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•A deep autoencoder feature learning method is proposed.•Maximum correntropy is used to design the new deep autoencoder loss function.•Artificial fish swarm algorithm is used to ...optimize parameters.
The operation conditions of the rotating machinery are always complex and variable, which makes it difficult to automatically and effectively capture the useful fault features from the measured vibration signals, and it is a great challenge for rotating machinery fault diagnosis. In this paper, a novel deep autoencoder feature learning method is developed to diagnose rotating machinery fault. Firstly, the maximum correntropy is adopted to design the new deep autoencoder loss function for the enhancement of feature learning from the measured vibration signals. Secondly, artificial fish swarm algorithm is used to optimize the key parameters of the deep autoencoder to adapt to the signal features. The proposed method is applied to the fault diagnosis of gearbox and electrical locomotive roller bearing. The results confirm that the proposed method is more effective and robust than other methods.
Nucleic acid circuits have shown promising potential for amplified detection of biomarkers with interest in biologically important engineering applications. In this work, by properly integrating two ...signal amplification approaches, catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR), a concatenated CHA-HCR system was established as an isothermal enzyme-free amplification strategy for highly sensitive and selective nucleic acid assay. The target catalyzes the self-assembly of CHA hairpin substrates into dsDNA products, where the split segments of HCR trigger are successively connected to drive the subsequent autonomous cross-opening of HCR hairpins, leading to the construction of HCR tandem copolymeric dsDNA nanowires. The resulting HCR copolymer brings a fluorophore donor/acceptor pair into close proximity that allows an efficient generation of FRET readout signal. Moreover, the optimized CHA-HCR circuit, upon the incorporation of an auxiliary sensing module, can be converted into a universal sensing platform for detecting cancerous biomarkers (
, a well-known oncogene miR-21) through a convenient easy-to-integrate procedure. The concatenated CHA-HCR amplifier enables accurate intracellular miRNA imaging in living cells, which is especially suitable for
amplified detection of lowly expressed endogenous analytes. The inherent synergistically accelerated recognition and hybridization features of CHA-HCR circuit contribute to the amplified detection of endogenous RNAs in living cells. The flexible and programmable nature of the homogeneous CHA-HCR system provides a versatile and robust toolbox for a wide range of research fields, such as
bioimaging, clinical diagnosis and environmental monitoring.
An enzyme-free amplified detection platform is described using the horseradish peroxidase (HRP)-mimicking DNAzyme as an amplifying label. Two hairpin structures that include three-fourths and ...one-fourth of the HRP-mimicking DNAzyme in caged, inactive configurations are used as functional elements for the amplified detection of the target DNA. In the presence of the analyte DNA, one of the hairpins is opened, and this triggers the autonomous cross-opening of the two hairpins using the strand displacement principle. This leads to the formation of nanowires consisting of the HRP-mimicking DNAzyme. The resulting DNA nanowires act as catalytic labels for the colorimetric or chemiluminescent readout of the sensing processes (the term “enzyme-free” refers to a protein-free catalyst). The analytical platform allows the sensing of the analyte DNA with a detection limit corresponding to 1 × 10–13 M. The optimized system acts as a versatile sensing platform, and by coaddition of a “helper” hairpin structure any DNA sequence may be analyzed by the system. This is exemplified with the detection of the BRCA1 oncogene with a detection limit of 1 × 10–13 M.
Hybrid systems consisting of nucleic-acid-functionalized silver nanoclusters (AgNCs) and graphene oxide (GO) are used for the development of fluorescent DNA sensors and aptasensors, and for the ...multiplexed analysis of a series of genes of infectious pathogens. Two types of nucleic-acid-stabilized AgNCs are used: one type includes the red-emitting AgNCs (616 nm) and the second type is near-infrared-emitting AgNCs (775 nm). Whereas the nucleic-acid-stabilized AgNCs do not bind to GO, the conjugation of single-stranded nucleic acid to the DNA-stabilized AgNCs leads to the adsorption of the hybrid nanostructures to GO and to the fluorescence quenching of the AgNCs. By the conjugation of oligonucleotide sequences acting as probes for target genes, or as aptamer sequences, to the nucleic-acid-protected AgNCs, the desorption of the probe/nucleic-acid-stabilized AgNCs from GO through the formation of duplex DNA structures or aptamer–substrate complexes leads to the generation of fluorescence as a readout signal for the sensing events. The hybrid nanostructures are implemented for the analysis of hepatitis B virus gene (HBV), the immunodeficiency virus gene (HIV), and the syphilis (Treponema pallidum) gene. Multiplexed analysis of the genes is demonstrated. The nucleic-acid-AgNCs-modified GO is also applied to detect ATP or thrombin through the release of the respective AgNCs-labeled aptamer–substrate complexes from GO.
DNAzymes have been recognized as promising transducing agents for visualizing endogenous biomarkers, but their inefficient intracellular delivery and limited amplification capacity (including ...insufficient cofactor supply) preclude their extensive biological application. Herein, an autocatalytic DNAzyme (ACD) biocircuit is constructed for amplified microRNA imaging in vivo based on a hybridization chain reaction (HCR) and DNAzyme biocatalysis, sustained by a honeycomb MnO2 nanosponge (hMNS). The hMNS not only delivers DNA probes, but also supplies Mn2+ as a DNAzyme cofactor and magnetic resonance imaging (MRI) agent. Through the subsequent cross‐activation of HCR and DNAzyme amplicons, the ACD amplifies the limited signal resulting from miRNA recognition. The hMNS/ACD system was used to image microRNA in vivo, thus demonstrating its great promise in cancer diagnosis.
An autocatalytic circuit is constructed for in vivo fluorescence/molecular resonance imaging based on a hybridization chain reaction (HCR) and DNAzyme biocatalysis, sustained by a honeycomb MnO2 nanosponge (hMNS). The hMNS was not only used to deliver the DNA, but also to supply the DNAzyme with Mn2+ as a cofactor. This system was used to detect microRNA in vivo and shows great promise in cancer diagnosis.
Powerful information processing and ubiquitous computing are crucial for all machines and living organisms. The Watson-Crick base-pairing principle endows DNA with excellent recognition and assembly ...abilities, which facilitates the design of DNA computers for achieving intelligent systems. However, current DNA computational systems are always constrained by poor integration efficiency, complicated device structures or limited computational functions. Here, we show a DNA arithmetic logic unit (ALU) consisting of elemental DNA logic gates using polymerase-mediated strand displacement. The use of an enzyme resulted in highly efficient logic gates suitable for multiple and cascaded computation. Based on our basic single-rail DNA configuration, additional combined logic gates (e.g., a full adder and a 4:1 multiplexer) have been constructed. Finally, we integrate the gates and assemble the crucial ALU. Our strategy provides a facile strategy for assembling a large-scale complex DNA computer system, highlighting the great potential for programming the molecular behaviors of complicated biosystems.
The systemic therapeutic utilisation of RNA interference (RNAi) is limited by the non-specific off-target effects, which can have severe adverse impacts in clinical applications. The accurate use of ...RNAi requires tumour-specific on-demand conditional activation to eliminate the off-target effects of RNAi, for which conventional RNAi systems cannot be used. Herein, a tumourous biomarker-activated RNAi platform is achieved through the careful design of RNAi prodrugs in extracellular vesicles (EVs) with cancer-specific recognition/activation features. These RNAi prodrugs are assembled by splitting and reconstituting the principal siRNAs into a hybridisation chain reaction (HCR) amplification machine. EVs facilitate the specific and efficient internalisation of RNAi prodrugs into target tumour cells, where endogenous microRNAs (miRNAs) promote immediate and autonomous HCR-amplified RNAi activation to simultaneously silence multiantenna hypoxia-related genes. With multiple guaranteed cancer recognition and synergistic therapy features, the miRNA-initiated HCR-promoted RNAi cascade holds great promise for personalised theranostics that enable reliable diagnosis and programmable on-demand therapy.
Biomolecular self-assembly circuits have been well developed for high-performance biosensing and bioengineering applications. Here we designed an isothermal concatenated nucleic acid amplification ...system which is composed of a lead-in catalyzed hairpin assembly (CHA), intermediate hybridization chain reaction (HCR) and ultimate DNAzyme amplifier units. The analyte initiates the self-assembly of hairpin reactants into dsDNA products in CHA, which generates numerous trigger sequences for activating the subsequent HCR-assembled long tandem DNAzyme nanowires. The as-acquired DNAzyme catalyzed the successive cleavage of its substrates, leading to an amplified fluorescence readout. The sophisticated design of our CHA-HCR-DNAzyme scheme was systematically investigated
in vitro
and showed dramatically enhanced detection performance. As a general sensing strategy, this CHA-HCR-DNAzyme method enables the amplified analysis of miRNA and its accurate intracellular imaging in living cells, originating from their synergistic signal amplifications. This method shows great potential for analyzing trace amounts of biomarkers in various clinical research studies.
A rationally and modularly engineered CHA-HCR-DNAzyme circuit was constructed for amplified biosensing and bioimaging with high performance.
A systematic study of the amplified optical detection of DNA by Mg2+-dependent DNAzyme subunits is described. The use of two DNAzyme subunits and the respective fluorophore/quencher-modified ...substrate allows the detection of the target DNA with a sensitivity corresponding to 1 × 10–9 M. The use of two functional hairpin structures that include the DNAzyme subunits in a caged, inactive configuration leads, in the presence of the target DNA, to the opening of one of the hairpins and to the activation of an autonomous cross-opening process of the two hairpins, which affords polymer DNA wires consisting of the Mg2+-dependent DNAzyme subunits. This amplification paradigm leads to the analysis of the target DNA with a sensitivity corresponding to 1 × 10–14 M. The amplification mixture composed of the two hairpins can be implemented as a versatile sensing platform for analyzing any gene in the presence of the appropriate hairpin probe. This is exemplified with the detection of the BRCA1 oncogene.
Extracellular vesicles (EVs) have emerged as promising tumor biomarkers for early cancer diagnosis, as primary tumor-secreted EVs carry characteristic molecular information on parent cells. It is ...thus desirable to realize the efficient discrimination of the signatured EVs-associated microRNAs (miRNAs) with low expression and subtle variation. Here, we introduce an autonomous nonlinear enzyme-free signal amplification paradigm for EVs discrimination through a highly sensitive and selective detection of their inherent miRNAs in situ. Our proposed amplifier consists of a modularized DNAzyme-amplified two-stage cascaded hybridization chain reaction (CHCR–DNAzyme) circuit, where the analyte-generated output of the preceding hybridization chain reaction (HCR1) stage serves as input to motivate the following hybridization chain reaction (HCR2) stage and the concomitant assembly of numerous DNAzyme biocatalysts. By incorporating a flexibly configurable sensing module, this modular CHCR–DNAzyme circuit can further extend to “plug-and-play” sensing mode that enables the miRNA assay with high specificity. The sophisticated design and the detecting performance of our CHCR–DNAzyme scheme were systematically investigated in vitro. The optimized CHCR–DNAzyme system was further applied for distinguishing EVs derived from different cells through the amplified detection of a putative miRNA biomarker in EVs. This compact CHCR–DNAzyme amplifier provides a universal and facile toolbox for highly efficient identification of multiple miRNAs-involved EVs and thus holds great potential for early cancer diagnosis.
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