Chromone and donepezil hybrids as new multipotent cholinesterase and monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease.

A series of chromone and donepezil hybrids were designed, synthesized, and evaluated as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential therapy of Alzheimer's disease (AD). In vitro studies showed that the great majority of these compounds exhibited potent inhibitory activity toward BuChE and AChE and clearly selective inhibition for hMAO-B. In particular, compound 5c presented the most balanced potential for ChE inhibition (BuChE: IC50 = 5.24 µM; AChE: IC50 = 0.37 µM) and hMAO-B selectivity (IC50 = 0.272 µM, SI = 247). Molecular modeling and kinetic studies suggested that 5c was a mixed-type inhibitor, binding simultaneously to peripheral and active sites of AChE. It was also a competitive inhibitor, which occupied the substrate and entrance cavities of MAO-B. Moreover, compound 5c could penetrate the blood-brain barrier (BBB) and showed low toxicity to rat pheochromocytoma (PC12) cells. Altogether, these results indicated that compound 5c might be a hopeful multitarget drug candidate with possible impact on Alzheimer's disease therapy.

A hemicyanine derivative for near-infrared imaging of ß-amyloid plaques in Alzheimer's disease.

The formation of amyloid-ß (Aß) plaques in the brain is one of the main pathological features of Alzheimer's disease (AD). The imaging probes, capable of detecting Aß deposition, are important tools for early diagnosis of AD. In this article, we designed, synthesized and evaluated a cyanine-based near-infrared fluorescence (NIRF) probe ZT-1 for the detection of Aß deposits in the brain. The probe had excellent fluorescent properties with an emission maximum above 720 nm upon binding to Aß aggregates with affinity of 445.0 nM (Kd). Furthermore, ZT-1 exhibited good biostability, photostability, and binding selectivity toward Aß1-42 aggregates by in vitro fluorescence staining experiments. In vivo NIRF imaging result also revealed that our probe could efficiently differentiate transgenic and wild-type mice. All these studies indicated that ZT-1 is a promising fluorescent probe for Aß plaques in the AD brains.

Measuring upper limb movement to analyze intra-body communication channel attenuation characteristics.

BACKGROUND: This experiment was designed to study the respective effects of the closed-state human palm and dynamic arm bending on intra-body communication channel attenuation. METHODS: We selected the right upper arm of a healthy adult male as the experimental object to measure channel attenuation variation in a closed or open palm, and when the arm was bent, so as to analyze channel characteristics. CONCLUSIONS: The experiment showed that, in a quasi-static stable system, the effects of a closed palm on channel attenuation were negligibly minimal. In contrast, the physiological signal of the living body significantly interfered with the channel in the low-frequency mode. In the dynamic arm-bending experiment, we found that the attenuation variation range corresponds to the intersection angle (90∘⩽θ⩽ 180∘) of the upper arm and forearm; these results provide the basis for the establishment of a theoretical model.

Modeling of sectionally continuous communication channel with inhomogeneously distributed tissues.

BACKGROUND: This study aimed to investigate effects on the transmission channel caused by heterogeneous distribution in tissues and joint characteristics. METHOD: Human arm section scans were taken using CT technology, and zoned, following which, a circumference measurement experiment was performed to analyze the effect of inhomogeneous distribution of tissues. In order to analyze the arm joint's effect on channel transmission, we proposed a piecewise modeling method in combination with connection conditions. CONCLUSIONS: It can be seen from the experiment that, in the quasi-static mode, the communication channel error caused by the inhomogeneous distribution of tissues is small enough to be negligible. The error between calculated and experimental results is reduced by 3.93 dB in this experiment relative to models that did not include joint characteristics, and the average error is lowered by 0.73 dB. The variation curve fit to experimental data is also improved in this method. As such, it can be quantitatively determined that a channel model with joint characteristics is superior to models excluding joint characteristics.