AMPK Attenuation of β-Adrenergic Receptor-Induced Cardiac Injury via Phosphorylation of β-Arrestin-1-ser330.

Background: β-adrenergic receptor (β-AR) overactivation is a major pathological cue associated with cardiac injury and diseases. AMPK (AMP-activated protein kinase), a conserved energy sensor, regulates energy metabolism and is cardioprotective. However, whether AMPK exerts cardioprotective effects via regulating the signaling pathway downstream of β-AR remains unclear.

Effect of Stroke Etiology on Endovascular Treatment for Acute Basilar-Artery Occlusion: A Post Hoc Analysis of the ATTENTION Randomized Trial.

Background: Stroke etiology could influence the outcomes in patients with basilar-artery occlusion (BAO). This study aimed to evaluate the differences in efficacy and safety of best medical treatment (BMT) plus endovascular treatment (EVT) versus BMT alone in acute BAO across different stroke etiologies.

Methods: The study was a post hoc analysis of the ATTENTION trial (Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022.

Predictors of lung cancer subtypes and lymph node status in non-small-cell lung cancer: intravoxel incoherent motion parameters and extracellular volume fraction.

Objective: To determine the performance of intravoxel incoherent motion (IVIM) parameters and the extracellular volume fraction (ECV) in distinguishing between different subtypes of lung cancer and predicting lymph node metastasis (LNM) status in patients with non-small-cell lung cancer (NSCLC).

Methods: One hundred sixteen patients with lung cancer were prospectively recruited. IVIM, native, and postcontrast T1 mapping examinations were performed, and the T1 values were measured to calculate the ECV.

Antibody-activation of connexin hemichannels in bone osteocytes with ATP release suppresses breast cancer and osteosarcoma malignancy.

Bone tissue represents the most frequent site of cancer metastasis. We developed a hemichannel-activating antibody, Cx43-M2. Cx43-M2, directly targeting osteocytes in situ, activates osteocytic hemichannels and elevates extracellular ATP, thereby inhibiting the growth and migration of cultured breast and osteosarcoma cancer cells.

Lung tumor discrimination by deep neural network model CanDo via DNA methylation in bronchial lavage.

Bronchoscopic-assisted discrimination of lung tumors presents challenges, especially in cases with contraindications or inaccessible lesions. Through meta-analysis and validation using the HumanMethylation450 database, this study identified methylation markers for molecular discrimination in lung tumors and designed a sequencing panel. DNA samples from 118 bronchial washing fluid (BWF) specimens underwent enrichment via multiplex PCR before targeted methylation sequencing.

Ultra-high spatio-temporal resolution imaging with parallel acquisition-readout structured illumination microscopy (PAR-SIM).

Structured illumination microscopy (SIM) has emerged as a promising super-resolution fluorescence imaging technique, offering diverse configurations and computational strategies to mitigate phototoxicity during real-time imaging of biological specimens. Traditional efforts to enhance system frame rates have concentrated on processing algorithms, like rolling reconstruction or reduced frame reconstruction, or on investments in costly sCMOS cameras with accelerated row readout rates. In this article, we introduce an approach to elevate SIM frame rates and region of interest (ROI) coverage at the hardware level, without necessitating an upsurge in camera expenses or intricate algorithms.

Accuracy of Modern Intraocular Lens Formulas in Highly Myopic Eyes Implanted With Plate-Haptic Intraocular Lenses.

Purpose: To evaluate the predictive accuracy of modern intraocular lens (IOL) formulas and axial length (AL) adjusted traditional IOL formulas, including Wang-Koch and Cooke-modified AL (CMAL) method, in long eyes with plate-haptic IOLs, and to compare refractive prediction error variances with C-loop IOLs.

Design: Retrospective consecutive case series study.

Methods: Data from 391 eyes with Zeiss 509 M and 302 eyes with Alcon SN6CWS implants in highly myopic patients, following cataract surgery from January 2019 to November 2023, were collected.

Heart Failure with Normal Natriuretic Peptide Levels and Preserved Ejection Fraction: A Prospective Clinical and Cardiac MRI Study.

Purpose To describe the clinical presentation, comprehensive cardiac MRI characteristics, and prognosis of individuals with predisposed heart failure with preserved ejection fraction (HFpEF). Materials and Methods This prospective cohort study (part of MISSION-HFpEF [Multimodality Imaging in the Screening, Diagnosis, and Risk Stratification of HFpEF]; NCT04603404) was conducted from January 1, 2019, to September 30, 2021, and included individuals with suspected HFpEF who underwent cardiac MRI. Participants who had primary cardiomyopathy and primary valvular heart disease were excluded.

Compare deep learning model and conventional logistic regression model for the identification of unstable saccular intracranial aneurysms in computed tomography angiography.

Background: It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM).

Methods: From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed.

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS.

Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria.

Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants.

Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes.

Background: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined.

Methods: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter.

Delayed Enhancement of Intracranial Atherosclerotic Plaque Can Better Differentiate Culprit Lesions: A Multiphase Contrast-Enhanced Vessel Wall MRI Study.

Background And Purpose: Intracranial plaque enhancement (IPE) identified by contrast-enhanced vessel wall MR imaging (VW-MR imaging) is an emerging marker of plaque instability related to stroke risk, but there was no standardized timing for postcontrast acquisition. We aim to explore the optimal postcontrast timing by using multiphase contrast-enhanced VW-MR imaging and to test its performance in differentiating culprit and nonculprit lesions.

Materials And Methods: Patients with acute ischemic stroke due to intracranial plaque were prospectively recruited to undergo VW-MR imaging with 1 precontrast phase and 4 consecutive postcontrast phases (9 minutes and 13 seconds for each phase).

Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells.

Background: Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells remains unclear. This study aimed to investigate the role of exercise-derived B cells in protecting against doxorubicin-induced cardiotoxicity and to further determine whether B cell activation and antibody secretion play a role in this protection.

Biomechanical Analysis Reveals Shoulder Instability With Bipolar Bone Loss Is Best Treated With Dynamic Anterior Stabilization for On-Track Lesions and With Remplissage for Off-Track Lesions.

Purpose: To compare the biomechanical effects of augmenting Bankart repair (BR) with either remplissage or dynamic anterior stabilization (DAS) in the treatment of anterior shoulder instability with on-track or off-track bipolar bone loss.

Methods: Eight fresh-frozen cadaveric shoulders were tested at 60° of glenohumeral abduction in the intact, injury, and repair conditions. Injury conditions included 15% glenoid bone loss with an on-track or off-track Hill-Sachs lesion as previously recommended.

Discovery of tricyclic PARP7 inhibitors with high potency, selectivity, and oral bioavailability.

PARP7 has been recently identified as an effective drug target due to its specific role in tumor generation and immune function recovery. Herin, we report the discovery of compound 8, which contained a tricyclic fused ring, as a highly selective PARP7 inhibitor against other PARPs. In particular, compound 8 strongly inhibits PARP7 with an IC of 0.

Prognostic Value of Non-alcoholic Fatty Liver Disease and RCA Pericoronary Adipose Tissue CT Attenuation in Patients with Acute Chest Pain.

Rationale And Objectives: Pericoronary adipose tissue (PCAT) CT attenuation of right coronary artery (RCA) and non-alcoholic fatty liver disease (NAFLD) have prognostic value for major adverse cardiovascular events (MACE) in patients with coronary artery disease. However, the superior prognostic value between RCA PCAT CT attenuation and NAFLD remains unclear in patients with acute chest pain. This study is to evaluate the prognostic value of NAFLD for MACE, and further assess the incremental prognostic value of NAFLD over PCAT CT attenuation.

Early cellular and molecular signatures correlate with severity of West Nile virus infection.

Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis.