DNA nanomachines have shown potential application in the construction of various biosensors. Here, an electrochemiluminescence biosensor for the sensitive detection of miRNA-21 were reported based on ...three-dimensional (3D) DNA nanomachine and duplex-specific nuclease (DSN)-mediated target recycle amplification strategy. First, the bipedal DNA walkers were obtained by DSN-mediated digestion reaction initiated by target miRNA-21.3D DNA tracks were prepared by modifying Fe3O4 magnetic beads (MBs) with ferrocene-labeled DNA (Fc-DNA). The produced DNA walkers autonomously moved along 3D DNA tracks powered by nicking endonuclease. During the movement, ferrocene-labeled DNA was cleaved, resulting in large amounts of Fc-labeled DNA fragments away from the MBs surface. Finally, the liberated Fc-labeled DNA fragments were dropped on the C-g-C3N4 modified electrode surface, leading to the quenching of C-g-C3N4 electrochemiluminescence (ECL). Benefiting from the dual amplification strategy of 3D DNA nanomachine and DSN-mediated target recycling, the developed ECL biosensor exhibited an excellent performance for miRNA-21 detection with a wide linear range of 10 fM to 10 nM and a low detection limit of 1.0 fM. This work offers a new thought for the application of DNA walkers in the construction of various biosensors.
•DSN-mediated target recycling converted a small number of target into a large number of DNA walkers, which greatly enhanced the sensitivity of the ECL biosensor.•Bipedal DNA walkers fasted walking speed.•3D DNA tracks immobilized MBs possess higher DNA density than 1D or 2D, which exhibited higher walking efficiency and better signal amplification effect.
The strong interaction between a typhoon and ocean air is one of the most important forms of typhoon and sea air interaction. In this paper, the daily mean sea surface temperature (SST) data of ...Advanced Microwave Scanning Radiometer for Earth Observation System (EOS) (AMSR-E) are used to analyze the reduction in SST caused by 30 westward typhoons from 1998 to 2018. The findings reveal that 20 typhoons exerted obvious SST cooling areas. Moreover, 97.5% of the cooling locations appeared near and on the right side of the path, while only one appeared on the left side of the path. The decrease in SST generally lasted 6–7 days. Over time, the cooling center continued to diffuse, and the SST gradually rose. The slope of the recovery curve was concentrated between 0.1 and 0.5.
As a new generation of electrochemiluminescence (ECL) technology, the electrochemical stripping chemiluminescence (ESCL), which combines the advantages of chemiluminescence and stripping voltammetry, ...has attracted increasing attention in the biosensor field. Here, Ag nanoclusters (NCs) were prepared using DNA double strands as a template and explored to construct an ESCL aptamer sensor (aptasensor) for the detection of a carcinoembryonic antigen (CEA). During the detection process, Ag NCs and the Ag+ cations stripped out from Ag NCs were found to respectively catalyze the electrochemical reduction and oxidation of H2O2, accelerating the decomposition of H2O2 to generate reactive oxygen species (ROSs) and thus effectively enhancing the ECL intensity of luminol. Coupled with the exonuclease I-assisted recycling amplification technology, the developed ESCL aptasensor enabled the sensitive detection of CEA, exhibiting a broad linear response from 100 ag/mL to 10 ng/mL with a low detection limit of 38.86 ag/mL (S/N = 3). In addition, the aptasensor showed good performance in the determination of CEA in human serum with a relative standard deviation (RSD) below 5 %. This work provides an effective method for constructing simple, fast, and sensitive biosensors.
•Ag NCs were explored to construct ESCL aptamer sensor.•The Ag NCs could distinctly enhance the ECL signal of luminol.•Coupled with the recycling amplification technology, the developed ESCL sensor exhibited a low detection limitation and a wide linear range.
A combination of cytoreductive surgery, either primary (PCS) or interval (ICS), and chemotherapy with a platinum-paclitaxel regimen is the well-accepted treatment for advanced-stage epithelial ...ovarian cancer (EOC), fallopian tube cancer (FTC), and primary peritoneal serous carcinoma (PPSC), but it is still uncertain whether a combination of dose-dense weekly paclitaxel and low-dose triweekly cisplatin is useful in the management of these patients. Therefore, we retrospectively evaluated the outcomes of women with advanced-stage EOC, FTC, and PPSC treated with PCS and subsequent dose-dense weekly paclitaxel (80 mg/m
) and low-dose triweekly cisplatin (20 mg/m
). Between January 2011 and December 2017, 32 women with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV EOC, FTC, or PPSC were enrolled. Optimal PCS was achieved in 63.5% of patients. The mean and median progression-free survival was 36.5 and 27.0 months, respectively (95% confidence interval (CI): 26.8-46.2 and 11.3-42.7 months, respectively). The mean overall survival was 56.0 months (95% CI: 43.9-68.1 months), and the median overall survival could not be obtained. The most common all-grade adverse events (AEs) were anemia (96.9%), neutropenia (50%), peripheral neuropathy (28.1%), nausea and vomiting (34.4%), and thrombocytopenia (15.6%). These AEs were predominantly grade 1/2, and only a few patients were complicated by grade 3/4 neutropenia (21.9%) and anemia (6.3%). A multivariate analysis indicated that only suboptimal PCS was significantly correlated with a worse prognosis, resulting in an 11.6-fold increase in the odds of disease progression. In conclusion, our data suggest that dose-dense weekly paclitaxel (80 mg/m
) combined with low-dose triweekly cisplatin (20 mg/m
) is a potentially effective and highly tolerable front-line treatment in advanced EOC, FTC, and PPSC. Randomized trials comparing the outcome of this regimen to other standard therapies for FIGO stage IIIC-IV EOC, FTC, and PPSC are warranted.
Display omitted
•A new low-potential-driven Ru(bpy)32+ ECL system was reported using oxalate as coreactant.•The excited potential (<0.1 V vs. Ag/AgCl) was quite lower than that in the typical ...Ru(bpy)32+-C2O42− ECL system.•The low excited potential was in favor of avoiding the damage of the modified electrodes and biomolecules.•The low-potential-driven ECL was further exploited to develop a sensitive label-free ECL biosensor for the detection of CEA.
Recently, tris(2,2′-bipyridine)ruthenium(ii) (Ru(bpy)32+) has been widely used in electrochemiluminescence (ECL) biosensors. However, its ECL has to be triggered at high positive or negative voltage, leading to a series of undesired side effects containing electrical damage toward biomolecules and hydrogen/oxygen evolution reaction. In this work, a new low-potential-triggered Ru(bpy)32+ ECL system was reported using oxalate as coreactant with the aid of platinum nanoparticles (Pt NPs) electrodeposited on the surface of the graphene-ionic liquid composite. When cyclic scanning in a potential range from 0.3 to −0.2 V, the ECL signal appeared at onset potential of 0.05 V (vs. Ag/AgCl), and reached the maximum at about −0.15 V (vs. Ag/AgCl), which were quite lower than that in the typical Ru(bpy)32+-oxalate (C2O42−) ECL system. The possible mechanism was discussed in detail. Meanwhile, the low-potential-triggered ECL signals were strong and stable, which were further exploited to detect the carcinoembryonic antigen (CEA). The constructed ECL sensor exhibited a good linearity between the ECL signals and the logarithm of the concentrations of CEA in a range from 0.1 pg mL−1 to 100 ng mL−1 with the detection limit of 0.01 pg mL−1. In addition, the sensor showed a promising potential in clinical detection.
The genetic risk of aggressive prostate cancer (PCa) is hard to be assessed due to the lack of aggressiveness-related single-nucleotide polymorphisms (SNPs). Prostate volume (PV) is a potential ...well-established risk factor for aggressive PCa, we hypothesize that polygenic risk score (PRS) based on benign prostate hyperplasia (BPH) or PV-related SNPs may also predict the risk of aggressive PCa or PCa death.
We evaluated a PRS using 21 BPH/PV-associated SNPs, two established PCa risk-related PRS and 10 guideline-recommended hereditary cancer risk genes in the population-based UK Biobank cohort (N = 209,502).
The BPH/PV PRS was significantly inversely associated with the incidence of lethal PCa as well as the natural progress in PCa patients (hazard ratio, HR = 0.92, 95% confidence interval CI: 0.87-0.98, P = 0.02; HR = 0.92, 95% CI 0.86-0.98, P = 0.01). Compared with men at the top 25th PRS, PCa patients with bottom 25
PRS would have a 1.41-fold (HR, 95% CI 1.16-1.69, P = 0.001) increased PCa fatal risk and shorter survival time at 0.37 yr (95% CI 0.14-0.61, P = 0.002). In addition, patients with BRCA2 or PALB2 pathogenic mutations would also have a high risk of PCa death (HR = 3.90, 95% CI 2.34-6.51, P = 1.79 × 10
; HR = 4.29, 95% CI 1.36-13.50, P = 0.01, respectively). However, no interactive but independent effects were detected between this PRS and pathogenic mutations.
Our findings provide a new measurement of PCa patients' natural disease outcomes via genetic risk ways.
In this work, an ultrasensitive aptasensor for the detection of Mucin 1 (MUC1) was presented based on the target-induced catalytic hairpin assembly combined with excellent mimic peroxidase ...performance of PtPd bimetallic nanoparticles (PtPdNPs). Traditionally, the cyclic reuse of target protein was achieved by protein conversion with enzyme cleavage or polymerization, which is costly and complex. However, in this work, it can be performed by simple strand displacement. In addition, PtPdNPs, a mimic peroxidase, was used a probe to catalyze the oxidation of tetramethylbenzidine (TMB) by H2O2, leading to the electrochemical signal amplification. With this ingenious design, the prepared aptasensor for MUC1 detection showed a favorable linear response from 100 fg mL−1 to 1 ng mL−1 and a relatively low detection limit of 16 fg mL−1. The proposed biosensor possessed acceptable stability, selectivity and reproducibility for MUC1 assay. Additionally, the fabricated aptasensor has been successfully applied to detect MUC1 in serum samples with satisfactory results. This new strategy supplied one efficient approach to improve signal amplification, which also open an avenue for sensitivity enhancement in targets detection.
Display omitted
•An aptasensor based on catalytic hairpin assembly and target recycling amplification.•PtPd bimetallic nanoparticles with mimic peroxidase performance was used as probe.•This aptasensor was simplicity, and high sensitivity.
A simple and novel one-step triggered “signal-on/off” ratiometric electrochemical biosensor based on the highly specific lead-dependent DNAzyme and dual-signal output mode was designed for the ...sensitive and selective determination of lead ions.
Display omitted
•A novel one-step triggered dual-signal ratiometric electrochemical Pb2+ biosensor is developed based on the electrode-bound DNAzyme assembly.•The biosensor can detect Pb2+ down to 45.8pM level with a dynamic range spanning 4 orders of magnitude.•The biosensor allows selective and sensitive detection of Pb2+ in clinical serum samples.•The proposed DNAzyme-based ratiometric electrochemical strategy could be easily expanded into the versatile detection of other metal ions.
A simple and novel one-step triggered ratiometric electrochemical biosensor was designed for lead (Pb2+) based on the highly specific lead-dependent DNAzyme and dual-signal output mode. The biosensor consists of a thiolated methylene blue-labeled DNA (MB-P1) as catalytic probe and “signal-on” readout, and a complementary strand modified with ferrocene (Fc-P2) as substrate probe and “signal-off” output. The presence of Pb2+ could activate the DNAzyme and cleave the sessile phosphodiester of the Fc-P2 into two fragments, which lead to the departure of Fc from the sensing interface along with the single stranded MB-P1 near the electrode surface. Therefore, the Pb2+ recognition event resulted in both the “signal-on” of MB and the “signal-off” of Fc for dual-signal ratiometric electrochemical readout. Combined with the efficient recognition capacity of the designed DNAzyme and the dual-signal amplification strategy, the proposed biosensor showed a wide detection range from 0.1nM to 5μM with a detection limit of 45.8pM (S/N=3). Meanwhile, this DNAzyme-based Pb2+ biosensor exhibits reasonable selectivity, fast analytical speed, acceptable fabrication reproducibility, and operational convenience. More importantly, the system is capable of detecting Pb2+ in biological fluid such as serum, suggesting promising applications of this biosensor in on-site and real-time clinical Pb2+ detection.
Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood ...with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL–1 to 10 ng mL–1), low detection limit (14.52 fg mL–1), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.