ACS Bio & Med Chem Au最新文献

{"title":"1,2,4-Triazole-Based First-in-Class Non-Nucleoside Inhibitors of the Bacterial Enzyme MraY.","authors":"Tomayo Berida, Tzu-Yu Huang, Stefanie C Weck, Marcel Lutz, Samuel R McKee, Nathalie Kagerah, Destinee L Manning, Mohamed E Jahan, Sushil Mishra, Jennifer Herrmann, Rolf Müller, Robert J Doerksen, Christina L Stallings, Christian Ducho, Sudeshna Roy","doi":"10.1021/acsbiomedchemau.5c00158","DOIUrl":"10.1021/acsbiomedchemau.5c00158","url":null,"abstract":"<p><p>MraY is an essential bacterial enzyme for peptidoglycan synthesis in cell walls and serves as a promising but unrealized target for developing effective antibacterial drugs. Nature has provided a remarkable array of nucleoside inhibitors of MraY, and researchers have skillfully refined these structures to develop inhibitors that effectively mimic natural products. Yet, both natural products and their synthetic variants often face challenges regarding inadequate <i>in vivo</i> efficacy, and the intricate nature of these structures complicates their synthesis and exploration of structure-activity relationships (SAR). Here, we present our findings on the discovery of first-in-class small molecule MraY inhibitors that are non-nucleoside-derived, based on 1,2,4-triazoles, using a structure-based drug design strategy. By leveraging the structural roadmap of the MraY binding site, we discovered the initial hit compound <b>1</b> with an IC₅₀ value of 171 μM <i>in vitro</i> against MraY from <i>Staphylococcus aureus</i> (MraY _<i>SA</i> ) that was refined to compound <b>12a</b>, exhibiting an IC₅₀ value of 25 μM. Molecular docking studies against MraY _<i>SA</i> provided critical insights into how the binding interactions of compounds directly influence their activity. Furthermore, we report that these compounds show broad-spectrum antibacterial activity against critical pathogens such as <i>Enterococcus</i> spp., methicillin-resistant <i>S. aureus</i> (MRSA), vancomycin-resistant <i>Enterococci</i> (VRE) strains, <i>Acinetobacter baumannii</i>, and <i>Mycobacterium tuberculosis</i>. This study showcases novel non-nucleoside inhibitors as a compelling proof-of-concept for crafting the next generation of antibacterial agents targeting MraY.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 6","pages":"966-981"},"PeriodicalIF":4.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prebiotic Roles of Formaldehyde as an Activating Agent and a Building Block in Solid-State Peptide Modification.","authors":"Jamie C Thuan, Anuja Koirala, James Pirez, Jun Ohata","doi":"10.1021/acsbiomedchemau.5c00167","DOIUrl":"10.1021/acsbiomedchemau.5c00167","url":null,"abstract":"<p><p>Signal transduction by gaseous small molecules is an essential process in modern living systems, where the gasotransmitters relay cellular signals to bio-(macro)-molecules through covalent bond formation. However, the origin or a primordial version of such signaling events in abiotic worlds has been poorly understood to date. Through examination of chemical reactivities between formaldehyde and cyclic dipeptide/diketopiperazine derivatives in prebiotically relevant solid-state environments, this study demonstrates that the gaseous small molecule may serve not only as a mere building block for the abiotic construction of biomolecules but also as an activating agent that transforms the inert peptide into reactive, prebiotically important chemical species. In addition, superiority of solid-state reactions or mechanochemistry to solution-based reaction conditions described in this article may be an indication of potential significance of the mechanical force-induced chemistry for chemical evolution, in particular for abiotic emergence of polypeptides.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 6","pages":"982-993"},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allosteric Modulation of Cannabinoid Type 1 Receptor by ZCZ011: Integration of In Vitro Pharmacology and Molecular Dynamics Simulation.","authors":"Tara Chand Yadav, Lakshmipriya Indira Swaminathan, Venkat R Chirasani, Zhixing Wu, Dai Lu, Bogna M Ignatowska-Jankowska, Aron H Lichtman, Sylvia Fitting, Barkha J Yadav-Samudrala","doi":"10.1021/acsbiomedchemau.5c00169","DOIUrl":"10.1021/acsbiomedchemau.5c00169","url":null,"abstract":"<p><p>Over the years, the cannabinoid type 1 receptor (CB₁R) has emerged as a promising therapeutic target for addressing various neurodegenerative diseases including HIV-associated neurocognitive disorders (HAND). However, the therapeutic application of direct CB₁R activation is often hindered by undesirable psychoactive side effects. To mitigate this issue, research has focused on utilizing positive allosteric modulators (PAMs) to enhance the CB₁R activity indirectly. Preclinical studies have highlighted the efficacy of CB₁R PAMs, such as ZCZ011 and GAT211, in mouse models of Huntington's disease, neuropathic pain, and, more recently, HAND. Building on this evidence, we employed primary frontal cortex neuronal cultures and whole brain microglial cultures to investigate the direct and indirect effects of racemic ZCZ011 against the HIV-1 trans-activator of transcription (Tat)-induced excitotoxicity. In parallel, molecular modeling and molecular dynamics simulations were conducted using the ZCZ011 enantiomers (<i>R</i>)-ZCZ011 and (<i>S</i>)-ZCZ011, to elucidate their binding profiles at CB₁R. Our in vitro studies revealed that ZCZ011 demonstrated neuroprotective effects against Tat-induced excitotoxicity in the presence of <i>N</i>-arachidonoylethanolamine (AEA) in a dose-dependent manner. Interestingly, racemic ZCZ011 exhibited neuroprotective properties even in the absence of AEA, deviating from the classical behavior of a true PAM. This prompted further investigation into the binding profiles of the enantiomers. Molecular modeling revealed that (<i>R</i>)-ZCZ011 and (<i>S</i>)-ZCZ011 bind to distinct sites on CB₁R, aligning with the binding profiles of other CB₁R allosteric modulators, GAT228 and GAT229. Notably, (<i>R</i>)-ZCZ011 exhibited a higher number of hydrogen bonds and both polar and nonpolar interactions with CB₁R, enhancing the stabilization of AEA binding to CB₁R. In summary, these findings suggest that (<i>R</i>)-ZCZ011 may function as both a PAM and an allosteric agonist, like GAT228, while (<i>S</i>)-ZCZ011 may act as a pure PAM, resembling GAT229. This dual functionality underscores the therapeutic potential of ZCZ011 in modulating CB₁R activity for a number of neuroprotective applications.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 5","pages":"906-919"},"PeriodicalIF":4.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning-Guided Design of Rhenium Tricarbonyl Complexes for Next-Generation Antibiotics.","authors":"Miroslava Nedyalkova, Gozde Demirci, Youri Cortat, Kevin Schindler, Fatlinda Rahmani, Justine Horner, Mahdi Vasighi, Aurelien Crochet, Aleksandar Pavic, Olimpia Mamula, Fabio Zobi, Marco Lattuada","doi":"10.1021/acsbiomedchemau.5c00125","DOIUrl":"10.1021/acsbiomedchemau.5c00125","url":null,"abstract":"<p><p>The escalating prevalence of antibiotic-resistant bacteria and the increasing complexity of managing severe infections emphasize the critical need for novel and effective antibiotics. Herein, we present a novel computational strategy focused on metal-based antibiotics, specifically rhenium (Re) complexes, for the rational design of next-generation antibacterial agents. Our approach integrates machine learning (ML) classification models to predict antibacterial potency, particularly against multidrug-resistant pathogens. A recognized limitation of conventional ML-driven antibiotic discovery is its dependence on structural similarity to known antibiotics, which hinders the exploration of structurally diverse and innovative antibiotic classes. To address this, we developed predictive ML models based on multi-layer perceptron (MLP) and random forest (RF) algorithms to estimate the minimum inhibitory concentration (MIC) of Re complexes against methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) <i>Staphylococcus aureus</i> strains. Utilizing structural descriptors, these models demonstrated strong predictive performance and were successfully applied to evaluate 26 novel Re complexes. Additionally, Shapley additive explanation (SHAP) analysis provided insights into the structural features influencing antibacterial activity predictions. The study's outcomes affirm the effectiveness of our ML-guided approach as a promising pathway for the rational, <i>de novo</i> design of potent Re based antibiotics capable of combating antibiotic-resistant bacterial infections.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 5","pages":"870-881"},"PeriodicalIF":4.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction \"<i>ACS Bio & Med Chem Au</i>: Introducing the 2024 Rising Stars in Biological, Medicinal, and Pharmaceutical Chemistry\".","authors":"Squire J Booker","doi":"10.1021/acsbiomedchemau.5c00147","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00147","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1021/acsbiomedchemau.5c00080.].</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 5","pages":"920"},"PeriodicalIF":4.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transition State Analysis of the Aldol-Like Reaction Catalyzed by NeuB, a Sialic Acid Synthase, Reveals a Stepwise Cationic Mechanism.","authors":"Pallavi Mukherjee, Chen Niu, Paul J Berti","doi":"10.1021/acsbiomedchemau.5c00126","DOIUrl":"10.1021/acsbiomedchemau.5c00126","url":null,"abstract":"<p><p>The sialic acid synthase NeuB, and other α-carboxyketose synthases, are long-standing targets for inhibition by potential antimicrobial compounds. NeuB catalyzes an aldol-like reaction of phosphoenolpyruvate (PEP) and <i>N</i>-acetylmannosamine (ManNAc) that passes through a tetrahedral intermediate (THI) to form <i>N</i>-acetylneuraminic acid. We measured multiple kinetic isotope effects (KIEs) in order to determine the transition state (TS) structure of the NeuB-catalyzed reaction. As part of this study, the use of incomplete <i>T</i> ₁ relaxation during KIE measurement by NMR was investigated, and then used to accelerate KIE measurements 9-fold. KIEs measured at the 3-¹³C, 2-¹³C and 2-¹⁸O positions in PEP reveal a stepwise mechanism of THI formation in which the PEP C3 to ManNAc C1'(aldehyde) bond (C3···C1') is formed first, leading to a cationic intermediate. However, the transition state is so early in C3···C1' bond formation, with a C3···C1' bond order of 0.17 to 0.35, that there is little cationic character in the transition state. The lack of change in geometry or charge in forming the transition state implies that NeuB may function primarily by \"catalysis-by-approximation\"; i.e., its main contribution to TS stabilization is bringing the reactants together in the correct orientation. It also implies that inhibitors designed to mimic a positive charge are unlikely to be effective. Instead, neutral inhibitors that maximize the number of active site interactions are more likely to be effective.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 5","pages":"882-894"},"PeriodicalIF":4.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Rational Design and Molecular Metadynamics for the Estimation of Changes in Trans-Splicing Efficiency during the Mutagenesis of Ssp DnaE Intein","authors":"Matvei O. Sabantsev,&nbsp;Andrew N. Brovin*,&nbsp;Maxim A. Gureev,&nbsp;Yuri B. Porozov,&nbsp;Sergey A. Chuvpilo and Alexander V. Karabelsky,&nbsp;","doi":"10.1021/acsbiomedchemau.5c00091","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00091","url":null,"abstract":"<p >Currently, inteins are some of the most popular multifunctional tools in the fields of molecular biology and biotechnology. In this study, we used the surface analysis method to identify the sites of intermolecular interactions between the N and C-parts of the Ssp DnaE intein. The obtained results were used to determine the key amino acids that define the binding energy and type of contact between intein subunits. <i>In silico</i> substitution of five neutral amino acids in the C-part of Ssp DnaE with methionine was validated by using oligomutagenesis of a previously assembled plasmid, which was then used for <i>in vitro</i> tests with HEK293 cells. GFP reconstruction assays were used to estimate changes in trans-splicing efficiency using quantitative metrics such as the number of GFP+ cells and median fluorescence intensity as well as qualitative metrics such as microphotography and fluorescence curve analysis using live-cell microscopy. The results of the <i>in vitro</i> tests revealed significantly decreased splicing efficiency in four out of six mutant variants, with no significant differences in the other two cases. Additionally, we performed metadynamics modeling to explain how these mutations affect the molecular mechanisms of intein-intein interactions. Finally, we found a positive correlation between the structural and free energy changes in the local minima distribution and the decrease in splicing efficiency in the I151M and A162M+A165M cases. The resulting method was used with control mutations that had an experimentally confirmed positive (A168H) or negative (T198A) effect on the splicing reaction. In summary, we propose a method of free energy surface analysis in collective variables for quick and visual evaluation of mutation effects. This approach could be applied for the development of new biotechnological and gene therapy products to overcome AAV capacity limitations.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 4","pages":"738–752"},"PeriodicalIF":4.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Throughput Microfluidic Technologies for Rapidly Screening Pollutant-Induced Cell Health Effects.","authors":"Blanca I Quiñones-Díaz, Niphattha Wongwiset, Pratik Kamat, Orian Stapleton, Sean M Engels, Matthew R Burroughs, S V Sreenivasan, Jude M Phillip, Lydia M Contreras","doi":"10.1021/acsbiomedchemau.5c00094","DOIUrl":"10.1021/acsbiomedchemau.5c00094","url":null,"abstract":"<p><p>Air pollution exposure is linked to diseases spanning multiple physiological systems. However, environmental stress is overwhelmingly associated with several lung diseases. Since the chemical composition of air pollutants varies widely across geographical locations, research on how specific components in pollutant mixtures contribute to cellular dysfunction is needed. In this work, we utilized microscopy-based morphological profiling as a tool to assess the cellular susceptibility to pollutants. Through our analysis, we established morphological profiles of formaldehyde-exposed cells that showed dose-dependent shifts in cell shape profiles correlating with overall cell health. As a real-world proof-of-concept validation, we evaluated the differences in particulate matter (PM) composition across multiple geographical areas, including both urban and suburban communities in Austin, Texas, USA. Data from this real-world study was used to inform a multicombinatorial study involving metals, selenium (Se) and manganese (Mn), which were differentially abundant across PM collection sites. As proof of concept to demonstrate the potential of establishing low-cost, high-throughput combinatorial screening of the biological effects of these metals, we incorporated microfluidic technology to simultaneously generate variable two-component metal mixtures in a multiwell plate format that enabled microscopy-based morphological screening as a proxy for toxicity. Combinatorial analysis of Se and Mn showed dynamic cell responses across a range of concentrations. Interestingly, exposure mixtures containing both Se and Mn yielded healthier cellular phenotypes relative to Se exposure as a single component. These results demonstrate the development of a high-throughput pipeline to detect dynamic biological responses to common air pollutants. Leveraging multiple technologies, we demonstrate the feasibility of a cost-effective approach that can serve as a starting point to inform focused screenings and studies of air pollutant mixtures that affect health outcomes.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 5","pages":"860-869"},"PeriodicalIF":4.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12617457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145542779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of a Water-Soluble BODIPY for Targeting and Assessing the Function of Endoplasmic Reticulum.","authors":"Jacopo Tricomi, Giacomo Biagiotti, Tommy Chastel, Serena Filiberti, Hana Kokot, Francesca Mancusi, Maja Žežlina, Layal Rajeh, Iztok Urbančič, Stéphane Bodin, Ernesto G Occhiato, Andrei Turtoi, Stefano Cicchi, Barbara Richichi","doi":"10.1021/acsbiomedchemau.5c00142","DOIUrl":"10.1021/acsbiomedchemau.5c00142","url":null,"abstract":"<p><p>We report here on a straightforward methodology to synthesize a new water-soluble fluorescent probe <b>Tris-BODIPY-OH 1</b> that contains three pH-independent hydrophilic arms. This probe has been prepared by exploiting a synthetic strategy that includes as a key step the combination of a Cu-(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and a Sonogashira cross-coupling in a sequential one-pot approach. <b>Tris-BODIPY-OH 1</b> provides a significant advancement in the field by expanding the BODIPY toolbox with a biocompatible water-soluble probe, which can be used to specifically label and assess the function of the endoplasmic reticulum.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 5","pages":"895-905"},"PeriodicalIF":4.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local and Global Breathing Motions Prime the Access to Buried Binding Site in an Antibiotic-Sequestering Protein.","authors":"Lawanya Natarajan, Dmitry Loginov, Alan Kadek, Petr Man, Athi N Naganathan","doi":"10.1021/acsbiomedchemau.5c00081","DOIUrl":"10.1021/acsbiomedchemau.5c00081","url":null,"abstract":"<p><p>Proteins frequently undergo large-scale conformational excursions in their native ensemble. Such structural transitions are particularly critical for enabling access to binding sites when they are buried in the protein interior. Here, we map the conformational landscape of AlbAS, a natural isoform of the transcription factor AlbA from the gut microbe <i>Klebsiella oxytoca</i>, which sequesters the antibiotic albicidin in a solvent-inaccessible binding tunnel. Combining equilibrium, time-resolved experiments, structural mass spectrometry and calorimetry with statistical modeling, we show that AlbAS displays large differences in local and global stability and dynamics, with ∼600-fold difference in unfolding rates across different parts of the structure. Several residues lining the ligand-binding pocket and the inter-sub-domain residues rapidly exchange protons with the solvent in hydrogen-deuterium exchange mass spectrometry experiments, indicative of anisotropic distributions of local stabilities, with the N-terminal subdomain being less stable. The AlbAS conformational landscape is thus quite rugged, encompassing numerous partially structured states in equilibrium, including partial unlocking of the N-terminal subdomain at a time-constant of 6 ms that exposes the binding sites to aid in albicidin binding.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 5","pages":"840-851"},"PeriodicalIF":4.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}