In Situ Assembly of Nanomaterials and Molecules for the Signal Enhancement of Electrochemical Biosensors.

The physiochemical properties of nanomaterials have a close relationship with their status in solution. As a result of its better simplicity than that of pre-assembled aggregates, the in situ assembly of nanomaterials has been integrated into the design of electrochemical biosensors for the signal output and amplification. In this review, we highlight the significant progress in the in situ assembly of nanomaterials as the nanolabels for enhancing the performances of electrochemical biosensors. The works are discussed based on the difference in the interactions for the assembly of nanomaterials, including DNA hybridization, metal ion-ligand coordination, metal-thiol and boronate ester interactions, aptamer-target binding, electrostatic attraction, and streptavidin (SA)-biotin conjugate. We further expand the range of the assembly units from nanomaterials to small organic molecules and biomolecules, which endow the signal-amplified strategies with more potential applications.

Surface plasmon resonance biosensor for the detection of miRNAs by combining the advantages of homogeneous reaction and heterogeneous detection.

The hybridization and enzymolysis reactions for nucleic acid detection were carried out on the chip surface in the traditional surface plasmon resonance (SPR) biosensors. Herein, we proposed an innovative method for microRNA (miRNA) detection in which the hybridization-enzymolysis recycling reactions were performed in solution. Duplex-specific nuclease (DSN) and streptavidin-modified gold nanoparticles (SA-AuNPs) were employed for enhancing the assay sensitivity. In the absence of miRNA, the biotinylated DNA probe (bio-DNA-bio, biotin tags at both the 3' and 5' termini of DNA) was attached to the SA-modified chip through the SA-biotin binding, allowing the capture of SA-AuNPs with the same interaction. As a result, a larger SPR signal was attained. However, in the presence of miRNA, bio-DNA-bio hybridized with miRNA was digested by DSN. In this process, the miRNA strand remained intact and participated in the next hybridization-enzymolysis recycling process. Thus, one miRNA could promote the hydrolysis of many bio-DNA-bio probes and allow the generation of numerous bio-DNA fragments. Meanwhile, the produced bio-DNA competed with the undigested bio-DNA-bio to bind SA on the chip surface. The digestion of bio-DNA-bio and the competitive binding between bio-DNA-bio and bio-DNA led to the attachment of fewer SA-AuNPs and then smaller SPR signals. The change in SPR signal at the concentration as low as 1 fM miRNA has been readily determined. The strategy possessed the advantageous properties of simple operation, fast response, high sensitivity and excellent specificity, serving as a viable means for the fabrication of novel sensing platforms.

Nanomaterials for Modulating the Aggregation of ß-Amyloid Peptides.

The aberrant aggregation of amyloid-ß (Aß) peptides in the brain has been recognized as the major hallmark of Alzheimer's disease (AD). Thus, the inhibition and dissociation of Aß aggregation are believed to be effective therapeutic strategiesforthe prevention and treatment of AD. When integrated with traditional agents and biomolecules, nanomaterials can overcome their intrinsic shortcomings and boost their efficiency via synergistic effects. This article provides an overview of recent efforts to utilize nanomaterials with superior properties to propose effective platforms for AD treatment. The underlying mechanismsthat are involved in modulating Aß aggregation are discussed. The summary of nanomaterials-based modulation of Aß aggregation may help researchers to understand the critical roles in therapeutic agents and provide new insight into the exploration of more promising anti-amyloid agents and tactics in AD theranostics.

A copper complex formed with neurokinin B: binding stoichiometry, redox properties, self-assembly and cytotoxicity.

The tachykinin neuropeptide of neurokinin B (NKB) is a copper-binding amyloid peptide with important roles in the regulation of physiological functions and pathophysiological processes in the central and peripheral nervous systems. In this work, the formation of a NKB-Cu2+ complex in a 1 : 1 stoichiometry was confirmed by mass spectrometry. The self-assembly of NKB and its mutant species was investigated by Thioflavin T (ThT) fluorescence assay and atomic force microscopy (AFM), and at the same time, the effect of Cu2+ on the aggregation of NKB was studied. As evidenced by cyclic voltammetry, the redox potential of NKB-Cu2+ was determined to be 0.77 V (vs. Ag/AgCl). It has been demonstrated that NKB at low concentrations exerts its neuroprotective function by inhibiting Cu2+-mediated reactive oxygen species (ROS) production in the presence of ascorbic acid (AA). In comparison with equivalent Cu2+, the peptide-Cu2+ aggregates aggravated the viability of PC-12 cells more seriously in the absence of AA. These results should be extremely valuable for understanding the NKB/Cu2+ interactions and the toxicity mechanism of Cu2+ associated with neurodegenerative diseases.

Modification-free amperometric biosensor for the detection of wild-type p53 protein based on the in situ formation of silver nanoparticle networks for signal amplification.

Sensitive and accurate quantification of wild-type p53 protein is of great importance for biological research and clinical diagnosis. Herein, a modification-free amperometric biosensor was proposed for sensitive detection of wild-type p53 protein by the signal amplification of silver nanoparticles (AgNPs) networks formed in situ on electrode surface. Double-stranded DNA (dsDNA) probe containing two consensus sites was immobilized on gold electrode surface to capture wild-type p53 protein. The cysteine thiol and amine groups on the exterior of the protein allowed for the attachment of bare AgNPs through the AgS or AgN interactions. Meanwhile, benzene-1,4-dithiol (BDT) molecules in solution triggered the assembly of more AgNPs on electrode surface through the AgS interactions, thus leading to the in situ formation of AgNPs networks for signal amplification. The target at the concentration as low as 0.1 pM can be readily determined. This method was further applied to determine wild-type p53 protein in spiked human serum and cell lysates with satisfactory results. Moreover, the biosensor is regenerative and does not require the modification of AgNPs with recognition element for signal readout. The modification-free strategy can potentially be applied to develop novel biosensors for detection of other biological macromolecules.

A porous carbon nitride modified with cobalt phosphide as an efficient visible-light harvesting nanocomposite for photoelectrochemical enzymatic sensing of glucose.

A porous carbon nitride (PCN) modified with cobalt phosphides (CoP) was synthesized. In this nanocomposite, the CoP (in different weight fractions) serves (a) as the electron acceptor to accelerate the photoinduced charge separation, and (b) as the photosensitizer to increase the photoelectrochemical (PEC) response to visible light. Dissolved oxygen acts as the electron acceptor to generate PEC current. If glucose oxidase (GOx) catalyzes the oxidation of glucose, dissolved oxygen is consumed. This leads to the suppression of photocurrent. The photocathode biosensor has a linear response in the 0.05 to 0.7 mM glucose concentration range and a 1.1 µM limit of detection. Graphical abstractSchematic of a photoelectrochemical glucose biosensor based on the use of cobalt phosphide-modified porous carbon nitrides. PCN: porous carbon nitride; CoP: cobalt phosphide.

Sensitive Hg2+ Sensing via Quenching the Fluorescence of the Complex between Polythymine and 5,10,15,20-tetrakis(N-methyl-4-pyridyl) Porphyrin (TMPyP).

The interaction between polythymine (dTn) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl) porphyrin (TMPyP) was systematically studied using various techniques. dTn remarkably enhanced the fluorescence intensity of TMPyP as compared to other oligonucleotides. The enhanced fluorescence intensity and the shift of the emission peaks were ascribed to the formation of a π-π complex between TMPyP and dTn. And the quenching of the dTn-enhanced fluorescence by Hg2+ through a synergistic effect occurs due to the heavy atom effect. The binding of Hg2+ to TMPyP plays an important role in the Hg-TMPyP-dT30 ternary complex formation. A TMPyP-dT30-based Hg2+ sensor was developed with a dynamic range of Hg2+ from 5 nM to 100 nM. The detection limit of 1.3 nM was low enough for Hg2+ determination. The sensor also exhibited good selectivity against other metal ions. Experiments for tap water and river water demonstrated that the detection method was applicable for Hg2+ determination in real samples. The Hg2+ sensor based on oligonucleotide dT30-enhanced TMPyP fluorescence was fast and low-cost, presenting a promising platform for practical Hg2+ determination.

Triple Stimuli-Responsive Magnetic Hollow Porous Carbon-Based Nanodrug Delivery System for Magnetic Resonance Imaging-Guided Synergistic Photothermal/Chemotherapy of Cancer.

The premature leakage of anticancer drugs during blood circulation may the damage immune system, normal cells, and tissues. Constructing targeted nanocarriers with pH, glutathione, and NIR triple-responsive property can effectively avoid the leakage of anticancer drugs before they arrive at the targeted site. In this paper, magnetic hollow porous carbon nanoparticles (MHPCNs) were successfully fabricated as nanocarrier. Poly(γ-glutamic acid) was used to cap the pores of MHPCNs. The photothermal conversion property of carbon and iron oxide (Fe3O4) nanomaterials was utilized to perform photothermal therapy to overcome multidrug-resistance produced by chemotherapy. The biodistribution of nanoparticles was investigated by magnetic resonance imaging. Experiments in vivo confirm the efficient accumulations of nanoparticles at tumor sites. Meanwhile, tumor growth was effectively inhibited via synergistic photothermal/chemotherapy with minimal side effects.

Value of free/total prostate-specific antigen (f/t PSA) ratios for prostate cancer detection in patients with total serum prostate-specific antigen between 4 and 10 ng/mL: A meta-analysis.

BACKGROUND: Prostate carcinoma is a common disease that occurs in men over 50 years old. Many studies have explored the effect of free/total prostate-specific antigen (f/t PSA) ratio in monitoring prostate cancer. We conducted a meta-analysis to identify the accuracy of the f/t PSA ratio in the diagnosis of prostate cancer in patients who have PSA levels of 4 to 10 ng/mL. METHODS: Databases searched included PubMed and OVID databases, from inception to March 2017, after a systematical review, sensitivity, specificity, and other measures of accuracy of the f/t PSA ratio in the diagnosis of prostate cancer were pooled. We used summary receiver operating characteristic curves to summarize overall test performance. RESULTS: Fifteen case-control studies from 14 articles were identified. The results indicated that the sensitivity of the f/t PSA ratio in the diagnosis of prostate cancer ranged from 0.5 to 0.94 (pooled sensitivity 0.70, 95% CI: 0.67-0.72), whereas its specificity ranged from 0.31 to 0.93 (pooled specificity 0.55, 95% CI: 0.57-0.60). The positive likelihood ratio was 1.85 (95% CI: 1.56-2.20), negative likelihood ratio was 0.42 (95% CI: 0.34-0.53), and diagnostic odds ratio was 4.81 (9.53% CI: 3.33-6.94). CONCLUSIONS: The f/t PSA ratio determination has a low sensitivity and specificity for the diagnosis of prostate cancer; it would not be useful for the diagnosis of prostate cancer by itself. The results of f/t PSA ratio measurements should refer to the clinical manifestations and the results of conventional tests such as biopsies.

The value of 18F-FDG-PET/CT in the diagnosis of solitary pulmonary nodules: A meta-analysis.

BACKGROUND: Solitary pulmonary nodules (SPNs) are common imaging findings. Many studies have indicated that F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT) is an accurate test for distinguishing benign and malignant SPNs. The aim of this study was to investigate the value of F-FDG-PET/CT in the diagnosis of malignant SPNs. METHODS: We systematically searched the PubMed and Embase databases up to March 2017, and published data on sensitivity, specificity, and other measures of diagnostic accuracy of F-FDG-PET/CT in the diagnosis of malignant SPNs were meta-analyzed. Statistical analyses were undertaken using Meta-DiSc 1.4 software and Stata version 12.0. The measures of accuracy of F-FDG-PET/CT in the diagnosis of malignant SPNs were pooled using random-effects models. RESULTS: A total of 20 publications reporting 21 studies were identified. Pooled results indicated that F-FDG-PET/CT showed a diagnostic sensitivity of 0.89 (95% confidence interval [CI], 0.87-0.91) and a specificity of 0.70 (95% CI, 0.66-0.73). The positive likelihood ratio was 3.33 (95% CI, 2.35-4.71) and the negative likelihood ratio was 0.18 (95% CI, 0.13-0.25). The diagnostic odds ratio was 22.43 (95% CI, 12.55-40.07). CONCLUSIONS: F-FDG-PET/CT showed insufficient sensitivity and specificity for diagnosing malignant SPNs; it cannot replace the "gold standard" pathology by resection or percutaneous biopsy. Larger studies are required for further evaluation.

A study into the extracted ion number for NASICON structured Na3V2(PO4)3 in sodium-ion batteries.

Excellent C-rate and cycling performance with a high specific capacity of 117.6 mA h g(-1) have been achieved on NASICON-structure Na3V2(PO4)3 sodium-ion batteries. Two different Na sites, namely Na(1) and Na(2), are reported in the open three-dimensional framework, of which the ions at the Na(2) sites should be mainly responsible for the electrochemical properties. It is vitally important and interesting to find that there are two kinds of possible ion occupation of Na ions in Na3V2(PO4)3 and the investigation of ion-extraction number is firstly explored by discussing ion occupations with the help of first-principles calculations. The ion occupation of 0.75 for all Na sites is suitable for the configuration of [Na3V2(PO4)3]2, and the two-step extraction process accompanied by structure reorganization can account for the theoretical capacity of Na3V2(PO4)3.