HNF4α-CDKL3 axis restricts MASLD progression by targeting FoxO1 via noncanonical phosphorylation.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a worldwide disease with a broad spectrum of symptoms. Though mild in early stages, further development of MASLD causes steatohepatitis, cirrhosis, liver cancers, and accompanied diabetes. Discovery of the critical regulators in MASLD progression hold great values in both basic and translational medicine.

Exploring the Perspectives of Older Adults on a Digital Brain Health Platform Using Natural Language Processing: Cohort Study.

Background: Although digital technology represents a growing field aiming to revolutionize early Alzheimer disease risk prediction and monitoring, the perspectives of older adults on an integrated digital brain health platform have not been investigated.

Objective: This study aims to understand the perspectives of older adults on a digital brain health platform by conducting semistructured interviews and analyzing their transcriptions by natural language processing.

Methods: The study included 28 participants from the Boston University Alzheimer's Disease Research Center, all of whom engaged with a digital brain health platform over an initial assessment period of 14 days.

Assessment of Wearable Device Adherence for Monitoring Physical Activity in Older Adults: Pilot Cohort Study.

Background: Physical activity has emerged as a modifiable behavioral factor to improve cognitive function. However, research on adherence to remote monitoring of physical activity in older adults is limited.

Objective: This study aimed to assess adherence to remote monitoring of physical activity in older adults within a pilot cohort from objective user data, providing insights for the scalability of such monitoring approaches in larger, more comprehensive future studies.

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Fluoroalkyl-grafted polyoxometalate nanoclusters are used as supramolecular additives to precisely modify the ionic domains of Nafion, which can increase the proton conductivity and selectivity simultaneously. The resulting hybrid membranes show significantly enhanced power density in fuel cells and improved energy efficiency in vanadium flow batteries.

Digital neuropsychological measures by defense automated neurocognitive assessment: reference values and clinical correlates.

Introduction: Although the growth of digital tools for cognitive health assessment, there's a lack of known reference values and clinical implications for these digital methods. This study aims to establish reference values for digital neuropsychological measures obtained through the smartphone-based cognitive assessment application, Defense Automated Neurocognitive Assessment (DANA), and to identify clinical risk factors associated with these measures.

Methods: The sample included 932 cognitively intact participants from the Framingham Heart Study, who completed at least one DANA task.

Intrinsic targeting of host RNA by Cas13 constrains its utility.

Cas13 can be used for the knockdown, editing, imaging or detection of RNA and for RNA-based gene therapy. Here by using RNA immunoprecipitation sequencing, transcriptome profiling, biochemical analysis, high-throughput screening and machine learning, we show that Cas13 can intrinsically target host RNA in mammalian cells through previously unappreciated mechanisms. Different from its known cis/trans RNA-cleavage activity, Cas13 can also cleave host RNA via mechanisms that are transcript-specific, independent of the sequence of CRISPR RNA and dynamically dependent on the conformational state of Cas13, as we show for several Cas13-family effectors encoded in one-vector and two-vector lentiviral systems.

USP10 strikes down β-catenin by dual-wielding deubiquitinase activity and phase separation potential.

Wnt/β-catenin signaling is a conserved pathway crucially governing development, homeostasis, and oncogenesis. Discoveries of its regulators hold great values in both basic and translational research. Through screening, we identified a deubiquitinase, USP10, as a critical modulator of β-catenin.

A deep learning-based drug repurposing screening and validation for anti-SARS-CoV-2 compounds by targeting the cell entry mechanism.

The recent outbreak of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a severe threat to the global public health and economy, however, effective drugs to treat COVID-19 are still lacking. Here, we employ a deep learning-based drug repositioning strategy to systematically screen potential anti-SARS-CoV-2 drug candidates that target the cell entry mechanism of SARS-CoV-2 virus from 2635 FDA-approved drugs and 1062 active ingredients from Traditional Chinese Medicine herbs. In silico molecular docking analysis validates the interactions between the top compounds and host receptors or viral spike proteins.

Modeling kidney development, disease, and plasticity with clonal expandable nephron progenitor cells and nephron organoids.

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here we report manipulation of p38 and YAP activity creates a synthetic niche that allows the long-term clonal expansion of primary mouse and human NPCs, and induced NPCs (iNPCs) from human pluripotent stem cells. Cultured iNPCs resemble closely primary human NPCs, generating nephron organoids with abundant distal convoluted tubule cells, which are not observed in published kidney organoids.

Modeling CRISPR-Cas13d on-target and off-target effects using machine learning approaches.

A major challenge in the application of the CRISPR-Cas13d system is to accurately predict its guide-dependent on-target and off-target effect. Here, we perform CRISPR-Cas13d proliferation screens and design a deep learning model, named DeepCas13, to predict the on-target activity from guide sequences and secondary structures. DeepCas13 outperforms existing methods to predict the efficiency of guides targeting both protein-coding and non-coding RNAs.

The Study of Alternative Splicing Events in Human Induced Pluripotent Stem Cells From a Down's Syndrome Patient.

Down's syndrome (DS) is one of the most commonly known disorders with multiple congenital disabilities. Besides severe cognitive impairment and intellectual disability, individuals with DS also exhibit additional phenotypes of variable penetrance and severity, with one or more comorbid conditions, including Alzheimer's disease, congenital heart disease, or leukemia. Various vital genes and regulatory networks had been studied to reveal the pathogenesis of the disease.

Lycopene Aggravates Acute Gastric Injury Induced by Ethanol.

Lycopene is an important natural red pigment with strong singlet oxygen and peroxide free radical quenching ability. Ethanol directly destroys the epithelial cells of gastric mucosa, causing oxidative damage and inflammation. To evaluate the effect of lycopene on the ethanol induced gastric injury, 112 adult male Kunming mice were randomly divided into normal control, lycopene control, gastric injury control, omeprazole (20 mg/kg) positive control, and lycopene experimental groups (at doses of 10, 50, 100, and 150 mg/kg body weight) in this study.

An drug repositioning workflow for host-based antivirals.

Drug repositioning represents a cost- and time-efficient strategy for drug development. Artificial intelligence-based algorithms have been applied in drug repositioning by predicting drug-target interactions in an efficient and high throughput manner. Here, we present a workflow of drug repositioning for host-based antivirals using specially defined targets, a refined list of drug candidates, and an easily implemented computational framework.

A chemical-enhanced system for CRISPR-Based nucleic acid detection.

The CRISPR-based nucleic acid detection systems have shown great potential for point-of-care testing of viral pathogens, especially in the context of COVID-19 pandemic. Here we optimize several key parameters of reaction chemistry and develop a Chemical Enhanced CRISPR Detection system for nucleic acid (termed CECRID). For the Cas12a/Cas13a-based signal detection phase, we determine buffer conditions and substrate range for optimal detection performance, and reveal a crucial role of bovine serum albumin in enhancing trans-cleavage activity of Cas12a/Cas13a effectors.

Untargeted Global Metabolomic Analysis Reveals the Mechanism of Tripropylamine-Enhanced Lycopene Accumulation in .

We previously determined that the cyclase inhibitor tripropylamine (TPA) significantly enhances lycopene accumulation in . To elucidate the mechanism of TPA-enhanced lycopene accumulation, the untargeted metabolome of treated with TPA was analyzed by UHPLC-Q-TOF/MS. Forty-two differential metabolites were identified, of which 15 significantly differential metabolites meeting the following parameters were screened: variable importance for the projection > 1, < 0.

A computational framework of host-based drug repositioning for broad-spectrum antivirals against RNA viruses.

RNA viruses are responsible for many zoonotic diseases that post great challenges for public health. Effective therapeutics against these viral infections remain limited. Here, we deployed a computational framework for host-based drug repositioning to predict potential antiviral drugs from 2,352 approved drugs and 1,062 natural compounds embedded in herbs of traditional Chinese medicine.

A Fully Conjugated 3D Covalent Organic Framework Exhibiting Band-like Transport with Ultrahigh Electron Mobility.

Although π-conjugated two dimensional (2D) covalent organic frameworks (COFs) have been extensively reported, developing fully π-conjugated 3D COFs is still an extremely difficult problem due to the lack of fully π-conjugated 3D linkers. We synthesize a fully conjugated 3D COF (BUCT-COF-1) by designing a saddle-shaped building block of aldehyde-substituted cyclooctatetrathiophene (COThP)-CHO. As a consequence of the fully conjugated 3D network, BUCT-COF-1 demonstrates ultrahigh Hall electron mobility up to ≈3.

Improving Cancer Immunotherapy with CRISPR-Based Technology.

The rapidly evolving field of immunotherapy has attracted great attention in the field of cancer research and already revolutionized the clinical practice standard for treating cancer. Genetically engineered T cells expressing either T cell receptors or chimeric antigen receptors represent novel treatment modalities and are considered powerful weapons to fight cancer. The immune checkpoint blockade, which harnesses the negative control signaling behind the anti-tumor immune response with therapeutic antibodies by blocking cytotoxic T lymphocyte-associated protein 4 or the programmed cell death 1 pathways are another mainstream direction for cancer immunotherapy.

CRISP-view: a database of functional genetic screens spanning multiple phenotypes.

High-throughput genetic screening based on CRISPR/Cas9 or RNA-interference (RNAi) enables the exploration of genes associated with the phenotype of interest on a large scale. The rapid accumulation of public available genetic screening data provides a wealth of knowledge about genotype-to-phenotype relationships and a valuable resource for the systematic analysis of gene functions. Here we present CRISP-view, a comprehensive database of CRISPR/Cas9 and RNAi screening datasets that span multiple phenotypes, including in vitro and in vivo cell proliferation and viability, response to cancer immunotherapy, virus response, protein expression, etc.

CDKL3 promotes osteosarcoma progression by activating Akt/PKB.

Osteosarcoma (OS) is a primary malignant bone neoplasm with high frequencies of tumor metastasis and recurrence. Although the Akt/PKB signaling pathway is known to play key roles in tumorigenesis, the roles of cyclin-dependent kinase-like 3 (CDKL3) in OS progression remain largely elusive. We have demonstrated the high expression levels of CDKL3 in OS human specimens and comprehensively investigated the role of CDKL3 in promoting OS progression both in vitro and in vivo.