Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH

DFNA9 is a late-onset, progressive, autosomal dominantly inherited sensorineural hearing loss with vestibular dysfunction, which is caused by mutations in the COCH (coagulation factor C homology) gene. In this study, we investigated a Chinese family segregating autosomal dominant nonsyndromic sensorineural hearing loss. We identified a missense mutation c.T275A p.V92D in the LCCL domain of COCH cosegregating with the disease and absent in 100 normal hearing controls. This mutation leads to substitution of the hydrophobic valine to an acidic amino acid aspartic acid. Our data enriched the mutation spectrum of DFNA9 and implied the importance for mutation screening of COCH in age related hearing loss with vestibular dysfunctions

One-step process for fabricating paper-based solid-state electrochemiluminescence sensor based on functionalized graphene

Taking advantage of simple manipulation of the screen printed electrodes, with the assistance of different functionalized graphene materials, a simple and time-saving one-step process was developed for fabricating solid-state electrochemiluminescence (ECL) sensors on paper-based chips (PCs). The solid-state Ru(bpy)32+ or co-reactant ECL sensors could be facilely obtained by screen-printing the mixture of Ru(bpy)32+/poly(sodium 4-styrenesulfonate) functionalized graphene nanosheets (PSSG)/carbon paste or branch poly(ethylenimine) (BPEI)-functionalized graphene nanosheets (BPEIG)/carbon paste through one-step process on the PCs, respectively. The ECL behavior of Ru(bpy)32+ ECL sensor was investigated using tripropylamine (TPA) and detection limit (S/N = 3) of 5.0 nM was obtained. It also exhibited excellent reproducibility and linear relationship with the concentration of TPA (R = 0.991). In addition, the ECL behaviors of the coreactant sensor were measured for tetracycline hydrochloride (TCH) by inhibition method. A linear relationship between the ECL intensity and logarithm of the concentration of TCH was gained in a range of 1 × 10−8 to 1 × 10−6 M and the detection limit was as low as 2.22 nM. Therefore the one-step process for fabricating paper-based ECL sensor was confirmed with the advantages of simplicity, high efficiency and potential applicability. Keywords: Paper-based chips, One-step process, Functionalized graphene, Electrochemiluminescence sensor, Tetracycline hydrochlorid

Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH

DFNA9 is a late-onset, progressive, autosomal dominantly inherited sensorineural hearing loss with vestibular dysfunction, which is caused by mutations in the COCH (coagulation factor C homology) gene. In this study, we investigated a Chinese family segregating autosomal dominant nonsyndromic sensorineural hearing loss. We identified a missense mutation c.T275A p.V92D in the LCCL domain of COCH cosegregating with the disease and absent in 100 normal hearing controls. This mutation leads to substitution of the hydrophobic valine to an acidic amino acid aspartic acid. Our data enriched the mutation spectrum of DFNA9 and implied the importance for mutation screening of COCH in age related hearing loss with vestibular dysfunctions

Introducing Ratiometric Fluorescence to MnO₂ Nanosheet-Based Biosensing: A Simple, Label-Free Ratiometric Fluorescent Sensor Programmed by Cascade Logic Circuit for Ultrasensitive GSH Detection

Glutathione (GSH) plays crucial roles in various biological functions, the level alterations of which have been linked to varieties of diseases. Herein, we for the first time expanded the application of oxidase-like property of MnO₂ nanosheet (MnO₂ NS) to fluorescent substrates of peroxidase. Different from previously reported fluorescent quenching phenomena, we found that MnO₂ NS could not only largely quench the fluorescence of highly fluorescent Scopoletin (SC) but also surprisingly enhance that of nonfluorescent Amplex Red (AR) via oxidation reaction. If MnO₂ NS is premixed with GSH, it will be reduced to Mn²⁺ and lose the oxidase-like property, accompanied by subsequent increase in SC’s fluorescence and decrease in AR’s. On the basis of the above mechanism, we construct the first MnO₂ NS-based ratiometric fluorescent sensor for ultrasensitive and selective detection of GSH. Notably, this ratiometric sensor is programmed by the cascade logic circuit (an INHIBIT gate cascade with a 1 to 2 decoder). And a linear relationship between ratiometric fluorescent intensities of the two substrates and logarithmic values of GSH’s concentrations is obtained. The detection limit of GSH is as low as 6.7 nM, which is much lower than previous ratiometric fluorescent sensors, and the lowest MnO₂ NS-based fluorescent GSH sensor reported so far. Furthermore, this sensor is simple, label-free, and low-cost; it also presents excellent applicability in human serum samples

A Controlled Release Aptasensor Utilizing AIE-Active MOFs as High-Efficiency ECL Nanoprobe for the Sensitive Detection of Adenosine Triphosphate

Improving the sensitivity in electrochemiluminescence (ECL) detection systems necessitates the integration of robust ECL luminophores and efficient signal transduction. In this study, we report a novel ECL nanoprobe (Zr-MOF) that exhibits strong and stable emission by incorporating aggregation-induced emission ligands into Zr-based metal–organic frameworks (MOFs). Meanwhile, we designed a high-performance signal modulator through the implementation of a well-designed controlled release system with a self-on/off function. ZnS quantum dots (QDs) encapsulated within the cavities of aminated mesoporous silica nanoparticles (NH2–SiO2) serve as the ECL quenchers, while adenosine triphosphate (ATP) aptamers adsorbed on the surface of NH2–SiO2 through electrostatic interaction act as “gatekeepers.” Based on the target-triggered ECL resonance energy transfer between Zr-MOF and ZnS QDs, we establish a coreactant-free ECL aptasensor for the sensitive detection of ATP, achieving an impressive low detection limit of 0.033 nM. This study not only demonstrates the successful combination of ECL with controlled release strategies but also opens new avenues for developing highly efficient MOFs-based ECL systems

High-Sensitivity Electrochemiluminescence Probe with Molybdenum Carbides as Nanocarriers for α‑Fetoprotein Sensing

Suitably designed electrochemiluminescence (ECL) carrying group acting as high-efficiency solid-state probe has attracted a lot of attention. Herein, molybdenum carbides with the two-dimensional ultrathin nanosheet structure on the surface and excellent conductivity were successfully employed as the nanocarriers for the capture of ECL reagent of luminol-capped Au nanoparticles (luminol-AuNPs). Notably, the luminol-AuNPs in the hybrid (luminol-AuNPs@Mo₂C) exhibited enhanced ECL performance (∼6-fold) as compared to individual luminol-AuNPs because of the facilitated electron transfer process. Ultimately, the as-prepared ECL label was used to construct a label-free ECL immunosensor for the detection of α-fetoprotein (AFP). The immunosensor shows high selectivity and high sensitivity to AFP detection with a wide linear range of 0.1 pg·mL^–1 to 30 ng·mL^–1 and an extremely low detection limit of 0.03 pg·mL^–1 (<i>S</i>/<i>N</i> = 3). Moreover, the fabricated ECL immunosensor exhibit satisfied performance in the practical application. This novel sensing strategy not only broadens the application of molybdenum carbides but also provides a new efficient approach to detect various biomolecules

Self-Powered Bipolar Electrochromic Electrode Arrays for Direct Displaying Applications

Here we report a self-powered-bipolar-electrochromic-electrode (termed SP-BP-EC-E) array for the displaying applications including catalyst screening, catalytic activity measurement, and enzyme substrate quantification. By replacing the directional (or active) power source with the isotropic chemical energy to drive the bipolar electrochemical reaction, the driving background signal, bipolar electrode (BPE) background signal, uneven reporting signal and the influence of electrolysis which commonly appear in traditional bipolar systems are effectively eliminated from origin. Thus, the reporting signals from the SP-BP-EC-E arrays can be more direct and reliable to reflect the target nature. Such a SP-BP-EC-E platform exhibits a sensitive response toward the fast analysis of commercial Pt black catalyst, NiPdAu hollow nanospheres, glucose dehydrogenase, and glucose. To our knowledge, this test paper-like SP-BP-EC-E is the simplest platform for high-throughput screening to date, which offers a very convenient approach for nonprofessional people to access the complicated screening and fast analysis of the electrocatalysts and biocatalyst activity and quantification of enzymatic substrates

Stabilized, Superparamagnetic Functionalized Graphene/Fe₃O₄@Au Nanocomposites for a Magnetically-Controlled Solid-State Electrochemiluminescence Biosensing Application

Herein, a multifunctional nanoarchitecture has been developed by integrating the branched poly­(ethylenimine) functionalized graphene/iron oxide hybrids (BGNs/Fe₃O₄) and luminol capped gold nanoparticles (luminol-AuNPs). The luminescent luminol-AuNPs as an electrochemiluminescence marker can be assembled on the nanocarrier of BGNs/Fe₃O₄ hybrids efficiently via the Au–N chemical bonds and electrostatic adsorption. Meanwhile, the multifunctional nanoarchitecture has been proved with excellent electron transfer, good stability, high emission intensity, etc. Furthermore, we successfully developed an ultrasensitive magnetically-controlled solid-state electrochemiluminescence (ECL) platform for label-free determination of HeLa cells using this multifunctional nanocomposite. Excellent performance of the magnetically-controlled ECL biosensing platform has been achieved including a high sensitivity for HeLa cells with a linear range from 20 to 1 × 10⁴ cells/mL, good stability, and reproducibility

Fine-Tuning Pyridinic Nitrogen in Nitrogen-Doped Porous Carbon Nanostructures for Boosted Peroxidase-Like Activity and Sensitive Biosensing

Carbon materials have been widely used as nanozymes in bioapplications, attributing to their intrinsic enzyme-like activities. Nitrogen (N)-doping has been explored as a promising way to improve the activity of carbon material-based nanozymes (CMNs). However, hindered by the intricate N dopants, the real active site of N-doped CMNs (N-CMNs) has been rarely investigated, which subsequently retards the further progress of high-performance N-CMNs. Here, a series of porous N-CMNs with well-controlled N dopants were synthesized, of which the intrinsic peroxidase (POD)like activity has a positive correlation with the pyridinic N content. Density functional theory calculations also reveal that pyridinic N boosts the intrinsic POD-like activity of N-CMNs. Pyridinic-N dopant can effectively promote the first H2O desorption process in comparison with the graphitic and pyrrolic N, which is the key endothermic reaction during the catalytic process. Then, utilizing the optimized nanozymes with high pyridinic N content (NP-CMNs) and superior POD-like activity, a facile total antioxidant capacity (TAC) assay was developed, holding great promise in the quality assessment of medicine tablets and antioxidant food for healthcare and healthy diet