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Large Language Model-Enhanced MFSSG Enables Effective and Accurate Integration Analysis for Microbiome−Metabolome Data
IF 7.4 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-21 DOI: 10.1021/acs.analchem.6c04275
Yuanyuan Ma,Lifang Liu,Yingjun Ma
The massive volume of paired microbiome and metabolome measurementsgenerated through high-throughput sequencing and mass spectrometryhas created an urgent need for dedicated, integrative analytical pipelines. Existing tools lack the capacity to simultaneously support sample clustering, multi-omics visualization, disease risk stratification, and biological age quantification using matched dual-modal datasets. To overcome this analytical bottleneck, we introduce the matrix factorization with shared and specific graph learning (MFSSG) toolkit: an unsupervised matrix factorization framework that jointly learns both shared and modality-specific graph structures. MFSSG preserves cross-omics spatial consistency by leveraging shared nearest-neighbor graphs derived from analytical profiles and incorporates two complementary regularization termsentropy regularization to enhance cluster discriminability and a pre-trained microbial graph Laplacianto mitigate measurement bias inherent in microbiome sequencing versus metabolomic mass spectrometry data. Validated across three independent multi-omics cohorts derived from gastric and gut biospecimensincluding gastric cancer, end-stage renal disease, and type 1 diabetesMFSSG consistently outperforms state-of-the-art integration methods in disease classification. Furthermore, a novel pairwise learning module enables parallel and accurate quantification of the metabolic age and microbial age, facilitating refined patient risk stratification. This versatile toolkit provides a robust chemometric strategy for uncovering latent biological patterns embedded within heterogeneous multi-omics analytical data.
{"title":"Large Language Model-Enhanced MFSSG Enables Effective and Accurate Integration Analysis for Microbiome−Metabolome Data","authors":"Yuanyuan Ma,Lifang Liu,Yingjun Ma","doi":"10.1021/acs.analchem.6c04275","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c04275","url":null,"abstract":"The massive volume of paired microbiome and metabolome measurementsgenerated through high-throughput sequencing and mass spectrometryhas created an urgent need for dedicated, integrative analytical pipelines. Existing tools lack the capacity to simultaneously support sample clustering, multi-omics visualization, disease risk stratification, and biological age quantification using matched dual-modal datasets. To overcome this analytical bottleneck, we introduce the matrix factorization with shared and specific graph learning (MFSSG) toolkit: an unsupervised matrix factorization framework that jointly learns both shared and modality-specific graph structures. MFSSG preserves cross-omics spatial consistency by leveraging shared nearest-neighbor graphs derived from analytical profiles and incorporates two complementary regularization termsentropy regularization to enhance cluster discriminability and a pre-trained microbial graph Laplacianto mitigate measurement bias inherent in microbiome sequencing versus metabolomic mass spectrometry data. Validated across three independent multi-omics cohorts derived from gastric and gut biospecimensincluding gastric cancer, end-stage renal disease, and type 1 diabetesMFSSG consistently outperforms state-of-the-art integration methods in disease classification. Furthermore, a novel pairwise learning module enables parallel and accurate quantification of the metabolic age and microbial age, facilitating refined patient risk stratification. This versatile toolkit provides a robust chemometric strategy for uncovering latent biological patterns embedded within heterogeneous multi-omics analytical data.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226095","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}
引用次数: 0
Deep-Learning-Assisted Rational Design of a High-Brightness Dual-Lock Chemiluminescent Probe for Ultrasensitive Detection of Salmonella
IF 7.4 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-21 DOI: 10.1021/acs.analchem.6c04331
Yanzhi Zhou,Pengfei Yang,Jun Jing,Yue Jiang,Deliang Wang,Peihong Xiao
The development of chemiluminescent probes that simultaneously achieve high brightness and stability remains a significant challenge for ultrasensitive bioassays. Herein, we report a deep-learning-assisted rational design of a novel dual-lock chemiluminescent probe for ultrasensitive Salmonella detection. A fully connected network was trained to predict chemiluminescence intensity, successfully identifying a cyclobutane-acrylonitrile-substituted phenoxy-1,2-dioxetane as an optimal high-brightness chemiluminophore. To circumvent its inherent instability, a dual-lock strategy was implemented: the first lock is opened by a Salmonella-associated C8-esterase activity to accumulate a stable pre-chemiluminophore, and the second lock is subsequently unlocked by in situ-generated singlet oxygen (1O2) via a [2 + 2] cycloaddition, triggering a burst of chemiluminescence. The resultant probe, DSCP-ANCB, exhibits exceptional performance, enabling Salmonella detection with a limit of detection (LOD) as low as 1.9 CFU mL−1 within a total turnaround time of 3 to 8 h, which represents a 1008-fold enhancement in sensitivity over the commercial MUCAP probe. Furthermore, it shows 100% positive and 96% negative agreement with mass spectrometry in clinical isolates (n = 113) and significantly outperforms the commercial fluorescent probe in complex food and environmental matrices. This work introduces a deep-learning-assisted strategy for developing high-performance chemiluminescent diagnostic tools. By integrating computational prediction with rational probe design, this framework provides a generalized approach to improve the overall performance of chemiluminescent probes.
{"title":"Deep-Learning-Assisted Rational Design of a High-Brightness Dual-Lock Chemiluminescent Probe for Ultrasensitive Detection of Salmonella","authors":"Yanzhi Zhou,Pengfei Yang,Jun Jing,Yue Jiang,Deliang Wang,Peihong Xiao","doi":"10.1021/acs.analchem.6c04331","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c04331","url":null,"abstract":"The development of chemiluminescent probes that simultaneously achieve high brightness and stability remains a significant challenge for ultrasensitive bioassays. Herein, we report a deep-learning-assisted rational design of a novel dual-lock chemiluminescent probe for ultrasensitive Salmonella detection. A fully connected network was trained to predict chemiluminescence intensity, successfully identifying a cyclobutane-acrylonitrile-substituted phenoxy-1,2-dioxetane as an optimal high-brightness chemiluminophore. To circumvent its inherent instability, a dual-lock strategy was implemented: the first lock is opened by a Salmonella-associated C8-esterase activity to accumulate a stable pre-chemiluminophore, and the second lock is subsequently unlocked by in situ-generated singlet oxygen (1O2) via a [2 + 2] cycloaddition, triggering a burst of chemiluminescence. The resultant probe, DSCP-ANCB, exhibits exceptional performance, enabling Salmonella detection with a limit of detection (LOD) as low as 1.9 CFU mL−1 within a total turnaround time of 3 to 8 h, which represents a 1008-fold enhancement in sensitivity over the commercial MUCAP probe. Furthermore, it shows 100% positive and 96% negative agreement with mass spectrometry in clinical isolates (n = 113) and significantly outperforms the commercial fluorescent probe in complex food and environmental matrices. This work introduces a deep-learning-assisted strategy for developing high-performance chemiluminescent diagnostic tools. By integrating computational prediction with rational probe design, this framework provides a generalized approach to improve the overall performance of chemiluminescent probes.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"32 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226103","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}
引用次数: 0
Single-Step Sample-Activated Alternating Sequential Flow Enables Autonomous Multistep Electrochemical Lateral Flow Detection of Mpox Virus DNA
IF 7.4 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-21 DOI: 10.1021/acs.analchem.6c03141
Vasita Lapee-e,Piyathida Phimdee,Hyo-Il Jung,Ekawat Pasomsub,Abdulhadee Yakoh
The 2022 multinational mpox virus (MPXV) outbreak and continued cross-border transmission have highlighted limitations of laboratory-confined PCR diagnostics. Here, we report an alternating lateral flow architecture (ALFA) that transforms traditional single-pass lateral flow into a programmable platform for autonomous multistep electrochemical nucleic acid detection following a single prepared-sample introduction. By regulating passive fluid delivery, ALFA enables sequential molecular processing and in situ signal generation without external intervention. Coupled with Ag(I)-mediated mismatch DNA nanocomplexes (MDNs), the system provides electrochemical signal amplification without nucleic acid amplification. ALFA detected MPXV DNA with a limit of detection (LOD) of 1.55 pM and a linear range of 101−105 pM. In urine and saliva spiked with structurally intact viral particles, the lowest statistically distinguishable concentration was 10 copies mL−1. Clinical evaluation of 50 PCR-characterized lesion swab samples yielded 92.11% sensitivity, 100% specificity, and 94.0% accuracy. The platform also maintained stable performance over an estimated 112 days. ALFA therefore provides a programmable lateral flow framework for rapid, amplification-free, decentralized nucleic acid diagnostics.
{"title":"Single-Step Sample-Activated Alternating Sequential Flow Enables Autonomous Multistep Electrochemical Lateral Flow Detection of Mpox Virus DNA","authors":"Vasita Lapee-e,Piyathida Phimdee,Hyo-Il Jung,Ekawat Pasomsub,Abdulhadee Yakoh","doi":"10.1021/acs.analchem.6c03141","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c03141","url":null,"abstract":"The 2022 multinational mpox virus (MPXV) outbreak and continued cross-border transmission have highlighted limitations of laboratory-confined PCR diagnostics. Here, we report an alternating lateral flow architecture (ALFA) that transforms traditional single-pass lateral flow into a programmable platform for autonomous multistep electrochemical nucleic acid detection following a single prepared-sample introduction. By regulating passive fluid delivery, ALFA enables sequential molecular processing and in situ signal generation without external intervention. Coupled with Ag(I)-mediated mismatch DNA nanocomplexes (MDNs), the system provides electrochemical signal amplification without nucleic acid amplification. ALFA detected MPXV DNA with a limit of detection (LOD) of 1.55 pM and a linear range of 101−105 pM. In urine and saliva spiked with structurally intact viral particles, the lowest statistically distinguishable concentration was 10 copies mL−1. Clinical evaluation of 50 PCR-characterized lesion swab samples yielded 92.11% sensitivity, 100% specificity, and 94.0% accuracy. The platform also maintained stable performance over an estimated 112 days. ALFA therefore provides a programmable lateral flow framework for rapid, amplification-free, decentralized nucleic acid diagnostics.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"19 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226096","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}
引用次数: 0
A Transformation-Guided Mass Spectrometry Workflow for Expanding In Vivo Metabolite Coverage and Revealing Noncanonical Metabolism of Epigallocatechin Gallate
IF 7.4 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-21 DOI: 10.1021/acs.analchem.6c02274
Zongde Jiang,Shuwei Zhang,Yingdong Zhu,Weixin Wang,Shengmin Sang
In vivo metabolism of dietary bioactive compounds generates extensive chemical diversity, but much of this metabolite space remains inaccessible to current metabolomics workflows because of limited acquisition depth, database dependence, and insufficient structural validation. Here, we present a closed-loop analytical workflow for the systematic in vivo discovery, annotation, and validation of bioactive metabolites. The workflow integrates iterative DeepScan acquisition to improve MS2 coverage, diagnostic fragment-guided screening to prioritize scaffold-related metabolites, transformation-driven annotation with fragment ion search (FISh) prediction, multistage MSn evidence chaining, and structured tracing of unresolved metabolites with verified precursor origin. Using (−)-epigallocatechin gallate (EGCG), a major green tea bioactive component, as a model compound, this approach substantially expanded scaffold-linked precursor coverage, with later DeepScan injections (IDs 02−05) contributing 75% of the recovered precursor candidates, while 63% of annotated metabolites required transformation-rule expansion. A total of 702 EGCG-related candidate metabolites were detected, including 343 annotated metabolites assigned at Levels 1, 2b, and 3. Among the 209 metabolites assigned at Levels 1 and 2b, 111 had not been previously reported in vivo. In addition to resolving multiple noncanonical metabolic pathways, the workflow established a curated database of 359 traceable but structurally unresolved candidate metabolites for progressive refinement of the accessible chemical space. For structural validation, EGCG-derived reference products were generated through 21 different in vitro transformations. This analytical strategy addresses major limitations of database-centric metabolomics and provides a transferable framework for in vivo metabolite discovery and structural characterization of dietary bioactive compounds and related small-molecule exposures.
{"title":"A Transformation-Guided Mass Spectrometry Workflow for Expanding In Vivo Metabolite Coverage and Revealing Noncanonical Metabolism of Epigallocatechin Gallate","authors":"Zongde Jiang,Shuwei Zhang,Yingdong Zhu,Weixin Wang,Shengmin Sang","doi":"10.1021/acs.analchem.6c02274","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c02274","url":null,"abstract":"In vivo metabolism of dietary bioactive compounds generates extensive chemical diversity, but much of this metabolite space remains inaccessible to current metabolomics workflows because of limited acquisition depth, database dependence, and insufficient structural validation. Here, we present a closed-loop analytical workflow for the systematic in vivo discovery, annotation, and validation of bioactive metabolites. The workflow integrates iterative DeepScan acquisition to improve MS2 coverage, diagnostic fragment-guided screening to prioritize scaffold-related metabolites, transformation-driven annotation with fragment ion search (FISh) prediction, multistage MSn evidence chaining, and structured tracing of unresolved metabolites with verified precursor origin. Using (−)-epigallocatechin gallate (EGCG), a major green tea bioactive component, as a model compound, this approach substantially expanded scaffold-linked precursor coverage, with later DeepScan injections (IDs 02−05) contributing 75% of the recovered precursor candidates, while 63% of annotated metabolites required transformation-rule expansion. A total of 702 EGCG-related candidate metabolites were detected, including 343 annotated metabolites assigned at Levels 1, 2b, and 3. Among the 209 metabolites assigned at Levels 1 and 2b, 111 had not been previously reported in vivo. In addition to resolving multiple noncanonical metabolic pathways, the workflow established a curated database of 359 traceable but structurally unresolved candidate metabolites for progressive refinement of the accessible chemical space. For structural validation, EGCG-derived reference products were generated through 21 different in vitro transformations. This analytical strategy addresses major limitations of database-centric metabolomics and provides a transferable framework for in vivo metabolite discovery and structural characterization of dietary bioactive compounds and related small-molecule exposures.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"14 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226104","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}
引用次数: 0
Single-Atom Pt-Anchored MoOx Matrix for On-Tissue Calibration in Quantitative Mass Spectrometry Imaging
IF 7.4 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-21 DOI: 10.1021/acs.analchem.6c05625
Tao Ning,Wangshu Qin,Yushu Shi,Yawei Feng,Yanmiao Huo,Xinyu Liu,Xianzhe Shi,Guowang Xu
Quantitative mass spectrometry imaging (qMSI) enables spatially resolved metabolite profiling in biological tissues, yet reliable concentration mapping remains constrained by high matrix-derived background interference, limited metabolite coverage, and insufficient calibration robustness. To overcome these challenges, a single-atom platinum-anchored molybdenum oxide matrix (denoted as Ptsa/MoOx) was developed for qMSI. Compared with conventional organic matrices, the Ptsa/MoOx matrix not only substantially enhances metabolite ion signals but also effectively suppresses low-mass background interference. Comprehensive structural characterization revealed oxygen-deficient MoOx with highly dispersed Pt single atoms, and mechanistic investigation indicated that charge-mediated desorption and ionization contribute to the enhanced matrix performance. Using Ptsa/MoOx-assisted qMSI, an on-tissue calibration strategy was established across a wide polarity range of metabolites, achieving excellent linear responses from 43 to 853 ng mm−2. For metabolites lacking authentic standards, a class-matched concentration-referencing strategy was applied to generate concentration-referenced spatial maps for 124 metabolites. Application to five paired pancreatic tumor and adjacent non-tumor specimens demonstrated region-dependent differences across multiple lipid-related pathways as a proof-of-concept tissue application. Collectively, these results establish Ptsa/MoOx-assisted qMSI as an on-tissue calibrated platform for spatial metabolomics and demonstrate its potential for characterizing metabolic heterogeneity in biological tissues.
{"title":"Single-Atom Pt-Anchored MoOx Matrix for On-Tissue Calibration in Quantitative Mass Spectrometry Imaging","authors":"Tao Ning,Wangshu Qin,Yushu Shi,Yawei Feng,Yanmiao Huo,Xinyu Liu,Xianzhe Shi,Guowang Xu","doi":"10.1021/acs.analchem.6c05625","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c05625","url":null,"abstract":"Quantitative mass spectrometry imaging (qMSI) enables spatially resolved metabolite profiling in biological tissues, yet reliable concentration mapping remains constrained by high matrix-derived background interference, limited metabolite coverage, and insufficient calibration robustness. To overcome these challenges, a single-atom platinum-anchored molybdenum oxide matrix (denoted as Ptsa/MoOx) was developed for qMSI. Compared with conventional organic matrices, the Ptsa/MoOx matrix not only substantially enhances metabolite ion signals but also effectively suppresses low-mass background interference. Comprehensive structural characterization revealed oxygen-deficient MoOx with highly dispersed Pt single atoms, and mechanistic investigation indicated that charge-mediated desorption and ionization contribute to the enhanced matrix performance. Using Ptsa/MoOx-assisted qMSI, an on-tissue calibration strategy was established across a wide polarity range of metabolites, achieving excellent linear responses from 43 to 853 ng mm−2. For metabolites lacking authentic standards, a class-matched concentration-referencing strategy was applied to generate concentration-referenced spatial maps for 124 metabolites. Application to five paired pancreatic tumor and adjacent non-tumor specimens demonstrated region-dependent differences across multiple lipid-related pathways as a proof-of-concept tissue application. Collectively, these results establish Ptsa/MoOx-assisted qMSI as an on-tissue calibrated platform for spatial metabolomics and demonstrate its potential for characterizing metabolic heterogeneity in biological tissues.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"1 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226098","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}
引用次数: 0
Defect-Engineering-Tailored Triple-Enzyme-Mimetic Heterojunction Nanozyme-Based Colorimetric Sensor Array for AI-Powered On-Site Intelligent Assay of Multiple Antibiotic Residues
IF 7.4 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-21 DOI: 10.1021/acs.analchem.6c06085
Jinwei Zhang,Liang Huang,Jiayue Hu,Shanxin Sun,Cancan Jia,Sha Liu,Ying Gu,Yongning Wu,Yizhong Shen
Maintaining high levels of multienzyme-like activities within a single nanoparticle-based sensing array to boost the efficient simultaneous on-site assay of multiple antibiotic residues at low regulatory threshold levels is critical for the “One Health” initiative, but remains an ongoing challenge. Herein, a defect-engineered Pt−CuO/Cu2O heterojunction nanozyme was rationally designed with enhanced peroxidase- (POD), oxidase- (OXD), and laccase-like (LAC) activities, in which each component performs its designated function with efficient coordination. The introduction of Pt sites and increased oxygen vacancy (OV) through defect engineering modulate the heterointerface electronic structure and optimize the d-band center, as corroborated by density functional theory calculations. Such electronic modulation enhances the adsorption energy of Pt−CuO/Cu2O towards the substrates such as H2O2 (−1.02 eV to −1.49 eV) and O2 (−0.76 eV to −1.12 eV), thus boosting its triple-enzyme-like catalytic performance concurrently. Leveraging the distinct modulatory effects of β-lactams (BLs), tetracyclines (TCs), and fluoroquinolones (FQs) on these three enzyme-like activities, a single-receptor, three-channel colorimetric sensing array was constructed. Coupled with a home-made, highly-integrated and portable device for RGB signal acquisition and machine learning-assisted classification-regression models, the array achieved accurate on-site intelligent analysis of the three types of antibiotics across 0.2 μM to 100.0 μM within only 15.0 min, with performance approaching and even exceeding the regulatory limits. Performing the on-site assay on spiked milk powder samples produced satisfactory accuracy and recoveries, which were validated against authoritative LC−MS. This work establishes a defect-engineering paradigm for maintaining triple-enzyme-mimetic activities at high catalytic levels in a single nanoparticle-based efficient sensing array, enabling the on-site sensitive and accurate discrimination of multiple antibiotic residues at low concentrations through a machine learning-assisted colorimetric sensing array, thus offering both theoretical guidance and a deployable solution for food safety monitoring of multiple antibiotic residues.
{"title":"Defect-Engineering-Tailored Triple-Enzyme-Mimetic Heterojunction Nanozyme-Based Colorimetric Sensor Array for AI-Powered On-Site Intelligent Assay of Multiple Antibiotic Residues","authors":"Jinwei Zhang,Liang Huang,Jiayue Hu,Shanxin Sun,Cancan Jia,Sha Liu,Ying Gu,Yongning Wu,Yizhong Shen","doi":"10.1021/acs.analchem.6c06085","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c06085","url":null,"abstract":"Maintaining high levels of multienzyme-like activities within a single nanoparticle-based sensing array to boost the efficient simultaneous on-site assay of multiple antibiotic residues at low regulatory threshold levels is critical for the “One Health” initiative, but remains an ongoing challenge. Herein, a defect-engineered Pt−CuO/Cu2O heterojunction nanozyme was rationally designed with enhanced peroxidase- (POD), oxidase- (OXD), and laccase-like (LAC) activities, in which each component performs its designated function with efficient coordination. The introduction of Pt sites and increased oxygen vacancy (OV) through defect engineering modulate the heterointerface electronic structure and optimize the d-band center, as corroborated by density functional theory calculations. Such electronic modulation enhances the adsorption energy of Pt−CuO/Cu2O towards the substrates such as H2O2 (−1.02 eV to −1.49 eV) and O2 (−0.76 eV to −1.12 eV), thus boosting its triple-enzyme-like catalytic performance concurrently. Leveraging the distinct modulatory effects of β-lactams (BLs), tetracyclines (TCs), and fluoroquinolones (FQs) on these three enzyme-like activities, a single-receptor, three-channel colorimetric sensing array was constructed. Coupled with a home-made, highly-integrated and portable device for RGB signal acquisition and machine learning-assisted classification-regression models, the array achieved accurate on-site intelligent analysis of the three types of antibiotics across 0.2 μM to 100.0 μM within only 15.0 min, with performance approaching and even exceeding the regulatory limits. Performing the on-site assay on spiked milk powder samples produced satisfactory accuracy and recoveries, which were validated against authoritative LC−MS. This work establishes a defect-engineering paradigm for maintaining triple-enzyme-mimetic activities at high catalytic levels in a single nanoparticle-based efficient sensing array, enabling the on-site sensitive and accurate discrimination of multiple antibiotic residues at low concentrations through a machine learning-assisted colorimetric sensing array, thus offering both theoretical guidance and a deployable solution for food safety monitoring of multiple antibiotic residues.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"75 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226097","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}
引用次数: 0
Analysis of N-Glycans Released from Glycosylated RNAs 糖基化rna释放的n -聚糖分析
IF 7.3 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-20 Epub Date: 2026-09-23 DOI: 10.1021/acs.analchem.6c03851
Khairul Islam Khan, Liqing He, Lexiao Jin, Eugene G. Mueller, Craig J. McClain, Xiang Zhang

GlycosylatedRNAs (glycoRNAs) are involved in immune response,cellular function, gene regulation, and disease development. We reporta liquid chromatography–mass spectrometry (LC-MS) method toanalyze glycans released from glycoRNAs. The developed method includesextracting RNA from mouse liver using TRIzol, digesting proteins withproteinase K under denaturing conditions, re-extracting RNA usingTRIzol, releasing N-glycans by enzymatic digestion,enriching glycans by solid-phase extraction, and analyzing glycansby LC-MS. The method was optimized to detect low-abundance N-glycans from a purchased mixture of N-glycan standards, and 65 glycans were identified. We then appliedthe method to analyze the glycans released from the glycoRNAs in mouseliver and identified 244 N-glycans from triplicateanalyses. We also detected 40 significantly changed N-glycans in the livers of 32-week-old female and male KvB2 mice.This study establishes a simple and efficient technique for characterizing N-glycans in glycoRNAs and paves the way for future studiesto understand the function of glycoRNAs.

糖基化rna (glycoRNAs)参与免疫反应、细胞功能、基因调控和疾病发展。我们报道了一种液相色谱-质谱(LC-MS)方法来分析glycoRNAs释放的聚糖。该方法包括用TRIzol从小鼠肝脏中提取RNA,在变性条件下用蛋白酶K消化蛋白质,用TRIzol再提取RNA,酶切释放n -聚糖,固相萃取富集聚糖,LC-MS分析聚糖。对该方法进行了优化,以检测购买的n -聚糖标准混合物中的低丰度n -聚糖,鉴定出65种聚糖。然后,我们应用该方法分析了小鼠肝脏中glycorna释放的聚糖,并从三次重复分析中鉴定出244个n -聚糖。我们还在32周龄的雌性和雄性KvB2小鼠的肝脏中检测到40种显著改变的n -聚糖。本研究建立了一种简单有效的表征glycoRNAs中n -聚糖的技术,为进一步研究glycoRNAs的功能奠定了基础。
{"title":"Analysis of N-Glycans Released from Glycosylated RNAs","authors":"Khairul Islam Khan,&nbsp;Liqing He,&nbsp;Lexiao Jin,&nbsp;Eugene G. Mueller,&nbsp;Craig J. McClain,&nbsp;Xiang Zhang","doi":"10.1021/acs.analchem.6c03851","DOIUrl":"10.1021/acs.analchem.6c03851","url":null,"abstract":"<p>GlycosylatedRNAs (glycoRNAs) are involved in immune response,cellular function, gene regulation, and disease development. We reporta liquid chromatography–mass spectrometry (LC-MS) method toanalyze glycans released from glycoRNAs. The developed method includesextracting RNA from mouse liver using TRIzol, digesting proteins withproteinase K under denaturing conditions, re-extracting RNA usingTRIzol, releasing <em>N</em>-glycans by enzymatic digestion,enriching glycans by solid-phase extraction, and analyzing glycansby LC-MS. The method was optimized to detect low-abundance <em>N</em>-glycans from a purchased mixture of <em>N</em>-glycan standards, and 65 glycans were identified. We then appliedthe method to analyze the glycans released from the glycoRNAs in mouseliver and identified 244 <em>N</em>-glycans from triplicateanalyses. We also detected 40 significantly changed <em>N</em>-glycans in the livers of 32-week-old female and male KvB2 mice.This study establishes a simple and efficient technique for characterizing <em>N</em>-glycans in glycoRNAs and paves the way for future studiesto understand the function of glycoRNAs.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 41","pages":"29588–29595"},"PeriodicalIF":7.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019603","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}
引用次数: 0
Ultrasensitive ppt-Level Detection of Perfluorooctanoic Acid (PFOA) via a Hybrid Nanozyme, Fe3O4@MWCNTs, with Enhanced Peroxidase-Like Activity 通过具有增强过氧化物酶样活性的混合纳米酶Fe3O4@MWCNTs超灵敏的pt水平检测全氟辛酸(PFOA)
IF 7.3 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-20 Epub Date: 2026-09-25 DOI: 10.1021/acs.analchem.6c02884
Pyone Pyone Chit, Khin Moe Lwin, Jungon Yu, Jaehan Lee, Younghoon Cho, Sangil Kim, Kyunghoon Kim

Increasing concerns over perfluorooctanoicacid (PFOA),a representativeper- and polyfluoroalkyl substance (PFAS) often referred to as “foreverchemicals”, underscore the urgent need for simple, rapid, andsensitive detection strategies for water monitoring. Herein, we reportan ultrasensitive colorimetric sensing platform for monitoring tracelevels of PFOA in environmental water using a highly efficient hybridnanozyme, Fe3O4@MWCNTs. UV–vis absorbanceanalysis confirmed that the nanozyme composite effectively catalyzesthe oxidation of chromogenic substrates, such as 3,3′,5,5′-tetramethylbenzidine(TMB), exhibiting a characteristic blue color in the presence of hydrogenperoxide (H2O2). Upon exposure to PFOA, theactive sites on the nanozyme interface were blocked by PFOA, suppressingTMB oxidation and resulting in a clear “Turn-off” opticalresponse. This sensing platform enabled quantitative detection ofultralow concentrations of PFOA, ranging from 10 to 1,000 ng/L, witha limit of detection (LOD) of 3.12 ng/L. This work provides a cost-effective,rapid, and practical approach for monitoring environmentally relevantPFOA concentrations in water.

全氟辛酸(PFOA)是被称为“永远的化学物质”的全氟烷基和多氟烷基物质(PFAS)的代表,人们对其日益关注,迫切需要简单、快速、灵敏的水监测检测策略。在此,我们报告了一个超灵敏的比色传感平台,用于监测环境水中痕量的PFOA水平,使用高效的混合纳米酶Fe3O4@MWCNTs。紫外-可见吸收分析证实,纳米酶复合物有效地催化显色底物的氧化,如3,3 ',5,5 ' -四甲基联苯胺(TMB),在过氧化氢(H2O2)存在下表现出典型的蓝色。暴露于PFOA后,纳米酶界面上的活性位点被PFOA阻断,抑制TMB氧化,导致明显的“关闭”光学响应。该传感平台可定量检测10 ~ 1000 ng/L的超低浓度PFOA,检出限(LOD)为3.12 ng/L。这项工作为监测水中与环境有关的全氟辛酸浓度提供了一种经济、快速和实用的方法。
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引用次数: 0
Machine-Learning-Driven Dual-Mode Immunoassay Based on Nanobody and Natural Fluorescent Probe for Ultrasensitive Quantification of Pseudomonas aeruginosa 基于纳米体和天然荧光探针的机器学习驱动双模式免疫分析用于铜绿假单胞菌的超灵敏定量
IF 7.3 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-20 Epub Date: 2026-10-06 DOI: 10.1021/acs.analchem.6c04879
Mengnan Wang, Guangsheng Ge, Xueyi Fan, Kai Zheng, Yuxin Miao, Qing Yao, Min Ma, Jianlong Wang, Yanru Wang

Pseudomonas aeruginosa is a Gram-negativeopportunisticbacterial pathogen posing severe threat to environmental safety andhuman health. To achieve rapid and accurate detection, we developeda nanobody-based colorimetric-fluorescent dual-mode sandwich immunosensorusing natural fluorescent probe and further integrated machine learningto enhance the signal readout and improve detection sensitivity. Here,specific nanobodies toward P. aeruginosa were successfullydeveloped for the first time by biopanning against an immune phage-displayednanobody library. Natural fluorescent quinine, which possesses intrinsicfluorescence and undergoes fluorescence quenching via an internalquenching effect, was employed as the fluorescent probe. With thebaseline LODs obtained by direct fitting of the raw optical signals(9.005 × 105 CFU/mL for colorimetry and 3.02 ×103 CFU/mL for fluorescence), an XGBoost model was introducedand further reduces the LOD to 3.269 × 103 CFU/mLand 3.96 × 102 CFU/mL, achieving a 275-fold and 7.6-foldimprovement in sensitivity, respectively. Furthermore, following abrief pre-enrichment, this method enables detection of P. aeruginosa at concentrations as low as 10 CFU/mL. Recoveriesin water samples ranged from 81.47% to 119.47%, with a coefficientof variation below 8.44%, showing good agreement with machine learningpredictions (R2 = 0.957). No cross-reactivitywas observed with closely related or heterologous bacteria. This methodprovides a technical approach for the precise quantitative monitoringof P. aeruginosa in complex environments.

摘要铜绿假单胞菌是一种革兰氏阴性条件致病菌,对环境安全和人类健康构成严重威胁。为了实现快速准确的检测,我们开发了一种基于纳米体的比色-荧光双模三明治免疫传感器,采用天然荧光探针,并进一步集成机器学习,以增强信号读出,提高检测灵敏度。本研究首次通过对免疫噬菌体展示的纳米体文库进行生物筛选,成功开发出针对铜绿假单胞菌的特异性纳米体。荧光探针采用天然荧光奎宁作为荧光探针,奎宁具有本征荧光,并通过内部猝灭效应猝灭荧光。以直接拟合原始光信号获得的基线LOD(比色法为9.005 × 105 CFU/mL,荧光法为3.02 × 103 CFU/mL)为基础,引入XGBoost模型,将LOD进一步降低至3.269 × 103 CFU/mL和3.96 × 102 CFU/mL,灵敏度分别提高275倍和7.6倍。此外,经过短暂的预富集后,该方法可以在低至10 CFU/mL的浓度下检测铜绿假单胞菌。水样回收率为81.47% ~ 119.47%,变异系数小于8.44%,与机器学习预测结果吻合较好(R2 = 0.957)。与近缘菌或异源菌无交叉反应。该方法为复杂环境中铜绿假单胞菌的精确定量监测提供了技术途径。
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引用次数: 0
An Integrating Sphere Based Method for Quantifying RNA Encapsulation Efficiency in Lipid Nanoparticles without Lysis 基于积分球的非裂解脂质纳米粒RNA包封效率定量方法
IF 7.4 1区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2026-10-20 DOI: 10.1021/acs.analchem.6c04173
Aida López Espinar,Eric C. Le Ru,Kirsty Smith,Brendan L. Darby
Encapsulation efficiency (EE) is a critical quality attribute of lipid nanoparticle (LNP)-RNA formulations, determining the fraction of active RNA payload available for delivery and influencing therapeutic potency, dose accuracy, and product consistency. Conventional fluorescence-based EE assays, such as RiboGreen (RG), require detergent-mediated LNP lysis, which can introduce systematic bias arising from incomplete particle disruption and additional sample handling steps. Here, we report a lysis-free method for direct EE determination using Scatter-Free Absorption Spectroscopy (SFAS) within an integrating sphere. In this approach, RG fluorescence appears as a quantitative negative absorbance feature in the SFAS spectrum, enabling direct quantification of free RNA from intact LNP suspensions in a single measurement. Applied to SM-102 LNPs loaded with polyA or mRNA in PBS or Tris/sucrose buffers, the method yielded EE in close agreement with conventional plate-reader measurements. This approach provides a practical, formulation-independent, and potentially more robust strategy for standardized routine EE analysis and LNP quality-control workflows.
包封效率(EE)是脂质纳米颗粒(LNP)-RNA制剂的关键质量属性,决定了可用于递送的活性RNA有效载荷的比例,并影响治疗效力、剂量准确性和产品一致性。传统的基于荧光的EE分析,如RiboGreen (RG),需要洗涤剂介导的LNP裂解,这可能会由于不完全的颗粒破坏和额外的样品处理步骤而引入系统偏差。在这里,我们报告了一种在积分球内使用无散射吸收光谱(SFAS)直接测定EE的无裂解方法。在这种方法中,RG荧光在SFAS光谱中表现为定量负吸光度特征,可以在一次测量中直接定量完整LNP悬浮液中的游离RNA。应用于PBS或Tris/蔗糖缓冲液中负载polyA或mRNA的SM-102 LNPs,该方法产生的EE与传统的平板阅读器测量结果密切一致。这种方法为标准化的常规EE分析和LNP质量控制工作流程提供了一种实用的、独立于配方的、潜在的更强大的策略。
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引用次数: 0
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Analytical Chemistry
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