The longitudinal (in)stability and cognitive underpinnings of children's cheating behavior.

There has been a long-standing debate about whether cheating is a stable behavior across various situations. However, there is a notable gap in our understanding about whether children's cheating behavior could exhibit stability over time. Moreover, research on the cognitive correlates of children's cheating is limited, yet exploring these cognitive factors is essential for understanding how children make (dis)honest decisions.

Isowalsuranolide targets TrxR1/2 and triggers lysosomal biogenesis and autophagy via the p53-TFEB/TFE3 axis.

The lysosome is transformed from a major degradative site to a dynamic regulator of cellular homeostasis. Cancer cells with altered redox environments could be exploited as potential targets for cancer therapy. The thioredoxin (Trx) system, which includes thioredoxin reductases (TrxRs), is a promising target for cancer drug development.

Exosomes inhibit ferroptosis to alleviate intervertebral disc degeneration via the p62-KEAP1-NRF2 pathway.

Ferroptosis, an iron-dependent form of regulated cell death, has been reported to affect the activity of nucleus pulposus (NP) cells in the intervertebral disc (IVD), thereby contributing to intervertebral disc degeneration (IVDD). Exosomes (EXOs), extracellular nanovesicles that participate in intercellular communication, are potential therapeutic options for IVDD. Interestingly, while EXOs play an important role in inhibiting ferroptosis, whether EXOs from mesenchymal stem cells (MSCs) modulate the progression of IVDD through regulating ferroptosis is unclear.

Clinical features and outcomes of unresectable locally advanced lung adenocarcinoma with uncommon mutations: a retrospective multi-center Chinese study.

Background: Uncommon epidermal growth factor receptor () gene mutant locally advanced non-small cell lung cancer (NSCLC) has been poorly documented in the literature. Our study aimed to investigate the clinical features and outcomes associated with these mutations.

Methods: A multi-center retrospective study was conducted to review 511 patients with mutant unresectable stage III lung adenocarcinoma, treated between 2012 and 2018 across 12 Chinese institutions.

Mechanism analysis and targeted therapy of IDH gene mutation in glioma.

Isocitrate dehydrogenase (IDH) is a pivotal enzyme responsible for catalyzing the oxidative decarboxylation of isocitrate into α-ketoglutarate (α-KG). This enzyme serves as a crucial regulator in the tricarboxylic acid cycle (TCA cycle), acting as a rate-limiting step. Its role extends beyond mere metabolic function, influencing cellular homeostasis and overall cell function.

Design, Synthesis, and Biological Evaluation of Novel Orally Available Covalent CDK12/13 Dual Inhibitors for the Treatment of Tumors.

Cyclin-dependent kinases 12 and 13 (CDK12/13) safeguard genomic integrity by preferentially regulating gene expression in the DNA damage response (DDR). The CDK12/13-mediated upregulation of DDR genes and pathways significantly contributes to both tumorigenesis and the development of resistance to antitumor therapies. Thus, the functional inhibition of CDK12/13 offers an attractive strategy to combat carcinogenesis, particularly for refractory and treatment-resistant cancers.

Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin.

Metformin (MET) is a commonly used drug for the treatment of type 2 diabetes in the department of endocrinology. In recent years, due to the few clinically effective treatment options including glioma, some scholars have proposed the possibility of metformin in the treatment of glioma, and studies have shown that metformin has a certain inhibitory effect on this tumor. This review explores the multiple mechanisms through which metformin exerts its antitumor effects, focusing on signaling pathways such as AMPK/mTOR, ferroptosis, autophagy, apoptosis and chloride ion channels (CLIC1).

A 32-year trend analysis of lower respiratory infections in children under 5: insights from the global burden of disease study 2021.

Objectives: Lower respiratory infections are the most significant health threat to children under 5 years old, leading to the highest disease burden across all age groups. This study aims to provide an up-to-date assessment of the global burden of lower respiratory infections in children under 5 years of age.

Methods: This study utilizes data and methodologies from the Global Burden of Disease Study 2021 to analyze changes in the burden of lower respiratory infections from 1990 to 2021, focusing on incidence, mortality, and disability-adjusted life years.

Discovery of Pyrrolopyrazine Carboxamide Derivatives as Potent and Selective FGFR2/3 Inhibitors that Overcome Mutant Resistance.

Fibroblast growth factor receptors (FGFRs) are established oncogenic drivers in various solid tumors. However, the approved FGFR inhibitors face challenges with acquired resistance and dose-limiting adverse effects associated with FGFR1/4 inhibition, limiting therapeutic efficacy. Herein, we systematically explored linker and electrophile moieties based on the pyrrolopyrazine carboxamide core and identified aniline α-fluoroacrylamide as an effective covalent warhead.

Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing to the regulation of gene transcription. Diverse mutations of TET2 are frequently found in various blood cancers, yet the full scope of their functional consequences has been unexplored. Here, we report that a subset of TET2 mutations identified in leukemia patients alter the substrate specificity of TET2 from acting on mC to thymine.

Correlation between night sweats and season fluctuation in China.

Background: Night sweats are a condition in which an individual sweats excessively during sleep without awareness, and stops when they wake up. Prolonged episodes of night sweats might result in the depletion of trace elements and nutrients, affecting the growth and development of children.

Purpose: To investigate the relationship between sweat nights and season.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

A novel small molecule NJH-13 induces pyroptosis via the Ca driven AKT-FOXO1-GSDME signaling pathway in NSCLC by targeting TRPV5.

Introduction: Pyroptosis represents a mode of programmed necrotic cell death (PCD), mediated by members of gasdermin family (GSDMs), such as GSDME. It is emerging as a promising approach for combating cancer. Notably, GSDME is the key modulator for the switch between apoptosis and pyroptosis in cells.

Development of an AI model for predicting hypoxia status and prognosis in non-small cell lung cancer using multi-modal data.

Background: Prognosis prediction is crucial for non-small cell lung cancer (NSCLC) treatment planning. While tumor hypoxia significantly impacts patient outcomes, identifying hypoxic genomic markers remains challenging. This study sought to identify hypoxic computed tomography (CT) radiomic features and create an artificial intelligence (AI) model for NSCLC through the integration of multi-modal data.

Discovery of Potent, Highly Selective, and Orally Bioavailable MTA Cooperative PRMT5 Inhibitors with Robust Antitumor Activity.

Protein arginine methyltransferase 5 (PRMT5), which catalyzes the symmetric dimethylation of arginine residues on target proteins, plays a critical role in gene expression regulation, RNA processing, and signal transduction. Aberrant PRMT5 activity has been implicated in cancers and other diseases, making it a potential therapeutic target. Here, we report the discovery of a methylthioadenosine (MTA) cooperative PRMT5 inhibitor.

Inflammatory Effects and Regulatory Mechanisms of Chitinase-3-like-1 in Multiple Human Body Systems: A Comprehensive Review.

Chitinase-3-like-1 (Chi3l1), also known as YKL-40 or BRP-39, is a highly conserved mammalian chitinase with a chitin-binding ability but no chitinase enzymatic activity. Chi3l1 is secreted by various cell types and induced by several inflammatory cytokines. It can mediate a series of cell biological processes, such as proliferation, apoptosis, migration, differentiation, and polarization.

AttenhERG: a reliable and interpretable graph neural network framework for predicting hERG channel blockers.

Cardiotoxicity, particularly drug-induced arrhythmias, poses a significant challenge in drug development, highlighting the importance of early-stage prediction of human ether-a-go-go-related gene (hERG) toxicity. hERG encodes the pore-forming subunit of the cardiac potassium channel. Traditional methods are both costly and time-intensive, necessitating the development of computational approaches.

Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.

Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

Discovery of Pyridine-2-Carboxamides Derivatives as Potent and Selective HPK1 Inhibitors for the Treatment of Cancer.

Hematopoietic progenitor kinase 1 (HPK1) has emerged as an attractive target for immunotherapy due to its critical role in T cell activation and proliferation. The major challenge in developing HPK1 inhibitors lies in balancing kinase selectivity, pharmacokinetic (PK) properties, and therapeutic efficacy. In this study, we report a series of pyridine-2-carboxamide analogues demonstrating strong HPK1 inhibitory activity in enzymatic and cellular assays, along with good kinase selectivity.

Panaroma of microglia in traumatic brain injury: a bibliometric analysis and visualization study during 2000-2023.

Background: Traumatic brain injury (TBI) is a critical global health concern characterized by elevated rates of both morbidity and mortality. The pathological and physiological changes after TBI are closely related to microglia. Microglia, the primary immune cells in the brain, are closely linked to the mechanisms and treatment of TBI.

Chisco: An EEG-based BCI dataset for decoding of imagined speech.

The rapid advancement of deep learning has enabled Brain-Computer Interfaces (BCIs) technology, particularly neural decoding techniques, to achieve higher accuracy and deeper levels of interpretation. Interest in decoding imagined speech has significantly increased because its concept akin to "mind reading". However, previous studies on decoding neural language have predominantly focused on brain activity patterns during human reading.

Design, Synthesis, and Biological Evaluation of a Series of Spiro Analogues as Novel HPK1 Inhibitors.

Hematopoietic progenitor kinase 1 (HPK1) negatively affects T cell activation and proliferation and is a promising target for immunotherapy. Although HPK1 inhibitors have shown promising efficacy in preclinical models, none have been approved for clinical use. One significant challenge in developing an HPK1 inhibitor is the difficulty in designing a potent inhibitor with good kinase selectivity and pharmacokinetic properties.