Contrasting water use strategies to climate warming in white birch and larch in a boreal permafrost region.

The effects of rising atmospheric CO2 concentrations (Ca) with climate warming on intrinsic water-use efficiency (iWUE) and radial growth in boreal forests are still poorly understood. We measured tree-ring cellulose δ13C, δ18O, and tree-ring width in Larix dahurica (larch) and Betula platyphylla (white birch), and analyzed their relationships with climate variables in a boreal permafrost region of northeast China over past 68 years covering a pre-warming period (1951-1984; base period) and a warm period (1985-2018; warm period). We found that white birch but not larch significantly increased their radial growth over the warm period. The increased iWUE in both species was mainly driven by elevated Ca but not climate warming. White birch but not larch showed significantly positive correlations between tree-ring δ13C, δ18O and summer maximum temperature as well as vapor pressure deficit in the warm period, suggesting a strong stomatal response in the broad-leaved birch to temperature changes. The climate warming-induced radial growth enhancement in white birch is primarily associated with a conservative water use strategy. In contrast, larch exhibits a profligate water use strategy. It implies an advantage for white birch over larch in the warming permafrost regions.

Disruption of Cdh23 exon 68 splicing leads to progressive hearing loss in mice by affecting tip-link stability.

Inner ear hair cells are characterized by the F-actin-based stereocilia that are arranged into a staircase-like pattern on the apical surface of each hair cell. The tips of shorter-row stereocilia are connected with the shafts of their neighboring taller-row stereocilia through extracellular links named tip links, which gate mechano-electrical transduction (MET) channels in hair cells. Cadherin 23 (CDH23) forms the upper part of tip links, and its cytoplasmic tail is inserted into the so-called upper tip-link density (UTLD) that contains other proteins such as harmonin. The Cdh23 gene is composed of 69 exons, and we show here that exon 68 is subjected to hair cell-specific alternative splicing. Tip-link formation is not affected in genetically modified mutant mice lacking Cdh23 exon 68. Instead, the stability of tip links is compromised in the mutants, which also suffer from progressive and noise-induced hearing loss. Moreover, we show that the cytoplasmic tail of CDH23(+68) but not CDH23(-68) cooperates with harmonin in phase separation-mediated condensate formation. In conclusion, our work provides evidence that inclusion of Cdh23 exon 68 is critical for the stability of tip links through regulating condensate formation of UTLD components.

A Semantic Segmentation Method Based on AS-Unet++ for Power Remote Sensing of Images.

In order to achieve the automatic planning of power transmission lines, a key step is to precisely recognize the feature information of remote sensing images. Considering that the feature information has different depths and the feature distribution is not uniform, a semantic segmentation method based on a new AS-Unet++ is proposed in this paper. First, the atrous spatial pyramid pooling (ASPP) and the squeeze-and-excitation (SE) module are added to traditional Unet, such that the sensing field can be expanded and the important features can be enhanced, which is called AS-Unet. Second, an AS-Unet++ structure is built by using different layers of AS-Unet, such that the feature extraction parts of each layer of AS-Unet are stacked together. Compared with Unet, the proposed AS-Unet++ automatically learns features at different depths and determines a depth with optimal performance. Once the optimal number of network layers is determined, the excess layers can be pruned, which will greatly reduce the number of trained parameters. The experimental results show that the overall recognition accuracy of AS-Unet++ is significantly improved compared to Unet.

Fine mapping and candidate gene analysis of qSB12YSB, a gene conferring major quantitative resistance to rice sheath blight.

KEY MESSAGE: qSB12YSB, a major quantitative sheath blight resistance gene originated from rice variety YSBR1 with good breeding potential, was mapped to a 289-Kb region on chromosome 12. Sheath blight (ShB), caused by Rhizoctonia solani kühn, is one of the most serious global rice diseases. Rice resistance to ShB is a typical of quantitative trait controlled by multiple quantitative trait loci (QTLs). Many QTLs for ShB resistance have been reported while only few of them were fine-mapped. In this study, we identified a QTL on chromosome 12, in which the qSB12YSB resistant allele shows significant ShB resistance, by using 150 BC4 backcross inbred lines employing the resistant rice variety YSBR1 as the donor and the susceptible variety Lemont (LE) as the recurrent parent. We further fine-mapped qSB12YSB to a 289-kb region by generating 34 chromosomal segment substitution lines and identified a total of 18 annotated genes as the most likely candidates for qSB12YSB after analyzing resequencing and transcriptomic data. KEGG analysis suggested that qSB12YSB might activate secondary metabolites biosynthesis and ROS scavenging system to improve ShB resistance. qSB12YSB conferred significantly stable resistance in three commercial rice cultivars (NJ9108, NJ5055 and NJ44) in field trials when introduced through marker assisted selection. Under severe ShB disease conditions, qSB12YSB significantly reduced yield losses by up to 13.5% in the LE background, indicating its great breeding potential. Our results will accelerate the isolation of qSB12YSB and its utilization in rice breeding programs against ShB.

Transmission Line-Planning Method Based on Adaptive Resolution Grid and Improved Dijkstra Algorithm.

An improved Dijkstra algorithm based on adaptive resolution grid (ARG) is proposed to assist manual transmission line planning, shorten the construction period and achieve lower cost and higher efficiency of line selection. Firstly, the semantic segmentation network is used to change the remote sensing image into a ground object-identification image and the grayscale image of the ground object-identification image is rasterized. The ARG map model is introduced to greatly reduce the number of redundant grids, which can effectively reduce the time required to traverse the grids. Then, the Dijkstra algorithm is combined with the ARG and the neighborhood structure of the grid is a multi-center neighborhood. An improved method of bidirectional search mechanism based on ARG and inflection point-correction is adopted to greatly increase the running speed. The inflection point-correction reduces the number of inflection points and reduces the cost. Finally, according to the results of the search, the lowest-cost transmission line is determined. The experimental results show that this method aids manual planning by providing a route for reference, improving planning efficiency while shortening the duration, and reducing the time spent on algorithm debugging. Compared with the comparison algorithm, this method is faster in running speed and better in cost saving and has a broader application prospect.

Bifunctional Hydrogel-Integrated 3D Printed Scaffold for Repairing Infected Bone Defects.

The clinical treatment of infectious bone defects is difficult and time-consuming due to the coexistence of infection and bone defects, and the simultaneous control of infection and repair of bone defects is considered a promising therapy. In this study, a dual-drug delivery scaffold system was fabricated by the combination of a three-dimensional (3D) printed scaffold with hydrogel for infected bone defects repair. The 3D printed polycaprolactone scaffold was incorporated with biodegradable mesoporous silica nanoparticles containing the small molecular drug fingolimod (FTY720) to provide structural support and promote angiogenesis and osteogenesis. The vancomycin (Van)-loaded hydrogel was prepared from aldehyde hyaluronic acid (AHA) and carboxymethyl chitosan (NOCC) by the Schiff base reaction, which can fill the pores of the 3D-printed scaffold to produce a bifunctional composite scaffold. The in vitro results demonstrated that the composite scaffold had Van concentration-dependent antimicrobial properties. Furthermore, the FTY720-loaded composite scaffold demonstrated excellent biocompatibility, vascularization, and osteogenic ability in vitro. In the rat femoral defect model with bacterial infection, the dual-drug composite scaffold showed a better outcome in both infection control and bone regeneration compared to other groups. Therefore, the prepared bifunctional composite scaffold has potential application in the treatment of infected bone defects.

Primary Synovial Sarcoma of the Nasopharynx in a Case-Case Report.

Synovial sarcoma (SS) is a rare malignant tumor with bidirectional differentiation potential in epithelial and mesenchymal tissues and is a more chemosensitive subtype of soft tissue sarcoma. It occurs around the synovial soft tissues of large joints of the extremities and rarely in the nasopharynx. We present a young man with recurrent left-sided nasal congestion with nosebleeds, confirmed by immunohistochemistry and cytogenetic examination as SS. SS is easily misdiagnosed, and the tumor should be considered in the differential diagnosis, with surgery combined with radiotherapy as the primary treatment option.

Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.

The ankle-link complex (ALC) consists of USH2A, WHRN, PDZD7, and ADGRV1 and plays an important role in hair cell development. At present, its architectural organization and signaling role remain unclear. By establishing Adgrv1 Y6236fsX1 mutant mice as a model of the deafness-associated human Y6244fsX1 mutation, the authors show here that the Y6236fsX1 mutation disrupts the interaction between adhesion G protein-coupled receptor V subfamily member 1 (ADGRV1) and other ALC components, resulting in stereocilia disorganization and mechanoelectrical transduction (MET) deficits. Importantly, ADGRV1 inhibits WHRN phosphorylation through regional cAMP-PKA signaling, which in turn regulates the ubiquitination and stability of USH2A via local signaling compartmentalization, whereas ADGRV1 Y6236fsX1 does not. Yeast two-hybrid screening identified the E3 ligase WDSUB1 that binds to WHRN and regulates the ubiquitination of USH2A in a WHRN phosphorylation-dependent manner. Further FlAsH-BRET assay, NMR spectrometry, and mutagenesis analysis provided insights into the architectural organization of ALC and interaction motifs at single-residue resolution. In conclusion, the present data suggest that ALC organization and accompanying local signal transduction play important roles in regulating the stability of the ALC.

Approaches to Reduce Rice Blast Disease Using Knowledge from Host Resistance and Pathogen Pathogenicity.

Rice is one of the staple foods for the majority of the global population that depends directly or indirectly on it. The yield of this important crop is constantly challenged by various biotic stresses. Rice blast, caused by Magnaporthe oryzae (M. oryzae), is a devastating rice disease causing severe yield losses annually and threatening rice production globally. The development of a resistant variety is one of the most effective and economical approaches to control rice blast. Researchers in the past few decades have witnessed the characterization of several qualitative resistance (R) and quantitative resistance (qR) genes to blast disease as well as several avirulence (Avr) genes from the pathogen. These provide great help for either breeders to develop a resistant variety or pathologists to monitor the dynamics of pathogenic isolates, and ultimately to control the disease. Here, we summarize the current status of the isolation of R, qR and Avr genes in the rice-M. oryzae interaction system, and review the progresses and problems of these genes utilized in practice for reducing rice blast disease. Research perspectives towards better managing blast disease by developing a broad-spectrum and durable blast resistance variety and new fungicides are also discussed.

CIB2 and CIB3 Regulate Stereocilia Maintenance and Mechanoelectrical Transduction in Mouse Vestibular Hair Cells.

The mechanoelectrical transduction (MET) protein complex in the inner-ear hair cells is essential for hearing and balance perception. Calcium and integrin-binding protein 2 (CIB2) has been reported to be a component of MET complex, and loss of CIB2 completely abolishes MET currents in auditory hair cells, causing profound congenital hearing loss. However, loss of CIB2 does not affect MET currents in vestibular hair cells (VHCs) as well as general balance function. Here, we show that CIB2 and CIB3 act redundantly to regulate MET in VHCs, as MET currents are completely abolished in the VHCs of Cib2/Cib3 double knock-out mice of either sex. Furthermore, we show that Cib2 and Cib3 transcripts have complementary expression patterns in the vestibular maculae, and that they play different roles in stereocilia maintenance in VHCs. Cib2 transcripts are highly expressed in the striolar region, and knock-out of Cib2 affects stereocilia maintenance in striolar VHCs. In contrast, Cib3 transcripts are highly expressed in the extrastriolar region, and knock-out of Cib3 mainly affects stereocilia maintenance in extrastriolar VHCs. Simultaneous knock-out of Cib2 and Cib3 affects stereocilia maintenance in all VHCs and leads to severe balance deficits. Taken together, our present work reveals that CIB2 and CIB3 are important for stereocilia maintenance as well as MET in mouse VHCs.SIGNIFICANCE STATEMENT Calcium and integrin-binding protein 2 (CIB2) is an important component of mechanoelectrical transduction (MET) complex, and loss of CIB2 completely abolishes MET in auditory hair cells. However, MET is unaffected in Cib2 knock-out vestibular hair cells (VHCs). In the present work, we show that CIB3 could compensate for the loss of CIB2 in VHCs, and Cib2/Cib3 double knock-out completely abolishes MET in VHCs. Interestingly, CIB2 and CIB3 could also regulate VHC stereocilia maintenance in a nonredundant way. Cib2 and Cib3 transcripts are highly expressed in the striolar and extrastriolar regions, respectively. Stereocilia maintenance and balance function are differently affected in Cib2 or Cib3 knock-out mice. In conclusion, our data suggest that CIB2 and CIB3 are important for stereocilia maintenance and MET in mouse VHCs.

Temporal and spatial assembly of inner ear hair cell ankle link condensate through phase separation.

Stereocilia are actin-based cell protrusions of inner ear hair cells and are indispensable for mechanotransduction. Ankle links connect the ankle region of developing stereocilia, playing an essential role in stereocilia development. WHRN, PDZD7, ADGRV1 and USH2A have been identified to form the so-called ankle link complex (ALC); however, the detailed mechanism underlying the temporal emergence and degeneration of ankle links remains elusive. Here we show that WHRN and PDZD7 orchestrate ADGRV1 and USH2A to assemble the ALC through liquid-liquid phase separation (LLPS). Disruption of the ALC multivalency for LLPS largely abolishes the distribution of WHRN at the ankle region of stereocilia. Interestingly, high concentration of ADGRV1 inhibits LLPS, providing a potential mechanism for ALC disassembly. Moreover, certain deafness mutations of ALC genes weaken the multivalent interactions of ALC and impair LLPS. In conclusion, our study demonstrates that LLPS mediates ALC formation, providing essential clues for understanding the pathogenesis of deafness.

RBM24 is required for mouse hair cell development through regulating pre-mRNA alternative splicing and mRNA stability.

As the sensory receptor cells in vertebrate inner ear and lateral lines, hair cells are characterized by the hair bundle that consists of one tubulin-based kinocilium and dozens of actin-based stereocilia on the apical surface of each hair cell. Hair cell development is tightly regulated, and deficits in this process usually lead to hearing loss and/or balance dysfunctions. RNA-binding motif protein 24 (RBM24) is an RNA-binding protein that is specifically expressed in the hair cells in the inner ear. Previously, we showed that RBM24 affects hair cell development in zebrafish by regulating messenger RNA (mRNA) stability. In the present work, we further investigate the role of RBM24 in hearing and balance using conditional knockout mice. Our results show that Rbm24 knockout results in severe hearing and balance deficits. Hair cell development is significantly affected in Rbm24 knockout cochlea, as the hair bundles are poorly developed and eventually degenerated. Hair bundle disorganization is also observed in Rbm24 knockout vestibular hair cells, although to a lesser extent. Consistently, significant hair cell loss is observed in the cochlea but not vestibule. RNAseq analysis identified several genes whose mRNA stability or pre-mRNA alternative splicing is affected by Rbm24 knockout. Among them are Cdh23, Pcdh15, and Myo7a, which have been shown to play important roles in stereocilia development as well as mechano-electrical transduction. Taken together, our present work suggests that RBM24 is required for mouse hair cell development through regulating pre-mRNA alternative splicing as well as mRNA stability.

Cotton cultivated area detection and yield monitoring combining remote sensing with field data in lower Indus River basin, Pakistan.

As the Earth's population continuously increase with the passage of time, the demand for agricultural raw material for human need increases. It is critical to maintaining updated and accurate information about the dynamics and properties of the world agricultural systems. As cash crop, the updated information of the spatial distribution of cotton field is necessary to monitor the crop area and growth changes at regional level. We used 8-day enhanced vegetation index (EVI) time series to detect cotton crop area and binomial probabilistic approach to obtain the probability distribution of cotton crop occurrence. We used Gaussian kriging to derive cotton yield inside the detected cotton crop areas through crop reporting data. We also used field data from farmers to validate the cotton yield results. A strong correlation between the MODIS-derived cotton cultivated area and statistical data at the tehsil level were achieved (R2 = 0.84) for all study years (2004-2019). The total accuracy for the cotton crop area detection was 84.6% and yield prediction was 92.1%. Our study presents new approaches to map cotton area and yield, which are applicable to other regions through machine learning.

Identification of Elite R-Gene Combinations against Blast Disease in Geng Rice Varieties.

Rice blast, caused by the Magnaporthe oryzae fungus, is one of the most devastating rice diseases worldwide. Developing resistant varieties by pyramiding different blast resistance (R) genes is an effective approach to control the disease. However, due to complex interactions among R genes and crop genetic backgrounds, different R-gene combinations may have varying effects on resistance. Here, we report the identification of two core R-gene combinations that will benefit the improvement of Geng (Japonica) rice blast resistance. We first evaluated 68 Geng rice cultivars at seedling stage by challenging with 58 M. oryzae isolates. To evaluate panicle blast resistance, we inoculated 190 Geng rice cultivars at boosting stage with five groups of mixed conidial suspensions (MCSs), with each containing 5-6 isolates. More than 60% cultivars displayed moderate or lower levels of susceptibility to panicle blast against the five MCSs. Most cultivars contained two to six R genes detected by the functional markers corresponding to 18 known R genes. Through multinomial logistics regression analysis, we found that Pi-zt, Pita, Pi3/5/I, and Pikh loci contributed significantly to seedling blast resistance, and Pita, Pi3/5/i, Pia, and Pit contributed significantly to panicle blast resistance. For gene combinations, Pita+Pi3/5/i and Pita+Pia yielded more stable pyramiding effects on panicle blast resistance against all five MCSs and were designated as core R-gene combinations. Up to 51.6% Geng cultivars in the Jiangsu area contained Pita, but less than 30% harbored either Pia or Pi3/5/i, leading to less cultivars containing Pita+Pia (15.8%) or Pita+Pi3/5/i (5.8%). Only a few varieties simultaneously contained Pia and Pi3/5/i, implying the opportunity to use hybrid breeding procedures to efficiently generate varieties with either Pita+Pia or Pita+Pi3/5/i. This study provides valuable information for breeders to develop Geng rice cultivars with high resistance to blast, especially panicle blast.

A Method of Merging Maps for MUAVs Based on an Improved Genetic Algorithm.

The merging of environmental maps constructed by individual UAVs alone and the sharing of information are key to improving the efficiency of distributed multi-UAVexploration. This paper investigates the raster map-merging problem in the absence of a common reference coordinate system and the relative position information of UAVs, and proposes a raster map-merging method with a directed crossover multidimensional perturbation variational genetic algorithm (DCPGA). The algorithm uses an optimization function reflecting the degree of dissimilarity between the overlapping regions of two raster maps as the fitness function, with each possible rotation translation transformation corresponding to a chromosome, and the binary encoding of the coordinates as the gene string. The experimental results show that the algorithm could converge quickly and had a strong global search capability to search for the optimal overlap area of the two raster maps, thus achieving map merging.

Loss of TMCC2 activates endoplasm reticulum stress and causes auditory hair cell death.

As the auditory and balance receptor cells in the inner ear, hair cells are responsible for converting mechanical stimuli into electrical signals, a process referred to as mechano-electrical transduction. Hair cell development and function are tightly regulated, and hair cell deficits are the main reasons for hearing loss and balance disorders. TMCC2 is an endoplasmic reticulum (ER)-residing transmembrane protein whose physiological function largely remains unknown. In the present work, we show that Tmcc2 is specifically expressed in the auditory hair cells of mouse inner ear. Tmcc2 knockout mice were then established to investigate its physiological role in hearing. Auditory brainstem responses measurements show that Tmcc2 knockout mice suffer from congenital hearing loss. Further investigations reveal progressive auditory hair cell loss in the Tmcc2 knockout mice. The general morphology and function of ER are unaffected in Tmcc2 knockout hair cells. However, increased ER stress was observed in Tmcc2 knockout mice and knockdown cells, suggesting that loss of TMCC2 leads to auditory hair cell death through elevated ER stress.

[Spatialization and Spatio-temporal Dynamics of Energy Consumption Carbon Emissions in China].

The adverse effects of global climate change on human production and life are becoming increasingly prominent. Responding to climate change has become a severe challenge faced by human society, and the reduction in greenhouse gas emissions has gradually become a common action by all countries. Therefore, analyzing carbon emissions through scientific methods has become an important foundation for responding to the national "dual carbon" strategy. This study used provincial-level carbon emission statistics, combined with nighttime light data and population data, and assigned carbon emissions to the grid scale. It also analyzed the temporal and spatial characteristics and evolution characteristics of carbon emissions in China in 2000, 2005, 2010, 2015, and 2018, as well as the correlation between carbon emissions and the economy. The results showed that:① from 2000 to 2018, the total CO2 emissions in China continued to grow, but the growth rate slowed over time. The average annual growth rate of carbon emissions dropped from 9.9% in 2000-2010 to 7.4% in 2010-2018. From the perspective of spatial distribution, carbon-free areas were mainly distributed in the northwest uninhabited area and northeast forest and mountainous areas, low-carbon emissions were mainly distributed in the vast small and medium-sized cities and towns, and high-carbon emissions were concentrated in northern, central, eastern coastal, and western provincial capitals and urban agglomerations. ② Carbon emissions had high-value or low-value agglomerations at prefecture-level cities; this agglomeration tended to stabilize as a whole and had strengthened after 2005. Low-low agglomeration areas were mainly distributed in the western contiguous areas and Hainan Island. With economic and social development, low-low agglomeration areas began to fragment and reduce in size; high-high agglomeration areas were mainly distributed in the Beijing-Tianjin-Hebei urban agglomeration, Taiyuan urban agglomeration, Yangtze River Delta urban agglomerations, and Pearl River Delta urban agglomerations, and the scale was gradually strengthened and consolidated; high-low and low-high agglomeration areas mainly appeared in neighboring cities with large differences in economic development levels. ③ Carbon emissions in most parts of China were relatively stable. The areas where carbon emissions had changed were mainly distributed in the peripheral areas of provincial capitals and key cities, and there was a circle structure with no changes in the central urban area and changes in carbon emissions in the peripheral areas. ④ The overall process of urban development in China from 2000 to 2018 followed a shift from "low emission-low income" to "high emission-low income" to "high emission-high income" and finally to "low emission-high income." The growth rate of carbon emissions in China is slowing down. Under the background of the "dual carbon" strategy, different regions face different carbon emission reduction tasks and pressures due to different carbon emission situations. Therefore, the differentiated carbon emissions policy should be implemented by regions and industries.

A New Positioning Method for Climbing Robots Based on 3D Model of Transmission Tower and Visual Sensor.

With the development of robot technology and the extensive application of robots, the research on special robots for some complex working environments has gradually become a hot topic. As a special robot applied to transmission towers, the climbing robot can replace humans to work at high altitudes to complete bolt tightening, detection, and other tasks, which improves the efficiency of transmission tower maintenance and ensures personal safety. However, it is mostly the ability to autonomously locate in the complex environment of the transmission tower that limits the industrial applications of the transmission tower climbing robot. This paper proposes an intelligent positioning method that integrates the three-dimensional information model of transmission tower and visual sensor data, which can assist the robot in climbing and adjusting to the designated working area to guarantee the working accuracy of the climbing robots. The experimental results show that the positioning accuracy of the method is within 1 cm.

FCHSD2 is required for stereocilia maintenance in mouse cochlear hair cells.

Stereocilia are F-actin-based protrusions on the apical surface of inner-ear hair cells and are indispensable for hearing and balance perception. The stereocilia of each hair cell are organized into rows of increasing heights, forming a staircase-like pattern. The development and maintenance of stereocilia are tightly regulated, and deficits in these processes lead to stereocilia disorganization and hearing loss. Previously, we showed that the F-BAR protein FCHSD2 is localized along the stereocilia of cochlear hair cells and cooperates with CDC42 to regulate F-actin polymerization and cell protrusion formation in cultured COS-7 cells. In the present work, Fchsd2 knockout mice were established to investigate the role of FCHSD2 in hearing. Our data show that stereocilia maintenance is severely affected in cochlear hair cells of Fchsd2 knockout mice, which leads to progressive hearing loss. Moreover, Fchsd2 knockout mice show increased acoustic vulnerability. Noise exposure causes robust stereocilia degeneration as well as enhanced hearing threshold elevation in Fchsd2 knockout mice. Lastly, Fchsd2/Cdc42 double knockout mice show more severe stereocilia deficits and hearing loss, suggesting that FCHSD2 and CDC42 cooperatively regulate stereocilia maintenance.

Template-independent genome editing in the Pcdh15av-3j mouse, a model of human DFNB23 nonsyndromic deafness.

Although frameshift mutations lead to 22% of inherited Mendelian disorders in humans, there is no efficient in vivo gene therapy strategy available to date, particularly in nondividing cells. Here, we show that nonhomologous end-joining (NHEJ)-mediated nonrandom editing profiles compensate the frameshift mutation in the Pcdh15 gene and restore the lost mechanotransduction function in postmitotic hair cells of Pcdh15av-3J mice, an animal model of human nonsyndromic deafness DFNB23. Identified by an ex vivo evaluation system in cultured cochlear explants, the selected guide RNA restores reading frame in approximately 50% of indel products and recovers mechanotransduction in more than 70% of targeted hair cells. In vivo treatment shows that half of the animals gain improvements in auditory responses, and balance function is restored in the majority of injected mutant mice. These results demonstrate that NHEJ-mediated reading-frame restoration is a simple and efficient strategy in postmitotic systems.