Discovery of Potent Dual PROTAC Degraders Targeting BET-Kinase To Overcome FLT3 Inhibitor Resistance.

FMS-like tyrosine kinase 3 (FLT3) is a validated therapeutic target in acute myeloid leukemia (AML). However, numerous single-agent FLT3 or multitarget inhibitors fail to achieve complete and sustained suppression of FLT3 signaling due to the development of drug resistance. Herein, we report the design, synthesis, and evaluation of a novel series of dual BET-kinase degraders targeting FLT3, JAK2, and BRD4.

SITA: Predicting site-specific immunogenicity for therapeutic antibodies.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.

Artificial Intelligence in Nursing Decision-Making: A Bibliometric Analysis of Trends and Impacts.

Nursing decision-making is pivotal for patient safety and care quality. While artificial intelligence (AI) offers transformative potential in this field, a comprehensive analysis of global research trends is lacking. We conducted a bibliometric analysis of 238 publications (197 research papers, 41 reviews) from the Web of Science Core Collection (2003-2025) using CiteSpace and VOSviewer.

The effect of hypertension, obesity, and type 2 diabetes on lacunar stroke: A network Mendelian randomization study.

Background And Aims: Previous studies have reported an association of lacunar stroke with hypertension, obesity, and type 2 diabetes (T2D). The aim of this study was to investigate whether the association was causal and whether body mass index mediated the effect of hypertension on lacunar stroke.

Methods And Results: The independence and causal association of hypertension, obesity, and T2D with lacunar stroke were assessed by multivariate Mendelian randomization (MVMR) and network Mendelian randomization (NMR) with inverse variance weighting (IVW).

Effect and mechanism of miRNA-144-5p-regulated autophagy in older adults with Sarcopenia.

Background: Advanced aging invariably triggers an overabundance of apoptosis, stemming from diminished autophagy or a disarray in cellular autophagic processes. This, in turn, leads to an accelerated breakdown of muscle proteins, which exacerbates the ongoing deterioration of skeletal muscle and intensifies the severity of senile sarcopenia. This study aimed to investigate the role and mechanism of miRNA-regulated autophagy in senile sarcopenia.

Is it possible to foot reflexology for infants with sensorineural hearing loss?

Foot reflexology is a non-invasive and safe complementary therapy that works by massaging the reflex zones of the feet and exerts systemic or whole-body regulation through meridian nerve conduction. This therapy is commonly used in the treatment of various conditions such as autism and Parkinson's disease. However, there is limited reporting on the use of foot reflexology therapy for infants with sensorineural hearing loss (SNHL).

Discovery of HZS60 as a Novel Brain Penetrant NMDAR/TRPM4 Interaction Interface Inhibitor with Improved Activity and Pharmacokinetic Properties for the Treatment of Cerebral Ischemia.

The death signaling complex comprising extrasynaptic NMDAR and TRPM4 plays a pivotal role in the pathogenesis of ischemic stroke. Targeting the protein-protein interactions between NMDAR and TRPM4 represents a promising therapeutic strategy for ischemic stroke. Herein, we describe the discovery of a novel series of NMDAR/TRPM4 interaction interface inhibitors aimed at enhancing neuroprotective efficacy and optimizing pharmacokinetic profiles.

A review on ethnobotany, phytochemistry, and pharmacology of the genus DC.

The botanical drugs of genus DC. have been traditionally utilized in folk medicine for the treatment of a wide array of illnesses, encompassing fractures, bone wounds, carbuncles and poisoning, bronchitis, bruises, giddy with hypertension of qi, and lung deficiency cough. The genus DC.

Artificial intelligence applied to development of predictive stability model for intracranial aneurysms.

Background: We aimed to develop multiple machine learning models to predict the risk of early intracranial aneurysms (IAs) rupture, evaluate and compare the performance of predictive models.

Methods: Information related to patients diagnosed with IA by CT angiography and clinicians in Central hospital of Dalian University of Technology from January 2010 to June 2022 was collected, including clinical characteristics, blood indicators and IA morphological parameters. IA with rupture or maximum growth ≥ 0.

A Method for Sorting High-Quality Fresh Sichuan Pepper Based on a Multi-Domain Multi-Scale Feature Fusion Algorithm.

Post-harvest selection of high-quality Sichuan pepper is a critical step in the production process. To achieve this, a visual system needs to analyze Sichuan pepper with varying postures and maturity levels. To quickly and accurately sort high-quality fresh Sichuan pepper, this study proposes a multi-scale frequency domain feature fusion module (MSF3M) and a multi-scale dual-domain feature fusion module (MS-DFFM) to construct a multi-scale, multi-domain fusion algorithm for feature fusion of Sichuan pepper images.

The effects of repetitive transcranial magnetic and transcranial direct current stimulation on memory functions in older adults with mild cognitive impairment: a systematic review and meta-analysis.

Unlabelled: Mild cognitive impairment (MCI) is a condition that impairs activities of daily living, and often transforms to dementia. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) show promise in improving cognitive functions in MCI patients. In this meta-analysis, we aimed to compare the effects of rTMS and tDCS on memory functions in MCI patients.

Enhancing kiwifruit flower pollination detection through frequency domain feature fusion: a novel approach to agricultural monitoring.

The pollination process of kiwifruit flowers plays a crucial role in kiwifruit yield. Achieving accurate and rapid identification of the four stages of kiwifruit flowers is essential for enhancing pollination efficiency. In this study, to improve the efficiency of kiwifruit pollination, we propose a novel full-stage kiwifruit flower pollination detection algorithm named KIWI-YOLO, based on the fusion of frequency-domain features.

ZX703: A Small-Molecule Degrader of GPX4 Inducing Ferroptosis in Human Cancer Cells.

Ferroptosis is a novel form of oxidative cell death triggered by iron-dependent lipid peroxidation. The induction of ferroptosis presents an attractive therapeutic strategy for human diseases, such as prostate cancer and breast cancer. Herein, we describe our design, synthesis, and biological evaluation of endogenous glutathione peroxidase 4 (GPX4) degraders using the proteolysis targeting chimera (PROTAC) approach with the aim of inducing ferroptosis in cancer cells.

Design, Synthesis, and Biological Evaluation of Hydrophobic-Tagged Glutathione Peroxidase 4 (GPX4) Degraders.

Ferroptosis is an iron-dependent form of oxidative cell death induced by lipid peroxidation accumulation. Glutathione peroxidase 4 (GPX4) plays a key role in the regulation of ferroptosis and is considered to be a promising therapeutic target for cancer and other human diseases. Herein, we describe our design, synthesis, and biological evaluation of a series of HyT-based degraders of the GPX4.

CSI Feedback Model Based on Multi-Source Characterization in FDD Systems.

In wireless communication, to fully utilize the spectrum and energy efficiency of the system, it is necessary to obtain the channel state information (CSI) of the link. However, in Frequency Division Duplexing (FDD) systems, CSI feedback wastes part of the spectrum resources. In order to save spectrum resources, the CSI needs to be compressed.

Characterization of oxidative stress-induced cgahp, a gene coding for alkyl hydroperoxide reductase, from industrial importance Corynebacterium glutamicum.

Alkyl hydroperoxide reductase (Ahp), comprised of four different subunits AhpC, AhpD, AhpE, and AhpF, is a thiol-based antioxidative enzyme with the ability to protect bacteria against oxidative stress. Functionally, AhpC and AhpE considered as peroxidases directly detoxify peroxides, while AhpD and AhpF as oxidoreductases restore oxidized peroxidases to their reduced form. Corynebacterium glutamicum ncgl0877 encodes a putative Ahp with a unique Cys-Pro-Phe-Cys (C-P-G-C) active-site motif, similar with those of the thiol-disulfide oxidoreductases such as thioredoxin (Trx), mycoredoxin-1 (Mrx1) and AhpD.

The genetic and clinical characteristics of WFS1 related diabetes in Chinese early onset type 2 diabetes.

Diabetes is one of the most common phenotypes of Wolfram syndrome owing to the presence of the variants of the WFS1 gene and is often misdiagnosed as other types of diabetes. We aimed to explore the prevalence of WFS1-related diabetes (WFS1-DM) and its clinical characteristics in a Chinese population with early-onset type 2 diabetes (EOD). We sequenced all exons of the WFS1 gene in 690 patients with EOD (age at diagnosis ≤ 40 years) for rare variants.

Combining body mass index and waist height ratio to assess the relationship between obesity and serum uric acid levels in adolescents.

Background: The study aims to explore the relationship between obesity and serum uric acid in adolescents by combining body mass index and waist height ratio.

Methods: 475 adolescents in our study were classified as normal weight without central obesity (NW), normal weight but central obesity (NWCO), overweight or obesity without central obesity (OB) and overweight or obesity with central obesity (OBCO). Odds ratios (OR) and 95% confidence intervals (CI) for hyperuricemia were calculated using a logistic regression model.

Altered adolescents obesity metabolism is associated with hypertension: a UPLC-MS-based untargeted metabolomics study.

Objective: This study aimed to explore the relationship between the plasma metabolites of adolescent obesity and hypertension and whether metabolite alterations had a mediating effort between adolescent obesity and hypertension.

Methods: We applied untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to detect the plasma metabolomic profiles of 105 adolescents. All participants were selected randomly based on a previous cross-sectional study.

Fibroblast-Derived Extracellular Vesicle-Packaged Long Noncoding RNA Upregulated in Diabetic Skin Enhances Keratinocyte MMP-9 Expression and Delays Diabetic Wound Healing.

Accurate communication between fibroblasts and keratinocytes is crucial for diabetic wound healing. Extracellular vesicles are being explored as essential mediators of intercellular communication in the skin. However, the mechanisms underlying wound healing mediated by fibroblast-derived extracellular vesicles (Fib-EVs) remain unclear.

The Hub Genes Related to Osteoporosis Were Identified by Bioinformatics Analysis.

Osteoporosis (OP) is commonly encountered, which is a kind of systemic injury of bone mass and microstructure, leading to brittle fractures. With the aging of the population, this disease will pose a more serious impact on medical, social, and economic aspects, especially postmenopausal osteoporosis (PMOP). This study is aimed at figuring out potential therapeutic targets and new biomarkers in OP via bioinformatics tools.

Expression and clinical significance of FGFR1 and FGFR2 in laryngeal squamous cell carcinoma.

Background: Fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor receptor 2 (FGFR2) may be of significance in the development of laryngeal squamous cell carcinoma (SCC) tissues. Examination of the expression results of these factors may offer new insights into treatment of the disease, such as genetic and histological targeted target therapy.

Methods: We selected tissue from 30 cases of laryngeal SCC, 23 cases of adjacent normal mucosa, and 26 cases of benign laryngeal mucosal tissues from patients who received surgery at the Otolaryngology Department of the Affiliated Hospital of Chengde Medical College between September 2020 and January 2022.