Investigating genotype-phenotype correlation of limb-girdle muscular dystrophy R8: association of clinical severity, protein biological function and protein oligomerization.

Limb-girdle muscular dystrophy R8 (LGMD R8) is a hereditary muscle disease caused by biallelic defects in E3 ubiquitinated ligase gene (TRIM32). LGMD R8 is featured by high genetic heterogeneity and phenotypic diversity, most pathogenic variants are missense variants located in the NHL domain, but the genotype-phenotype correlation remains unclear. We hypothesized that various missense variants in NHL domain might have different degrees of impact on the structure and function of the protein, thus resulting in disease variability.

Elevated Bile Acids Induce Circadian Rhythm Sleep Disorders in Chronic Liver Diseases.

Background & Aims: Sleep disorders (SDs) are common in chronic liver diseases (CLDs). Some SDs arise from impaired internal clock and are, hence, circadian rhythm SDs (CRSDs). Bile acids (BAs), whose levels are increased in many CLDs, reciprocally interact with circadian rhythm.

Silica nanoparticles cause ovarian dysfunction and fertility decrease in mice via oxidative stress-activated autophagy and apoptosis.

Silica nanoparticles (SiNPs) are widely used in various commercial applications, which inevitably increase the risk of human exposure. It's reported that SiNPs have toxic effects on fertility, however, the specific mechanism of female reproductive toxicity induced by SiNPs remains confusing. In this study, female C57BL/6 mice at the age of 8 weeks were administrated orally with SiNPs at doses of 0, 3, and 10 mg/kg bw.

SNPscan Combined With CNVplex as a High-Performance Diagnostic Method for Thalassemia.

Objective: Thalassemia is a Mendelian-inherited blood disorder with severe consequences, including disability and mortality, making it a significant public health concern. Therefore, there is an urgent need for precise diagnostic technologies. We introduce two innovative diagnostic techniques for thalassemia, SNPscan and CNVplex, designed to enhance molecular diagnostics of thalassemia.

Photoredox Ring Opening 1,2-Alkylarylation of Alkenes with Sulfonium Salts Toward Thioether-Substituted Oxindoles.

A novel strategy for the difunctionalization of electron-deficient alkenes with aryl sulfonium salts to access remote sulfur-containing oxindole derivatives by using in situ-formed copper(I)-based complexes as a photoredox catalyst is presented. This method enables the generation of the C(sp)-centered radicals through site selective cleavage of the C-S bond of aryl sulfonium salts under mild conditions. Moreover, the oxidation reactions of desired products provide a new strategy for the preparation of sulfoxide or sulfone-containing compounds.

Precise diagnosis of a hereditary spherocytosis patient with complicated hematological phenotype.

Hereditary spherocytosis (HS) is one of the most common causes of hereditary hemolytic anemia. The current diagnostic guidelines for HS are mainly based on a combination of physical examination and laboratory investigation. However, some patients present with complicated clinical manifestations that cannot be explained by routine diagnostic protocols.

Oxidant-Assisted Sulfonylation/Cyclization Cascade Synthesis of Alkylsulfonylated Oxindoles via the Insertion of SO.

An oxidant-assisted tandem sulfonylation/cyclization of electron-deficient alkenes with 4-alkyl-substituted Hantzsch esters and NaSO for the preparation of 3-alkylsulfonylated oxindoles under mild conditions in the absence of a photocatalyst and transition metal catalyst is established. The mechanism studies show that the alkyl radicals, which come from the cleavage of the C-C bond in 4-substituted Hantzsch esters under oxidant conditions, subsequently undergo the insertion of sulfur dioxide to generate the crucial alkylsulfonyl radical intermediates. This three-component reaction provides an efficient and facile route for the construction of alkylsulfonylated oxindoles and avoids the use of highly toxic alkylsulfonyl chlorides or alkylsulfonyl hydrazines as alkylsulfonyl sources.

SUPT5H mutations associated with elevation of Hb A level: Identification of two novel variants and literature review.

β-thalassemia is one of the most common monogenic disorders in areas of the tropics and subtropics, which represents a major familial and social burden to local people. The elevated Hb A level, generally specified as greater than 3.5 %, is commonly used as a high efficiency index for screening of β-thalassemia carriers.

Silica nanoparticles induces sperm granuloma formation and blood-epididymal barrier disruption via the p38 MAPK pathway in mice.

Previous researches have demonstrated that the silica nanoparticles (SiNPs), which are widely used in all aspects of life, are hazardous to the male reproductive system. However, the cellular and molecular mechanism underlying SiNPs toxicity to the epididymis remain unclear. In this present study, a total of 60 male mice were separated into 4 groups and then treated to SiNPs for 7 consecutive days at a dose of 0, 2.

Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis.

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.

A novel gain-of-function PIP4K2A mutation elevates the expression of β-globin and aggravates the severity of α-thalassemia.

Haemoglobin H (Hb H) disease (intermediate status of α-thalassemia) shows marked phenotypic variability from asymptomatic to severe anaemia. Apart from the combined β-thalassemia allele ameliorating clinical severity, reports of genetic modifier genes affecting the phenotype of Hb H disease are scarce which bring inconvenience to precise diagnosis and genetic counselling of the patients. Here, we present a novel mutation (c.

TRIM32 biallelic defects cause limb-girdle muscular dystrophy R8: identification of two novel mutations and investigation of genotype-phenotype correlation.

Background: Limb-girdle muscular dystrophy R8 (LGMD R8) is a rare autosomal recessive muscle disease caused by TRIM32 gene biallelic defects. The genotype-phenotype correlation of this disease has been reported poorly. Here, we report a Chinese family with two female LGMD R8 patients.

The Phosphorylation Status of Hsp82 Regulates Mitochondrial Homeostasis During Glucose Sensing in Saccharomyces cerevisiae.

Sensing extracellular glucose, budding yeast switches from aerobic glycolysis to oxidative phosphorylation to adapt to environmental changes. During the conversion of metabolic mode, mitochondrial function and morphology change significantly. Mitochondria are the main supply factories of energy for various life activities in cells.

Role of OAS gene family in COVID-19 induced heart failure.

Background: COVID-19, the current global pandemic caused by SARS-CoV-2 infection, can damage the heart and lead to heart failure (HF) and even cardiac death. The 2',5'-oligoadenylate synthetase (OAS) gene family encode interferon (IFN)-induced antiviral proteins which is associated with the antiviral immune responses of COVID-19. While the potential association of OAS gene family with cardiac injury and failure in COVID-19 has not been determined.

A novel splicing mutation of ANK1 is associated with phenotypic heterogeneity of hereditary spherocytosis in a Chinese family.

Hereditary spherocytosis (HS) is a common hematological genetic disorder that results in anemia, jaundice and splenomegaly. It is caused by mutations in the ANK1, SPTA, SPTB, SLC4A1 and EPB42 genes, which encode red blood cell membrane and skeletal proteins. Patients show high heterogeneity in phenotype and genotype and the genotype-phenotype correlation still requires clarification.

Investigation of the mechanism of copy number variations involving the α-globin gene cluster on chromosome 16: two case reports and literature review.

Thalassemia is one of the most common single-gene disorder worldwide. An important genetic cause of thalassemia is copy number variations (CNVs) in the α-globin gene cluster. However, there is no unified summary and discussion on the detailed information and mechanisms of these CNVs.

Diamond-Blackfan anaemia caused by a de novo initiation codon mutation resulting in a shorter isoform of GATA1.

Diamond-Blackfan anaemia (DBA) is an inherited marrow failure disorder characterised by selective erythroid aplasia. Herein, we reported a case of DBA caused by a novel GATA1 gene mutation. The proband manifested normocytic normochromic anaemia, while the parents were asymptomatic.

Stemness Analysis Uncovers That The Peroxisome Proliferator-Activated Receptor Signaling Pathway Can Mediate Fatty Acid Homeostasis In Sorafenib-Resistant Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) stem cells are regarded as an important part of individualized HCC treatment and sorafenib resistance. However, there is lacking systematic assessment of stem-like indices and associations with a response of sorafenib in HCC. Our study thus aimed to evaluate the status of tumor dedifferentiation for HCC and further identify the regulatory mechanisms under the condition of resistance to sorafenib.

A Novel Hemoglobin Variant Hb Liaobu [α107(G14)Val→Leu, : c.322G>C] Detected by Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry.

We here describe a novel hemoglobin (Hb) variant, Hb Liaobu [α107(G14)Val→Leu, : c.322G>C], in a Chinese family. The structurally abnormal α chain variant could not be detected using capillary electrophoresis (CE) and was subsequently characterized by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS), and further confirmed by reversed phase high performance liquid chromatography (HPLC).

A study on non-invasive prenatal screening for the detection of aneuploidy.

Objectives: To explore the feasibility of clinical application of non-invasive prenatal screening to detect aneuploidy diseases.

Material And Methods: A total of 14,574 singleton pregnant women who underwent Non-invasive prenatal testing (NIPT) in the Southern Hospital from 2015 to June 2017 were selected, and 6471 pregnant women with twin pregnancy who underwent NIPT in the laboratory of Bei Rui He Kang Southern Hospital from June 2016 to October 2017 were included in this study. We analyzed NIPT screening efficiency (sensitivity, specificity) in twin pregnancies and singleton pregnancies, compared the positive detection rate of NIPT in patients with or without clinical symptoms.

Reproductive toxicity investigation of silica nanoparticles in male pubertal mice.

Silica nanoparticles (SiNPs), one of the most produced nanoparticles (NPs) in the world, are used in all aspects of life. The increased application of SiNPs, especially in medicine, has raised considerable concern regarding their toxicological impact. Previous studies have shown that SiNPs can pass through the reproductive barrier and cause reproductive organ dysfunction by destroying Sertoli cells, Leydig cells, and germ cells.