Identification of the sites of 4-hydroxy-2-nonenal and neprilysin adduction using a linear trap quadrapole Velos Pro-Orbitrap Elite mass spectrometer.

Amyloid-ßdegrading enzyme neprilysin (NEP) plays a pivotal role in eliminating Aß The oxidized modification of NEP by 4-hydroxy-2-nonenal (HNE) may reduce the clearance of Aß in cultured cells and Alzheimer's disease (AD) brains. The aim of this research is to study whether HNE could modify the NEP protein and identify the specific sites of HNE-NEP modification using a linear trap quadrapole (LTQ) Velos Pro-Orbitrap Elite mass spectrometer. NEP activity was determined after SH-SY5Y cells had incubated with HNE (20 µM) for 24 hours. To identify the sites of NEP modification, samples of both native and HNE-modified NEP digested by trypsin were analyzed using a LTQ Velos Pro-Orbitrap Elite mass spectrometer. The NEP peptide sequence information from the fragment ion masses was used to search for the sites of NEP adduction. HNE-treated cells showed a 60% loss of NEP activity. NEP was covalently adducted at Lys 93, Lys 472 by HNE via Michael addition. Compared to the control group, the sites of modified peptide in NEP showed a consistent 156 Da increased in m/z, which provides sequence information and might contribute to further studies on drug design and the therapeutics of AD.

Real-Time Single Frequency Precise Point Positioning Using SBAS Corrections.

Real-time single frequency precise point positioning (PPP) is a promising technique for high-precision navigation with sub-meter or even centimeter-level accuracy because of its convenience and low cost. The navigation performance of single frequency PPP heavily depends on the real-time availability and quality of correction products for satellite orbits and satellite clocks. Satellite-based augmentation system (SBAS) provides the correction products in real-time, but they are intended to be used for wide area differential positioning at 1 meter level precision. By imposing the constraints for ionosphere error, we have developed a real-time single frequency PPP method by sufficiently utilizing SBAS correction products. The proposed PPP method are tested with static and kinematic data, respectively. The static experimental results show that the position accuracy of the proposed PPP method can reach decimeter level, and achieve an improvement of at least 30% when compared with the traditional SBAS method. The positioning convergence of the proposed PPP method can be achieved in 636 epochs at most in static mode. In the kinematic experiment, the position accuracy of the proposed PPP method can be improved by at least 20 cm relative to the SBAS method. Furthermore, it has revealed that the proposed PPP method can achieve decimeter level convergence within 500 s in the kinematic mode.

An ESIPT-based fluorescent probe for sensitive detection of hydrazine in aqueous solution.

A fluorescent probe for sensitive detection of hydrazine based on an ESIPT mechanism and a substitution-cyclization-elimination cascade was developed. After the addition of hydrazine, an approximately 50-fold enhancement in fluorescence intensity at 465 nm was observed and the subsequent decrease at 375 nm was observed in 10 min with a detection limit of 0.147 µM. We also detected hydrazine in HeLa cells successfully.

Antiproliferative and apoptosis-inducing activities of novel naphthalimide-cyclam conjugates through dual topoisomerase (topo) I/II inhibition.

A novel series of naphthalimide-cyclam conjugates were designed and synthesized. Among them, compounds 4c, 4d, 8c and 8d which bearing long lipophilic alkyl chains, displayed comparable or more potent cytotoxic activities against human tumor cell lines than amonafide. Furthermore, the four compounds were proved to possess strong inhibition against both topoisomerase I and II. The representative compound 8c exhibited moderate DNA intercalation activity. Molecular modeling studies identified the possible interaction of compound 8c with the molecular target by forming topoisomerase/DNA/drug ternary complex. Finally, derivatives with long lipophilic alkyl chains could efficiently induce apoptosis.

The impact of accelerating population aging on service industry development: Evidence from China.

The demographic structure is an important factor influencing the development of the services industry. As the country with the world's most serious aging problem, China's service industry structure is likely to undergo profound changes in response to the rapid demographic transition. Therefore, this paper examines the effect of population aging on the development of the service industry in the context of China's accelerating population aging. The study found that: (1) Population aging has a significant "inverted U" effect on the development of the services industry. (2) The impact of population aging on the development of the service industry has obvious regional and industry heterogeneity. The study of regional heterogeneity found that population aging in economically developed regions has a more obvious effect on the development of the service industry than in economically less developed regions. Industry heterogeneity studies found that population aging has an obvious promotional effect on the development of medical and other rigid demand industries, while the effect on other non-rigid demand industries is not significant. (3) The threshold effect test found that when the degree of population aging exceeds the threshold, the stimulating effect of population aging on the development of the services industry is no longer significant. The research in this paper provides useful insights into the likely response to changes in the industrial structure of the services industry, and offers some implications for countries with similar demographic profiles to China.

Linkage structure of China's housing market and its risk-defusing capability.

There have been many recent fears of severe house-price decreases in some provinces in China causing a nationwide collapse of the housing market. Therefore, this paper aims to clarify the linkage structure of China's housing market and its risk contagion routes. Given monthly data of provincial housing and stock-market capital returns from 2001M01 to 2019M12, on the basis of graph theory, this paper first explores the linkage structure of provincial housing markets. Relying on the linkage structure, this paper then simulates the effect of unexpected negative shocks from the stock market on the probabilities of a housing-market collapse based on the epidemic model. The results show that (i) consistently with practical evidence, the probability of housing-market collapse is relatively high in the southwest of China and (ii) reducing housing-market linkage, such as through a blocking mechanism, to prevent collapse is helpful.

Dynamic alteration of neprilysin and endothelin-converting enzyme in age-dependent APPswe/PS1dE9 mouse model of Alzheimer's disease.

Imbalance of Aß production and Aß removal leads to Aß accumulation. Aß degrading enzyme (including neprilysin-NEP, endothelin converting enzyme-ECE) as a therapeutic strategy for lowering brain Aß deposition has attracted increasing attention. In this study, we investigated alteration of age and region-dependent in APP/PS1 double transgenic mice (3, 6, 9, 12 months) and their age-matched wild type mice including the ability of spatial memory, Aß deposits, the protein expression, location and activity of NEP and ECE. Our data demonstrated that, as compared with wild type mice, APP/PS1 mice displayed significant cognitive deficit at 9 month revealed by obviously longer in the latency and distance to find the platform and shorter in time spent and swimming distance in the target quadrant. Aß40 and Aß42 levels exhibited a significant increase with age in the cerebral cortex and hippocampus of APP/PS1 mice after 6 month, compared with their age-matched wild type mice. And Aß42 levels were significantly higher than Aß40 levels in the same age of APP/PS1 mice. Furthermore, NEP protein and activity displayed a marked decrease with age in the cerebral cortex and hippocampus of APP/PS1 mice older than 6 month. Slightly different from NEP, ECE protein was up-regulated with age, while ECE activity showed a significantly decrease with age in cortex and hippocampus of APP/PS1 mice older than 6 month. Double immunofluorescence staining also demonstrated that ECE and NEP highly colocalized in cytoplasmic and membrane, and ECE immunoreactivity tended to increase with age in APP/PS1 mice, especially 12 month APP/PS1 mice. Correlation analysis showed the negative correlation between enzyme (NEP or ECE) activity and Aß levels in the cerebral cortex and hippocampus of APP/PS1 mice, which was correlated with Aß accumulation. These results indicate NEP rather than ECE plays more important role in resisting Aß accumulation. The compensatory upregulation of NEP and ECE could balance Aß metabolism and protect neuronal functions in infant and juvenile mice. These evidence might provide some clues for the treatment of Alzheimer's disease.