Dietary melatonin attenuates age-related changes in morphology and in levels of key proteins in globus pallidus of mouse brain.

The ability of melatonin treatment of aged animals to partially restore the pattern of gene expression characterizing the younger animal has been frequently reported. The current study examines the effect of melatonin upon age-related changes of some key proteins relevant to the aging process. Male B6C3F1 mice, aged 5.5 months and 23.4 months were used as a model for aging and half of each group received a diet supplemented with 40-ppm (w/w) melatonin for 9.3 weeks. Protein components of the globus pallidus were studied including glial fibrillary acidic protein (GFAP), NF-κB, protein disulfide isomerase (PDI), and Nissl staining. Some age-related changes were in an upward direction (GFAP and NF-κB), while others were depressed with age (PDI and intensity of Nissl staining). However, in either case, melatonin treatment of aged mice generally altered these parameters so that they came to more closely resemble the levels found in younger animals. The extent of this reversal to a more youthful profile, ranged from complete (for NF-κB) to very minor (for Nissl staining and PDI). Overall, these findings are in accord with prior data on the effect of melatonin on cortical gene expression and confirm the value of melatonin as a means of retarding events associated with senescence

Complexity of Wake Electroencephalography Correlates With Slow Wave Activity After Sleep Onset

Sleep electroencephalography (EEG) provides an opportunity to study sleep scientifically, whose chaotic, dynamic, complex, and dissipative nature implies that non-linear approaches could uncover some mechanism of sleep. Based on well-established complexity theories, one hypothesis in sleep medicine is that lower complexity of brain waves at pre-sleep state can facilitate sleep initiation and further improve sleep quality. However, this has never been studied with solid data. In this study, EEG collected from healthy subjects was used to investigate the association between pre-sleep EEG complexity and sleep quality. Multiscale entropy analysis (MSE) was applied to pre-sleep EEG signals recorded immediately after light-off (while subjects were awake) for measuring the complexities of brain dynamics by a proposed index, CI1−30. Slow wave activity (SWA) in sleep, which is commonly used as an indicator of sleep depth or sleep intensity, was quantified based on two methods, traditional Fast Fourier transform (FFT) and ensemble empirical mode decomposition (EEMD). The associations between wake EEG complexity, sleep latency, and SWA in sleep were evaluated. Our results demonstrated that lower complexity before sleep onset is associated with decreased sleep latency, indicating a potential facilitating role of reduced pre-sleep complexity in the wake-sleep transition. In addition, the proposed EEMD-based method revealed an association between wake complexity and quantified SWA in the beginning of sleep (90 min after sleep onset). Complexity metric could thus be considered as a potential indicator for sleep interventions, and further studies are encouraged to examine the application of EEG complexity before sleep onset in populations with difficulty in sleep initiation. Further studies may also examine the mechanisms of the causal relationships between pre-sleep brain complexity and SWA, or conduct comparisons between normal and pathological conditions

Age-Related Alterations in Electroencephalography Connectivity and Network Topology During n-Back Working Memory Task

The study of the healthy brain in elders, especially age-associated alterations in cognition, is important to understand the deficits created by Alzheimer's disease (AD), which imposes a tremendous burden on individuals, families, and society. Although, the changes in synaptic connectivity and reorganization of brain networks that accompany aging are gradually becoming understood, little is known about how normal aging affects brain inter-regional synchronization and functional networks when items are held in working memory (WM). According to the classic Sternberg WM paradigm, we recorded multichannel electroencephalography (EEG) from healthy adults (young and senior) in three different conditions, i.e., the resting state, 0-back (control) task, and 2-back task. The phase lag index (PLI) between EEG channels was computed and then weighted and undirected network was constructed based on the PLI matrix. The effects of aging on network topology were examined using a brain connectivity toolbox. The results showed that age-related alteration was more prominent when the 2-back task was engaged, especially in the theta band. For the younger adults, the WM task evoked a significant increase in the clustering coefficient of the beta-band functional connectivity network, which was absent in the older adults. Furthermore, significant correlations were observed between the behavioral performance of WM and EEG metrics in the theta and gamma bands, suggesting the potential use of those measures as biomarkers for the evaluation of cognitive training, for instance. Taken together, our findings shed further light on the underlying mechanism of WM in physiological aging and suggest that different EEG frequencies appear to have distinct functional correlates in cognitive aging. Analysis of inter-regional synchronization and topological characteristics based on graph theory is thus an appropriate way to explore natural age-related changes in the human brain

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.We thank W. Liu and L. Xu from the Huazhen Laboratory Animal Breeding Centre for helping in the collection of monkey tissues, D. Zhu and H. Li from the Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) for technical help, G. Guo and H. Sun from Zhejiang University for providing HCL and MCA gene expression data matrices, G. Dong and C. Liu from BGI Research, and X. Zhang, P. Li and C. Qi from the Guangzhou Institutes of Biomedicine and Health for experimental advice or providing reagents. This work was supported by the Shenzhen Basic Research Project for Excellent Young Scholars (RCYX20200714114644191), Shenzhen Key Laboratory of Single-Cell Omics (ZDSYS20190902093613831), Shenzhen Bay Laboratory (SZBL2019062801012) and Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011). In addition, L.L. was supported by the National Natural Science Foundation of China (31900466), Y. Hou was supported by the Natural Science Foundation of Guangdong Province (2018A030313379) and M.A.E. was supported by a Changbai Mountain Scholar award (419020201252), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), a Chinese Academy of Sciences–Japan Society for the Promotion of Science joint research project (GJHZ2093), the National Natural Science Foundation of China (92068106, U20A2015) and the Guangdong Basic and Applied Basic Research Foundation (2021B1515120075). M.L. was supported by the National Key Research and Development Program of China (2021YFC2600200).S

Microstructure and Mechanical Properties of High Vacuum Die-Cast AlSiMgMn Alloys at as-Cast and T6-Treated Conditions

Al–Si–Mg based alloys can provide high strength and ductility to satisfy the increasing demands of thin wall castings for automotive applications. This study has investigated the effects of T6 heat-treatment on the microstructures, the local mechanical properties of alloy phases and the fracture behavior of high vacuum die-cast AlSiMgMn alloys using in-situ scanning electron microscopy (SEM) in combination with nano-indentation testing. The microstructures of the alloys at as-cast and T6 treated conditions were compared and analyzed. It is found that the T6 heat treatment plays different roles in affecting the hardness and the Young’s modulus of alloy phases. This study also found that the T6 heat treatment would influence the failure modes of the alloys. The mechanisms of crack propagation in the as-cast and T6 treated alloys were also analyzed and discussed

Investigation on the Prediction of Cardiovascular Events Based on Multi-Scale Time Irreversibility Analysis

Investigation of the risk factors associated with cardiovascular disease (CVD) plays an important part in the prevention and treatment of CVD. This study investigated whether alteration in the multi-scale time irreversibility of sleeping heart rate variability (HRV) was a risk factor for cardiovascular events. The D-value, based on analysis of multi-scale increments in HRV series, was used as the measurement of time irreversibility. Eighty-four subjects from an open-access database (i.e., the Sleep Heart Health Study) were included in this study. None of them had any CVD history at baseline; 42 subjects had cardiovascular events within 1 year after baseline polysomnography and were classed as the CVD group, and the other 42 subjects in the non-CVD group were age matched with those in the CVD group and had no cardiovascular events during the 15-year follow-up period. We compared D-values of sleeping HRV between the CVD and non-CVD groups and found that the D-values of the CVD group were significantly lower than those of the non-CVD group on all 10 scales, even after adjusting for gender and body mass index. Moreover, we investigated the performance of a machine learning model to classify CVD and non-CVD subjects. The model, which was fed with a feature space based on the D-values on 10 scales and trained by a random forest algorithm, achieved an accuracy of 80.8% and a positive prediction rate of 86.7%. These results suggest that the decreased time irreversibility of sleeping HRV is an independent predictor of cardiovascular events that could be used to assist the intelligent prediction of cardiovascular events

A novel oversampling technique based on the manifold distance for class imbalance learning

The file attached to this record is the author's final peer reviewed version.Oversampling is a popular problem-solver for class imbalance learning by generating more minority samples to balance the dataset size of different classes. However, resampling in original space is ineffective for the imbalance datasets with class overlapping or small disjunction. Based on this, a novel oversampling technique based on manifold distance is proposed, in which a new minority sample is produced in terms of the distances among neighbors in manifold space, rather than the Euclidean distance among them. After mapping the original data to its manifold structure, the overlapped majority and minority samples will lie in areas easily being partitioned. In addition, the new samples are generated based on the neighbors locating nearby in manifold space, avoiding the adverse effect of the disjoint minority classes. Following that, an adaptive adjustment method is presented to determine the number of the newly generated minority samples according to the distribution density of the matched-pair data. The experimental results on 48 imbalanced datasets indicate that the proposed oversampling technique has the better classification accuracy