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In spatial missions, it is important to estimate kinematic state and to identify the shape of non-cooperative targets. In order to improve the accuracy and generality of the existing algorithm, a real-time recognition and detection method for tumbling non-cooperative target is proposed. First, we design a key point detection network to identify non-cooperative targets and their feature points in the process of long-distance non-cooperative target recognition. At the same time, the detected image is combined with the PNP algorithm to obtain the target’s 6D attitude. Then, a BiSeNet based model is trained for real-time semantic segmentation of satellite components as the base satellite is pursued close to its target. The segmented image is selected with depth information and the relative position of the capturing point is transmitted to the manipulator. Finally, we complete physical experiments under different lighting conditions with a spinning non-cooperative target on a 6-DOF air-bearing table. The experimental results show that the satellite recognition accuracy and object segmentation accuracy are 99.48% and 98.11%, respectively. The position measurement error is less than 1 mm, which achieves more than 50% improvement over the conventional methods.

Gene therapy focuses on genetic modification to produce therapeutic effects or treat diseases by repairing or reconstructing genetic material, thus being expected to be the most promising therapeutic strategy for genetic disorders. Due to the growing attention to hearing impairment, an increasing amount of research is attempting to utilize gene therapy for hereditary hearing loss (HHL), an important monogenic disease and the most common type of congenital deafness. Several gene therapy clinical trials for HHL have recently been approved, and, additionally, CRISPR-Cas tools have been attempted for HHL treatment. Therefore, in order to further advance the development of inner ear gene therapy and promote its broad application in other forms of genetic disease, it is imperative to review the progress of gene therapy for HHL. Herein, we address three main gene therapy strategies (gene replacement, gene suppression, and gene editing), summarizing the strategy that is most appropriate for particular monogenic diseases based on different pathogenic mechanisms, and then focusing on their successful applications for HHL in preclinical trials. Finally, we elaborate on the challenges and outlooks of gene therapy for HHL.

Antheraea pernyiGuérin-Méneville (Lepidoptera: Saturniidae) is of high economic value as a source of silk, food, and bioactive substances with medicinal properties. A. pernyilarvae are prone to A. pernyivomit disease (AVD), which results in substantial economic losses during cultivation; however, the relationship between AVD and A. pernyigut microbiota remains unclear. Here, we investigated the bacterial community in the midgut and feces of A. pernyilarvae with and without AVD using 16SrRNA gene sequencing with Illumina MiSeq technology. Compared with healthy larvae, intestinal bacterial diversity and community richness increased and decreased in larvae with mild and severe AVD, respectively. In addition, the proportion of gut EnterobacterHormaeche and Edwards(Enterobacteriales: Enterobacteriaceae) and EnterococcusThiercelin and Jouhaud (Lactobacillales: Enterococcaceae) was higher and lower, respectively, in larvae with mild AVD than those in healthy larvae. A. pernyivomit disease infection significantly increased the genera with abundance <1%. In the gut of larvae with severe AVD, the proportion of TuricibacterBosshard et al. (Erysipelotrichales: Turicibacteraceae) increased significantly to 81.53–99.92%, whereas that of Enterobacterdecreased compared with healthy larvae. However, the diversity of fecal bacteria was similar between healthy larvae and those with mild AVD. Overall, the findings demonstrate that intestinal microflora in A. pernyilarvae are altered by AVD infection and may cause secondary bacterial infection. This is the first report of the presence of Turicibacterin the intestinal tract of lepidopterans.

Cellular mechanotransduction plays an essential role in the development and differentiation of many cell types, but if and how mechanical cues from the extracellular matrix (ECM) influence the fate determination of inner ear progenitor cells (IEPCs) remains largely unknown. In the current study, we compared the biological behavior of IEPCs in Matrigel‐based suspension and encapsulated culture systems, and we found that the mechanical cues from the ECM promote the survival and expansion of IEPCs. Furthermore, we found that the mechanical cues from the ECM induced the accumulation of Ras homolog family member A (RhoA) and caused the polymerization of actin cytoskeleton in IEPCs. These changes in turn resulted in increased Yes‐associated protein (YAP) nuclear localization and enhanced expansion of IEPCs, at least partially through upregulating the canonical Wnt signaling pathway. We therefore provide the first demonstration that the RhoA‐YAP‐β‐catenin signaling axis senses and transduces mechanical cues from the ECM and plays crucial roles in promoting the expansion of IEPCs. The study demonstrates that the essential role of RhoA–YAP–β‐catenin signaling axis on inner ear progenitor cells expansion. The response of inner ear progenitor cells to mechanical cues from their microenvironment via RhoA‐mediated actin cytoskeleton contraction, which lead to nuclear Yes‐associated protein (YAP) accumulation. YAP as a mediator of mechanotransduction signaling to promote the expansion of inner ear progenitor cells through regulating β‐catenin activity.

ABSTRACTWe report a new laminopathy that includes generalized lipoatrophy, insulin-resistant diabetes, micrognathia and biopsy-proven, focal segmental glomerulosclerosis in a female, caused by a de novo heterozygous mutation R133L in the lamin A/C gene (LMNA). We analysed the nuclear morphology and laminar distribution in 3T3-L1 pre-adipocytes overexpressing human wild-type lamin A/C (LMNAWT) or lamin A/C with the R133L mutation (LMNAR133L). We found the nuclear size was varied, nuclear membrane invagination or blebbing, and an irregular A-type lamin meshwork in cells overexpressing LMNAR133L.3T3-L1 pre-adipocyte differentiation into adipocytes was impaired in cells expressing LMNAR133L; contemporaneously, the expression levels of genes associated with adipose tissue self-renewal, including adipogenesis, angiogenesis, and extracellular matrix maintenance, were downregulated. Furthermore, the insulin-signalling pathway was inhibited in LMNAR133L adipocytes. Microarray gene expression profiling showed that the most prominent differences between 3T3-L1 cells expressing wild-type LMNAand LMNAR133L were in genes implicated in metabolic pathways, the cellular response to DNA damage and repair. We thus expand the clinical spectrum of laminopathy and conclude that the LMNAR133L mutation associated with lipodystrophic features and multisystem disorders likely impairs adipocyte renewal and disrupts the expression of genes implicated in the induction and repair of DNA damage.

ABSTRACTIntroduction: The rapid progress of bioinformatics and high-throughput screening techniques in recent years has led to the identification of many candidate genes and small-molecule drugs that have the potential to make significant contributions to our understanding of the developmental and pathological processes of hearing, but it remains unclear how these genes and regulatory factors are coordinated. Increasing evidence suggests that epigenetic mechanisms are essential for establishing gene expression profiles and likely play an important role in the development of inner ear and in the pathology of hearing-associated diseases. Zebrafish are a valuable and tractable in vivomodel organism for monitoring changes in the epigenome and for identifying new epigenetic processes and drug molecules that can influence vertebrate development.Areas covered: In this review, the authors focus on zebrafish as a model to summarize recent findings concerning the roles of epigenetics in the development, regeneration, and protection of hair cells.Expert opinion: Using the zebrafish model in combination with high-throughput screening and genome-editing technologies to investigate the function of epigenetics in hearing is crucial to help us better understand the molecular and genetic mechanisms of auditory development and function. It will also contribute to the development of new strategies to restore hearing loss.

Cisplatin is a widely used chemotherapeutic drug, but one of its side effects is ototoxicity. Epigenetic-related drugs, such as lysine-specific demethylase 1 (LSD1) inhibitors, have been reported to protect against cisplatin-induced hair cell loss by preventing demethylation of histone H3K4 (H3K4me2). However, the protective effect of LSD1 inhibitors in spiral ganglion neurons (SGNs) remains unclear. To investigate whether LSD1 inhibitors exert similar protective effects on SGNs, we treated mouse cochlear explant cultures with LSD1 inhibitors (2PCPA, S2101, or CBB1007) together with cisplatin. Low concentrations of cisplatin damaged SGNs much more than high concentrations, and blocking the demethylation of H3K4me2 with LSD1 inhibitors prevented the SGNs from injury. Reactive oxygen species are also involved in the injury process, and LSD1 inhibitors protected SGNs by increasing the expression level of the antioxidant gene Slc7a11and decreasing the level of the pro-oxidant gene lactoperoxidase (Lpo). Our findings show that LSD1 inhibitors prevent cisplatin-induced SGN loss by regulating the demethylation of H3K4 and preventing increases of reactive oxygen species levels, which might provide a potential therapeutic strategy for cisplatin-induced hearing loss.

Based on the idea of reference-trajectory guidance, an integrated guidance and control (IGC) design approach is proposed for the landing of a reusable launch vehicle (RLV) by using backstepping and adaptive control. The nonlinear IGC model for the landing phase is formulated, and in order to handle the influence of the nonlinearity term, an adaptation law is introduced into the backstepping scheme to design an IGC law that can make flight path angle robustly track its reference value and keep the heading angle near zero (heading to the runway). Comparing with the existing guidance and control methods, the IGC law designed in this paper can guarantee the stability of the overall system that composed of guidance and control systems, and the law also has robustness with respect to uncertainties. The numerical simulation confirms the effectiveness of the proposed design approach.

In this paper, an autonomous relative navigation and joint attitude determination algorithm in asteroid exploration descent stage is researched based on feature point information of perpendicular asteroid surface image observed by optical navigation camera, distance vectors from spacecraft to asteroid measured by three angled installed lidars and relative velocity increment measured by accelerometer when the relative distance vector to the centroid of asteroid can not be obtained. The inertial attitude of spacecraft is determined by sun vector, star vectors and inertial angular velocity respectively measured by sun sensor, star trackers and inertial reference unit. Also, in order to obtain measurement error model transferred from sensor noise, a covariance matrix solver considering error correlation is presented via the error model of normalized vector to first order. Numerical simulation and improved observability evaluation of filtering are undertaken to discuss the results of complete sensor observation and weak observation of lidars, and verify the effectiveness of the presented relative navigation and attitude determination algorithm.

Rutin is a natural flavonoid, with typical effects including interaction with enzymes and scavenging of free radicals. However, the role of rutin in the auditory system is still unclear. In the present study, we used neonatal organ of Corti explants in vitroto investigate the effects of rutin in cisplatin-induced ototoxicity. The TUNEL assay and the cleaved caspase-3 immunohistochemistry were used to detect the apoptosis of hair cell (HCs) in cochlear explants, and the MitoSox-Red staining was used to detect the difference in mitochondrial superoxide among different groups. Western blot was used to investigate the expression of genes. Confocal microscopy showed that after pretreatment with rutin, the accumulation of reactive oxygen species in HCs caused by cisplatin exposure was significantly reduced. Furthermore, the expression levels of p-P38 and p-JNK were significantly decreased, while ratio of p-AKT/AKT was significantly upregulated. Our study showed that rutin reduced cisplatin-induced HCs death in neonatal cochlear explants in vitro. The potential mechanism involved the alleviation of mitochondrial damage, the scavenging of reactive oxygen species (ROS), the suppression of MAPK signaling pathway, and the activation of PI3K/AKT signaling pathway.

Histone deacetylases are involved in many biological processes and have roles in regulating cell behaviors such as cell cycle entry, cell proliferation and apoptosis. However, the effect of histone deacetylases on the development of hair cells (HCs) has not been fully elucidated. In this study, we examined the influence of histone deacetylases on the early development of neuromasts in the lateral line of zebrafish. Hair cell development was evaluated by fluorescent immunostaining in the absence or presence of histone deacetylase inhibitors. Our results suggested that pharmacological inhibition of histone deacetylases with inhibitors, including trichostatin A, valproic acid and MS-275, reduced the numbers of both HCs and supporting cells in neuromasts. We also found that the treatment of zebrafish larvae with inhibitors caused accumulation of histone acetylation and suppressed proliferation of neuromast cells. Real-time PCR results showed that the expression of both p21 and p27 mRNA was increased following trichostatin A treatment and the increase in p53 mRNA was modest under the same conditions. However, the expression of p53 mRNA was significantly increased by treatment with a high concentration of trichostatin A. A high concentration of trichostatin A also led to increased cell death in neuromasts as detected in a TUNEL assay. Moreover, the nuclei of most of these pyknotic cells were immunohistochemically positive for cleaved caspase-3. These results suggest that histone deacetylase activity is involved in lateral line development in the zebrafish and might have a role in neuromast formation by altering cell proliferation through the expression of cell cycle regulatory proteins.