Trim21 modulates endoplasmic reticulum-associated degradation and sensitizes cancer cells to ER stress-induced apoptosis by inhibiting VCP/Npl4/UFD1 assembly.

Endoplasmic reticulum-associated degradation (ERAD) serves as a crucial quality and quantity control system that removes misfolded or unassembled proteins from the Endoplasmic Reticulum (ER) through the cytoplasmic ubiquitin-proteasome system (UPS), which is critical for cell fate decision. ER stress arises when misfolded proteins accumulated within the ER lumen, potentially leading to cell death via proapoptotic unfolded protein response (UPR). UFD1 in associated with VCP-Npl4, is recognized as a key regulator of protein homeostasis in ERAD.

AZD7762 induces CRBN dependent BAG3 degradation through ubiquitin-proteasome pathway.

Protein degraders are currently under rapid development as a promising modality for drug discovery. They are compounds that orchestrate interactions between a target protein and an E3 ubiquitin ligase, prompting intracellular protein degradation through proteasomal pathway. More protein degraders identification will greatly promote the development of this field.

Triptolide inhibits the progression of Glioblastoma U251 cells targeting PROX1.

Background: Glioblastoma multiforme (GBM) is the most lethal brain cancer in adults, characterized by rapid growth, extensive invasiveness, and poor prognosis, and there is still a lack of effective treatments. Here, we aimed to explore the role of triptolide (TPL), purified from Hook F, on glioblastoma cell growth, apoptosis, proliferation, migration and invasion, as well as potential underlying mechanisms.

Methods: The publicly available clinical data of Brain Lower Grade Glioma (LGG) from The Cancer Genome Atlas (TCGA) had been screened to observe PROX1 expression.

HMOX1 Promotes Ferroptosis Induced by Erastin in Lens Epithelial Cell through Modulates Fe Production.

Purpose: Ferroptosis is defined by the iron-dependent cell death caused by the accumulation of lipid peroxidation. As a major intracellular Fe pools, heme could be metabolized into ferrous iron, carbon monoxide, and biliverdin by Heme oxygenase-1 (HMOX1). Aged human lens epithelium was reported to highly susceptible to ferroptosis, the functional molecular involved in this progress is not explored.

Identification of a Novel 15q21.1 Microdeletion in a Family with Marfan Syndrome.

Background: Marfan syndrome (MFS) is a connective tissue disease involving multiple systems, with thoracic aortic aneurysm (TAA) as the most common life-threatening manifestation.

Method: A pedigree with TAA was investigated, and peripheral venous blood was extracted from six family members. After whole exome sequencing (WES) and chromosomal microarray analysis (CMA) in these individuals, bioinformatics and inheritance analyses were performed.

A Modified Ascending Aortic Cannulation Technique in Minimally Invasive Totally Thoracoscopic Cardiac Surgery.

Cannulation through the femoral artery is the preferred method of establishing peripheral cardiopulmonary bypass in minimally invasive totally thoracoscopic cardiac surgery. However, faced with the contraindication of femoral artery cannulation, modified ascending aortic cannulation is an alternative approach to minimally invasive totally thoracoscopic cardiac surgery.

Total Thoracoscopic Surgery for Late Mitral Paravalvular Leakage Repair in A Beating Heart.

Paravalvular leakage (PVL) after mitral valve replacement is a troublesome complication that may lead to severe symptoms and reoperation. Previous case reports on total thoracoscopic cardiac surgery without aortic cross-clamping for repairing late PVL are rare. We describe a 64-year-old man who had undergone aortic and mitral valve replacement via median sternotomy eight years earlier, and who recently developed cardiac failure due to severe tricuspid regurgitation (TR) and PVL in the posterior mitral annulus.

miR-198 inhibits the progression of renal cell carcinoma by targeting BIRC5.

Background: miR-198 is involved in the formation, migration, invasion, and metastasis of various malignant cancers. However, the function and mechanism of action of miR-198 in the tumorigenesis of renal cell carcinoma (RCC) remain elusive. Here, we aimed to explore the role of miR198 in RCC.

Global identification of phospho-dependent SCF substrates reveals a FBXO22 phosphodegron and an ERK-FBXO22-BAG3 axis in tumorigenesis.

SKP1-CUL1-F-box (SCF) ubiquitin ligases play fundamental roles in cellular functions. Typically, substrate phosphorylation is required for SCF recognition and subsequent degradation. However, phospho-dependent substrates remain largely unidentified.

The risk factors of the early postoperative residual tricuspid regurgitation after concomitant thoracoscopic tricuspid valve repair.

Objective: Secondary tricuspid regurgitation will be aggravated if left uncorrected during the initial surgery. Recently, an aggressive strategy of routine concomitant tricuspid valve repair has been warranted. Follow this strategy, routine concomitant thoracoscopic tricuspid valve repair was performed and the surgical effect and postoperative residual TR were reviewed.

One-stage minimally surgical treatment for myocardial bridge with other cardiac malformations.

The myocardial bridge (MB) refers to the epicardial coronary artery being abnormally covered by the superficial myocardium and running within the cardiac muscle. Surgery should be considered as an optimal choice for severe symptomatic MBs or simultaneous surgery for other heart diseases with severe MBs. Median sternotomy is the most commonly used surgical method.

Transcriptome-wide study of the response of human trabecular meshwork cells to the substrate stiffness increase.

Elevated intraocular pressure, a major risk factor of glaucoma, is caused by the abnormal function of trabecular outflow pathways. Human trabecular meshwork (HTM) tissue plays an important role in the outflow pathways. However, the molecular mechanisms that how TM cells respond to the elevated IOP are largely unknown.

Combined one-stage minimally invasive surgery for primary pulmonary carcinoma and mitral regurgitation.

Background: We report the first successful short-term outcome of one-stage minimally invasive surgery (MIS) mitral valve repair and video-assisted thoracoscopic surgery (VATS) lobectomy.

Case Presentation: We report the first successful short-term outcome of combined one-stage video-assisted thoracoscopic surgery lobectomy and minimally invasive surgery in a patient with operable primary right upper lobe adenocarcinoma and mitral regurgitation. Post- operative recovery was uneventful, and follow-up at 6 weeks confirmed an excellent surgical and oncologic outcome.

Sustained ER stress promotes hyperglycemia by increasing glucagon action through the deubiquitinating enzyme USP14.

Endoplasmic reticulum (ER) stress plays an important role in metabolic diseases like obesity and type 2 diabetes mellitus (T2DM), although the underlying mechanisms and regulatory pathways remain to be elucidated. Here, we induced chronic low-grade ER stress in lean mice to levels similar to those in high-fat diet (HFD)-fed obese mice and found that it promoted hyperglycemia due to enhanced hepatic gluconeogenesis. Mechanistically, sustained ER stress up-regulated the deubiquitinating enzyme ubiquitin-specific peptidase 14 (USP14), which increased the stability and levels of 3',5'-cyclic monophosphate-responsive element binding (CREB) protein (CBP) to enhance glucagon action and hepatic gluconeogenesis.

Transcriptome analysis reveals downregulation of virulence-associated genes expression in a low virulence Verticillium dahliae strain.

Verticillium dahliae causes wilt diseases and early senescence in numerous plants, including agricultural crops such as cotton. In this study, we studied two closely related V. dahliae strains, and found that V991w showed significantly reduced virulence on cotton than V991b.

MicroRNA-transcription factor network analysis reveals miRNAs cooperatively suppress RORA in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) represents over 90% of oral cancer incidence, while its mechanisms of tumorigenesis remain poorly characterized. In this study, we applied RNA-seq and microRNA-seq methodologies in four pairs of cancer and adjacent normal tissues to profile the contribution of miRNAs to tumorigenesis-altered functional pathways by constructing a comprehensive miRNA-mediated mRNA regulatory network. There were 213 differentially expressed (DE) miRNAs and 2172 DE mRNAs with the involvement of negative miRNA-mRNA interactions identified by at least two pairs of cancerous tissues.

SRY-Box Containing Gene 4 Promotes Liver Steatosis by Upregulation of SREBP-1c.

Obesity is usually associated with an increased risk of nonalcoholic fatty liver disease that is characterized by accumulation of excessive triglyceride (TG) in hepatocytes. However, the factors involved in the obesity-induced hepatosteatosis are poorly defined. Here, we report that SRY-box containing gene 4 (), a transcription factor that regulates cell proliferation and differentiation, plays an important role in hepatic TG metabolism.

HSF4 transcriptional regulates HMOX-1 expression in HLECs.

The major causes for cataract formation are free radicals, which are neutralized by the endogenous antioxidants. However, how the human lens clean these harmful free radicals is still unclear. Transcriptional factor heat shock factor 4 (HSF4) is a cataract-causing gene and plays important roles during lens development.

HSF4 regulates lens fiber cell differentiation by activating p53 and its downstream regulators.

Cataract refers to opacities of the lens that impede the passage of light. Mutations in heat shock transcription factor 4 (HSF4) have been associated with cataract; however, the mechanisms regarding how mutations in HSF4 cause cataract are still obscure. In this study, we generated an hsf4 knockout zebrafish model using TALEN technology.

Activation of the intronic cryptic 5' splice site depends on its distance to the upstream cassette exon.

Splice site selection is a key step that determines the mRNA isoforms generated from a single transcript. The large diversity in splice site sequences emphasizes the plasticity of splice site recognition and selection. In this report, a cell-based reporter system using a SMN1/2 cassette exon was applied to study the roles governing the activation of a cryptic 5'SS from the intron 4 of the CT/CGRP gene.

Transcriptome analysis reveals the complexity of alternative splicing regulation in the fungus Verticillium dahliae.

Background: Alternative splicing (AS) regulation is extensive and shapes the functional complexity of higher organisms. However, the contribution of alternative splicing to fungal biology is not well studied.

Results: This study provides sequences of the transcriptomes of the plant wilt pathogen Verticillium dahliae, using two different strains and multiple methods for cDNA library preparations.

Whole exome sequencing identifies a novel NRL mutation in a Chinese family with autosomal dominant retinitis pigmentosa.

Purpose: To investigate the genetic basis and its relationship to the clinical manifestations in a four generation Chinese family with autosomal dominant retinitis pigmentosa.

Methods: Ophthalmologic examinations including fundus photography, fundus autofluorescence imaging, fundus fluorescein angiography, optical coherence tomography, and a best-corrected visual acuity test were performed to define the clinical features of the patients. We extracted the genomic DNA from peripheral blood samples.

Loss-of-function Mutation in PMVK Causes Autosomal Dominant Disseminated Superficial Porokeratosis.

Disseminated superficial porokeratosis (DSP) is a rare keratinization disorder of the epidermis. It is characterized by keratotic lesions with an atrophic center encircled by a prominent peripheral ridge. We investigated the genetic basis of DSP in two five-generation Chinese families with members diagnosed with DSP.

Percutaneous trans-jugular vein closure of atrial septal defect with steerable introducer under echocardiographic guidance.

Background: The aim of this study is to discuss a novel surgical approach of percutaneous trans-jugular vein closure of atrial septal defect (ASD) with steerable introducer under echocardiographic guidance.

Methods: From January 2015 to June 2015, ten ASD patients underwent percutaneous trans-jugular vein ASD closure, the occluder placement could be perpendicular to the plane of ASD using the steerable introducer.

Results: All cases succeeded.