Investigation of Antimicrobial Effects of Polydopamine-Based Composite Coatings.

Herein, polydopamine (PDA)-based antimicrobial coatings loaded with silver nanoparticles (Ag NPs) and gentamicin were designed and prepared on glass slides using two different approaches. To our knowledge, this study was performed for the first time with the aim to compare these methods (viz., in situ loading and physical adsorption method) regarding the loading and release behavior of payloads. In one method, gentamicin was in situ loaded on PDA-coated substrates during PDA polymerization followed by Ag NPs immobilization (named as Ag@Gen/PDA); for the second method, Ag NPs and gentamicin were simultaneously loaded onto PDA via physical adsorption by immersing pre-formed PDA coatings into a mixed solution of Ag NPs and gentamicin (named as Ag/Gen@PDA). The loading and release characteristics of these antimicrobial coatings were compared, and both gave variable outcomes. The in situ loading method consequently provided a relatively slow release of loaded antimicrobials, i.e., approx. 46% for Ag@Gen/PDA as compared to 92% from physically adsorbed Ag/GenPDA in an immersion period of 30 days. A similar trend was observed for gentamicin release, i.e., ~0.006 µg/mL from Ag@Gen/PDA and 0.02 µg/mL from Ag/Gen@PDA each day. The slower antimicrobial release from Ag@Gen/PDA coatings would ultimately provide an effective long-term antimicrobial property as compared to Ag/Gen@PDA. Finally, the synergistic antimicrobial activities of these composite coatings were assessed against two microbial species, namely, Staphylococcus aureus and Escherichia coli, hence providing evidence in the prevention of bacterial colonization.

Multifunctional Fe3O4 Nanoparticles Filled Polydopamine Hollow Rods for Antibacterial Biofilm Treatment.

This work reports the use of mesoporous silica rods as templates for the step-wise preparation of multifunctional Fe3O4 NPs filled polydopamine hollow rods (Fe3O4@PDA HR). The capacity of as-synthesized Fe3O4@PDA HR as a new drug carrier platform was assessed by its loading and the triggered release of fosfomycin under various stimulations. It was found that the release of fosfomycin was pH dependent with ~89% of fosfomycin being released in pH 5 after 24 h, which was 2-fold higher than that in pH 7. The magnetic properties of Fe3O4 NPs and the photothermal properties of PDA enabled the triggered release of fosfomycin upon the exposure to rotational magnetic field, or NIR laser irradiation. Additionally, the capability of using multifunctional Fe3O4@PDA HR to eliminate preformed bacterial biofilm was demonstrated. Upon exposure to the rotational magnetic field, the biomass of a preformed biofilm was significantly reduced by 65.3% after a 20 min treatment with Fe3O4@PDA HR. Again, due to the excellent photothermal properties of PDA, a dramatic biomass decline (72.5%) was achieved after 10 min of laser exposure. This study offers an alternative approach of using drug carrier platform as a physical mean to kill pathogenic bacteria along with its traditional use for drug delivery.

Switchable C2/C3 positional selectivity of thioisatins in a three-component domino reaction: combined computational and experimental studies.

The nucleophile-induced domino reaction is a featured reactivity mode of thioisatin, but the C2/C3 positional selectivity towards a nucleophile has not been understood in-depth. In this work, a domino reaction of thioisatin with bromoacetophenone and tryptamine hydrochloride to produce a benzothiophene-fused eight-membered N-heterocycle was described, showing that the Brønsted acid-base form of the amine partner was crucial for the selectivity, because using tryptamine instead of tryptamine hydrochloride gave a different product. Control experiments and density functional calculations revealed that the domino reaction using tryptamine or tryptamine hydrochloride was triggered by a condensation reaction at the C2 or C3 position of thioisatin, respectively. A delicate balance between local electrophilicity and polarization effect may be responsible for the observed selectivity.

Divergent Construction of Benzothiophene-Fused N-Heterocycles via Stereotunable Three-Component Domino Reactions.

A stereotunable three-component domino strategy among thioisatin, 2-bromo-1-phenylethan-1-one, and cyclohexane-1,2-diamine under catalyst-free conditions was disclosed. A wide range of benzothiophene-fused polycycles and eight-membered N-heterocycles were synthesized by regulating the stereoconfiguration of cyclohexane-1,2-diamines. The detailed mechanism and the origin of the chemoselectivity were explored by density functional calculations. Analysis of the geometrical structures of key transition states revealed that the existence of favorable intramolecular attractions, and the steric effect governed the chemoselectivity observed.

Fe3O4@polydopamine and Exo III-assisted homogeneous biorecognition reaction for convenient and ultrasensitive detection of kanamycin antibiotic.

Herein, we report a Fe3O4@polydopamine (PDA) nanocomposite and exonuclease III (Exo III)-assisted homogeneous fluorescence biosensing method for ultrasensitive detection of kanamycin (Kana) antibiotic. A hairpin DNA containing the Kana-aptamer sequence (HP) was first designed for the highly specific biorecognition of the target analyte. Because of the aptamer biorecognition-induced structural change of HP and the highly effective catalyzed reaction of Exo III, a large amount of fluorophore labels were released from the designed fluorescence DNA probe. During the homogeneous reaction process, the Exo III-assisted dual recycling significantly amplified the fluorescence signal output. Moreover, the excessive probes were easily adsorbed and separated by the Fe3O4@PDA nanocomposite, which decreased the background signal and increased the signal-to-noise ratio. These strategies result in the excellent analytical performance of the method, including a very low detection limit of 0.023 pg mL-1 and a very wide linear range of six orders of magnitude. In addition, this method has convenient operation, excellent selectivity, repeatability and satisfactory reliability, and does not involve the design and utilization of complicated DNA sequences. Thus, it exhibits a promising prospect for practical applications.

Catalyst-controlled switchable [4 + 1], [4 + 3] and [3 + 2] domino reactions of azadienes and MBH carbonates: diverse synthesis of benzothiophene fused derivatives.

Catalyst-controlled switchable domino reactions between azadienes bearing a benzothiophene moiety and isatin-derived MBH carbonates were developed. The [4 + 1] annulation was triggered in the presence of DABCO, giving a variety of benzothiophene fused pyrrole derivatives, while the [4 + 3] annulation occurred when changing the catalyst to DMAP. Furthermore, the [3 + 2] annulation mode was observed with the use of catalytic Ph2PMe. Additionally, the synthetic utility of these domino reactions was demonstrated by gram-scale experiments and simple transformations of the products. To the best of our knowledge, catalyst-controlled synthesis of benzothiophene fused or spiro derivatives has rarely been reported.

Stereoselective [4 + 3] annulation of azadienes and ethyl 4-bromo-3-oxobutanoate: construction of benzindeno-fused azepine derivatives.

The benzindenoazepine ring system is an attractive scaffold for biologically active compounds. This work reported a NaH-promoted cycloaddition between azadienes and ethyl 4-bromo-3-oxobutanoate, which delivered a series of benzindenoazepines with good yields and stereoselectivities. Such benzindenoazepine derivatives were not easily obtained by using a traditional approach. The application of this cycloaddition strategy has been extended to azadienes bearing a benzofuran or benzothiophene moiety. The utility of this method was showcased by gram-scale experiments and synthetic transformations of the product.

Intertwined Carbon Nanotubes and Ag Nanowires Constructed by Simple Solution Blending as Sensitive and Stable Chloramphenicol Sensors.

Chloramphenicol (CAP) is a harmful compound associated with human hematopathy and neuritis, which was widely used as a broad-spectrum antibacterial agent in agriculture and aquaculture. Therefore, it is significant to detect CAP in aquatic environments. In this work, carbon nanotubes/silver nanowires (CNTs/AgNWs) composite electrodes were fabricated as the CAP sensor. Distinguished from in situ growing or chemical bonding noble metal nanomaterials on carbon, this CNTs/AgNWs composite was formed by simple solution blending. It was demonstrated that CNTs and AgNWs both contributed to the redox reaction of CAP in dynamics, and AgNWs was beneficial in thermodynamics as well. The proposed electrochemical sensor displayed a low detection limit of up to 0.08 µM and broad linear range of 0.1-100 µM for CAP. In addition, the CNTs/AgNWs electrodes exhibited good performance characteristics of repeatability and reproducibility, and proved suitable for CAP analysis in real water samples.

Proximity Binding-Triggered Assembly of Two MNAzymes for Catalyzed Release of G-Quadruplex DNAzymes and an Ultrasensitive Homogeneous Bioassay of Platelet-Derived Growth Factor.

When the target biorecognition-triggered assembly of two Mg2+-dependent DNAzymes (MNAzymes) is employed for dually catalytic release of peroxidase-mimicking G-quadruplex DNAzymes (G-DNAzymes), this work develops a novel homogeneous colorimetric method for an ultrasensitive bioassay of platelet-derived growth factor-BB (PDGF-BB). The first MNAzyme assembly is realized through a highly specific aptamer biorecognition-driven proximity ligation reaction. Its catalytic cleavage toward the two designed hairpin substrates not only releases a large amount of G-DNAzymes for colorimetric signal transduction but also enables the spontaneous assembly of another MNAzyme for signal amplification. This leads to the successful detection of PDGF-BB in a wide linear range from 2.0 pg mL-1 to 20 ng mL-1 with a very low detection down to 0.088 pg mL-1. As the whole reactions including aptamer biorecognitions, DNA hybridizations, and catalytic cleavages of MNAzymes are conducted in a homogeneous solution, this method has very simple manipulations and also has high repeatability. In addition, the high specificity of the aptamer biorecognition-triggered signal transduction decides the excellent selectivity of the method. This bioassay does not require an expensive instrument and nucleic acid labeling for signal readout or any nanomaterial, enzyme, or nuclease for signal amplification. Thus, it displays an extensive potential for clinical diagnostic applications.

Construction of [6-5-5-6-6] Pentacyclic Skeleton via a Phosphine-Catalyzed Domino Reaction and Mechanism Study.

A novel phosphine-promoted domino reaction between thioaurone or aurone derivatives and MBH carbonate is described. A wide range of [6-5-5-6-6] pentacyclic compounds was prepared efficiently. Interestingly, the stereoselectivity was affected by the sulfur or oxygen atom in the substrates. Moreover, the reaction mechanism was explored by density functional calculations, which identified the 1,4-hydrogen-shift step to be the selectivity-determining step.

Construction of Benzothiophene or Benzothiopheno[2,3-e]azepinedione Derivatives via Three-Component Domino or One-Pot Sequences.

An efficient three-component domino or one-pot strategy has been developed for the synthesis of medicinally important benzothiophene and benzothiopheno[2,3-e]azepinedione derivatives for the first time. Amine-promoted selective cleavage of C-S bond of thioisatin is the key step in this process. The reported methodology benefits from environmentally friendly solvent (H2O), wide substrate scope, good functional group tolerance, and high reaction yields.

Enzymatic deposition of gold nanoparticles at vertically aligned carbon nanotubes for electrochemical stripping analysis and ultrasensitive immunosensing of carcinoembryonic antigen.

Herein we combine the sandwich immunoreaction at a vertically aligned single-walled carbon nanotube (SWCNT)-based immunosensor and the enzymatically catalytic deposition of gold nanoparticles (Au NPs) by a gold nanoprobe to develop a novel electrochemical immunosensing method. The vertically arranged nanostructure was prepared through the covalent linking of terminally carboxylated SWCNTs at an aryldiazonium-modified electrode. It not only provides an excellent platform for the high density immobilization of antibodies to obtain the immunosensor but also serves as useful molecular wires to accelerate electron transfer during the electrochemical immunosensing process. Meanwhile, the enzymatic reaction of the nanoprobe prepared by surface functionalization of the nanocarrier of Au NPs by high-content glucoamylases can catalyze the deposition of a large number of Au NPs at the immunosensor. The electrochemical stripping analysis of these nanoparticles enabled the convenient signal transduction of the method. Due to the sensitive gold stripping analysis at the vertically aligned SWCNTs and the multi-enzyme signal amplification of the nanoprobe, the electrochemical signal response was greatly enhanced. Thus, the method can be used for the ultrasensitive detection of the tumor biomarker of carcinoembryonic antigen in a wide linear range of 5 orders of magnitude with a low detection limit of 0.48 pg mL-1. Considering its obvious performance superiorities, this immunosensing method exhibits an extensive prospect for practical applications.

Risk factors of pharyngocutaneous fistula after total laryngectomy: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to systematically evaluate the risk factors of pharyngocutaneous fistula (PCF) after total laryngectomy. METHODS: We systematically searched Pubmed, Web of Science, Cochrane Library, and Embase databases and included the literature according to the inclusion and exclusion criteria. RESULTS: A total of 52 studies with 8605 patients were included in the meta-analysis. The total incidence of PCF was 21% (1808/8605). Meta-analysis results indicated that age (OR = 1.29, 95% CI 1.06-1.58, P = 0.01), smoking (OR = 1.62, 95% CI 1.27-2.07, P < 0.01), COPD (chronic obstructive pulmonary disease) (OR = 1.62, 95% CI 1.19-2.22, P < 0.01), CAD (coronary atherosclerotic heart disease) (OR = 1.82, 95% CI 1.36-2.45, P < 0.01), T-stage (OR = 0.81, 95% CI 0.67-0.98, P = 0.03), previous radiotherapy (OR = 2.41, 95% CI 2.00-2.90, P < 0.01), preoperative albumin (OR = 2.95, 95% CI 1.47-5.91, P < 0.01), preoperative hemoglobin (OR = 1.97, 95% CI 1.28-3.03, P < 0.01), tumor site (OR = 0.28, 95% CI 0.22-0.36, P < 0.01), and treatment method (OR = 1.85, 95% CI 1.44-2.38, P < 0.01) were risk factors associated with PCF. CONCLUSIONS: In our study, age, smoking, COPD, CAD, T-stage, previous radiotherapy, preoperative albumin, preoperative hemoglobin, tumor site, and treatment method were risk factors of PCF.

An epidemiological survey of laryngopharyngeal reflux disease at the otorhinolaryngology-head and neck surgery clinics in China.

PURPOSE: Using the Reflux Symptom Index (RSI), this nationwide study aimed to investigate the incidence, diagnostic status, risk factors, and common symptoms of adult laryngopharyngeal reflux disease (LPRD) at otorhinolaryngology-head and neck surgery (OHNS) clinics in China. METHODS: This multicenter cross-sectional survey began at the different institutions ranged from July to October 2017, and the duration was 12 months. A total of 90,440 eligible patients were finally enrolled from 72 medical institutions in China. All these patients completed the questionnaire based on RSI. In this study, LPRD was defined as RSI > 13. RESULTS: There were 9182 with LPRD among the 90,440 eligible participants (10.15%). However, only 1294 had a history of LPRD diagnosis among those with LPRD (14.09%). There were regional differences in the frequency of LPRD (P < 0.001). The proportions of patients with LPRD in males (vs. females), middle- and old-aged patients (vs. young), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking) were significantly higher (all P < 0.001). Middle and old age, current smoking, and drinking history were independent predictors of LPRD (all P < 0.001, OR 1.240, 1.261, and 1.481, respectively). "Sensations of something stuck in throat or a lump in throat", "clearing throat", and "excess throat mucus or postnasal drip" were the most frequent clinical symptoms in patients with LPRD. CONCLUSIONS: LPRD has a high incidence at the OHNS clinics in China. However, the diagnostic status of this disease is not optimistic. Older age, smoking, and drinking history were risk factors for LPRD.

Dually enhanced homogenous synthesis of molybdophosphate by hybridization chain reaction and enzyme nanotags for the electrochemical bioassay of carcinoembryonic antigen.

A magnetic bead (MB)-based sandwich biorecognition reactions is combined with a gold nanoprobe-induced homogenous synthesis of molybdophosphate to develop a novel bioassay method for the electrochemical detection of the tumor biomarker of carcinoembryonic antigen (CEA). The nanoprobe is prepared through the specific loading of numerous alkaline phosphatase (ALP)-functionalized gold nanoparticles (Au NPs) on a double-stranded DNA (dsDNA) produced by the CEA aptamer-triggered hybridization chain reaction (HCR). Both the large amounts of PO43- produced by the ALP catalytic hydrolysis of pyrophosphate and the phosphate backbones of dsDNA can react with the added MoO42- to generate electroactive molybdophosphates. So, the gold nanoprobe was used for signal tracing of the sandwich bioassay of CEA at a constructed antibody-functionalized MB platform. The sensitive electrochemical measurement of molybdophosphate produced from the quantitatively captured nanoprobes at a carbon nanotube-modified electrode (measured at about 0.12 V vs. Ag/AgCl, 3 M KCl) enabled the convenient signal transduction of the method. Due to the dually enhanced synthesis of molybdophosphate by the HCR and multi-enzyme Au NP nanotags, this method shows a wide linear range from 0.05 pg mL-1 to 10 ng mL-1 along with a low detection limit of 0.027 pg mL-1. In addition, the MB-based biorecognition reaction and the homogeneous synthesis of molybdophosphate are much convenient in manipulations. These excellent performances decide the extensive application potentials of the method. Graphical abstract A magnetic bead-based bioassay method was simply developed for the electrochemical detection of carcinoembryonic antigen. The dually enhanced homogenous synthesis of molybdophosphate by hybridization chain reaction (HCR) and enzyme nanotags and the sensitive electrochemical measurement of molybdophosphate at a carbon nanotube (CNT)-electrode enable ultrasensitive signal transduction of the method.

Polydopamine Nanosphere with In-Situ Loaded Gentamicin and Its Antimicrobial Activity.

The mussel inspired polydopamine has acquired great relevance in the field of nanomedicines, owing to its incredible physicochemical properties. Polydopamine nanoparticles (PDA NPs) due to their low cytotoxicity, high biocompatibility and ready biodegradation have already been widely investigated in various drug delivery, chemotherapeutic, and diagnostic applications. In addition, owing to its highly reactive nature, it possesses a very high capability for loading drugs and chemotherapeutics. Therefore, the loading efficiency of PDA NPs for an antibiotic i.e., gentamicin (G) has been investigated in this work. For this purpose, an in-situ polymerization method was studied to load the drug into PDA NPs using variable drug: monomer ratios. Scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) confirmed the successful loading of drug within PDA NPs, mainly via hydrogen bonding between the amine groups of gentamicin and the hydroxyl groups of PDA. The loading amount was quantified by liquid chromatography-mass spectrometry (LC-MS) and the highest percentage loading capacity was achieved for G-PDA prepared with drug to monomer ratio of 1:1. Moreover, the gentamicin loaded PDA NPs were tested in a preliminary antibacterial evaluation using the broth microdilution method against both Gram-(+) Staphylococcus aureus and Gram-(-) Pseudomonas aeruginosa microorganisms. The highest loaded G-PDA sample exhibited the lowest minimum inhibitory concentration and minimum bactericidal concentration values. The developed gentamicin loaded PDA is very promising for long term drug release and treating various microbial infections.

Synthesis of Benzothiophene-Fused Oxa[6.6.5]tricyclic Skeletons through a Cinchonidine- or NaOH-Promoted Quadruple Domino Sequence.

Two base-promoted quadruple domino reactions between thioaurones and allylic phosphonium salts have been developed to synthesize benzothiophene-fused oxa[6.6.5]tricyclic skeletons in moderate to good yields with excellent stereoselectivity and broad functional-group tolerance. This is a simple and useful protocol for the rapid construction of the umbrella-like oxa[6.6.5]tricyclic skeleton.

Hybridization chain reaction-enhanced enzyme biomineralization for ultrasensitive colorimetric biosensing of a protein biomarker.

By employment of an aptamer-initiated hybridization chain reaction (HCR) to enhance the enzyme biomineralization of cupric subcarbonate, this work develops a novel colorimetric biosensing method for protein analysis. The HCR product was used to specifically attach a large amount of urease-functionalized gold nanoparticles (Au NPs) for the preparation of a gold nanoprobe. After the sandwich biorecognition reactions, this nanoprobe could be quantitatively captured onto the antibody-functionalized magnetic bead (MB) platform. Then, numerous copper ions would be enriched onto the MB surface through the urease-induced biomineralization of cupric subcarbonate. Based on the complete release of Cu2+ ions for the sensitive copper chromogenic reaction, convenient colorimetric signal transduction was thus achieved for the quantitative analysis of the target analyte of the carcinoembryonic antigen. The HCR product provides a large number of biotin sites for the attachment of Au NP nanotags. The biomineralization reaction of high-content urease loaded onto Au NPs leads to highly efficient Cu2+ enrichment for signal amplification. So this method features excellent performance including a very wide linear range and a low detection limit down to 0.071 pg mL-1. In addition, the satisfactory results of real sample experiments reveal that this method possesses huge potential for practical applications.

Application of Cu2+-based electron spin resonance spectroscopy in measurement of antioxidant capacity of fruits.

The antioxidant capacity of 22 kinds of fruits was measured by the developed electron spin resonance (ESR) method based on Cu2+ sensor. Cu2+ is reduced to Cu+ by the antioxidants in the fruits, and the remaining Cu2+ was determined by ESR and UV-Vis spectroscopy. Cu2+ can give an ESR signal whereas Cu+ cannot, and the loss of the ESR signal was used to quantify the antioxidant capacity of various fruits. The results were shown as vitamin C equivalent antioxidant capacity (VCEAC). The VCEAC values obtained by ESR and UV-Vis methods ranged from 24.23 to 688.61 mg/100 g and from 24.12 to 677.79 mg/100 g, respectively. Cupric ion reducing antioxidant capacity (CUPRAC) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) methods were employed for comparison. Based on Pearson's correlation test, the results obtained by CUPRAC and DPPH methods were both significantly correlated with these obtained by the present method, which indicated that the novel method was reliable. Total phenolic content for all kinds of fruits was measured with the Folin-Ciocalteu reagent, and VCEAC values obtained by the ESR method were significantly correlated with total phenolic contents. Graphical abstract.

Correction to: A glassy carbon electrode modified with N-doped carbon dots for improved detection of hydrogen peroxide and paracetamol.

The authors of "A glassy carbon electrode modified with N-doped carbon dots for improved detection of hydrogen peroxide and paracetamol (Microchimica Acta 185, no. 2 (2018): 87)" wish to replace the incorrect images of Fig. 1C, 1D shown below.