Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca-PIK3CA pathway.

Phenotypic screening of existing drugs is a good strategy to discover new drugs. Herein, 33 psychotherapeutic drugs in our drug library were screened by phenotypic screening and penfluridol (PFD) was found to exhibit excellent anti-endometrial cancer (EC) activity both and . Furthermore, the molecular target of PFD was identified as septin7, a tumor suppressor in EC.

A legume-enriched diet improves metabolic health in prediabetes mediated through gut microbiome: a randomized controlled trial.

Healthy dietary patterns rich in legumes can improve metabolic health, although their additional benefits in conjunction with calorie restriction have not been well-established. We investigated effects of a calorie-restricted, legume-enriched, multicomponent intervention diet compared with a calorie-restricted control diet in 127 Chinese prediabetes participants, living in Singapore. The study was a 16-week, single-blind, parallel-design, randomized controlled trial (n = 63 intervention group (IG), n = 64 control group (CG); mean ± SD age 62.

A Serial MRI-based Deep Learning Model to Predict Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

Purpose To develop and evaluate a deep learning-based prognostic model for predicting survival in locoregionally- advanced nasopharyngeal carcinoma (LA-NPC) using serial MRI before and after induction chemotherapy (IC). Materials and Methods This multicenter retrospective study included 1039 LA-NPC patients (779 male, 260 female, mean age 44 [standard deviation: 11]) diagnosed between April 2009 and December 2015. A radiomics- clinical prognostic model (Model RC) was developed using pre-and post-IC MRI and other clinical factors using graph convolutional neural networks (GCN).

Acute Myeloid Leukemia with Normal Cytogenetics and -Mutation: Impact of Mutation Topography on Outcomes.

: About half of adults with acute myeloid leukemia with normal cytogenetics (CN-AML) have mutations. There is controversy regarding their prognosis and best therapy. : We studied 150 subjects with these features using targeted regional sequencing.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

The de novo synthesis of GABA and its gene regulatory function control hepatocellular carcinoma metastasis.

The neurotransmitter gamma-aminobutyric acid (GABA) has been thought to be involved in the development of some types of cancer. Yet, the de novo synthesis of GABA and how it functions in hepatocellular carcinoma (HCC) remain unclear. Here, we report that SLC6A12 acts as a transporter of GABA, and that aldehyde dehydrogenase 9 family member A1 (ALDH9A1), not glutamate decarboxylase 1 (GAD1), generates GABA in human HCC.

ROS scavenging and corneal epithelial wound healing by a self-crosslinked tissue-adhesive hydrogel based-on dual-functionalized hyaluronic acid.

Reactive oxygen species (ROS) scavenging is a viable approach to promote corneal epithelium wound healing. This study created a single-component hydrogel (HA Gel) with a novel dual-functionalized hyaluronic acid derivative (HA-GA-PBA) containing gallol and phenylboronic acid (PBA) moieties. Both of these moieties were dual-functional.

Ultrasensitive Protein Aggregate Quantification Assays for Neurodegenerative Diseases on the Simoa Platform.

Nanoscale aggregates play a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. However, quantifying these aggregates in complex biological samples, such as biofluids and postmortem brain tissue, has been challenging due to their low concentration and small size, necessitating the development of methods with high sensitivity and specificity. Here, we have developed ultrasensitive assays utilizing the Quanterix Simoa platform to detect α-synuclein, β-amyloid and tau aggregates, including those with common posttranslational modifications such as truncation of α-synuclein and AT8 phosphorylation of tau aggregates.

Advances in biopharmaceutical products for hemophilia.

Hemophilia is caused by the deficiency of clotting factors due to a single genetic abnormality. Replacement therapies have evolved from plasma-derived to recombinant coagulation factor concentrates but continue to have certain limitations. Monoclonal antibodies are clinical prophylactic treatment options unaffected by inhibitors and have better compliance than coagulation factor concentrates for patients with hemophilia.

SOX2-induced IL1α-mediated immune suppression drives epithelial dysplasia malignant transformation.

Squamous cell carcinomas (SCC) are often preceded by potentially malignant precursor lesions, most of which remain benign. The terminal exhaustion phenotypes of effector T-cells and the accumulation of myeloid-derived suppressor cells (MDSC) have been thoroughly characterized in established SCC. However, it is unclear what precancerous lesions harbor a bona fide high risk for malignant transformation and how precancerous epithelial dysplasia drives the immune system to the point of no return.

Developing the biomarker panels and drugs by proteomic analysis for autoimmune uveitis and posterior scleritis.

Autoimmune uveitis and posterior scleritis are ocular diseases caused by immune dysregulation. Their pathogenesis remains elusive, and delayed diagnosis can exacerbate vision loss. Our study analyzed proteomic profiles of 190 patients with Behcet's disease uveitis, posterior scleritis, and Vogt-Koyanagi-Harada syndrome.

Endothelial FUNDC1 Deficiency Drives Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is associated with endothelial dysfunction. However, the cause of endothelial dysfunction and its impact on PH remain incompletely understood. We aimed to investigate whether the hypoxia-inducible FUNDC1 (FUN14 domain-containing 1)-dependent mitophagy pathway underlies PH pathogenesis and progression.

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

Clinical and Genomic Prediction of Coronary Artery Disease Subtypes.

Background: Coronary artery disease (CAD) is a complex, heterogeneous disease with distinct etiological mechanisms. These different etiologies may give rise to multiple subtypes of CAD that could benefit from alternative preventions and treatments. However, so far, there have been no systematic efforts to predict CAD subtypes using clinical and genetic factors.

Integrative mapping of human CD8 T cells in inflammation and cancer.

CD8 T cells exhibit remarkable phenotypic diversity in inflammation and cancer. However, a comprehensive understanding of their clonal landscape and dynamics remains elusive. Here we introduce scAtlasVAE, a deep-learning-based model for the integration of large-scale single-cell RNA sequencing data and cross-atlas comparisons.

Abnormally enhanced Hall Lorenz number in the magnetic Weyl semimetal NdAlSi.

In Landau's celebrated Fermi liquid theory, electrons in a metal obey the Wiedemann-Franz law at the lowest temperatures. This law states that electron heat and charge transport are linked by a constant L, i.e.

Histogram analysis of advanced diffusion-weighted MRI models for evaluating the grade and proliferative activity of meningiomas.

Rationale And Objectives: To explore the value of diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator (MAP) magnetic resonance imaging histogram analysis in evaluating the grade and proliferative activity of meningiomas.

Materials And Methods: A total of 134 meningioma patients were prospectively included and underwent magnetic resonance diffusion imaging. The whole-tumor histogram parameters were extracted from multiple functional maps.

Bowel preparation efficacy and discomfort of 2 L polyethylene glycol combined with linaclotide versus 3 L polyethylene glycol: a noninferiority, prospective, multicenter, randomized controlled trial.

Background: Three liters of polyethylene glycol administered in a split dose is a commonly recommended regimen for bowel preparation before colonoscopy.

Objectives: The aim of this study was to compare the quality and tolerability of low-dose (2 L) polyethylene glycol combined with linaclotide (2 L+L) versus the 3 L polyethylene glycol (PEG) bowel preparation regimen.

Design: A noninferiority, prospective, multicenter, randomized controlled trial.

ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm.

Background: Disturbed metabolism and transport of citrate play significant roles in various pathologies. However, vascular citrate regulation and its potential role in aortic aneurysm (AA) development remain poorly understood.

Methods: Untargeted metabolomics by mass spectrometry was applied to identify upregulated metabolites of the tricarboxylic acid cycle in AA tissues of mice.