Case report: A novel mutation in the EYA1 gene in a child with branchiootic syndrome with secretory otitis media and bilateral vestibular hypofunction.

Branchiootic syndrome (BOS) is a rare, autosomal dominant syndrome characterized by malformations of the ear associated with hearing loss, second branchial arch anomalies, and the absence of renal anomalies. Herein, we report the case of an 8-year-old male patient with BOS. The proband also experiences mixed conductive and sensorineural hearing loss in the right ear, and severe-to-profound sensorineural hearing loss in the left ear. Preauricular pits, branchial fistulae, and cochlear hypoplasia were present bilaterally. Type III cup-shaped ear, and external auditory canal stenosis were detected in the right ear. Lateral semicircular canal-vestibule dysplasia was detected in the left ear. Moreover, the patient had unilateral secretory otitis media (SOM) in the right ear and bilateral vestibular hypofunction (VH), which has not been reported in previous studies. The patient's hearing on the right side was restored to nearly normal after myringotomy. Whole exome sequencing identified a novel frameshift mutation in EYA1 (NM_000503.6): c.1697_1698delinT [p.(Lys566IlefsTer73)] in the proband, which was defined a "pathogenic" mutation according to American College of Medical Genetics and Genomics guidelines. This is the first report of a child presenting with BOS, SOM and VH, which expands the known clinical manifestations of this syndrome. We also observed a novel EYA1 gene mutation in this patient with BOS, which enriches the mutation map and provides a reference for genetic diagnosis of this syndrome.

Mitochondrial stress response in drug-induced liver injury.

Drug-induced liver injury (DILI) caused by the ingestion of medications, herbs, chemicals or dietary supplements, is a clinically widespread health problem. The underlying mechanism of DILI is the formation of reactive metabolites, which trigger mitochondrial oxidative stress and the opening of mitochondrial permeability transition (MPT) pores through direct toxicity or immune response, leading to cell inflammation, apoptosis, and necrosis. Traditionally, mitochondria play an indispensable role in maintaining the physiological and biochemical functions of cells by producing ATP and mediating intracellular signal transduction; drugs can typically stimulate the mitochondria and, in the case of sustained stress, can eventually cause impairment of mitochondrial function and metabolic activity. Meanwhile, the mitochondrial stress response, as an adaptive protective mechanism, occurs when mitochondrial homeostasis is threatened. In this review, we summarize the relevant frontier researches of the protective effects of mitochondrial stress response in DILI as well as the potential related mechanisms, thus providing some thoughts for the clinical treatment of DILI.

Involvement of SIRT1 in amelioration of schistosomiasis-induced hepatic fibrosis by genistein.

Previous study revealed that genistein alleviate the extent of hepatic fibrosis in schistosomiasis-infected mice, however, the potential mechanism is still incomplete. Present study was, therefore, carried out to investigate the underlying mechanism of ameliorating schistosomiasis-induced hepatic fibrosis by genistein. α-smooth muscle actin (α-SMA) expression, as a critical fibrotic marker, was markedly upregulated in Schistosoma japonicum (S. japonicum) egg-induced liver fibrosis, and gradually inhibited by genistein administration in infected mice. Contrary to the changes of α-SMA expression, hepatic SIRT1 expression and activity was greatly inhibited in mice upon S. japonicum infection, and the repression was reversed in liver tissues after receiving 25 mg/kg genistein. 50 mg/kg genistein treatment gave rise to the higher SIRT1 expression and activity than that of the control group. In hepatic stellate cells (HSCs), genistein (5, 10, 20 µM) treatment resulted in the increases of SIRT1 expression and activity in concentration-dependent manner. Moreover, to mimic the fibrogenesis in vivo, macrophage was treated with soluble egg antigen (SEA) to obtain macrophage-conditioned medium (MφCM), which was used to stimulate HSCs. Intriguingly, SIRT1 overexpression decreased fibrosis associated gene expression in HSCs exposed to MφCM or not. Additionally, MφCM gave rise to high levels of α-SMA and p-Smad3 and the increments were reversed upon genistein treatment in HSCs. Furthermore, EX527, SIRT1 specific inhibitor, abrogated the inhibitory effects of genistein on HSCs activation. Together, the results support the notion that the strong elevation of SIRT1 expression and activity may represent a potential mechanism of protection against schistosomiasis-induced hepatic fibrosis by genistein.

Water-soluble thermoresponsive α-helical polypeptide with an upper critical solution temperature: synthesis, characterization, and thermoresponsive phase transition behaviors.

Water-soluble polypeptides bearing 1-alkylimidazolium (methyl or n-butyl) and various counter-anions (i.e., Cl(-), I(-) or BF4 (-)) are prepared by ring-opening polymerization of γ-4-chloromethylbenzyl-l-glutamate-based N-carboxyanhydride (3), post-polymerization of poly(γ-4-chloromethylbenzyl-l-glutamate) (4), and ion-exchange reaction. Circular dichroism (CD) analysis reveals that the resulting polypeptides adopt an α-helical conformation in water with a fractional helicity in the range of 30%-56% at 20 °C and exhibit good conformational stability against temperature variations. The polypeptides exhibit lower critical solution temperature (LCST)-type or upper critical solution temperature (UCST)-type transitions in organic solvents or in water. The UCST-type transition temperature (Tpt ) in water is independent on the molecular weight, yet it decreases upon addition of NaCl and increases upon addition of NaI or NaBF4, suggesting a mainly electrostatic interaction mechanism.

One-pot synthesis of molecular bottle-brush functionalized single-walled carbon nanotubes with superior dispersibility in water.

Molecular bottle-brush functionalized single-walled carbon nanotubes (SWCNTs) with superior dispersibility in water are prepared by a one-pot synthetic methodology. Elongating the main-chain and side-chain length of molecular bottle-brushes can further increase SWCNT dispersibility. They show significant enhancement of SWCNT dispersibility up to four times higher than those of linear molecular functionalized SWCNTs.