Discovery of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) inhibitors using an artificial intelligence model and their effects on tau and tubulin dynamics.

The dual-specificity tyrosine-phosphorylation-regulated kinase 1 A (DYRK1A) presents a promising therapeutic target for neurological diseases. However, current inhibitors lack selectivity, which can lead to unexpected side effects and increase the difficulty of studying DYRK1A. Therefore, identifying selective inhibitors targeting DYRK1A is essential for reducing side effects and facilitating neurological disease research.

Discovering a novel dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) inhibitor and its impact on tau phosphorylation and amyloid-β formation.

Dual-specificity tyrosine-regulated kinase 1 A (DYRK1A) is crucial in neurogenesis, synaptogenesis, and neuronal functions. Its dysregulation is linked to neurodegenerative disorders like Down syndrome and Alzheimer's disease. Although the development of DYRK1A inhibitors has significantly advanced in recent years, the selectivity of these drugs remains a critical challenge, potentially impeding further progress.

Syntheses of LSD1/HDAC Inhibitors with Demonstrated Efficacy against Colorectal Cancer: and Studies Including Patient-Derived Organoids.

Precedential evidence ascertaining the overexpression of LSD1 and HDACs in colorectal cancer spurred us to design a series of dual LSD1-HDAC inhibitors. Capitalizing on the modular nature of the three-component HDAC inhibitory model, tranylcypromine as a surface recognition motif was appended to zinc-binding motifs via diverse linkers. A compendium of hydroxamic acids was generated and evaluated for cytotoxicity against HCT-116 cells (human colorectal cancer cell lines).

Application of Phosphorylated Tau for Predicting Outcomes Among Sudden Cardiac Arrest Survivors.

Background: Phosphorylated Tau (p-Tau), an early biomarker of neuronal damage, has emerged as a promising candidate for predicting neurological outcomes in cardiac arrest (CA) survivors. Despite its potential, the correlation of p-Tau with other clinical indicators remains underexplored. This study assesses the predictive capability of p-Tau and its effectiveness when used in conjunction with other predictors.

Adolescents and Children Age Estimation Using Machine Learning Based on Pulp and Tooth Volumes on CBCT Images.

Objectives: To estimate adolescents and children age using stepwise regression and machine learning methods based on the pulp and tooth volumes of the left maxillary central incisor and cuspid on cone beam computed tomography (CBCT) images, and to compare and analyze the estimation results.

Methods: A total of 498 Shanghai Han adolescents and children CBCT images of the oral and maxillofacial regions were collected. The pulp and tooth volumes of the left maxillary central incisor and cuspid were measured and calculated.

An ensemble machine learning model generates a focused screening library for the identification of CDK8 inhibitors.

The identification of an effective inhibitor is an important starting step in drug development. Unfortunately, many issues such as the characterization of protein binding sites, the screening library, materials for assays, etc., make drug screening a difficult proposition.

Nontargeted metabolomics and enzyme inhibitory and antioxidant activities for chemical and biological characterization of jujube (Ziziphus jujuba) extracts.

The chemical and biologically active characterization of jujube samples (fruits, cores, and leaves) were carried out by the integrated nontargeted metabolomics and bioassay. Firstly, collision cross-section values of active compounds in jujubes were determined by ultrahigh-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry. Then, a multidimensional statistical analysis that contained principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis was employed to effectively cluster different tissues and types of jujubes, making identification more scientific.

Identification of selective dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors and their effects on tau and microtubule.

The overexpression of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), commonly observed in neurodegenerative diseases like Alzheimer's disease (AD) and Down syndrome (DS), can induce the formation of neurofibrillary tangles (NFTs) and amyloid plaques. Hence, designing a selective DYRK1A inhibitor would result in a promising small molecule for treating neurodegenerative diseases. Developing selective inhibitors for DYRK1A has been a difficult challenge due to the highly preserved ATP-binding site of protein kinases.

Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed expeditious synthesis from isoquinolin-5-ol.

The KSO-mediated generation of -iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione. This hydroxyl group-guided substitution was also applied to selected heterocycles and addressed the regioselectivity issue of quinones. This study has provided an expeditious pathway from isoquinolin-5-ol (5) to ellipticine (1) and isoellipticine (2), which benefits the comprehensive comparison of their activity.

β-Cyclodextrin-assisted mechanical inclusion extraction of lipophilic flavonoids and hydrophilic terpenoids from functional food.

This study presents an innovative, efficient, environmentally friendly and rapid mechanical inclusion extraction (MIE) method for active ingredients in functional food. 2-hydroxypropyl-beta-cyclodextrin was used as the inclusion reagent, and water was used as the extraction solvent in MIE. The experimental parameters affecting the extraction efficiency of the target compounds were systematically investigated using single-factor experiments and surface response methodology optimization.

Three-dimensional ultrasound-based radiomics nomogram for the prediction of extrathyroidal extension features in papillary thyroid cancer.

Purpose: To develop and validate a three-dimensional ultrasound (3D US) radiomics nomogram for the preoperative prediction of extrathyroidal extension (ETE) in papillary thyroid cancer (PTC).

Methods: This retrospective study included 168 patients with surgically proven PTC (non-ETE, n = 90; ETE, n = 78) who were divided into training (n = 117) and validation (n = 51) cohorts by a random stratified sampling strategy. The regions of interest (ROIs) were obtained manually from 3D US images.

[Superstitious Beliefs Among Healthcare Providers: A Concept Analysis].

Evidence-based practice is a problem-solving approach to healthcare delivery that reflects the best current scientific evidence. When healthcare providers face unexpected changes in a patient's condition or uncontrollable situations during care delivery, they may have less confidence or feel fearful / anxious about the care process and result. As people, healthcare providers may hold beliefs regarding the effect of external, supernatural forces on events, which may lead to superstitious beliefs and behaviors.

Development and Validation of a Radiomics Model Based on 3-Dimensional Endoanal Rectal Ultrasound of Rectal Cancer for Predicting Lymph Node Metastasis.

Background: Development of a radiomics model for predicting lymph node metastasis status in rectal cancer patients based on 3-dimensional endoanal rectal ultrasound images.

Methods: This study retrospectively included 79 patients (41 with lymph node metastasis positive and 38 with lymph node metastasis negative) diagnosed with rectal cancer in our hospital from January 2018 to February 2022. The tumor's region of interest is first delineated by radiologists, from which radiomics features are extracted.

Modeling Heme Peroxidase: Heme Saddling Facilitates Reactions with Hyperperoxides To Form High-Valent Fe -Oxo Species.

Saddle-shaped hemes have been discovered in the structures of most peroxidases. How such a macrocycle deformation affects the reaction of Fe hemes with hydrogen peroxide (H O ) to form high-valent Fe-oxo species remains uncertain. Through examination of the ESI-MS spectra, absorption changes and H NMR chemical shifts, we investigated the reactions of two Fe porphyrins with different degrees of saddling deformation, namely Fe (OETPP)ClO (1 ) and Fe (OMTPP)ClO (1 ), with tert-butyl hydroperoxide (tBuOOH) in CH Cl at -40 °C, which quickly resulted in O-O bond homolysis from a highly unstable Fe -alkylperoxo intermediate, Fe -O(H)OR (2) into Fe -oxo porphyrins (3).

Combined cardiomegaly and aortic arch calcification predict mortality in hemodialysis patients.

Introduction: This study aimed to investigate the relationship between cardiomegaly and aortic arch calcification (AAC) and overall/cardiovascular mortality in hemodialysis patients.

Methods: We conducted a retrospective cohort study and enrolled patients who underwent initial hemodialysis. Cardiomegaly and AAC were determined by chest radiography and classified into four groups according to cross-classification of cardiothoracic ratio (CTR) of 0.

O-methylated flavonol as a multi-kinase inhibitor of leukemogenic kinases exhibits a potential treatment for acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a heterogeneous disease with poor overall survival characterized by various genetic changes. The continuous activation of oncogenic pathways leads to the development of drug resistance and limits current therapeutic efficacy. Therefore, a multi-targeting inhibitor may overcome drug resistance observed in AML treatment.

A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo.

Acute leukemia is a highly heterogeneous disease; therefore, combination therapy is commonly used for patient treatment. Drug-drug interaction is a major concern of combined therapy; hence, dual/multi-target inhibitors have become a dominant approach for cancer drug development. HDACs and HSP90 are involved in the activation of various oncogenic signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, and RAF/MEK/ERK, which are also highly enriched in acute leukemia gene expression profiles.

Systematic Placement of the Enigmatic Southeast Asian Genus and an Updated Phylogeny of Tribe Pogostemoneae (Lamiaceae Subfamily Lamioideae).

(Lamiaceae) is a monotypic genus within the subfamily Lamioideae and has a sporadic distribution in subtropical mountains of southeast Asia. Although recent studies have greatly improved our understanding of generic relationships within Lamioideae, the second most species-rich subfamily of Lamiaceae, the systematic position of within the subfamily remains unclear. In this study, we investigate the phylogenetic placement of the genus using three datasets: (1) a 69,276 bp plastome alignment of Lamiaceae; (2) a five chloroplast DNA region dataset of tribe Pogostemoneae, and (3) a nuclear ribosomal internal transcribed spacer region dataset of Pogostemoneae.

Ring-opening of five-membered heterocycles conjugated 4-isopropylresorcinol scaffold-based benzamides as HSP90 inhibitors suppressing tumor growth in vitro and in vivo.

A series of ring-opened dihydroxybenzamides have been designed and synthesized as heat shock protein 90 inhibitors. One of derivatives, compound 6b ((N-ethyl-2,4-dihydroxy-5-isopropyl-N-(pyridin-3-yl)benzamide)) demonstrated remarkable antiproliferative activity against in human KRAS mutant A549 and EGFR T790 M mutant H1975 lung cancer cell lines with GI values of 0.07 and 0.