Lei Zhu,Fengying Yuan,Yuanlong Zhang,Li Yang,Kaicheng Wang,Yerim Lee,Jing-Ye Pan,Yu Qi,Juyoung Yoon,Shan Wang
{"title":"Unveiling Lipid Droplet Dynamics in Parkinson's Disease via a Polarity-Responsive Alkenyl Indole-Based Fluorophore.","authors":"Lei Zhu,Fengying Yuan,Yuanlong Zhang,Li Yang,Kaicheng Wang,Yerim Lee,Jing-Ye Pan,Yu Qi,Juyoung Yoon,Shan Wang","doi":"10.1021/acs.analchem.5c02829","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c02829","url":null,"abstract":"Lipid droplets (LDs) are dynamic organelles implicated in Parkinson's disease (PD) pathology, yet their polarity dynamics and therapeutic relevance remain poorly understood. Herein, we rationally designed a polarity-responsive alkenyl indole-based fluorophore, PD3, through systematic molecular engineering to enable real-time tracking of LD polarity in PD models. By modulating intramolecular charge transfer (ICT) effects via electron-donating/withdrawing substitutions, PD3 exhibited exceptional polarity sensitivity, with a dramatic fluorescence enhancement in low-polarity environments and negligible viscosity interference. Density functional theory calculations confirmed that the polarity response originated from ICT-driven solvatochromism and solvent-dependent internal conversion rates. In rotenone-induced PD cellular models, PD3 revealed significant LD accumulation (4.2-fold intensity increase, 74% higher LD density, and 46% enlarged diameter) and organelle crosstalk, particularly with the endoplasmic reticulum (ER) and mitochondria. Furthermore, PD3-enabled evaluation of PD drugs demonstrated that amantadine (AMA) and pramipexole (PPX) restored LD homeostasis, linking their therapeutic effects to LD modulation. Ex vivo studies in methyl-phenyl-tetrahydropyridine (MPTP)-induced PD mice confirmed LD accumulation in brain tissues, correlating with motor deficits and neuronal loss in the substantia nigra. This work establishes PD3 as a powerful tool for deciphering LD-associated PD pathology and advancing LD-targeted therapeutic strategies.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"120 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693447","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":"Oriented Antibody Functionalized Plasmonic Yolk-Shell-Satellite Nanostructures for Ultrasensitive SERS-Based Lateral Flow Immunoassay.","authors":"Jiaojiao Sun,Lei Li,Rui Sun,Huancai Yin,Jie Liu","doi":"10.1021/acs.analchem.5c02561","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c02561","url":null,"abstract":"Conventional gold nanoparticle (AuNP)-based lateral flow immunoassays (LFIAs) for detecting matrix metalloproteinase-9 (MMP-9), a biomarker associated with dry eye disease and cancer, often suffer from limited sensitivity. To address this, we developed an ultrasensitive surface-enhanced Raman scattering (SERS)-based LFIA using plasmonic yolk-shell-satellite nanostructures (YSSNs) functionalized with bifunctional 4-mercaptophenylboronic acid (MPBA) as SERS tags. The YSSNs, composed of a gold nanorod core enclosed by a gold nanocage and decorated with satellite nanoparticles, provided strong SERS enhancement. MPBA not only acted as a robust Raman reporter but also improved the orientation of antibodies. The SERS-LFIA achieved a limit of detection of 0.0056 ng·mL-1 in PBS, a 305-fold improvement over conventional AuNP-LFIA, and demonstrated favorable linear detection in biological samples, with limits of 0.051 ng·mL-1 in serum and 0.030 ng·mL-1 in tears. This assay offers a sensitive and reliable platform for MMP-9 detection and has great potential for disease diagnostics.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"1 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684399","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}
Chloé Gioiosa,Kshama Sharma,Thomas C Robinson,David Gajan,Sami Jannin,Ségolène Laage,Anne Lesage
{"title":"Elucidating the Substitution Pattern of a Hydroxyethyl Cellulose Thickening Agent by DNP-Enhanced Solid-State NMR.","authors":"Chloé Gioiosa,Kshama Sharma,Thomas C Robinson,David Gajan,Sami Jannin,Ségolène Laage,Anne Lesage","doi":"10.1021/acs.analchem.5c00487","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c00487","url":null,"abstract":"Hydroxyethyl cellulose (HEC) is a widely used industrial thickening agent added to formulations such as water-based lubricants. The nature and location of the substituents on the cellulose backbone impact its physicochemical properties. In this study, we investigated the functionalization pattern of a commercially available HEC sample using a multifaceted solid-state NMR study. First, leveraging the substantial signal amplification provided by Dynamic Nuclear Polarization (DNP), we performed a 13C-13C DNP-enhanced refocused INADEQUATE experiment on natural abundance HEC. This enabled the identification of the substitution sites within the cellulose backbone. Then, we acquired a room-temperature quantitative single-pulse 13C spectrum to quantify the length and distribution of the functionalized groups. This approach comprehensively describes the HEC substitution scheme, yielding crucial structural information. We unambiguously identified two substitution sites C2 and C6, and determined their degree of substitution (respectively 75 and 60%), as well as the ratio between single and multiple hydroxyethyl groups (33%). The proposed methodology opens the way to the development of new industrial analytical tools to ensure the quality and consistency of hydroxyethyl cellulose in its solid state or in complex formulations.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"25 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684406","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}
Shaoning Zheng,Runqiu Wang,Hanxu Ma,Ying He,Shunda Qiao,Renpeng Yan,Yufei Ma
{"title":"A Clamp-Shaped Quartz Tuning Fork-Based Laser Spectroscopy Sensor.","authors":"Shaoning Zheng,Runqiu Wang,Hanxu Ma,Ying He,Shunda Qiao,Renpeng Yan,Yufei Ma","doi":"10.1021/acs.analchem.5c02454","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c02454","url":null,"abstract":"A novel clamp-shaped quartz tuning fork (QTF)-based laser spectroscopy sensor is reported in this paper. The clamp-type structure was created to enhance stress and temperature gradient while optimizing the distribution of surface charges in QTF-based laser spectroscopy. Additionally, this structure eliminates the sharp right angles of the QTF, thereby minimizing performance degradation caused by residual unexpected materials. The QTF features a low resonant frequency (f0, ∼7.59 kHz) and a broad tine spacing. These characteristics contribute to an extended energy accumulation period and a simplified optical alignment process. Quartz-enhanced photoacoustic spectroscopy (QEPAS) and light-induced thermoelastic spectroscopy (LITES) were used to validate its functionality. In QEPAS and LITES simulations, the integrated surface charge of the clamp-shaped QTF was enhanced by 2.48 and 2.96 times, respectively, compared to the widely used standard QTF with an f0 of 32.768 kHz. Experimental data indicate that the signal-to-noise ratio (SNR) of the QEPAS sensor based on the clamp-shaped QTF was improved by 1.92 times compared to the standard QTF. The signal intensity was enhanced 41.3-fold in the clamp-shaped QTF upon integration of an acoustic microresonator (AmR). When the system average time reached 1000 s, a reduction of the acetylene (C2H2) minimum detection limit (MDL) to 28.27 ppb was observed. In the LITES technique, the SNR of the clamp-shaped QTF-based sensor was improved by 2.45 times compared with the standard QTF, with an MDL of 251.4 ppb at a system average time of 100 s. Both theoretical simulations and experimental results in this paper clearly demonstrate the advantages of this clamp-shaped QTF in laser spectroscopy sensing.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"110 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693448","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":"Mass In Situ Hybridization Enables Mass Cytometry to Detect Telomere Length.","authors":"Kaixian Yan,Hao Zhang,Guojun Han,Ran Kong,Yang Zhao","doi":"10.1021/acs.analchem.5c01665","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c01665","url":null,"abstract":"Single-cell resolution detection of DNA sequences is crucial for advancing our understanding of cellular differentiation and disease mechanisms. Mass cytometry has had a transformative impact on single-cell protein analysis; however, the potential of mass cytometry in genomics remains limited due to the inability to integrate DNA sequence detection. Bridging this gap is essential to expanding the capabilities of mass cytometry for comprehensive genomic and proteomic studies. In this work, we presented a novel mass in situ hybridization (MISH) strategy that enables the detection of specific DNA sequences─telomeres at single-cell resolution. At first, we synthesized a dendritic oligomer chelated with holmium (Ho), which had enough sensitivity and proper molecular size, and then conjugated it with a high-specificity telomere oligo-DNA probe containing the (AATCCC)3 sequence, a short complementary nucleic acid sequence of telomere. Finally, we successfully applied MISH to detect the telomere length via mass cytometry and imaging mass cytometry (IMC). Our method establishes the first successful strategy for telomere length detection via mass cytometry, marking a significant technological breakthrough. This innovation offers considerable potential for expanding the application of mass cytometry for the detection of specific DNA sequences.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"25 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684401","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":"Early Stage Soft Protein Corona Identification on Nanoparticles via Extended Size Exclusion Chromatography.","authors":"Ali Akbar Ashkarran","doi":"10.1021/acs.analchem.5c02364","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c02364","url":null,"abstract":"Unlike the hard protein corona (HPC), the soft protein corona (SPC) is a dynamic and complex layer for which limited knowledge exists regarding its structure and composition, primarily due to critical challenges in separating and purifying SPC from nanoparticles (NPs). In this study, we report the identification of SPC on the surface of polystyrene NPs at low time scales (i.e., a few to a hundred seconds). Using extended size exclusion chromatography (SEC) columns (i.e., 200 mm) and relatively large NPs (i.e., 300 nm), we successfully separated SPC-coated NPs from excess plasma. Our results show that SPC-coated NPs elute in early fractions, while excess plasma elutes in later fractions due to the significant size difference between plasma proteins and NPs, as well as the long column length. Additionally, SPC-coated NPs exhibit a relatively thicker shell compared with HPC-coated NPs, likely due to the rapid adsorption of large, abundant proteins such as albumin, as confirmed by both TEM and DLS measurements. Liquid chromatography-mass spectrometry (LC-MS) analysis further revealed that SPC formed at early incubation times (5-120 s) exhibited significantly lower protein diversity (59-93 proteins) compared to the hard protein corona (HPC, 152 proteins). The SPC composition dynamically evolved within seconds, highlighting the rapid competitive adsorption and displacement of abundant plasma proteins at nanoparticle interfaces in the first few seconds. These findings underscore the critical need for time-resolved approaches to accurately characterize nanoparticle-protein interactions at biologically relevant time scales.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"143 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693449","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}
Xinyi Li,Yongqi Wang,Yuhang Zhang,Fangying Shi,Chuan-Fan Ding,Yinghua Yan
{"title":"Multilevel Hydrangea-like Heterogeneous Oxides Enabling COVID-19 Progression Surveillance via Metabolic Fingerprints.","authors":"Xinyi Li,Yongqi Wang,Yuhang Zhang,Fangying Shi,Chuan-Fan Ding,Yinghua Yan","doi":"10.1021/acs.analchem.5c02442","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c02442","url":null,"abstract":"Coronavirus disease 2019 (COVID-19), a global pandemic infectious disease, requires early diagnosis and dynamic monitoring to enable timely intervention and reduce the risks of adverse outcomes. To support these needs, we developed an advanced metabolic monitoring platform by incorporating a silica template to engineer a hierarchical interlocked and closely intertwined multilevel hydrangea-like heterogeneous oxide (dubbed as MHHOs) matrix to extract serum metabolic fingerprints (SMFs) efficiently for early diagnosis and monitoring COVID-19 progression. Decoded by machine learning algorithms, this approach achieves 100% classification accuracy in distinguishing between different stages of the COVID-19 progression. Furthermore, the integrated screening model, optimized in accordance with clinical requirements, consistently surpasses a threshold of 0.98 across multiple key performance metrics, including accuracy, precision, recall, F1 score, and Matthews correlation coefficient, thereby demonstrating its robustness and practical applicability in clinical settings. In addition, by investigating the associated pathways and expression patterns of key biomarkers throughout disease progression, we explored their dynamic regulatory mechanism, enhancing the characterization of COVID-19 pathological features. Collectively, this work provides a perspective for the metabolite-based analytical platform and holds promise for advancing the clinical implementation of personalized therapeutic strategies.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"17 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693450","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":"Dehybridization-Free and Fluorescent Cleavage-Active DNAzyme by a Catalytic Core-Associative Fluorogen.","authors":"Jiahui Chen,Qiyao Chen,Qinxin Li,Jiahuan Zhou,Sihui Huang,Dandan Wang,Xiaoshun Zhou,Yong Shao","doi":"10.1021/acs.analchem.5c01820","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c01820","url":null,"abstract":"Metal-ion-dependent cleavage-active DNAzymes (caDz) are increasingly utilized in fields of sensing, environmental monitoring, and diagnostics. Currently, screening caDz and programming its cleavage activity rely on the \"catalytic beacon\" approach needing covalent duplex arm modifications by fluorophores and quenchers (thus named AM-caDz). Although this approach is widely used, the tedious modifications for operation limit its utilization in ordinary laboratories. Furthermore, dehybridization of cleaved substrate strands from DNAzyme strands is needed to signal the cleavage events. Thus, the arm length must meet a compromise to keep AM-caDz at a duplex state for cleavage and ensure a dehybridization state after cleavage for signaling, which is highly susceptible to environmental fluctuation. Herein, we developed fluorescent caDz (F-caDz) that can operate in a label-free and dehybridization-free manner. A fluorogen of hypericin (Hyp) was found to be able to specifically associate with the folding catalytic core of the GR5 caDz, resulting in a turn-on fluorescence (thus named F-caDz). The Pb2+-mediated cleavage subsequently unfolded the catalytic core and released Hyp but without dehybridization of cleaved substrates. The resultant fluorescence alteration was used to evaluate the cleavage activity of F-caDz. Furthermore, this folding catalytic core association did not affect the final cleavage efficiency but caused a modification in the cleavage kinetics. This F-caDz provides a sensitive and specific method to detect Pb2+. By finding the appropriate fluorogens, this method can be applied to other caDz. We expect that F-caDz will also provide a convenient approach to regulating the cleavage behavior of caDz.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"16 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684404","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}
Ida Marie M Løber,Mette S Hedemann,Palle Villesen,Kirstine L Nielsen
{"title":"Untangling the Postmortem Metabolome: A Machine Learning Approach for Accurate PMI Estimation.","authors":"Ida Marie M Løber,Mette S Hedemann,Palle Villesen,Kirstine L Nielsen","doi":"10.1021/acs.analchem.4c05796","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c05796","url":null,"abstract":"Accurate estimation of the postmortem interval (PMI) is crucial for medico-legal investigations, providing critical timelines for criminal cases. Current PMI methods, however, often lack precision, limiting their forensic utility. In this study, we developed models to estimate PMI with high accuracy across various tissues within the first 4 days after death. Using untargeted UHPLC-qTOF-MS, we analyzed thousands of molecules in rat tissues with different PMIs. We employed machine learning on stable and highly reproducible molecules in each tissue to select candidate biomarkers and then built a second model using only the top 15 molecules. Both Lasso and Random Forest approaches yielded high cross-validation accuracy across all tissues, with the latter showing slightly superior performance. Validation was conducted using an independently collected and analyzed set of rats. The identified metabolites, including amino acids, derivatives, nucleosides, and other markers, are common to humans and mammals, underscoring their potential applicability in human forensic contexts. Our findings highlight the tissue-specific predictive potential and variability in predictive accuracy across different tissues in a rodent model.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684405","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":"Quantitative Detection of Pyrazines in Edible Oils Using SABRE Hyperpolarized NMR Spectroscopy.","authors":"Anran Dai,Ao Xue,Huijun Sun,Zitao Duan,Xiaohong Cui,Xinchang Wang,Zhong Chen","doi":"10.1021/acs.analchem.5c00040","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c00040","url":null,"abstract":"Pyrazines are key flavor compounds in various foods, and their detection is essential for assessing quality, authenticity, and potential adulteration. However, because food matrices are complex mixtures, detecting pyrazines typically requires complex pretreatment steps to eliminate interference from structurally similar molecules. In this study, we present a highly selective detection method for pyrazines in food using sensitive and quantitative hyperpolarized NMR. Trace pyrazine compounds in edible oils were detected on a benchtop NMR system (60 MHz, 1.4 T) utilizing signal amplification by reversible exchange (SABRE) hyperpolarization through cosubstrate strategy. Thanks to the high selectivity of SABRE toward pyrazines, our method requires only a simple extraction procedure to achieve accurate quantification of pyrazine with the concentration of 59.3 μmol/L in sesame oil, and the limit of quantification is as low as 21.0 μmol/L. Compared to conventional high-field NMR (500 MHz, 11.7 T), our approach demonstrates high sensitivity and accuracy on a low-field NMR spectrometer. Our works validate SABRE as a powerful tool for highly selective trace analysis, with potential applications in food quality assessment, flavor profiling, and bioactivity analysis.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"144 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684400","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}