Trem2/Tyrobp Signaling Protects Against Aortic Dissection and Rupture by Inhibiting Macrophage Activation in Mice.

Background: The development of aortic dissection (AD) is closely associated with inflammation. The Trem2 (triggering receptor expressed on myeloid cells 2)/Tyrobp (TYRO protein tyrosine kinase-binding protein) signaling pathway critically regulates innate immunity and has emerged as an important target in cardiovascular diseases; however, its role in AD remains unclear.

Methods: Transcriptome data from human and mouse ADs were used to perform differentially expressed gene-based protein-protein interaction network analyses.

The Induction of Drug Uptake Transporter Organic Anion Transporting Polypeptide 1A2 by Radiation Is Mediated by the Nonreceptor Tyrosine Kinase v-YES-1 Yamaguchi Sarcoma Viral Oncogene Homolog 1.

Organic anion transporting polypeptides (OATP, gene symbol ) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate.

Single-Nucleus Transcriptomic Atlas of Human Pericoronary Epicardial Adipose Tissue in Normal and Pathological Conditions.

Background: Pericoronary epicardial adipose tissue (EAT) is a unique visceral fat depot that surrounds the adventitia of the coronary arteries without any anatomic barrier. Clinical studies have demonstrated the association between EAT volume and increased risks for coronary artery disease (CAD). However, the cellular and molecular mechanisms underlying the association remain elusive.

Circulating DNA genome-wide fragmentation in early detection and disease monitoring of hepatocellular carcinoma.

Genome-wide circulating cell-free DNA (ccfDNA) fragmentation for cancer detection has been rarely evaluated using blood samples collected before cancer diagnosis. To evaluate ccfDNA fragmentation for detecting early hepatocellular carcinoma (HCC), we first modeled and tested using hospitalized HCC patients and then evaluated in a population-based study. A total of 427 samples were analyzed, including 270 samples collected prior to HCC diagnosis from a population-based study.

BRCC3 Regulation of ALK2 in Vascular Smooth Muscle Cells: Implication in Pulmonary Hypertension.

Background: An imbalance of antiproliferative BMP (bone morphogenetic protein) signaling and proliferative TGF-β (transforming growth factor-β) signaling is implicated in the development of pulmonary arterial hypertension (PAH). The posttranslational modification (eg, phosphorylation and ubiquitination) of TGF-β family receptors, including BMPR2 (bone morphogenetic protein type 2 receptor)/ALK2 (activin receptor-like kinase-2) and TGF-βR2/R1, and receptor-regulated Smads significantly affects their activity and thus regulates the target cell fate. BRCC3 modifies the activity and stability of its substrate proteins through K63-dependent deubiquitination.

Assisted reproductive technology treatment failure and the detection of intrauterine HPV through spent embryo transfer media sample.

Cervical human papillomavirus (HPV) infection is believed to increase the risks of pregnancy failure and abortion, however, whether the uterine cavity HPV infection reduces pregnancy rate or increases miscarriage rate remains unclarified in infertile women undergoing assisted reproductive technology (ART) treatment. Therefore, we aimed to assess ART outcomes in the presence of intrauterine HPV. This was a hospital-based multicenter (five reproductive medicine centers) matched cohort study.

Application of Spinal Subtraction and Bone Background Fusion CTA in the Accurate Diagnosis and Evaluation of Spinal Vascular Malformations.

Background And Purpose: Accurate pretreatment diagnosis and assessment of spinal vascular malformations using spinal CTA are crucial for patient prognosis, but the postprocessing reconstruction may not be able to fully depict the lesions due to the complexity inherent in spinal anatomy. Our purpose was to explore the application value of the spinal subtraction and bone background fusion CTA (SSBBF-CTA) technique in precisely depicting and localizing spinal vascular malformation lesions.

Materials And Methods: In this retrospective study, patients (between November 2017 and November 2022) with symptoms similar to those of spinal vascular malformations were divided into diseased (group A) and nondiseased (group B) groups.

Optic Nerve Head Capillary Network Quantified by Optical Coherence Tomography Angiography and Decline of Renal Function in Type 2 Diabetes: A Three-Year Prospective Study.

Purpose: To assess the association of optic capillary perfusion with decline in the estimated glomerular filtration rate (eGFR) and to clarify its added value.

Design: Prospective, observational cohort study.

Methods: Patients with type 2 diabetes mellitus without diabetic retinopathy (non-DR) underwent standardized examinations annually during a 3-year follow-up period.

Association Between Regular Laxative Use and Incident Dementia in UK Biobank Participants.

Background And Objectives: The use of over-the-counter laxatives is common in the general population. The microbiome-gut-brain axis hypothesis suggests that the use of laxatives could be associated with dementia. We aimed to examine the association between the regular use of laxatives and the incidence of dementia in UK Biobank participants.

Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

Background: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations.

Methods: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone.

Effects of Blood Pressure and Arterial Stiffness on Retinal Neurodegeneration: Cross-Sectional and Longitudinal Evidence From UK Biobank and Chinese Cohorts.

Background: Hypertension might be a modifiable risk factor for neurodegeneration diseases. However, the associations between blood pressure (BP), arterial stiffness index and retinal neurodegeneration remain unclear.

Methods: This study used cross-sectional data from the United Kingdom BioBank (UKB) and longitudinal data from the Chinese Ocular Imaging Project (COIP).

Young Patients With Colorectal Cancer Have Higher Early Mortality but Better Long-Term Survival.

Introduction: To define the prognosis of colorectal cancer (CRC) in young patients and to compare their postoperative treatment with that of older patients.

Methods: This multicenter study enrolled 5,457 patients with primary CRC who underwent surgical resection. The overall survival (OS), clinicopathologic characteristics, and postoperative treatment of 253 young patients aged 18-44 years and 5,204 older patients aged 44-80 years were analyzed.

Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

Background: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited.

Methods: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control).

Remarkable ferroelectricity-modulated electronic and magnetic properties in a 2H-VS/BiAlO(0001) hybrid system.

In the present work, a 2H-VS/BiAlO(0001) hybrid system is constructed to perform first-principles density functional theory (DFT) calculations. The results reveal that, in addition to the ionic-vdW interface coupling, the ferromagnetic semiconductive 2H-VS monolayer on the ferroelectric BiAlO(0001) substrate exhibits n-type or p-type doping behavior and even half-metal characteristics. Furthermore, the magnetoelectric coefficient () for the 2H-VS/BiAlO(0001) structures can reach a value of 10 G cm V with ferroelectric polarization reversal.

Design, Synthesis, and Characterization of TNP-2198, a Dual-Targeted Rifamycin-Nitroimidazole Conjugate with Potent Activity against Microaerophilic and Anaerobic Bacterial Pathogens.

TNP-2198, a stable conjugate of a rifamycin pharmacophore and a nitroimidazole pharmacophore, has been designed, synthesized, and evaluated as a novel dual-targeted antibacterial agent for the treatment of microaerophilic and anaerobic bacterial infections. TNP-2198 exhibits greater activity than a 1:1 molar mixture of the parent drugs and exhibits activity against strains resistant to both rifamycins and nitroimidazoles. A crystal structure of TNP-2198 bound to a RNA polymerase transcription initiation complex reveals that the rifamycin portion of TNP-2198 binds to the rifamycin binding site on RNAP and the nitroimidazole portion of TNP-2198 interacts directly with the DNA template-strand in the RNAP active-center cleft, forming a hydrogen bond with a base of the DNA template strand.

High-Fidelity Patient Simulation Incorporated Into a Flipped Classroom Improves Students' Long-Term Knowledge Retention of Acute Organophosphorus Pesticide Poisoning.

Introduction: The flipped classroom (FC) approach and high-fidelity patient simulation (HFPS) training have shown promising effects in short-term acquisition or long-term retention of knowledge in medical education. In this study, we aimed to explore the incorporation of HFPS into the FC and the impact on the long-term (3 months after classes) knowledge retention of medical undergraduate students learning about acute organophosphorus pesticide poisoning (AOPP).

Methods: Eighty-two fifth-year medical students were randomly divided into an HFPS group (HG, n = 40) and an FC group (FG, n = 42).

Micronutrients and Diabetic Retinopathy: Evidence From The National Health and Nutrition Examination Survey and a Meta-analysis.

Purpose: To investigate the associations between circulating micronutrients (vitamins A, C, D, E, and carotenoids) and risk of diabetic retinopathy (DR).

Design: Cross-sectional study and meta-analysis.

Methods: The cross-sectional study included 517 diabetic participants aged ≥40 years in the 2005-2006 National Health and Nutrition Examination Survey.

Acceleration of Brain TOF-MRA with Compressed Sensitivity Encoding: A Multicenter Clinical Study.

Background And Purpose: The clinical practice of three-dimensional TOF-MRA, despite its capability in brain artery assessment, has been hampered by the relatively long scan time, while recent developments in fast imaging techniques with random undersampling has shed light on an improved balance between image quality and imaging speed. Our aim was to evaluate the effectiveness of TOF-MRA accelerated by compressed sensitivity encoding and to identify the optimal acceleration factors for routine clinical use.

Materials And Methods: One hundred subjects, enrolled at 5 centers, underwent 8 brain TOF-MRA sequences: 5 sequences using compressed sensitivity encoding with acceleration factors of 2, 4, 6, 8, and 10 (CS2, CS4, CS6, CS8, and CS10), 2 using sensitivity encoding with factors of 2 and 4 (SF2 and SF4), and 1 without acceleration as a reference sequence (RS).

Upregulation of Piezo1 (Piezo Type Mechanosensitive Ion Channel Component 1) Enhances the Intracellular Free Calcium in Pulmonary Arterial Smooth Muscle Cells From Idiopathic Pulmonary Arterial Hypertension Patients.

[Figure: see text].

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Single-Cell RNA Sequencing Uncovers Paracrine Functions of the Epicardial-Derived Cells in Arrhythmogenic Cardiomyopathy.

Background: Arrhythmogenic cardiomyopathy (ACM) manifests with sudden death, arrhythmias, heart failure, apoptosis, and myocardial fibro-adipogenesis. The phenotype typically starts at the epicardium and advances transmurally. Mutations in genes encoding desmosome proteins, including DSP (desmoplakin), are major causes of ACM.

The Negative Allosteric Modulator EU1794-4 Reduces Single-Channel Conductance and Ca Permeability of GluN1/GluN2A -Methyl-d-Aspartate Receptors.

NMDA receptors are ligand-gated ion channels that mediate a slow, Ca-permeable component of excitatory synaptic currents. These receptors are involved in several important brain functions, including learning and memory, and have also been implicated in neuropathological conditions and acute central nervous system injury, which has driven therapeutic interest in their modulation. The EU1794 series of positive and negative allosteric modulators of NMDA receptors has structural determinants of action near the preM1 helix that is involved in channel gating.

Automated Quantification of Reduced Sulcal Volume Identifies Early Brain Injury After Aneurysmal Subarachnoid Hemorrhage.

Background And Purpose: Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accepted manifestation of early brain injury but is currently assessed only through subjective, qualitative or semi-quantitative means.