ACS Central Science最新文献_第4页

Discovery of Clonixeril as a Sub-Femtomolar Modulator of the Human STING Receptor. 克罗昔利作为人STING受体亚飞摩尔调制剂的发现。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-06-06 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.4c01982

Robert P Sparks, William Lawless, Anna Kharitonova, Rainer Metcalf, Jamie Nunziata, Grace A Binder, Sauradip Chaudhuri, Christine S R Gambino, Michelle Wilde, Linette S Harding, Jaret J Crews, Mansi Gopu, Emilia Dalamangas, Sarah Lawless, Mark Eschenfelder, Robert M Green, Elizabeth X Nompleggi, Timothy H Tran, Yan Yang, Donna V Trask, Paul R Thompson, Rekha Patel, Niketa A Patel, Wesley H Brooks, Guy Bradley, Mildred E Acevedo-Duncan, Alan C Mullen, James W Leahy, Kenyon G Daniel, Wayne C Guida

{"title":"Discovery of Clonixeril as a Sub-Femtomolar Modulator of the Human STING Receptor.","authors":"Robert P Sparks, William Lawless, Anna Kharitonova, Rainer Metcalf, Jamie Nunziata, Grace A Binder, Sauradip Chaudhuri, Christine S R Gambino, Michelle Wilde, Linette S Harding, Jaret J Crews, Mansi Gopu, Emilia Dalamangas, Sarah Lawless, Mark Eschenfelder, Robert M Green, Elizabeth X Nompleggi, Timothy H Tran, Yan Yang, Donna V Trask, Paul R Thompson, Rekha Patel, Niketa A Patel, Wesley H Brooks, Guy Bradley, Mildred E Acevedo-Duncan, Alan C Mullen, James W Leahy, Kenyon G Daniel, Wayne C Guida","doi":"10.1021/acscentsci.4c01982","DOIUrl":"10.1021/acscentsci.4c01982","url":null,"abstract":"Stimulator of interferon genes (STING) is a transmembrane endoplasmic reticulum (ER) resident protein involved in innate immunity. STING activation occurs by binding of cyclic guanosine-(2'→5')-monophosphate-adenosine-(3'→5')-monophosphate (2',3'-cGAMP) to STING, which leads to downstream production of type 1 interferons (IFN-1). We generated molecular dynamics (MD) equilibrated agonist and antagonist models of human STING (hSTING) for computer-based screening and now report the discovery of clonixeril (CXL) as the most potent non-nucleotide hSTING modulator discovered to date. We demonstrate in vitro and in cellulo that CXL has two modes of interaction with hSTING, one with an EC50 above 1 nM and the other with an EC50 in the 1 fM-100 aM range (10-15-10-16 M). In cell-based experiments, when CXL is titrated below 1 nM, it displays inverse dose-dependent antagonistic behavior toward hSTING. We have substantiated that CXL displays this exceptionally strong inhibitory effect on hSTING mediated IFN-1 production using a THP-1 cell luciferase reporter for interferon regulatory factor 3 (IRF3). Further characterization of CXL was performed in HEK293 cells by using biophysical and biochemical techniques.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"994-1008"},"PeriodicalIF":12.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conformational Plasticity in Amyloid Assemblies: A Paradigm Shift from Structural Rigidity to Functional Adaptability. 淀粉样蛋白组装中的构象可塑性：从结构刚性到功能适应性的范式转变。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-06-06 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00983

Alan H Weible, Xiaoguang Wang

引用次数: 0

Light-Powered Late-Stage Alkylation of N‑Heteroaromatics in Flow. 流动中N -杂芳烃的光催化后期烷基化。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-06-05 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00926

Shun Wang, Zhiwei Zuo

引用次数: 0

Dual-Wavelength Simultaneous Patterning of Degradable Thermoset Supports for One-Pot Embedded 3D Printing. 一锅嵌入式3D打印可降解热固性支架的双波长同步图案。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-06-04 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00337

Isabel Arias Ponce, Bryan Moran, Craig J Hawker, Maxim Shusteff, Sijia Huang

{"title":"Dual-Wavelength Simultaneous Patterning of Degradable Thermoset Supports for One-Pot Embedded 3D Printing.","authors":"Isabel Arias Ponce, Bryan Moran, Craig J Hawker, Maxim Shusteff, Sijia Huang","doi":"10.1021/acscentsci.5c00337","DOIUrl":"10.1021/acscentsci.5c00337","url":null,"abstract":"Vat photopolymerization (VP) techniques have enabled the fabrication of complex geometries while balancing high precision and fast processing times. 3D printed objects are traditionally built layer-by-layer with newly cured layers being structurally supported by previous ones. Fabricating unsupported features such as overhangs and arches risks misalignment and sagging, limiting the range of accessible designs. To overcome this issue, support structures are fabricated along with the primary object as temporary scaffolds that provide stability and conserve print fidelity. For VP specifically, patterning dissolvable sacrificial supports is attractive to avoid manual removal after printing. In this study, we demonstrate a base-degradable thermoset to pattern print supports in a one-pot formulation along with the primary structural material. Efficient printing is enabled using a dual-wavelength negative imaging (DWNI) DLP printer that patterns the degradable thermoset with visible light and the permanent network with UV light, which are simultaneously projected using a single digital micromirror device (DMD). Printed objects undergo thermal postprocessing to enhance the final conversion of the primary material, after which thermoset supports are degraded in a basic, aqueous solution. This approach provides a robust method for the dual-wavelength patterning of sacrificial thermoset supports, broadening the range of accessible 3D printable materials and geometries.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"967-974"},"PeriodicalIF":12.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing Carbon Nanotube Fibers: Addressing Challenges from Production to Application. 推进碳纳米管纤维：解决从生产到应用的挑战。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-06-03 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00155

Hao Guo, Chunlei Dong, Qingquan Han, Hongyu Jiang, Hongji Sun, Xuemei Sun, Songlin Zhang, Huisheng Peng

{"title":"Advancing Carbon Nanotube Fibers: Addressing Challenges from Production to Application.","authors":"Hao Guo, Chunlei Dong, Qingquan Han, Hongyu Jiang, Hongji Sun, Xuemei Sun, Songlin Zhang, Huisheng Peng","doi":"10.1021/acscentsci.5c00155","DOIUrl":"10.1021/acscentsci.5c00155","url":null,"abstract":"Carbon nanotube (CNT) fibers, renowned for their theoretically high tensile strength, low density, and outstanding electrical conductivity, are promising candidates for cutting-edge applications in wearable electronics, bioengineering, and aerospace engineering. Despite their immense potential, the widespread adoption of CNT fibers faces critical barriers, including the challenge of enhancing macroscopic fiber performance and achieving scalable, consistent production. The extraordinary intrinsic properties of individual CNTs are not fully transferred to macroscopic fibers due to weak intertube interactions, misalignment, and structural defects. Among the available production methods, floating catalyst chemical vapor deposition stands out for its promise to enable the large-scale synthesis of CNT fibers. However, achieving consistent quality and scalability via this technique remains a significant obstacle. This outlook highlights the importance of innovative strategies for multiscale performance optimization and advances in scalable fabrication methodologies. A distinctive perspective on CNT fiber production is provided, emphasizing the integration of machine learning with process optimization strategies to enhance the uniformity and efficiency. The outlook systematically discusses these challenges, exploring strategies for multiscale performance optimization, scaled-up fabrication methodologies, and efficient manufacturing processes. Additionally, it examines the transformative applications of CNT fibers across diverse industries, underscoring their potential to revolutionize next-generation technologies.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"855-867"},"PeriodicalIF":12.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthetic Mucins as Glycan-Defined Prebiotics. 合成粘蛋白作为聚糖定义的益生元。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-06-02 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00317

Jill W Alty, Carolyn E Barnes, Agnese M Nicoli, Bradley S Turner, Ekua A Beneman, Amanda E Dugan, Spencer D Brucks, Austin G Kruger, Richard R Schrock, Katharina Ribbeck, Laura L Kiessling

{"title":"Synthetic Mucins as Glycan-Defined Prebiotics.","authors":"Jill W Alty, Carolyn E Barnes, Agnese M Nicoli, Bradley S Turner, Ekua A Beneman, Amanda E Dugan, Spencer D Brucks, Austin G Kruger, Richard R Schrock, Katharina Ribbeck, Laura L Kiessling","doi":"10.1021/acscentsci.5c00317","DOIUrl":"10.1021/acscentsci.5c00317","url":null,"abstract":"The human microbiome contains at least as many bacterial cells as human cells. Some bacteria offer benefits, like improving gut barrier function, suppressing pathobiont growth, and modulating immunity. These benefits have popularized probiotics, but probiotic retention is often hindered by low colonization efficiency in the mucosal layer that lines all epithelial cells. Mucins, the primary components of mucus, are essential for the organization and regulation of microbial populations. The molecular mechanisms of mucin-probiotic interactions remain understudied due, in part, to the inability to incisively manipulate native mucin sequences or their glycans. Here, we used synthetic mucins with defined glycan presentations to interrogate glycan-dependent interactions between mucus and three probiotic lactobacilli species. The nutrient conditions under which bacteria were cultured influenced glycan binding preferences, suggesting mucin-probiotic interactions change with nutrient availability. The addition of synthetic mucins to native mucin increased Limosilactobacillus fermentum adherence. Additionally, an increase in glycosidase activity indicated that native and synthetic mucins function as prebiotics, as probiotic bacteria can cleave the displayed O-glycans. Thus, synthetic mucins can cultivate target probiotic bacteria and increase adhesion as binding sites, highlighting their value as tools for elucidating native mucin functions and as promising agents for promoting human health.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"918-926"},"PeriodicalIF":12.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Measurements of Surrogate Respiratory Sessile Droplet pH and Implications for Exhaled Respiratory Aerosol and Airborne Disease Transmission. 替代呼吸无底液滴pH值的测量及其对呼出呼吸道气溶胶和空气传播疾病的影响。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-06-02 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00284

Jianghan Tian, Beiping Luo, Aidan Rafferty, Allen E Haddrell, Ulrich K Krieger, Jonathan P Reid

{"title":"Measurements of Surrogate Respiratory Sessile Droplet pH and Implications for Exhaled Respiratory Aerosol and Airborne Disease Transmission.","authors":"Jianghan Tian, Beiping Luo, Aidan Rafferty, Allen E Haddrell, Ulrich K Krieger, Jonathan P Reid","doi":"10.1021/acscentsci.5c00284","DOIUrl":"10.1021/acscentsci.5c00284","url":null,"abstract":"Respiratory aerosol pH has been proposed as a key factor driving the infectivity loss of SARS-CoV-2 viruses and influenza A virus in exhaled aerosols, thus affecting the airborne transmission of respiratory diseases. Sodium bicarbonate acts as a principal buffer in biological systems, regulating blood pH and the CO2 balance between gas and liquid phases. Upon exhalation, changes in gas-phase conditions alter aerosol composition and pH. Despite Raman spectroscopy being used to quantify atmospherically relevant aerosol pH, the kinetics of CO2 partitioning and pH variability in respiratory droplets remain poorly understood. In this paper, a method to investigate the HCO3 -/CO3 2- equilibrium in a surrogate respiratory fluid system within sessile droplets is proposed to elucidate the pH evolution of an exhaled respiratory aerosol. The enzymatic catalysis of CO2 hydration and H2CO3 dehydration is explored. Experimental results were used to benchmark the ResAM model, which simulates respiratory aerosol droplet thermodynamics and pH evolution. Simulated pH evolution profiles of picoliter droplets show size independence. Simulations for both sessile droplets and respiratory aerosols show that carbonic anhydrase significantly increases the rate of pH increase, and gas-phase CO2 levels are important for determining the final droplet pH. Consequences for understanding the aerobiological pathways for virus transmission are considered.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"1009-1019"},"PeriodicalIF":12.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correspondence on "The Open DAC 2023 Dataset and Challenges for Sorbent Discovery in Direct Air Capture". 关于“开放DAC 2023数据集和直接空气捕获中吸附剂发现的挑战”的通信。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-29 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00255

Xin Jin, Susana Garcia, Berend Smit

引用次数: 0

Multicolor Digital Light Processing 3D Printing Enables Dissolvable Supports for Freestanding and Non-Assembly Structures. 多色数字光处理3D打印使独立和非组装结构的可溶解支撑成为可能。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-29 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00289

Keldy S Mason, Ji-Won Kim, Elizabeth A Recker, Jenna M Nymick, Mingyu Shi, Franz A Stolpen, Jaechul Ju, Zachariah A Page

{"title":"Multicolor Digital Light Processing 3D Printing Enables Dissolvable Supports for Freestanding and Non-Assembly Structures.","authors":"Keldy S Mason, Ji-Won Kim, Elizabeth A Recker, Jenna M Nymick, Mingyu Shi, Franz A Stolpen, Jaechul Ju, Zachariah A Page","doi":"10.1021/acscentsci.5c00289","DOIUrl":"10.1021/acscentsci.5c00289","url":null,"abstract":"The limited diversity in photocurable resin chemistries has precluded access to certain geometries using digital light processing (DLP) 3D printing, a rapid, precise, economical, and low-waste manufacturing technology. Specifically, freestanding structures with floating overhangs (e.g., hooks) and mobile nonassembly structures that cannot be physically separated (e.g., joints) represent two such geometries that are difficult or impossible to access with contemporary DLP 3D printing. Herein, we disclose novel resins that selectively react with different colors of light to form soluble thermoplastics and insoluble thermosets. Systematic characterization of the acrylate- and epoxy-based resins and corresponding polymers from simultaneous UV and visible (violet or blue) light exposure revealed a rapid multimaterial 3D printing process (∼0.75 mm/min) capable of providing supports that dissolve in ethyl acetate, a \"green\" solvent, within 10 min at room temperature. Relative to manual support removal, the present process provides comparable or improved surface finishes and higher throughput. Finally, several proof-of-concept structures requiring dissolvable supports were 3D printed, including hooks, chains, and joints, which were scanned using computed tomography to showcase the process's geometric versatility and high fidelity. This work provides fundamental design principles for multimaterial resin chemistry and lays a foundation for automating next generation additive manufacturing.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"975-982"},"PeriodicalIF":12.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atom-by-Atom Iterative Synthetic Logic: Laying the Foundation for Programmable Automated Construction of Small Organic Molecules. 原子-原子迭代合成逻辑：为有机小分子的可编程自动化构建奠定基础。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-29 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00526

Miao Chen, Guangbin Dong

{"title":"Atom-by-Atom Iterative Synthetic Logic: Laying the Foundation for Programmable Automated Construction of Small Organic Molecules.","authors":"Miao Chen, Guangbin Dong","doi":"10.1021/acscentsci.5c00526","DOIUrl":"10.1021/acscentsci.5c00526","url":null,"abstract":"Fully automated preparation of diverse small organic molecules remains a formidable challenge due to the inherent constraints of conventional synthetic philosophies. The existing automation approaches require access to either almost unlimited kinds of chemical reagents or custom-made building blocks (BBs). Herein we propose atom-by-atom iterative synthesis (AIS) as a new synthetic logic to tackle this challenge. By viewing complex organic molecules as assemblies of single-carbon- or heteroatom-based units, AIS aims to construct molecular skeletons through iterative coupling of simple atomic-scale BBs by a unified type of reactionboron homologations. Compared with conventional approaches, the AIS strategy uses only a few types of chemical reactions and a small set of BBs, making it more suitable for automation and artificial intelligence-assisted synthetic route design. To date, enormous progresses have been made on the synthetic chemistry that serves for the purpose of AIS, such as introducing heteroatoms and sp2-carbons, forming ring structures, developing thermostable carbenoid reagents, and achieving stereochemical controls. On the other hand, substantial challenges and limitations remain to be overcome for realizing fully automated construction of diverse molecules. This Outlook article describes the AIS concept, recent progress, current limitations, and future opportunities in this field.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"843-854"},"PeriodicalIF":12.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0