Mechanism of ITGB2 in Osteoclast Differentiation in Osteoarthritis.

Transcriptomics studies have identified integrin receptor β2 subunit (ITGB2) as a core gene in osteoarthritis (OA), strongly linked to osteoclast function in the subchondral bone. However, the mechanism through which ITGB2 regulates osteoclast function in OA remains unclear. In this study, we found that ITGB2 was negatively correlated with ITGB1 in the human subchondral bone.

Calreticulin-driven immunogenic cell death promotes osteoclast differentiation and osteoarthritis progression via the LRP1/Rac1 signaling.

Aberrant osteoclast activation in subchondral bone is a hallmark of osteoarthritis (OA). This study identifies calreticulin (CALR), a key immunogenic cell death (ICD) marker, as a critical regulator of osteoclast differentiation and OA pathogenesis. Proteomic analysis revealed elevated CALR expression in subchondral bone from OA patients, which was further validated in human specimens and a destabilization of the medial meniscus (DMM)-induced murine OA model.

Long-term exercise enhances meningeal lymphatic vessel plasticity and drainage in a mouse model of Alzheimer's disease.

Background: Meningeal lymphatic drainage is crucial for the clearance of amyloid β (Aβ), supporting the maintenance of brain homeostasis. This makes it a promising therapeutic target for Alzheimer's disease (AD). Long-term exercise can reduce the risk of AD; however, the underlying mechanism is not fully understood.

Maintaining high levels of HIF-1α protects osteoarthritis cartilage by activating autophagy.

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and subchondral bone remodeling, with hypoxia-inducible factor-1α (HIF-1α) playing a pivotal role in chondrocyte survival under hypoxic and inflammatory conditions. This study investigated the protective mechanisms of HIF-1α in OA by examining its effects on autophagy and oxidative stress in both human OA cartilage samples and murine models. Proteomic and immunohistochemical analyses revealed elevated HIF-1α expression alongside reduced autophagy markers Microtubule-Associated Protein 1 Light Chain 3(LC3) and increased cartilage damage indicators Matrix Metalloproteinase 13(MMP13), decreased Type 2 Collagen (COL2) in OA-affected tissues.

Melatonin Mitigates Sleep Restriction-Induced Cognitive and Glymphatic Dysfunction Via Aquaporin-4 Polarization.

Chronic sleep restriction (SR) impairs the glymphatic clearance of macromolecular toxic metabolites, which is associated with the loss of perivascular polarization of aquaporin-4 (AQP4). Melatonin (Mel) has been shown to maintain the circadian rhythm of AQP4 polarization. However, the role of AQP4 polarization in Mel's protective effects against SR-induced brain dysfunction remains unclear.

Stenting Versus Medical Therapy for Symptomatic Intracranial Artery Stenosis: Long-Term Follow-Up of a Randomized Trial.

Background: Whether the long-term benefit of stroke prevention when stenting is added to medical therapy (MT) over MT alone for symptomatic severe intracranial artery stenosis offsets the perioperative risks of the stenting has not been directly evaluated in a randomized trial. We aimed to compare the long-term (>3 years) effect of stenting versus MT alone in patients with symptomatic severe intracranial artery stenosis in a randomized trial.

Methods: We extended the follow-up of 358 subjects enrolled in a multicenter, open-label, randomized trial conducted at 8 centers in China.

Macrophage A2aR Alleviates LPS-Induced Vascular Endothelial Injury and Inflammation via Inhibiting M1 Polarisation and Oxidative Stress.

Vascular inflammation and endothelial dysfunction secondary to unchecked activation of endothelium are key mechanisms underlying sepsis and organ failure. However, the intrinsic processes that mitigate excessive endothelial cell activation remain incompletely understood. To determine the central role of adenosine A2a receptor (A2aR) on macrophages in modulating lipopolysaccharide (LPS)-induced vascular endothelial dysfunction, we constructed macrophage A2aR-conditional knockout (Mac-A2aR KO) mice, and stimulated the mice and macrophages with LPS.

Study on the use of black phosphorus quantum dots in the treatment of atherosclerosis.

Atherosclerosis is the pathological basis of cardiovascular disease, and there are no clinical drugs that can safely and efficiently remove atherosclerotic plaques. In this study, black phosphorus quantum dots (BPQDs) were applied to the treatment of atherosclerosis in high fat diet ApoE model mice that BPQDs were given every other day for 3 weeks without changing the high-fat diet. 45.

Brd4 modulates metabolic endotoxemia-induced inflammation by regulating colonic macrophage infiltration in high-fat diet-fed mice.

High-fat diet (HFD) induces low-grade chronic inflammation, contributing to obesity and insulin resistance. However, the precise mechanisms triggering obesity-associated metabolic inflammation remain elusive. In this study, we identified epigenetic factor Brd4 as a key player in this process by regulating the expression of Ccr2/Ccr5 in colonic macrophage.

Aerobic exercise improves astrocyte mitochondrial quality and transfer to neurons in a mouse model of Alzheimer's disease.

Mitochondrial dysfunction is a well-established hallmark of Alzheimer's disease (AD). Despite recent documentation of transcellular mitochondrial transfer, its role in the pathogenesis of AD remains unclear. In this study, we report an impairment of mitochondrial quality within the astrocytes and neurons of adult 5 × FAD mice.

Unveiling the Role of Sik1 in Osteoblast Differentiation: Implications for Osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative disease characterized by subchondral osteosclerosis, mainly due to osteoblast activity. This research investigates the function of Sik1, a member of the AMP-activated protein kinase family, in OA. Proteomic analysis was conducted on clinical samples from 30 OA patients, revealing a negative correlation between Sik1 expression and OA.

Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis.

Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone.

Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases.

The phenomenon of an aging population is advancing at a precipitous rate. Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most common age-associated neurodegenerative diseases, both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures. Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles, including the clearance of macromolecular waste and the trafficking of immune cells.

Contamination of neonicotinoid insecticides in source water and their fate during drinking water treatment in the Dongguan section of the Pearl River.

Neonicotinoid insecticides (NEOs) as well as their metabolites are highly mobile on the subsurface and can potentially contaminate drinking water sources; however, their pollution status and fate in the drinking water system remains ambiguous. In this study, six parent NEOs and two characteristic metabolites were measured in drinking water source protection area (source water, n = 52) and two related drinking water treatment plants (DWTPs) (n = 88) located in the Dongguan section of the Pearl River. The ubiquitous of NEOs was observed in source water with the mean concentration of total NEOs (ΣNEOs) at 240 ng/L.

Three-dimensional aneurysm wall enhancement in fusiform intracranial aneurysms is associated with aneurysmal symptoms.

Background And Purpose: Aneurysm wall enhancement (AWE) in high-resolution magnetic resonance imaging (HR-MRI) is a potential biomarker for evaluating unstable aneurysms. Fusiform intracranial aneurysms (FIAs) frequently have a complex and curved structure. We aimed to develop a new three-dimensional (3D) aneurysmal wall enhancement (AWE) characterization method to enable comprehensive FIA evaluation and to investigate the ability of 3D-AWE to predict symptomatic FIA.

Aneurysm wall enhancement, atherosclerotic proteins, and aneurysm size may be related in unruptured intracranial fusiform aneurysms.

Objective: This cross-sectional study aimed to investigate the associations between aneurysm wall enhancement (AWE), atherosclerotic protein levels, and aneurysm size in unruptured intracranial fusiform aneurysms (IFAs).

Methods: Patients with IFAs underwent high-resolution magnetic resonance imaging (HR-MRI) and atherosclerotic protein examinations from May 2015 to December 2021 were collected. A CR (signal intensity [SI] of IFA wall/SI of pituitary stalk) > 0.

Systemic immune-inflammation index is associated with aneurysmal wall enhancement in unruptured intracranial fusiform aneurysms.

Introduction: Inflammation plays a key role in the progression of intracranial aneurysms. Aneurysmal wall enhancement (AWE) correlates well with inflammatory processes in the aneurysmal wall. Understanding the potential associations between blood inflammatory indices and AWE may aid in the further understanding of intracranial aneurysm pathophysiology.

Transmission of multidrug-resistant tuberculosis in Beijing, China: An epidemiological and genomic analysis.

Background: Understanding multidrug-resistant tuberculosis (MDR-TB) transmission patterns is crucial for controlling the disease. We aimed to identify high-risk populations and geographic settings of MDR-TB transmission.

Methods: We conducted a population-based retrospective study of MDR-TB patients in Beijing from 2018 to 2020, and assessed MDR-TB recent transmission using whole-genome sequencing of isolates.

Locomotor Hyperactivity in the Early-Stage Alzheimer's Disease-like Pathology of APP/PS1 Mice: Associated with Impaired Polarization of Astrocyte Aquaporin 4.

Non-cognitive behavioral and psychological symptoms often occur in Alzheimer's disease (AD) patients and mouse models, although the exact neuropathological mechanism remains elusive. Here, we report hyperactivity with significant inter-individual variability in 4-month-old APP/PS1 mice. Pathological analysis revealed that intraneuronal accumulation of amyloid-β (Aβ), c-Fos expression in glutamatergic neurons and activation of astrocytes were more evident in the frontal motor cortex of hyperactive APP/PS1 mice, compared to those with normal activity.