Combining Deep Learning and Structural Modeling to Identify Potential Acetylcholinesterase Inhibitors from Hericium erinaceus.

Alzheimer's disease (AD) is the most common type of dementia, affecting over 50 million people worldwide. Currently, most approved medications for AD inhibit the activity of acetylcholinesterase (AChE), but these treatments often come with harmful side effects. There is growing interest in the use of natural compounds for disease prevention, alleviation, and treatment. This trend is driven by the anticipation that these substances may incur fewer side effects than existing medications. This research presents a computational approach combining machine learning with structural modeling to discover compounds from medicinal mushrooms with a high potential to inhibit the activity of AChE. First, we developed a deep neural network capable of rapidly screening a vast number of compounds to indicate their potential to inhibit AChE activity. Subsequently, we applied deep learning models to screen the compounds in the BACMUSHBASE database, which catalogs the bioactive compounds from cultivated and wild mushroom varieties local to Thailand, resulting in the identification of five promising compounds. Next, the five identified compounds underwent molecular docking techniques to calculate the binding energy between the compounds and AChE. This allowed us to refine the selection to two compounds, erinacerin A and hericenone B. Further analysis of the binding energy patterns between these compounds and the target protein revealed that both compounds displayed binding energy profiles similar to the combined characteristics of donepezil and galanthamine, the prescription drugs for AD. We propose that these two compounds, derived from Hericium erinaceus (also known as lion's mane mushroom), are suitable candidates for further research and development into symptom-alleviating AD medications.

De Novo Design of Molecules with Multiaction Potential from Differential Gene Expression using Variational Autoencoder.

The modulating effect of chemical compounds and therapeutics on gene transcription is well-reported and has been intensively studied for both clinical and research purposes. Emerging research points toward the utility of drug-induced transcriptional alterations in de novo molecular design and highlights the idea of phenotype-matching an expression signature of interest to the structures being designed. In this work, we build an autoencoder-based generative model, BiCEV, around this concept. Our generative autoencoder has demonstrably generated a set of new molecules from gene expression input with notable validity (96%), uniqueness (98%), and internal diversity (0.77). Further, we attempted to validate BiCEV by testing the model on gene-knockdown profiles and combined signatures of synergistic drug pairs. From these investigations, we found the designed structures to be consistently high in collective quality. However, when their similarities to the supposed functional equivalents as determined by shared targets were considered, the findings were somewhat mixed. In spite of this, we believe the generative model merits further development in conjunction with in vitro corroboration to lend itself to being an assistive tool for drug discovery experts, particularly to support the initial stages of hit identification and lead optimization.

Potential Applications of Mobile and Wearable Devices for Psychological Support During the COVID-19 Pandemic: A Review.

The coronavirus disease 19 (COVID-19) pandemic that has been raging in 2020 does affect not only the physical state but also the mental health of the general population, particularly, that of the healthcare workers. Given the unprecedented large-scale impacts of the COVID-19 pandemic, digital technology has gained momentum as invaluable social interaction and health tracking tools in this time of great turmoil, in part due to the imposed state-wide mobilization limitations to mitigate the risk of infection that might arise from in-person socialization or hospitalization. Over the last five years, there has been a notable increase in the demand and usage of mobile and wearable devices as well as their adoption in studies of mental fitness. The purposes of this scoping review are to summarize evidence on the sweeping impact of COVID-19 on mental health as well as to evaluate the merits of the devices for remote psychological support. We conclude that the COVID-19 pandemic has inflicted a significant toll on the mental health of the population, leading to an upsurge in reports of pathological stress, depression, anxiety, and insomnia. It is also clear that mobile and wearable devices (e.g., smartwatches and fitness trackers) are well placed for identifying and targeting individuals with these psychological burdens in need of intervention. However, we found that most of the previous studies used research-grade wearable devices that are difficult to afford for the normal consumer due to their high cost. Thus, the possibility of replacing the research-grade wearable devices with the current smartwatch is also discussed.