Discovery of A G-Quadruplex Unwinder That Unleashes the Translation of G-Quadruplex-Containing mRNA without Inducing DNA Damage.

To explore the mechanisms and therapeutic strategies for G-quadruplex (G4) mediated diseases, it is crucial to manipulate and intervene in intracellular G4 structures using small molecular tools. While hundreds of G4 stabilizers have been developed, there is a significant gap in the availability of G4 unwinding agents. Here, we propose a strategy to disrupt G-quadruplexes by forming G-C hydrogen bonds with chemically modified cytidine trimers. We validated a good G4 unwinder, the 2'-F cytidine trimer (2'-F C3). 2'-F C3 does not inhibit cell growth nor cause severe DNA damage at a concentration below 10 µM. Moreover, 2'-F C3 does not affect gene transcription nor RNA splicing, while it significantly enhances the translation of G4-containing mRNA and upregulates RNA splicing, RNA processing and cell cycle pathways. The discovery of this G4 unwinder provides a functional tool for the chemical modulation of G4s in living cells.

The effects of aging on peripheral and central auditory function in adults with normal hearing.

This study was designed to investigate the effects of the aging process on peripheral and central auditory functions in adults with normal hearing. In this study, 149 participants with normal hearing were divided into four groups: aged 20-29, 30-39, 40-49 and 50-59 years for statistical purposes. Electrocochleography (EcochG), transient evoked otoacoustic emissions (TEOAE), Mandarin Hearing in Noise Test (MHINT) and the Gap Detection Test (GDT) were used. Our study found: (1) MHINT is significantly associated with aging (left ear R2=0.29, right ear R2=0.35). (2) TEOAE amplitude, TEOAE contralateral acoustic stimulation (CS) amplitude, EcochG action potential (AP), EcochG AP latency, EcochG summating potential (SP) and GDT progressively declined with age. (3) The EcochG SP/AP has no statistically significant difference among different age groups. (4) The peripheral auditory function of the right ear declines more slowly than that of the left ear. (5) Hypofunction of the central auditory system accelerates after age 40. The results demonstrate: (1) The age-related decline in the ability of speech recognition in a noisy environment may be the most sensitive indicator that reflects auditory function. (2) The decline of central auditory function is independent of peripheral auditory function, according to the auditory characteristics of the right ear. (3) Auditory function needs to be assessed individually to allow early prevention before age 40.