Molecular beacon

The expression level of human apurinic/apyrimidinic endonuclease 1 (APE1) is closely associated with the onset of various diseases, establishing it as a crucial clinical biomarker and a target in anti-cancer efforts. This study accomplished colorimetric and visual detection of APE1 by harnessing its endonuclease activity through catalytic hairpin self-assembly (CHA) and G-quadruplex/hemin DNAzyme. Optimization of the freedom degrees of the G-rich sequence significantly improved the detection performance of the strategy by influencing DNAzyme formation...

A biosensor that can detect biomarkers accurately, quickly, and conveniently is important for the diagnosis of various diseases. However, most of the existing detection methods require sample extraction, which makes it difficult to detect and image intracellular molecules or to detect two different types of biomarkers simultaneously. In this study, we constructed a DNA tetrahedral nanoprobe (DTP) capable of detecting both miR378 and telomerase, both of which are tumor markers. In the presence of miR378, FAM on the molecular beacon of DTP fluoresced via Förster resonance energy transfer (FRET), and the limit of detection was 476 pM with excellent specificity...

Mitochondrial dysfunction represents a pivotal aspect of the pathogenesis and progression of diabetic kidney disease (DKD). Central to the orchestration of mitochondrial biogenesis is the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α), a master regulator with a profound impact on mitochondrial function. In the context of DKD, PGC1-α exhibits significant downregulation within intrinsic renal cells, precipitating a cascade of deleterious events. This includes a reduction in mitochondrial biogenesis, heightened levels of mitochondrial oxidative stress, perturbed mitochondrial dynamics, and dysregulated mitophagy...

Benefiting from specific target recognition and trans-cleavage capabilities, the CRISPR/Cas12a system has great application prospects in the design of highly sensitive and rapid fluorescence biosensors. The CRISPR/Cas12a-based fluorophore-quencher molecular beacons exhibit single-color emission and are easily exposed to interference from environmental factors. Herein, we design a CRISPR/Cas12a-derived ratiometric fluorescence sensor for Pb2+ detection based on embedded carbon dots@zeolitic imidazolate framework-8 (CDs@ZIF-8) composites and DNAzyme...

To address the limitations of typical hairpin-structural molecular beacons, exploring the ability of a quasi-molecular beacon ( q MB) to create label-free fluorescence biosensors is intriguing and remains a challenge. Herein, we propose the first example of modular q MB with the feature of a stimulation-responsive conformation switch to develop an aggregated Ag nanocluster ( a AgNC) in a bifurcated DNA scaffold for fluorescently sensing a specific initiator ( I *). This q MB was well designed to program four functional modules: I *-recognizable element adopting metastable stem-loop bihairpin structure and two DNA splits (exposed C3 GT4 and locked C4 AC4 T) of a AgNC template that is separated by a tunable hairpin spacer for the customized combination of selective recognition and signaling readout...

Diabetic kidney disease (DKD) stands as a pressing health challenge, with mesangial cell fibrosis identified as a pivotal hallmark leading to glomerular sclerosis. Gaining a deeper grasp on the molecular dynamics behind this can potentially introduce groundbreaking therapeutic avenues. Recent revelations from studies on ROCK1-deficient mice, which displayed resilience against high-fat diet (HFD)-induced glomerulosclerosis and mitochondrial fragmentation, spurred our hypothesis regarding ROCK1's potential role in mesangial cell fibrosis...

The Mango I and II RNA aptamers have been widely used in vivo and in vitro as genetically-encodable fluorogenic markers that undergo large increases in fluorescence upon binding to their ligand, TO1-biotin. However, while studying nucleic acids sequences, it is often desirable to have trans-acting probes that induce fluorescence upon binding to a target sequence. Here, we rationally design three types of light-up RNA Mango Beacons based on a minimized Mango core, that induce fluorescence upon binding to a target RNA strand...

Conjoint analysis of multiple protein biomarkers can improve the accuracy of disease analysis. Rolling circle amplification (RCA) generates different products by designing circular templates, which can subsequently bind with specific probes to generate various fluorescence signals; thus, it has potential for application in the analysis of various protein biomarkers. Current RCA approaches to detect proteins commonly follow an indirect primer-controlled RCA mode. And the molecular beacon probe combines with RCA products through free collision to generate signals, resulting in lower reaction efficiency...

The intersection of mathematical modeling, nanotechnology, and epidemiology marks a paradigm shift in our battle against infectious diseases, aligning with the focus of the journal on the regulation, expression, function, and evolution of genes in diverse biological contexts. This exploration navigates the intricate dance of viral transmission dynamics, highlighting mathematical models as dual tools of insight and precision instruments, a theme relevant to the diverse sections of Gene. In the context of virology, ethical considerations loom large, necessitating robust frameworks to protect individual rights, an aspect essential in infectious disease research...

Multidrug resistance (MDR) remains a significant challenge in cancer therapy, with inherent and acquired resistance distinct. While conventional drug selection processes enable the isolation of cancer cells with acquired multidrug resistance, identifying cancer cells with inherent drug resistance remains challenging. Herein, we proposed a molecular beacon (MB)-based strategy to identify and isolate the inherent MDR cancer cells. A lipid/PLGA core-shell nanoparticulate system (DNCP) was designed to deliver MB for intracellular MDR1 mRNA imaging...

BACKGROUND: Bladder cancer (BC) has attracted significant attention on account of its recurrence as well as mortality. Tumor recurrence plays a significant role in cancer patients' individual treatment. Secreted phosphoprotein 1 (SPP1) has been recognized as a potential target for treating BC and served as a useful biomarker for prognosis; it is commonly tested by immunohistochemistry (IHC). However, this conventional method has the disadvantage of being time-consuming and costly. This study aimed to develop a molecular beacon (MB) for the detection of SPP1 messenger RNA (mRNA) for the recurrence prognosis of BC...

In vivo optical imaging of trace biomarkers in residual microtumors holds significant promise for cancer prognosis but poses a formidable challenge. Here, a novel hydrogel sensor is designed for ultrasensitive and specific imaging of the elusive biomarker. This hydrogel sensor seamlessly integrates a molecular beacon nanoprobe with fibroblasts, offering both high tissue retention capability and an impressive signal-to-noise ratio for imaging. Signal amplification is accomplished through exonuclease I-mediated biomarker recycling...

Cervical cancer poses a substantial worldwide health challenge, especially in low- and middle-income nations, caused by high-risk types of human papillomavirus. It accounted for a significant percentage of cancer-related deaths among women, particularly in areas with limited healthcare resources, necessitating innovative therapeutic approaches, and single-targeted studies have produced significant results, with a considerable chance of developing resistance. Therefore, the multitargeted studies can work as a beacon of hope...

8-oxo guanine DNA glycosylase (8-oxoG DNA glycosylase), a crucial DNA repair enzyme, is essential for maintaining genome integrity and preventing diseases caused by DNA oxidative damage. Imaging 8-oxoG DNA glycosylase in living cells requires a dependable technique. In this study, we designed a DNAzyme-modified DNA tetrahedral nanomachine (DTDN) powered by 8-oxoG restoration. Incorporating a molecular beacon probe (MB), the constructed platform was used for amplified in situ monitoring of 8-oxoG DNA glycosylase...

The continued emergence of vaccine-resistant SARS-CoV-2 variants of concern (VOC) requires specific identification of each VOC as it arises. Here, we report an expanded version of our previously described sloppy molecular beacon (SMB) melting temperature (Tm) signature-based assay for VOCs, now modified to include detection of Delta (B.1.617.2) and Omicron (B.1.1.529) sub-variants. The SMB-VOC assay targets the signature codons 501, 484 and 452 in the SARS-CoV-2 spike protein which we show can specifically detect and differentiate all known VOCs including the Omicron subvariants (BA...

There is an urgent need to accurately quantify tumor-derived exosomes, which have emerged as promising non-invasive tumor diagnostic biomarkers. Herein, a bispecific-aptamer sandwich-type gold nanoparticle-modified electrochemical aptasensor was developed based on a four-way junction (4-WJ)-triggered dual rolling circle amplification (RCA)-assisted methylene blue (MB)/G-quadruplex strategy for extremely specific and sensitive exosome detection. This aptamer/exosome/aptamer sandwich-type design contained a CD63-specific aptamer and a cancerous mucin-1 (MUC1) protein-specific aptamer...

Beyond storage and transmission of genetic information in cellular life, nucleic acids can perform diverse interesting functions, including specific target recognition and biochemical reaction acceleration; the versatile biopolymers, however, are acutely vulnerable to hydrolysis-driven degradation. Here, we demonstrate that the cage effect of choline dihydrogen phosphate permits active folding of nucleic acids like water, but prevents their phosphodiester hydrolysis unlike water. The choline-based ionic liquid not only serves as a universal inhibitor of nucleases, exceptionally extending half-lives of nucleic acids up to 6 500 000 times, but highly useful tasks of nucleic acids (e...

Neisseria gonorrhoeae is the only pathogen that causes gonorrhea, and can have serious consequences if left untreated. A simple and accurate detection method for N. gonorrhoeae is essential for the diagnosis of gonorrhea and the appropriate prescription of antibiotics. The application of isothermal recombinase polymerase amplification (RPA) to detect this pathogen is advantageous because of its rapid performance, high sensitivity, and minimal dependency on equipment. However, this simplicity is offset by the risk of false-positive signals from primer-dimers and primer-probe dimers...

Advantages of biosensors based on surface enhanced Raman scattering (SERS) rely on improved sensitivity and specificity, and suited reproducibility in detecting a target molecule that is localized in close proximity to a SERS-active surface. Herein, a comprehensive study on the realization of a SERS biosensor designed for detecting miRNA-183, a miRNA biomarker that is specific for chronic obstructive pulmonary disease (COPD), is presented. The used strategy exploits a signal-off mechanism by means of a labelled molecular beacon (MB) as the oligonucleotide biorecognition element immobilized on a 2D SERS substrate, based on spot-on silver nanowires (AgNWs) and a multi-well low volume cell...

Apolipoprotein A4 (Apo-A4) is considered as a prospective molecular biomarker for diagnosis of depression due to its neurosynaptic toxicity. We develop a proximity hybridization-induced DNAzyme-driven bipedal DNA walker strategy for Apo-A4 quantification based on rolling circle amplification (RCA) triggered by poly adenine binding to Ag nanoparticles (AgNPs). With the help of DNAzyme, the free-running bipedal DNA walker can quickly and sequentially shear a molecular beacon that acts as a primer to initiate the RCA process, producing a large number of long DNA strands containing numerous adenines...