METTL3-catalyzed m6A methylation facilitates the contribution of vascular smooth muscle cells to atherosclerosis.

Aims: Vascular smooth muscle cells (VSMCs) are involved in the etiology of atherosclerosis, but whether methyltransferase-like 3 (METTL3)-catalyzed N6-methyladenosine (m6A) modulates the contribution of VSMCs to atherosclerosis remains elusive.

Methods And Results: We generated tamoxifen-inducible VSMC-specific METTL3 knockout mice with VSMC lineage tracing, and found that VSMC-specific METTL3 deficiency substantially attenuated atherosclerosis and reduced the proportion of VSMCs in plaques, due to the inhibition of VSMC atheroprone phenotype as characterized by macrophage-like and inflammatory features as well as high migratory and proliferative capacity. m6A-methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with polysome profiling analysis mechanistically displayed METTL3 catalyzed m6A methylation of myocardin-related transcription factor A (MRTFA) mRNA, and further enhanced YTH N6-methyladenosine RNA binding protein F3 (YTHDF3)-dependent MRTFA mRNA translation.

ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm.

Background: Disturbed metabolism and transport of citrate play significant roles in various pathologies. However, vascular citrate regulation and its potential role in aortic aneurysm (AA) development remain poorly understood.

Methods: Untargeted metabolomics by mass spectrometry was applied to identify upregulated metabolites of the tricarboxylic acid cycle in AA tissues of mice.

Alkaline ceramidase 1-mediated platelet ceramide catabolism mitigates vascular inflammation and abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a highly lethal vascular disease. The role of platelets in AAA remains incompletely understood. Here we show that platelet ceramides, rather than other phospholipids, were elevated in an angiotensin II (AngII)-induced AAA murine model and in patients with AAA by using targeted lipidomic analysis.

Superposition of Substrate Deformation Fields Induced by Molecular Clutches Explains Cell Spatial Sensing of Ligands.

Cells can sense the physical properties of the extracellular matrices (ECMs), such as stiffness and ligand density, through cell adhesions to actively regulate their behaviors. Recent studies have shown that varying ligand spacing of ECMs can influence adhesion size, cell spreading, and even stem cell differentiation, indicating that cells have the spatial sensing ability of ECM ligands. However, the mechanism of the cells' spatial sensing remains unclear.

The impact of ankle-foot orthoses on mobility of dual-task walking in stroke patients? A cross-sectional two-factor factorial design clinical trial.

To assess the impact of ankle-foot orthoses (AFOs) on mobility and gait during dual-task walking in post-stroke survivors. In this cross-sectional, factorial design trial, stroke survivors performed four randomized tasks: (1) dual-task walking with AFOs, (2) single-task walking with AFOs, (3) dual-task walking without AFOs, and (4) single-task walking without AFOs. Primary outcome was the Timed Up and Go (TUG) test, with secondary outcomes including gait metrics, Tinetti scores, and auditory N-back tests.

The association between anterior cruciate ligament degeneration and incident knee osteoarthritis: Data from the osteoarthritis initiative.

Background: Though anterior cruciate ligament (ACL) tear has been widely accepted as an important accelerator for knee osteoarthritis (KOA), the role of intrinsic ACL degeneration in developing KOA has not been fully investigated.

Purpose: To determine whether ACL degeneration, in the absence of ACL tear, is associated with incident KOA over 4 years.

Study Design: Cohort study; Level of evidence, 2.

Line Laser Scanning Combined with Machine Learning for Fish Head Cutting Position Identification.

Fish head cutting is one of the most important processes during fish pre-processing. At present, the identification of cutting positions mainly depends on manual experience, which cannot meet the requirements of large-scale production lines. In this paper, a fast and contactless identification method of cutting position was carried out by using a constructed line laser data acquisition system.

GRSF1 antagonizes age-associated hypercoagulability via modulation of fibrinogen mRNA stability.

Age-associated hypercoagulability is accompanied by the increase of plasma levels of some coagulation factors including fibrinogen which may contribute to the increased risk of cardiovascular, cerebrovascular, and thrombotic diseases in elderly people. However, the underlying mechanism of increased plasma fibrinogen concentration during aging is still elusive. GRSF1 belongs to the heterogeneous nuclear ribonucleoproteins F/H (hnRNP F/H) subfamily.

Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice.

A high-methionine (HM) diet leads to hyperhomocysteinemia (HHcy), while gastrointestinal tissue is an important site of net homocysteine (Hcy) production. However, the role of the gut microbiota in host HHcy remains obscure. This study aimed to determine whether gut microbiota ablation could alleviate host HHcy and glucose intolerance and reveal the underlying mechanism.

Targeting cytokine-like protein FAM3D lowers blood pressure in hypertension.

Current antihypertensive options still incompletely control blood pressure, suggesting the existence of uncovered pathogenic mechanisms. Here, whether cytokine-like protein family with sequence similarity 3, member D (FAM3D) is involved in hypertension etiology is evaluated. A case-control study exhibits that FAM3D is elevated in patients with hypertension, with a positive association with odds of hypertension.

Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes.

Immune cells, such as macrophages and dendritic cells, can utilize podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual podosomes probe their microenvironment through periodic protrusion and retraction cycles (height oscillations), while oscillations of multiple podosomes in a cluster are coordinated in a wave-like fashion. However, the mechanisms governing both the individual oscillations and the collective wave-like dynamics remain unclear.

Urate-Lowering Therapy Inhibits Thoracic Aortic Aneurysm and Dissection Formation in Mice.

Background: Thoracic aortic aneurysm and dissection (TAAD) is a highly lethal vascular disease without effective drug therapy. Whether elevated serum concentrations of uric acid are involved in TAAD development remains unclear.

Methods: Serum uric acid levels were detected in different TAAD mouse models and patients.

Electrical impedance myography combined with quantitative assessment techniques in paretic muscle of stroke survivors: Insights and challenges.

Aging is a non-modifiable risk factor for stroke and the global burden of stroke is continuing to increase due to the aging society. Muscle dysfunction, common sequela of stroke, has long been of research interests. Therefore, how to accurately assess muscle function is particularly important.

Activin Receptor-Like Kinase 3 Directly Couples Gαq (Guanine Nucleotide-Binding Protein Subunit αq)/ Gαq (Guanine Nucleotide-Binding Protein Subunit α11) to Regulate Vascular Contractility.

Background: Vascular smooth muscle cell (VSMC) contractility is critical for blood pressure regulation and vascular homeostasis. Identifying the key molecule that maintains VSMC contractility may provide a novel therapeutic target for vascular remodeling. ALK3 (activin receptor-like kinase 3) is a serine/threonine kinase receptor, and deletion of ALK3 causes embryonic lethality.

ADAMTS-7 deficiency attenuates thoracic aortic aneurysm and dissection in mice.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening cardiovascular disease with severe extracellular matrix (ECM) remodeling that lacks efficient early stage diagnosis and nonsurgical therapy. A disintegrin and metalloproteinase with thrombospondin motif 7 (ADAMTS-7) is recognized as a novel locus for human coronary artery atherosclerosis. Previous work by us and others showed that ADAMTS-7 promoted atherosclerosis, postinjury neointima formation, and vascular calcification.

Pain-Related Risk Factors Among Radiologic Stages of Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

Objective: To investigate whether risk factors related to pain vary at different stages of knee osteoarthritis (OA).

Methods: Individuals from the Osteoarthritis Initiative with available Kellgren/Lawrence (K/L) grade and numerical rating scale (NRS) data at baseline were included in this study. Pain severity was classified into 3 categories based on NRS scores: no pain, mild pain, and moderate/severe pain.

The Association Between Quadriceps Strength and Synovitis in Knee Osteoarthritis: An Exploratory Study From the Osteoarthritis Initiative.

Objective: The aim of this study was to explore the association between quadriceps strength and synovitis in knee osteoarthritis (KOA).

Methods: This study was derived from the Osteoarthritis Initiative (OAI), which recruited adults from the OAI cohort with or at risk of KOA. Knees with complete records of isometric quadriceps strength and effusion-synovitis and Hoffa-synovitis assessments were included.

Quadriceps strength is negatively associated with knee joint structural abnormalities-data from osteoarthritis initiative.

Objective: The aim of this study was to explore the longitudinal associations between baseline quadriceps strength and knee joint structural abnormalities in knee osteoarthritis (KOA).

Methods: This study is a longitudinally observational study based on Osteoarthritis Initiative (OAI) cohort, including men and women aged 45-79. Quadriceps strength was measured by isometric knee extension testing at baseline.

MRI-based Texture Analysis of Infrapatellar Fat Pad to Predict Knee Osteoarthritis Incidence.

Background Infrapatellar fat pad (IPFP) quality has been implicated as a marker for predicting knee osteoarthritis (KOA); however, no valid quantification for subtle IPFP abnormalities has been established. Purpose To investigate whether MRI-based three-dimensional texture analysis of IPFP abnormalities could help predict incident radiographic KOA. Materials and Methods In this prospective nested case-control study, 690 participants whose knees were at risk for KOA were included from the Pivotal Osteoarthritis Initiative MRI Analyses incident osteoarthritis cohort.

Unspliced XBP1 Counteracts β-Catenin to Inhibit Vascular Calcification.

Background: Vascular calcification is a prevalent complication in chronic kidney disease and contributes to increased cardiovascular morbidity and mortality. XBP1 (X-box binding protein 1), existing as the XBP1u (unspliced XBP1) and XBP1s (spliced XBP1) forms, is a key component of the endoplasmic reticulum stress involved in vascular diseases. However, whether XBP1u participates in the development of vascular calcification remains unclear.

Enhanced substrate stress relaxation promotes filopodia-mediated cell migration.

Cell migration on two-dimensional substrates is typically characterized by lamellipodia at the leading edge, mature focal adhesions and spread morphologies. These observations result from adherent cell migration studies on stiff, elastic substrates, because most cells do not migrate on soft, elastic substrates. However, many biological tissues are soft and viscoelastic, exhibiting stress relaxation over time in response to a deformation.

Mechanisms of Local Stress Amplification in Axons near the Gray-White Matter Interface.

Diffuse axonal injury is a primary neuropathological feature of concussion and is thought to greatly contribute to the classical symptoms of decreased processing speed and memory dysfunction. Although previous studies have investigated the injury biomechanics at the micro- and mesoscale of concussion, few have addressed the multiscale transmission of mechanical loading at thresholds that can induce diffuse axonal injury. Because it has been recognized that axonal pathology is commonly found at anatomic interfaces across all severities of traumatic brain injury, we combined computational, analytical, and experimental approaches to investigate the potential mechanical vulnerability of axons that span the gray-white tissue interface.

Vascular Extracellular Matrix Remodeling and Hypertension.

The vascular extracellular matrix (ECM) not only provides mechanical stability but also manipulates vascular cell behaviors, which are crucial for vascular function and homeostasis. ECM remodeling, which alters vascular wall mechanical properties and exposes vascular cells to bioactive molecules, is involved in the development and progression of hypertension. This brief review summarized the dynamic changes in ECM components and their modification and degradation during hypertension and after antihypertensive treatment.

Fundamental Characteristics of Neuron Adhesion Revealed by Forced Peeling and Time-Dependent Healing.

A current bottleneck in the advance of neurophysics is the lack of reliable methods to quantitatively measure the interactions between neural cells and their microenvironment. Here, we present an experimental technique to probe the fundamental characteristics of neuron adhesion through repeated peeling of well-developed neurite branches on a substrate with an atomic force microscopy cantilever. At the same time, a total internal reflection fluorescence microscope is also used to monitor the activities of neural cell adhesion molecules (NCAMs) during detaching.