Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

Fusion of FDG and FMZ PET Reduces False Positive in Predicting Epileptogenic Zone.

Background And Purpose: Epilepsy, a globally prevalent neurological disorder, necessitates precise identification of the epileptogenic zone (EZ) for effective surgical management. While the individual utilities of FDG PET and FMZ PET have been demonstrated, their combined efficacy in localizing the epileptogenic zone remains underexplored. We aim to improve the non-invasive prediction of epileptogenic zone (EZ) in temporal lobe epilepsy (TLE) by combining FDG PET and FMZ PET with statistical feature extraction and machine learning.

Deficiency of Endothelial Impairs Pulmonary Vascular Angiogenesis and Predisposes Pulmonary Hypertension.

Background: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.

Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.

Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial.

Background: Previous trials have failed to demonstrate the benefits of extracranial-intracranial (EC-IC) bypass surgery for patients with carotid or middle cerebral artery occlusion. However, little evidence has focused on the effect of age on prognosis. This study aimed to explore whether EC-IC bypass surgery can provide greater benefits than medical therapy alone in specific age groups.

Rare earth benzene tetraanion-bridged amidinate complexes.

The benzene tetraanion-bridged rare earth inverse arene amidinate complexes [{Ln(κ:η-Piso)}(μ-η:η-CH)] (2-Ln, Ln = Gd, Tb, Dy, Y; Piso = {(NDipp)C Bu}, Dipp = CH Pr-2,6) were prepared by the reduction of parent Ln(iii) bis-amidinate halide precursors [Ln(Piso)X] (Ln = Tb, Dy; X = Cl, I) or [Ln(Piso)I] (Ln = Gd, Y) with 3 eq. KC in benzene, or by the reaction of the homoleptic Ln(ii) complexes [Ln(Piso)] (Ln = Tb, Dy) with 2 eq. KC in benzene.

Diagnostic Efficacy of Ventilation-Perfusion Single Photo Emission Computed Tomography/Computed Tomography for Pulmonary Hypertension due to Fibrinous Mediastinitis.

Rationale And Objectives: Comprehensive data on the use of ventilation-perfusion single-photo emission computed tomography/computed tomography (V/Q SPECT/CT), an established diagnostic tool for chronic thromboembolic pulmonary hypertension, in identifying pulmonary hypertension secondary to fibrinous mediastinitis (PH-FM) is scarce. This study aimed to assess its diagnostic efficacy for PH-FM.

Materials And Methods: Patients with PH due to pulmonary artery stenosis were assessed using V/Q SPECT/CT, computed tomography pulmonary angiography (CTPA), and digital subtraction pulmonary angiography (PAG).

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.

Developing Hyperpolarized Butane Gas for Ventilation Lung Imaging.

NMR hyperpolarization dramatically improves the detection sensitivity of magnetic resonance through the increase in nuclear spin polarization. Because of the sensitivity increase by several orders of magnitude, additional applications have been unlocked, including imaging of gases in physiologically relevant conditions. Hyperpolarized Xe gas recently received FDA approval as the first inhalable gaseous MRI contrast agent for clinical functional lung imaging of a wide range of pulmonary diseases.

The analgesic effect and mechanism of the active components screening from Corydalis yanhusuo by P2X3 receptors.

Ethnopharmacological Relevance: Cavidine (CAV) is the main bioactive ingredient of Corydalis ternata f. yanhusuo (Y.H.

Preparation and Characterization of Responsive Cellulose-Based Gel Microspheres for Enhanced Oil Recovery.

As an important means to enhance oil recovery, ternary composite flooding (ASP flooding for short) technology has achieved remarkable results in Daqing Oilfield. Alkalis, surfactants and polymers are mixed in specific proportions and injected into the reservoir to give full play to the synergistic effect of each component, which can effectively enhance the fluidity of crude oil and greatly improve the oil recovery. At present, the technology for further improving oil recovery after ternary composite flooding is not mature and belongs to the stage of technical exploration.

Development and validation of risk prediction model for recurrent cardiovascular events among Chinese: the Personalized CARdiovascular DIsease risk Assessment for Chinese model.

Aims: Cardiovascular disease (CVD) is a leading cause of mortality, especially in developing countries. This study aimed to develop and validate a CVD risk prediction model, Personalized CARdiovascular DIsease risk Assessment for Chinese (P-CARDIAC), for recurrent cardiovascular events using machine learning technique.

Methods And Results: Three cohorts of Chinese patients with established CVD were included if they had used any of the public healthcare services provided by the Hong Kong Hospital Authority (HA) since 2004 and categorized by their geographical locations.

SMYD2-Methylated PPARγ Facilitates Hypoxia-Induced Pulmonary Hypertension by Activating Mitophagy.

Background: Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown.

Methods: PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks.

Modified lentiviral globin gene therapy for pediatric β/β transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial.

β/β thalassemia is the most severe type of transfusion-dependent β-thalassemia (TDT) and is still a challenge facing lentiviral gene therapy. Here, we report the interim analysis of a single-center, single-arm pilot trial (NCT05015920) evaluating the safety and efficacy of a β-globin expression-optimized and insulator-engineered lentivirus-modified cell product (BD211) in β/β TDT. Two female children were enrolled, infused with BD211, and followed up for an average of 25.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

Background: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1.

Patient and public involvement in systematic reviews: frequency, determinants, stages, barriers, and dissemination.

Objectives: To investigate the frequency, determinants, stages, and barriers of patient and public involvement (PPI) in systematic reviews and to explore its association with the dissemination of reviews.

Study Design And Setting: We examined systematic reviews that required the inclusion of a PPI declaration, published in The BMJ between January 1, 2015, and December 31, 2022. Multivariable analysis was used to assess the association between PPI and key variables.

Burden of Stroke Attributable to Nonoptimal Temperature in 204 Countries and Territories: A Population-Based Study, 1990-2019.

Background And Objectives: Stroke attributable to nonoptimal temperature needs more attention with dramatic climate change. The aim of this study was to estimate the global burden and distribution characteristics of the burden.

Methods: In this ecological study, we collected data from the Climate Research Unit Gridded Time Series, the World Bank databases, and the Global Burden of Diseases study to estimate the distribution of burden.

Pioneering a chick embryo model to explore the intrauterine etiology of developmental dysplasia of the hip in oligohydramnios conditions.

Objective: To explore the impact of oligohydramnios on fetal movement and hip development, given its association with developmental dysplasia of the hip (DDH) but unclear mechanisms.

Methods: Chick embryos were divided into four groups based on the severity of oligohydramnios induced by amniotic fluid aspiration (control, 0.2 mL, 0.

Deep Learning-Based Reconstruction Improves the Image Quality of Low-Dose CT Colonography.

Rationale And Objectives: To evaluate the image quality of low-dose CT colonography (CTC) using deep learning-based reconstruction (DLR) compared to iterative reconstruction (IR).

Materials And Methods: Adults included in the study were divided into four groups according to body mass index (BMI). Routine-dose (RD: 120 kVp) CTC images were reconstructed with IR (RD-IR); low-dose (LD: 100kVp) images were reconstructed with IR (LD-IR) and DLR (LD-DLR).

Development of novel superconductivity with higherTcvia the suppression of magnetism in quasi-two-dimensional electrideY2Cunder high pressures.

Discovery of superconductivity in electride materials has been a topic of interest as their intrinsic electron-rich properties might suggest a considerable electron-phonon interaction. LayeredY2Cis a ferromagnetic quasi-two-dimensional electride with polarized anionic electrons confined in the interlayer space. In this theoretical study, we reportY2Cundergoes a series of structural phase transitions into two superconducting phases with estimatedTcof 9.

Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial.

KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS-MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC.

A dual-receptor T-cell platform with Ab-TCR and costimulatory receptor achieves specificity and potency against AML.

Chimeric antigen receptor T-cell (CAR T) therapy has produced remarkable clinical responses in B-cell neoplasms. However, many challenges limit this class of agents for the treatment of other cancer types, in particular the lack of tumor-selective antigens for solid tumors and other hematological malignancies, such as acute myeloid leukemia (AML), which may be addressed without significant risk of severe toxicities while providing sufficient abundance for efficient tumor suppression. One approach to overcome this hurdle is dual targeting by an antibody-T-cell receptor (AbTCR) and a chimeric costimulatory signaling receptor (CSR) to 2 different antigens, in which both antigens are found together on the cancer cells but not together on normal cells.

An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants.

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)-the cellular receptor of SARS-CoV-2-into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern.