Photocurrent Polarity Switchable Sensing of Hyaluronidase Activity by Regulating Electrostatic Interactions between Two Semiconductors.

Photocurrent polarity switchable photoelectrochemical (PEC) sensing has superior accuracy and anti-interference ability to conventional PEC sensing. The development of a novel strategy for photocurrent polarity switchable sensing is of great interest. Herein, a novel strategy for photocurrent polarity switchable sensing is reported by regulating electrostatic interactions between two semiconductor photoactive materials. Hyaluronic acid (HA)-modified CuO nanosheets show a negatively charged surface, which prevents the attachment of CuO nanosheets to negatively charged CdS nanodendrite-modified photoelectrodes because of the strong electrostatic repulsion. In the presence of hyaluronidase (HAase), the specific hydrolysis of HA on the surface of CuO by HAase can yield a positively charged surface, so CuO can be attached to a CdS-modified photoelectrode via electrostatic attraction, leading to photocurrent polarity switching. The photocurrent polarity switchable detection of HAase activity is achieved with an ultralow detection limit of 2 × 10-3 U mL-1 and a wide linear detection range between 0.01 and 100 U mL-1. This work provides a new and effective photocurrent polarity switching strategy for PEC sensing and a simple and efficient method for detecting HAase activity.

A Novel Signaling Strategy for an Ultrasensitive Photoelectrochemical Immunoassay Based on Electro-Fenton Degradation of Liposomes on a Photoelectrode.

A signaling strategy can directly determine the analytical performance and application scope of photoelectrochemical (PEC) immunoassays, so it is of great significance to develop an effective signaling strategy. The electro-Fenton reaction has been extensively used to degrade organic pollutants, but it has not been applied to PEC immunoassays. Herein, we report a novel signaling strategy for a PEC immunoassay based on electro-Fenton degradation of liposomes (Lip) on a photoelectrode. Lip vesicles are coated on Au@TiO2 core-shell photoactive material, which can prevent ascorbic acid (AA) from scavenging photogenerated holes. In the presence of a target, the immunomagnetic bead labels are converted to Fe3+ for electro-Fenton reaction, and hydroxyl radicals generated by the electro-Fenton reaction can degrade the Lip vesicles on the photoelectrode. Because of the degradation of Lip vesicles, photogenerated holes can be scavenged more effectively by AA, leading to an increase in photocurrent. Based on the electro-Fenton-regulated interface electron transfer, the sensitive "signal on" PEC immunoassay of a carcinoembryonic antigen is achieved, which features a dynamic range from 0.05 to 5 × 104 pg mL-1 and a detection limit of 0.01 pg mL-1. Our work provides a novel and efficient PEC immunoassay platform by introducing the electro-Fenton reaction into PEC analysis.

Au nanoclusters-decorated WO3 nanorods for ultrasensitive photoelectrochemical sensing of Hg2.

Photosensitizers and enzyme mimics are extensively used in photoelectrochemical (PEC) sensing, but few materials can be used as both photosensitizers and enzyme mimics in PEC sensing. Herein, we report Au nanoclusters (AuNCs) as both photosensitizers and peroxidase mimics for sensitive PEC sensing of Hg2+. It is found that AuNCs can act as photosensitizers to improve the PEC activity of WO3 nanorods; so the WO3/AuNCs composite material can be used as an advanced photosensitive material for PEC detection. AuNCs can also catalyze precipitate formation on the photoelectrode because of their peroxidase mimetic activity, and the interface electron transfer is hindered by the formed precipitate. Thus, the photocurrent of the WO3/AuNCs-based photoelectrode is quenched. When Hg2+ is present, the AuNCs-catalyzed precipitate formation is inhibited by Hg2+ because of the binding of Hg2+ to AuNCs through Hg2+-Au+ interactions. The photocurrent of the WO3/AuNCs-based photoelectrode increases accordingly, enabling "signal on" PEC detection of Hg2+. A broad linear range for Hg2+ detection is achieved between 1.0 pM and 50 nM with a detection limit of 0.2 pM. We have developed an advanced photosensitive material and introduced a simple method for PEC detection of Hg2+.

Tailoring the Photoelectrochemical Activity of Hexametaphosphate-Capped CdS Quantum Dots by Ca2+-Triggered Surface Charge Regulation: A New Signaling Strategy for Sensitive Immunoassay.

The development of efficient signaling strategies is highly important for photoelectrochemical (PEC) immunoassay. We report here a new and efficient strategy for sensitive PEC immunoassay by tailoring the electrostatic interaction between the photoactive material and the electron donor. The photoelectric conversion of hexametaphosphate (HMP)-capped CdS quantum dots (QDs) in Na2SO3 solution is significantly boosted after Ca2+ incubation. The negative surface charges on CdS@HMP QDs decrease because of the complexation reaction between HMP and Ca2+, and the electrostatic repulsion between CdS@HMP QDs and electron donor (SO32-) becomes weak accordingly, leading to an improved electron-hole separation efficiency. Inspired by the PEC response of CdS@HMP QDs to Ca2+, a novel "signal-on" PEC immunoassay platform is established by employing CaCO3 nanoparticles as labels. By regulating the surface charge of CdS@HMP QDs with in situ-generated Ca2+ from CaCO3 labels, sensitive detection of the carcinoembryonic antigen (CEA) is achieved. The linear detection range is 0.005-50 ng mL-1 and the detection limit is 1 pg mL-1 for CEA detection. Our work not only provides a facile route to tailor the photoelectric conversion but also lays the foundation for sensitive PEC immunoassay by simply regulating the surface charge of photoactive materials.

NiCoO2@CeO2 Nanoboxes for Ultrasensitive Electrochemical Immunosensing Based on the Oxygen Evolution Reaction in a Neutral Medium: Application for Interleukin-6 Detection.

The development of highly active electrocatalytic labels is important for constructing sensitive electrochemical immunosensors. Great progress has been made in developing non-noble-metal nanocatalysts toward the oxygen evolution reaction (OER) in the past decade, but non-noble-metal OER nanocatalysts have not been explored as electrocatalytic labels for immunosensing. Herein, we report NiCoO2@CeO2 nanoboxes (NBs) as novel electrocatalytic labels for ultrasensitive immunosensing based on the excellent OER activity of NiCoO2@CeO2 NBs in a neutral solution. The synthesis of NiCoO2@CeO2 NBs involves Ni2+ exchange and heat treatment of ZIF-67 nanocubes to produce NiCoO2 NBs, followed by the growth of CeO2 nanoparticles on the surface of NiCoO2 NBs. The NiCoO2@CeO2 NBs offer superior OER activity to NiCoO2 NBs because of the synergetic effect between NiCoO2 NBs and CeO2 nanoparticles. The formation of ester-like bridging between CeO2 and the carboxylic groups of antibody enables direct immobilization of the antibody on the NiCoO2@CeO2 surface. A sandwich-type electrochemical immunosensor using NiCoO2@CeO2 NBs as electrocatalytic labels features a broad linear range for interleukin-6 detection from 2.5 × 10-5 to 10 ng mL-1, with a low detection limit of 7 fg mL-1. Our work lays the foundation for developing electrochemical immunosensors and aptasensors based on non-noble-metal OER electrocatalysts.

Three-dimensional macroporous gold electrodes superior to conventional gold disk electrodes in the construction of an electrochemical immunobiosensor for Staphylococcus aureus detection.

Herein, a three-dimensional macroporous gold (3DMG) electrode is demonstrated to be a better choice than a conventional gold disk electrode in the construction of an electrochemical immunobiosensor for Staphylococcus aureus (S. aureus) detection. The 3DMG electrode was prepared on a gold disk electrode by one-step electrodeposition using hydrogen bubbles as dynamic templates. The 3DMG electrode has a high electrochemically active surface area with pore sizes ranging from 20 to 50 µm, and these unique features are conducive to the immobilization of primary antibodies and the capture of S. aureus. Secondary antibodies (Ab2) and alkaline phosphatase (ALP) were immobilized on mesoporous silica nanospheres (MSNs), and the resulting ALP-MSNs-Ab2 composites were utilized as signal tags to construct a sandwich-type electrochemical immunobiosensor. S. aureus was measured based on alkaline phosphatase-catalyzed silver deposition and differential pulse voltammetric detection. The linear range is from 5 to 109 CFU mL-1, and the detection limit is 2 CFU mL-1 for S. aureus detection. Due to the signal amplification of the 3DMG electrode, the sensitivity of the immunobiosensor constructed on the 3DMG electrode is 9 times that of an immunobiosensor constructed on a gold disc electrode. The proposed biosensor was successfully applied for detecting S. aureus in milk samples.

Sensitive photoelectrochemical immunoassay of Staphylococcus aureus based on one-pot electrodeposited ZnS/CdS heterojunction nanoparticles.

We report here a facile synthesis of ZnS/CdS heterojunction nanoparticles on an indium-tin oxide (ITO) electrode and their application in the ultrasensitive photoelectrochemical detection of Staphylococcus aureus (S. aureus). The ZnS/CdS/ITO electrode was prepared using one-pot electrodeposition in an acidic solution containing ZnCl2, CdCl2 and Na2S2O3. The optimal ZnS/CdS heterojunction nanoparticles with a Zn/Cd atomic ratio of 1 : 1 showed a high photoelectrochemical response to l-cysteine. l-Cysteine-encapsulated liposome (cysteine@liposome) immunonanocapsules were prepared and used as the labels for photoelectrochemical detection of S. aureus. By coupling cysteine@liposome immunonanocapsule labeling with immunomagnetic separation/enrichment and photoelectrochemical analysis using the ZnS/CdS/ITO electrode, sensitive photoelectrochemical detection of S. aureus was achieved. Under optimal conditions, the linear range for photoelectrochemical detection of S. aureus was from 1 to 4000 CFU mL-1. The proposed method was successfully used for photoelectrochemical detection of S. aureus in milk and juice samples.

Au nanocluster-embedded chitosan nanocapsules as labels for the ultrasensitive fluorescence immunoassay of Escherichia coli O157:H7.

Herein, Au nanocluster (AuNC)-embedded chitosan (CS) nanocapsules were prepared and used as a novel signal amplification system for the sensitive fluorescence immunoassay of Escherichia coli O157:H7 (E. coli O157:H7). AuNCs were embedded in CS to form AuNCs@CS nanocapsules, where a large number of AuNCs were embedded in each nanocapsule. A rapid, ultrasensitive, and selective method for the fluorescence detection of E. coli O157:H7 was developed by coupling the nanocapsule-amplification strategy with immunological recognition and magnetic separation. Compared with a conventional immunoassay using AuNCs as labels, the fluorescence signals of the proposed immunoassay were greatly amplified, because much more fluorescent AuNCs are linked to each bacterial cell. As a result, a linear range was obtained from 3 to 700 CFU mL-1, with a detection limit of 1 CFU mL-1. This method was successfully used to detect E. coli O157:H7 in drinking water and milk samples.

Facile Fabrication of Graphene-Containing Foam as a High-Performance Anode for Microbial Fuel Cells.

Facile fabrication of novel three-dimensional anode materials to increase the bacterial loading capacity and improve substrate transport in microbial fuel cells (MFCs) is of great interest and importance. Herein, a novel graphene-containing foam (GCF) was fabricated easily by freeze-drying and pyrolysis of a graphene oxide-agarose gel. Owing to the involvement of graphene and stainless-steel mesh in the GCF, the GCF shows high electrical conductivity, enabling the GCF to be a conductive electrode for MFC applications. With the aid of agarose, the GCF electrode possesses a supermacroporous structure with pore sizes ranging from 100-200 µm and a high surface area, which greatly increase the bacterial loading capacity. Cell viability measurements indicate that the GCF possesses excellent biocompatibility. The MFC, equipped with a 0.4 mm-thick GCF anode, shows a maximum area power density of 786 mW m(-2) , which is 4.1 times that of a MFC equipped with a commercial carbon cloth anode. The simple fabrication route in combination with the outstanding electrochemical performance of the GCF indicates a promising anode for MFC applications.

Three-dimensional activated graphene network-sulfonate-terminated polymer nanocomposite as a new electrode material for the sensitive determination of dopamine and heavy metal ions.

We report here that three-dimensional activated graphene networks (3DAGNs) are a better matrix to prepare graphene-polymer nanocomposites for sensitive electroanalysis than two-dimensional graphene nanosheets (2DGNs). 3DAGNs were synthesized in advance by the direct carbonization and simultaneous chemical activation of a cobalt ion-impregnated D113-type ion exchange resin, which showed an interconnected network structure and a large specific surface area. Then, the 3DAGN-sulfonate-terminated polymer (STP) nanocomposite was prepared via the in situ chemical co-polymerization of m-aminobenzene sulfonic acid and aniline in the presence of 3DAGNs. The 3DAGN-STP nanocomposite can adsorb dopamine (DA) and heavy metal ions, which was confirmed by quartz crystal microbalance studies. The 3DAGN-STP modified glassy carbon electrode (GCE) was used for the electrochemical detection of DA in the presence of ascorbic acid and uric acid, with a linear response range of 0.1-32 µM and a limit of detection of 10 nM. In addition, differential pulse voltammetry was used for the simultaneous determination of Cd(2+) and Pb(2+) at the 3DAGN-STP/GCE further modified with a bismuth film, exhibiting linear response ranges of 1-70 µg L(-1) for Cd(2+) and 1-80 µg L(-1) for Pb(2+) with limits of detection of 0.1 µg L(-1) for Cd(2+) and 0.2 µg L(-1) for Pb(2+). Because the 3DAGN-STP can integrate the advantages of 3DAGNs with STPs, the 3DAGN-STP/GCE was more sensitive than the bare GCE, 3DAGN/GCE, and 2DGN-STP/GCE for the determination of DA and heavy metal ions.

A sensitive immunosensing platform based on the high cathodic photoelectrochemical activity of Zr-MOF and dual-signal amplification of peroxidase-mimetic Fe-MOF.

Cathodic photoelectrochemical (PEC) analysis has received special concerns because of its outstanding anti-interference capability toward reductive substances in samples, so it is highly desirable to develop high-performance photocathodic materials for PEC analysis. Herein, a Zr-based metal-organic framework (Zr-MOF), MOF-525, is explored as a photoactive material in aqueous solution for the first time, which shows a narrow band-gap of 1.82 eV, excellent visible-light absorption, and high cathodic PEC activity. A sandwiched-type PEC immunosensor for detecting prostate-specific antigen (PSA) is fabricated by using MIL-101-NH2(Fe) label and MOF-525 photoactive material. MIL-101-NH2(Fe) as a typical Fe-MOF can serve as a peroxidase mimic to catalyze the production of precipitates on the photoelectrode. Both the produced precipitates and the MIL-101-NH2(Fe) labels can quench the photocathodic current, enabling "signal-off" immunosensing of PSA. The detection limit is 3 fg mL-1, and the linear range is between 10 fg mL-1 and 100 ng mL-1 for detecting PSA. The present study not only develops a high-performance Zr-MOF photoactive material for cathodic PEC analysis but also constructs a sensitive PEC immunosensing platform based on the dual-signal amplification of peroxidase-mimetic Fe-MOF.

Respiration and growth of Paracoccus denitrificans R-1 with nitrous oxide as an electron acceptor.

In the nitrogen biogeochemical cycle, the reduction of nitrous oxide (N2O) to N2 by N2O reductase, which is encoded by nosZ gene, is the only biological pathway for N2O consumption. In this study, we successfully isolated a strain of denitrifying Paracoccus denitrificans R-1 from sewage treatment plant sludge. This strain has strong N2O reduction capability, and the average N2O reduction rate was 5.10 ± 0.11 × 10-9 µmol·h-1·cell-1 under anaerobic condition in a defined medium. This reduction was accompanied by the stoichiometric consumption of acetate over time when N2O served as the sole electron acceptor and the reduction can yield energy to support microbial growth, suggesting that microbial N2O reduction is related to the energy generation process. Genomic analysis showed that the gene cluster encoding N2O reductase of P. denitrificans R-1 was composed of nosR, nosZ, nosD, nosF, nosY, nosL, and nosZ, which was identified as that in other strains in clade I. Respiratory inhibitors test indicated that the pathway of electron transport for N2O reduction was different from that of the traditional electron transport chain for aerobic respiration. Cu2+, silver nanoparticles, O2, and acidic conditions can strongly inhibit the reduction, whereas NO3- or NH4+ can promote it. These findings suggest that modular N2O reduction of P. denitrificans R-1 is linked to the electron transport and energy conservation, and dissimilatory N2O reduction is a form of microbial anaerobic respiration. IMPORTANCE: Nitrous oxide (N2O) is a potent greenhouse gas and contributor to ozone layer destruction, and atmospheric N2O has increased steadily over the past century due to human activities. The release of N2O from fixed N is almost entirely controlled by microbial N2O reductase activities. Here, we investigated the ability to obtain energy for the growth of Paracoccus denitrificans R-1 by coupling the oxidation of various electron donors to N2O reduction. The modular N2O reduction process of denitrifying microorganism not only can consume N2O produced by itself but also can consume the external N2O generated from biological or abiotic pathways under suitable condition, which should be critical for controlling the release of N2O from ecosystems into the atmosphere.

Tailoring enzymatic loading capacity on 3D macroporous gold by catalytic hairpin assembly and hybridization chain reaction: Application for ultrasensitive self-powered microRNA detection.

It is important to develop effective strategies to construct enzymatic biofuel cell based self-powered biosensors. We report here the facile regulation of enzymatic loading capacity on the bioanode by utilizing a concatenated catalytic hairpin assembly (CHA)/hybridization chain reaction (HCR) and its application for self-powered microRNA-141 (miRNA-141) detection. To construct the bioanode, a concatenated CHA/HCR process triggered by miRNA-141 was conducted on the three-dimensional macroporous gold (3DMG) electrode to generate long double-stranded DNA nanowires for glucose oxidase immobilization. Quartz crystal microbalance study reveals that the enzymatic loading capacity on the bioanode increases at an increasing miRNA-141 concentration, leading to enhanced catalytic performance for glucose oxidation. The short-circuit currents of the assembled glucose/O2 biofuel cells increase at increasing miRNA-141 concentrations, enabling ultrasensitive detection of miRNA-141. The self-powered biosensor features a wide dynamic range for detecting miRNA-141 from 10-17 to 10-11 M, with an ultralow detection limit of 1.3 aM. This work provides a highly sensitive self-powered biosensing platform for miRNA detection.

[Preparation of berberine-naringin dual drug-loaded composite microspheres and evaluation of their antibacterial-osteogenic properties].

Objective: To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects. Methods: The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively. Results: NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05). Conclusion: NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.

A glucose/O2 biofuel cell integrated with an exonuclease-powered DNA walker for self-powered sensing of microRNA.

With the aid of an exonuclease-powered DNA walker, the amount of glucose oxidase immobilized on the bioanode can be facilely tailored by varying the concentration of microRNA-141, so a glucose/O2 biofuel cell is employed as a self-powered sensor for sensitive and selective detection of microRNA-141.

Sensitive photoelectrochemical determination of T4 polynucleotide kinase using AuNPs/SnS2/ZnIn2S4 photoactive material and enzymatic reaction-induced DNA structure switch strategy.

We report here Au nanoparticles (AuNPs)/SnS2/ZnIn2S4 as a high-performance active material for sensitive photoelectrochemical (PEC) determination of T4 polynucleotide kinase (T4 PNK) using an enzymatic reaction-induced DNA structure switch strategy. To construct the PEC biosensor, a double-stranded DNA probe consisting of a CdS quantum dots (QDs)-labeled single-stranded DNA (sDNA) and its complementary DNA (cDNA) is immobilized on the AuNPs/SnS2/ZnIn2S4 photoactive material. T4 PNK can catalyze the phosphorylation of 5'-OH-terminated sDNA in the double-stranded DNA probe when ATP is present, and λ-exonuclease can catalyze the degradation of the phosphorylated sDNA into small fragments. Then the cDNA forms a hairpin structure so that CdS QDs and AuNPs are in close contact, which can induce exciton-plasma interactions between CdS QDs and AuNPs. The exciton-plasma interactions significantly boost the photocurrent, enabling the "signal on" PEC determination of T4 PNK in the range of 10-4 - 1 U mL-1 with a detection limit of 6 × 10-5 U mL-1. The PEC biosensor can also be used to screen enzyme inhibitors.

Controllable sensitization of Zr-MOFs by using CdS and its application for photoelectrochemical detection of alkaline phosphatase.

CdS quantum dots (QDs) are attached onto zirconium-based metal-organic frameworks (Zr-MOFs) with DNA as a bridge to boost the photoelectrochemical (PEC) activity of Zr-MOFs, and the sensitization of Zr-MOFs by using CdS QDs is regulated by the alkaline phosphatase (ALP)-catalyzed hydrolysis of tripolyphosphate, enabling sensitive "signal-on" PEC detection of ALP activity.

Novel database and cut-off value for bacterial amoA gene revealed a spatial variability pattern of the ammonia-oxidizing bacteria community from river to sea.

Ammonia-oxidizing bacteria (AOB) catalyze the first step of nitrification, oxidizing ammonia to nitrite, and are characterized by amoA gene encoding ammonia monooxygenase. To analyze the AOB community effectively, an integral taxonomy database containing 14,058 amoA sequences and the optimal cut-off value at 95 % for OTU clustering were determined. This method was evaluated to be efficient by the analysis of environmental samples from the river, estuary, and sea. Using this method, a significant spatial variance of the AOB community was found. The diversity of AOB was highest in the estuary and lowest in the ocean. Nitrosomonas were the predominant AOB in the sediments of the freshwater river and estuary. Nearly all the AOB-amoA sequences belonged to uncultured bacterium in the sediments of deep sea. In general, an integral AOB taxonomic database and a suitable cut-off value were constructed for the comprehensive exploration of the diversity of AOB from river to sea.

Comparison of diagnostic value of SWE, FNA and BRAF gene detection in ACR TI-RADS 4 and 5 thyroid nodules.

OBJECTIVES: To compare the diagnostic value of shear wave elastography (SWE), fine needle aspiration (FNA) and BRAF gene detection (BRAFV600E gene mutation detection) in ACR TI-RADS 4 and 5 thyroid nodules. METHODS: SWE images, FNA cytological results and BRAF detection results of ACR TI-RADS 4 and 5 thyroid nodules confirmed by pathology were analyzed retrospectively. The receiver operating characteristic (ROC) curve was drawn to determine the best cutoff value of SWE Emax. In the combined diagnosis of SWE, FNA and BRAF, firstly, the nodules with BRAF gene mutation were included in the positive ones, secondly, the nodules with benign and malignant FNA were included in the FNA + SWE or FNA + SWE + BRAF negative and positive ones respectively, finally, for FNA uncertain nodules: those whose SWE Emax were less than or equal to the cutoff value were included in FNA + SWE or FNA + SWE + BRAF negative ones, and those whose SWE Emax were greater than the cutoff value were included in positive ones. The diagnostic efficacy of SWE, FNA, SWE + FNA, FNA + BRAF and their combination in ACR TI-RADS 4 and 5 thyroid nodules were compared. RESULTS: The ROC curve showed that the best cutoff value of SWE Emax was 40.9 kpa, and the area under ROC curve (AUC) was 0.842 (0.800∼0.885). The sensitivity, specificity and accuracy of SWE were 76.3% (270/354), 75.5% (80/106) and 76.1% (350/460), respectively. The sensitivity, specificity and accuracy of FNA were 58.2% (206/354), 88.7% (94/106) and 65.2(300/460), respectively. The sensitivity, specificity and accuracy of FNA + BRAF were 95.5% (338/354), 88.7% (94/106) and 93.9% (432/460), respectively. The sensitivity, specificity and accuracy of SWE + FNA were 85.9% (304/354), 98.1% (104/106) and 88.7% (408/460), respectively. The sensitivity, specificity and accuracy of SWE + FNA + BRAF were 98.3% (348/354), 98.1% (104/106) and 98.3% (452/460), respectively. For the diagnostic accuracy, SWE + FNA + BRAF > FNA + BRAF > FNA + SWE > SWE > FNA, the difference was statistically significant (all P > 0.05). CONCLUSIONS: For ACR TI-RADS 4 and 5 thyroid nodules, SWE and FNA have high diagnostic efficiency. For the diagnostic accuracy, FNA + BRAF is better than FNA + SWE. FNA combination with BRAF gene detection further improves the diagnostic sensitivity and accuracy of FNA. The combined application of the three is the best.

MWCNTs-CoP hybrids for dual-signal electrochemical immunosensing of carcinoembryonic antigen based on overall water splitting.

Great efforts have been made to search for highly active catalysts toward electrochemical water splitting, but double-signal immunosensors have not been reported based on bifunctional water splitting electrocatalysts. We report here a dual-signal electrochemical immunosensor for detecting carcinoembryonic antigen (CEA) using multi-wall carbon nanotubes (MWCNTs)-cobalt phosphide (CoP) as an electrocatalytic label. The preparation of MWCNTs-CoP involves the growth of Co3O4 nanoparticles on MWCNTs and low-temperature phosphatization of Co3O4 nanoparticles. The MWCNTs-CoP catalyst shows excellent electrocatalytic activities in a neutral medium toward both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), enabling MWCNTs-CoP as the electrocatalytic label for sensitive immunosensing. The linear range of the sandwich-type immunosensor for detecting CEA based on the HER signal is from 10-4-100 ng mL-1, whereas a linear range for detecting CEA based on the OER signal is achieved from 10-4 to 10 ng mL-1. The detection limits for detecting CEA using HER and OER signals are 10 and 12 fg mL-1, respectively. This work can provide a new double-signal immunosensing platform based on a bifunctional water splitting electrocatalyst.