The growing antibiotic resistance and high mortality rates associated with methicillin-resistant Staphylococcus aureus (MRSA) pose a global health threat, highlighting the urgent need for novel therapeutic strategies. Phenol-soluble modulin α3 (PSMα3) is a critical virulence factor in MRSA pathogenesis and immune evasion. However, its underlying mechanisms remain unclear. Here, we demonstrate that PSMα3 promotes both M1 macrophage polarization and necroptosis. These processes are mechanistically linked through an interaction between the interferon-stimulated gene factor 3 (ISGF3) and necrosome complexes, with formyl peptide receptor 2 (FPR2) serving as the key receptor. Based on this mechanism, we show that targeting signal transducer and activator of transcription 1 (STAT1), a key component of the ISGF3 complex, with the clinically approved drug fludarabine effectively mitigates MRSA infection in murine sepsis and pneumonia models. These findings reveal the mechanisms of MRSA pathogenesis and highlight the potential of anti-virulence strategies as innovative therapeutic approaches against MRSA infections.

Sulfur Mustard (SM) is a potent vesicant chemical agent with profound and complex toxic effects. Traditionally, its toxic mechanism has been attributed to DNA alkylation-induced cytotoxicity and genomic instability. However, growing evidence indicates that dysregulation of epigenetic regulatory mechanisms constitutes a central link in SM toxicity, particularly in its long-term and delayed effects. Our study establishes an in vitro SM exposure model and employs integrated multi-omics profiling-including six histone modifications, DNA methylation, transcriptomic, and non-coding RNA analyses-to systematically investigate SM-induced epigenetic reprogramming. Our results demonstrate that SM drives extensive chromatin state remodeling, accompanied by altered expression of genes involved in DNA damage repair, cell cycle regulation, and immune response. We further constructed a predicted ceRNA network, identifying key lncRNAs, potentially associated with promoter hypomethylation, that may participate in ceRNA interactions involving cancer- and apoptosis-related genes. Additionally, we developed and validated a mass spectrometry-based method for precise quantification of 37 histone H3 modifications, providing a robust tool for profiling epigenetic biomarkers of exposure. These findings provide systems-level evidence for acute epigenetic reprogramming induced by SM exposure and reveal relevant associations between epigenomic dysregulation and genomic instability-related pathways in keratinocytes, suggesting candidate targets for future functional validation and early intervention studies.

The increasing frequency of castor bean or ricin-induced intoxication or terror events threatens public safety and national security, making the tracing of castor bean origins critical for law enforcement and counterterrorism efforts. Chemical attribution signatures (CAS) could address this issue by providing inherent and forensic links between ricin-containing samples and their geographical origins; however, practical implementations of this approach remain scarce. Omics data sets offer substantial potential to generate comprehensive biological insights and high-dimensional data for provenance attribution, where transcriptomics and proteomics profiling are better suited to castor beans than traditional genomics and metabolomics, regarding that castor beans exhibit low genetic diversity but high phenotypic polymorphism. In this work, toward castor bean samples from 14 provinces or autonomous regions in China and three international locations, including Ethiopia, Pakistan, and South Sudan, we proposed an integrated local-global data-mining strategy by systematically integrating RNA-seq transcriptomics and data-independent acquisition quantitative proteomics, and developed a straightforward feature-screening pipeline to prioritize 59 signature peptides as provenance-related CAS with distinct interregional and international expression patterns. A subsequent machine learning model trained on these CAS achieved 93.7% classification accuracy, identifying robust discriminative patterns among samples from different global regions, as well as fine-scale differences across altitude gradients and north-south divisions in China, in which the attribution index of altitude and latitude is reported for the first time. Finally, after validation by parallel reaction monitoring in nanoLC-HRMS/MS, we confirmed a minimum signature panel of 24 peptides as molecular CAS markers for the origin attribution of castor beans.

BACKGROUND/OBJECTIVES:Orofacial inflammatory pain remains a significant clinical challenge due to the lack of effective therapeutic agents that specifically target its complex pathophysiology. Conventional analgesics often provide inadequate relief and fail to address the profound negative affective states that frequently accompany chronic pain, further diminishing patients' quality of life. This study evaluated the therapeutic potential of cannabidiol (CBD) in mitigating sensory and affective dimensions of inflammatory pain and elucidated its underlying mechanisms. METHODS:Acute orofacial inflammatory pain was induced via subcutaneous formalin injection into the upper lip of mice. Chronic inflammatory pain and associated negative affect were modeled using intraplantar injection of complete Freund's adjuvant (CFA). A comprehensive behavioral battery-including von Frey filament testing, open field test, elevated plus maze, forced swim test, tail suspension test, sucrose preference test, and Y-maze-was employed to assess nociception and affective states. Mechanistic studies involved RT-qPCR, ELISA, LC-MS/MS, immunofluorescence and in vivo fiber photometry was employed to examine inflammatory, oxidative, endocannabinoid, and serotonergic pathways. RESULTS:Local administration of CBD significantly suppressed formalin-induced acute orofacial pain, specifically attenuating Phase II inflammatory sensitization. At the peripheral level, CBD downregulated FAAH and PGE2, reduced levels of pro-inflammatory cytokines (IL-1β, TNF-α) and oxidative stress markers, and increased levels of endocannabinoids in the blood-effects mediated primarily through CB2 receptor activation. Central actions of CBD were evidenced by reduced neuronal activation (c-Fos) in the spinal trigeminal nucleus caudalis (Sp5C) and anterior cingulate cortex, as well as increased anandamide (AEA) in the Sp5C and periaqueductal gray, which were mediated through CB1 receptor signaling. In the CFA-induced chronic pain model, systemic CBD administration not only alleviated mechanical allodynia but also markedly ameliorated anxiety- and depression-like behaviors and restored cognitive performance. Fiber photometry further revealed that CBD normalized deficits in serotonin transient activity in the central amygdala. CONCLUSIONS:CBD exerts robust multi-dimensional therapeutic effects across sensory, affective, and cognitive domains in inflammatory pain models. The findings underscore the translational potential of CBD as a novel therapeutic strategy for comprehensive management of orofacial pain and pain-related debilitating emotional comorbidities.

Vesicant mustards are a class of highly toxic chemical warfare agents, posing a serious societal and environmental threat. Early and accurate diagnosis of exposure is essential to guide effective medical countermeasures and minimize bodily injuries. However, developing specific, rapid and on-site diagnostic methods remains challenging owing to complex matrix interference and low analyte abundance. Herein, we designed a label-free, non-invasive and sensitive method combining capillary-driven surface-enhanced Raman spectroscopy (SERS) with reversed-phase thin-layer chromatography (RP-TLC) for detecting mustard-DNA adducts as exposure biomarkers. In this strategy, trace acetonitrile (ACN) and perfluoropolyether (PFPE) lubricant were employed to optimize interfacial kinetics for efficient analyte extraction and confine droplet diffusion for high reproducibility, respectively. Target molecules were further trapped in plasmonic nanogaps during evaporation, yielding strong SERS enhancement. Subsequently, 24 kinds of DNA adduct from 10 different mustards were distinguished assisted by machine learning, and the lowest absolute detection limit of 12.5 pg was achieved. Compared to conventional TLC-SERS, the detection sensitivity was improved by four orders of magnitude (similar to 10(4)). Finally, trace adducts were successfully identified from the urine of individuals exposed to sulfur mustard HD. To our knowledge, this is the first systematic study on rapid diagnosis of vesicant exposure via DNA adduct profiling.

Nucleic acids are one of the key cellular targets for chemical exposure and stress responses, and nucleic acid modification induced by chemical toxicants represents a core research area in toxicology. Toxicant-induced nucleic acid modifications are categorized into two interconnected pathways. First is the exogenous modifications arising from direct covalent or noncovalent interactions between toxicants or their reactive metabolites and nucleic acids. Second is the endogenous modifications generated secondarily through toxicant-triggered oxidative stress, lipid peroxidation, inflammation, endogenous alkylation, and epigenetic or epitranscriptomic dysregulation. Taking prototypical electrophilic agents, chemical warfare agents (CWAs), as the focal point, this review maps a comprehensive landscape of nucleic acid modification induced by CWAs, mainly including exogenous monoadducts, cross-links, and endogenous oxidative damage and regulatory modifications. We systematically elucidate the chemical reactivity, structural diversity, and toxicokinetic behaviors of key lesions, further exploring the differential roles of these lesions as exposure or effect biomarkers and their contribution to adverse biological outcomes induced by CWAs. For different CWAs, bifunctional reactions producing DNA-DNA and DNA-protein cross-links constitute the most cytotoxic lesions, and single-base adducts represent the predominant and best-characterized modifications. In this context, nucleic acid adductomics has emerged as an untargeted strategy for comprehensively profiling diverse induced lesions at the molecular level. Mass spectrometry (MS) serves as the core analytical platform for adductomics, enabling structural identification and accurate picogram-level quantification of nucleic acid adducts. Meanwhile, next-generation sequencing (NGS) achieves high-resolution localization of endogenous modifications in certain contexts, although its applicability to bulky and chemically complex lesions remains technically challenging. It is expected that the combination of MS and NGS will unlock the capability to dissect the inherent relationship between specific modification sites, gene function perturbation, and resultant toxicological effects.

Spontaneous calcification of the treated hepatocellular carcinoma (HCC) has been proven to be a good prognosis predictor in the clinic. In line with this concept, artificially induced biomineralization in the tumor tissue is considered to be an unconventional yet promising therapeutic modality for HCC. However, the limited mineral ions concentration in/around tumor tissue and the modest ion-chelating capabilities of conventional biomineralization initiators often resulted slow biomineralization process and compromised antitumor efficacy. Herein, an in situ biomineralization inducing nanotherapeutic was developed for achieving precise and speedy HCC mineralization block therapy. Specifically, cytomembrane-insertion moiety DSPE-PEG was first conjugated with ion-chelating motif alendronate (ALN) to obtain the chelator DPA. And then, DPA was modified on sorafenib (SF)-loaded acidic tumor microenvironment (TME)-sensitive mesoporous MnCO3 nanoparticles. After intravenous injection into HCC-bearing mice, the SF@MnC@DPA could accumulate in tumor site medicated by EPR effect. Subsequently, SF@MnC@DPA responds to the acidic TME to releases DPA, Mn2+ and SF. Benefiting from the similar chemical structure of DSPE and phospholipid layer, DPA can be easily inserted into the cell membrane, and the bisphosphonic acid group of ALN could bind with the Mn2+ to in situ construct a mineralized barrier around the tumor, thereby achieving synergistic chemotherapy and mineralization block therapy. In vitro and in vivo results demonstrated that SF@MnC@DPA successfully induced the tumor mineralization and sharply inhibited tumor growth for subcutaneous and orthotopic HCC without evidence of systemic side effects. Altogether, the proposed selective biomineralization provides an outlook for a new avenue in HCC therapy and anticancer drug development.

Ricin is a highly lethal plant-derived biotoxin posing severe threats to public security and necessitating rapid, sensitive, and on-site detection methods. To overcome the inherent batch-to-batch variability of traditional antibodies, synthetic peptides have emerged as promising alternative recognition elements. Herein, we report a de novo screening and surface plasmon resonance (SPR)-guided affinity maturation of novel anti-ricin cyclononapeptides for the development of a highly sensitive fluorescent lateral flow assay (LFA). Through a virtual-experimental iterative strategy integrating phage display, in silico molecular docking, alanine/histidine scanning, and double-site saturation mutagenesis, we evolved an optimum variant cyclopeptide (F7) with a 100-fold enhanced binding affinity (KD = 165 nM). Based on F7, we constructed two novel sandwich LFAs involving cyclopeptide-monoclonal antibody (mAb) or cyclopeptide-glycoprotein using time-resolved fluorescent microspheres as sensitive signal reporters. Facilitated by a self-developed ultracompact handheld reader, this optimized LFA achieved a high sensitivity of 0.1 ng/mL without requiring complicated signal amplification. Crucially, the developed LFA method demonstrated excellent matrix tolerance, enabling reliable semi-quantification of trace ricin in complex authentic samples, including human plasma, beverages, castor plant tissues, and suspected white powder mixtures. Combined with the self-developed ultracompact handheld LFA reader, the LFA platform exhibited satisfactory capture efficiency in simulated bioterrorism surface-swabbing scenarios. It is expected that this field-deployable, high-performance LFA platform could prove instrumental in the rapid risk assessment, on-site screening of complex environmental matrices, and emergency monitoring of severe biological hazards.

Synthesis route attribution enables accurate source tracing of chemical warfare agents and effective discrimination between distinct synthetic pathways. In the current study, we report for the first time the identification of trace process-related impurities derived from the synthesis of the vesicant ethyl sesquimustard, which is listed in Schedule 1.A.04 of the Chemical Weapons Convention (CWC). Using 1,2-ethanedithiol and 2-mercaptoethanol as precursors, 22 different synthetic routes were designed, and 88 batches of samples were produced through micro-synthesis. Gas chromatography-high resolution mass spectrometry (GC-HRMS) coupled with a non-targeted screening strategy was employed to analyze route-specific compounds. The obtained dataset was further used to train the orthogonal partial least squares discriminant analysis algorithm and generate a classification model consisting of eight sub-models. The verification results showed that the overall classification accuracy of the model was 21/22 (about 95%).

The development of high-performance solution-gated graphene field-effect transistor (SGGT)-based bio- and chemosensors relies on the effective integration of selective molecular recognition and efficient signal transduction. In this study, a molecularly imprinted recognition mode was incorporated into an SGGT to construct a molecularly imprinted polymer-functionalized SGGT sensor (MIP-SGGT) for the highly sensitive detection and determination of chloramphenicol (CAP). A polydopamine-based MIP film with recognizing sites selective for chloramphenicol was electrochemically deposited onto a conductive MXene/carbon nanotubes (MXene/CNTs) framework. The embedding of CAP molecules within the MXene/CNTs/MIP composite effectively hindered the diffusion of Fe(CN)64- ions, thereby influencing the redox reaction at the gate electrode, altering the effective gate voltage distribution, and ultimately modulating the drain-source channel current (IDS) of the MIP-SGGT device. A wide linear response range from 1 pM to 0.1 mu M and an ultralow detection limit of 0.17 pM, highlighting the exceptional sensing performance of the proposed system. This work confirms the feasibility of integrating molecularly imprinted recognition modules into SGGT platforms and provides a versatile and effective strategy for the rapid and accurate detection of small molecules, showing great promise for real-world analytical applications

Alkylthiophosphonates, listed in Schedule 2.B.04 of the Chemical Weapons Convention, are key environmental markers and stable degradation products of V-series nerve agents. However, their reliable identification is hampered by some fundamental challenges: over one million theoretical structures are possible, whereas standard reference databases contain only a limited number of entries. This disparity highlights the need for high-throughput, nontargeted screening strategies capable of detecting compounds beyond library coverage. Previous research has indicated that liquid chromatography-mass spectrometry shows limited sensitivity for sulfur-rich analogues, exhibiting an exponential signal attenuation as the number of sulfur atoms increases. To address these gaps, a set of over 100 typical compounds was synthesized and their fragmentation behaviors were systematically investigated using gas chromatography-high resolution mass spectrometry. The analysis revealed that McLafferty (+1) rearrangement and α-cleavage are the dominant mechanisms generating their characteristic fragment ions. Building on these mechanistic insights and leveraging the complementary strengths of electron ionization and chemical ionization, 33 groups of alerting ions and 171 theoretical accurate masses were derived. These were used to construct a nontargeted screening strategy for millions of alkylthiophosphonates. The strategy was successfully applied to identify unknown chemicals in authentic samples, enabling effective discrimination between phosphonothiolate/phosphonothionate and phosphonodithiolate/phosphonothiolothionate isomeric pairs. The method demonstrated high sensitivity, with limits of detection as low as 1-10 ppb, along with good repeatability. These results confirm the practical utility of the developed strategy for the verification and monitoring of alkylthiophosphonates in environmental and forensic contexts.

The practical verification analysis of chemical warfare agents, notably the G-series organophosphorus nerve agents, and their related chemicals─including precursors, byproducts, and degradation products─is critical not only for attributing the use of chemical weapons but also for retrospection of illicit production networks and gathering crucial forensic evidence. However, this task is significantly challenged by the vast "chemical space explosion" of potential analogues and the limitations of conventional database-dependent methods, necessitating high-throughput nontargeted screening approaches. In this study, following systematic characterization of fragmentation pathways and characteristic ions through integration of mass spectral libraries and clustering analysis, an integrated dual-ion source nontargeted screening strategy based on gas chromatography high-resolution mass spectrometry was established for the identification of unknown nerve agents and their related chemicals. Under electron ionization mode, a set of 52 specific "Alerting Ions" and 12 types of structures was established and applied for the rapid screening and classification of millions of suspected compounds. These candidates, after being located via retention index, were further verified under chemical ionization mode through Kendrick Mass Defect analysis of their molecular ions. Plausible structures were proposed through comprehensive spectral interpretation, and the candidate list was significantly refined using an RI prediction model. Final confirmation was achieved by comparison with reference standards. This strategy was validated using 73 home-synthesized compounds and exhibited a low limit of detection of 10-50 ng/mL. It was successfully applied to the analysis of environmental authentic samples from the Organization for the Prohibition of Chemical Weapons.

Identifying diverse, uncharacterized plant-derived nerve agent adducts is a formidable challenge for environmental exposure confirmation and forensic attribution. We developed a fragmentation pattern-driven nontargeted screening strategy integrating in-source fragmentation with Full MS, all-ion fragmentation (AIF), and neutral loss (NL)-triggered ddMS2 acquisition. By utilizing agent-specific neutral losses and diagnostic fragment ions, 256 tentative adduct-related features were identified across four nerve agents and four plant species, establishing an expansive repository of previously unreported candidate markers. Structural characteristics and preferential adduction sites were elucidated through integrated interpretation of high-resolution MS data, fragmentation pathways, and density functional theory calculations. Notably, 9 features exhibited conservation across plant species, while 11 features remained detectable at low-level exposure in Arabidopsis thaliana, highlighting their potential as viable markers. This strategy expands the detectable chemical space for plant-derived nerve agent adducts and provides a transferable framework for environmental exposure assessment and emerging contaminants research.

C18 (up)-graphitized carbon (down) solid-phase extraction disks were used for the first time to simultaneously and rapidly enrich 35 dissolved marine algal toxins (MATs) from seawater, with a maximum difference in log Kow values of 12.3. The enriched MATs were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The flow rate of the pretreatment process was 100 mL/min, and a 2000-fold enrichment was achieved for seawater, with recoveries of the target MATs exceeding 65.9%. The developed method demonstrated high sensitivity and excellent precision, with limits of detection as low as 2.0 × 10-4 ng/L and average relative standard deviations ≤12.8%. Real seawater samples from Liaodong Bay and Beibu Bay were analyzed using this method to detect dissolved MATs. Nine MATs, including gymnodimine, pectenotoxin-2, okadaic acid (OA), 19-epi-OA, dinophysistoxin-1 (DTX1), 19-epi-DTX1, homo-yessotoxin, gonyautoxin-2 (GTX2), and GTX3, were detected in seawater samples from the selected research areas. Notably, 19-epi-OA and 19-epi-DTX1 were identified for the first time in China. The concentrations of dissolved ∑MATs in Liaodong Bay and Beibu Bay ranged from 26.12 to 56.95 ng/L and 28.12 to 51.98 ng/L, respectively. This study proposes a potential technique for exploring the distribution characteristics of multiple MATs across large-scale coastal seawater.

A chemical vapor deposition strategy is reported to develop a simple and efficient carbon oxide cloth (OCC)/MoS2 flexible SERS substrate with acid-treated OCC as the deposition substrate, capable of detecting Rhodamine 6G concentrations as low as 1.0 × 10− 12 M. By combining experimental analysis and density functional theory calculations, we found that the charge transfer between acid-treated carbon cloth and adsorbed molecules is enhanced because of its abundant oxygen-containing functional groups. More significantly, the flexible OCC/MoS₂ substrate enables the in-situ detection and efficient on-site photocatalytic degradation of organic contaminant residues on fish surfaces and in aquatic environments through simple swabbing or immersion sampling. Moreover, the flexible matrix exhibits excellent recyclability in both practical detection and photocatalysis applications.

An innovative photoelectrochemical solution-gated graphene transistor (PEC-SGGT) was developed in this work for the sensitive detection of diquat (DQ). In this system, DQ acts as a molecular bridge that directs the pre-formation of a DQ@carbon quantum dots (DQ@CQDs) complex in solution and subsequently guides its assembly onto the WS2 quantum dots-gold nanoparticles-cyclodextrin (WS2/Au/CD) substrate. This process leads to the formation of a WS2/Au/CD@DQ/CQDs photosensitizer with enhanced photoelectronic properties. When integrated as a PEC gate electrode, this material effectively modulates the channel current of the PEC-SGGT device, enabling accurate quantification of DQ with an ultralow detection limit of 0.45 pM. The sensing strategy combines host-guest recognition with electrostatic self-assembly to achieve selective DQ capture while generating robust, device-compatible gating signals. Overall, this work presents a promising paradigm for the ultrasensitive detection of small-molecule toxins.

The conventional electrochemical detection of organophosphorus pesticides (OPs) predominantly relies on acetylcholinesterase-based sensing strategies, which often suffer from poor operational stability and limited robustness. Herein, we report a conceptually new, enzyme-free sensing paradigm based on a solution-gated graphene field-effect transistor (SGGT) functionalized with a graphene-MXene-cerium dioxide (Gr-M-Ce) nanocomposite, enabling ultrasensitive and broad-spectrum detection of OPs via a molecular-gating mechanism. In this platform, pralidoxime (PAM) is employed as a broad-spectrum molecular probe that interacts with the phosphate ester moieties commonly present in OPs. Upon exposure to OPs, PAM rapidly undergoes phosphorylation to form an electrochemically inert derivative (PAM-OPs), which adsorbs onto the Gr-M-Ce surface and selectively suppresses its catalytic activity toward PAM oxidation. This chemical conversion-catalytic inhibition cascade induces an effective gating modulation along the gate-source pathway of the SGGT, which is transduced and amplified by the device, yielding a pronounced shift in the source-drain current (IDS). As a result, the sensor achieves ultrahigh sensitivity over a wide linear range from 1 & times; 10-12 to 1 & times; 10-7 M, with a detection limit down to 0.24 pM. More importantly, this work establishes a generalizable molecular-gating strategy that integrates solution-phase chemical recognition with transistor-based signal amplification, offering a new design principle for constructing high-performance enzyme-free sensors for small-molecule analysis.

The depletion degree of reduced glutathione is a critical indicator for assessing the toxicity of alkylating agents. In the present research, we have developed a novel method to evaluate the glutathione (GSH) depletion induced by a series of alkylating agents and the protective effect of various active thiol compounds based on a high-content cell analysis system. The cytotoxicity of some alkylating agents was first assessed using the CCK-8 assay. The results showed that bis(2-Choroethyl) methylamine (nitrogen mustard, HN2) and 1,2-bis(2-chloroethythio) ethane (Q) exhibited the highest cytotoxicity, with IC50 values of 14.45 μM and 23.27 μM, respectively. The cytotoxicity of 2-choroethylchoromethylsufide (CECM) and bis(2-choroethylthioethyl) ether (T) was comparable to that of bis(2-choroethyl) sulfide (HD), and bis(2-choroethylthiomethyl) ether (CEMEE) showed the lowest cytotoxicity. At the same exposure dose, Q exhibited the strongest GSH depletion ability, followed by HD > CECM > CEPR(1,3-bis(2-Chloroethylthio)-n-propane) > CEBU(1,4-bis(2-Chloroethylthio)-n-butane) > CEPE(1,5-bis(2-Chloroethylthio)-n-pentane) > CEME(bis(2-Chloroethylthio) methane) > T(bis(2-Choroethylthioethyl) ether) > CEMEE, and the depletion ability of nitrogen mustard compounds followed the order HN2 > HN1(bis(2-Choroethyl) ethylamine) > HN3(tri(2-Choroethyl) amine). In addition, the protective effect of four active thiol compounds was investigated. The results revealed that reduced glutathione ethyl ester (GSH-MEE) was most effective in preventing GSH depletion, whereas glutathione monoethyl ester (MEE) showed the highest efficacy in restoring GSH levels. The proposed method holds significant potential for analyzing the damaging effects of various alkylating agents and screening protective drugs.

This study develops a photoelectrochemical solution-gated graphene field-effect transistor (PEC-SGGT) for ultrasensitive organophosphates (OPs) detection, merging optoelectronic modulation with enzymatic signal amplification. The sensor employs a hybrid system of cadmium sulfide quantum dots (CdS QDs) and acetylcholinesterase (AChE), using acetylthiocholine (ATCh) as the substrate. Under light, CdS QDs generate electron-hole pairs, while AChE hydrolyzes ATCh into thiocholine (TCh), which enhances charge separation and amplifies photocurrent. OPs-induced inhibition of AChE reduces TCh production, decreasing photocurrent and enabling PEC-SGGT gate-controlled OPs quantification. The sensor achieves a detection limit of 0.21 pM and a linear range of 0.1 nM to 1 mM. This work demonstrates the potential of light-assisted, enzyme-functionalized, gate-modulated PEC-SGGT systems for diverse biosensing applications, including enzymatic sensors, enzyme-labeled immunosensors, and enzyme-labeled DNA biosensors, advancing bioelectronics.

Agricultural products are usually contaminated by various mycotoxins, the rapid and sensitive detection of mycotoxins at the early stage is significant for food safety and human health. Here, we develop a rapid and ultrasensitive surface-enhanced Raman scattering-based vertical flow assay (VFA) for simultaneous detection of multiple mycotoxins by using Fe3O4@Au magnetic SERS nanotags. In this competitive immunoassay, three test zones are designed on the sensing membrane, and modified with multiple capture antigens. Moreover, three kinds of specific monoclonal antibodies conjugated Fe3O4NBA@Au, Fe3O44-MBA@Au, and Fe3O4DNTB@Au SERS nanotags were synthesized as probes to identify fumonisin B1 (FB1), aflatoxin B1 (AFB1), and deoxnivalenol (DON), respectively. The magnetic nanoparticles have three following merits: specific recognition, SERS signal enhancement, and magnetic enrichment of the target without any sample preprocessing steps. The limits of detection for FB1, AFB1, and DON are 0.053, 0.028 and 0.079 pg mL-1, respectively, which are 1000 times more sensitive than those conventional standard colloidal gold methods. Furthermore, the proposed biosensor is easy to operate, rapid, accurate, and can achieve high throughput and is expected to be a powerful analytic platform for early detection of multiple mycotoxins in food.