{"title":"Dual-State Emissive Mitochondrial Viscosity Probe for Long-Term Imaging of Rheumatoid Arthritis","authors":"Shiya Zhang, Shengyi Gong, Jiaxin Hong, Jinzheng Zhang, Guoqiang Feng","doi":"10.1021/acs.analchem.4c05676","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c05676","url":null,"abstract":"Rheumatoid arthritis (RA) is a destructive autoimmune disease that seriously affects human health. Due to the lack of a cure for RA, a good prognosis largely depends on early diagnosis and effective treatment monitoring of RA. Therefore, the development of fluorescent probes capable of real-time detection of RA is of great significance. Dual-state emission (DSE) molecules can emit light in both dilute solution and solid state, making them ideal fluorophores for constructing fluorescent probes. However, there are currently no reports of DSE molecule-based fluorescent probes for RA imaging. Herein, we report a fluorescent probe <b>MQP-Boc</b> based on a novel DSE molecule for effective RA imaging. <b>MQP-Boc</b> selectively responds to viscosity with sensitive fluorescence changes at 667 nm and is mitochondria targetable. Cell imaging studies show that <b>MQP-Boc</b> can detect changes in mitochondrial viscosity and perform long-term imaging of mitochondria, which is significantly superior to that of the control probe <b>MQP-Ac</b>. Imaging studies on a mouse model of RA induced by λ-carrageenan show that <b>MQP-Boc</b> has excellent real-time and long-term imaging capabilities for RA. Besides, with <b>MQP-Boc</b>, significant increases in joint tissue viscosity were found during the RA process. All results indicate that <b>MQP-Boc</b> is an effective new tool for studying and diagnosing RA.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"105 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020209","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":"Viral Membrane-Targeting Amphipathic Helical Peptide-Based Fluorogenic Probes for the Analysis of Infectious Titers of Enveloped Viruses","authors":"Yusuke Sato, Yusaku Hatanaka, Yoshitaka Sato, Kota Matsumoto, Shion Osana, Ryoichi Nagatomi, Seiichi Nishizawa","doi":"10.1021/acs.analchem.4c04852","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04852","url":null,"abstract":"Enveloped viruses have caused the majority of epidemics and pandemics over the past decade. Direct sensing of virus particles (virions) holds great potential for the functional analysis of enveloped viruses. Here, we explore a series of viral membrane-targeting amphipathic helical (AH) peptide-based molecular probes for the assessment of infectious titers of the human coronavirus 229E virus (HCoV-229E). The M2-protein-derived AH peptide is identified as a strong binder for HCoV-229E, and its conjugate with Nile Red, M2-NR, exhibits fluorogenic response upon selective binding to the viral membrane of HCoV-229E. We demonstrate that the response of M2-NR toward the HCoV-229E virus enables the rapid, simple, and reliable assessment of the infectivity of HCoV-229E. In addition, the present fluorescence assay for infectivity analysis is applicable to various kinds of enveloped virus including influenza A virus, herpes simplex virus-1, and lentivirus.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"69 2 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992097","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":"Polyfluorene-Enhanced Near-Infrared Electrochemiluminescence of Heptamethine Cyanine Dye for Coreactants-Free Bioanalysis","authors":"Xin Wen, Yingying Chen, Ying He, Ruo Yuan, Shihong Chen","doi":"10.1021/acs.analchem.4c04722","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04722","url":null,"abstract":"The near-infrared electrochemiluminescence (NIR-ECL) technique has received special attention in cell imaging and biomedical analysis due to its deep tissue penetration, low background interference, and high sensitivity. Although cyanine-based dyes are promising NIR-ECL luminophores, limited ECL efficiency and the need for exogenous coreactants have prevented their widespread application. In this work, poly[9,9-bis(3′-(<i>N,N</i>-dimethylamino)propyl)-2,7-fluorene]-<i>alt</i>-2,7-(9,9-dioctylfluorene)] (PFN) was innovatively developed to significantly invigorate the NIR-ECL performance of heptamethine cyanine dye IR 783 by the resonance energy transfer (RET) strategy. Astonishingly, the IR@PFN nanoparticles (NPs) synthesized from IR 783 and PFN by a nanoprecipitation method emitted a strong coreactant-free NIR-ECL signal at +1.05 V, and the maximum emission wavelength was 815 nm. IR@PFN NPs were integrated in a spontaneous entropy-driven chain replacement (ESDR) reaction to achieve ECL analysis of microRNA-21 (miRNA-21), and the limit of detection was as low as 0.25 fM. IR@PFN NPs created a promising coreactant-free NIR-ECL platform for bioanalysis and imaging, providing a novel NIR-ECL detection method for miRNA-21.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"19 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020171","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":"Super-Resolution Fluorescence Imaging Reveals the Mechanism of NRP1 Clustering on Non-Small-Cell Lung Cancer Membranes","authors":"Meng Li, Jing Gao, Xiao Qi, Baofeng Li, Yinghao Zhao, Xiangyu Liu, Guangxin Zhang, Hongda Wang, Ti Tong","doi":"10.1021/acs.analchem.4c05675","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c05675","url":null,"abstract":"Neuropilin 1 (NRP1) is upregulated in various types of malignant tumors, especially non-small-cell lung cancer (NSCLC). However, the precise mechanisms for membrane localization and regulation are not fully understood. Observations from super-resolution microscopy have revealed that NRP1 tends to form nanoscale clusters on the cell membrane, with these clusters varying significantly in size and density across different regions. Further research has shown that stimulation by hepatocyte growth factor (HGF) can reorganize the distribution of NRP1, reducing the number of small clusters while promoting the formation of larger ones. This suggests a propensity for internalization after activation. Additionally, dual-color dSTORM imaging has demonstrated a certain degree of colocalization between NRP1 and c-MET, indicating that c-MET plays an important role in stabilizing NRP1 clusters. This study provides new insights into the mechanism behind NRP1’s clustered distribution on cell membranes and paves the way for developing more effective therapeutic strategies targeting NRP1 within tumors.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"37 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992098","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}
Barbora Papoušková, Petr Fryčák, Filip Gregar, Karel Lemr, Tomáš Pluháček
{"title":"Remote Deep-Ultraviolet Laser Ablation in Connection with Electrospray Ionization–Atmospheric Pressure Chemical Ionization (rDUVLAESCI): A Novel Dual Ionization Source for Molecular Mass Spectrometry","authors":"Barbora Papoušková, Petr Fryčák, Filip Gregar, Karel Lemr, Tomáš Pluháček","doi":"10.1021/acs.analchem.4c04392","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04392","url":null,"abstract":"A novel remote deep ultraviolet laser ablation inlet connected to a dual electrospray ionization–atmospheric pressure chemical ionization (rDUVLAESCI) source is presented. This system allows for the simultaneous and spatial acquisition of mass spectrometry (MS) data for organic molecules with diverse polarities and molecular weights. Deep 193 nm UV laser ablation was used to sample analytes from dried spots for molecular MS analysis precisely. Furthermore, molecular MS imaging (MSI) with a variable laser spot size down to 3 μm was demonstrated. The complementary ionization modes generated mass spectra with sufficient analyte signals, detecting a broad range of molecules from polar compounds like caffeine and PEG 600, to nonpolar analytes, such as anthracene and wax esters, all within a single analytical run. Detection limits were found in the tens of attomoles per ablated/desorbed pixel. The powerful capabilities of the fully automated rDUVLAESCI dual source were demonstrated by visualizing the spatial distribution of new psychoactive substances on latent fingerprints. MSI for both sebum components and psychoactive substances revealed a connection between the chemical evidence and biometrical information. The rDUVLAESCI–MSI enabled the unambiguous identification of individuals, even using partially overlapped latent fingerprints. This unique rDUVLAESCI approach, with its remote laser ablation unit, improved spatial resolution and analyte coverage, particularly for nonpolar compounds.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"12 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992154","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}
Ahmed Bahti, Ahmad Telfah, Roland Hergenröder, Dieter Suter
{"title":"NMR Spectral Editing, Water Suppression, and Dipolar Decoupling in Low-Field NMR Spectroscopy Using Optimal Control Pulses and Multiple-Pulse Sequence","authors":"Ahmed Bahti, Ahmad Telfah, Roland Hergenröder, Dieter Suter","doi":"10.1021/acs.analchem.3c05226","DOIUrl":"https://doi.org/10.1021/acs.analchem.3c05226","url":null,"abstract":"Spectral dispersion in low-field nuclear magnetic resonance (NMR) can significantly affect NMR spectral analysis, particularly when studying complex mixtures like metabolic profiling of biological samples. To address signal superposition in these spectra, we employed spectral editing with selective excitation pulses, proving it to be a suitable approach. Optimal control pulses were implemented in low-field NMR and demonstrated their capability to selectively excite and eliminate specific amino acids, such as phenylalanine and taurine, either individually or simultaneously. The broadening of NMR signals in viscous samples, like bio samples, due to homonuclear dipolar coupling often leads to loss of spectral details, impacting spectral assignments. Therefore, in this work, the multiple-pulse WAHUHA sequence at both high and low field NMR was employed resulting in approximately 63 and 25% reduction in line widths respectively, evident from line width changes in the NMR spectra. The effectiveness of this process was validated by comparing its performance with that of magic angle spinning NMR. Additionally, water suppression was achieved through selective excitation by adding a term representing the water signal to the overall Hamiltonian, expressing the water signal peak frequency, and covering adjacent frequencies on both sides of the water peak within the water signal.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"16 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992096","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}
Tingting Liu, Lina Dong, Nan Yue, Jing Lv, Bin Ji, Susu Xia, Cen Wang, Jiaxin Li, Jing Wang, Jinglin Wang, Na Xu, Shan Gao, Lin Kang, Wenwen Xin
{"title":"Innovative Ricin Toxin Detection: Unraveling Apurinic/Apyrimidinic Lyase Activity and Developing Fluorescence Sensors","authors":"Tingting Liu, Lina Dong, Nan Yue, Jing Lv, Bin Ji, Susu Xia, Cen Wang, Jiaxin Li, Jing Wang, Jinglin Wang, Na Xu, Shan Gao, Lin Kang, Wenwen Xin","doi":"10.1021/acs.analchem.4c06016","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c06016","url":null,"abstract":"Ricin toxin (RT) is a potential bioterrorism agent because of its high potency, extremely small lethal dose, ease of preparation, and notable stability. Therefore, a portable method is urgently required to efficiently detect and determine the presence of toxicity of RT and evaluate its potency for public health monitoring and counter-bioterrorism responses. Currently, enzyme-based assays for detecting RT mainly focus on its <i>N</i>-glycosidase activity. In this study, we demonstrated that RT exhibits apurinic/apyrimidinic (AP) lyase activity using several methods. Characterization of the enzyme reaction and kinetics revealed that AP lyase activity is optimal at 59 °C and pH 4.0. This activity is highly pH-sensitive, remaining active between pH 3.0 and pH 4.6. Furthermore, we developed a portable fluorescence-based lateral flow assay (FLFA) that detects RT much faster than existing assays based on its <i>N</i>-glycosidase activity. Moreover, this assay can efficiently detect RT at nanogram levels from complex matrix samples within 1.5 h while simultaneously determining its biological activity. In conclusion, the discovery of the AP lyase activity of RT and the development of FLFA represent novel approaches for studying the enzymatic profiles of other ribosome-inactivating proteins.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"51 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020212","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}
Xianjie Qiu, Wenqi Li, Xiaoqin Li, Bin Wu, Minxian Dai, Yi Xia, Gong Zhang, Yizhou Bian, Jiayi Chen, Kunzhong Wu, Yongzhi Lu, Miru Tang, Hua Lin, Jinsai Shang
{"title":"Discovery of Fluorescent Probe ABDS-2 for Farnesoid X Receptor Modulator Characterization and Cell-Based Imaging","authors":"Xianjie Qiu, Wenqi Li, Xiaoqin Li, Bin Wu, Minxian Dai, Yi Xia, Gong Zhang, Yizhou Bian, Jiayi Chen, Kunzhong Wu, Yongzhi Lu, Miru Tang, Hua Lin, Jinsai Shang","doi":"10.1021/acs.analchem.4c03743","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c03743","url":null,"abstract":"The farnesoid X receptor (FXR) regulates key physiological processes, such as bile acid homeostasis and lipid metabolism, making it an important target for drug discovery. However, the overactivation of FXR often leads to adverse effects. This study presents the development of a novel fluorescent probe utilizing the computer-aided drug design (CADD) approach to optimize linkers between more potent warhead and FITC fluorescent groups. The probes were designed and assessed via molecular dynamics simulations, and four were selected for synthesis to be evaluated in in vitro biochemical assays. Among these, ABDS-2 exhibited high sensitivity and stability, which demonstrated satisfactory validation in high-throughput screening assays. Furthermore, ABDS-2 facilitated real-time bioimaging to monitor FXR homeostasis at the cellular level, providing spatially resolved insights into molecular interactions critical for cellular function studies. This research underscores the efficiency of CADD in probe design and positions ABDS-2 as a valuable chemical tool for in vitro assays and cellular-level bioimaging.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"32 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992095","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":"Complex and Non-sequential Current Signatures of a β-Hairpin Peptide Confined in a Nanopore","authors":"Misa Yamaji, Mauro Chinappi, Blasco Morozzo della Rocca, Kenji Usui, Ryuji Kawano","doi":"10.1021/acs.analchem.4c04150","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04150","url":null,"abstract":"Nanopore sensing is widely used for single-molecule detection, originally applied to nucleic acids and now extended to protein sensing. Our study focuses on the complex conformational changes of peptides in nanopores, which may have implications for peptide fingerprinting and protein identification. Specifically, we investigated the interaction of a β-hairpin peptide (SV28) within an α-hemolysin (αHL) nanopore. Our experiments revealed that SV28 is captured via dielectrophoresis and exhibits long dwell times within the nanopore, leading to multiple current blockade levels. Unlike DNA hairpins, the peptide showed non-sequential transitions among four distinct blockade levels. This complex behavior indicates that the peptide dynamics in nanopores cannot be simply modeled along a single reaction coordinate. Our findings provide insights into peptide-nanopore interactions, which are potentially useful for developing nanopore-based peptide identification technologies.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"33 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020170","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}
Yao Gao, Xue Fan, Xuechen Zhang, Qinglin Guan, Yongheng Xing, Wenbo Song, Daqian Song
{"title":"Rapid Recognition and Monitoring of Multiple Core Biomarkers with Point-of-Care Importance through Combinatorial DNA Logic Operation","authors":"Yao Gao, Xue Fan, Xuechen Zhang, Qinglin Guan, Yongheng Xing, Wenbo Song, Daqian Song","doi":"10.1021/acs.analchem.4c05904","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c05904","url":null,"abstract":"The early diagnosis of a disease relies on the reliable identification and quantitation of multiple core biomarkers in real-time point-of-care (POC) testing. To date, most of the multiplex photoelectrochemical (PEC) assays are inaccessible to home healthcare due to cumbersome steps, long testing time, and limited detection efficiency. The rapid and fast-response generation of independent photocurrent for multiple targets is still a great challenge. Herein, a combinatorial DNA logic operation-guided multiplex PEC sensor is constructed to facilely distinguish and simultaneously monitor two core biomarkers that are essential for identifying asymptomatic Alzheimer patients and predicting the progression of the disease. The aptamers of amyloid-β oligomers (AβO) and Tau<sub>441</sub> protein are simply integrated at the high-performance In-TBAPy photocathode. In the presence of AβO and Tau<sub>441</sub> protein, the aptamer–target affinity complexes are formed and subsequently detached from the electrode surface, resulting in an increase of photocurrent. Through programming concatenated DNA molecular circuits, a 2-target input OR logic gate not only simplifies the manufacturing process of the multiplex PEC sensor but also realizes rapid and intelligent multiple-target recognition. As a conceptual prototype for the development of more sophisticated and complicated logic devices, the proposed DNA molecular logic system may open a new horizon for rapid disease diagnosis and POC analysis.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"32 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992574","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}