Evaluation of the Efficacy and Safety of Tenofovir Disoproxil Fumarate in Intercepting Mother-to-Child Transmission of Hepatitis B Virus.

Vertical transmission of hepatitis B virus (HBV), especially in Asia, is a key target in the global elimination of HBV. This study assessed the effects of tenofovir disoproxil fumarate (TDF) in pregnant women for mother-to-infant transmission of HBV. A total of 122 pregnant women at our hospital met the inclusion criteria for high HBV DNA viral loads. They were randomly divided into TDF-treatment (n=70) and placebo (n=52) groups. Maternal liver function and serum HBV DNA load were tested before and after treatment. Clinical and laboratory data of infants were assayed at delivery and 7-months post-partum visit and compared between the two groups. There was no difference in clinical characteristics of participants between the two groups. There were no significant differences in liver function markers, including alanine aminotransferase, total bilirubin, blood creatinine, and blood urea nitrogen levels before and after TDF treatment. The serum HBV DNA viral load of the TDF-treated group became significantly lower than those of the control group and their own pre-medication levels. Infants showed no significant difference in body growth, including weight, height, head size, and five-min Apgar score. At 7 months after birth, 94.29% of infants in the TDF group and 86.54% of control-group infants had protective HBsAb levels ≥ 10 mIU/ml (p>0.05). The HBV infection rate of infants in the TDF-treated group was lower than that in the non-treated group. In high-HBV-DNA-load pregnant women, TDF administered from 28 weeks gestational age to delivery was associated with a lower risk of mother-to-infant transmission of HBV.

Single-holed cobalt - nitrogen - carbon hollow structure with oxidase-mimicking activity for the chemiluminescence determination of ß - galactosidase activity.

A single-holed cobalt - nitrogen - carbon (Co - N - C) hollow structure nanozyme has been fabricated by in situ growth of zeolitic imidazolate framework (ZIF - 67) on the polystyrene (PS) sphere and following treatment by high-temperature carbonization. The Co - N - C nanostructure mimics the activity of oxidase and can activate O2 into reactive oxygen species (ROS), giving a remarkable enhancement on the chemiluminescence (CL) signal of luminol - O2 reaction. The Co - N - C oxidase mimic has further been exploited in the biosensing field by the determination of the activity of ß - galactosidase (ß - gal). The CL method for ß - gal activity has a linear range of 0.5 mU·L-1 to 5.0 U·L-1, a detection limit of 0.167 mU·L-1, and the precision of 3.1% (5.0 U·L-1, n = 11). This method has been employed to assess inhibitor screening of ß - gal and determine activity of ß - gal in spiked human serum samples.

Green-emission nitrogen-doped carbon quantum dots from alkaline N-methyl-2-pyrrolidinone for determination of ß-galactosidase and its inhibitors.

A new fluorescence method was established for sensitive detection of ß-galactosidase (ß-gal) activity in spiked human serum and screening of inhibitor. Nitrogen-doped carbon quantum dots (N-CQDs) were prepared by solvothermal polymerization of N-methyl-2-pyrrolidinone in an alkaline condition. The colloidal N-CQDs exhibit good water solubility, stability, and emit bright green fluorescence with a maximum emission peak at 528 nm upon excitation at 420 nm. ß-gal specifically catalyzes the decomposition of its substrate P-nitrophenyl-ß-D-galactopyranoside into 4-nitrophenol, whose absorption spectrum overlaps well with the excitation spectrum of the N-CQDs. As a result, the fluorescence of the N-CQDs is remarkably quenched by 4-nitrophenol via an inner filter effect. The sensing platform presents a linear response range for ß-gal activity from 0.05 to 3.0 U·L-1 with a low limit of detection of 0.023 U·L-1. An acceptable precision is obtained with a relative standard deviation (RSD) of 3.1% for 1.0 U·L-1 ß-gal (n = 11). The method was applied to determine ß-gal in spiked human serums with recoveries in the range  96.3-104.7%. The method was employed to evaluate inhibitor screening with D-galactal and chloroquine diphosphate as models.

Light-accelerating oxidase-mimicking activity of black phosphorus quantum dots for colorimetric detection of acetylcholinesterase activity and inhibitor screening.

A feasible and sensitive colorimetric platform was established for the assay of acetylcholinesterase (AChE) activity and evaluation of its inhibitor screening, based upon the light-accelerating oxidase-mimicking activity of black phosphorus quantum dots (BP QDs). The BP QDs were synthesized through a thermal exfoliation method and characterized using various techniques. The BP QDs exhibit oxidase-mimicking catalytic activity on dissolved oxygen-mediating oxidation of 3,3',5,5'-tetramethylbenzidine, a typical substrate of oxidase. This results in a transformation of 3,3',5,5'-tetramethylbenzidine into its blue oxidized product, which has a visible absorption peak at 652 nm. The exposure of 365 nm light irradiation significantly accelerates the oxidase-mimicking activity of the BP QDs and speeds up the reaction efficiency. AChE can specifically catalyze the decomposition of its substrate acetylthiocholine chloride to thiocholine. Thiocholine has reducing capacity and can thus reduce the oxidase-mimicking activity of the BP QDs. As a result, the oxidation of 3,3',5,5'-tetramethylbenzidine is hindered and the blue solution becomes paler. This gives a linear response for AChE ranging from 0.5 to 10.0 mU mL-1 and a detection limit of 0.17 mU mL-1. The assay was successfully applied to evaluate inhibitor screening with neostigmine as the model.

Black phosphorus quantum dots are useful oxidase mimics for colorimetric determination of biothiols.

Black phosphorus quantum dots (BP QDs) with small size are synthesized using an easy to operate thermal method. It was found that BP QDs possess oxidase-mimicking activity. They can catalyze the oxidation of the substrate 3,3',5,5'-tetramethylbenzidine to produce a blue-colored product even in the absence of hydrogen peroxide. Active oxygen species are proved to be involved in the reaction through the experiments of radical scavenging and electron spin resonance. Biothiols including reduced glutathione and cysteine inactivate the oxidase-mimicking activity of BP QDs, concomitant to the fading of the blue solution. This provides the  base for a colorimetric method for the determination of glutathione and cysteine. The decreased absorbance at 652 nm displays linear response to the concentrations of glutathione ranging from 0.1 to 5.0 µmol L-1, and cysteine from 0.1 to 10.0 µmol L-1. The detection limits are 0.02 µmol L-1 and 0.03 µmol L-1 for glutathione and cysteine, respectively. Successive determinations of 1.0 µmol L-1 glutathione and 5.0 µmol L-1 cysteine solution give relative standard deviations of 0.8% and 1.7% (n = 11), respectively. As a preliminary application, the practicability of the method was evaluated by the determination of glutathione in pharmaceutical preparations. This work not only discovers a useful oxidase mimics but also sets up a reliable platform based on BP QDs in colorimetric detection. Graphical abstract Schematic representation of colorimetric determination for biothiols through inactivating oxidase mimetic-like catalytic activity of black phosphorus quantum dots (BP QDs) on the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with dissolved oxygen to produce its blue oxidized product (oxTMB).

Ratiometric fluorometric determination of mercury(II) by exploiting its quenching effect on glutathione-stabilized and tetraphenylporphyrin modified gold nanoclusters.

A ratiometric fluorometric assay for mercury(II) ion is described. It is making use of glutathione-stabilized gold nanoclusters (GSH-AuNCs) modified with tetraphenylporphyrin tetrasulfonic acid (TPPS). The resultant GSH-AuNC/TPPS nanocomposite displays dual emission (at 572 and 664 nm) under a single excitation wavelength of 365 nm. Mercury(II) ion intensively quenches the yellow fluorescence of GSH-AuNCs (peaking at 572 nm) but has a negligible effect on the red fluorescence of TPPS (at 664 nm). The ratio of fluorescence intensities at 572 and 664 nm drops linearly with Hg(II) ion concentration in the 0.02-2.0 µmol·L-1 range, and the detection limit is 7 nmol·L-1 (3sb/S). The relative standard deviation (RSD) of the assay is 2.0% at a 0.5 µmol·L-1 concentration level (n = 11). The method was successfully applied to the determination of Hg(II) ion in spiked water samples, with recoveries within the range of 87.5-107.5%. Graphical abstract Ratiometric fluorescence detection of mercury(II).

A fluorometric aptamer-based assay for ochratoxin A by using exonuclease III-assisted recycling amplification.

A fluorometric assay is described for ochratoxin A (OTA) using an aptamer. The method is based on exonuclease-assisted recycling amplification. The OTA-binding aptamer partially hybridizes with complementary DNA (cDNA) that is released when the aptamer recognizes OTA. Then, cDNA hybridizes with a specifically designed hairpin DNA. Next, short ssDNA and cDNA are, respectively, released by exonuclease III catalyzed hydrolysis of the dsDNA. The cDNA induces the next ring opening and digestion. The short ssDNA captures the sDNA that is labeled with fluorescent FAM and is absorbed on graphene oxide (GO). The green fluorescence of the sDNA/GO system is quenched but is recovered if the sDNA is released from GO. This assay is high sensitive, works in the 5 nM to 200 nM OTA concentration range and has a 0.96 nM lower detection limit. It was applied to the quantitation of OTA in spiked wine and coffee samples. Graphical abstractSchematic of a fluorometric assay based on exonuclease-assisted recycling amplification for quantitative monitoring of OTA without the need of sample separation and multiple washing steps.

A covalent triazine framework as an oxidase mimetic in the luminol chemiluminescence system: application to the determination of the antioxidant rutin.

It is found that a covalent triazine framework (CTF-1) (that was prepared from 1,4-dicyanobenzene) exhibits oxidase-like activity toward the oxidation of luminol with dissolved oxygen in alkaline condition to produce intense blue chemiluminescence (CL). The reaction follows Michaelis-Menten kinetics and shows strong specificity for luminol. Reactive oxygen species including 1O2, •OH and O2•- are testified to be involved in the reaction and responsible for the CL. The reaction was applied to the determination of the radical-scavenging activity of antioxidants, with rutin, kaempferol and ferulic acid serving as model scavengers. A sensitive CL method was developed for the determination of rutin based on its inhibitory effect on the reaction. The CL system gave a linear response to the concentration of rutin in the range of 0.03-0.25 µmol·L-1 with a limit of detection of 0.015 µmol·L-1. The practicability of the method was demonstrated by successful determination of rutin in tablets and in Flos Sophorae Immaturus. Graphical Abstract.

Label-free, non-derivatization CRET detection platform for 6-mercaptopurine based on the distance-dependent optical properties of gold nanoparticles.

A label-free, non-derivatization chemiluminescence resonance energy transfer (CRET) detection platform has been developed for the detection of the non-fluorescent small molecule 6-mercaptopurine. This CRET process arose from a chemiluminescent (CL) donor-acceptor system in which the reaction of bis(2,4,6-trichlorophenyl)oxalate (TCPO)-H(2)O(2)-fluorescein (maximum emission at 521.6 nm) served as the donor and gold nanoparticles (AuNPs, maximum absorption at 520.0 nm) served as the acceptor. This process caused a significant decrease in the CL signal of the TCPO-H(2)O(2)-fluorescein reaction. The presence of 6-mercaptopurine induced an aggregation of AuNPs with the assistance of Cu(2+) ions through cooperative metal-ligand interactions that was accompanied by a distinct change in color and optical properties. The maximum absorption band of the AuNPs was red-shifted to 721.0 nm and no longer overlapped with the CL spectrum of the reaction; as a result, the CL signal was restored. This CRET system exhibited a wide linear range, from 9.0 nmol L(-1) to 18.0 µmol L(-1), and a low detection limit (0.62 nmol L(-1)) for 6-mercaptopurine. The applicability of the proposed CRET system was evaluated by analysis of 6-mercaptopurine in spiked human plasma samples.

Substrate-free fluorescence ratiometric detection of serum acetylcholinesterase activity with a self-assembled CsPbBr3 perovskite nanocrystals/tetraphenylporphyrin tetrasulfonic acid nanocomposite.

A dual-emission fluorescent nanoprobe was successfully constructed through self-assembling CsPbBr3 perovskite nanocrystals (CsPbBr3 PNCs) and tetraphenylporphyrin tetrasulfonic acid (TPPS). Acetylcholinesterase (AChE) is observed to directly quench the green fluorescence of CsPbBr3 PNCs at 520 nm in the absence of an enzyme substrate, but has no significant influence on the red emission of TPPS at 650 nm. The decreased value of the fluorescence intensities ratio at 520 to 650 nm (ΔF520/F650) is proportional to the logarithmic value of AChE activity ranging from 0.05 to 1.0 U/L. The limit of detection is as low as 0.0042 U/L. The relative standard deviation is 3.6% in eleven consecutive measurements of 0.2 U/L AChE. The method exhibits a good anti-interference capacity since it does not respond to most concomitant species. Satisfactory results are acquired for the determination of AChE activity in human serum samples.

Aptamer biorecognition-triggered hairpin switch and nicking enzyme assisted signal amplification for ultrasensitive colorimetric bioassay of kanamycin in milk.

A colorimetric aptasensing strategy for detection of kanamycin was designed based on aptamer biorecognition and signal amplification assisted by nicking enzyme. The aptamer of kanamycin was designed to be contained in the metastable state hairpin DNA. The target DNA as recycling DNA was located in the loop of hairpin DNA. The presence of kanamycin stimulates the continuous actions, including specific recognition of the aptamer to kanamycin, the hybridization between target DNA and signal probe, the cleavage function of nicking enzyme. The actions induced accumulation of numerous free short sequences modified by platinum nanoparticles (PtNPs), which can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2 to produce a colorimetric response. The aptasensor exhibited good selectivity and sensitivity for kanamycin in milk with a detection limit as low as 0.2 pg·mL-1. In addition, the proposed assay is potentially to be extended for other antibiotics detection in foods by adapting the corresponding aptamer sequence.

A novel luminol chemiluminescence system induced by black phosphorus quantum dots for cobalt (II) detection.

Black phosphorus quantum dots (BP QDs) were prepared through a solvothermal exfoliation method in alkaline N-methyl-2-pyrrolidinone. The BP QDs induce distinct chemiluminescence (CL) of alkaline luminol directly. A possible reaction mechanism is proposed by the study of CL spectrum, ultraviolet-visible absorption spectra, electron paramagnetic resonance spectra as well as radical scavenging experiments. The presence of BP QDs significantly increases generation of active oxygen species, which oxidize luminol and lead to intense CL emission at 425 nm. The reaction of luminol with BP QDs are specifically catalyzed by cobalt (II) ion, this presents a sensitive CL method for cobalt (II) ion. A linear response range extends from 2.5 to 2000.0 pmol/L cobalt (II) ion and a detection limit of 0.7 pmol/L (3sb) is acquired. The method displays a good precision approved by a relative standard deviation of 1.9% at 100.0 pmol/L cobalt (II) ion solution (n = 11). A preliminary application of the method was conducted by successful determination of cobalt amount in silica gel and rain water samples.

Chemiluminescence determination of naproxen based on europium(III)-sensitized KIO4-H2O2 reaction.

A simple and sensitive chemiluminescence (CL) method combined with flow injection technique was developed for the determination of naproxen. It was based upon the weak CL signal arising from the reaction of KIO(4) with H(2)O(2) being significantly increased by naproxen in the presence of europium(III) ion. The experimental conditions that affected the CL signal were carefully optimized and the CL reaction mechanism was briefly discussed. Under the optimum conditions, the increment of CL intensity was proportional to the concentration of naproxen ranging from 5.0 x 10(-8) to 5.0 x 10(-6) g/mL. The detection limit was 1 x 10(-8) g/mL naproxen and the relative standard deviation for 5.0 x 10(-7) g/mL naproxen solution was 2.1% (n = 11). The proposed method was applied to the determination of naproxen in tablets and in spiked human urine samples with satisfactory results.

Perovskite nanocrystals fluorescence nanosensor for ultrasensitive detection of trace melamine in dairy products by the manipulation of inner filter effect of gold nanoparticles.

Barium sulfate-coated CsPbBr3 perovskite nanocrystals (CsPbBr3 NCs@BaSO4) was successfully synthesized that exhibited stable and intense fluorescence property in aqueous buffer. With the CsPbBr3 NCs@BaSO4 as signal readout, an ultrasensitive fluorescence nanosensor was developed for turn-on determination of melamine by the manipulation of inner filter effect of citrate-protected gold nanoparticles (AuNPs). The fluorescence of the CsPbBr3 NCs@BaSO4 was remarkably quenched by the AuNPs due to inner filter effect. This inner filter effect could be weakened by the addition of melamine as a result of melamine-triggering aggregation of the AuNPs and subsequently led to a recovery in the fluorescence of the CsPbBr3 NCs@BaSO4. The recovery ratio was proportional to the concentration of melamine in the range of 5.0-500.0 nmol/L. The limit of detection was 0.42 nmol/L and the relative standard deviation was 4.0% for the repetitive determination of 500.0 nmol/L melamine solution (n = 11). The nanosensor was successfully applied to analysis of melamine in dairy product samples.

Luminescent metal organic frameworks-based chemiluminescence resonance energy transfer platform for turn-on detection of fluoride ion.

A luminescent metal organic frameworks (MOFs)-based chemiluminescence resonance energy transfer (CRET) platform was constructed for turn-on detection of fluoride ion. A hybrid MOFs was prepared by encapsulating strong fluorescence 2',7'-dichlorofluorescein (DCF) into the frames of NH2-MIL-101(Al) MOFs, which led to a significant suppression of fluorescence signal of DCF. In the presence of fluoride ion, it destroyed the structure of the hybrid MOFs and released DCF molecules from the frames due to the formation of more stable aluminum hexafluoride complex ions [AlF63-] between fluoride ion and aluminum ion. The released DCF molecules accepted the energy originating from the chemical reaction of bis(2,4,6-trichlorophenyl)oxalate (TCPO) with hydrogen peroxide (H2O2), producing a strong chemiluminescence (CL) emission. The CL signal was strong dependent on the concentration of fluoride ion presented and showed a linear response in the range of 0.5-80.0 µmol L-1 (9.5 µg L-1-1.52 mg L-1). The detection limit was 0.05 µmol L-1 (about 0.95 µg L-1) fluoride ion and the relative standard deviations was 2.3% for 40.0 µmol L-1 fluoride ion solution (n = 11). This MOFs-based CRET method was successfully applied to the determination of fluoride ion in drinking water samples, demonstrating its potential application in analysis of real samples.

Bifunctional gold nanoclusters enable ratiometric fluorescence nanosensing of hydrogen peroxide and glucose.

The accurate quantification of hydrogen peroxide (H2O2) and glucose is essential significance in clinical diagnosis. Herein a selective and sensitive ratiometric fluorescent nanosensor was developed for the determination of H2O2 and glucose by integrating peroxidase-like catalytic and fluorescent bifunctional properties of glutathione protected gold nanoclusters (GSH-AuNCs). The GSH-AuNCs exhibit inherent peroxidase-like activity and accelerate the decomposition of H2O2 into hydroxyl radicals. The produced hydroxyl radicals oxidize terephthalic acid (TA), a typical non-fluorescent substrate of peroxidase, to a highly fluorescent product hydroxyterephthalate (TAOH). Upon excitation with single-wavelength at 315 nm, dual-emission fluorescence peaks were recorded at 430 and 600 nm simultaneously. The fluorescence signal of TAOH at 430 nm continuously increased with increasing the concentration of H2O2 while the fluorescence signal of GSH-AuNCs at 600 nm remained unchangeable. Based upon on these facts, a ratiometric fluorescent nanosensor was fabricated for H2O2 assay with TAOH as response unit and GSH-AuNCs as reference, respectively. By converting glucose into H2O2 with catalytic oxidation of glucose oxidase (GOx), this nanosensor was further exploited for glucose assay. Under the optimum conditions, the detection limits of 10 nmol/L H2O2 and 20 nmol/L glucose were acquired. The relative standard deviations were less than 5% for both H2O2 and glucose (5.0 µmol/L solution, n = 11). The practicability of the nanosensor was verified by the determination of glucose in human serum samples. This nanosensor can be easily expanded as a general platform for the detection of other substances involving H2O2 produced or consumed.

Fluorescein and its derivatives: New coreactants for luminol chemiluminescence reaction and its application for sensitive detection of cobalt ion.

Fluorescein and its derivatives, including 4',5'-dibromofluorescein, 2',7'-dichlorofluorescein and 2',4',5',7'-tetrabromofluorescein can be employed as efficient coreactants for luminol reaction. Under an alkaline condition they reacted with luminol to produce measureable chemiluminescence (CL) in the absence of any extra-oxidant. Cobalt ion (Co2+) significantly enhanced the CL emission of the reaction. The CL emission was strongly dependent on the concentration of carbonate buffer used; higher concentration of carbonate buffer provided more intense CL emission. The system had two emission peaks locating at 425 nm and 535 nm, respectively. With 4',5'-dibromofluorescein as the coreactant for luminol reaction, a new CL method was developed for the detection of Co2+. The procedure allowed the linear detection of Co2+ in the range of 5-1000 nmol/L. The limit of detection (LOD) and limit of quantitation (LOQ) were 1.8 nmol/L and 5.0 nmol/L, respectively. The intra-day precision (n = 11) and inter-day precision (n = 3) was 3.2% and 4.7% for replicated measurements of 0.2 µmol/L Co2+ solution. The method was successfully applied to the determination of Co2+ in blue silica gel samples.

Distance dependent fluorescence quenching and enhancement of gold nanoclusters by gold nanoparticles.

The interaction between fluorescent gold nanoclusters (AuNCs) and gold nanoparticles (AuNPs) has been investigated. It was observed that the fluorescence of AuNCs was remarkably quenched when direct contact with AuNPs. The fluorescence quenching of AuNCs by AuNPs was dynamic quenching and exhibited size-dependent property. A larger size of AuNPs displayed a stronger quenching effect and gave a larger quenching constant. When a silica spacer shell was introduced between AuNPs and AuNCs, a fluorescence enhancement of AuNCs by Au@SiO2 NPs was observed. The fluorescence enhancement was strongly dependent on the separation distance between the AuNPs and the AuNCs. A maximal enhancement of 3.72 times was observed when Au@SiO2 NPs have a silica shell thickness of 12nm. This nanocomposite consisting of relatively nontoxic AuNPs and AuNCs may have a potential application in developing novel fluorescent sensor.

A novel electrochemiluminescence resonance energy transfer system of luminol-graphene quantum dot composite and its application in H2O2 detection.

Luminol-nitrogen doped graphene quantum dot (luminol-NGQDs) nanocomposite was synthesized and a novel electrochemiluminescence resonance energy transfer (ECL-RET) process occurred between luminol as the donor and NGQDs as the acceptor in the composite. This ECL-RET effect helped luminol-NGQDs composite produced an anodic ECL signal without coreactants. The ECL-RET mechanism was also studied based on the fluorescence spectra, the ultraviolet-visible absorption spectra and the electrochemiluminescence (ECL) spectra. Based on the significant sensitization effect of hydrogen peroxide on luminol-NGQDs ECL signal, an ECL method for the sensitive determination of hydrogen peroxide was established and then applied to the detection of hydrogen peroxide in water samples.

Flow injection chemiluminescence determination of imipramine in tablets, human plasma and urine samples based upon oxidation with singlet oxygen generated in N-bromosuccinimide-hydrogen peroxide reaction.

Singlet oxygen generated in a reaction between N-bromosuccinimide and hydrogen peroxide was used for the chemiluminescence oxidation of imipramine. A strong chemiluminescence signal was observed when imipramine was mixed with N-bromosuccinimide and hydrogen peroxide under an alkaline condition. The chemiluminescence signal was linearly dependent on the concentration of imipramine in the range of 0.01 - 1.0 mg/L. The detection limit was 0.005 mg/L imipramine and the relative standard deviation was 1.5% for a 0.4 mg/L imipramine solution in 11 repeated measurements. The proposed method was successfully applied to the determination of imipramine in tablets, human plasma and urine samples.