SCN5A-L256del and L1621F exhibit loss-of-function properties related to autosomal recessive congenital cardiac disorders presenting as sick sinus syndrome, dilated cardiomyopathy, and sudden cardiac death.

Pathogenic mutations in SCN5A could result in dysfunctions of Nav1.5 and consequently lead to a wide range of inherited cardiac diseases. However, the presence of numerous SCN5A-related variants with unknown significance (VUS) and the comprehensive genotype-phenotype relationship pose challenges to precise diagnosis and genetic counseling for affected families. Here, we functionally identified two novel compound heterozygous variants (L256del and L1621F) in SCN5A in a Chinese family exhibiting complex congenital cardiac phenotypes from sudden cardiac death to overlapping syndromes including sick sinus syndrome and dilated cardiomyopathy in an autosomal recessive pattern. In silico tools predicted decreased stability and hydrophobicity of the two mutated proteins due to conformational changes. Patch-clamp electrophysiology revealed slightly decreased sodium currents, accelerated inactivation, and reduced sodium window current in the Nav1.5-L1621F channels as well as no sodium currents in the Nav1.5-L256del channels. Western blotting analysis demonstrated decreased expression levels of mutated Nav1.5 on the plasma membrane, despite enhanced compensatory expression of the total Nav1.5 expression levels. Immunofluorescence imaging showed abnormal condensed spots of the mutated channels within the cytoplasm instead of normal membrane distribution, indicating impaired trafficking. Overall, we identified the loss-of-function characteristics exhibited by the two variants, thereby providing further evidence for their pathogenic nature. Our findings not only extended the variation and phenotype spectrums of SCN5A, but also shed light on the crucial role of patch-clamp electrophysiology in the functional analysis of VUS in SCN5A, which have significant implications for the clinical diagnosis, management, and genetic counseling in affected individuals with complex cardiac phenotypes.

The benefits of propofol on cancer treatment: Decipher its modulation code to immunocytes.

Anesthetics are essential for cancer surgery, but accumulated research have proven that some anesthetics promote the occurrence of certain cancers, leading to adverse effects in the lives of patients. Although anesthetic technology is mature, there is no golden drug selection standard for surgical cancer treatment. To afford the responsibility of human health, a more specific regimen for cancer resection is indeed necessary. Immunosuppression in oncologic surgery has an adverse influence on the outcomes of patients. The choice of anesthetic strategies influences perioperative immunity. Among anesthetics, propofol has shown positive effects on immunity. Apart from that, propofol's anticancer effect has been generally reported, which makes it more significant in oncologic surgery. However, the immunoregulative function of propofol is not reorganized well. Herein, we have summarized the impact of propofol on different immunocytes, proposed its potential mechanism for the positive effect on cancer immunity, and offered a conceivable hypothesis on its regulation to postoperative inflammation. We conclude that the priority of propofol is high in oncologic surgery and propofol may be a promising immunomodulatory drug for tumor therapy.

Late-onset multiple acyl-CoA dehydrogenase deficiency with cardiac syncope: A case report.

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an uncommon autosomal recessive disorder of mitochondrial fatty acid beta-oxidation. Syncope is a transient loss of consciousness due to acute global cerebral hypoperfusion. Late-onset MADD with syncope has not been reported previously. CASE SUMMARY: We report a 17-year-old girl with exercise intolerance and muscle weakness. She felt palpitation and shortness of breath after short bouts of exercise. She also suffered from a transient loss of consciousness many times. Muscle biopsy showed lipid storage. Genetic mutation analysis indicated a compound heterozygous mutation c.250G > A (p.A84T) and c.872T > G (p.V291G) in the ETFDH gene. The results of Holter electrocardiogram monitoring showed supraventricular tachycardia when the patient experienced a loss of consciousness. After treatment with riboflavin and carnitine, muscle weakness and palpitation symptoms improved rapidly. No loss of consciousness occurred, and the Holter electrocardiogram monitoring was normal. CONCLUSION: Late-onset MADD with supraventricular tachycardia can cause cardiac syncope. Carnitine and riboflavin supplement were beneficial for treating the late-onset MADD with cardiac syncope. Attention should be paid to the prevention of cardiac syncope when diagnosing late-onset MADD.

[Cloning of flocculent gene and expression in industrial yeast strain].

The partial genomic library of Saccharomyce cerevisiae FL189 possessing strong flocculation ability was constructed using Yeast-E. coli shuttle plasmid YCp50 as vector. Recombinant plasmid containing flocculation gene was obtained by screening the growth of transformants on the selective medium and measurement flocculation, designated as pCF1.pCF1 was introduced into industrial yeast strain PJ208-5-15. Six transformants PJ208-5-15-1(pCF1)-PJ208-5-15-6(pCF1) possessing strong flocculation ability were obtained. The results of Southern blot and restriction endonuclease analysis showed that the insert is about 4.3 kb and could hybridize with the probe (2.6 kb Eco RV fragment of FLO1). Flocculation ability assay indicated that the transformants possess strong flocculation ability. Hence, the gene controlling flocculation phenotype exists in the cloned DNA fragment. The restriction endonuclease analysis and the sequence analysis of the insert DNA fragment are in progress.

[Sequencing and analysis of flocculation gene(FLO1G)].

The sequence of the flocculation gene (FLO1G) was determined. The result of sequcencing showed that: the cloned gene contains a large open reading frame (ORF) of 3936 bp and encodes for a protein of 1312 amino acid. According to the result of homologous analysis, the cloned gene is homologous to FLO1 but with 675 bp deletion in the ORF region. The missing part belongs to one of the four repeated sequence family of FLO1. Since the cloned DNA fragment can trigger strong flocculence to non-flocculent strain S. cerevisiae YS58, we concluded that the missing part is not the crutical part for the flocculent ability of the gene.