IFE based nanosensor composed of UCNPs and Fe(Ⅱ)-phenanthroline for detection of hypochlorous acid and periodic acid

Oxidizing CIO^(-)and IO_(4)^(-)exist widely in environment and are closely related to the health of organisms.Accordingly,fast,sensitive,and direct detection of the two species is significant.Using IFE in UCNPs@PAA and Fe(Ⅱ)-phenanthroline system,an elegant ratiometric fluorescent nanosensor,without noble metal nanoparticle,was designed for the detection of CIO-and IO4-.Fe(Ⅱ)-phenanthroline complex is used as fluorescent absorber,which can quench green light of UCNPs with gradually varied extent depending on the concentration of Fe(Ⅱ).The linear zone extends to 800 and 120μmol/L while the detection limit is 1.30 and 0.58μmol/L for NaCIO and NaIO_(4),respectively.Finally,the nanosensor was successfully applied to detect NaCIO and NaIO4spiked in milk,spring water,and tap water with good recoveries.

AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization

Auditory neuropathy spectrum disorder(ANSD)represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function,but with the preservation of outer hair cell function.ANSD represents up to 15%of individuals with hearing impairments.Through mutation screening,bioinformatic analysis and expression studies,we have previously identified several apoptosis-inducing factor(AIF)mitochondria-associated 1(AIFM1)variants in ANSD families and in some other sporadic cases.Here,to elucidate the pathogenic mechanisms underlying each AIFM1 variant,we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system and constructed AIF-wild type(WT)and AIF-mutant(mut)(p.T260A,p.R422W,and p.R451Q)stable transfection cell lines.We then analyzed AIF structure,coenzyme-binding affinity,apoptosis,and other aspects.Results revealed that these variants resulted in impaired dimerization,compromising AIF function.The reduction reaction of AIF variants had proceeded slower than that of AIF-WT.The average levels of AIF dimerization in AIF variant cells were only 34.5%-49.7%of that of AIF-WT cells,resulting in caspase-independent apoptosis.The average percentage of apoptotic cells in the variants was 12.3%-17.9%,which was significantly higher than that(6.9%-7.4%)in controls.However,nicotinamide adenine dinucleotide(NADH)treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells.Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD,and introduce NADH as a potential drug for ANSD treatment.Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.