Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML.

Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development of multiple cancers. Targeted regulation of deubiquitination has been recognized as an important strategy in tumor therapy. However, the mechanism by which drugs regulate deubiquitinase is not clear.

Utilizing explainable machine learning for progression-free survival prediction in high-grade serous ovarian cancer: insights from a prospective cohort study.

Background: High-grade serous ovarian cancer (HGSOC) remains one of the most challenging gynecological malignancies, with over 70% of ovarian cancer patients ultimately experiencing disease progression. The current prognostic tools for progression-free survival (PFS) in HGSOC patients have limitations. This study aims to develop an explainable machine learning (ML) model for predicting PFS in HGSOC patients.

Comparison of the efficacy of neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients: meta-analysis of randomized controlled trials.

Background: Preoperative neoadjuvant chemoradiotherapy (nCRT) is considered to be the standard treatment strategy for locally advanced rectal cancer (LARC); however, the risk of adverse events and postoperative recurrence remains significant. This study aimed to evaluate the non-inferiority of neoadjuvant chemotherapy (nCT) compared with nCRT in patients with LARC and to assess the possibility of eliminating radiotherapy on the basis of guaranteed efficacy.

Materials And Methods: We searched the PubMed, Embase, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing the efficacy of nCRT and nCT for LARC.

Palladium-Catalyzed Modular Synthesis of Thiophene-Fused Polycyclic Aromatics via Sequential C-H Activation.

A palladium-catalyzed Catellani-type [2+2+2] annulation reaction of aryl iodides, bromothiophenes, and norbornadiene, which proceeds via a tandem Heck coupling/double C-H bond activation and retro-Diels-Alder pathway to access thiophene-fused polyaromatics, is reported. The key feature of this protocol represents a NBD/NBE retaining annulation.

Distribution and Biological Response of Nanoplastics in Constructed Wetland Microcosms: Mechanistic Insights into the Role of Photoaging.

Concern over nanoplastic contamination of wetland ecosystems has been increasing. However, little is known about the effect of photoaging on the distribution and biological response of the nanoplastics. Here, palladium-labeled polystyrene nanoplastics (PS-Pd NPs) at 0.

aux orchestrates the phosphorylation-dependent assembly of the lysosomal V-ATPase in glia and contributes to SNCA/α-synuclein degradation.

Glia contribute to the neuropathology of Parkinson disease (PD), but how they react opposingly to be beneficial or detrimental under pathological conditions, like promoting or eliminating SNCA/α-syn (synuclein alpha) inclusions, remains elusive. Here we present evidence that aux (auxilin), the homolog of the PD risk factor GAK (cyclin G associated kinase), regulates the lysosomal degradation of SNCA/α-syn in glia. Lack of glial GAK/aux increases the lysosome number and size, regulates lysosomal acidification and hydrolase activity, and ultimately blocks the degradation of substrates including SNCA/α-syn.

Neural Correlates of Narrative Reading Development: A Comparative fMRI Study of Adults and Children Using Time-Locked Inter-Subject Correlation Analyses.

The naturalistic paradigm and analytical methods present new approaches that are particularly suitable for research concentrating on narrative reading development. We analyzed fMRI data from 44 adults and 42 children engaged in story reading using time-locked inter-subject correlation (ISC), inter-subject representation similarity analysis (IS-RSA), and inter-subject functional correlation (ISFC). The ISC results indicated that for both children and adults, narrative reading recruited not only traditional reading areas but also regions that are sensitive to long-time-scale information, such as the medial prefrontal cortex and hippocampus, which increased involvement from children to adults.

Single-Cell Proteomics Uncovers Dual Traits of Dermal Sheath Cells in Wound Repair.

Wound healing is a dynamic process involving multiple cell types and signaling pathways. Dermal sheath cells (DSCs), residing surrounding hair follicles, play a critical role in tissue repair, yet their regulatory mechanisms remain unclear. This study used single-cell proteomics with the mouse model to explore DSC function across different healing stages.

Computer-aided design of novel anthranilic diamides containing fluorinated alkoxy groups as potential ryanodine receptor insecticides.

Background: Increasing the diversity of lead compounds has been shown to enhance the efficacy of diamide insecticides. Fifty novel compounds were precisely designed and synthesized utilizing fragment-based assembly and virtual screening coupling.

Results: The median lethal concentration (LC) values of compounds X-30 and X-40 against Mythimna separata were 0.

Trafficking of Muscarinic 1 Acetylcholine Receptor Regulated by VPS35 in Alzheimer's Disease.

Introduction: Muscarinic 1 acetylcholine receptor (M1AChR) is a member of the Gprotein- coupled receptor superfamily, with the dysfunction being linked to the onset of Alzheimer's Disease (AD).

Aims: Retromer complex with Vacuolar Protein Sorting-35 (VPS35) as the core plays an important role in the transport of biological proteins and has been confirmed to be closely related to the pathogenesis of AD. This study was designed to determine whether VPS35 could affect the trafficking mechanism of M1AChRs.

A phase II study of anlotinib as first-line maintenance therapy for advanced ovarian cancer.

Anlotinib, a tyrosine kinase inhibitor, has shown encouraging antitumor activity in platinum-resistant/refractory ovarian cancer. The efficacy of anlotinib as maintenance therapy in advanced ovarian cancer remains unclear. Therefore, we designed this study to evaluate the efficacy and safety of anlotinib maintenance therapy following first-line treatment with paclitaxel and platinum-based chemotherapy in advanced ovarian cancer.

Estrogen Promotes the Proliferation and Migration of Endometrial Cancer Through the GPER-Mediated NOTCH Pathway.

This study aims to investigate the expression of GPER in EC, assess the impact of estrogen on the proliferation and migration of EC via GPER, and examine the potential role of GPER in mediating the NOTCH pathway to influence EC proliferation and migration. The expression of GPER and its correlation with clinicopathological features were investigated using clinical data. Cell proliferation was assessed through MTT and EdU assays, while cell migration ability was evaluated using wound healing and transwell assays.

The Pro-Migratory and Pro-Invasive Roles of Cancer-Associated Fibroblasts Secreted IL-17A in Prostate Cancer.

Cancer-associated fibroblasts (CAFs) are key stroma cells that play dominant roles in the migration and invasion of several types of cancer through the secretion of inflammatory cytokine IL-17A. This study aims to identify the potential role and regulatory mechanism of CAFs-secreted IL-17A in the migration and invasion of prostate cancer (PC). CAFs and normal fibroblasts (NFs) were obtained from fresh PC and its adjacent normal tissues, respectively.

A critical review on effects of artificial sweeteners on gut microbiota and gastrointestinal health.

Artificial sweeteners have emerged as popular alternatives to traditional sweeteners, driven by the growing concern over sugar consumption and its associated rise in obesity and metabolic disorders. Despite their widespread use, the safety and health implications of artificial sweeteners remain a topic of debate, with conflicting evidence contributing to uncertainty about their long-term effects. This review synthesizes current scientific evidence regarding the impact of artificial sweeteners on gut microbiota and gastrointestinal health.

Best evidence summary for the management of exercise in patients with central venous access devices.

Background: Central venous access devices (CVAD) are widely used in patient care, providing an essential, reliable pathway for patients to receive chemotherapy, long-term infusions, and nutritional support. However, a system of exercise management has not been developed in patients with CVAD.

Purpose: To evaluate and summarize the evidence for management exercise in patients with CVAD and provide guidance for clinical practice.

Could less be enough: sublobar resection vs lobectomy for clinical stage IA non-small cell lung cancer patients with visceral pleural invasion or spread through air spaces.

Background: While recent randomized controlled trials have demonstrated that sublobar resection is non-inferior to lobectomy, the comparative efficacy of these procedures remains uncertain for early-stage non-small cell lung cancer (NSCLC; ≤ 3 cm) exhibiting invasive features postoperatively, such as visceral pleural invasion (VPI) or spread through air spaces (STAS).

Materials And Methods: To identify eligible studies, a comprehensive search of PubMed, Embase, MEDLINE, the Cochrane Library, and Web of Science was conducted through 25 July 2024. Studies were screened according to predefined criteria in accordance with PRISMA guidelines.

Non-enhanced abbreviated MRI as a periodic surveillance protocol for colorectal liver metastases compared with contrast-enhanced CT: a prospective observational study.

Background: Adopting appropriate noninvasive radiological method is crucial for periodic surveillance of liver metastases in colorectal cancer (CRC) patients after surgery, which is closely related to clinical management and prognosis. This study aimed to prospectively enroll stage II-III CRC patients for the surveillance of liver metastases, and compare the diagnostic performance of contrast-enhanced CT (CE-CT) and non-enhanced abbreviated MRI (NE-AMRI) during this process.

Methods: 587 CRC patients undergoing radical resection of the primary tumor were evaluated by 1 to 3 rounds of surveillance tests, consisting of abdominal CE-CT and contrast-enhanced MRI (CE-MRI) within 7 days at 6-month intervals.

MutualDTA: An Interpretable Drug-Target Affinity Prediction Model Leveraging Pretrained Models and Mutual Attention.

Efficient and accurate drug-target affinity (DTA) prediction can significantly accelerate the drug development process. Recently, deep learning models have been widely applied to DTA prediction and have achieved notable success. However, existing methods often encounter several common issues: first, the data representations lack sufficient information; second, the extracted features are not comprehensive; and third, most methods lack interpretability when modeling drug-target binding.

In Vitro and In Vivo Anticancer Activities of Water-Soluble Ru(II)(η6--cymene) Complexes via Activating Apoptosis Central Regulators and Possibilities of New Antitumor Strategies in Triple Negative Breast Cancers.

In this study, we synthesized 12 monofunctional tridentate ONS-donor salicylaldimine ligand ()-based Ru(II) complexes with general formula [(Ru()(-cymene)]·Cl (-), characterized by H NMR, C NMR, UV, FT-IR spectroscopy, HR-ESI mass spectrometry, and single-crystal X-ray analysis showing ligand's orientation around the Ru(II) center. All 12 of these 12 complexes were tested for their anticancer activities in multiple cancer cells. The superior antitumor efficacy of , , and was demonstrated by reduced mitochondrial membrane potential, impaired proliferative capacity, and disrupted redox homeostasis, along with enhanced apoptosis through caspase-3 activation and downregulation of Bcl-2 expression.

IGF2BP3 is upregulated in endometrial cancer and tightly regulates the growth of drug-resistant endometrial cancer cells via HMGA1.

Objective: Endometrial cancer (EC) is a malignant tumor with various histological subtypes and molecular phenotypes. The evaluation of drug resistance is important for cancer treatment. Progesterone resistance is the major challenge in EC.

Design, Synthesis and Anti-Inflammatory Evaluation of 3-Substituted 5-Amidobenzoate Derivatives as Novel P2Y Receptor Antagonists via Structure-Guided Molecular Hybridization.

The P2YR is activated by UDP and UDP glucose and is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2YR antagonists and the crystallographic overlap study between PPTN and compound , a series of 3-substituted 5-amidobenzoate derivatives were designed, synthesized, and identified as promising P2YR antagonists. The optimal compound (methyl 3-(1-benzo[]imidazol-2-yl)-5-(2-(-tolyl) acetamido)benzoate, IC = 0.

Application of Contrast-Enhanced Ultrasound Parameters of Metastatic Axillary Lymph Nodes in Breast Cancer Patients in Predicting the Efficacy of Neoadjuvant Chemotherapy in Early Stage.

Background: To investigate the performance of contrast-enhanced ultrasound(CEUS) parameters of metastatic axillary lymph nodes (ALNs) before and after two courses of neoadjuvant chemotherapy (NAC) in breast cancer patients in predicting the efficacy of NAC.

Methods: A total of 41 postoperative breast cancer patients were selected. All patients underwent NAC, and ALN biopsy was positive before chemotherapy.

Sophoricoside Inhibited Glioblastoma Cell Progression Through Activated AMP-Activated Protein Kinase (AMPK).

Glioblastoma (GBM) is the most common malignant primary brain tumor, with a mean survival of less than 2 years. Unique brain structures and the microenvironment, including blood-brain barriers, put great challenges on clinical drug development. Sophoricoside (Sop), an isoflavone glycoside isolated from seeds of Sophora japonica L.