Atomically Dispersed Mn-Ir Sites on 2D Amorphous Carbon Materials Synergistically Boost Electrochemical Overall Water Splitting.

Enhancing the activity and durability of noble-metal-based catalysts for overall water splitting is crucial for advancing sustainable energy conversion. In this study, a novel catalyst, PBN-Ir/Mn, is reported, developed through a self-healing process of the polyhexabenzocoronene network (PBN) that incorporates both Mn and Ir atoms. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC-HAADF-STEM) and X-ray absorption spectroscopy (XAS) characterizations confirm a unique atomic-scale Ir-Ir-Mn triangular structure on the porous PBN substrate.

Chemoresistance mechanisms to 5-Fluorouracil and reversal strategies in lung and breast cancer.

Chemotherapy drug 5-Fluorouracil (5-FU) is a major treatment for many cancers; however, its efficacy is limited by chemoresistance. Here, we investigate the resistance mechanisms to 5-FU and reversal strategies in lung and breast cancer cells. Using multiple 5-FU-resistant lung cancer and breast cancer cell models, we reveal differential cellular and molecular features of 5-FU resistance between different cancer types.

Efficacy of atypical antipsychotics in schizophrenia patients: effects of 5-HTR SNPs.

The 5-hydroxytryptamine receptor (5-HTR) is a key protein responsible for the effects of 5-hydroxytryptamine (5-HT) and an important target for many antipsychotics. 5-HTR has a high degree of genetic polymorphism, and atypical antipsychotics are 5-HTR antagonists widely used in treating schizophrenia. With the increasing development of medical technology, antipsychotics are being updated rapidly, and their efficacy and safety are being optimised.

Blood-Based Whole-Genome Methylation Analysis of Yili Horses Pre- and Post-Racing.

This study aims to analyze the whole-genome DNA methylation differences in Yili horses before and after racing, with the goal of identifying differentially methylated genes associated with racing performance and exploring the epigenetic mechanisms underlying exercise in horses. Blood samples were collected from the jugular veins of the top 3 Yili horses in a 5000 m race, which included 25 competitors, both prior to and within 5 min after the race. Genomic DNA was extracted, followed by sequencing using Whole-Genome Bisulfite Sequencing (WGBS) to assess DNA methylation levels, differentially methylated regions (DMRs), and differentially methylated genes (DMGs).

A comprehensive benchmark for multiple highly efficient base editors with broad targeting scope.

As the toolbox of base editors (BEs) expands, selecting appropriate BE and guide RNA (gRNA) to achieve optimal editing efficiency and outcome for a given target becomes challenging. Here, we construct a set of 10 adenine and cytosine BEs with high activity and broad targeting scope, and comprehensively evaluate their editing profiles and properties head-to-head with 34,040 BE-gRNA-target combinations using genomically integrated long targets and tiling gRNA strategies. Interestingly, we observe widespread non-canonical protospacer adjacent motifs (PAMs) for these BEs.

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.

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

[This corrects the article DOI: 10.3389/fneur.2024.

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.