Combination of Ternary Electrochemiluminescence System of BNQDs/AgMOG-K2S2O8 and Electrochemiluminescence Resonance Energy Transfer Strategy for Ultrasensitive Immunoassay of Amyloid-ß Protein.

In this work, based on boron nitride quantum dots (BNQDs) as energy donors and MnO2@MWCNTs-COOH as energy receptors, we designed an efficient electrochemiluminescence resonance energy transfer (ECL-RET) immunosensor for the detection of amyloid-ß (Aß42) protein, a biomarker of Alzheimer's disease (AD). First, the signal amplification of a ternary ECL system composed of BNQDs (as the ECL emitter), K2S2O8 (as the coreactant), and silver metal-organic gels (AgMOG, as the coreaction accelerator) was realized, and PDDA as stabilizer was added, a strong and stable initial ECL signal was obtained. AgMOG could not only support a large amount of BNQDs and Aß42 capture antibody (Ab1) through Ag-N bond but also exhibit excellent ECL catalytic performance and enhance the luminescent intensity of BNQDs@PDDA-K2S2O8 system. In addition, due to the broad absorption spectrum of MnO2@MWCNTs-COOH and the extensive overlap with the ECL emission spectrum of BNQDs, the quenching probe Ab2-MnO2@MWCNTs-COOH could be introduced into the ternary system through a sandwich immune response. On this basis, the signal on-off ECL immunosensor was constructed to achieve the ultrasensitive detection of Aß42 through signal transformation. Under the optimal conditions, the prepared ECL biosensor manifested a wide linear range (10 fg/mL-100 ng/mL) with a detection limit of 2.89 fg/mL and showed excellent stability, selectivity, and repeatability, which provided an effective strategy for the ultrasensitive detection of biomarkers in clinical analysis.

Room-Temperature Synthesized Iron/Cobalt Metal-Organic Framework Nanosheets with Highly Efficient Catalytic Activity toward Luminol Chemiluminescence Reaction.

Two-dimensional (2D) iron/cobalt metal-organic framework nanosheets (Fe/Co-MOF NSs) were synthesized via the cooperative self-assembly reaction of Fe3+/Co2+ and terephthalic acid at room temperature. The as-prepared 2D Fe/Co-MOF NSs display superior performance in catalysis of the chemiluminescence (CL) reaction between luminol and H2O2. The CL spectrum, UV-vis absorption spectroscopy, radical scavenger experiments, and electron spin resonance (ESR) spectroscopy are utilized to research the possible CL mechanism of the luminol-H2O2-Fe/Co-MOF NSs system. All results indicate that Fe/Co-MOF NSs present outstanding peroxidase-like activity and could catalyze H2O2 to produce 1O2, O2·-, and ·OH, which could react rapidly with the luminol anion radical and result in strong CL. With the highly efficient CL of the luminol-H2O2-Fe/Co-MOF NSs system, a sensitive sensor for the detection of dopamine (DA) is developed based on the inhibitory effect of DA on the CL intensity. Good linearity over the range of 50-800 nM is achieved with a limit of detection of 20.88 nM (S/N = 3). This research demonstrates that 2D Fe/Co-MOF NSs is a highly effective catalyst for luminol CL reaction and has great application potential in the CL field.

Sensitive and Amplification-Free Electrochemiluminescence Biosensor for HPV-16 Detection Based on CRISPR/Cas12a and DNA Tetrahedron Nanostructures.

Rapid and accurate detection of biomarkers was very important for early screening and treatment of diseases. Herein, a sensitive and amplification-free electrochemiluminescence (ECL) biosensor based on CRISPR/Cas12a and DNA tetrahedron nanostructures (TDNs) was constructed. Briefly, 3D TDN was self-assembled on the Au nanoparticle-deposited glassy carbon electrode surface to construct the biosensing interface. The presence of the target would activate the trans-cleavage activity of Cas12a-crRNA duplex to cleave the single-stranded DNA signal probe on the vertex of TDN, causing the Ru(bpy)32+ to fall from the electrode surface and weakened the ECL signal. Thus, the CRISPR/Cas12a system transduced the change of target concentration into an ECL signal enabling the detection of HPV-16. The specific recognition of CRISPR/Cas12a to HPV-16 made the biosensor have good selectivity, while the TDN-modified sensing interface could reduce the cleaving steric resistance and improve the cleaving performance of CRISPR/Cas12a. In addition, the pretreated biosensor could complete sample detection within 100 min with a detection limit of 8.86 fM, indicating that the developed biosensor possesses the potential application prospect for fast and sensitive nucleic acid detection.

Ferrocene-Functionalized Covalent Organic Frameworks and Target Catalyzed Hairpin Assembly Strategy for Amplified Electrochemical Determination of MicroRNAs.

MicroRNAs (miRNAs) are considered as significant biomarkers in early diagnosis and treatment of diseases. Herein, an electrochemical biosensor that uses ferrocene (Fc)-functionalized covalent organic frameworks (COFs), a DNA tetrahedron nanostructure (DTN) biosensing interface, and a target catalyzed hairpin assembly (CHA) strategy has been fabricated and successfully developed for the sensitive and specific determination of microRNA-21 (miR-21). The COF served as a linked substrate for immobilization of gold nanoparticles (AuNPs), Fc-COOH, and complementary DNA probe L1 to prepare the electrochemical signal probe COF/Au/Fc/L1, which has a large surface area, extraordinary catalytic properties, and superior biocompatibility to amplify the current signal. The DTN containing a hairpin sequence H1 at one vertex was elaborately designed to construct the biosensing interface; thus, the CHA could be implemented on the electrode surface. In the presence of miR-21, the CHA reaction between H1 and the hairpin H2 was triggered to produce a great number of duplex DNA (H1/H2) with sticky ends. Then, the signal probe COF/Au/Fc/L1 was modified on the electrode surface through the hybridization between L1 and the sticky end of H1/H2, thereby obtaining an amplified Fc current signal. Under optimal conditions, the biosensor showed a wide linear response ranging from 1 fM to 10 nM miR-21, with a low detection limit of 0.33 fM (S/N = 3). Meanwhile, the method showed acceptable accuracy and precision for the determination of miR-21 in human serum.

Novel and sensitive electrochemical/fluorescent dual-mode biosensing platform based on the cascaded cyclic amplification of enzyme-free DDSA and functional nucleic acids.

Herein, we present a novel electrochemical (EC)/fluorescent (FL) dual-mode biosensor for sensitive and accurate detection of target nucleic acids, which was based on the functional nucleic acids-involved enzyme-free dynamic DNA self-assembly of catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) for cascaded cyclic amplification. Originally, the CHA reaction of three well-designed hairpin probes were initiated by target sequence, forming abundant Mg2+-dependent three-way DNAzyme junctions (MTWDJ) which could recognize and cleave the methylene blue-labeled substrate hairpin (MB-Hs) to generate the MB-labeled fragments s1 (MB-s1) and the HCR initiator s2. Then, s2 triggered the HCR of four hairpins to produce long DNA nanowires which contained numerous G-quadruplex sequences and the same Mg2+-dependent DNAzyme (MNAzyme) sequences as MTWDJ. Therefore, the HCR copolymer could not only emerge the fluorescent signals through combining thioflavin T with G-quadruplex, but also generate MB-s1 and s2 via MNAzyme cleavage of MB-Hs to continue initiating the HCR. Meanwhile, MB-s1, the cleavage product of MTWDJ and MNAzyme, was captured on the DNA tetrahedron nanostructure modified electrode surface to bring electrochemical signals. Benefiting from integrating the efficient cyclic cleavage of MTWDJ and MNAzyme, the concatenated CHA and HCR amplification circuit, and the dual-mode detection, the sensitivity and accuracy of this biosensor were significantly improved. Under the optimal conditions, the proposed EC/FL dual-mode sensing strategy exhibited a superior analytical performance toward target nucleic acids, showing the promising application in bioanalysis and early disease diagnosis.

Versatile Electrochemiluminescence Biosensing Platform Based on DNA Nanostructures and Catalytic Hairpin Assembly Signal Amplification.

Achieving rapid and highly sensitive detection of biomarkers is crucial for disease diagnosis and treatment. Here, a highly sensitive and versatile dual-amplification electrochemiluminescence (ECL) biosensing platform was constructed for target detection based on DNA nanostructures and catalyzed hairpin assembly (CHA). Specifically, when the target DNA was present, it would hybridize with the auxiliary strands (D1 and D2) to form an I-shaped nanostructure, which in turn triggered the subsequent catalytic hairpin assembly reaction to generate plenty of double-stranded DNA complexes (H1-H2). The resulting double-stranded complex could be trapped on the electrode surface and adsorbed the ECL signal probe Ru(phen)32+.We found that the I-shaped nanostructure-triggered CHA reaction had higher amplification efficiency compared with traditional CHA amplification. Thus, a sensitive "signal-on" ECL biosensor was constructed for target DNA detection with a detection limit of 1.09 fM. Additionally, by combining the binding properties of C-Ag+-C with an elaborately designed "Ag+-helper" probe, the proposed strategy could be immediately utilized for the highly sensitive and selective detection of silver ions, demonstrating the versatility of the developed biosensing platform. This strategy provided a new approach with potential applications in disease diagnosis and environmental monitoring.

SAR ship target detection method based on CNN structure with wavelet and attention mechanism.

Ship target detection in synthetic aperture radar (SAR) images is an important application field. Due to the existence of sea clutter, especially the SAR imaging in huge wave area, SAR images contain a lot of complex noise, which brings great challenges to the effective detection of ship targets in SAR images. Although the deep semantic segmentation network has been widely used in the detection of ship targets in recent years, the global information of the image cannot be fully utilized. To solve this problem, a new convolutional neural network (CNN) method based on wavelet and attention mechanism was proposed in this paper, called the WA-CNN algorithm. The new method uses the U-Net structure to construct the network, which not only effectively reduces the depth of the network structure, but also significantly improves the complexity of the network. The basic network of WA-CNN algorithm consists of encoder and decoder. Dual tree complex wavelet transform (DTCWT) is introduced into the pooling layer of the encoder to smooth the speckle noise in SAR images, which is beneficial to preserve the contour structure and detail information of the target in the feature image. The attention mechanism theory is added into the decoder to obtain the global information of the ship target. Two public SAR image datasets were used to verify the proposed method, and good experimental results were obtained. This shows that the method proposed in this article is effective and feasible.

An electrochemical sensor for sensitive detection of dopamine based on a COF/Pt/MWCNT-COOH nanocomposite.

Herein, an electrochemical sensor was developed for sensitive detection of dopamine (DA) based on a novel COF-based nanocomposite named COF/Pt/MWCNT-COOH, which possesses large specific surface area, excellent electrical conductivity, and high catalytic activity, thus broadening the application of COFs in the electrochemical sensing area.

A dual-amplification mode and Cu-based metal-organic frameworks mediated electrochemical biosensor for sensitive detection of microRNA.

In this work, we developed a novel label-free and highly sensitive electrochemical (EC) biosensor for detection of microRNA (miRNA), which was based on the target-triggered and the Cu-based metal-organic frameworks (Cu-MOFs) mediated CHA-HCR dual-amplification process. Initially, the target miRNA triggered the catalytic hairpin assembly (CHA) process of hairpin DNA 1 (H1) and hairpin DNA 2 (H2) to produce massive double-stranded DNA (H1/H2) which could hybridize with the single-stranded DNA 1 (P1) to form capture probe (P1/H1/H2) on electrode surface, realizing the first amplification of input signals. Subsequently, hybridization chain reaction (HCR) between signal probe (H3-AuNPs/Cu-MOFs) and hairpin DNA 4 (H4) was activated by above capture probe (P1/H1/H2), leading to the second amplification of input signals. After the HCR process, numerous Cu-MOFs were immobilized on the electrode surface, which brought out the enhancement of electrochemical signals generating by Cu-MOFs. Herein, Cu-MOFs not only offered the lager surface area to decorate with gold nanoparticles (AuNPs) and hairpin DNA 3 (H3), but also served as the signal probe (H3-AuNPs/Cu-MOFs) to produce electrochemical signals by hybridizing with the capture probe on electrode surface. Therefore, the ingenious design of CHA-HCR-Cu-MOFs scheme enables the sensitive analysis of microRNA-21 (miR-21) with a broad linear range from 0.1 fM to 100 pM and a lower LOD of 0.02 fM. In addition, the outstanding specificity of this sensing strategy allows it successfully to be applied for determining miR-21 in real biological samples.

Electrochemical Immunosensor for Cardiac Troponin I Detection Based on Covalent Organic Framework and Enzyme-Catalyzed Signal Amplification.

Herein, a highly sensitive electrochemical immunosensor was presented for the cardiac troponin I (cTnI) determination using a multifunctional covalent organic framework-based nanocomposite (HRP-Ab2-Au-COF) as the signal amplification probe. The spherical COF with a large surface area was synthesized in a short time by a simple solution-based method at room temperature. The good biocompatibility, low toxicity, and high stability in water of the COF guarantee its application in biosensing. Besides, its high porosity makes it an excellent carrier for loading abundant horseradish peroxidase (HRP). The modified gold nanoparticles on the surface of COF not only provide a load platform for secondary antibody (Ab2) but also improve the conductivity of COF. Under the synergistic effect of the hydrogen peroxide (H2O2) and HRP, hydroquinone (HQ) in the solution is catalytically oxidized to benzoquinone (BQ), which is then reduced on the electrode surface to generate the electrochemical signal. The designed probes not only show the specific recognition behavior of Ab2 to cTnI but also improve the sensitivity of the biosensing system due to the signal amplification caused by the excellent enzyme catalytic performance of HRP. Based on the H2O2-HRP-HQ signal amplification system, the biosensor for cTnI was fabricated and exhibited a linear response as a function of logarithmic cTnI concentration ranging from 5 pg/mL to 10 ng/mL, and the detection limit was 1.7 pg/mL. Moreover, the biosensor exhibited excellent recovery and reproducibility in the actual sample testing. This work provided a simple approach to determine cTnI quantitatively in practical samples and broadened the utilization scope of the COF-based nanocomposite in the electrochemical immunosensor.

Electrochemiluminescence Biosensor Based on Entropy-Driven Amplification and a Tetrahedral DNA Nanostructure for miRNA-133a Detection.

The early and rapid diagnosis of acute myocardial infarction (AMI) is of great significance to its treatment. Here, we developed an electrochemiluminescence biosensor based on an entropy-driven strand displacement reaction (ETSD) and a tetrahedral DNA nanostructure (TDN) for the detection of the potential AMI biomarker microRNA-133a. In the presence of the target, numerous Ru(bpy)32+-labeled signal probes (SP) were released from the preformed three-strand complexes through the process of ETSD. The ETSD reaction cycle greatly amplified the input signal of the target. The released SP could be captured by the TDN-engineered biosensing interface to generate a strong ECL signal. The rigid structure of TDN could significantly improve the hybridization efficiency. With the assistant of double amplification of TDN and ETSD, the developed biosensor has a good linear response ranging from 1 fM to 1 nM for microRNA-133a, and the detection limit is 0.33 fM. Additionally, the constructed biosensor has excellent repeatability and selectivity, demonstrating that the biosensor possesses a great application prospect in clinical diagnosis.

Label-free immunosensor for cardiac troponin I detection based on aggregation-induced electrochemiluminescence of a distyrylarylene derivative.

Herein, the aggregation-induced electrochemiluminescence (AIECL) of a distyrylarylene derivative, 4,4'-bis(2,2-diphenylvinyl)-1,1'-biphenyl (DPVBi), was investigated for the first time. This luminophore exhibits significantly enhanced photoluminescence (PL) and electrochemiluminescence (ECL) emission with the increases of water content in organic/water mixtures. This high luminescence efficiency of DPVBi in aggregate state is due to the fact that the aggregates can reduce the energy loss by restricting the intramolecular motions. The ECL behavior of DPVBi in acetonitrile was investigated by ECL transients and so-called "half-scan" technology, where singlet-singlet annihilation ECL was generated under continuous potential switching. The DPVBi nanobulks (DPVBi NBs) were prepared to improve its application in aqueous media, which could be conveniently cast on electrode surface for developing sensing platform due to its good film-forming nature. The constructed heterogeneous AIECL platform can produce reductive-oxidative and oxidative-reductive ECL by using trimethylamine (TEA) and potassium peroxodisulfate (K2S2O8) as coreactant. On the basis of the higher ECL efficiency of DPVBi NBs/TEA system, a label free immunosensor for cardiac troponin I (cTnI) was developed with the assistance of electrodeposited gold nanoparticles, and it showed a wide linear range of 20 ng/mL~100 fg/mL and low detection limit of 43 fg/mL. Moreover, the constructed immunosensor also exhibited good specificity, stability and satisfied performance in practical sample analysis.

Label-Free and Sensitive Electrochemical Biosensor for Amplification Detection of Target Nucleic Acids Based on Transduction Hairpins and Three-Leg DNAzyme Walkers.

Nucleic acids are regarded as reliable biomarkers for the early diagnosis of various diseases. By ingeniously combining a transduction hairpin (THP) with the toehold-mediated strand displacement reaction (TSDR) to form three-leg DNAzyme walkers, for the first time, we constructed a label-free and sensitive electrochemical sensing system for the amplification detection of target nucleic acids. With microRNA-155 (miR-155) as a model target, the feasibility of the biosensing strategy and the conformational states of DNA in the recognition process were studied in detail on the basis of electrochemical and dual polarization interferometry techniques. With the assistance of THP, miR-155 indirectly triggered the TSDR between three hairpins (H1, H2, and H3), then massive Mg2+-dependent three-leg DNAzyme walkers were formed in aqueous solutions. After the binding/cleaving/moving process of three-leg DNAzyme walkers on the electrode surface modified with substrate hairpins (SHPs), a number of single-stranded DNAs (ssDNAs) were generated. Hence, the interaction of methylene blue (MB) with the duplex section of SHPs was impeded, which brought about a decreased electrochemical signal. Benefiting from the cyclic amplification of the TSDR and the higher cleavage activity of three-leg DNAzyme walkers, the proposed sensing strategy showed remarkable improvement in sensitivity with a low detection limit of 0.27 fM for miR-155. Owing to the precise design of the THP, this method exhibited excellent specificity to distinguish miR-155 from the single-base and triplex-base mismatched sequences. This sensing strategy importing the flexible THP can be utilized to detect various nucleic acid biomarkers by only redesigning the THP without changing the main circuit or reporter constructs, showing the great versatility and potential for the early diagnostics and biological analysis.

An intensive and glow-type chemiluminescence of luminol-embedded, guanosine-derived hydrogel.

In this paper, an intensive and glow-type chemiluminescence (CL) hydrogel was prepared by simultaneous incorporation of chemiluminescence reagent (luminol) and catalytic cofactor (hemin) into the scaffold of guanosine-derived hydrogel. The self-assembled hydrogel consisted of K+ stabilized hemin/G-quartet structures, showing significant enzyme-like activity to H2O2-mediated oxidation of luminol. After adding H2O2 into the hydrogel, blue light visible to naked eyes would come into being and last for over 8 h. The lasting-time CL emission of hydrogel was achieved due to a mechanism of slow-diffusion-controlled heterogeneous catalysis. Moreover, this self-assembled hydrogel performed a good response to H2O2 and the CL emission images could be recorded by smartphone. The hydrogel could remain excellent lifetime stability for months and the stable, enhanced and glow-type CL emission could improve the reliability and precision of CL detection, which has a promising application in cold light source and H2O2 detection of real biological samples.

Electrochemistry and Electrochemiluminescence of Coumarin Derivative Microrods: Mechanism Insights.

Organic molecules and related nanomaterials have attracted extensive attention in the realm of electrochemiluminescence (ECL). Herein, a well-known electroluminescence (EL) dopant 2,3,6,7-tetrahydro-1,1,7,7,-tetramethyl-1H,5H,11H-10-(2-benzothiazolyl)quinolizino-[9,9a,1gh] coumarin (C545T) is selected as a new ECL illuminant, which shows a high photoluminescence quantum yield of nearly 100% and excellent ECL performance in the organic phase. For utilizing C545T to achieve ECL detection in aqueous solution, organic microrods of C545T (C545T MRs) were synthesized by a precipitation method. Cyclic voltammetry and differential pulse voltammetry of C545T and C545T MRs in acetonitrile or phosphate buffer showed one reduction and multiple oxidation peaks, suggesting that the multiple charge states of C545T could be produced by continuous electron- or hole-injection processes. The annihilated ECL emission of C545T and C545T MRs was observed using ECL transient technology. In the presence of triethanolamine (TEOA) or potassium persulfate (K2S2O8), C545T MRs can also give bright anodic and cathodic ECL emission at the GCE/water interface. The proposed ECL system not only has multichannel ECL emission but also shows intense yellow emission (569 nm) with a relative ECL efficiency of 0.81 when TEOA was used as a coreactant. Benefiting from the strong ECL emission of the C545T MRs/TEOA system and the quenching effect of dopamine (DA) on ECL, a convenient sensor for DA was developed with high selectivity and sensitivity.

Sensitive and Programmable "Signal-Off" Electrochemiluminescence Sensing Platform Based on Cascade Amplification and Multiple Quenching Mechanisms.

A versatile and sensitive quantum dot (QD)-based "signal-off" electrochemiluminescence (ECL) sensing system was constructed using target-initiated dual Mg2+-dependent DNAzyme (MNAzyme) recycling and catalytic hairpin assembly (CHA) amplification strategies. After the cascade amplification, numerous ferrocene-labeled Y-shaped DNA complexes generated on the QD-modified electrode surface. In the presence of hemin, moreover, the terminal sequence of the formed complex could assemble into hemin/G-quadruplex. Therefore, the highly efficient ECL quenching was achieved due to the multiple quenching mechanisms, including electron/energy transfer between ferrocene and QDs, the steric hindrance effects, and the horseradish peroxidase-mimicking activity of hemin/G-quadruplex. Furthermore, owing to the flexibility in regulating the recognition sequences of MNAzyme, the assaying targets can be programmed. Based on the cascade amplification and multiple ECL quenching mechanisms, the developed programmable "signal-off" ECL sensing platform demonstrates excellent sensitivity and the detection limits of 35.00 aM, 3.71 fM, and 0.28 pM (S/N = 3) for target DNA, aptamer substrate (ATP as a model), and ion (Ag+ as a model), respectively.

A ratiometric electrochemiluminescence strategy based on two-dimensional nanomaterial-nucleic acid interactions for biosensing and logic gates operation.

Two-dimensional (2D) nanomaterial-nucleic acid interactions have been widely used in the construction of fluorescent sensors, but they are rarely used in the construction of electrochemiluminescent (ECL) sensors and have never been used in the design of ratiometric ECL sensors. Therefore, a ratiometric ECL sensing platform was developed in this study based on the ECL resonance energy transfer (ECL-RET) of graphitic carbon nitride nanosheets (GCNNs)/Ru(bpy)32+ donor/acceptor pair. The 2D GCNNs showed much weaker affinity to the long dsDNA duplexes formed by hybridization chain reaction (HCR) than Ru(bpy)32+-lableled fuel hairpin DNAs (H1 and H2) for HCR. Therefore, the target-initiated HCR resulted in the luminescence enhancement of the GCNNs at 460 nm and the luminescence attenuation of the Ru(bpy)32+ at 610 nm. By measuring the I460 nm/I610 nm ratios, quantitative analysis of microRNA-133a was realized with a limit of detection of 0.41 pM. In addition, this ECL-RET sensing platform can be easily extended to detect metal ions or aptamer substrates by simply redesigning helper DNAs without changing the sequences of fuel hairpin DNAs. Moreover, due to the programmability of HCR, a series of sensitive logic gates ("OR", "INHIBIT", "AND", "NAND" and "INHIBIT-OR") based on the ECL-RET ratiometry can be constructed and responded to as low as 100 pM of Hg2+ or Ag+.

Real-Time Analysis of Specific Binding between Apolipoprotein E Isoforms and Amyloid ß-Peptide by Dual Polarization Interferometry.

One of the pathogenesis hypotheses of Alzheimer's disease (AD) is amyloid depositions and neurofibrillary tangles. Apolipoprotein E (Apo E) acts a vital part in the development of AD by affecting the aggregation and clearance of amyloid-ß (Aß). In this paper, a dual polarization interferometry (DPI) technique was employed for a real-time investigation toward the binding events of Apo E isoforms, for instance, Apo E2, Apo E3, and Apo E4, with Aß1-40. By evaluation of detailed binding information provided by DPI, the affinities between Apo E isoforms and Aß1-40 follow the order of E4 > E3 > E2, and the dissociation constants (KD) of Aß1-40 with Apo E2, Apo E3, and Apo E4 were determined to be 251 ± 37, 40 ± 0.65, and 24.6 ± 2.42 nM, respectively. Our findings reveal the isoform-specific binding behaviors from a kinetics perspective, which can help us understand that Apo E4 has a higher risk of causing AD because of its promoting effect on Aß aggregation and fibrillation and inefficient clearance of Aß. Remarkably, this work provides a promising method for exploring the dynamics of interactions between biomolecules and expectantly contributes to the development of AD drugs and therapies targeting Apo E and Aß.

Holey nitrogen-doped graphene aerogel for simultaneously electrochemical determination of ascorbic acid, dopamine and uric acid.

In this paper, holey nitrogen-doped graphene aerogel (HNGA) was synthesized and applied to the concurrently electrochemical determination of small biological molecules including ascorbic acid (AA), dopamine (DA) and uric acid (UA). Firstly, holey graphene hydrogel was synthesized by the hydrothermal reaction in the presence of H2O2, which subsequently was lyophilized and further annealed in the mixed gas of ammonia and argon to obtain HNGA. Electron microscopy characterization exhibited a great number of nanopores formed on the basal surface of graphene sheets, and HNGA possessed a hierarchically porous structure. The unique structure and composition of HNGA make it an ideal material for electroanalytical application through accelerating mass and electron transfer. HNGA modified glassy carbon electrode (HNGA/GCE) displayed significantly enhanced electrochemical response to AA, DA, and UA, namely reducing overpotential, increasing current density, and improving the reversibility. The oxidation peaks of these three biomolecules can be entirely separated with evident peak potential differences which are 0.216 V (AA-DA), 0.120 V (DA-UA), and 0.336 V (AA-UA), which it allowed the determination of the three substances at the same time. This sensor shows high sensitivity for the determination of AA, DA, and UA with the detection limit of 16.7 µM, 0.22 µM, and 0.12 µM (S/N = 3), respectively. The proposed sensor was applicable for the practical sample analysis as well and desirable recovery was obtained.

A thiamine-triggered fluormetric assay for acetylcholinesterase activity and inhibitor screening based on oxidase-like activity of MnO2 nanosheets.

Acetylcholinesterase (AChE) plays an essential role in biological signal transmission, the aberrant expression of which could cause diverse neurodegenerative diseases. Herein, based on the oxidase-like activity of manganese dioxide nanosheets (MnO2 NSs), we found that MnO2 NSs could directly oxidize thiamine into intensely fluorescent thiochrome without the need of peroxides. When AChE was introduced, acetylthiocholine could be hydrolyzed to generate thiocholine, which efficiently triggered the reduction of MnO2 NSs into Mn2+, resulting in the decrease of fluorescence. Owing to the inhibiting effect of tacrine to the AChE activity, the decomposition of MnO2 was hindered, thus leading to the fluorescence recovery. According to the above mechanism, we constructed a simple, low-cost, label-free, facile and rapid synthetic fluorescent biosensor for highly sensitive and selective detection of AChE activity and screening of its inhibitor. This biosensor obtained a good linear range from 0.02 to 1 mU/mL and an extremely low detection limit of 15 µU/mL for AChE assay, as well as a sensitive screening for tacrine and an excellent applicability in human serum samples. These results suggested that our proposed method would be potentially applied in monitoring the disease progression.