PCSK9 Promotes LDLR Degradation by Preventing SNX17-Mediated LDLR Recycling.

Background: Low-density lipoprotein (LDL) is internalized into cells mainly through LDLR (LDL receptor)-mediated endocytosis. In an acidic endosome, LDLR is released from LDL and recycles back to the cell surface, whereas LDL is left in the endosome and degraded in the lysosome. Circulating PCSK9 (proprotein convertase subtilisin/kexin 9) binds with LDLR and is internalized into the endosome, similar to LDL.

Prognostic value of extracellular volume fraction in myocardial infarction and myocardial infarction with nonobstructive coronary arteries: A multicenter study.

Rationale And Objectives: The aim of the present retrospective study was to evaluate the prognostic role of the extracellular volume fraction (ECV) in patients with myocardial infarction (MI) and myocardial infarction with nonobstructive coronary arteries (MINOCA). The present study hypothesized that ECV is associated with major adverse cardiovascular events (MACEs) in MI and MINOCA patients.

Materials And Methods: Cardiac magnetic resonance (CMR) imaging was performed on 351 consecutive patients (mean age: 58 ± 12 years; 252 [71.

Myocardial Fibrosis Assessment at 3-T versus 5-T Myocardial Late Gadolinium Enhancement MRI: Early Results.

Background Cardiac MRI at 5 T has recently become available and potentially improves tissue contrast enhancement at gadolinium chelate-enhanced T1-weighted imaging. Purpose To evaluate the feasibility of 5-T myocardial late gadolinium enhancement (LGE) MRI in assessing myocardial fibrosis by comparing image quality and LGE quantification with reference-standard 3-T myocardial LGE MRI. Materials and Methods Consecutive patients with confirmed myocardial fibrosis on previous 3-T MRI scans between January 2023 and July 2023 prospectively underwent follow-up imaging from August 2023 to November 2023.

Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging.

To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging.

Lysozyme 1 Inflamed CCR2 Macrophages Promote Obesity-Induced Cardiac Dysfunction.

Background: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

Background: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.

Methods: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients.

PD-1/PD-L1 Provides Protective Role in Hypoxia-Induced Pulmonary Vascular Remodeling.

Background: Hypoxia-induced pulmonary hypertension (HPH) is a T helper 17 cell response-driven disease, and PD-1 (programmed cell death 1)/PD-L1 (programmed cell death-ligand 1) inhibitor-associated pulmonary hypertension has been reported recently. This study is designed to explore whether the PD-1/PD-L1 pathway participates in HPH via regulating endothelial dysfunction and T helper 17 cell response.

Methods: Lung tissue samples were obtained from eligible patients.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

Background: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this.

Objective: To assess the efficacy of VMMC in preventing incident HIV infection among MSM.

Large Animal Translational Validation of 3 Mitral Valve Repair Operations for Mitral Regurgitation Using a Mitral Valve Prolapse Model: A Comprehensive In Vivo Biomechanical Engineering Analysis.

Background: Various mitral repair techniques have been described. Though these repair techniques can be highly effective when performed correctly in suitable patients, limited quantitative biomechanical data are available. Validation and thorough biomechanical evaluation of these repair techniques from translational large animal in vivo studies in a standardized, translatable fashion are lacking.

Circular olefin copolymers made de novo from ethylene and α-olefins.

Ethylene/α-olefin copolymers are produced in huge scale and widely used, but their after-use disposal has caused plastic pollution problems. Their chemical inertness made chemical re/upcycling difficult. Ideally, PE materials should be made de novo to have a circular closed-loop lifecycle.

Contrast-Enhanced Mammography Radiomics Analysis for Preoperative Prediction of Breast Cancer Molecular Subtypes.

Background: Predicting breast cancer molecular subtypes can help guide individualised clinical treatment of patients who need the rational preoperative treatment. This study aimed to investigate the efficacy of preoperative prediction of breast cancer molecular subtypes by contrast-enhanced mammography (CEM) radiomic features.

Methods: This retrospective two-centre study included women with breast cancer who underwent CEM preoperatively between August 2016 and May 2022.

Skin derived precursors induced Schwann cells mediated tissue engineering-aided neuroregeneration across sciatic nerve defect.

A central question in neural tissue engineering is how the tissue-engineered nerve (TEN) translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes. Here, we report a skin-derived precursor-induced Schwann cell (SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft (SKP-SCs-TEN) that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral, histological, and electrophysiological evidence. For achieving better effect of neuroregeneration, this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix (ECM).

Intermittent Theta-Burst Stimulation for Stroke: Primary Motor Cortex Versus Cerebellar Stimulation: A Randomized Sham-Controlled Trial.

Background: Stroke survivors with impaired balance and motor function tend to have relatively poor functional outcomes. The cerebellum and primary motor cortex (M1) have been suggested as targets for neuromodulation of balance and motor recovery after stroke. This study aimed to compare the efficacy and safety of intermittent theta-burst stimulation (iTBS) to the cerebellum or M1 on balance and motor recovery in patients with stroke.

Reduced Mitochondrial Protein Translation Promotes Cardiomyocyte Proliferation and Heart Regeneration.

Background: The importance of mitochondria in normal heart function are well recognized and recent studies have implicated changes in mitochondrial metabolism with some forms of heart disease. Previous studies demonstrated that knockdown of the mitochondrial ribosomal protein S5 (MRPS5) by small interfering RNA (siRNA) inhibits mitochondrial translation and thereby causes a mitonuclear protein imbalance. Therefore, we decided to examine the effects of MRPS5 loss and the role of these processes on cardiomyocyte proliferation.

CTE-Based Radiomics Models Can Identify Mucosal Healing in Patients with Crohn's Disease.

Rationale And Objectives: To develop computed tomography enterography (CTE)-based radiomics models to assess mucosal healing (MH) in patients with Crohn's disease (CD).

Materials And Methods: CTE images were retrospectively collected from 92 confirmed cases of CD at the post-treatment review. Patients were randomly divided into developing (n = 73) and testing (n = 19) groups.

Endothelial PHACTR1 Promotes Endothelial Activation and Atherosclerosis by Repressing PPARγ Activity Under Disturbed Flow in Mice.

Background: Numerous genome-wide association studies revealed that SNPs (single nucleotide polymorphisms) at the (phosphatase and actin regulator 1) locus strongly correlate with coronary artery disease. However, the biological function of PHACTR1 remains poorly understood. Here, we identified the proatherosclerotic effect of endothelial PHACTR1, contrary to macrophage PHACTR1.

Metformin Monotherapy Alters the Human Plasma Lipidome Independent of Clinical Markers of Glycemic Control and Cardiovascular Disease Risk in a Type 2 Diabetes Clinical Cohort.

Type 2 diabetes (T2D) is a rising pandemic worldwide. Diet and lifestyle changes are typically the first intervention for T2D. When this intervention fails, the biguanide metformin is the most common pharmaceutical therapy.

β2-microglobulin functions as an endogenous NMDAR antagonist to impair synaptic function.

Down syndrome (DS) is a neurological disorder with multiple immune-related symptoms; however, crosstalk between the CNS and peripheral immune system remains unexplored. Using parabiosis and plasma infusion, we found that blood-borne factors drive synaptic deficits in DS. Proteomic analysis revealed elevation of β2-microglobulin (B2M), a major histocompatibility complex class I (MHC-I) component, in human DS plasma.

Integrated proteomics reveals alterations in sarcomere composition and developmental processes during postnatal swine heart development.

The neonatal swine heart possesses an endogenous ability to regenerate injured myocardium through the proliferation of pre-existing cardiomyocyte (CM) populations. However, this regenerative capacity is lost shortly after birth. Normal postnatal developmental processes and the regenerative capacity of mammalian hearts are tightly linked, but not much is known about how the swine cardiac proteome changes throughout postnatal development.

Robust single-cell matching and multimodal analysis using shared and distinct features.

The ability to align individual cellular information from multiple experimental sources is fundamental for a systems-level understanding of biological processes. However, currently available tools are mainly designed for single-cell transcriptomics matching and integration, and generally rely on a large number of shared features across datasets for cell matching. This approach underperforms when applied to single-cell proteomic datasets due to the limited number of parameters simultaneously accessed and lack of shared markers across these experiments.

The impact of informal caregivers' preparedness on short-term outcomes of heart failure patients with insufficient self-care.

Aims: Even though self-care is essential in the long-term management of heart failure (HF), it is often not performed adequately in HF populations. Mobilizing informal caregivers may be one way to help patients perform self-care, support individual needs, and maintain health. However, informal caregivers often face insufficient preparation for providing long-term care.