BackgroundAuditory neuropathy spectrum disorder (ANSD) is a form of hearing loss in which auditory signal transmission from the inner ear to the auditory nerve and brain stem is distorted, giving rise to speech perception difficulties beyond that expected for the observed degree of hearing loss. For many cases of ANSD, the underlying molecular pathology and the site of lesion remain unclear. The X-linked form of the condition, AUNX1, has been mapped to Xq23-q27.3, although the causative gene has yet to be identified.MethodsWe performed whole-exome sequencing on DNA samples from the AUNX1 family and another small phenotypically similar but unrelated ANSD family.ResultsWe identified two missense mutations in AIFM1 in these families: c.1352G>A (p.R451Q) in the AUNX1 family and c.1030C>T (p.L344F) in the second ANSD family. Mutation screening in a large cohort of 3 additional unrelated families and 93 sporadic cases with ANSD identified 9 more missense mutations in AIFM1. Bioinformatics analysis and expression studies support this gene as being causative of ANSD.ConclusionsVariants in AIFM1 gene are a common cause of familial and sporadic ANSD and provide insight into the expanded spectrum of AIFM1-associated diseases. The finding of cochlear nerve hypoplasia in some patients was AIFM1-related ANSD implies that MRI may be of value in localising the site of lesion and suggests that cochlea implantation in these patients may have limited success.

Development of nanocarriers, which can selectively accumulate and remain within the tumor tissue matrix, is beneficial for non-invasive cancer diagnosis and therapy. In this study, a well-defined pH-sensitive block copolymer, i.e., succinic anhydride (SA)-modified poly(2-diisopropylaminoethyl methacrylate)-block-poly(2aminoethyl methacrylate hydrochloride) (PDPA-b-PAMA/SA), was prepared by a two-step atom transfer radical polymerization (ATRP) and subsequent amidation. The low critical micelle concentration (CMC, 40.7 Â 10 À4 mg mL À1 ) of PDPA-b-PAMA/SA investigated in pH 7.4 aqueous solution confirmed the adequate thermodynamic stability of its self-assembly. In addition, the pH-sensitive aggregation behaviors of blank and drug-loaded PDPA-b-PAMA/SA were systematically studied at typical pH conditions (7.4 and 6.5) using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Compared with the control sample, i.e., poly(D,L-lactide)-block-poly(2-aminoethyl methacrylate hydrochloride (PLA-b-PAMA/ SA), both blank and drug-loaded PDPA-b-PAMA/SA (PDPA-b-PAMA/SA@DOX$HCl) exhibited obvious aggregation through electric interaction between the positive charge of the protonated PDPA block and the negative charge of the PAMA/SA block at tumor sites under slightly acidic condition. Moreover, the drug-loaded nanocarriers exhibited accelerated drug release profiles in response to the acidic condition due to the electric repulsion between the protonated PDPA block and positive DOX$HCl. Cytotoxicity assay results demonstrated that the pH-sensitive block copolymer did not demonstrate obvious cytotoxicity, even at a concentration up to 100 mg mL À1 . The enhanced intracellular DOX$HCl distribution in nuclei was also confirmed by confocal laser scanning microscopy (CLSM). Thus, these results suggest that PDPA-b-PAMA/SA provides a feasible platform for efficient tumor-targeted therapy.

Block polymers are synthesized to prepare nanocarriers with dual pHsensitivity, which are expected to prolong blood circulation time, reduce systemic toxicity, enhance tumor cell uptake and accelerate intracellular drug release for efficient anti-cancer therapy.

Rational design and preparation of bioinspired polydopamine (PDA)-based synthetic melanin hybrid materials with well-controlled morphologies and improved properties face a grand challenge at the current situation. Herein, we report the facile fabrication of photocatalytic CdS@PDA patchy nanoparticles with tunable inorganic patchy densities via different Cd2+-loaded PDA precursors. Both of “postdoping” and “predoping” strategies can be used to fabricate CdS@PDA hybrid NPs with distinct CdS patchy densities, which could further induce distinct physical properties and catalytic behaviors. Those resulting functional nanocomposites exhibited significantly enhanced photoactivity and photostability toward the catalytic degradation of methylene blue under visible light irradiation. We believe that the excellent adsorption, redox potential, and free-radical scavenging properties of PDA substrates could provide the outstanding photoactivity and photostability for CdS photocatalytic reaction. This work could inspire more kinds of synthetic melanin-based functional hybrids for stable, efficient, and sustainable photocatalysis.

in the CMP networks could adsorb and confine the guest molecules, which makes CMPs perfect candidates for chemical sensing. To further improve sensing performances, rationally designed CMPs with high fluorescence and large surface areas should be used.Fluorene-based conjugated polymers have been widely used as active materials in organic optoelectronic devices [16,17] and chemical sensing agents [18,19] because of their easy synthesis, good processability, and high fluorescence quantum yield. In recent years, different types of microporous organic polymers containing fluorene units have been prepared and used as gas adsorbents [20,21] and thermoelectric materials. [22] More specifically, Huang and coworkers reported a series of fluorene-based metal-organic frameworks (MOFs) for the detection of nitro explosives and metal ions with high efficiency. [23][24][25] Since long-term stability of MOFs under various conditions remains a big problem, incorporating fluorene units into more robust CMPs would be a good method to enhance stability while retaining their outstanding fluorescent properties.In this context, three novel fluorene-based conjugated microporous polymers (FCMP1-FCMP3) with different electronic structures were prepared using rational-designed monomers. The FCMPs show high degree of microporosity, decent specific surface areas, and variable fluorescence. Chemical sensing performance of FCMPs toward a range of nitroaromatic compounds was studied and it was found that FCMP3, which possesses the largest specific surface area and the highest solid-state photoluminescence (PL) quantum yield, exhibits the highest sensitivity for the detection of nitroaromatic compounds. Experimental Section Synthesis of the MonomersThe synthetic routes and physical characterizations of monomers M1-M3 were described in the Supporting Information. Synthesis of the Polymer Networks by Yamamoto Coupling ReactionThe CMPs (FCMP1-FCMP3) were synthesized by Yamamoto coupling reactions with similar experimental conditions. A