Small molecule inhibits KCNQ channels with a non-blocking mechanism.

Voltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.

Diagnostic Accuracy and Value of CXCR4-targeted PET/MRI Using Ga-Pentixafor for Tumor Localization in Cushing Disease.

Background Gallium 68 (Ga) pentixafor has emerged as a potential C-X-C chemokine receptor type 4 (CXCR4)-targeted radiotracer for neuroendocrine tumor, yet its application in Cushing disease remains uncertain. Purpose To assess the diagnostic accuracy and value of Ga-pentixafor PET/MRI in localizing adrenocorticotropic hormone (ACTH)-secreting pituitary tumors in Cushing disease. Materials and Methods A prospective single-center study was conducted from March 2023 to February 2024 in participants with Cushing disease scheduled for surgical pituitary tumor resection.

β-asarone relieves Parkinson's disease through reducing intracellular Ca in PINK1 mutant Drosophila melanogaster.

β-asarone, an effective volatile oil component of Acorus chinensis, has been found to hold beneficial effects on Parkinson's disease (PD), but its mechanism remains incompletely understood. Drosophila melanogaster with PTEN induced kinase 1 (PINK1) mutations, a prototype PD model, was used in this study. We found that calcium chelation profoundly alleviated a spectrum of PD symptoms.

Incremental Prognostic Value of Cardiac MRI Feature Tracking and T1 Mapping in Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose To explore the role of cardiac MRI feature tracking (FT) and T1 mapping in predicting sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and to investigate their possible incremental value beyond ARVC risk score. Materials and Methods The retrospective study analyzed 91 patients with ARVC (median age, 36 years [IQR, 27-50 years]; 60 male, 31 female) who underwent cardiac MRI examinations between November 2010 and March 2022. The primary end point was the first occurrence of sustained VA after cardiac MRI to first VA, with censoring of patients who were alive without VA at last follow-up.

Development and Validation of a Contrast-Enhanced US VI-RADS for Evaluating Muscle Invasion in Bladder Cancer.

Background Contrast-enhanced US (CEUS) can be used preoperatively for evaluating muscle invasion in bladder cancer, which is important for determining appropriate treatment. However, diagnostic criteria for assessing this at CEUS have not been standardized. Purpose To develop and validate a CEUS Vesical Imaging Reporting and Data System (VI-RADS) for evaluating muscle invasion in bladder cancer.

The Impact of Intraocular Pressure Changes on Corneal Biomechanics in Primary Open-angle Glaucoma.

Purpose: To investigate the relationship between intraocular pressure (IOP) changes and corneal biomechanical properties, determine the quantitative relationship between IOP changes and corneal biomechanical properties in patients with glaucoma and observe the differences among different types of glaucoma when the effects of high-level IOP were excluded.

Design: Prospective clinical cohort study.

Methods: Setting: Institutional.

Serum Anion Gap at Admission Predicts All-Cause Mortality in Critically Ill Patients With Cirrhosis: A Retrospective Cohort Study.

Introduction: The primary objective of this study was to evaluate admission serum anion gap (AG) as a predictor of all-cause mortality in critically ill patients with cirrhosis.

Methods: A total of 3,084 cirrhotic patients were included and randomly divided into training and validation cohorts (n = 2,159 and 925, respectively). Patients were categorized into high and normal AG groups based on their AG values.

Circular RNA vaccines against monkeypox virus provide potent protection against vaccinia virus infection in mice.

Since the outbreak of monkeypox (mpox) in 2022, widespread concern has been placed on imposing an urgent demand for specific vaccines that offer safer and more effective protection. Using an efficient and scalable circular RNA (circRNA) platform, we constructed four circRNA vaccines that could induce robust neutralizing antibodies as well as T cell responses by expressing different surface proteins of mpox virus (MPXV), resulting in potent protection against vaccinia virus (VACV) in mice. Strikingly, the combination of the four circular RNA vaccines demonstrated the best protection against VACV challenge among all the tested vaccines.

Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability.

Tumor cells must rewire nucleotide synthesis to satisfy the demands of unbridled proliferation. Meanwhile, they exhibit augmented reactive oxygen species (ROS) production which paradoxically damages DNA and free deoxy-ribonucleoside triphosphates (dNTPs). How these metabolic processes are integrated to fuel tumorigenesis remains to be investigated.

Research Progress on the Correlation between Acetaldehyde Dehydrogenase 2 and Hepatocellular Carcinoma Development.

Hepatocellular carcinoma (HCC) is the predominant pathologic type of primary liver cancer. It is a malignant tumor of liver epithelial cells. There are many ways to treat HCC, but the survival rate for HCC patients remains low.

Construction of single-cell cross-species chromatin accessibility landscapes with combinatorial-hybridization-based ATAC-seq.

Despite recent advances in single-cell genomics, the lack of maps for single-cell candidate cis-regulatory elements (cCREs) in non-mammal species has limited our exploration of conserved regulatory programs across vertebrates and invertebrates. Here, we developed a combinatorial-hybridization-based method for single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) named CH-ATAC-seq, enabling the construction of single-cell accessible chromatin landscapes for zebrafish, Drosophila, and earthworms (Eisenia andrei). By integrating scATAC censuses of humans, monkeys, and mice, we systematically identified 152 distinct main cell types and around 0.

A Novel Score Based on Controlled Attenuation Parameter Accurately Predicts Hepatic Steatosis in Individuals With Metabolic Dysfunction Associated Steatotic Liver Disease: A Derivation and Independent Validation Study.

Introduction: In metabolic dysfunction-associated steatotic liver disease, the diagnostic efficacy of controlled attenuation parameter (CAP) was not very accurate in evaluating liver fat content. The aim of this study was to develop a score, based on CAP and conventional clinical parameters, to improve the diagnostic performance of CAP regarding liver fat content.

Methods: A total of 373 participants from 2 independent Chinese cohorts were included and divided into derivation (n = 191), internal validation (n = 75), and external validation (n = 107) cohorts.

Prediction of Receptor Status in Radiomics: Recent Advances in Breast Cancer Research.

Breast cancer is a multifactorial heterogeneous disease and the leading cause of cancer-related deaths in women; its diagnosis and treatment require clinical sensitivity and a comprehensive disciplinary research approach. The expression of different receptors on tumor cells not only provides the basis for molecular typing of breast cancer but also has a decisive role in the diagnosis, treatment, and prognosis of breast cancer. To date, immunohistochemistry (IHC), which uses invasive histological sampling, has been extensively used in clinical practice to analyze the status of receptors and to make an accurate diagnosis of breast cancer.

Predicting clinical progression trajectories of early Alzheimer's disease patients.

Background: Models for forecasting individual clinical progression trajectories in early Alzheimer's disease (AD) are needed for optimizing clinical studies and patient monitoring.

Methods: Prediction models were constructed using a clinical trial training cohort (TC; n = 934) via a gradient boosting algorithm and then evaluated in two validation cohorts (VC 1, n = 235; VC 2, n = 421). Model inputs included baseline clinical features (cognitive function assessments, APOE ε4 status, and demographics) and brain magnetic resonance imaging (MRI) measures.

Twenty-Year Radiographic Outcomes Following Single-Level Cervical Disc Arthroplasty: Results From a Prospective Randomized Controlled Trial.

Study Design: Prospective randomized controlled trial.

Objective: Compare range of motion (ROM) and adjacent segment degeneration (ASD) following cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) at 20-year follow-up.

Summary Of Background Data: Anterior cervical discectomy and fusion is the standard of treatment for single-level cervical disc degeneration causing radiculopathy.

Performance of Corvis ST Parameters Including Updated Stress-Strain Index in Differentiating Between Normal, Forme-Fruste, Subclinical, and Clinical Keratoconic Eyes.

Purpose: This study seeks to evaluate the ability of the updated stress strain index (SSIv2) and other Corvis ST biomechanical parameters in distinguishing between keratoconus at different disease stages and normal eyes.

Design: Diagnostic accuracy analysis to distinguish disease stages.

Methods: 1084 eyes were included and divided into groups of normal (199 eyes), forme fruste keratoconus (FFKC, 194 eyes), subclinical keratoconus (SKC, 113 eyes), mild clinical keratoconus (CKC-Ⅰ, 175 eyes), moderate clinical keratoconus (CKC-Ⅱ, 204 eyes), and severe clinical keratoconus (CKC-Ⅲ, 199 eyes).

MRI-Based Radiomics Nomogram for Preoperatively Differentiating Intrahepatic Mass-Forming Cholangiocarcinoma From Resectable Colorectal Liver Metastases.

Rationale And Objectives: To establish a radiomics nomogram based on multiparameter magnetic resonance (MR) images for preoperatively differentiating intrahepatic mass-forming cholangiocarcinoma (IMCC) from colorectal cancer liver metastasis (CRLM).

Materials And Methods: A total of 133 patients in training cohort (64 IMCC and 69 CRLM), 57 patients in internal validation cohort (29 IMCC and 28 CRLM), and 51 patients (23 IMCC and 28 CRLM) in external validation cohort were included. Radiomics features were extracted from the multiparameter MR images and selected by the least absolute shrinkage and selection operator algorithm to establish the radiomics model.

Photon Counting CT: Technical Principles, Clinical Applications, and Future Prospects.

Photon-counting computed tomography (PCCT) is a new technique that utilizes photon-counting detectors to convert individual X-ray photons directly into an electrical signal, which can achieve higher spatial resolution, improved iodine signal, radiation dose reduction, artifact reduction, and multienergy imaging. This review introduces the technical principles of PCCT, and summarizes its first-in-human experience and current applications in clinical settings, and discusses the future prospects of PCCT.

A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems.

The differentiation of pluripotent stem cells (PSCs) into diverse functional cell types provides a promising solution to support drug discovery, disease modeling, and regenerative medicine. However, functional cell differentiation is currently limited by the substantial line-to-line and batch-to-batch variabilities, which severely impede the progress of scientific research and the manufacturing of cell products. For instance, PSC-to-cardiomyocyte (CM) differentiation is vulnerable to inappropriate doses of CHIR99021 (CHIR) that are applied in the initial stage of mesoderm differentiation.