Erinacine A-Enriched Mycelium Ethanol Extract Lessens Cellular Damage in Cell and Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation.

Spinocerebellar ataxia type 3 (SCA3), caused by the abnormal expansion of polyglutamine (polyQ) in the ataxin-3 protein, is one of the inherited polyQ neurodegenerative diseases that share similar genetic and molecular features. Mutant polyQ-expanded ataxin-3 protein is prone to aggregation in affected neurons and is predominantly degraded by autophagy, which is beneficial for neurodegenerative disease treatment. Not only does mutant polyQ-expanded ataxin-3 increase susceptibility to oxidative cytotoxicity, but it also hampers antioxidant potency in neuronal cells.

Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials.

The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.

ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm.

Background: Disturbed metabolism and transport of citrate play significant roles in various pathologies. However, vascular citrate regulation and its potential role in aortic aneurysm (AA) development remain poorly understood.

Methods: Untargeted metabolomics by mass spectrometry was applied to identify upregulated metabolites of the tricarboxylic acid cycle in AA tissues of mice.

Machine-learning-based predictive classifier for bone marrow failure syndrome using complete blood count data.

Accurate risk assessment of bone marrow failure syndrome (BMFS) is crucial for early diagnosis and intervention. Interpreting complete blood count (CBC) data is challenging without hematological expertise. To support primary physicians, we developed a predictive model using basic demographics and CBC data collected retrospectively from two major hospitals in South Korea.

Selective degradation of multimeric proteins by TRIM21-based molecular glue and PROTAC degraders.

Targeted protein degradation (TPD) utilizes molecular glues or proteolysis-targeting chimeras (PROTACs) to eliminate disease-causing proteins by promoting their interaction with E3 ubiquitin ligases. Current TPD approaches are limited by reliance on a small number of constitutively active E3 ubiquitin ligases. Here, we report that (S)-ACE-OH, a metabolite of the antipsychotic drug acepromazine, acts as a molecular glue to induce an interaction between the E3 ubiquitin ligase TRIM21 and the nucleoporin NUP98, leading to the degradation of nuclear pore proteins and disruption of nucleocytoplasmic trafficking.

Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders.

Background: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.

Methods: To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC).

GLO1 regulates hepatocellular carcinoma proliferation and migration through the cell cycle pathway.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor characterized by a high mortality rate. The occurrence and progression of HCC are linked to oxidative stress. Glyoxalase-1 (GLO1) plays an important role in regulating oxidative stress, yet the underlying mechanism remains unclear.

Testing the Ability and Limitations of ChatGPT to Generate Differential Diagnoses from Transcribed Radiologic Findings.

Background The burgeoning interest in ChatGPT as a potentially useful tool in medicine highlights the necessity for systematic evaluation of its capabilities and limitations. Purpose To evaluate the accuracy, reliability, and repeatability of differential diagnoses produced by ChatGPT from transcribed radiologic findings. Materials and Methods Cases selected from a radiology textbook series spanning a variety of imaging modalities, subspecialties, and anatomic pathologies were converted into standardized prompts that were entered into ChatGPT (GPT-3.

De novo design of mini-protein binders broadly neutralizing Clostridioides difficile toxin B variants.

Clostridioides difficile toxin B (TcdB) is the key virulence factor accounting for C. difficile infection-associated symptoms. Effectively neutralizing different TcdB variants with a universal solution poses a significant challenge.

DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging.

Background: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty.

Multi-Adaptive Strategies-Based Higher-Order Quantum Genetic Algorithm for Agile Remote Sensing Satellite Scheduling Problem.

The agile remote sensing satellite scheduling problem (ARSSSP) for large-scale tasks needs to simultaneously address the difficulties of complex constraints and a huge solution space. Taking inspiration from the quantum genetic algorithm (QGA), a multi-adaptive strategies-based higher-order quantum genetic algorithm (MAS-HOQGA) is proposed for solving the agile remote sensing satellites scheduling problem in this paper. In order to adapt to the requirements of engineering applications, this study combines the total task number and the total task priority as the optimization goal of the scheduling scheme.

HER2-CD3-Fc Bispecific Antibody-Encoding mRNA Delivered by Lipid Nanoparticles Suppresses HER2-Positive Tumor Growth.

The human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor and tumor-associated antigen abnormally expressed in various types of cancer, including breast, ovarian, and gastric cancer. HER2 overexpression is highly correlated with increased tumor aggressiveness, poorer prognosis, and shorter overall survival. Consequently, multiple HER2-targeted therapies have been developed and approved; however, only a subset of patients benefit from these treatments, and relapses are common.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.

RNA Helicase DDX5 Maintains Cardiac Function by Regulating Alternative Splicing.

Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. RNA-binding proteins are identified as regulators of cardiac disease; DDX5 (dead-box helicase 5) is a master regulator of many RNA processes, although its function in heart physiology remains unclear.

Methods: We assessed DDX5 expression in human failing hearts and a mouse HF model.

A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets for breast cancer.

Background: Adhesion G protein-coupled receptors (aGPCRs), a distinctive subset of the G protein-coupled receptor (GPCR) superfamily, play crucial roles in various physiological and pathological processes, with implications in tumor development. Despite the global prevalence of breast cancer (BRCA), specific aGPCRs as potential drug targets or biomarkers remain underexplored.

Methods: UALCAN, GEPIA, Kaplan-Meier Plotter, MethSurv, cBiopportal, String, GeneMANIA, DAVID, Timer, Metascape, and qPCR were applied in this work.

A Biomimetic Cement-Based Solid-State Electrolyte with Both High Strength and Ionic Conductivity for Self-Energy-Storage Buildings.

Cement-based materials are the foundation of modern buildings but suffer from intensive energy consumption. Utilizing cement-based materials for efficient energy storage is one of the most promising strategies for realizing zero-energy buildings. However, cement-based materials encounter challenges in achieving excellent electrochemical performance without compromising mechanical properties.