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The food contamination with Ochratoxin A (OTA) has highlighted the need to create precise, sensitive, and convenient techniques. Herein, we proposed a label-free and immobilization-free ratiometric homogeneous electrochemical aptasensor based on dual catalytic hairpin self-assembly (CHA) for OTA detection. Methylene blue (MB) and ferrocene (Fc) in solution were utilized as label-free signaling molecules, generating a response signal (I MB ) and a reference signal (I Fc ), respectively. The ratio of I MB /I Fc was utilized as a measure to quantify OTA. Dual CHA was exploited to increase the ratiometric signal and enhance the amplification efficiency. This aptasensor achieved trace-level detection for OTA over a linear range of lower concentrations (1.0 × 10 -3 ng/mL-1.0 × 10 3 ng/mL) with LOD of 92 fg/mL. The aptasensor was successfully applied to detect OTA in cereal and wine, with comparable results of HPLC-MS/MS. This strategy provided a viable platform for rapid, sensitive, and accurate detection of OTA in food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Herein, a novel surface enhanced Raman spectroscopy (SERS) aptasensor was developed for amantadine (AMD) detection, based on magnetite nanoparticles coated with polyethylenimine, silver nanoclusters and aptamers (Fe 3 O 4 @PEI@AgNC-apt) as the capture probe and complementary DNA-modified gold nanorods (AuNRs@4-MPBA@Ag-c-DNA containing 4-mercaptophenylboric acid molecules) as the reporter probe. In the presence of AMD, the AMD and the reporter probe competed for the aptamer on the surface of the capture probe, resulting in the reporter probe detaching from the capture probe leading to a decrease in intensity of the SERS signal at 1067 cm -1 for 4-MPBA. Under optimal conditions, a good linear relationship was established between the SERS intensity at 1067 cm -1 and the logarithm of the AMD concentration over the range 10 -6 -10 2  mg L -1 , with a LOD of 0.50 × 10 -6  mg L -1 . The AMD levels in spiked samples were evaluated using the SERS aptasensor, with good recoveries ranging from 90.57% to 113.49% being obtained., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aflatoxin B 1 (AFB 1 ) is a common mycotoxin that is of significant global concern due to its impact on food safety. Herein, we innovatively develop a sensing platform to detect AFB 1 based on evaporation of surfactant solutions on the hydrophobic surface, resulting in dried patterns with varied sizes. The surfactant CTAB solution produces a relatively large dried pattern due to the surface wetting. However, the reduction in the dried pattern size is found when the mixture of CTAB and AFB 1 aptamer is tested, because the formation of CTAB/aptamer complex. Moreover, the dried pattern size of the mixture of CTAB, aptamer, and AFB 1 increases due to the specific binding of AFB 1 to its aptamer. Using this innovative strategy, the AFB 1 detection can be fulfilled with a detection limit of 0.77 pg/mL. As a simple, convenient, inexpensive, and label-free method, the surfactant-mediated surface droplet evaporation-based biosensor is very promising for various potential applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study reports the fabrication of three-dimensional gold nanocrystals as sensing material in the presence of l-glutathion and high-performance aptamer with 20 bases of α-amanitin via truncation and optimization of along aptamer. The resulting maple leaf-like gold nanocrystal (ML-Au) exhibits an improved catalytic activity due to more exposed high-index facets. The use of truncated aptamer increases the sensitivity by 15 times and reduces the reaction time by two times compared with those of original aptamer. An α-amanitin electrochemical biosensor constructed by integrating ML-Au nanocrystals with truncated aptamer exhibits high sensitivity, selectivity and rapidity. An increase of the α-amanitin concentration in the range of 1 × 10 -14 -1 × 10 -9 M causes a linear decrease in the amperometric current with a limit of detection of 2.9 × 10 -15 M (S/N = 3). The proposed analytical method is satisfactorily used for electrochemical sensing of α-amanitin in urine and wild mushroom samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aptamers are molecular recognition elements that have been extensively deployed in a wide array of applications ranging from diagnostics to therapeutics. Due to their unique properties as compared to antibodies, aptamers were also largely isolated during the COVID-19 pandemic for multiple purposes. Typically generated by conventional SELEX, the inherent drawbacks of the process including the time-consuming, cumbersome and resource-intensive nature catalysed the move to adopt in silico approaches to isolate aptamers. Impressive performances of these in silico -derived aptamers in their respective assays have been documented thus far, bearing testimony to the huge potential of the in silico approaches, akin to the traditional SELEX in isolating aptamers. In this study, we provide an overview of the in silico selection of aptamers against SARS-CoV-2 by providing insights into the basic steps involved, which comprise the selection of the initial single-stranded nucleic acids, determination of the secondary and tertiary structures and in silico approaches that include both rigid docking and molecular dynamics simulations. The different approaches involving aptamers against SARS-CoV-2 were illuminated and the need to verify these aptamers by experimental validation was also emphasized. Cognizant of the need to continuously improve aptamers, the strategies embraced thus far for post- in silico selection modifications were enumerated. Shedding light on the steps involved in the in silico selection can set the stage for further improvisation to augment the functionalities of the aptamers in the future.

While it is recognized that early diagnosis of cancer-related biomarkers can become an effective avenue for timely treatment and successfully improve patient survival, it remains challenging to get accurate inspection results. Currently, most reported cancer biomarker sensing methods are focused on the quantitative detection of a single type of biomarker, which makes accurate medical diagnostics difficult. In this work, we constructed a DNA walker nanomachine aptasensor based on gold nanoparticles for the simultaneous sensing of dual cancer biomarkers. The aptamers, labelled with a fluorophore, hybridized with complementary strands on the gold nanoparticle surface, serve as a walking track. Target analytes bind to their specific aptamers, leading to the dissociation of the unstable double-strand spherical nucleic acid. Exonuclease I (Exo I) selectively digested the aptamers bound with the target analytes, then the released targets go back to the next apamers on the gold nanopareticles surface for walking. The use of spherical nucleic acid probes improved the sensitivity of analyte detection. Exo I provided a driving power for target recycling and considerably improved the sensitivity of the aptasensor as well. The DNA walker nanomachine aptasensor was successfully applied for the detection of carcinoembryonic antigen (CEA) in the range of 0.167 to 3.34 ng mL -1 , and mucin-1 (MUC-1) in the same range. Moreover, we used the two aptamers to construct the DNA walker nanomachine and achieved the simultaneous detection of CEA and MUC-1, thus having great potential for biomolecular logic gate construction and early disease diagnosis.

Nucleic acid tests (NATs) are essential for biomedical diagnostics. Traditional NATs, often complex and expensive, have prompted the exploration of toehold-mediated strand displacement (TMSD) circuits as an economical alternative. However, the wide application of TMSD-based reactions is limited by 'leakage'-the spurious activation of the reaction leading to high background signals and false positives. Here, we introduce the Y-Switch, a new TMSD cascade design that recognizes a custom nucleic acid input and generates an amplified output. The Y-Switch is based on a pair of thermodynamically spring-loaded DNA modules. The binding of a predefined nucleic acid target triggers an intermolecular reaction that activates a T7 promoter, leading to the perpetual transcription of a fluorescent aptamer that can be detected by a smartphone camera. The system is designed to permit the selective depletion of leakage byproducts to achieve high sensitivity and zero-background signal in the absence of the correct trigger. Using Zika virus (ZIKV)- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived nucleic acid sequences, we show that the assay generates a reliable target-specific readout. Y-Switches detect native RNA under isothermal conditions without reverse transcription or pre-amplification, with a detection threshold as low as ∼200 attomole. The modularity of the assay allows easy re-programming for the detection of other targets by exchanging a single sequence domain. This work provides a low-complexity and high-fidelity synthetic biology tool for point-of-care diagnostics and for the construction of more complex biomolecular computations., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Mycotoxins, a class of secondary metabolites produced by molds, are widely distributed in nature and are very common in food contamination. Aflatoxin B1 (AFB1) is a highly stable natural mycotoxin, and many agricultural products are easily contaminated by AFB1, it is important to establish a sensitive and efficient AFB1 detection method for food safety. The fluorescence aptamer sensor has shown satisfactory performance in AFB1 detection, but most of the fluorescence aptasensors are not sensitive enough, so improving the sensitivity of the aptasensor becomes the focus of this work., Results: Herein, an innovative fluorescent aptasensor for AFB1 detection which is based on catalytic hairpin assembly (CHA) and rolling circle amplification (RCA) driven by triple helix molecular switch (THMS) is proposed. A functional single-strand with an AFB1 aptamer, here called an APF, is first designed to lock onto the signal transduction probe (STP), which separates from THMS when target AFB1 is present. Subsequently, STP initiates the RCA reaction along the circular probe, syntheses macro-molecular mass products through repeated triggering sequences, triggers the CHA reaction to produce a large number of H1-H2 structures, which causes FAM to move away from BHQ-1 and recover its fluorescence signal. The fluorescence signal from FAM at 520 nm was collected as the signal output of aptasensor in this work. With high amplification efficiency of RCA and CHA of the fluorescence sensor, resulting in a low LOD value of 2.95 pg mL -1 (S/N = 3)., Significance: The successful establishment of the sensor designed in this work shows that the cascade amplification reaction is perfectly applied in the fluorescent aptamer sensor, and the signal amplification through the reaction between DNA strands is a simple and efficient method. In addition, it's also important to remember that the aptasensor can detect other targets only by changing the sequence of the aptamer, without redesigning other DNA sequences in the reaction system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Aflatoxin B1 (AFB1), is a potent hepatic carcinogen which causes cancer by inducing DNA changes in the liver cells. Variety of methods have been developed for detection of AFB1 which are based on single mode detection strategy. Fabrication of novel platform which are compatible for multimodal detection of AFB1 provide robust performance for reliable detection of AFB1. In this study, we aimed to develop a robust biosensing platform that combines electrochemical and fluorescence techniques for the sensitive and specific detection of Aflatoxin B1., Results: The sensing platform includes the magnetic core-shell Fe 3 O 4 @AuNPs and zeolitic imidazolate framework-8 (ZIF-8). In electrochemical mode, the applied voltametric approach was used through functionalization of glassy carbon electrode and exhibited a linear range between 0.5 and 10000 pg mL -1 with LOD of 0.32 pg mL -1 . Fluorescence analysis was based on the FRET on/off status of FAM-functionalized aptamer deposited on the same platform. The FAM emission recovered by the addition of AFB1 concentration in the range of 6-60 fg mL -1 with the LOD of 0.20 fg mL -1 . The real sample analysis demonstrated satisfactory relative recoveries in the range of 92.81-105.32 % and 91.66-106.66 % using the electrochemical and fluorescence methods, respectively, and its reliability was confirmed by the HPLC technique., Significance: The experimental results affirm that the proposed aptasensor serves as a sensitive, efficient, and precise platform for monitoring AFB1 in both electrochemical and fluorescence detection approaches. Proposed strategy showed efficient selectivity among different analytes and was reproducible. Furthermore, the applicability of biosensor was confirmed in food and biological samples., Competing Interests: Declaration of competing interest We wish to draw the attention of the Editor to the following facts which may be considered as potential conflicts of interest and to significant financial contributions to this work. [OR] We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nonenzymatic electrochemical biosensors, renowned for their high sensitivity, multi-target analysis capabilities, and miniaturized integration, align well with the requirements of non-invasive, multi-index integrated, continuous monitoring, and user-friendly wearable biosensors in sports science. In the past three years, novel strategies targeting specific responses to sports biomarkers have opened new avenues for applications in sports science. However, these advancements also pose challenges in achieving adequate sensitivity and specificity for online analysis of complex sweat bio-samples. Our article focuses on three key nonenzymatic electrochemical biosensing strategies: antigen-antibody reactions, nucleic acid aptamer recognition, and molecular imprinting capture. We delve into strategies to enhance specificity and sensitivity in the application of biosensors in sports science, including shortening signal transduction paths through built-in signal probes, increasing reaction sites through increased surface area and the introduction of nanostructures, multi-target analyses, and microfluidic techniques.

The emergence of lysosome-targeting chimeras (LYTACs), which represents a promising strategy for membrane protein degradation based on lysosomal pathways, has attracted much attention in disease intervention and treatment. However, the expression level of commonly used lysosome-targeting receptors (LTRs) varies in different cell lines, thus limiting the broad applications of LYTACs. To overcome this difficulty, we herein report the development of integrin α3β1 (ITGA3B1)-facilitated bispecific aptamer chimeras (ITGBACs) as a platform for the degradation of membrane proteins. ITGBACs consist of two aptamers, one targeting ITGA3B1 and another binding to the membrane-associated protein of interest (POI), effectively transporting the POI into lysosomes for degradation. Our findings demonstrate that ITGBACs effectively eliminate pathological membrane proteins, such as CD71 and PTK7, inducing significant cell-cycle arrest and apoptosis and markedly inhibiting tumor growth in tumor-bearing mice models. Therefore, this work provides a novel and versatile membrane protein degradation platform, offering a promising targeted therapy based on tumor-specific LTRs.

Foodborne illnesses caused by Salmonella bacteria pose a significant threat to public health. It is still challenging to detect them effectively. Herein, biotemplated Janus disk-shaped magnetic microrobots (BJDMs) based on diatomite are developed for the highly efficient detection of Salmonella in milk. The BJDMs were loaded with aptamer, which can be magnetically actuated in the swarm to capture Salmonella in a linear range of 5.8 × 10 2 to 5.8 × 10 5 CFU/mL in 30 min, with a detection limit as low as 58 CFU/mL. In addition, the silica surface of BJDMs exhibited a large specific surface area to adsorb DNA from captured Salmonella, and the specificity was also confirmed via tests of a mixture of diverse foodborne bacteria. These diatomite-based microrobots hold the advantages of mass production and low cost and could also be extended toward the detection of other types of bacterial toxins via loading different probes. Therefore, this work offers a reliable strategy to construct robust platforms for rapid biological detection in practical applications of food safety.

Lysosome-targeting chimera (LYTAC) shows great promise for protein-based therapeutics by targeted degradation of disease-associated membrane or extracellular proteins, yet its efficiency is constrained by the limited binding affinity between LYTAC reagents and designated proteins. Here, we established a programmable and multivalent LYTAC system by tandem assembly of DNA into a high-affinity protein degrader, a heterodimer aptamer nanostructure targeting both pathogenic membrane protein and lysosome-targeting receptor (insulin-like growth factor 2 receptor, IGF2R) with adjustable spatial distribution or organization pattern. The DNA-based multivalent LYTACs showed enhanced efficacy in removing immune-checkpoint protein programmable death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) in tumor cell membrane that respectively motivated a significant increase in T cell activity and a potent effect on cancer cell growth inhibition. With high programmability and versatility, this multivalent LYTAC system holds considerable promise for realizing protein therapeutics with enhanced activity.

Prostate cancer is the most prevalent malignant tumor affecting male individuals worldwide. The accurate early detection of prostate cancer is crucial to preventing unnecessary diagnosis and subsequent excessive treatment. Prostate-specific membrane antigen (PSMA) has emerged as a promising biomarker for the diagnosis of prostate cancer. In this study, a dual-modality imaging probe utilizing aptamer technology was developed for positron emission tomography/near-infrared fluorescence (PET/NIRF) imaging, and the specificity and sensitivity of the probe toward PSMA were evaluated both in vitro and in vivo. The probe precursor NOTA-PSMA-Cy5 was synthesized via automated solid-phase oligonucleotide synthesis. Subsequently, the PET/NIRF dual-modality probe [ 68 Ga]Ga-NOTA-PSMA-Cy5 was successfully prepared and exhibited favorable fluorescence properties and stability in vitro. The binding specificity of [ 68 Ga]Ga-NOTA-PSMA-Cy5 to PSMA was assessed through flow cytometry, fluorescence imaging, and cellular uptake experiments in LNCaP cells and PC-3 cells. In vivo PET/NIRF imaging studies demonstrated the sensitive and specific binding of [ 68 Ga]Ga-NOTA-PSMA-Cy5 to PSMA. Overall, the PET/NIRF dual-modality probe [ 68 Ga]Ga-NOTA-PSMA-Cy5 shows promise for the diagnosis of prostate cancer and for the fluorescence-guided identification of PSMA-positive cancer lesions during surgical procedures.

Aptamers are oligonucleotide sequences that can connect to particular target molecules, similar to monoclonal antibodies. They can be chosen by systematic evolution of ligands by exponential enrichment (SELEX), and are modifiable and can be synthesized. Even if the SELEX approach has been improved a lot, it is frequently challenging and time-consuming to identify aptamers experimentally. In particular, structure-based methods are the most used in computer-aided design and development of aptamers. For this purpose, numerous web-based platforms have been suggested for the purpose of forecasting the secondary structure and 3D configurations of RNAs and DNAs. Also, molecular docking and molecular dynamics (MD), which are commonly utilized in protein compound selection by structural information, are suitable for aptamer selection. On the other hand, from a large number of sequences, artificial intelligence (AI) may be able to quickly discover the possible aptamer candidates. Conversely, sophisticated machine and deep-learning (DL) models have demonstrated efficacy in forecasting the binding properties between ligands and targets during drug discovery; as such, they may provide a reliable and precise method for forecasting the binding of aptamers to targets. This research looks at advancements in AI pipelines and strategies for aptamer binding ability prediction, such as machine and deep learning, as well as structure-based approaches, molecular dynamics and molecular docking simulation methods.

Riboswitches are structured RNA elements that regulate gene expression upon binding to small molecule ligands. Understanding the mechanisms by which small molecules impact riboswitch activity is key to developing potent, selective ligands for these and other RNA targets. We report the structure-informed design of chemically diverse synthetic ligands for PreQ 1 riboswitches. Multiple X-ray co-crystal structures of synthetic ligands with the Thermoanaerobacter tengcongensis (Tte)-PreQ 1 riboswitch confirm a common binding site with the cognate ligand, despite considerable chemical differences among the ligands. Structure probing assays demonstrate that one ligand causes conformational changes similar to PreQ 1 in six structurally and mechanistically diverse PreQ 1 riboswitch aptamers. Single-molecule force spectroscopy is used to demonstrate differential modes of riboswitch stabilization by the ligands. Binding of the natural ligand brings about the formation of a persistent, folded pseudoknot structure, whereas a synthetic ligand decreases the rate of unfolding through a kinetic mechanism. Single round transcription termination assays show the biochemical activity of the ligands, while a GFP reporter system reveals compound activity in regulating gene expression in live cells without toxicity. Taken together, this study reveals that diverse small molecules can impact gene expression in live cells by altering conformational changes in RNA structures through distinct mechanisms., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Accurate and rapid imaging of tumor cells is of vital importance for early cancer diagnosis and intervention. Aptamer-based fluorescence sensors have become a potent instrument for bioimaging, while false positives and on-target off-tumors linked to single-biomarker aptasensors compromise the specificity and sensitivity of cancer imaging. In this paper, we describe a sequential response aptasensor for precise cancer cell identification that is based on a DNA "AND" logic gate. Specifically, the sensor consists of three single-stranded DNA, including the P-strand that can sensitively respond to an acid environment, the L-strand containing the ATP aptamer sequence, and the R-strand for target cell anchoring. These DNA strands hybridize with one another to create a Y-shaped structure (named Y-ALGN). The aptamer in the R-strand is utilized to anchor the sensor to the target cell membrane primarily. Responding to the extracellular acidic environment of the tumor (input 1), the I-motif sequence forms a tetramer structure so that the P-strand is released from the Y-shaped structure and exposes the ATP binding sites in the L-strand. Extracellular ATP, as input 2, continuously operates the DNA aptasensor to complete the logic computation. Upon the sequential response of both protons and ATP molecules, the aptasensor is activated with restored fluorescence on a particular cancer cell membrane. Benefiting from the precise computation capacity of the "AND" logic gate, the Y-ALGN aptasensor can distinguish between MCF-7 cells and normal cells with high accuracy. As a simple and dual-stimuli-responsive strategy, this nanodevice would offer a fresh approach for accurately diagnosing tumor cells.

The long-term operation feature of enzymatic biofuel cell-based self-powered biosensor (EBFC-SPB) endows them with the potential to execute dual-signal biosensing without having to integrate an extra signal acquisition device. Herein, cobalt and manganese codoped CeO 2 nanospheres (CoMn-CeO 2 NSs) with glucose-oxidase-like and peroxidase-like activities have been developed as substrate-switched dual-channel signal transduction components in EBFC-SPB for a dual-signal assay of aflatoxin B1 (AFB1). The CoMn-CeO 2 NSs modified with aptamer are anchored to a complementary DNA-attached bioanode of EBFC-SPB by base complementary pairing, which catalyze the glucose oxidation together with the glucose oxidase (GOx) on the bioanode. Once the AFB1 appears, CoMn-CeO 2 NSs will be released from the bioanode due to the binding specificity of the aptamer, resulting in a decreased catalytic efficiency and the first declining stage of EBFC-SPB. Accompanied by the introduction of H 2 O 2 , the residual CoMn-CeO 2 NSs on the bioanode switch to peroxidase-like activity and mediate the production of benzo-4-chlorohexadienone (4-CD) precipitate, which increases the steric hindrance and yields another declining stage of EBFC-SPB. By assessing the variation amplitudes during these two declining stages, the dual-signal assay of AFB1 has been realized with satisfying results. This work not only breaks ground in dual-signal bioassays but also deepens the application of nanozymes in EBFC-SPB.

In conventional metal-organic framework (MOF) luminophore-involved electrochemiluminescence (ECL) systems, the aggregation-caused quenching commonly exists for the organic luminescent ligands, limiting the ECL efficiency and detection sensitivity. Herein, by employing the aggregation-induced emission luminogen (AIEgen) 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene (H 4 TCBPE) as a ligand, one high-efficiency ECL emitter (Zr-MOF) was synthesized through a simple hydrothermal reaction. Compared with H 4 TCBPE monomers and their aggregates, the resultant Zr-MOF possesses the strongest ECL emission, which is mainly attributed to the framework-induced ECL enhancement. Specifically, the heterostructure was prepared by the deposition of silver nanoparticles on TiO 2 microflowers and utilized as an efficient coreaction accelerator. Remarkably, the formative heterojunction can increase the interfacial charge transfer efficiency and promote the carrier separation, facilitating the oxidation of coreactant tripropylamine. In this way, a novel aptamer-mediated ECL sensing platform is constructed, achieving the sensitive analysis of adenosine triphosphate with a low detection limit of 0.17 nM. As a proof-of-concept study, this work may enlighten the rational design of new-type MOF-based ECL materials and expand the application scope of the ECL technology.

A fluorescent and photoelectrochemical (PEC) dual-mode biosensor based on target biorecognition-triggered cyclic amplification was constructed for Kana detection. With the assistance of the catalyzed reaction of exonuclease III, a Kana-aptamer DNA duplex was designed for conducting the cyclic release of G-rich DNA sequence as well as output DNA S2. The released G-rich sequence triggers the fluorescence (FL) of thioflavin T (ThT), the intensity of which is positively correlated with the Kana concentration. The linear range is 0.2 to 30 nM, and the detection limit reaches 0.07 nM. Simultaneously, the released output DNA S2 was captured by Fe 3 O 4 @CdTe-probe ssDNA and then combined with methylene blue to realize the transduction of polarity-reversed PEC signal, leading to the sensitive detection of Kana with a linear range of 0.2 to 40 nM and a calculated detection limit of 0.2 nM. The outstanding performance endows the dual-mode biosensor a promising prospect for practical application., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A cortisol biosensor was developed based on double-conducting polymer nanowires, which exhibits excellent conductivity, resistance to biological contamination, and outstanding sensing performance. The biosensor employs dual-mode electrochemical techniques, namely, differential pulse voltammetry (DPV) and chronoamperometry (CA), for the sensitive and low fouling detection of the glucocorticoid hormone cortisol. Experimental results demonstrated that the linear detection range of the biosensor in DPV mode was 1.0 × 10 -14 -1.0 × 10 -8  M, with a detection limit of 0.131 × 10 -14  M. In CA mode, the biosensor exhibited a detection range of 1.0 × 10 -13 -1.0 × 10 -7  M and a detection limit of 0.313 × 10 -13  M. The biosensor was successfully utilized for the rapid detection of cortisol in human saliva. The combination of a high-specificity cortisol aptamer and functionalized double-conducting polymer nanowires ensured the exceptional specificity and sensitivity of the biosensor in detecting real biological samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Electrochemical detection of miRNA biomarkers in complex physiological samples holds great promise for accurate evaluation of tumor burden in the perioperative period, yet limited by reproducibility and bias issues. Here, nanosensors installed with hybrid probes that responsively release catalytic DNAzymes (G-quadruplexes/hemin) were developed to solve the fidelity challenge in an immobilization-free detection. miRNA targets triggered toehold-mediated strand displacement reactions on the sensor surface and resulted in amplified shedding of DNAzymes. Subsequently, the interference background was removed by Fe 3 O 4 core-facilitated magnetic separation. Binding aptamers of the electrochemical reporter (dopamine) were tethered closely to the catalytic units for boosting H 2 O 2 -mediated oxidation through proximity catalysis. The one-to-many conversion by dual amplification from biological-chemical catalysis facilitated sufficient homogeneous sensing signals on electrodes. Thereby, the nanosensor exhibited a low detection limit (2.08 fM), and high reproducibility (relative standard deviation of 1.99%). Most importantly, smaller variations (RSD of 0.51-1.04%) of quantified miRNAs were observed for detection from cell lysates, multiplexed detection from unprocessed serum, and successful discrimination of small upregulations in lysates of tumor tissue samples. The nanosensor showed superior diagnostic performance with an area under curve (AUC) of 0.97 and 94% accuracy in classifying breast cancer patients and healthy donors. These findings demonstrated the synergy of signal amplification and interference removal in achieving high-fidelity miRNA detection for practical clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The rapid and accurate identification of live pathogens with high proliferative ability is in great demand to mitigate foodborne infection outbreaks. Herein, we have developed an ultrasensitive image-based aptasensing array to directly detect live Salmonella typhimurium (S.T) cells. This method relies on the long-range orientation of surfactant-decorated liquid crystals (LCs) and the superiority of aptamers (apt ST ). The self-assembling of hydrophobic surfactant tails leads to a perpendicular/vertical ordered film at the aqueous/LC interface and signal-off response. The addition of apt ST perturbed LCs' ordering into a planar/tilted state at the aqueous phase due to electrostatic interactions between the surfactant with the apt ST , and a signal-on response. Following the conformational switch of apt ST in the presence of live S. typhimurium, a relative reversing signal-off response was observed upon the target concentration. This aptasensor could promptly confirm the presence of S. typhimurium without intricate DNA-extraction or pre-enrichment stats over a linear range of 1-1.1 × 10 6 CFU/mL and a detection limit of 1.2 CFU/mL within ∼30 min. These results were successfully validated using molecular and culture-based methods in spiked-milk samples, with a 92.61-104.61 % recovery value. Meanwhile, the flexibility of this portable sensing platform allows for its development and adoption for the precise detection of various pathogens in food and the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An optical photonic biosensor for the detection of microcystin (MC) has been developed using an aptamer-immobilized interpenetrating polymeric network (IPN aptamer ) intertwined with solid-state cholesteric liquid crystals (CLC solid s). The IPN was constructed with a polyacrylic acid hydrogel (PAA). Aptamer immobilization enhances polarity while blocking hydrogen bonding between the carboxylic groups of PAA-IPN hydrogel, thereby increasing the swelling ratio of the PAA-IPN hydrogel. This leads to an expansion in the helical pitch of the corresponding IPN aptamer -CLC solid biosensor chip and results in a red-shift in the reflected color. Upon exposure to an aqueous MC solution, the IPN aptamer -CLC solid biosensor chip exhibits aptamer-mediated engulfment of MC, resulting in reduced polarity of the IPN aptamer complex and a consequential blue-shift in the biosensor chip color occurred. The wavelength shift of the IPN aptamer -CLC solid biosensor chip demonstrates a linear change with an increase in MC concentration from 3.8 to 150 nM, with a limit of detection of 0.88 nM. This novel optical biosensor is characterized by its low cost, simplicity, selectivity, and sensitivity, offering a promising strategy for designing similar toxin biosensors through the modification of biological receptors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this work, a potential-controlled electrochromic visual biosensor was developed for detecting zearalenone (ZEN) using a distance readout strategy. The sensor chip includes a square detection area and a folded signal output area created with laser etching technology. The detection area is modified with graphene oxide and ZEN aptamer, while Prussian blue (PB) is electrodeposited onto the signal output channel. When an appropriate voltage is applied, PB in the signal output area is reduced to colorless Prussian white (PW). The target ZEN molecules have the capability to release aptamers from graphene oxide (GO) surface in the detection area, resulting in a subsequent change in the potential of the visual signal output channel. This change determines the length of the channel that changes from blue to colorless, with the color change distance being proportional to the ZEN concentration. Using this distance readout strategy, ZEN detection within the range of 1 ng/mL to 300 ng/mL was achieved, with a detection limit of 0.29 ng/mL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To address the potential hazards of organophosphorus pesticides (OPs) residues in tea, an electrochemiluminescence (ECL) aptasensor based on functionalized nanomaterials was constructed in this work. Firstly, gold nanoparticles (AuNPs) were attached on the surface of multi-walled carbon nanotubes (MWCNTs) by the constant potential electrodeposition to form a compound, and it was utilized to provide excellent immobilization sites for complementary DNA (cDNA). Subsequently, composite nanomaterials were synthesized by a one-pot method with aminated Luminol/silver nanoparticles@silica nanospheres (NH 2 -Luminol/Ag@SiO 2 NSs). Finally, NH 2 -Luminol/Ag@SiO 2 NSs was combined with a malathion aptamer (Apt) to obtain signal probes (SPs) for the construction of an aptasensor. The aptasensor had a wide linear range (1×10 -3 -1×10 3 ng/mL) and a low limit of detection (LOD) (0.3×10 -3 ng/mL). It had the virtues of high sensitivity, wonderful stability and excellent specificity, which could be used for the detection of malathion residue in tea. The work provides a proven way for the construction of a rapid and ultrasensitive aptasensor with low-cost., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier B.V.)

Aptamer-based electrochemical sensors are frequently used as independent, surface-functionalized, passive electrodes. However, their sensitivity and detection limits become limited, particularly when the electrode area is reduced to facilitate miniaturization. A mobile phone-based microfluidic electrochemical aptamer sensing platform for 3,3',4,4'-tetrachlorobiphenyl (PCB77) detection was developed in this work. This aptamer sensor utilized Exonuclease I (Exo I) and DNA/AuNPs/horseradish peroxidase (DNA/AuNPs/HRP) nanoprobes as a merged signal amplification method, which resulted in an increase in the electrochemical sensing performance. Sensitive detection of PCB77 was accomplished by functionalizing the hierarchically structured Au@MoS 2 /CNTs/GO modified working/sensing electrode with the specific aptamer. The aptamer sensor was tested with different concentrations of PCB77 within the microfluidic platform. Afterward, the differential pulse voltammograms were recorded using a wireless integrated circuit device. Subsequently, the collected data was transmitted to a smartphone using Bluetooth communication. A detection limit of 0.0085 ng/L was obtained for PCB77 detection, with a detection range from 0.1 to 1000 ng/L. In addition, the detection of PCB77 in spiked water samples validated the possibility of using this aptamer sensor in a real environment, and the aptamer sensor demonstrated high selectivity in distinguishing PCB77 from other potential interfering species. The merging of electrochemical aptamer sensors with purposefully engineered microfluidic and integrated devices in this study is a novel and promising method that provides a dependable platform for on-site applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, an ultrasensitive photoelectrochemical (PEC) aptasensor based on dual-sensitized heterojunction Ag 2 S/ZnS/NiS composites as a signal probe was proposed for the detection of tobramycin (TOB) by combining a cascaded quadratic signal amplification strategy. Specifically, compared to the limited visible light-harvesting capability of single sensitized composites, Ag 2 S/ZnS/NiS composites with p-n and n-n heterojunction could greatly improve the light energy utilization to tremendously strengthen the optical absorption in the entire visible-light region. Moreover, dual-sensitized heterojunction could effectively hinder the rapid recombination of photoelectrons and holes (carriers) to obtain a good photocurrent for improving the sensitivity of the aptasensor. Furthermore, a cascaded quadratic signal amplification strategy was applied to convert trace target TOB into plentiful gold nanoclusters (Au NCs) labelled double-stranded DNA for the construction of PEC aptasensor, with a broad linear detection range from 0.01 to 100 ng mL -1 and a low detection limit of 3.38 pg mL -1 . Importantly, this study provided a versatile and sensitive PEC biosensing platform for TOB analysis, and demonstrated its successful application for TOB detection in milk samples. This protocol provides a novel dual-sensitized heterojunction composites to develop a highly efficient and harmfulless PEC aptasensor, which is expected to be used in food safety, environmental monitoring and other areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A mid-infrared label-free immunoassay-based biosensor is an effective device to help identify and quantify biomolecules. This biosensor employs a surface-enhanced infrared absorption spectroscopy, which is a highly potent sensing technique for detecting minute quantities of analytes. In this study, a biosensor was constructed using a metamaterial absorber, which facilitated strong coupling effects. For maximum coupling effect, it is necessary to enhance the near-field intensity and the spatial and spectral overlap between the optical cavity resonance and the vibrational mode of the analyte. Due to significant peak splitting, conventional baseline correction methods fail to adequately analyze such a coupling system. Therefore, we employed a coupled harmonic oscillation model to analyze the spectral distortion resulting from the peak splitting induced by the strong coupling effect. The proposed biosensor with a thrombin-binding aptamer-based immunoassay could achieve a limit of detection of 267.4 pM, paving the way for more efficient protein detection in clinical practice., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jongwon Lee reports financial support was provided by National Research Foundation of Korea. Joo-Yun Jung reports financial support was provided by Korea Ministry of Trade Industry and Energy. Joo-Yun Jung reports financial support was provided by National Research Council of Science and Technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The depletion of β cell mass is widely recognized as a significant contributor to the progression of type 2 diabetes mellitus (T2DM). Exosomes derived from mesenchymal stem cells (MSC-EXOs) hold promise as cell-free therapies for treating T2DM. However, the precise effects and mechanisms through which MSC-EXO affects β cell function remain incompletely understood, and the limited ability of MSC-EXO to target β cells and the short blood circulation time hampers its therapeutic effectiveness., Methods: The effects of MSC-EXO were investigated in T2DM mice induced by a high-fat diet combined with STZ. Additionally, the high glucose-stimulated INS-1 cell line was used to investigate the potential mechanism of MSC-EXO. Michael addition reaction-mediated chemical coupling was used to modify the surface of the exosome membrane with a β-cell-targeting aptamer and polyethylene glycol (PEG). The β-cell targeting and blood circulation time were evaluated, and whether this modification enhanced the islet-protective effect of MSC-EXO was further analyzed., Results: We observed that the therapeutic effects of MSC-EXO on T2DM manifested through the reduction of random blood glucose levels, enhancement of glucose and insulin tolerance, and increased insulin secretion. These effects were achieved by augmenting β cell mass via inhibiting nuclear factor erythroid 2-related factor 2 (NRF2)-mediated ferroptosis. Mechanistically, MSC-EXOs play a role in the NRF2-mediated anti-ferroptosis mechanism by transporting active proteins that are abundant in the AKT and ERK pathways. Moreover, compared to MSC-EXOs, aptamer- and PEG-modified exosomes (Apt-EXOs) were more effective in islet protection through PEG-mediated cycle prolongation and aptamer-mediated β-cell targeting., Conclusion: MSC-EXO suppresses NRF2-mediated ferroptosis by delivering bioactive proteins to regulate the AKT/ERK signaling pathway, thereby improving the function and quantity of β cells. Additionally, Apt-EXO may serve as a novel drug carrier for islet-targeted therapy., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2024 Xia et al.)

Molecular biosensors that accurately measure protein concentrations without external equipment are critical for solving numerous problems in diagnostics and therapeutics. Modularly transducing the binding of protein antibodies, protein switches or aptamers into a useful output remains challenging. Here, we develop a biosensing platform based on aptamer-regulated transcription in which aptamers integrated into transcription templates serve as inputs to molecular circuits that can be programmed to a produce a variety of responses. We modularly design molecular biosensors using this platform by swapping aptamer domains for specific proteins and downstream domains that encode different RNA transcripts. By coupling aptamer-regulated transcription with diverse transduction circuits, we rapidly construct analog protein biosensors and digital protein biosensors with detection ranges that can be tuned over two orders of magnitude and can exceed the binding affinity of the aptamer. Aptamer-regulated transcription is a straightforward and inexpensive approach for constructing programmable protein biosensors that could have diverse applications in research and biotechnology., (© 2024. The Author(s).)

A sandwich electrochemical sensor was fabricated based on multi-walled carbon nanotubes/ordered mesoporous carbon/AuNP (MWCNTs/CMK-3/AuNP) nanocomposites and porous core-shell nanoparticles Au@PdNPs to achieve rapid and sensitive detection of AFB 1 in complex matrices. MWCNTs/CMK-3/AuNP nanocomposite, which was prepared by self-assembly method, served as a substrate material to increase the aptamer loading and improve the conductivity and electrocatalytic activity of the electrode for the first signal amplification. Then, Au@PdNPs, which were synthesized by one-pot aqueous phase method, were applied as nanocarriers loaded with plenty of capture probe antibody (Ab) and signal molecule toluidine blue (Tb) to form the Au@PdNPs-Ab-Tb bioconjugates for secondary signal amplification. The sensing system could still significantly improve the signal output intensity even in the presence of ultra-low concentration target compound due to the dual signal amplification of MWCNTs/CMK-3/AuNP nanocomposites and Au@PdNPs-Ab-Tb. The method exhibited high selectivity, low detection limit (9.13 fg/mL), and strong stability to differentiate AFB 1 from other mycotoxins. Furthermore, the sensor has been successfully applied to the quantitative determination of AFB 1 in corn, malt, and six herbs, which has potential applications in food safety, quality control, and environmental monitoring., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Gliomas remain challenging brain tumors to treat due to their infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful resection. This study introduces an innovative intraoperative visualization method utilizing surgical fluorescence microscopy to precisely locate tumor cell dissemination. Here, the focus is on the development of a novel contrasting agent (IR-Glint) for intraoperative visualization of human glial tumors comprising infrared-labeled Glint aptamers. The specificity of IR-Glint is assessed using flow cytometry and microscopy on primary cell cultures. In vivo effectiveness is studied on mouse and rabbit models, employing orthotopic xenotransplantation of human brain gliomas with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. The experiments validate the potential of IR-Glint for the intraoperative visualization of gliomas using infrared imaging. IR-Glint penetrates the blood-brain barrier and can be used for both intravenous and surface applications, allowing clear visualization of the tumor. The surface application directly to the brain reduces the dosage required and mitigates potential toxic effects on the patient. The research shows the potential of infrared dye-labeled aptamers for accurately visualizing glial tumors during brain surgery. This novel aptamer-assisted fluorescence-guided surgery (AptaFGS) may pave the way for future advancements in the field of neurosurgery.

DNA-aptamer-functionalized electrode arrays can provide an intriguing method for detecting pathogen-derived exometabolites. This work addresses the limitations of previous aptamer-based pathogen detection methods by introducing a novel surface design that bridges the gap between initial efforts in this area and the demands of a point-of-care device. Specifically, the use of a diblock copolymer coating on a high-density microelectrode array and Cu-mediated cross coupling reactions that allow for the exclusive functionalization of that coating by any electrode or set of electrodes in the array provides a device that is stable for 1 year and compatible with the multiplex detection of small-molecule targets. The new chemistry developed allows one to take advantage of a large number of electrodes in the array with one experiment described herein capitalizing on the use of 960 individually addressable electrodes.

In this work, we explored the potential of thiol-capped CdZnTe quantum dots (QDs) as an exceptional signal tag for fluorescence aptasensing applications. Employing a one-pot hydrothermal approach, we modulated the terminal functional groups of CdZnTe QDs using l-cysteine (Lcys), 3-mercaptopropionic acid (MPA), and N-acetyl-l-cysteine (NAC) as ligands. Our comparative analysis revealed that NAC-capped CdZnTe QDs (NAC-CdZnTe QDs) exhibited superior anti-interference capabilities and storage stability across various temperatures, pH levels, and storage durations. Encouraged by these promising results, we further optimized the use of ultrastable NAC-CdZnTe QDs encapsulated in dendritic mesoporous silica nanoparticles (DMSN@QDs) as an exceptional tag for the development of an advanced anti-interference fluorescence aptasensor for aflatoxin B1 (AFB1) detection. The developed aptasensor using DMSN@QDs as signal tags achieved a remarkable signal amplification of approximately 10.2 fold compared to the NAC-CdZnTe QDs coated silica (SiO 2 @QDs) labeled fluorescence aptasensor. This aptasensor was able to detect AFB1 within a wide range of 1 pg mL -1 to 200 ng mL -1 , achieving a limit of detection as low as 0.41 pg mL -1 (S/N = 3). Crucially, the specific binding affinity between the aptamer and the target enabled the aptasensor to be easily customized for various targets by simply replacing the aptamer sequence with the desired one. The exceptional potential of NAC-CdZnTe QDs, particularly when encapsulated in DMSNs, leads to the development of highly sensitive and selective anti-interference fluorescence aptasensors for various targets, thereby, paving the way for advancements in a diverse range of applications.

Uranium is a nuclear fuel but also a hazardous contaminant due to its radioactivity and chemical toxicity. To prevent and mitigate its potential threat, the accurate monitoring of ultratrace uranium (orders of magnitude of pg g -1 ) in practical environmental samples has become an important scientific problem. To meet this challenge, we developed an efficient electrochemiluminescence (ECL) UO 2 2+ detection device by a novel dual-enhancement mechanism. In detail, poly[(9,9-dioctylfuor-enyl-2,7-diyl)- alt -co-(1,4-benzo-{2,1,3}-thiadiazole)] polymer dots (Pdots) are modified by the UO 2 2+ DNA aptamer, and rhodamine B (RhB) is combined with dsDNA to quench the ECL signal via a resonance energy transfer (RET) process. UO 2 2+ can cut off the DNA aptamer to release RhB, which generates an ECL enhancement process, and then, UO 2 2+ continuously combines with the DNA chain, inducing another ECL enhancement by the RET process from UO 2 2+ to Pdots. This device achieves an ultralow detection limit (12 pg L -1 ) and a wide linear range (113 pg L -1 -11.3 mg L -1 ), which can successfully give accurate determination results to the ultratrace uranium in biosamples (<1 pg g -1 ) to monitor the uranium simulation of fish. This work presents an efficient strategy for ultratrace uranium determination in the environment, highlighting its significance in public health and environmental fields.

Metal-organic frameworks and hydrogen-organic frameworks (MOFs and HOFs) are attractive hosts for enzyme immobilization, but they are limited to immobilizing the purified enzymes, making industrial upscaling unattractive. Herein, aptamer-modified dual thermoresponsive polymeric micelles with switchable self-assembly and core-shell structure are constructed, which enable selective immobilization of trypsin directly from complex biological systems through a cascade operation of separation and immobilization. Their steric self-assembly provides a large amount of adsorption sites on the soluble micellar shell, resulting in high adsorption capacity and excellent selectivity. Meanwhile, their aptamer affinity ligand and cavity maintain the native conformations of trypsin and offer protective effects even in harsh conditions. The maximum adsorption capacity of the polymeric micelles for trypsin was determined to be 197 mg/g at 60 min, superior to those of MOFs and HOFs. 67.2 and 86.6% of its original activity was retained for trypsin immobilized in the cavity under strong alkaline and acidic conditions, respectively.

Multi-aptamer recognition of breast cancer cells (MCF-7) is utilized to achieve high specificity. The method comprises two parts, aptamer-functionalized mesoporous silica nanoparticles (MSNs) loaded with dissimilar dyes (thymolphthalein or curcumin) as signal transducers and aptamer-modified magnetic beads (MBs) as capture agents, which worked together to detect MCF-7 cells sensitively and accurately. The results indicated that the aptasensor has a linear detection range of 100 to 4000 cells and a detection threshold of 10 cells/mL. The method had been successfully employed to detect breast cancer cells in real blood samples to distinguish between breast cancer patients and healthy individuals. In conclusion, the development of the multi-aptamer-based colorimetric sensor offered a novel method for the highly selective detection of MCF-7 cells, contributing to the accurate identification of breast cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Neurotransmitters are crucial for the proper functioning of neural systems, with dopamine playing a pivotal role in cognition, emotions, and motor control. Dysregulated dopamine levels are linked to various disorders, underscoring the need for accurate detection in research and diagnostics. Single-stranded DNA (ssDNA) aptamers are promising bioreceptors for dopamine detection due to their selectivity, improved stability, and synthesis feasibility. However, discrepancies in dopamine specificity have presented challenges. Here, we surface-functionalized a nano-plasmonic biosensing platform with a dopamine-specific ssDNA aptamer for selective detection. The biosensor, featuring narrowband hybrid plasmonic resonances, achieves high specificity through functionalization with aptamers and passivation processes. Sensitivity and selectivity for dopamine detection are demonstrated across a wide range of concentrations, including in diverse biological samples like protein solutions, cerebrospinal fluid, and whole blood. These results highlight the potential of plasmonic "aptasensors" for developing rapid and accurate diagnostic tools for disease monitoring, medical diagnostics, and targeted therapies.

Histamine has been known as a momentous cause of biogenic amine poisoning. Therefore, the content of histamine in foods is strictly required to be controlled within a certain range. Here, an aptamer fluorescent sensor was developed for detection of histamine. Poly [(9, 9-di-n-octylfluorenyl-2, 7-diyl)-alt-(benzo [2,1,3] thiadia-zol-4, 8-diyl)] (PF8BT) and the styrene maleic anhydride copolymer (PSMA) were used for the preparation of PF8BT-Polymer dots (PF8BT-Pdots). PF8BT-Pdots and the cyanine3-phosphoramidite (Cy3) were linked through aptamer to achieve the ratiometric detection for histamine. PF8BT-Pdots were partly quenched by Cy3 due to the fluorescence resonance energy transfer (FRET), when the histamine molecule was recognized by aptamer on the surface of PF8BT-Pdots. A linear range (3-21 μmol/L) was obtained for histamine detection with a low limit of detection (LOD = 0.38 μmol/L). PF8BT aptamer Pdots (PF8BT-A) were used to detect histamine in simply treated aquaculture water and tuna. The cell imaging of HeLa cells presented a good biosecurity and outstanding fluorescent imaging capability of PF8BT-A. The aptamer fluorescent sensors provided a new platform for rapid and accurate detection of histamine in aquatic products and had great potential for the application in food safety and quality control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In light of the significant risks that mycotoxins posed to public health and environmental safety, this research developed an adsorbent MIPs/Apt/AuNPs@ZIF-67 (MA-AZ) utilizing a dual-recognition approach combining molecularly imprinted polymers (MIPs) and aptamer (Apt). This innovative method enabled the effective and highly selective recognition and enrichment of ochratoxin A (OTA). ZIF-67 was utilized as a carrier with a substantial specific surface area, and gold nanoparticles (AuNPs) were loaded on its surface to fix the thiol-modified Apt on the surface of the carrier. Then, an initiator was used to initiate a polymerization reaction, and the generated MIPs coated Apt/AuNPs@ZIF-67, thereby synthesizing the MA-AZ with a "synergistic recognition" effect. The Apt significantly increased the number of recognition sites within the imprinted cavities, and MIPs played roles in identifying targets, fixing and protecting Apt. The combination of the both produced the effect of "1+1>2". The study on the adsorption performance of MA-AZ found that the adsorption capacity of MA-AZ could reach 65.1 mg/g, and the imprinted factor was 5.48. In addition, MA-AZ exhibited excellent stability, specificity, reusability and recovery rate. Thus, this study offers valuable insights for the recognition and enrichment of hazardous substances, and helps to promote the rapid development of safety detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The use of messenger RNA (mRNA) as a cancer vaccine and gene therapy requires targeted vehicle delivery to the site of disease. Here, we designed a mRNA-encapsulating lipid nanoparticle (LNP) conjugated with anti-programmed death-ligand 1 (PD-L1) DNA aptamer that delivers mRNA encoding a tumor suppressor gene, namely phosphatase and tensin homolog (PTEN), to castration-resistant prostate cancer (CRPC) cells expressing PD-L1 on the cell surface. The DNA aptamer-conjugated LNP-based mRNA delivery system (Apt-LNP[PTEN mRNA]) mediated efficient mRNA delivery and transfection in CRPC cells than LNPs without targeting ligands. Cancer-targeted PTEN mRNA delivery using Apt-LNPs achieved significantly higher PTEN expression via aptamer-mediated endocytosis in target cancer cells compared with non-targeted LNP delivery, resulting in significant downregulation of AKT phosphorylation. This enhanced PI3K/AKT pathway regulation, and in turn reduced cell migration after two days along with a 70 % decrease in cell viability, leading to effective apoptotic cell death. In a CRPC xenograft model, Apt-LNP[PTEN mRNA] led to an approximate 60 % reduction in tumor growth, which was attributable to the effective PTEN restoration and PI3K/AKT signaling pathway regulation. PTEN expression was significantly enhanced in CRPC tumor tissues, which abolished cancer cell tumorigenicity. These findings demonstrated the potential of Apt-LNPs for targeted mRNA delivery to cancer cells, thus providing a promising tool for targeted mRNA delivery to a range of cancers and tissues using a conventional LNP systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Developing sensors with high selectivity and sensitivity is of great significance for pesticide analysis in environmental assessment. Herein, a versatile three-way sensor array was designed for the detection of the pesticide atrazine, based on the integration of catalytic hairpin assembly (CHA) amplification and three-mode signal transducers. With atrazine, CHA was triggered to generate abundant G-quadruplex. The produced G-quadruplex hybrid could assemble with thioflavin T (TFT) or hemin to mimic enzyme and induce the fluorescence enhancement by TFT, or the colorimetric increase by the oxidized chromogenic substrate and the naked-eye color change by inhibiting the L-cysteine-mediated aggregation of gold nanoparticles. A distinctive three-mode array was successfully constructed with convenience, on-site accessibility and high sensitivity for enzyme-free practical analysis of atrazine. It is also effective and reliable for analyzing real samples including paddy water, paddy soil and polished rice. The detection limits for atrazine were as low as 7.4 pg/mL by colorimetric observation and 0.25 pg/mL by fluorescent detection. Furthermore, the array was exploited to monitor the residue, distribution and bioaccumulation of atrazine in maize and rice for food security and environmental assessment. Hence, this work presented a versatile example for sensitive and on-site all-in-one pesticide analysis arrays with multiple signal report modes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

5-Fluorouracil (5-FU) is a conventional nucleotide analogue used for cancer treatment. However, its clinical application faces challenges such as low stability and non-specific toxicity. With the remarkable advancements in DNA nanotechnology, DNA-based self-assembled nanocarriers have emerged as powerful tools for delivering nucleotide drugs. In this study, we have designed a non-linear hybrid chain reaction involving a fuel strand with AS1411 aptamer sequence to construct a dendritic structure capable of carrying 5-FU. This structure specifically targets cancer cells with overexpressed nucleolin on their surface, allowing the 5-FU to exert its anticancer effects and achieve therapeutic outcomes. Furthermore, we have also investigated the mechanistic action of this drug delivery system, aiming to establish a novel therapeutic platform for 5-FU treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Herein, a novel sandwich electrochemiluminescence (ECL) aptasensor was developed based on the resonance energy transfer (RET) with iridium complex doped silicate nanoparticles (SiO 2 @Ir) as energy donor and gold nanoparticles modified TiVC MXene (AuNPs@TiVC) as energy acceptor. Strong anodic ECL signal of SiO 2 @Ir was obtained through both co-reactant pathway and annihilation pathway. Electrochemical results showed that SiO 2 @Ir has good electron transfer rate and large specific surface area to immobilize more aptamers. AuNPs@TiVC apparently quenched the ECL signal of SiO 2 @Ir due to the ECL resonance energy transfer between them. In the presence of kanamycin (KAN), a sandwich type sensor was formed with the aptamer probes as connecters between the donor and the acceptor, resulting in the decrease of ECL intensity. Under the optimal condition, KAN could be sensitively detected in the range of 0.1 pg/mL to 10 ng/mL with a low detection limit of 24.5 fg/mL. The proposed ECL system exhibited satisfactory analytical performance, which can realize the detection of various biological molecules by adopting suitable aptamer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Over the last 30 years, despite considerable research and endeavors aimed at harnessing aptamers as pharmaceutical molecules, the progress in developing aptamer-based drugs has been falling short of expectations. Sequential steps of affinity molecule acquisition and functional screening are typically required for discovering affinity-based macromolecule therapeutics, which can be time-consuming and limiting in candidate selection. Additionally, aptamers often necessitate tedious postselection modifications to overcome pharmacokinetic limitations, which usually impede the binding affinity. Herein, we propose a novel in vitro screening platform termed Functional Aptamers in vitro Evolution (FAIVE), which integrates affinity molecule acquisition with functional screening and introduces chemical diversity during the process. This platform aims to rapidly generate functional aptamers capable of binding to target proteins and regulating their functions. Illustrated by targeting intranuclear RNA-protein interactions involving HIV-1 Tat protein and TAR RNA, FAIVE demonstrates a selection of functional aptamers with significant intracellular blocking effects. The study also explores lipid nanoparticle delivery systems to enhance intracellular delivery efficiency, expanding aptamer targeting potential to broader intracellular and intranuclear domains. This study emphasizes the potential of FAIVE to expedite the development of aptamer-based drugs and facilitate the creation of more versatile and effective therapeutics.

Structure-switching aptamers have become ubiquitous in several applications, notably in analytical devices such as biosensors, due to their ease of supporting strong signaling. Aside from their ability to bind specifically with their respective target, this class of aptamers also undergoes a conformational rearrangement upon target recognition. While several well-studied and early-developed aptamers (e.g., cocaine, ATP, and thrombin) have been found to have this structure-switching property, the vast majority do not. As a result, it is common to try to engineer aptamers into switches. This proves challenging in part because of the difficulty in obtaining structural and functional information about aptamers. In response, we review various readily available biophysical characterization tools that are capable of assessing structure switching of aptamers. In doing so, we delve into the fundamentals of these different techniques and detail how they have been utilized in characterizing structure-switching aptamers. While each of these biophysical techniques alone has utility, their real power to demonstrate the occurrence of structural change with ligand binding is when multiple techniques are used. We hope that through a deeper understanding of these techniques, researchers will be better able to acquire biophysical information about their aptamer-ligand systems and accelerate the translation of aptamers into biosensors.

In electrochemical analysis, developing biosensors that can resist the nonspecific adsorption of interfering biomolecules in human serum remains a huge challenge, which depends on the design of efficient antifouling materials. Herein, 3-aminopropyldimethylamine oxide (APDMAO) biomimetic zwitterions were prepared as antifouling interfaces. Among them, the unique positive and negative charges (N + -O - ) of APDMAO promoted its hydrogen bonding with water molecules, forming a firm hydration barrier that endowed it with strong and stable antifouling performance. Meanwhile, its inherent amino groups could copolymerize with the biomimetic adhesive dopamine to form a thin layer of quinone intermediates, providing conditions for the subsequent binding of aptamers and signal probes. Importantly, the biomimetic APDMAO with functional groups and one-step oxidation characteristics solved the challenges of zwitterionic synthesis and modification, as well as improved biocompatibility of the sensing interface, thereby expanding the application potential of zwitterions as antifouling materials in sensing analysis. Thiol-containing alpha-fetoprotein (AFP) aptamers modified with methylene blue (MB) were coupled under controllable potential, greatly reducing the incubation time, which promoted the productization application of biosensors. In addition, the ratio sensing strategy using MB as internal standard factors and concanavalin-silver nanoparticles (ConA-Ag NPs) as signal probes was introduced to reduce background and instrument interferences, thus improving detection accuracy. On this basis, the proposed antifouling electrochemical biosensor achieved sensitive and accurate AFP detection over a wide dynamic range (10 fg/mL-10 ng/mL), with a low detection limit of 3.41 fg/mL (3σ/ m ). This work provides positive insights into the development of zwitterionic antifouling materials and clinical detection of liver cancer markers in human serum.

The viral infectivity factor (Vif) of human immunodeficiency virus 1 forms a complex with host proteins, designated as Vif-CBFβ-ELOB-ELOC-CUL5 (VβBCC), initiating the ubiquitination and subsequent proteasomal degradation of the human antiviral protein APOBEC3G (A3G), thereby negating its antiviral function. Whilst recent cryo-electron microscopy (cryo-EM) studies have implicated RNA molecules in the Vif-A3G interaction that leads to A3G ubiquitination, our findings indicated that the VβBCC complex can also directly impede A3G-mediated DNA deamination, bypassing the proteasomal degradation pathway. Employing the Systematic Evolution of Ligands by EXponential enrichment (SELEX) method, we have identified RNA aptamers with high affinity for the VβBCC complex. These aptamers not only bind to the VβBCC complex but also reinstate A3G's DNA deamination activity by inhibiting the complex's function. Moreover, we delineated the sequences and secondary structures of these aptamers, providing insights into the mechanistic aspects of A3G inhibition by the VβBCC complex. Analysis using selected aptamers will enhance our understanding of the inhibition of A3G by the VβBCC complex, offering potential avenues for therapeutic intervention., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

The quality of food is one of the emergent points worldwide. Many microorganisms produce toxins that are harmful for human and animal health. In particular, mycotoxins from Fusarium fungi are strictly controlled in cereals. Simple and robust biosensors are necessary for 'in field' control of the crops and processed products. Nucleic acid-based sensors (aptasensors) offer a new era of point-of-care devices with excellent stability and limits of detection for a variety of analytes. Here we report the development of a surface-enhanced Raman spectroscopy (SERS)-based aptasensor for the detection of T-2 and deoxynivalenol in wheat grains. The aptasensor was able to detect as low as 0.17% of pathogen fungi in the wheat grains. The portable devices, inexpensive SERS substrate, and short analysis time encourage further implementation of the aptasensors outside of highly equipped laboratories.