Identification of Eukaryotic Translation Initiation Factor 4B as a Novel Candidate Gene for Congenital Hypothyroidism.

CONTEXT: Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates, but its etiology is still poorly understood. OBJECTIVE: We performed whole exome sequencing to identify novel causative gene for CH and functional studies to validate its role in the occurrence of CH. METHODS: Whole exome sequencing in 98 CH patients not harboring known CH candidate genes and bioinformatic analysis were performed. Functional analysis was performed using morpholino, a synthetic short antisense oligonucleotide that contains 25 DNA bases on a methylene morpholine backbone, in zebrafish and CRISPR‒Cas9-mediated gene knockout in mice. RESULTS: Eukaryotic translation initiation factor 4B (EIF4B) was identified as the most promising candidate gene. The EIF4B gene was inherited in an autosomal recessive model, and one patient with thyroid dysgenesis carried EIF4B biallelic variants (p.S430F/p.P328L). In zebrafish, the knockdown of eif4ba/b expression caused thyroid dysgenesis and growth retardation. Thyroid hormone levels were significantly decreased in morphants compared with controls. Thyroxine treatment in morphants partially rescued growth retardation. In mice, the homozygous conceptuses of Eif4b+/- parents did not survive. Eif4b knockout embryos showed severe growth retardation, including thyroid dysgenesis and embryonic lethality before E18.5. CONCLUSION: These experimental data supported a role for EIF4B function in the pathogenesis of the hypothyroid phenotype seen in CH patients. Our work indicated that EIF4B was identified as a novel candidate gene in CH. EIF4B is essential for animal survival, but further studies are needed to validate its role in the pathogenesis of CH.

Influence of earthquake on radon exhalation law at the beach of the uranium tailing reservoir under high temperature environment.

In this paper, the influence of an earthquake on radon exhalation rate of uranium tailings reservoir beach under high temperature environment is studied by using a self-made integrated simulation test device for natural disasters, and a scale model test based on similarity and dimensional laws. The results show that, (1)When the peak acceleration reaches 0.6g, the radon exhalation rate increases sharply with the increase of peak acceleration, and tends to be gentle after 1.0g. (2)Under the action of high temperature, the radon exhalation rate increases rapidly with the increase of high temperature time, and gradually becomes flat after the 4th hour. (3)Compared with loading the earthquake condition only, the coupling effect of high temperatures and earthquakes causes a greater degree of damage to the beach surface of a uranium tailings reservoir under the same acceleration conditions, and the fissure rate and radon exhalation rate of the beach surface are substantially increased.