Intramolecular distance-regulated G4 DNA enzymatic activity-based chromophotometric system for visual monitoring of diquat.

Background: As global food production continues to surge, the widespread use of herbicides has also increased concurrently, posing challenges like health risks and environmental pollution. Traditional detection methods for pesticide residues, such as diquat (DQ), were hampered by limitations like high expenses, lengthy detection times and complex operations, restricting their practical application in rapid clinical diagnosis.

Results: In light of the pressing necessity for the identification of minute pesticide residues and the intrinsic constraints of small molecule analysis, a novel chromophotometric biosensor targeting small molecules was developed based on bi-epitopes on single antibody to immobilize two DQ-PAL, inhibiting the hybridization of DQ-PAL.

DNA lesion-gated dumbbell nanodevices enable on-demand activation of the cGAS-STING pathway for enhancing cancer immunotherapy.

Utilizing the cGAS-STING pathway to combat immune evasion is one of the most promising strategies for enhancing cancer immunotherapy. However, current techniques for activating the cGAS-STING pathway often face a dilemma, mainly due to the balance between efficacy and safety. Here, we develop a uracil base lesion-gated dumbbell DNA nanodevice (UBLE) that allows on-demand activation and termination of the cGAS-STING pathway in tumor cells, thereby enhancing cancer immunotherapy.

Engineering of a Multi-Modular DNA Nanodevice for Spatioselective Imaging and Evaluation of NK Cell-Mediated Cancer Immunotherapy.

Granzyme A (GzmA) secreted by natural killer (NK) cells has garnered considerable interest as a biomarker to evaluate the efficacy of cancer immunotherapy. However, current methodologies to selectively monitor the spatial distribution of GzmA in cancer cells during NK cell-targeted therapy are extremely challenging, primarily due to the existence of diverse cell populations, the low levels of GzmA expression, and the limited availability of GzmA probes. Herein we develop a multi-modular, structurally-ordered DNA nanodevice for evaluating NK cell-mediated cancer immunotherapy (MODERN), that permits spatioselective imaging of GzmA in cancer cells through GzmA-induced apurinic/apyrimidinic endonuclease 1 (APE1) inactivation.

Pyrene-Based Metal-Organic Frameworks with Coordination-Enhanced Electrochemiluminescence for Fabricating a Biosensing Platform.

Enhancing the electrochemiluminescence (ECL) properties of polycyclic aromatic hydrocarbons (PAHs) is a significant topic in the ECL field. Herein, we elaborately chose PAH derivative luminophore 1,3,6,8-tetrakis(-benzoic acid)pyrene (HTBAPy) as the organic ligand to synthesize a new Ru-complex-free ECL-active metal-organic framework Dy-TBAPy. Interestingly, Dy-TBAPy exhibited a more brilliant ECL emission and higher ECL efficiency than HTBAPy aggregates.

Multienzymatic Orthogonal Activation of DNA Codec Enables Tumor-Specific Imaging of Base Excision Repair Activity.

Accurate monitoring of base excision repair (BER) activity in cancer cells is critical for advancing the comprehension of DNA repair processes, gaining insights into cancer development, and guiding treatment strategies. However, current assay techniques for assessing BER activity in cancer cells face challenges due to the heterogeneous origins and diversity of BER enzymes. In this work, we present a hihly relible riple loop-intrlocked DNA coec (GATED) that enables precise assessment of BER activity in cancer cells through signal amplification mediated by multienzyme orthogonal activation.

Pyrenetetrasulfonate-grafted 2D ultrathin metal-organic layer as new electrochemiluminescence emitters for ultrasensitive microRNA-21 assay.

The exploration of novel electrochemiluminescence (ECL) luminophores with excellent ECL properties is a current research hotspot in the ECL field. Herein, a novel high-efficiency Ru-complex-free ECL emitter PyTS-Zr-BTB-MOL has been prepared by using porous ultrathin Zr-BTB metal-organic layer (MOL) as carrier to coordinatively graft the cheap and easily available polycyclic aromatic hydrocarbon (PAH) derivative luminophore PyTS whose ECL performance has never been investigated. Gratifyingly, the ECL intensity and efficiency of PyTS-Zr-BTB-MOL were markedly enhanced compared to both PyTS monomers and PyTS aggregates.

Rigidifying AIEgens in covalent organic framework nanosheets for electrochemiluminescence enhancement: TABE-PZ-CON as a novel emitter for microRNA-21 detection.

Enhancing electrochemiluminescence (ECL) properties of luminophores is a hot direction in the current ECL field. Herein, we found that covalent rigidification of the aggregation-induced emission luminogens (AIEgens) TABE (TABE = tetra-(4-aldehyde-(1,1-biphenyl))ethylene) into covalent organic framework nanosheets (TABE-PZ-CON, PZ = piperazine) could result in stronger ECL emission than those of TABE aggregates and TABE monomers. We termed the interesting phenomenon "covalent rigidification-triggered electrochemiluminescence (CRT-ECL) enhancement".

AND Logic Gate-Regulated DNAzyme Nanoflower for Monitoring the Activity of Multiple DNA Repair Enzymes.

Despite the progress that has been made in diverse DNA-based nanodevices to in situ monitor the activity of the DNA repair enzymes in living cells, the significance of improving both the sensitivity and specificity has remained largely neglected and understudied. Herein, we propose a regulatable DNA nanodevice to specifically monitor the activity of DNA repair enzymes for early evaluation of cancer mediated by genomic instability. Concretely, an AND logic gate-regulated DNAzyme nanoflower was rationally designed by the self-assembly of the DNA duplex modified with both apurinic/apyrimidinic (AP) site and methyl lesion site.

Universal Signal Switch Based on a Mesostructured Silica Xerogel-Confined ECL Polymer for Epigenetic Quantification.

The development of a highly accurate electrochemiluminescence (ECL) signal switch to avoid nonspecific stimulus responses is currently a significant and challenging task. Here, we constructed a universal signal switch utilizing a luminophore-quencher pair of mesostructured silica xerogel-confined polymer and gold nanoparticles (Au NPs) that can accurately detect low-abundance epigenetic markers in complex sample systems. Notably, the ECL polymer encapsulated in mesostructured silica xerogel acts as a luminophore, which demonstrated a highly specific dependence on the Au NPs-mediated energy transfer quenching.

Circular DNAzyme-Switched CRISPR/Cas12a Assay for Electrochemiluminescent Response of Demethylase Activity.

DNA nanostructure provides powerful tools for DNA demethylase activity detection, but its stability has been significantly challenged. By virtue of circular DNA with resistance to exonuclease degradation, herein, the circular DNAzyme duplex with artificial methylated modification was constructed to identify the target and output the DNA activators to drive the CRISPR/Cas12a, constructing an "on-off-on" electrochemiluminescence (ECL) biosensor for monitoring the activity of the O-methylguanine-DNA methyltransferase (MGMT). Specifically, the circular DNAzyme duplex consisted of the chimeric RNA-DNA substrate ring with double activator sequences and two single-stranded DNAzymes, whose catalytic domains were premodified with the methyl groups.

Engineering Molecular Emission Centers of Carbon Dots to Boost the Electrochemiluminescence for the Detection of Cancer Cells.

Despite the fact that electrochemiluminescent (ECL) performance of carbon dots (CDs) could be improved by modulating their surface defects, they are still restricted by inferior controllability and poor reproducibility. In this work, we disclosed a new approach for synthesizing luminescent groups rich in CDs (Lu-CDs) by engineering the luminol as molecular emission centers into the CDs, which exhibited an 80-fold stronger ECL intensity at an ECL onset potential of 0.6 V than the CDs without pre-implanted luminol.

Ultrasensitive quantitation of Paraquat based on a small molecule-induced dual-cycle amplification strategy.

Paraquat (PQ) is a typical biotoxic small molecule. Knowledge of how to directly introduce it into cyclic amplification rather than transform it into a secondary target is lacking in current analytical methods. Considering the urgent need for trace pesticide residue detection and the inherent defects of small molecule analysis, a CRISPR/Cas12a-driven small molecule-induced dual-cycle strategy was developed based on the immune competition method.

Target-induced multipath-to-one-substrate approach for high-efficient bioanalysis of microRNA.

Considering the significant potential of microRNA (miRNA) as an efficient biomarker and great challenge of accurate analysis of lowly abundant miRNA, herein, we proposed a target-induced multipath-to-one-substrate strategy to monitor miRNA in vivo and in vitro accurately with high-efficient performances. In presence of target miRNA, it could directly generate the catalytic hairpin assembly (CHA) amplification cycle based on hybridizing with hairpin 1 (H1) and H2 respectively to structure the H1-H2 duplex, then the H1-H2 duplex could activate the cleavage ability of CRISPR/Cas12a to cleavage H1 which represent miRNA indirectly consume H1, which achieve co-consumption of the same substrate H1 by multiple pathways. And thus, the quenched fluorescent signal on H1 could be recovered due to the enlarger distance between fluorescent probe and quencher by the formation of H1-H2 duplex or cleavage of H1, all of which were related directly with target miRNA or indirectly with H1-H2 duplex activated cleavage ability of CRISPR/Cas12a, generating ultrahigh sensitive analytical ability and high-efficient analytical performances, such as more simple, fast, efficient and so on, especially a linear correlation from 100 pM to 100 nM with a detection limit of 78 pM, opening a new door to monitor expression level of biomolecules for early diagnosis and prognosis evaluation of various diseases.

Spherical nucleic acid enzyme programmed network to accelerate CRISPR assays for electrochemiluminescence biosensing applications.

Given the targeted binding ability and cleavage activity of the emerging CRISPR/Cas12a assay which transduces the target into its cleavage activity exhibited broadly prospective applications in integrated sensing and actuating system. Here, we elaborated a universal approach to quickly activate CRISPR/Cas12a for low-abundance biomarker detection based on the amplification strategy of a target-induced spherical nucleic acid enzyme (SNAzyme) network that could accelerate the output of activators. Specifically, multifunctional Y-shaped probes and hairpin probes (HPs, which contained the specific sequence of the activators of CRISPR/Cas12a and the substrate chain of DNAzyme) were rationally designed to construct SNAzyme.

Identification and Quantification of 5-Methylcytosine and 5-Hydroxymethylcytosine on Random DNA Sequences by a Nanoconfined Electrochemiluminescence Platform.

5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are two of the most abundant epigenetic marks in mammalian genomes, and it has been proven that these dual epigenetic marks give a more accurate prediction of recurrence and survival in cancer than the individual mark. However, due to the similar structure and low expression of 5mC and 5hmC, it is challenging to distinguish and quantify the two methylation modifications. Herein, we employed the ten-eleven translocation family dioxygenases (TET) to convert 5mC to 5hmC a specific labeling process, which realized the identification of the two marks based on a nanoconfined electrochemiluminescence (ECL) platform combined with the amplification strategy of a recombinase polymerase amplification (RPA)-assisted CRISPR/Cas13a system.

Insights of Life Molecules' Dynamic Distribution in Live Cells via Sequence-Structure Bispecific Fluorescent RNA.

Life molecules' distributions in live systems construct the complex dynamic reaction networks, whereas it is still challenging to demonstrate the dynamic distributions of biomolecules in live systems. Herein, we proposed a dynamic analysis strategy sequence-structure bispecific RNA with state-adjustable molecules to monitor the dynamic concentration and spatiotemporal localization of these biomolecules in live cells based on the new insight of fluorescent RNA (FLRNA) interactions and their mechanism of fluorescence enhancement. Typically, computer-based nucleic acid-molecular docking simulation and molecular theoretical calculation have been proposed to provide a simple and straightforward method for guiding the custom-design of FLRNA.

Ruthenium(II) complex-grafted conductive metal-organic frameworks with conductivity- and confinement-enhanced electrochemiluminescence for ultrasensitive biosensing application.

Improving the electrochemiluminescence (ECL) performance of luminophores is an ongoing research hotspot in the ECL realm. Herein, a high-performance metal-organic framework (MOF)-based ECL material (Ru@Ni(HITP), HITP = 2,3,6,7,10,11-hexaiminotriphenylene) with conductivity- and confinement-enhanced ECL was successfully constructed by using conductive MOF Ni(HITP) as the carrier to graft Ru(bpydc) (Hbpydc = 2,2'-bipyridine-4,4'-dicarboxylic acid) into the channels of Ni(HITP). Compared to Ru@Cu(HITP) and Ru@Co(HITP) with relatively low conductivity, the ECL intensity of Ru@Ni(HITP) was prominently increased about 6.

Identifying 5-Hydroxymethylcytosine without Sequence Specificity Using MOF-Derived MnOS Nanoflowers for Boosting Electrochemiluminescence.

It is universally recognized that the quantification of DNA hydroxymethylation at random gene sequences still remains challenging. Herein, the highly sensitive identifying strategy of 5-hydroxymethylcytosine (5-hmC) without sequence specificity was achieved with a novel electrochemiluminescence (ECL) biosensor, which deftly integrated metal-organic framework (MOF)-derived amorphous MnOS nanoflowers (MnOS NFs) as a bifunctional co-reaction accelerator and cross-shaped DNA tracks as a well-regulated signal switch. Specifically, the target recognition process of 5-hmC was performed through specific chemical modification, where the hydroxymethyl sites were first aminated and then labeled with a 5'-carboxyl-functioned DNA walker, thus forming the target labeled DNA walker (5-ghmC-walker).

In situ growth of metal-organic layer on ultrathin TiCT MXene nanosheet boosting fast electron/ion transport for electrochemiluminescence enhancement.

Ultrathin metal-organic layers (MOLs) have attracted substantial attention in fabricating highly efficient electrochemiluminescence (ECL) materials due to their porous structure, small diffusion blockage, and short electron/ion-diffusion pathway, yet MOLs suffer from the inherent poor electrical conductivity that astricted the electrochemical activation, resulting in the unsatisfactory utilization ratio of ECL emitters. Herein, to address this limitation, we in situ hybridized Zr-based ultrathin MOL (Zr-TCBPE-MOL, HTCBPE = 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene) with the highly conductive TiCT MXene nanosheet to obtain a unique 2D-2D hybrid nanocomposite (Zr-TCBPE-MOL/MXene). Benefiting from the above-mentioned attractive virtues of ultrathin MOLs and the superior conductivity of TiCT MXene nanosheet, the resulting Zr-TCBPE-MOL/MXene nanocomposite permitted fast electron/ion transport across the whole framework of Zr-TCBPE-MOL/MXene, which efficiently boosted the electrochemical activation of TCBPE luminophores and thus improved the utilization ratio of luminophores to realize a remarkable ECL emission.

Pyrene-Based Hydrogen-Bonded Organic Frameworks as New Emitters with Porosity- and Aggregation-Induced Enhanced Electrochemiluminescence for Ultrasensitive MicroRNA Assay.

Exploring new electrochemiluminescence (ECL) luminophores with strong ECL emission is highly desirable for developing ultrasensitive ECL sensors. Herein, a pyrene-based hydrogen-bonded organic framework (Py-HOF) featuring prominent ECL performance was prepared by utilizing 1,3,6,8-tetrakis(-benzoic acid) pyrene (HTBAPy) with an aggregation-induced enhanced emission (AIEE) property as a building block, exhibiting a stronger ECL emission than those of HTBAPy monomers, HTBAPy aggregates, the low-porosity Py-HOF-210 °C and Py-HOF-180 °C. We have coined the term "the porosity- and aggregation-induced enhanced ECL (PAIE-ECL)" for this intriguing phenomenon.

Programmable Y-Shaped Probes with Proximity Bivalent Recognition for Rapid Electrochemiluminescence Response of Acute Myocardial Infarction.

Herein, an exogenous luminophore-free and disposable electrochemiluminescence (ECL) biosensor was established for rapid response of acute myocardial infarction (AMI) using programmable Y-shaped probes (Y-probes) with proximity bivalent recognition. Specifically, the indium tin oxide thin film coated glass electrode (ITO) was modified with urchin-like porous TiO microspheres (pTiO MSs), which could achieve strong and stable ECL in SO solution due to the dual promoting effect of the coreaction accelerator pTiO MSs, exhibiting 2.7-fold higher ECL intensity in comparison with that of bare ITO.

Macroscopic Heterostructure Membrane of Graphene Oxide/Porous Graphene/Graphene Oxide for Selective Separation of Deuterium Water from Natural Water.

Deuterium water (D O) is a strategic material that is widely used in and scientific research and has applications in fields such as nuclear energy generation. However, its content in natural water is extremely low. Therefore, the development of a room-temperature technology for achieving simple, efficient, and low-cost separation of D O from natural water is challenging.

Ordered heterogeneity in dual-ligand MOF to enable high electrochemiluminescence efficiency for bioassay with DNA triangular prism as signal switch.

Herein, the microRNA-141 electrochemiluminescence (ECL) bioassay was developed using the dual-ligand metal-organic framework (d-MOF) with ordered heterogeneity, which simultaneously contained the luminophore ligands (1,1,2,2-tetra(4-carboxylbiphenyl)ethylene, denoted as TCBPE) and the coreactant ligands (1,4-diazabicyclo[2.2.2]octane, denoted as DNH).