Engineering a Novel NIR RNA-Specific Probe for Tracking Stress Granule Dynamics in Living Cells.

Real-time monitoring of the dynamics of cytosolic RNA-protein condensates, termed stress granules (SGs), is vital for understanding their biological roles in stress response and related disease treatment but is challenging due to the lack of simple and accurate methods. Compared with protein visualization that requires complex transfection procedures, direct RNA labeling offers an ideal alternative for tracking SG dynamics in living cells. Here, we propose a novel molecular design strategy to construct a near-infrared RNA-specific fluorescent probe () for tracking SGs in living cells.

Generating a human induced pluripotent stem cell line (XACHi018-A) from a Timothy syndrome infant carrying heterozygous CACNA1C c.1216G>A (p.G406R) mutation.

Timothy syndrome, an extremely rare disease, is closely associated with a mutation in CACNA1C gene, which encodes the cardiac L-type voltage-gated calcium channel (Cav1.2). In this study, we generated a human induced pluripotent stem cell (iPSC) line from a Timothy syndrome infant carrying heterozygous CACNA1C mutation (transcript variant NM_000719.

Gene Expression, Morphology, and Electrophysiology During the Dynamic Development of Human Induced Pluripotent Stem Cell-Derived Atrial- and Ventricular-Like Cardiomyocytes.

Background And Objectives: Gene expression, morphology, and electrophysiological combination are essential for assessing the dynamic development of human induced pluripotent stem cell-derived atrial- and ventricular-like cardiomyocytes (iPS-AM and iPS-VM, respectively).

Methods: For iPS-AM/VM differentiation, we performed the small molecule-based temporal modulation of the retinoic acid and bone morphogenetic protein signaling pathways. We investigated the gene expression and morphology using immunofluorescence, quantitative real-time polymerase chain reaction, flow cytometry, and transmission electron microscopy as well as registered electrophysiological functions using a whole-cell patch clamp on days 20, 30, and 60 post-differentiations.

Development and validation of a clinical prediction model for ischemic stroke recurrence after successful stent implantation in symptomatic intracranial atherosclerotic stenosis.

Objective: This study aimed to analyze the risk factors for recurrent ischemic stroke in patients with symptomatic intracranial atherosclerotic stenosis (ICAS) who underwent successful stent placement and to establish a nomogram prediction model.

Methods: We utilized data from a prospective collection of 430 consecutive patients at Jining NO.1 People's Hospital from November 2021 to November 2022, conducting further analysis on the subset of 400 patients who met the inclusion criteria.

Effect of flaxseed-derived diglyceride-based high internal phase Pickering emulsion on the quality characteristics of reformulated beef burgers.

The study aimed to fabricate healthier beef burgers using high internal phase Pickering emulsion (HIPPE) as animal fat substitute. In this context, HIPPE stabilized by modified soy protein isolates was produced with flaxseed-derived diglycerides (DAGs). Beef burgers were prepared by substituting beef backfat with HIPPE at varying levels (0%, 25%, 50%, 75%, and 100%).

Mitochondrial dysfunction is associated with hypertrophic cardiomyopathy in Pompe disease-specific induced pluripotent stem cell-derived cardiomyocytes.

Pompe disease (PD) is a rare autosomal recessive disorder that presents with progressive hypertrophic cardiomyopathy. However, the detailed mechanism remains clarified. Herein, PD patient-specific induced pluripotent stem cells were differentiated into cardiomyocytes (PD-iCMs) that exhibited cardiomyopathic features of PD, including decreased acid alpha-glucosidase activity, lysosomal glycogen accumulation and hypertrophy.

Establishment of a novel human induced pluripotent stem cell line (SIPDi001-A) with compound heterozygous mutations in the UBR7 gene from a Li-Campeau syndrome patient.

Li-Campeau syndrome (LICAS) is a syndromic neurodevelopmental disorder characterized by autosomal recessive inheritance and global developmental delay. In this study, we reported the generation of a novel induced pluripotent stem cell (iPSC) line derived from peripheral blood mononuclear cells (PBMCs) obtained from a 7-year-old male patient with Li-Campeau syndrome. The patient carries compound heterozygous variants in the UBR7 gene (c.

Small-conductance calcium-activated potassium channels in the heart: expression, regulation and pathological implications.

Ca-activated K channels are critical to cellular Ca homeostasis and excitability; they couple intracellular Ca and membrane voltage change. Of these, the small, 4-14 pS, conductance SK channels include three, encoded, SK1/KCa2.1, SK2/KCa2.

Generation of cardiomyocytes from human-induced pluripotent stem cells resembling atrial cells with ability to respond to adrenoceptor agonists.

Atrial fibrillation (AF) is the most common chronic arrhythmia presenting a heavy disease burden. We report a new approach for generating cardiomyocytes (CMs) resembling atrial cells from human-induced pluripotent stem cells (hiPSCs) using a combination of Gremlin 2 and retinoic acid treatment. More than 40% of myocytes showed rod-shaped morphology, expression of CM proteins (including ryanodine receptor 2, -actinin-2 and F-actin) and striated appearance, all of which were broadly similar to the characteristics of adult atrial myocytes (AMs).

Cardiac deficiency of P21-activated kinase 1 promotes atrial arrhythmogenesis in mice following adrenergic challenge.

P21-activated kinase 1 (Pak1) signalling plays a vital and overall protective role in the heart. However, the phenotypes of deficiency in the cardiac atria have not been well explored. In this study, cardiac-conditional knock-out (cKO) mice were studied under baseline and adrenergic challenge conditions.

Patient-specific induced pluripotent stem cell properties implicate Ca-homeostasis in clinical arrhythmia associated with combined heterozygous and variants.

We illustrate use of induced pluripotent stem cells (iPSCs) as platforms for investigating cardiomyocyte phenotypes in a human family pedigree exemplified by novel heterozygous RYR2-A1855D and SCN10A-Q1362H variants occurring alone and in combination. The proband, a four-month-old boy, presented with polymorphic ventricular tachycardia. Genetic tests revealed double novel heterozygous RYR2-A1855D and SCN10A-Q1362H variants inherited from his father (F) and mother (M), respectively.

Case report: Catecholamine cardiomyopathy in children with neuroblastoma.

Introduction: Many endocrine diseases, such as neuroblastoma (NB), can be linked with acquired cardiomyopathy and heart failure. Neuroblastoma's cardiovascular manifestations are typically hypertension, electrocardiogram (ECG) changes, and conduction disturbances.

Case Presentation: A 5-year-old 8-month-old girl was admitted to the hospital with ventricular hypertrophy and hypertension (HT) and heart failure.

A Clinical Prediction Model for Patients with Acute Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Stenosis.

Background: Acute large vessel occlusion due to underlying intracranial atherosclerotic stenosis (ICAS-LVO) increases the difficulty of revascularization, resulting in frequent re-occlusion. The establishment of its pathogenesis before endovascular treatment (EVT) is beneficial for patients. We aimed at developing and validating a clinical prediction model for ICAS-LVO patients before EVT.

Generation of one human induced pluripotent stem cell line (XACHi004-A) with heterozygous mutation of RYR2 gene from an atrial fibrillation patient.

As the most frequently diagnosed arrhythmia, atrial fibrillation (AF) has been recently reported to be closely related to ryanodine receptor (RyR2) dysfunction and calcium leak. Here, using non-integrating sendai viral method, we generated one iPSC line from peripheral blood mononuclear cells (PBMC) isolated a 10-year-old boy with simple atrial fibrillation which carries the heterozygous mutation in RYR2 gene (c.14638G > A, p.

Generation of two heterozygous GAA mutation-carrying human induced pluripotent stem cell lines (XACHi005-A, XACHi006-A) from parents of an infant with Pompe disease.

Pompe disease results from GAA mutations that leads to lysosomal glycogen accumulation and cardiac and skeletal muscle pathology. We have previously generated an infantile-onset Pompe disease patient-derived human-induced pluripotent stem cells (iPSCs) line carrying compound GAA mutations (R608X and E888X). Using his parents' peripheral blood mononuclear cells (PBMCs), we here generated two iPSCs lines which carry mutations of R608X E888X respectively.

The Biphasic Effect of Retinoic Acid Signaling Pathway on the Biased Differentiation of Atrial-like and Sinoatrial Node-like Cells from hiPSC.

Background And Objectives: Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs.

The safety and efficacy of the Neuroform EZ stent for the treatment of symptomatic atherosclerotic stenosis in the middle cerebral artery.

Objective: To evaluate the safety and efficacy of Neuroform EZ stent placement for patients with symptomatic atherosclerotic stenosis of the middle cerebral artery (MCA).

Method: We retrospectively reviewed the clinical data of 70 patients (36 males and 34 females; mean age: 62.5 ± 1.

Generation of induced pluripotent stem cells (iPSCs) from a Chinese infant (XACHi015-A) with type 2 Long QT syndrome carrying the heterozygous mutation c.1814C>T(p.P605L) in KCNH2.

Induced pluripotent stem cell lines (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a ten years old boy with the type 2 Long QT syndrome carrying the heterozygous mutation c.1814C>T(p.P605L) in KCNH2.

Establishment of iPSC line from a Chinese infant (XACHi012-A) with Jervell and Lange-Nielsen syndrome carrying combined KCNQ1 frameshift c.431delC(p.I145Sfs*92) and nonsense c.1175G > A (p.W392X) variants and two iPSC lines from the parents (XACHi013-A, XACHi014-A).

Induced pluripotent stem cell lines (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a two month-old boy and the parents. Jervell and Lange-Nielsen syndrome (JLNS) was diagnosed in the boy carrying combined KCNQ1 frameshift c.431delC (p.

Downregulation of microRNA‑221 facilitates H1N1 influenza A virus replication through suppression of type‑IFN response by targeting the SOCS1/NF‑κB pathway.

Accumulating data has indicated that host microRNAs (miRNAs/miRs) play essential roles in innate immune responses to viral infection; however, the roles and the underlying mechanisms of miRNAs in influenza A virus (IAV) replication remain unclear. The present study examined on the effects of miRNAs on hemagglutinin (H)1 neuraminidase (N)1 replication and antiviral innate immunity. Using a microarray assay, the expression profiles of miRNA molecules in IAV‑infected A549 cells were analyzed.

P21‑activated kinase 1 mediates angiotensin II‑induced differentiation of human atrial fibroblasts via the JNK/c‑Jun pathway.

Cardiac fibrosis is a common pathophysiological condition involved in numerous types of cardiovascular disease. The renin‑angiotensin system, particularly angiotensin II (AngII), serves an important role in cardiac fibrosis and remodeling. Furthermore, p21‑activated kinase 1 (PAK1) is a highly conserved serine/threonine protein kinase, which is abundantly expressed in all regions of the heart.

RAD-Deficient Human Cardiomyocytes Develop Hypertrophic Cardiomyopathy Phenotypes Due to Calcium Dysregulation.

Ras associated with diabetes (RAD) is a membrane protein that acts as a calcium channel regulator by interacting with cardiac L-type Ca channels (LTCC). RAD defects can disrupt intracellular calcium dynamics and lead to cardiac hypertrophy. However, due to the lack of reliable human disease models, the pathological mechanism of RAD deficiency leading to cardiac hypertrophy is not well understood.