Electrochemical Performance and Microstructure Evolution of a Quasi-Solid-State Lithium Battery Prepared by Spark Plasma Sintering.

Solid-state lithium batteries are promising next-generation energy storage systems for electric vehicles due to their high energy density and high safety and require achieving and maintaining intimate solid-solid interfaces for lithium-ion and electron transport. However, the solid-solid interfaces may evolve over cycling, disrupting the ion and electron diffusion pathways and leading to rapid performance degradation. The development of solid-state lithium batteries has been hindered by the lack of fundamental understanding of the interfacial microstructure change over cycling and its relation to electrochemical properties. Herein, we prepared a quasi-solid-state lithium battery, 30%LiFePO4-55%Li1.5Al0.5Ge1.5(PO4)3-15%C| Li1.5Al0.5Ge1.5(PO4)3|Li, by spark plasma sintering, and employed it as a model system to reveal the microstructure evolution at the solid-solid interfaces with electrochemical performance of the batteries. The electrochemical assessment showed that the quasi-solid-state lithium battery exhibited a discharge specific capacity of about 150 mAh g-1 in the first 80 cycles and then experienced severe capacity attenuation afterward, accompanied by a gradual internal resistance increase. Scanning electron microscopy observation showed that more cracks were formed inside the solid-state electrolyte and at the solid-solid interfaces as the battery cycled from 10 to 67 and 157 cycles. Detailed microstructure and phase analysis by high-resolution transmission electron microscopy and selected area electron diffraction discovered that the crack formation and performance decay were mainly caused by (1) the volume change of the LiFePO4 composite cathode during cycling, (2) the grain expansion of the Li1.5Al0.5Ge1.5(PO4)3 solid-state electrolyte at its interface with lithium anode, and (3) the formation of a solid electrolyte interphase layer, comprising Li2CO3, LiF, and LiTFSI, at the cathode-solid-state electrolyte interface. These microstructure changes built up over repeated battery cycling, ultimately causing the structure collapse and battery failure. The microstructure evolution information is expected to guide the design of better structures and interfaces for solid-state lithium batteries.

Label-free and highly sensitive detection of microRNA from cancer cells via target-induced cascade amplification generation of lighting-up RNA aptamers.

The abnormal expression levels of miRNAs have been proven to be highly related to the generation of various diseases and are also closely associated with the stages and types of disease development. The novel RNA aptamers-based homogenous fluorescent methods were simple, with low background signal and high signal-to-noise ratio, but lacked effective signal amplification technology to achieve sensitive detection of trace miRNA markers. There is an urgent need for combining effective nucleic acid amplification technology with RNA aptamer to achieve highly sensitive and accurate detection of miRNA. For this purpose, a new DNA multi-arm nanostructure-based dual rolling circle transcription machinery for the generation of lighting-up MG RNA aptamers is constructed for label-free and highly sensitive sensing of miRNA-21. In this system, the target miRNA-21 induces a structural transformation of the DNA multi-arm nanostructure probe to recycle miRNA-21 and trigger two independent rolling circle transcription reactions to generate two long RNAs, which can partially hybridize with each other to generate large amounts of complete MG RNA aptamers. These RNA aptamers can associate with organic MG dye to produce significantly enhanced fluorescence signals to accomplish ultrasensitive miRNA-21 detection down to 0.9 fM. In addition, this method exhibits high selectivity to distinguish miRNA-21 even with single nucleotide mismatch, and also has potential application capability to monitor different expression levels of miRNA-21 from different cancer cells. The effective collaboration between MG RNA aptamer and rolling circle transcription reaction makes this fluorescent method show the significant advantages of low background signal, high signal-to-noise ratio and high detection sensitivity. It has great potential to be a promising means to achieve label-free and highly sensitive monitoring of other trace biological markers via a simple change of target sequence.

Programmable bidirectional dynamic DNA nano-device for accurate and ultrasensitive fluorescent detection of trace MUC1 biomarker in serums.

Accurate and ultrasensitive detection of biomarkers is significance for the diagnosis of diseases at early stage. For this purpose, we herein develop a bidirectional dynamic DNA nano-device for amplified fluorescent detection of tumor marker of mucin 1 (MUC1). The nano-device is constructed by immobilizing two sets of DNA cascade catalytic probes on two opposite directions of a single-stranded DNA tracker to limit probe reactants to a compact space. Once target MUC1 binds to the aptamer sequence, the initiator DNA locked in the duplex DNA substrate can be released to induce DNA-initiated cascade hybridization reactions (DCHRs) simultaneously in two opposite directions along the tracker DNA, accompanying the displacement of two quencher labeled-DNA intermediate initiators to facilitate successively execution of DCHRs on the DNA nano-devices, which results in the separation of fluorophore (FAM) and quencher (Dabycl) to produce substantially recovered fluorescent signals for rapid and sensitive detection of MUC1 with a detection limit down to 0.18 pM. In addition, this strategy also exhibits high selectivity against other interfering proteins and potential application capacity in real serum samples, indicating its promising application prospects in disease diagnosis and treatment.

A stimulus-responsive hexahedron DNA framework facilitates targeted and direct delivery of native anticancer proteins into cancer cells.

The targeted and direct intracellular delivery of proteins plays critical roles in biological research and disease treatments, yet remains highly challenging. Current solutions to such a challenge are limited by the modification of proteins that may potentially alter protein functions inside cells or the lack of targeting capability. Herein, we develop a stimulus-responsive and bivalent aptamer hexahedron DNA framework (HDF) for the targeted and direct delivery of native therapeutic proteins into cancer cells. The unmodified proteins are caged inside the HDF nanostructures assembled from six programmable single stranded DNAs to protect the proteins from degradation by cathepsins and enhance their targeting capability and delivery efficiency with the nanostructure-integrated aptamers. In addition, the protein drugs can be selectively released from the HDF nanostructures by the intracellular ATP molecules to induce tumor cell apoptosis, highlighting their promising application potential for cell biology and precise protein medicines.

A rare cause of abdominal pain managed unconventionally: acute renal infarction caused by atrial fibrillation: a case report.

BACKGROUND: Atrial fibrillation is one of the most common arrhythmias. The main thrombotic complication of arterial fibrillation is ischemic stroke, but it can also cause acute renal infarction from embolization. The low incidence and nonspecific clinical manifestations of acute renal infarction make it difficult to diagnose, often leading to either delayed diagnosis or misdiagnosis. Due to its rarity, more efficient treatment guidelines are helpful for the management of acute renal infarction related to the thromboembolic complication of arterial fibrillation. CASE REPORTS: We report a case of acute renal infarction due to underlying arterial fibrillation, where a novel interventional therapeutic method was used. A 66-year-old Chinese man with arterial fibrillation, not on anticoagulation due to the patient's preference, and coronary artery disease post-percutaneous coronary intervention to left anterior descending artery about 1 year ago, was currently on dual antiplatelet therapy. He suddenly developed intermittent and sharp left-sided abdominal pain and was found to have an acute left renal infarction on computed tomography scan. Angiogram showed acute occlusion of the left renal artery due to thromboembolism. For this patient, a combination method of local thrombus aspiration, angioplasty, and infusion of nitroglycerin and diltiazem were used, restoring blood flow to the left kidney. After recovery, the patient was discharged on aspirin, clopidogrel, and warfarin. At 6 months follow-up, there was no residual kidney dysfunction. CONCLUSIONS: Acute renal infarction from thromboembolism is a rare but serious complication of arterial fibrillation. More efficient and different options for intervention methods will benefit the treatment of this disease. Here, we report a combination therapeutic method that has not been used in acute renal infarction associated with arterial fibrillation, and which restored renal perfusion and prevented long-term kidney injury.

Cascaded and nonlinear DNA assembly amplification for sensitive and aptamer-based detection of kanamycin.

Simple, selective and sensitive monitoring of antibiotic residues in food is essential for food safety and human health because of its side effects upon inappropriate usage. Here, with a new label- and enzyme-free significant signal enhancement approach by the coupling of catalytic hairpin assembly (CHA) with nonlinear hybridization chain reaction (nHCR), we developed a fluorescence aptamer sensor for the detection of trace kanamycin in milk samples with high selectivity and sensitivity. The binding of the target kanamycin to the aptamer probe could initiate the CHA between two hairpins for the formation of partial DNA duplexes, which further triggered the nHCR of other three hairpins to yield branched DNA complexes with a multitude of active G-quadruplex structures. The subsequent intercalation of the organic dye, thioflavin T, into G-quadruplex structures resulted in significantly enhanced fluorescence responses for realizing sensitive sensing of kanamycin in the dynamic range of 0.1-300 nM with a detection limit of 46.1 pM. Besides, this strategy could also achieve the monitoring of kanamycin selectively in spiked milk samples. With features of high sensitivity and simplicity in a non-enzyme/label fashion, our signal amplification strategy has high potentials for establishing sensitive and convenient means to monitor various antibiotics.

Highly sensitive and label-free detection of DILI microRNA biomarker via target recycling and primer exchange reaction amplifications.

MicroRNAs (miRNA) are closely associated with the development of diseases in life processes, and the sensitive detection of microRNA biomarkers is beneficial to disease diagnosis and treatment at early stage. Herein, by coupling the target sequence recycling with the primer exchange reaction (PER), a highly sensitive and non-label approach is constructed to detect miRNA-122, the biomarker for drug-induced liver injury. The target sequence cyclically displaces two hairpins on the DNA track via toehold-mediated strand displacement reactions with the assistance of the fuel DNA. The released hairpins further bind the primer to trigger the polymerase-aided PER process for the yield of plenty of G-quadruplex sequences, which then combine with the thioflavin T to drastically enhance its fluorescence for sensing miRNA-122 with a low 49.4 fM detection limit. Highly specific discrimination of the target miRNA-122 can also be realized with the proposed method. Because of the non-label format, high selectivity and sensitivity, such a method can be a convenient and universal means for sensing various biomarkers for disease diagnosis at the early stages.

Target-initiated autonomous synthesis of metal-ion dependent DNAzymes for label-free and amplified fluorescence detection of kanamycin in milk samples.

Accurate and sensitive monitoring of the abused antibiotics is vital because excessive antibiotics in human body can cause toxicity to kidney or lead to potential loss of hearing. In this work, we described a label-free and highly sensitive fluorescent aptasensing platform for detecting kanamycin in milk samples based on the synchronization signal amplification of primer exchange reaction (PER) and metal-ion dependent DNAzyme. The target kanamycin binds the aptamer sequence hybridized on a hairpin template and initiates PER for autonomous synthesis of Mg2+-dependent DNAzyme sequences with aid of Bst-DNA polymerase at isothermal conditions. Such a synthesis process can be repeated many times to produce lots of DNAzymes to cyclically cleave the rA site in the signal hairpin substrates under the assistance of Mg2+ cofactor to liberate numerous free G-quadruplex fragments. The organic dye thioflavin T (ThT) further associates with these G-quadruplex fragments to yield substantially intensified fluorescence for sensitive detection of kanamycin with a low detection limit of 0.36 nM. In addition, the developed aptamer sensing method also shows a good selectivity for kanamycin against other interfering antibiotics, and can realize the monitoring of kanamycin added in milk samples, highlighting its potential for sensitive monitoring of trace amount of kanamycin for food safety applications.

The synchronization of multiple signal amplifications for label-free and sensitive aptamer-based sensing of a protein biomarker.

The abnormal variation of the mucin 1 (MUC1) protein level is associated with the development of multiple cancers, and the monitoring of trace MUC1 can be useful for early disease diagnosis. Here, on the basis of the synchronization of DNA-fueled sequence recycling and dual rolling circle amplification (RCA), the establishment of a non-label and highly sensitive fluorescent aptamer-based detection strategy for the MUC1 protein biomarker is described. The target MUC1 binds the aptamer hairpin probe and causes its structure switching to release an ssDNA tail to trigger the recycling of the complex via two toehold-mediated strand displacement reactions under assistance of a fuel DNA. Such a recycling amplification leads to the formation of a partial dsDNA duplex with two primers at both ends, which cooperatively bind the circular DNA ring template to start the dual RCA to produce many G-quadruplex sequences. The protoporphyrin IX dye further associates with the G-quadruplex structures to show a dramatically elevated fluorescent signal for sensitively detecting MUC1 with a low detection limit of 0.5 pM. The established aptamer-based detecting strategy is also highly selective and can realize assay of MUC1 in diluted human serums, highlighting its potential for the detection of different protein biomarkers at low contents.

DNA-Origami-Based Fluorescence Brightness Standards for Convenient and Fast Protein Counting in Live Cells.

Fluorescence microscopy has been one of the most discovery-rich methods in biology. In the digital age, the discipline is becoming increasingly quantitative. Virtually all biological laboratories have access to fluorescence microscopes, but abilities to quantify biomolecule copy numbers are limited by the complexity and sophistication associated with current quantification methods. Here, we present DNA-origami-based fluorescence brightness standards for counting 5-300 copies of proteins in bacterial and mammalian cells, tagged with fluorescent proteins or membrane-permeable organic dyes. Compared to conventional quantification techniques, our brightness standards are robust, straightforward to use, and compatible with nearly all fluorescence imaging applications, thereby providing a practical and versatile tool to quantify biomolecules via fluorescence microscopy.

Improved electrochemical performance of 2D accordion-like MnV2O6 nanosheets as anode materials for Li-ion batteries.

MnV2O6 is a promising anode material for lithium ion batteries with high theoretical specific capacity, abundant reserves and inexpensive constituent elements. However, in the process of lithization and de-lithization, the MnV2O6 anode material will form an amorphous phase, leading to collapse of its original layered structure; this greatly decreases its lithium storage capacity and specific capacity and affects its long-term cycle performance. In this study, 2D accordion-like MnV2O6 nanosheets with Co-doping are obtained via a hydrothermal route. The cobalt ions partially replace the positions of the manganese ions, and the emergence of Co3+ ions is inferred to induce the formation of a built-in electric field in the electrode to enhance the electrochemical behaviour of MnV2O6, presenting a high capacity of 1005.9 mA h g-1 after hundreds of cycles. The capacitive contribution to the total capacity is investigated to obtain insight into the kinetic analysis of its electrochemical behaviour. This study sheds light on an effective strategy to obtain excellent electrochemical behavior of MnV2O6-based materials and other transition metal oxides as electrodes for lithium storage.

Targeted and direct intracellular delivery of native DNAzymes enables highly specific gene silencing.

DNAzymes exhibit high potential as gene silencing agents for therapeutic applications. Such purposes, however, are significantly challenged by the targeted and successful delivery of unmodified DNAzymes into cells with minimal side effects. Here, we set out to formulate and demonstrate a new stimuli-responsive and constrained aptamer/DNAzyme (Apt/Dz) catenane nanostructure for highly specific gene silencing. The rational design of the Apt/Dz catenane nanostructure with the respective integration of the aptamer sequence and the completely closed catenane format enables both the targeted capability and significantly improved nuclease resistance, facilitating the stable and targeted delivery of unmodified Dz into cancer cells. Moreover, the Dz enzymatic activity in the constrained structure can only be conditionally regulated by the specific intracellular mRNA sequences to silence the target gene with highly reduced side effects. Results show that the Apt/Dz catenane nanostructure can effectively inhibit the expression of the target gene and the proliferation of cancer cells with high specificity.

Coupling strand extension/excision amplification with target recycling enables highly sensitive and aptamer-based label-free sensing of ATP in human serum.

Detection of aberrant ATP concentrations with high sensitivity and selectivity is of critical importance for monitoring many biological processes and disease stages. By coupling extension/excision amplification with target recycling, we have established an aptamer-based method for label-free fluorescence ATP detection in human serum with high sensitivity. The ATP target molecules associate with the aptamer-containing double hairpin probes and cause conformational changes of the probes to initiate the cyclic strand extension/excision processes in the presence of polymerase, endonuclease and assistance sequences for the recycling of ATP and the production of a large number of G-quadruplex sequences. The organic dye thioflavin T subsequently binds these G-quadruplex sequences to yield substantially enhanced fluorescence emission for achieving highly sensitive detection of ATP down to 2.2 nM in the range of 5 to 200 nM without using any labels. The developed aptamer sensing method also exhibits high selectivity and allows the monitoring of ATP at low concentrations in diluted real samples, which offers promising opportunities to establish effective signal magnification means for the detection of various biomolecules at trace levels.

A meta-analysis on the association of genetic polymorphism of the angiotensin-converting enzyme and coronary artery disease in the chinese population.

OBJECTIVE: To investigate the association between genotype insertion or deletion polymorphism of the angiotensin-converting enzyme gene (ACE) and susceptibility to coronary artery disease (CAD) in Chinese Han population. METHODS: We conducted a comprehensive search for the OR value of contrast between the group of genotype insertion or deletion polymorphism of the ACE and the group of CAD as an effective index. A meta-analysis (Stata 12.0) was used to test the heterogeneity of the results, combine the values for effect, conduct sensitivity analysis, and basic evaluation. RESULTS: A total of 638 studies were found on the association between polymorphisms of the angiotensin-converting enzyme gene and CAD, of which 44 studies met the inclusion criteria. In total, our study included 5619 cases and 4865 controls. The heterogeneity test of each study (P < 0.001) was carried out using a random effect model. The OR value of DD/ID+II was 1.95, 95% confidence interval (95%CI) (1.66-2.29). The OR value of II/DI+DD was 0.63, 95%CI (0.55-0.72). The funnel figure is basically symmetrical and the results of the sensitivity analysis were stable. CONCLUSION: The DD genotype of the angiotensin converting enzyme gene may be a weaker risk factor for CAD in the Chinese Han population.

A meta-analysis on the association of genetic polymorphism of the angiotensin-converting enzyme and coronary artery disease in the chinese population

SUMMARY OBJECTIVE: To investigate the association between genotype insertion or deletion polymorphism of the angiotensin-converting enzyme gene (ACE) and susceptibility to coronary artery disease (CAD) in Chinese Han population. METHODS: We conducted a comprehensive search for the OR value of contrast between the group of genotype insertion or deletion polymorphism of the ACE and the group of CAD as an effective index. A meta-analysis (Stata 12.0) was used to test the heterogeneity of the results, combine the values for effect, conduct sensitivity analysis, and basic evaluation. RESULTS: A total of 638 studies were found on the association between polymorphisms of the angiotensin-converting enzyme gene and CAD, of which 44 studies met the inclusion criteria. In total, our study included 5619 cases and 4865 controls. The heterogeneity test of each study (P < 0.001) was carried out using a random effect model. The OR value of DD/ID+II was 1.95, 95% confidence interval (95%CI) (1.66-2.29). The OR value of II/DI+DD was 0.63, 95%CI (0.55-0.72). The funnel figure is basically symmetrical and the results of the sensitivity analysis were stable. CONCLUSION: The DD genotype of the angiotensin converting enzyme gene may be a weaker risk factor for CAD in the Chinese Han population.

RESUMO OBJETIVO: Investigar a associação entre o polimorfismo de inserção ou deleção do genótipo do gene da enzima conversora da angiotensina (ACE) e a susceptibilidade da etnia Han chinesa para a doença arterial coronariana (DAC). Métodos: Foi realizada uma pesquisa abrangente para o valor de OR (Odds Ratio) de contraste entre o grupo de polimorfismo de inserção ou deleção do genótipo do gene da enzima conversora da angiotensina (ACE) e o grupo de doença arterial coronariana (DAC) como um índice de eficácia. Uma meta-análise (Stata 12,0) foi utilizada para testar a heterogeneidade dos resultados, combinar os valores de eficácia, realizar análises de sensibilidade e de avaliação básica. RESULTADOS: Um total de 638 estudos foram encontrados sobre a associação entre polimorfismos do gene da enzima conversora da angiotensina e doença arterial coronariana, dos quais 44 satisfaziam os critérios de inclusão. Nosso estudo incluiu 6246 casos e 5713 controles. O teste de heterogeneidade de cada estudo (p < 0,001) foi realizado seguindo o modelo de efeito randômico. O valor de OR para DD/ID+II foi 1,95, com 95% de intervalo de confiança de (95%CI) (1,66-2,29). O valor de OR para II/DI+DD foi 0,63, com 95% IC (0,55-0,72). A figura do funil é basicamente simétrica e os resultados da análise de sensibilidade foram estáveis. CONCLUSÃO: O genótipo DD do gene da enzima conversora da angiotensina podem ser um fator de risco mais fraco para doença coronariana na população chinesa Han.

Programmable DNA Ring/Hairpin-Constrained Structure Enables Ligation-Free Rolling Circle Amplification for Imaging mRNAs in Single Cells.

Self-assembled functional DNA structures have proven to be excellent materials for designing and implementing a variety of nanoscale devices. We demonstrate here that a rationally designed and programmable DNA ring/hairpin-constrained structure can achieve in situ ligation-free rolling circle amplification (RCA), which further leads to highly specific, sensitive, and multicolor imaging of mRNA molecules in single cells. Such a structure aims at addressing current challenges in terms of simplicity, sensitivity, and multiplexing capability related to the detection and imaging of intracellular mRNA sequences. With this new DNA ring/hairpin-RCA approach, we are able to detect the target mRNAs with high sensitivity at the subpicomolar levels in vitro. Besides, the multiplexing capability of the DNA structures can be readily realized by barcoding the DNA rings and hairpins with distinct sequences. Due to the excellent sequence recognition ability of the hairpins, the DNA structures exhibit single-base variation discrimination capability for the target mRNA and can be used to image trace amounts of down-expressed mRNAs in single cells. Moreover, drug-dependent mRNA expression variations can also be clearly differentiated by these DNA structures, highlighting the great potential of such structures for early disease diagnosis and for screening possible therapeutic drugs.

Aptamer proximity recognition-dependent strand translocation for enzyme-free and amplified fluorescent detection of thrombin via catalytic hairpin assembly.

By coupling a new aptamer proximity recognition-dependent strand translocation strategy with catalytic hairpin assembly (CHA) signal amplification, we have developed a simple and sensitive method for detecting thrombin in human serums. Simultaneous binding of two engineered aptamer probes to the thrombin target significantly increases the local concentrations of the two probes and facilitates the translocation of a ssDNA strand from one of the probes to the other through toehold mediated strand displacement. Such a strand translocation leads to the generation of a ssDNA tail in the aptamer sequence for subsequent initiation of the assembly of two fluorescently quenched hairpins into many DNA duplexes via CHA. The formation of the DNA duplexes thus results in significant fluorescence recovery for amplified detection of thrombin down to 8.3 pM. The developed method is highly selective to the thrombin target against other interference proteins due to the dual recognition mode, and can be employed to monitor thrombin in human serum samples. With the advantage of simplicity, sensitivity and selectivity, this method can be a universal non-enzymatic and nanomaterial-free amplified sensing platform for detecting different protein molecules.

Click chemistry-mediated cyclic cleavage of metal ion-dependent DNAzymes for amplified and colorimetric detection of human serum copper (II).

The determination of the level of Cu2+ plays important roles in disease diagnosis and environmental monitoring. By coupling Cu+-catalyzed click chemistry and metal ion-dependent DNAzyme cyclic amplification, we have developed a convenient and sensitive colorimetric sensing method for the detection of Cu2+ in human serums. The target Cu2+ can be reduced by ascorbate to form Cu+, which catalyzes the azide-alkyne cycloaddition between the azide- and alkyne-modified DNAs to form Mg2+-dependent DNAzymes. Subsequently, the Mg2+ ions catalyze the cleavage of the hairpin DNA substrate sequences of the DNAzymes and trigger cyclic generation of a large number of free G-quadruplex sequences, which bind hemin to form the G-quadruplex/hemin artificial peroxidase to cause significant color transition of the sensing solution for sensitive colorimetric detection of Cu2+. This method shows a dynamic range of 5 to 500 nM and a detection limit of 2 nM for Cu2+ detection. Besides, the level of Cu2+ in human serums can also be determined by using this sensing approach. With the advantages of simplicity and high sensitivity, such sensing method thus holds great potential for on-site determination of Cu2+ in different samples. Graphical abstract Sensitive colorimetric detection of copper (II) by coupling click chemistry with metal ion-dependentDNAzymes.

A DNA-Fueled and Catalytic Molecule Machine Lights Up Trace Under-Expressed MicroRNAs in Living Cells.

The detection of specific intracellular microRNAs (miRNAs) in living cells can potentially provide insight into the causal mechanism of cancer metastasis and invasion. However, because of the characteristic nature of miRNAs in terms of small sizes, low abundance, and similarity among family members, it is a great challenge to monitor miRNAs in living cells, especially those with much lower expression levels. In this work, we describe the establishment of a DNA-fueled and catalytic molecule machinery in cell signal amplification approach for monitoring trace and under-expressed miRNAs in living cells. The presence of the target miRNA releases the hairpin sequences from the dsDNA (containing the fluorescence resonance energy transfer (FRET) pair-labeled and unfolded hairpin sequences)-conjugated gold nanoparticles (dsDNA-AuNPs), and the DNA fuel strands assist the recycling of the target miRNA sequences via two cascaded strand displacement reactions, leading to the operation of the molecular machine in a catalytic fashion and the release of many hairpin sequences. As a result, the liberated hairpin sequences restore the folded hairpin structures and bring the FRET pair into close proximity to generate significantly amplified signals for detecting trace miRNA targets. Besides, the dsDNA-AuNP nanoprobes have good nuclease stability and show low cytotoxicity to cells, and the application of such a molecular system for monitoring trace and under-expressed miRNAs in living cells has also been demonstrated. With the advantages of in cell signal amplification and reduced background noise, the developed method thus offers new opportunities for detecting various trace intracellular miRNA species.