Search

Alzheimer's disease is hallmarked by microtubule-associated protein tau tangles and amyloid-β plaques. The β-structure propensity of tau inclusions is closely related to the hexapeptide motif VQIVYK (termed PHF6), and disruption of this motif prevents tau aggregation. Small-molecule inhibitors are considered a promising therapeutic strategy, but the molecular mechanisms underlying the correlation between dose and inhibitory effects are still unclear. In this work, we investigated the dose-induced influence of purpurin, an anthraquinone derivative, on the structural stability of the PHF6 fibrillar nucleus by performing microsecond all-atom molecular dynamics simulations in explicit water. The stability of PHF6 protofibrils of different sizes was first examined, and it was found that the structural stability of fibrillar oligomers increases with oligomer size, and that the octamer is the minimal stable nucleus for fibril formation. When purpurin molecules were added to the protofibril octamer at a low purpurin/peptide ratio, they bound to the octamer with different coupling states, and the different states may transition to each of the other states through an uncoupling state or directly through a short-time transition. With increasing purpurin/peptide ratio, purpurins tend to self-aggregate rather than bind to the protein surface. Interestingly, the contacts between individual purpurins and the octamer as a function of the purpurin number show a power-law behavior, which may serve as a useful indicator to reflect the binding efficiency of ligands to proteins in drug screening. The interaction analysis reveals that purpurin prefers to bind to the hydrophilic and aromatic Tyr and has the lowest probability with the hydrophobic Val located in the middle of PHF6. Aromatic stacking plays a key role in the octamer–purpurin interaction, in which the three aromatic rings of purpurin have different contributions. In addition, purpurin shows a remarkable disruptive effect on the protofibril octamer when the molar ratio of purpurin to peptide is 1 : 2; above this ratio, the binding mode and disruption effect of purpurin do not change significantly. Our work provides a detailed picture of the dynamics and interactions of purpurin binding to the PHF6 protofibril and expands the understanding of the dose-induced inhibitory mechanism. [ABSTRACT FROM AUTHOR]

A novel type of enzyme–antibody conjugation using mesoporous silicon nanospheres (MSN) was developed, which amplified the labeling signal and highly increased the sensitivity of enzyme-linked immunosorbent assay (ELISA) for the determination of pesticide and veterinary drug residues in food. First, conjugates were prepared through layer-by-layer immobilization of an enzyme and an antibody on an MSN scaffold. Then the MSN scaffold was employed for labeling and signal amplification to develop a sensitive colorimetric immunoassay through the catalytic oxidation reaction of 5,50-tetramethylbenzidine (TMB). When this MSN-based ELISA was applied to detect chloramphenicol, avermectin, tetracycline and streptomycin in food samples, it provided linear ranges of 0.025 ng ml−1–25 ng ml−1, 0.05 ng ml−1–10 ng ml−1, 0.025 ng ml−1–10 ng ml−1 and 0.05 ng ml−1–25 ng ml−1, respectively, with low detection limits down to 0.011 ng mL−1, 0.134 ng mL−1, 0.015 ng ml−1 and 0.106 ng ml−1, respectively. For avermectin, it provided a 16.7-fold decrease of the limit of detection in contrast to that of standard ELISA without the loss of method specificity and accuracy. This novel immunoassay was hypersensitive, simple and easy-to-use, which made it high potential in applying for the accurate analysis of harmful substances in food. [ABSTRACT FROM AUTHOR]

Flexible films of polytungstate (PT) as active ingredients were fabricated in PDMS as a “band-Aid” to achieve controllable H2O2 release. In these different systems of an amorphous PT building block, the lengthened lifetime (bleaching process) of photo-electron–hole separation is attributed to the electron trapping of the PT network and the existence of hole scavengers. The hole scavengers further prevent recombination of electrons and holes, so that the long-lived photoelectron could provide sustainable reactive oxygen species (ROS) by trapped electrons. Transient absorption illustrates the kinetic competition between the process of photohole induced bleaching and coloration induced by weak irradiation, which suggests that the hole scavenger is vital for ROS generation. The signals of electron spin resonance further confirm the existence of ROS. The profiles of controllable H2O2 with various release efficiency were obtained via fluorescence studies. The results indicate that the H2O2 release efficiency is related to both the hole scavenger and the tungstate cluster. The released H2O2 on the responses of tumor cells were evaluated. Compared with a cancer drug, the controllable and reversible released H2O2 delivery is highly efficient in preventing the proliferation and inducing apoptosis of A375 melanoma cells. [ABSTRACT FROM AUTHOR]

Magnetically functionalized PDMS-based micropillar arrays have been successfully designed, fabricated and implanted for controllable microfluidic mixing. The arrangement of PDMS micropillar arrays inside the microchannel can be flexibly controlled by an external magnetic field. As a consequence, the flow fields inside the microchannel can be regulated at will via magnetic activation conveniently. When a microchannel is implanted with such micropillar arrays, two microstreams can be mixed easily and controllably upon the simple application of an on/off magnetic signal. Mixing efficiencies based on micropillar arrays with different densities were investigated and compared. It was found that micropillar arrays with higher density (i.e. smaller pillar pitch) would render better mixing performance. Our microfluidic system is capable of generating highly reproducible results within many cycles of mixing/non-mixing conversion. We believe that the simple mixing–triggering method together with rapid and controllable mixing control will be extraordinarily valuable for various biological or chemical applications in the future. [ABSTRACT FROM AUTHOR]

A novel turn-on mode fluorescent diarylethene containing a 4,6-dimethylpyrimidine unit was developed to fluorescently sense Zn 2+ . Its multiple-responsive properties induced by Zn 2+ /EDTA and ultraviolet/visible light have been systematically studied. The fluorescence sensor could efficiently detect Zn 2+ with a 10 times enhancement of emission intensity and fluorescence color change (dark-green). In addition, the sensor showed clear discrimination from Cd 2+ . The limit of detection of the sensor was measured to be 8.48 × 10 -8 mol L -1 for Zn 2+ . Finally, a molecular logic circuit was fabricated with the emission at 528 nm as the output signal and light and chemical stimuli as input signals., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Flexible films of polytungstate (PT) as active ingredients were fabricated in PDMS as a "band-Aid" to achieve controllable H 2 O 2 release. In these different systems of an amorphous PT building block, the lengthened lifetime (bleaching process) of photo-electron-hole separation is attributed to the electron trapping of the PT network and the existence of hole scavengers. The hole scavengers further prevent recombination of electrons and holes, so that the long-lived photoelectron could provide sustainable reactive oxygen species (ROS) by trapped electrons. Transient absorption illustrates the kinetic competition between the process of photohole induced bleaching and coloration induced by weak irradiation, which suggests that the hole scavenger is vital for ROS generation. The signals of electron spin resonance further confirm the existence of ROS. The profiles of controllable H 2 O 2 with various release efficiency were obtained via fluorescence studies. The results indicate that the H 2 O 2 release efficiency is related to both the hole scavenger and the tungstate cluster. The released H 2 O 2 on the responses of tumor cells were evaluated. Compared with a cancer drug, the controllable and reversible released H 2 O 2 delivery is highly efficient in preventing the proliferation and inducing apoptosis of A375 melanoma cells.