No abstract

Background To examine the patterns of longitudinal tau accumulation and cortical atrophy and their association in patients with mild cognitive impairment (MCI). Methods We collected 23 participants (60-89 years old, 11 male/12 female) with MCI from the Alzheimer's Disease Neuroimaging Initiative database. All participants underwent 18 F flortauirpir (FTP) positron emission tomography (PET) and structural magnetic resonance imaging (MRI) scans at the baseline and follow-up visits (12-36 months). General linear models with covariates (baseline age, sex) were used to detect brain areas of significant tau accumulation and atrophy over time. The mediation analysis was employed to explore the potential reason for sequential biomarker changes in MCI progression, adjusting for baseline age, sex, education. Results Voxelwise tau accumulation in MCI patients was predominantly located in inferior temporal, middle temporal, parietal cortex, posterior cingulate, precuneus as well as temporo-parietal regions (P < 0.001), and MRI atrophy included inferior-middle temporal, parietal lobe, cerebellum and precuneus (P < 0.001). Longitudinal FTP accumulation was moderately associated with MRI cortical atrophy (r = 0.409, 95% CI: 0.405-0.414, P < 0.01). Regional analyses indicated significant bivariate associations between MRI cortical atrophy and FTP accumulation (baseline FTP cortical uptake and longitudinal FTP change). The result of the mediation analysis showed the relationship between baseline FTP uptake and longitudinal cortical atrophy was partly mediated by the longitudinal FTP cortical change (indirect effect: 0.0107, P = 0.04). Conclusions Our finding provides a preliminary description of the patterns of longitudinal FTP accumulation and cortical atrophy in MCI progression, and MCI patients with high tau binding level show increase risk of longitudinal tau accumulation, atrophy and cognitive decline.

A visually meaningful double-image encryption scheme using 2D compressive sensing and multi-rule DNA encoding is presented. First, scrambling, diffusing and 2D compressive sensing are performed on the two plain images, and two privacy images are obtained, respectively. Then, the two privacy images are re-encrypted using DNA encoding theory to obtain two secret images. Finally, integer wavelet transform (IWT) is performed on the carrier image to obtain the wavelet coefficients, then the two secret images are embedded into the wavelet coefficients and 2k correction is performed, and the obtained result is processed by inverse IWT to obtain a visually meaningful encrypted image. DNA encoding rules selected for the pixel values of different positions in the two privacy images, and DNA operations performed between the two privacy images and the key streams at different positions are controlled by the chaotic system. The application of 2D compressive sensing reduces the amount of data, thus increasing the encryption capacity of the system. The introduction of DNA encoding theory and the double-image embedding process increases the security of the system. The simulation results demonstrate the feasibility of the scheme, and it has high data security and visual security.

Hydrogen sulfide (H2S), which is generated mainly by cystathionine γ-lyase (CSE) in the cardiovascular system, plays a pivotal role in a wide range of physiological and pathological processes. However, the regulatory mechanism of the CSE/H2S system is poorly understood. Herein, we show that oxidation induces the disulfide bond formation between Cys252 and Cys255 in the CXXC motif, thus stimulating the H2S-producing activity of CSE. The activity of oxidized CSE is approximately 2.5 fold greater than that of the reduced enzyme. Molecular dynamics and molecular docking suggest that the disulfide bond formation induces the conformational change in the active site of CSE and consequently increases the affinity of the enzyme for the substrate L-cysteine. Mass spectrometry and mutagenesis studies further established that the residue Cys255 is crucial for oxidation sensing. Oxidative stress-mediated sulfenylation of Cys255 leads to a sulfenic acid intermediate that spontaneously forms an intramolecular disulfide bond with the vicinal thiol group of Cys252. Moreover, we demonstrate that exogenous hydrogen peroxide (H2O2) and endogenous H2O2 triggered by vascular endothelial growth factor (VEGF) promote cellular H2S production through the enhancement of CSE activity under oxidative stress conditions. By contrast, incubation with H2O2 or VEGF did not significantly enhance cellular H2S production in the presence of PEG-catalase, an enzymatic cell-permeable H2O2 scavenger with high H2O2 specificity. Taken together, we report a new posttranslational modification of CSE that provides a molecular mechanism for H2O2/H2S crosstalk in cells under oxidative stress.