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Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9. This single-arm, single-centre trial enrolled children (aged 1–18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing. Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1–2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40–57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5–4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery. AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.

Background Osmanthus fragrans is an important economical plant containing multiple secondary metabolites including flavonoids and anthocyanins. During the past years, the roles of miRNAs in regulating the biosynthesis of secondary metabolites in plants have been widely investigated. However, few studies on miRNA expression profiles and the potential roles in regulating flavonoid biosynthesis have been reported in O. fragrans. Results In this study, we used high-throughput sequencing technology to analyze the expression profiles of miRNAs in leaf and flower tissues of O. fragrans . As a result, 106 conserved miRNAs distributed in 47 families and 88 novel miRNAs were identified. Further analysis showed there were 133 miRNAs differentially expressed in leaves and flowers. Additionally, the potential target genes of miRNAs as well as the related metabolic pathways were predicted. In the end, flavonoid content was measured in flower and leaf tissues and potential role of miR858 in regulating flavonoid synthesis was illustrated in O. fragrans . Conclusions This study not only provided the genome-wide miRNA profiles in the flower and leaf tissue of O. fragrans , but also investigated the potential regulatory role of miR858a in flavonoid synthesis in O. fragrans . The results specifically indicated the connection of miRNAs to the regulation of secondary metabolite biosynthesis in non-model economical plant.

This study aims to analyze the demands of older people for care services and to evaluate and position care facilities to accommodate the requirements of healthy aging. Data on the demand for care services in Chengdu were collected. Fuzzy-set qualitative comparison analysis was used for demands analysis. Probabilistic linguistic term sets were used to assess and position facilities. Finally, the recommendations methods were provided by different demands of older people. There were four paths to produce the high demands for care services of older people. Among the six types of services, medical services, psychological counseling, and nursing services had the greatest impact, while diet conditions had the least. The older people with clear demands can select facilities by the first recommendation method, while those with unclear demands can choose from four types of facilities: recommended, non-recommended, suitable for forward-thinking customers, and suitable for concerned customers. This study provides valuable insights into older people, care facilities, and governments. The older people can choose suitable facilities by their demands, while facilities can enhance service quality accordingly. Governments can allocate resources efficiently and promote healthy aging.

Color in urban public spaces is often approached as an aesthetic issue, yet it also governs psychological responses, legibility and safety, place identity, and environmental performance. Despite three decades of research, planners and designers still lack measurable, audit-ready guidance that links color decisions to verifiable outcomes. This paper presents a systematic review that consolidates evidence from environmental psychology, architecture and urban design, cultural studies, and building and urban physics. Studies were screened for outdoor or outward-facing settings and for explicitly reported color variables and performance indicators. The findings are organized into four domains in which color operates as a system variable: psychological and physiological effects; cultural expression and place identity; functional zoning and wayfinding; and sustainability and environmental adaptation. Across these domains, the review identifies robust patterns—such as the central role of luminance and saturation in shaping affect, attention, and visibility—while highlighting where outcomes are strongly conditioned by cultural, climatic, and material context. On this basis, the paper proposes an Objective–Strategy–Metric–Validation (OSMV) framework that connects design objectives to color strategies, quantitative metrics (e.g., color difference, contrast, and reflectance measures), and procedures for simulation or field validation. Framed in this way, color emerges not as a decorative accessory but as a measurable design variable that can be integrated into performance-based planning, regulation, and multi-objective optimization of urban public spaces.

Due to limited spectral resolution, cochlear implants (CIs) do not convey pitch information very well. Pitch cues are important for perception of music and tonal language; it is possible that music training may improve performance in both listening tasks. In this study, we investigated music training outcomes in terms of perception of music, lexical tones, and sentences in 22 young (4.8 to 9.3 years old), prelingually deaf Mandarin-speaking CI users. Music perception was measured using a melodic contour identification (MCI) task. Speech perception was measured for lexical tones and sentences presented in quiet. Subjects received 8 weeks of MCI training using pitch ranges not used for testing. Music and speech perception were measured at 2, 4, and 8 weeks after training was begun; follow-up measures were made 4 weeks after training was stopped. Mean baseline performance was 33.2%, 76.9%, and 45.8% correct for MCI, lexical tone recognition, and sentence recognition, respectively. After 8 weeks of MCI training, mean performance significantly improved by 22.9, 14.4, and 14.5 percentage points for MCI, lexical tone recognition, and sentence recognition, respectively (p < .05 in all cases). Four weeks after training was stopped, there was no significant change in posttraining music and speech performance. The results suggest that music training can significantly improve pediatric Mandarin-speaking CI users’ music and speech perception.

Objective. The aim of this study was to investigate the benefits of residual hair cell function for speech and music perception in bimodal pediatric Mandarin-speaking cochlear implant (CI) listeners. Design. Speech and music performance was measured in 35 Mandarin-speaking pediatric CI users for unilateral (CI-only) and bimodal listening. Mandarin speech perception was measured for vowels, consonants, lexical tones, and sentences in quiet. Music perception was measured for melodic contour identification (MCI). Results. Combined electric and acoustic hearing significantly improved MCI and Mandarin tone recognition performance, relative to CI-only performance. For MCI, performance was significantly better with bimodal listening for all semitone spacing conditions (p<0.05 in all cases). For tone recognition, bimodal performance was significantly better only for tone 2 (rising; p<0.05). There were no significant differences between CI-only and CI + HA for vowel, consonant, or sentence recognition. Conclusions. The results suggest that combined electric and acoustic hearing can significantly improve perception of music and Mandarin tones in pediatric Mandarin-speaking CI patients. Music and lexical tone perception depends strongly on pitch perception, and the contralateral acoustic hearing coming from residual hair cell function provided pitch cues that are generally not well preserved in electric hearing.

Patients with single-sided deafness (SSD) often experience poor sound localization, reduced speech understanding in noise, reduced quality of life, and tinnitus. The present study aims to evaluate effects of tinnitus and duration of deafness on sound localization and speech recognition in noise by SSD subjects. Sound localization and speech recognition in noise were measured in 26 SSD and 10 normal-hearing (NH) subjects. Speech was always presented directly in front of the listener. Noise was presented to the deaf ear, in front of the listener, or to the better hearing ear. Tinnitus severity was measured using visual analog scale and Tinnitus Handicap Inventory. Relative to NH subjects, SSD subjects had significant deficits in sound localization and speech recognition in all listening conditions (p < .001). For SSD subjects, speech recognition in noise was correlated with mean hearing thresholds in the better hearing ear (p < .001) but not in the deaf ear. SSD subjects with tinnitus performed poorer in sound localization and speech recognition in noise than those without tinnitus. Shorter duration of deafness was associated with greater tinnitus and sound localization difficulty. Tinnitus visual analog scale and Tinnitus Handicap Inventory were highly correlated; the degree of tinnitus was negatively correlated with sound localization and speech recognition in noise. Those experiencing noticeable tinnitus may benefit more from cochlear implantation than those without; subjective tinnitus reduction may be correlated with improved sound localization and speech recognition in noise. Subjects with longer duration of deafness demonstrated better sound localization, suggesting long-term compensation for loss of binaural cues.

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181 . An interim analysis of a single-arm trial in 5 children with hereditary deafness shows that binaural AAV gene therapy is safe and leads to hearing improvement up to 13–26 weeks of follow-up.

As people spend more time indoors, the impact of the built environment on psychological health has attracted growing attention. Yet existing studies often have difficulty capturing decision-makers’ reference dependence and loss aversion under uncertainty. To bridge this gap, we propose an evaluation framework comprising three first-level criteria—Outdoor Environment, Physical Comfort (including thermal, lighting, and color environments), and Acoustic Comfort—and determine combined weights by integrating subjective analytic hierarchy process (AHP) judgments with objective entropy weighting based on triangular fuzzy numbers (TFNs). We further incorporate prospect–regret theory to represent loss aversion, expectation-based reference points, and counterfactual regret/rejoicing, and couple it with the VIKOR compromise ranking method, forming an integrated “TFN + Prospect–Regret + VIKOR” approach. The proposed method is applied to four retrofit alternatives for an open-plan office floor (approximately 1200 m2), each emphasizing outdoor environment, physical comfort, acoustic comfort, or no single priority. Experts assessed the schemes using fuzzy linguistic variables. The results show that lighting conditions, thermal comfort, color scheme, and internal noise control receive the highest comprehensive weights. Extensive sensitivity analyses across value/weighting functions and regret-aversion parameters indicate that the ranking of alternatives remains stable while exhibiting clearer separation. Comparative analyses further suggest that, although the overall ordering is consistent with baseline methods, the proposed model increases score dispersion and improves discriminative power. Overall, by explicitly accounting for decision-makers’ psychological behavior and information uncertainty, the framework enables robust and interpretable selection of retrofit schemes for existing office spaces.