Long-term glucosamine supplementation aggravates atrial fibrillation susceptibility by impairing AMPK signaling.

Aims: Glucosamine, a widely used dietary supplement, has been linked to potential cardiovascular risks, including atrial fibrillation (AF). This study aimed to investigate the effects of long-term glucosamine supplementation on AF susceptibility and the underlying mechanisms.

Materials And Methods: C57BL/6 J mice were treated with low-dose (15 mg/kg/day) or high-dose (250 mg/kg/day) glucosamine via drinking water for 6 weeks.

Value of the combination of intraepithelial tumor-infiltrating lymphocyte density and the heterogeneity of density as a prognostic marker in stage III colorectal cancers.

Tumor-infiltrating lymphocyte (TIL) density is both a prognostic and a predictive factor in colorectal cancer (CRC). Whether the heterogeneity of TIL density across the tumor plays an important role in the clinical outcome of CRC is not well known. Adjuvant chemotherapy-treated patients with stage III CRC were analyzed for survival according to TIL density and density heterogeneity, which were determined on CD8-immunostained slides using a machine learning method and by calculating the Simpson evenness index, respectively.

Efficacy of wearable transcutaneous electrical acupoint stimulation bracelet on moderate-to-severe postoperative nausea and vomiting in patients after general anesthesia: a study protocol for a multicenter randomized controlled trial.

Background: Postoperative nausea and vomiting (PONV) is the most common complication following general anesthesia. Currently, pharmaceutical therapy is the primary method of treatment, but it has reached a plateau, and it is accompanied by inherent adverse reactions and high costs. Stimulation of the wrist acupuncture point PC6 is recommended as an effective means of preventing PONV.

Validation of the I- and D-type epistemic curiosity scale among young Chinese children and implications on early curiosity nurture.

Curiosity, an innate and intrinsic motivation to explore, makes vital contributions to learning in individuals of various ages. Epistemic curiosity centers on the drive to close information gaps and can be classified into joyous exploration and interest (I) and deprivation sensitivity (D) types. Each subtype is associated with different academic achievements, personality traits, emotions, and aspects of creativity.

The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.

Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.

Clinicopathological and molecular features of genome-stable colorectal cancers.

Colorectal cancers (CRCs) are traditionally divided into those with either chromosomal instability (CIN) or microsatellite instability (MSI). By utilizing TCGA data, the Laird team found a subset of CRCs, namely, genome-stable CRCs (GS CRCs), which lack both CIN and MSI. Although the molecular features of GS CRCs have been described in detail, the clinicopathological features are not well defined.

Concomitant expression patterns of CDX2 and SATB2 as prognostic factors in stage III colorectal cancers.

CDX2 and SATB2 are often used as biomarkers for identification of colorectal origin in primary or metastatic adenocarcinomas. Loss of CDX2 or SATB2 expression has been associated with poor prognosis in patients with colorectal cancer (CRC). However, little is known regarding clinicopathological features, including prognosis, of CRCs with concomitant loss of CDX2 and SATB2.

Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivity.

Moderate exercise decreases the risk for atrial fibrillation (AF), an effect which is probably mediated via exercise-stimulated release of exerkines. β-Aminoisobutyric acid (BAIBA), a novel exerkine, has been reported to provide protective benefits against many cardiovascular diseases, yet its role in AF remains elusive. Herein, using a mouse model of obesity-related AF through high-fat diet (HFD) feeding, we found that 12-week drinking administration of BAIBA (170 mg/kg/day) decreased AF susceptibility in obese mice.

[Metabolic mechanism and intervention strategy of atrial fibrillation in the elderly].

Atrial fibrillation (AF) is a cardiovascular epidemic that occurs primarily in the elderly with primary cardiovascular diseases, leading to severe consequences such as stroke and heart failure. The heart is an energy-consuming organ, which requires a high degree of metabolic flexibility to ensure a quick switch of metabolic substrates to meet its energy needs in response to physiological and pathological stimulation. Metabolism is closely related to the occurrence of AF, and AF patients manifest metabolic inflexibility, such as insulin resistance and the metabolic shift from aerobic metabolism to anaerobic glycolysis.

Prognostic significance of STING expression in solid tumor: a systematic review and meta-analysis.

Objective: Stimulator of interferon genes (STING) is a key regulator in initiating innate immune response from sensing cytosolic DNA. Recent studies have revealed that the cGAS-STING signaling pathway has a crucial role in tumor development and progression across cancer types. Herein, we conducted a meta-analysis to explore the relationship between the immunoexpression of STING and the survival outcome of patients in various solid tumors.

Construction and validation of a cuproptosis-related diagnostic gene signature for atrial fibrillation based on ensemble learning.

Background: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Nonetheless, the accurate diagnosis of this condition continues to pose a challenge when relying on conventional diagnostic techniques. Cell death is a key factor in the pathogenesis of AF.

Left bundle branch area pacing: A promising modality for cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is recognized as the first-line management for patients with heart failure (HF) and conduction disorders. As a conventional mode for delivering CRT, biventricular pacing (BVP) improves cardiac function and reduces HF hospitalizations and mortality, but there are still limitations given the high incidence of a lack of response rates. Alternative pacing methods are needed either for primary or rescue therapy.

Application of patient-centered care using guidelines of the Joint Commission on Accreditation of Healthcare Organizations in patients with acute subarachnoid hemorrhage.

Objective: This study was designed to explore the feasibility and effectiveness of patient-centered care (PCC) on basis of guidelines of Joint Commission on Accreditation of Healthcare Organizations (JCI) in patients with acute subarachnoid hemorrhage (SAH).

Methods: A total of 180 SAH patients who received treatment in our hospital were selected as prospective research objects, and were divided into a study group (n=90) and a control group (n=90) by convenience sampling. Patients in the control group received conventional SAH-targeted care, and patients in the study group were additionally nursed with PCC on the basis of conventional SAH-targeted care.

Hyper-O-GlcNAcylation impairs insulin response against reperfusion-induced myocardial injury and arrhythmias in obesity.

Myocardial ischemia/reperfusion (I/R) injury is a major determinant of morbidity and mortality in patients undergoing treatment for cardiac disease. A variety of treatments are reported to have benefits against reperfusion injury, yet their cardioprotective effects seem to be diminished in obesity, and the underlying mechanism remains elusive. In this study, we found that db/db mice exhibit cardiac hyper-O-GlcNAcylation.

Regulation of Tumor-Associated Myeloid Cell Activity by CBP/EP300 Bromodomain Modulation of H3K27 Acetylation.

Myeloid-derived suppressor cells (MDSCs) are found in most cancer malignancies and support tumorigenesis by suppressing immunity and promoting tumor growth. Here we identify the bromodomain (BRD) of CBP/EP300 as a critical regulator of H3K27 acetylation (H3K27ac) in MDSCs across promoters and enhancers of pro-tumorigenic target genes. In preclinical tumor models, in vivo administration of a CBP/EP300-BRD inhibitor (CBP/EP300-BRDi) alters intratumoral MDSCs and attenuates established tumor growth in immunocompetent tumor-bearing mice, as well as in MDSC-dependent xenograft models.

Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation.

Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer activity. However, the functional impact of this modification at enhancers is poorly understood. Here, we use a chemical genetics approach to acutely block the function of the cAMP response element binding protein (CREB) binding protein (CBP)/P300 bromodomain in models of hematological malignancies and describe a consequent loss of H3K27Ac specifically from enhancers, despite the continued presence of CBP/P300 at chromatin.

A novel device for air removal from vascular access line: a bench study.

Efficient air removal from a vascular access line is a key step to prevent air embolism. Existing devices, especially for rapid infusers, are far from optimum. In this study, we developed a novel device, vascular access line air removal device (VALARD), and compared its efficiency of air removal and pause time of forward bulk flow with a commonly used device, the Belmont pump.

Therapeutic Targeting of the CBP/p300 Bromodomain Blocks the Growth of Castration-Resistant Prostate Cancer.

Resistance invariably develops to antiandrogen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here, we report that the transcriptional coactivator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth and Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression.

Targeting protein-protein interaction by small molecules.

Protein-protein interactions (PPIs) are critical regulatory events in physiology and pathology, and they represent an important target space for pharmacological intervention. However, targeting PPIs with small molecules is challenging owing to the large surface area involved in protein-protein binding and the lack of obvious small-molecule-binding pockets at many protein-protein interfaces. Nonetheless, successful examples of small-molecule modulators of PPIs have been growing in recent years.

BDNF-TrkB signaling pathway is involved in pentylenetetrazole-evoked progression of epileptiform activity in hippocampal neurons in anesthetized rats.

Pentylenetetrazole (PTZ) is a widely-used convulsant used in studies of epilepsy; its subcutaneous injection generates an animal model with stable seizures. Here, we compared the ability of PTZ via the intravenous and subcutaneous routes to evoke progressive epileptiform activity in the hippocampal CA1 neurons of anesthetized rats. The involvement of the BDNF-TrkB pathway was then investigated.

Ubiquitin-dependent regulation of COPII coat size and function.

Packaging of proteins from the endoplasmic reticulum into COPII vesicles is essential for secretion. In cells, most COPII vesicles are approximately 60-80 nm in diameter, yet some must increase their size to accommodate 300-400 nm procollagen fibres or chylomicrons. Impaired COPII function results in collagen deposition defects, cranio-lenticulo-sutural dysplasia, or chylomicron retention disease, but mechanisms to enlarge COPII coats have remained elusive.

Eucommia ulmoides Oliv. antagonizes H2O2-induced rat osteoblastic MC3T3-E1 apoptosis by inhibiting expressions of caspases 3, 6, 7, and 9.

Eucommia ulmoides Oliv. (EuO), also known as Duzhong, native to China, has been reported to have antioxidative function, but its cellular mechanism is not fully examined yet. We investigated inhibitory effects of EuO leaf ethanol extracts on H(2)O(2)-induced apoptosis in rat osteoblastic MC3T3-E1 cells and underlying mechanisms.

[Influence of dental metallic materials on MR imaging].

Magnetic resonance imaging (MRI) technique is one of the most commonly used imaging diagnostic techniques for pate diseases at present.Metal and alloy are commonly used in dental practice. The artifacts on MRI caused by metal and alloy may result in attenuation of signal intensity, image distortion and signal loss, which severely influences imaging quality.

Preparation of synchronized human cell extracts to study ubiquitination and degradation.

Ubiquitination and protein degradation regulate cell cycle progression in all eukaryotes. During mitosis, ubiquitination by the Anaphase-Promoting Complex/Cyclosome (APC/C) triggers sister chromatid separation and mitotic exit. The APC/C is tightly regulated by phosphorylation, ubiquitination, association of activators or inhibitors, and competitive binding of substrates.