Discovery of novel 3-Benzyloxyaminopyridines as orally available and intracranially active selective ROS1 inhibitors for combating the resistant ROS1 mutation.

The selectivity, central nervous system progression and drug-resistant mutations have raised significant concerns regarding the effectiveness of ROS1 inhibitors. Novel entities have been designed through precise molecular simulation. Introducing larger biphenyl groups in the hydrophobic region enhances ROS1 selectivity and improves lipid solubility for better blood-brain barrier penetration.

Prediction of lymphovascular invasion in invasive breast cancer via intratumoral and peritumoral multiparametric magnetic resonance imaging machine learning-based radiomics with Shapley additive explanations interpretability analysis.

Background: The use of multiparametric magnetic resonance imaging (MRI) in predicting lymphovascular invasion (LVI) in breast cancer has been well-documented in the literature. However, the majority of the related studies have primarily focused on intratumoral characteristics, overlooking the potential contribution of peritumoral features. The aim of this study was to evaluate the effectiveness of multiparametric MRI in predicting LVI by analyzing both intratumoral and peritumoral radiomics features and to assess the added value of incorporating both regions in LVI prediction.

Direct -SF and -SFCF Bond Formation through Strain-Release Functionalization of 3-Substituted [1.1.0]Azabicyclobutanes.

In comparison to modern methods for carbon-SF bond formation, methods for are exceptionally scarce, rendering motifs such as "-SF" virtually unexplored in the context of organic and medicinal chemistry. Herein, we demonstrate that direct -SF bond formation can be accomplished through strain-release pentafluorosulfanylation of 3-aryl [1.1.

The Role of Multiparametric MRI Radiomics for Preoperative Prediction of Axillary Lymph Node Metastasis in Patients With Invasive Breast Cancer: A Comparative Study.

Background: The predictive value of different MRI sequences for axillary lymph node metastasis (ALNM) in patients with invasive breast cancer remains unclear. This study compared the performance of radiomics models based on individual and combined MRI sequences for the preoperative prediction of ALNM and evaluated the clinical application value of the optimal model.

Methods: This retrospective study included 454 patients (mean ± SD age 50.

Development and validation of an MRI spatiotemporal interaction model for early noninvasive prediction of neoadjuvant chemotherapy response in breast cancer: a multicentre study.

Background: The accurate and early evaluation of response to neoadjuvant chemotherapy (NAC) in breast cancer is crucial for optimizing treatment strategies and minimizing unnecessary interventions. While deep learning (DL)-based approaches have shown promise in medical imaging analysis, existing models often fail to comprehensively integrate spatial and temporal tumor dynamics. This study aims to develop and validate a spatiotemporal interaction (STI) model based on longitudinal MRI data to predict pathological complete response (pCR) to NAC in breast cancer patients.

Investigating the role of 1,8-Cineole in mitigating ferroptosis in a HFSD/STZ diabetes mellitus type 2-induced model: A GEO data analysis approach.

Fructus Alpiniae Zerumbet (FAZ), a folk medicinal herb used by the Miao people in Guizhou, China, is rich in 1,8-Cineole - a bioactive monoterpene oxide with antioxidant and neuroprotective properties. However, its therapeutic potential against pancreatic β cells dysfunction, a hallmark of type 2 diabetes mellitus (T2DM), remains unexplored. This study investigated the molecular mechanism by which 1,8-Cineole mitigates hyperglycemia induced β cells ferroptosis.

Single-cell RNA-seq uncovers lineage-specific regulatory alterations of fibroblasts and endothelial cells in ligamentum flavum hypertrophy.

Background: Lumbar spinal stenosis (LSS) represents a major global healthcare burden resulting in back pain and disorders of the limbs among the elderly population. The hypertrophy of ligamentum flavum (HLF), marked by fibrosis and inflammation, significantly contributes to LSS. Fibroblasts and endothelial cells are two important cells in the pathological process of ligamentum flavum (LF) fibrosis and inflammation.

as a causative gene of developmental and epileptic encephalopathy and generalized epilepsies.

Genetic factors are the major causes of epilepsies, such as developmental and epileptic encephalopathy (DEE) and idiopathic generalized epilepsy (IGE). However, the etiology of most patients remains elusive. This study performed exon sequencing in a cohort of 173 patients with IGE.

Discovery of 3-phenyl-[1,2,4]triazolo[4,3-a]pyridine derivatives as potent smoothened inhibitors against colorectal carcinoma.

Smoothened (SMO) in Hedgehog (Hh) signaling pathway is intricately associated with the genesis of colorectal carcinoma (CRC), but SMO inhibitor Vismodegib lacks of therapeutic benefits. Based on the principles of preserving critical interactions and ring substitution, a series of 3-phenyl-[1,2,4]triazolo[4,3-a]pyridine derivatives were designed and synthesized. Among them, compound A11 exhibited significant inhibitory activity against SMO (IC = 0.

Mechanical stress contributes to ligamentum flavum hypertrophy by inducing local inflammation and myofibroblast transition in the innovative surgical rabbit model.

Background: Lumbar spinal canal stenosis (LSCS) ranks as a prevalent spinal disorder in senior populations. Ligamentum flavum hypertrophy (LFH) is a significant feature of LSCS, yet its cause is unclear. The purpose of this study was to create a novel animal model for LFH and explore the pathological mechanisms involved.

Habitat Radiomics Based on Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Assessing Axillary Lymph Node Burden in Clinical T1-T2 Stage Breast Cancer: A Multicenter and Interpretable Study.

Background: Axillary lymph node burden(ALNB) is a critical factor in determining treatment strategies for clinical T-T (cT-T) stage breast cancer. However, as ALNB assessment relies on invasive procedures, exploring non-invasive methods is essential.

Purpose: To develop and validate a habitat radiomics model for assessing ALNB in cT-T breast cancer, incorporating radiogenomic data to improve interpretability.

Artesunate demonstrates neuroprotective effect through activation of lysosomal function and inhibition of cGAS-STING pathway.

Artesunate, a derivative of artemisinin, has a variety of pharmacological effects. Its potential application in ischemic brain injury still largely unknown. This study investigated the therapeutic effect and pharmacological mechanism of artesunate in neuronal injury following cerebral ischemia, and explore the potential role of lysosomal function and cGAS-STING signaling pathway in ischemia injury and artesunate treatment.

The role of autophagy in fibrosis: Mechanisms, progression and therapeutic potential (Review).

Various forms of tissue damage can lead to fibrosis, an abnormal reparative reaction. In the industrialized countries, 45% of deaths are attributable to fibrotic disorders. Autophagy is a highly preserved process.

Gastrointestinal complications of hepatic glycogen storage disease: a national survey questionnaire study in China.

Background: Hepatic glycogen storage diseases (GSD) are inborn errors of metabolism with abnormal storage or utilization of glycogen, a complex disease with significant genetic heterogeneity and similar clinical manifestations. This study aimed to describe the gastrointestinal symptoms and endoscopic features of hepatic GSD, including types Ia, Ib, III, VI, and IX, to provide evidence for etiology and treatment.

Methods: A national cohort survey questionnaire was distributed to patients diagnosed with GSD type Ia, Ib, III, VI, and IX through genetic testing or their parents in mainland China in May 2022.

Discovery of novel Macrocyclic small molecules Based on 2-Amino-4-thiazolylpyridineas selective EGFR inhibitors with high Blood-Brain barrier penetration for the treatment of glioblastoma.

Because epidermal growth factor receptor (EGFR) is the most commonly mutated oncogene in glioblastoma (GBM), the development of EGFR inhibitors has become a promising direction for the treatment of GBM. However, due to factors such as limited blood-brain barrier (BBB) permeability and pathway compensation mechanisms, current EGFR inhibitors targeting GBM are not satisfactory. In the previous study, we obtained compound 10c with strong anti-cell proliferation activity.

1,8-Cineole alleviates Nrf2-mediated redox imbalance and mitochondrial dysfunction in diabetes mellitus by targeting Sirt1.

Background: Type 2 diabetes mellitus (T2DM) is primarily attributed to impaired insulin secretion caused by β cell dysfunction. 1,8-Cineole is a key bioactive compound in the essential oil extracted from Fructus Alpiniae Zerumbet, which possesses anti-inflammatory and antioxidant properties. Nevertheless, it remains elusive about the protective effect and precise mechanisms of 1,8-Cineole against the β cell deterioration in T2DM.

Gastrodin alleviates mitochondrial dysfunction by regulating SIRT3-mediated TFAM acetylation in vascular dementia.

Background: Mitochondrial dysfunction is key to the pathogenesis of vascular dementia (VaD). Sirtuin-3 (SIRT3), an essential member of the sirtuins family, has been proven to be a critical sirtuin in regulating mitochondrial function. The phenolic glucoside gastrodin (GAS), a bioactive ingredient from Gastrodiae Rhizome (known in Chinese as Tian ma) demonstrates significant neuroprotective properties against central nervous system disorders; however, the precise mechanisms through which GAS modulates VaD remain elusive.

Pharmacological approaches for targeting lysosomes to induce ferroptotic cell death in cancer.

Lysosomes are crucial organelles responsible for the degradation of cytosolic materials and bulky organelles, thereby facilitating nutrient recycling and cell survival. However, lysosome also acts as an executioner of cell death, including ferroptosis, a distinctive form of regulated cell death that hinges on iron-dependent phospholipid peroxidation. The initiation of ferroptosis necessitates three key components: substrates (membrane phospholipids enriched with polyunsaturated fatty acids), triggers (redox-active irons), and compromised defence mechanisms (GPX4-dependent and -independent antioxidant systems).

Sirt6 promotes DNA damage repair in osteoarthritis chondrocytes by activating the Keap1/Nrf2/HO-1 signaling pathway.

The aim of this study was to explore the effect and mechanism of Sirt6 on DNA damage repair in OA chondrocytes. Cartilage tissues were collected from OA patients with knee arthroplasty and traumatic amputation patients without OA. Besides, 7-week-old male C57BL/6 mice were randomly divided into Control and OA groups; CHON-001 cells of corresponding groups were treated with 10 ng/ml interleukin (IL)-1β, respectively.

Efficiency and safety of hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD1 therapy versus HAIC monotherapy for advanced hepatocellular carcinoma: A multicenter propensity score matching analysis.

Purpose: To investigate the clinical efficacy and safety of combination therapy of hepatic arterial infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) therapy in the treatment of advanced hepatocellular carcinoma (HCC).

Methods: In this retrospective clinical research, from March 2018 to December 2019, 1158 HCC patients categorized as BCLC stage C were reviewed for eligibility. We utilized propensity score matching (PSM) to mitigate initial disparities between the groups.

Peroxymonosulfate Activation by Cu-OMS-2 Nanofibers for Efficient Degradation of N-Containing Heterocycles in Aquatic Solution.

In this research, the degradation of different types of N-containing heterocycle (NHC) contaminants by Cu-OMS-2 via peroxymonosulfate (PMS) activation in an aqueous environment was investigated. First, the effects of different reaction parameters were optimized using benzotriazole (BTR) as the model contaminant, and the optimal reaction conditions were 8 mM PMS, 0.35 g/L Cu-OMS-2, and 30 °C.

An Analytical Method for Mechanical Analysis of Offshore Pipelines during Lifting Operation.

The lifting operation of offshore pipelines is an important step in ocean pipeline engineering. An effective analytical method is developed for investigating the mechanical properties of the pipeline based on mechanical, physical, and geometric relationships. By using the shooting and the secant methods to transform the boundary value problem into an initial value one and then solving them with the Runge-Kutta method, the deformation and mechanical properties of the pipeline are calculated.