Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

Background: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive.

Epicardial CCM2 Promotes Cardiac Development and Repair Via its Regulation on Cytoskeletal Reorganization.

The epicardium provides epicardial-derived cells and molecular signals to support cardiac development and regeneration. Zebrafish and mouse studies have shown that , a cerebral cavernous malformation disease gene, is essential for cardiac development. Endocardial cell-specific deletion of in mice has previously established that Ccm2 is essential for maintenance of the cardiac jelly for cardiac development during early gestation.

Integration of scRNA-seq data by disentangled representation learning with condition domain adaptation.

Background: The integration of single-cell RNA sequencing data from multiple experimental batches and diverse biological conditions holds significant importance in the study of cellular heterogeneity.

Results: To expedite the exploration of systematic disparities under various biological contexts, we propose a scRNA-seq integration method called scDisco, which involves a domain-adaptive decoupling representation learning strategy for the integration of dissimilar single-cell RNA data. It constructs a condition-specific domain-adaptive network founded on variational autoencoders.

Foxp1 Is Required for Renal Intercalated Cell Differentiation and Acid-Base Regulation.

Key Points: Foxp1 is a key transcriptional factor for the differentiation of intercalated cells in collecting ducts. Dmrt2 and Hmx2 act downstream of Foxp1 to control the differentiation of type A and type B intercalated cells, respectively. Foxp1 and Dmrt2 are essential for body acid–base balance regulation.

Delivery of Therapeutic miRNA via Plasma-Polymerised Nanoparticles Rescues Diabetes-Impaired Endothelial Function.

MicroRNAs (miRNAs) are increasingly recognised as key regulators of the development and progression of many diseases due to their ability to modulate gene expression post-translationally. While this makes them an attractive therapeutic target, clinical application of miRNA therapy remains at an early stage and in part is limited by the lack of effective delivery modalities. Here, we determined the feasibility of delivering miRNA using a new class of plasma-polymerised nanoparticles (PPNs), which we have recently isolated and characterised.

[Animal experimental study on the effects of different levels of amputation on cardiovascular system].

Vascular injury resulting from lower limb amputation leads to the redistribution of blood flow and changes in vascular terminal resistance, which can affect the cardiovascular system. However, there was no clear understanding of how different amputation levels affect the cardiovascular system in animal experiments. Therefore, this study established two animal models of above-knee amputation (AKA) and below-knee amputation (BKA) to explore the effects of different amputation levels on the cardiovascular system through blood and histopathological examinations.

Overexpression of VIRMA confers vulnerability to breast cancers via the mA-dependent regulation of unfolded protein response.

Virilizer-like mA methyltransferase-associated protein (VIRMA) maintains the stability of the mA writer complex. Although VIRMA is critical for RNA mA deposition, the impact of aberrant VIRMA expression in human diseases remains unclear. We show that VIRMA is amplified and overexpressed in 15-20% of breast cancers.

Factors Affecting Users' Continuous Usage in Online Health Communities: An Integrated Framework of SCT and TPB.

Background: Online health communities (OHCs) provide a new channel for users to obtain more health-related information and support, playing an important role in alleviating hospital congestion and uneven medical resource distribution, especially during the COVID-19 pandemic in China. An in-depth study of users' continuous usage is of great value for the long-term development of OHCs.

Objective: The purpose of this study is to explore the factors that influence users' continuous usage in online health communities based on the theory of planned behavior (TPB) and social cognitive theory (SCT).

Release of STK24/25 suppression on MEKK3 signaling in endothelial cells confers cerebral cavernous malformation.

Loss-of-function mutations in cerebral cavernous malformation (CCM) genes and gain-of-function mutation in the MAP3K3 gene encoding MEKK3 cause CCM. Deficiency of CCM proteins leads to the activation of MEKK3-KLF2/4 signaling, but it is not clear how this occurs. Here, we demonstrate that deletion of the CCM3 interacting kinases STK24/25 in endothelial cells causes defects in vascular patterning during development as well as CCM lesion formation during postnatal life.

Arterial dissections: Common features and new perspectives.

Arterial dissections, which involve an abrupt tear in the wall of a major artery resulting in the intramural accumulation of blood, are a family of catastrophic disorders causing major, potentially fatal sequelae. Involving diverse vascular beds, including the aorta or coronary, cervical, pulmonary, and visceral arteries, each type of dissection is devastating in its own way. Traditionally they have been studied in isolation, rather than collectively, owing largely to the distinct clinical consequences of dissections in different anatomical locations - such as stroke, myocardial infarction, and renal failure.

Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis.

Platelets have emerged as key inflammatory cells implicated in the pathology of sepsis, but their contributions to rapid clinical deterioration and dysregulated inflammation have not been defined. Here, we show that the incidence of thrombocytopathy and inflammatory cytokine release was significantly increased in patients with severe sepsis. Platelet proteomic analysis revealed significant upregulation of gasdermin D (GSDMD).

Cerebral cavernous malformation development in chronic mouse models driven by dual recombinases induced gene deletion in brain endothelial cells.

Cerebral cavernous malformation (CCM) is a brain vascular disease which can cause stroke, cerebral hemorrhage and neurological deficits in affected individuals. Loss-of-function mutations in three genes (, and ) cause CCM disease. Multiple mouse models for CCM disease have been developed although each of them are associated with various limitations.

The Expanding Role of Alternative Splicing in Vascular Smooth Muscle Cell Plasticity.

Vascular smooth muscle cells (VSMCs) display extraordinary phenotypic plasticity. This allows them to differentiate or dedifferentiate, depending on environmental cues. The ability to 'switch' between a quiescent contractile phenotype to a highly proliferative synthetic state renders VSMCs as primary mediators of vascular repair and remodelling.

Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting.

PDCD10, also known as CCM3, is a gene found to be associated with the human disease cerebral cavernous malformations (CCMs). PDCD10 forms a complex with GCKIII kinases including STK24, STK25, and MST4. Studies in C.

Cell Cycle Withdrawal Limit the Regenerative Potential of Neonatal Cardiomyocytes.

Purpose: The neonatal mouse possesses a transient capacity for cardiac regeneration during the first few days of life. The regenerative response of neonatal mouse is primarily mediated by pre-existing cardiomyocyte (CM) proliferation, which has been identified as the primary source of myocardial regeneration. Postnatal 4-day-old (P4) mouse CMs appear to undergo a rapid transition from hyperplastic to hypertrophic growth and binucleation.

Circular RNA CircMAP3K5 Acts as a MicroRNA-22-3p Sponge to Promote Resolution of Intimal Hyperplasia Via TET2-Mediated Smooth Muscle Cell Differentiation.

Background: Aberrant expression of circular RNA contributes to human diseases. Circular RNAs regulate gene expression by sequestering specific microRNAs. In this study, we investigated whether circMAP3K5 (circular mitogen-activated protein kinase 5) could act as a competing endogenous microRNA-22-3p (miR-22-3p) sponge and regulate neointimal hyperplasia.

Fatigue Limit of Custom 465 with Surface Strengthening Treatment.

In order to study the effect of nitriding or shot peening on the surface modification and fatigue properties of martensitic stainless-steel Custom 465, the residual stress and micro-hardness of the strengthened layer are determined by X-ray and micro-hardness tester, respectively. The up-and-down method is used to measure the rotational bending fatigue strength at 1 × 10 cycles, and the fatigue fracture characteristic is observed by scanning electron microscopy. The relationship between surface residual stress and internal fatigue limit of surface strengthening treatment is discussed.

Platelet-derived miR-223 promotes a phenotypic switch in arterial injury repair.

Upon arterial injury, endothelial denudation leads to platelet activation and delivery of multiple agents (e.g., TXA2, PDGF), promoting VSMC dedifferentiation and proliferation (intimal hyperplasia) during injury repair.

Specific functions of TET1 and TET2 in regulating mesenchymal cell lineage determination.

Background: The 5 hydroxymethylation (5hmC) mark and TET DNA dioxygenases play a pivotal role in embryonic stem cell differentiation and animal development. However, very little is known about TET enzymes in lineage determination of human bone marrow-derived mesenchymal stem/stromal cells (BMSC). We examined the function of all three TET DNA dioxygenases, responsible for DNA hydroxymethylation, in human BMSC cell osteogenic and adipogenic differentiation.

Biodegradation of triphenylmethane dye crystal violet by Cedecea davisae.

The present study focuses on the biodegradation of triphenylmethane dye crystal violet (CV) by Cedecea davisae. The degradation of CV was evaluated via ultraviolet absorbance at 254 nm (UV) and chemical oxygen demand (COD) removal, and the kinetics was used to evaluate the degradation efficiency. Intermediate products were analyzed via UV-vis spectroscopy (UV), Fourier transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC).

Ponatinib (AP24534) inhibits MEKK3-KLF signaling and prevents formation and progression of cerebral cavernous malformations.

Cerebral cavernous malformation (CCM) is a common cerebrovascular disease that can occur sporadically or be inherited. They are major causes of stroke, cerebral hemorrhage, and neurological deficits in the younger population. Loss-of-function mutations in three genes, , , and , have been identified as the cause of human CCMs.

Notoginsenoside R1 inhibits vascular smooth muscle cell proliferation, migration and neointimal hyperplasia through PI3K/Akt signaling.

Restenosis caused by neointimal hyperplasia significantly decreases long-term efficacy of percutaneous transluminal angioplasty (PTA), stenting, and by-pass surgery for managing coronary and peripheral arterial diseases. A major cause of pathological neointima formation is abnormal vascular smooth muscle cell (VSMC) proliferation and migration. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng and has reported cardioprotective, neuroprotective and anti-inflammatory effects.