Integration of multi-omics summary data reveals the role of N6-methyladenosine in neuropsychiatric disorders.

N6-methyladenosine (m6A) methylation regulates gene expression/protein by influencing numerous aspects of mRNA metabolism and contributes to neuropsychiatric diseases. Here, we integrated multi-omics data and genome-wide association study summary data of schizophrenia (SCZ), bipolar disorder (BP), attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), major depressive disorder (MDD), Alzheimer's disease (AD), and Parkinson's disease (PD) to reveal the role of m6A in neuropsychiatric disorders by using transcriptome-wide association study (TWAS) tool and Summary-data-based Mendelian randomization (SMR). Our investigation identified 86 m6A sites associated with seven neuropsychiatric diseases and then revealed 7881 associations between m6A sites and gene expressions. Based on these results, we discovered 916 significant m6A-gene associations involving 82 disease-related m6A sites and 606 genes. Further integrating the 58 disease-related genes from TWAS and SMR analysis, we obtained 61, 8, 7, 3, and 2 associations linking m6A-disease, m6A-gene, and gene-disease for SCZ, BP, AD, MDD, and PD separately. Functional analysis showed the m6A mapped genes were enriched in "response to stimulus" pathway. In addition, we also analyzed the effect of gene expression on m6A and the post-transcription effect of m6A on protein. Our study provided new insights into the genetic component of m6A in neuropsychiatric disorders and unveiled potential pathogenic mechanisms where m6A exerts influences on disease through gene expression/protein regulation.

xWAS analysis in neuropsychiatric disorders by integrating multi-molecular phenotype quantitative trait loci and GWAS summary data.

BACKGROUND: Integrating quantitative trait loci (QTL) data related to molecular phenotypes with genome-wide association study (GWAS) data is an important post-GWAS strategic approach employed to identify disease-associated molecular features. Various types of molecular phenotypes have been investigated in neuropsychiatric disorders. However, these findings pertaining to distinct molecular features are often independent of each other, posing challenges for having an overview of the mapped genes. METHODS: In this study, we comprehensively summarized published analyses focusing on four types of risk-related molecular features (gene expression, splicing transcriptome, protein abundance, and DNA methylation) across five common neuropsychiatric disorders. Subsequently, we conducted supplementary analyses with the latest GWAS dataset and corresponding deficient molecular phenotypes using Functional Summary-based Imputation (FUSION) and summary data-based Mendelian randomization (SMR). Based on the curated and supplemented results, novel reliable genes and their functions were explored. RESULTS: Our findings revealed that eQTL exhibited superior ability in prioritizing risk genes compared to the other QTL, followed by sQTL. Approximately half of the genes associated with splicing transcriptome, protein abundance, and DNA methylation were successfully replicated by eQTL-associated genes across all five disorders. Furthermore, we identified 436 novel reliable genes, which enriched in pathways related with neurotransmitter transportation such as synaptic, dendrite, vesicles, axon along with correlations with other neuropsychiatric disorders. Finally, we identified ten multiple molecular involved regulation patterns (MMRP), which may provide valuable insights into understanding the contribution of molecular regulation network targeting these disease-associated genes. CONCLUSIONS: The analyses prioritized novel and reliable gene sets related with five molecular features based on published and supplementary results for five common neuropsychiatric disorders, which were missed in the original GWAS analysis. Besides, the involved MMRP behind these genes could be given priority for further investigation to elucidate the pathogenic molecular mechanisms underlying neuropsychiatric disorders in future studies.

A bidirectional interaction-based hybrid network architecture for EEG cognitive recognition.

BACKGROUND AND OBJECTIVE: Extracting cognitive representation and computational representation information simultaneously from electroencephalography (EEG) data and constructing corresponding information interaction models can effectively improve the recognition capability of brain cognitive status. However, due to the huge gap in the interaction between the two types of information, existing studies have yet to consider the advantages of the interaction of both. METHODS: This paper introduces a novel architecture named the bidirectional interaction-based hybrid network (BIHN) for EEG cognitive recognition. BIHN consists of two networks: a cognitive-based network named CogN (e.g., graph convolution network, GCN; capsule network, CapsNet) and a computing-based network named ComN (e.g., EEGNet). CogN is responsible for extracting cognitive representation features from EEG data, while ComN is responsible for extracting computational representation features. Additionally, a bidirectional distillation-based coadaptation (BDC) algorithm is proposed to facilitate information interaction between CogN and ComN to realize the coadaptation of the two networks through bidirectional closed-loop feedback. RESULTS: Cross-subject cognitive recognition experiments were performed on the Fatigue-Awake EEG dataset (FAAD, 2-class classification) and SEED dataset (3-class classification), and hybrid network pairs of GCN + EEGNet and CapsNet + EEGNet were verified. The proposed method achieved average accuracies of 78.76% (GCN + EEGNet) and 77.58% (CapsNet + EEGNet) on FAAD and 55.38% (GCN + EEGNet) and 55.10% (CapsNet + EEGNet) on SEED, outperforming the hybrid networks without the bidirectional interaction strategy. CONCLUSIONS: Experimental results show that BIHN can achieve superior performance on two EEG datasets and enhance the ability of both CogN and ComN in EEG processing as well as cognitive recognition. We also validated its effectiveness with different hybrid network pairs. The proposed method could greatly promote the development of brain-computer collaborative intelligence.

MSFR-GCN: A Multi-Scale Feature Reconstruction Graph Convolutional Network for EEG Emotion and Cognition Recognition.

Graph Convolutional Network (GCN) excels at EEG recognition by capturing brain connections, but previous studies neglect the important EEG feature itself. In this study, we propose MSFR-GCN, a multi-scale feature reconstruction GCN for recognizing emotion and cognition tasks. Specifically, MSFR-GCN includes the MSFR and feature-pool characteristically, with the MSFR consisting of two sub-modules, multi-scale Squeeze-and-Excitation (MSSE) and multi-scale sample re-weighting (MSSR). MSSE assigns weights to channels and frequency bands based on their separate statistical information, while MSSR assigns sample weights based on combined channel and frequency information. The feature-pool, which pools across the feature dimension, is applied after GCN to retain EEG channel information. The MSFR-GCN achieves excellent results in emotion recognition when first tested on two public datasets, SEED and SEED-IV. Than the MSFR-GCN is tested on our self-collected Emotion and Cognition EEG dataset (ECED) for both emotion and cognition classification tasks. The results show MSFR-GCN's good performance in emotion and cognition classification tasks and reveal the implicit relationship between the two, which may provide aid in the rehabilitation of people with cognitive impairments from an emotional perspective.

Identify novel, shared and disorder-specific genetic architecture of major depressive disorder, insomnia and chronic pain.

Major depressive disorder (MDD), insomnia (INS) and chronic pain (CP) often have high comorbidity and show high genetic correlation. Here we aimed to better characterize their novel, shared and disorder-specific genetic architecture. Based on genome-wide association study (GWAS) summary data, we applied the conditional false discovery rate (condFDR) and conjunctional FDR (conjFDR) approach to investigate the novel and overlapped genetic loci for MDD, INS and CP. In addition, putative disorder-specific SNP associations were analyzed by conditioning the other two traits. The functions of the identified genomic loci were explored by performing gene set enrichment analysis (GSEA) for the loci mapped genes. We identified 22, 43 and 91 novel risk loci for MDD, INS and CP. GSEA for the loci mapped genes highlighted olfactory signaling pathway for MDD novel loci, breast cancer related gene set for both INS and CP novel loci, and nervous system related development, structure and activity for CP. Furthermore, we identified three loci jointly associated with the three disorders, including 13q14.3 locus with nearby gene OLFM4, 14q21.1 locus with nearby gene LRFN5 and 5q21.2 locus located in intergenic region. In addition, we identified one specific loci for MDD, 7 for INS and 11 for CP respectively by conditioning the other two traits, which were mapped to 68 genes for MDD, 85 for INS and 100 for CP. The MDD specific genes are enriched in immune system related pathways. This study increases understanding of the genetic architectures underlying MDD, INS and CP. The shared underlying genetic risk may help to explain the high comorbidity rates of the disorders.

EMCI: A Novel EEG-Based Mental Workload Assessment Index of Mild Cognitive Impairment.

As aging deepens, early detection of mild cognitive impairment (MCI) is increasingly important to prevent Alzheimer Dementia (AD) and improve the quality of life of older adults. In recent years, a large number of studies focus on the abnormal brain cognitive function of MCI, while ignoring the quantitative evaluation of MCI's mental workload. In this study, we propose a workload index for MCI screening, named EMCI, which is a linear discriminant cumulative estimate of subjects' electroencephalography (EEG) power spectra in α and ß rhythms. Then, we design a matched prototype system to verify the effectiveness of EMCI. The results show that the EMCI is sensitive to changes of subjects' mental workload, and is significantly lower in MCI than in HC (Health control), which may be precisely caused by cognitive dysfunction. The proposed EMCI index can be used for online assessment of mental workload in older adults, which can help achieve quick screening of MCI and provide a critical window for clinical treatment interventions.

The effect of perceived stress on cognition is mediated by personality and the underlying neural mechanism.

Perceived stress impairs cognitive function across the adult lifespan, but the extent to which cognition decline is variable across individuals. Individual differences in the stress response are described as personality traits. Substantial individual differences in the magnitude of cognitive impairment that is induced by short-term perceived stress are poorly understood. The present study tested the hypothesis that the relationship between short-term perceived stress and different aspects of cognition is mediated by personality traits. The study included 1066 participants with behavior and neuroimaging data from the Human Connectome Project after excluding individuals with missing variables. In the result, the parallel multiple mediation model demonstrated that the influence of perceived stress on the total and crystalized cognition is mainly mediated by neuroticism (indirect effect = -0.04, p < 0.05) and conscientiousness (indirect effect = 0.05, p < 0.05) in adults. Cortical thickness value (n = 1066) of the right superior frontal gyrus (SFG) showed not only positive correlations with short-term perceived stress and neuroticism, but negative associations with cognition. The chain mediation model found that the right SFG and neuroticism play a small but significant chain mediating effect between stress and total cognition. The strength of the resting-state functional connectivity (n = 968) between the left orbitofrontal cortex versus the left superior medial frontal cortex was positively correlated with crystallized cognition and negatively associated with conscientiousness. These results extend previous findings by the impacts of short-term perceived stress on cognitive function is mediated by neuroticism and the right SFG was the underlying neural mechanism.

DNA Methylation Markers and Prediction Model for Depression and Their Contribution for Breast Cancer Risk.

Background: Major depressive disorder (MDD) has become a leading cause of disability worldwide. However, the diagnosis of the disorder is dependent on clinical experience and inventory. At present, there are no reliable biomarkers to help with diagnosis and treatment. DNA methylation patterns may be a promising approach for elucidating the etiology of MDD and predicting patient susceptibility. Our overarching aim was to identify biomarkers based on DNA methylation, and then use it to propose a methylation prediction score for MDD, which we hope will help us evaluate the risk of breast cancer. Methods: Methylation data from 533 samples were extracted from the Gene Expression Omnibus (GEO) database, of which, 324 individuals were diagnosed with MDD. Statistical difference of DNA Methylation between Promoter and Other body region (SIMPO) score for each gene was calculated based on the DNA methylation data. Based on SIMPO scores, we selected the top genes that showed a correlation with MDD in random resampling, then proposed a methylation-derived Depression Index (mDI) by combining the SIMPO of the selected genes to predict MDD. A validation analysis was then performed using additional DNA methylation data from 194 samples extracted from the GEO database. Furthermore, we applied the mDI to construct a prediction model for the risk of breast cancer using stepwise regression and random forest methods. Results: The optimal mDI was derived from 426 genes, which included 245 positive and 181 negative correlations. It was constructed to predict MDD with high predictive power (AUC of 0.88) in the discovery dataset. In addition, we observed moderate power for mDI in the validation dataset with an OR of 1.79. Biological function assessment of the 426 genes showed that they were functionally enriched in Eph Ephrin signaling and beta-catenin Wnt signaling pathways. The mDI was then used to construct a predictive model for breast cancer that had an AUC ranging from 0.70 to 0.67. Conclusion: Our results indicated that DNA methylation could help to explain the pathogenesis of MDD and assist with its diagnosis.

Investigation on the micromorphology and thermophysical properties of NaNO3 heat storage materials modified by solution combustion.

Nitrate has a wide temperature range, wide operating temperature, low vapor pressure, low cost, strong heat transfer and stable chemical properties. It is widely used in solar thermal power generation heat storage material. In this paper, the alkali salt NaNO3 was modified by solution combustion method with citric acid as fuel. The structure and thermal properties of the prepared salts were studied by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The results show that the solution combustion process improves the structure and thermal properties of NaNO3, and the resulting product has a new phase. The particle size and microscopic morphology of the prepared salt were changed. As the proportion of fuel increases, the hollow cuboid structure gradually grows on the surface and inside of the modified salt. The microstructure obtained is different at different ignition temperatures, and a finer and even rod-like structure is obtained at an ignition temperature of 600 °C. The specific heat capacity of all modified samples has been improved, among which solid specific heat and liquid specific heat have increased the most, respectively 3.10 J/g·K and 3.19 J/g·K, which are 140.31% and 131.16% higher than the base salt, respectively. This work not only studies the specific heat capacity of NaNO3 modified by solution combustion, but also explores the effect of micromorphology and new phase formation on its performance, which provides innovative ideas for improving the specific heat capacity of molten salt heat storage materials.

Green oxidation of indoles using halide catalysis.

Oxidation of indoles is a fundamental organic transformation to deliver a variety of synthetically and pharmaceutically valuable nitrogen-containing compounds. Prior methods require the use of either organic oxidants (meta-chloroperoxybenzoic acid, N-bromosuccinimide, t-BuOCl) or stoichiometric toxic transition metals [Pb(OAc)4, OsO4, CrO3], which produced oxidant-derived by-products that are harmful to human health, pollute the environment and entail immediate purification. A general catalysis protocol using safer oxidants (H2O2, oxone, O2) is highly desirable. Herein, we report a unified, efficient halide catalysis for three oxidation reactions of indoles using oxone as the terminal oxidant, namely oxidative rearrangement of tetrahydro-ß-carbolines, indole oxidation to 2-oxindoles, and Witkop oxidation. This halide catalysis protocol represents a general, green oxidation method and is expected to be used widely due to several advantageous aspects including waste prevention, less hazardous chemical synthesis, and sustainable halide catalysis.