concentrations was 18-26%, while intraindividual variability was similar to assay variability. RBP4 and TTR quantitation correlated with commercially available enzyme-linked immunoassays (ELISA) assays. The developed LC-MS/MS method enables simultaneous absolute quantitation of RBP4 and TTR in serum and plasma. It can be applied to clinical biomarker studies and stoichiometric measurements of circulating RBP4, TTR, and retinol.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028531","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":"Selective Coupling of Aminophosphole-Based Fluorophores to Unprotected Peptides through P-S Bond Formation.","authors":"Miyanou Rosales-Hurtado, Laure Liénart, Vladyslava Lunova, Jean-Louis Banères, Yvan Cuminal, Sébastien Clément, Jean-Alain Fehrentz, Arie Van Der Lee, Florine Cavelier, Emmanuelle Rémond","doi":"10.1021/acs.bioconjchem.5c00342","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00342","url":null,"abstract":"<p><p>Phosphole-based fluorophores are attractive dyes for bioimaging due to their relatively compact molecular structures, strong fluorescence up to the near-infrared region with large Stokes shifts, and remarkable resistance to photobleaching. Therefore, the development of efficient and chemoselective coupling methods for functionalizing phospholes is of significant interest for biomolecular labeling. Herein, we describe the synthesis of novel P-aminophospholes and their use for direct conjugation to cysteinyl peptides under mild conditions. The utility of this approach was demonstrated by successfully labeling the bioactive peptide ghrelin(1,8)-Cys9, as well as the growth hormone secretagogue receptor, without affecting its biological activity.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028581","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":"Violacein-Loaded Outer Membrane Vesicles from <i>Salmonella enterica</i> Exhibit Potent Anti-Melanoma Activity <i>in Vitro</i> and <i>in Vivo</i>.","authors":"Genesy Pérez Jorge, Marco Gontijo, Marina Flóro E Silva, Raquel Bester Liszbinski, Renata Spagolla Napoleão Tavares, Cyro von Zuben de Valega Negrão, Carlismari Oliveira Grundmann, Isabella Carolina Rodrigues Dos Santos Goes, Lilian de Oliveira Coser, Elizabeth Bilsland, Francisca Janaína Soares Rocha, Monica Tallarico Pupo, Selma Giorgio, Sandra Martha Gomes Dias, Fausto Almeida, Marcelo Brocchi","doi":"10.1021/acsbiomaterials.5c00933","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00933","url":null,"abstract":"<p><p>Violacein exhibits antitumor activity, indicating potential for future clinical application. However, an efficient delivery system is required for the clinical use of this hydrophobic compound. Effective delivery systems can enhance the solubility and bioavailability of hydrophobic compounds like violacein, facilitating its clinical application for antitumor therapy. Recent studies have demonstrated that outer membrane vesicles (OMVs) can serve as nanocarriers. This article constitutes the first report to present both <i>in vivo</i> and <i>in vitro</i> investigations of OMVs derived from a hypervesiculating mutant of <i>Salmonella enterica</i> Typhimurium as a delivery vehicle for violacein. In this study, <i>S. enterica</i> Typhimurium Δ<i>tolRA</i> (with a hypervesiculated phenotype) was transformed with a plasmid encoding the violacein biosynthesis operon. OMVs and violacein-loaded OMVs were isolated, characterized, and used in the treatment of murine melanoma. We assessed the cytotoxic effect of these violacein-loaded OMVs in both two-dimensional (2D) and three-dimensional (3D) cell cultures. Violacein-loaded OMVs reduced melanoma cell viability (IC₅₀: 9.30 × 10⁸ vesicles/mL) and delivered violacein in melanoma cells. Additionally, tumor regression was associated with treating tumor-bearing mice with violacein-loaded OMVs or nonviolacein-loaded OMVs (5 × 10⁹ vesicles/mouse). The antitumor response was linked to the accumulation of M1-type macrophages in the tumor microenvironment and the overexpression of mRNA for antitumor mediators Inducible Nitric Oxide Synthase, Tumor Necrosis Factor-alpha, and Interleukin-6 (iNOS, TNF-α, and IL-6). Our results suggest that OMVs can act as nanocarriers for highly hydrophobic agents and induce antitumor responses to eliminate tumors.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032340","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":"Charge-Transfer Complex κ-(BEST)₂Cu₂(CN)₃ Analogous to Organic Spin Liquid Candidate.","authors":"Takuya Kobayashi, Kent A Sakurai, Shinji Michimura, Hiromi Taniguchi","doi":"10.1021/acs.inorgchem.5c02320","DOIUrl":"https://doi.org/10.1021/acs.inorgchem.5c02320","url":null,"abstract":"<p><p>We report the structural, electrical, and magnetic properties of the organic conductor κ-(BEST)₂Cu₂(CN)₃ (BEST: bis(ethylenediseleno)-tetrathiafulvalene; abbreviated as κ-BEST-CN), which is isostructural with the quantum spin liquid candidate κ-(ET)₂Cu₂(CN)₃ (ET: bis(ethylenedithio)tetrathiafulvalene; abbreviated as κ-ET-CN). Resistivity measurements demonstrate that κ-BEST-CN exhibits semiconducting behavior, governed by the same conducting mechanism as κ-ET-CN. Under a pressure of ∼0.1 GPa, κ-BEST-CN undergoes a superconducting transition with an onset temperature of ∼4 K. From the comparison of the critical pressures of superconductivity between κ-ET-CN and κ-BEST-CN, κ-BEST-CN can be regarded as a chemically pressurized analogue of κ-ET-CN. Therefore, κ-BEST-CN, in which only the effective pressure changes without altering the anion structure, is considered a valuable reference material for elucidating the enigmatic properties observed in κ-ET-CN. Furthermore, the spin susceptibility of κ-BEST-CN is slightly larger than that of κ-ET-CN and shows weaker temperature dependence, which cannot be explained by the localized spin model. This behavior clarifies the anomalous magnetic properties of a system with frustration near the Mott transition, serving to stimulate future theoretical research.</p>","PeriodicalId":40,"journal":{"name":"Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032444","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}