Oligogenic effect is associated with the clinical heterogeneity of autosomal dominant deafness-15.

Autosomal dominant deafness-15 which is caused by mutation in the POU4F3 gene, has been reported with a wide degree of clinical heterogeneity, even between intrafamilial members. However, the reason is still elusive. In this study, A four-generation Chinese family with 11 patients manifesting late-onset progressive non-syndromic hearing loss was recruited.

PIGK defects induce apoptosis in Purkinje cells and acceleration of neuroectodermal differentiation.

Biallelic mutations in PIGK cause GPI biosynthesis defect 22 (GPIBD22), characterized with developmental delay, hypotonia, and cerebellar atrophy. The understanding of the underlying causes is limited due to the lack of suitable disease models. To address this gap, we generated a mouse model with PIGK deficits, specifically in Purkinje cells (Pcp2-cko) and an induced pluripotent stem cell (iPSC) model using the c.

RAB17 promotes endometrial cancer progression by inhibiting TFRC-dependent ferroptosis.

Studies have indicated that RAB17 expression levels are associated with tumor malignancy, and RAB17 is more highly expressed in endometrial cancer (EC) tissues than in peritumoral tissues. However, the roles and potential mechanisms of RAB17 in EC remain undefined. The present study confirmed that the expression of RAB17 facilitates EC progression by suppressing cellular ferroptosis-like alterations.

Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway.

Endometrial cancer (EC) is a common malignant tumor that is closely associated with metabolic disorders such as diabetes and obesity. Advanced glycation end products (AGEs) are complex polymers formed by the reaction of reducing sugars with the amino groups of biomacromolecules, mediating the occurrence and development of many chronic metabolic diseases. Recent research has demonstrated that the accumulation of AGEs can affect the tumor microenvironment, metabolism, and signaling pathways, thereby affecting the malignant progression of tumors.

[Preoperative Evaluation of Cervical Lymph Node Metastasis in Patients With Hashimoto's Thyroiditis Combined With Thyroid Papillary Carcinoma Using Machine Learning and Radiomics-Based Features: A Preliminary Study].

Objective: To analyze the radiomic and clinical features extracted from 2D ultrasound images of thyroid tumors in patients with Hashimoto's thyroiditis (HT) combined with papillary thyroid carcinoma (PTC) using machine learning (ML) models, and to explore the diagnostic performance of the method in making preoperative noninvasive identification of cervical lymph node metastasis (LNM).

Methods: A total of 528 patients with HT combined with PTC were enrolled and divided into two groups based on their pathological results of the presence or absence of LNM. The groups were subsequently designated the With LNM Group and the Without LNM Group.

O-Sialoglycoprotein Endopeptidase Deficiency Impairs Proteostasis and Induces Autophagy in Human Embryonic Stem Cells.

The gene encodes O-sialoglycoprotein endopeptidase, a catalytic unit of the highly conserved KEOPS complex (Kinase, Endopeptidase, and Other Proteins of small Size) that regulates the second biosynthetic step in the formation of N-6-threonylcarbamoyladenosine (t6A). Mutations in KEOPS cause Galloway-Mowat syndrome (GAMOS), whose cellular function in mammals and underlying molecular mechanisms are not well understood. In this study, we utilized lentivirus-mediated knockdown to generate -deficient human embryonic stem cells (hESCs).

IGF2BP2-modified circular RNA circCHD7 promotes endometrial cancer progression via stabilizing PDGFRB and activating JAK/STAT signaling pathway.

Circular RNAs (circRNAs) represent a class of covalently closed, single-stranded RNAs and have been linked to cancer progression. N6-methyladenosine (mA) methylation is a ubiquitous RNA modification in cancer cells. Increasing evidence suggests that mA can mediate the effects of circRNAs in cancer biology.

Characterization and validation of fatty acid metabolism-related genes predicting prognosis, immune infiltration, and drug sensitivity in endometrial cancer.

Endometrial cancer is considered to be the second most common tumor of the female reproductive system, and patients diagnosed with advanced endometrial cancer have a poor prognosis. The influence of fatty acid metabolism in the prognosis of patients with endometrial cancer remains unclear. We constructed a prognostic risk model using transcriptome sequencing data of endometrial cancer and clinical information of patients from The Cancer Genome Atlas (TCGA) database via least absolute shrinkage and selection operator regression analysis.

Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma.

The current study tested the expression and potential functions of Gαi1 in nasopharyngeal carcinoma (NPC). The Cancer Genome Atlas (TCGA) database results demonstrate that Gαi1 transcripts' number in NPC tissues is significantly higher than that in the normal nasal epithelial tissues. Its overexpression correlates with poor survival in certain NPC patients.

Treatment of stroke in aged male and female rats with Vepoloxamer and tPA reduces neurovascular damage.

Unlabelled: Stroke is a leading cause of death and disability worldwide, mainly affecting the elderly. Unfortunately, current treatments for acute ischemic stroke warrant improvement. To date, tissue plasminogen activator (tPA) is of limited use in stroke patients mainly due to its narrow therapeutic window and potential for hemorrhagic complication.

PTC-MAS: A Deep Learning-Based Preoperative Automatic Assessment of Lymph Node Metastasis in Primary Thyroid Cancer.

Background: Identifying cervical lymph node metastasis (LNM) in primary thyroid cancer preoperatively using ultrasound is challenging. Therefore, a non-invasive method is needed to assess LNM accurately.

Purpose: To address this need, we developed the Primary Thyroid Cancer Lymph Node Metastasis Assessment System (PTC-MAS), a transfer learning-based and B-mode ultrasound images-based automatic assessment system for assessing LNM in primary thyroid cancer.

The role of left ventricular hypertrophy measured by echocardiography in screening patients with ischaemia with non-obstructive coronary arteries: a cross-sectional study.

Many patients with ischaemia with non-obstructive coronary arteries (INOCA) have a poor prognosis. This study aims to explore the diagnostic value of left ventricular hypertrophy (LVH)-related ultrasound parameters in INOCA patients. The study group consisted of 258 patients with INOCA in this retrospective cross-sectional study, and these patients were free of obstructive coronary artery disease, previous revascularization, atrial fibrillation, ejection fraction < 50%, major distortions of left ventricular geometry, suspected non-ischaemic causes.

Ultra-sensitive biosensor based on CRISPR-Cas12a and Endo IV coupled DNA hybridization reaction for uracil DNA glycosylase detection and intracellular imaging.

As an essential biomarker associated with various diseases, Uracil-DNA Glycosylase (UDG) detection is vital for disease diagnosis, treatment selection, and prognosis assessment. In recent years, the signal amplification effect of the CRISPR-Cas12a trans-cleaved single-stranded DNA probe has provided an available strategy for constructing highly sensitive biosensors. However, its superior trans-cleavage activity has become a "double-edged sword" for building biosensors that can amplify the target signal while also amplifying the leakage signal, causing out of control.

WDR73 Depletion Destabilizes PIP4K2C Activity and Impairs Focal Adhesion Formation in Galloway-Mowat Syndrome.

(1) Background: Galloway-Mowat syndrome (GAMOS) is a rare genetic disease, classically characterized by a combination of various neurological symptoms and nephrotic syndrome. WDR73 is the pathogenic gene responsible for GAMOS1. However, the pathological and molecular mechanisms of GAMOS1, especially nephrotic syndrome caused by WDR73 deficiency, remain unknown.

CircRAPGEF5 interacts with RBFOX2 to confer ferroptosis resistance by modulating alternative splicing of TFRC in endometrial cancer.

Endometrial cancer (EC) is one of the most common gynecological cancers. Ferroptosis is a newly identified form of cell death characterized by iron-dependent lipid peroxide accumulation. Circular RNAs (circRNAs) have emerged as critical regulators for cancer development.

Cerebral endothelial cell derived small extracellular vesicles improve cognitive function in aged diabetic rats.

Small extracellular vesicles (sEVs) mediate cell-cell communication by transferring their cargo biological materials into recipient cells. Diabetes mellitus (DM) induces cerebral vascular dysfunction and neurogenesis impairment, which are associated with cognitive decline and an increased risk of developing dementia. Whether the sEVs are involved in DM-induced cerebral vascular disease, is unknown.

Novel variants in OSGEP leading to Galloway-Mowat syndrome by altering its subcellular localization.

Galloway-Mowat syndrome (GAMOS) is an extremely rare clinically heterogeneous autosomal or X-linked inherited recessive disease characterized by early-onset steroid-resistant nephrotic syndrome (SRNS), microcephaly and neurological impairment. In this study, two siblings mainly presenting with decreased head circumference, hypotonia, gross motor delay, and dysmorphic features were initially detected without pathogenic variants by karyotyping, SNP-array and WES. After a 3 year's follow-up, the proband manifested additional proteinuria, hematuria and "deeper sulci" with a sign of brain atrophy.

Therapeutic effect of Cerebrolysin on reducing impaired cerebral endothelial cell permeability.

Cerebrolysin has been shown to promote neurovascular protection and repair in preclinical models of stroke and neural injury and is demonstrating promise for stroke and neural injury therapeutic application in the clinic. The effect of Cerebrolysin on the human cerebral endothelial cell function has not been investigated. Using an in-vitro cerebral endothelial cell permeability assay and western blot analyses of tight junction and proinflammatory and procoagulant proteins, the present study showed that tissue plasminogen activator (tPA) and fibrin substantially impaired human cerebral endothelial cell barrier function and increased permeability, which persisted for at least 24 h.

Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) created using covered stents of different diameters: A systematic review and meta-analysis.

Purpose: The purpose of this study was to make a systematic review and meta-analysis to determine the stent diameter (8mm vs. 10mm) that conveys better safety and clinical efficacy for transjugular intrahepatic portosystemic shunt (TIPS).

Materials And Methods: Four databases were used to identify clinical trials published from inception until March 2020.

NLRP3 inflammasome activation by estrogen promotes the progression of human endometrial cancer.

Background: Activation of NLPR3 inflammasome is associated with the development and progression of some types of malignant tumors, but its role in endometrial cancer is unclear. This study aimed to investigate the expression and function of NLRP3 inflammasome in endometrial cancer.

Materials And Methods:  The expression levels of NLRP3, its inflammasome components and estrogen receptor β in endometrial cancer and paired non-tumor tissues were detected.

N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Augments Thrombolysis of tPA (Tissue-Type Plasminogen Activator) in Aged Rats After Stroke.

Background and Purpose- Stroke is a leading cause of disability worldwide, mainly affecting the elderly. However, preclinical studies in aged ischemic animals are limited. N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a naturally occurring tetrapeptide with vascular-protective properties.

Identification of key pathways and genes in endometrial cancer using bioinformatics analyses.

Endometrial cancer (EC) is one of the most common gynecological cancer types worldwide. However, to the best of our knowledge, its underlying mechanisms remain unknown. The current study downloaded three mRNA and microRNA (miRNA) datasets of EC and normal tissue samples, GSE17025, GSE63678 and GSE35794, from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) and miRNAs (DEMs) in EC tumor tissues.

Diagnostic performance of two-dimensional shear wave elastography for evaluating tibial nerve stiffness in patients with diabetic peripheral neuropathy.

Objectives: To evaluate the stiffness of the tibial nerve with two-dimensional shear wave elastography (2D-SWE) and to determine whether 2D-SWE can be used to diagnose diabetic peripheral neuropathy (DPN).

Methods: The study included 70 consecutive diabetic patients with DPN or without DPN and 20 healthy volunteers. The tibial nerve stiffness measured with 2D-SWE was studied.