miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database.

MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.

[Prospective Study on Corneal Safety Evaluation of Children/Adolescents with Low and Moderate Myopia after Long-Term Orthokeratology].

OBJECTIVE: To observe the possible changes in the integrity of the cornea and corneal endothelial cells of children/adolescents with low or moderate myopia after long-term wearing of orthokeratology (ortho-k) lenses, as well as the time when the relevant changes occur, so as to evaluate the safety of long-term wearing of ortho-k lens and to provide a reference for the safety evaluation of subjects wearing ortho-k lenses. METHODS: Subjects were recruited in the Contact Lens Clinic, West China Hospital, Sichuan University for a three-year prospective study. Ortho-k of the same brand was matched for the subjects. The central corneal thickness (CCT), corneal endothelial cell density (ECD), and hexagonal cell ratio (HEX) were measured prior to the wearing of ortho-k lenses and after wearing ortho-k lenses for 1 month, 3 months, 6 months, and every 3 months until 36 months. The results of corneal fluorescence staining were recorded during each follow-up. When corneal staining was observed, the Efron grading standard was used for grading and corresponding treatment was given. RESULTS: A total of 33 (66 eyes) myopic patients were included in the study. 15 cases (46.2%) reported having binocular foreign body sensations and tearing within the first week of wearing the lenses. After the subjects became adapted to wearing the lenses, the symptoms disappeared without intervention. During the follow-up period, 31 cases (93.94%) of binocular corneal staining were observed, of which, 24 cases (72.73%) were graded as G0, receiving no treatment, 5 cases (15.15%) were graded as GⅠ, and 2 cases (6.06%) were graded as GⅡ. Corresponding clinical treatment for corneal staining was given to the GⅠ and GⅡ subjects. This study found that the corneal ECD was inversely proportional to age ( r=－0.380, P=0.002). During the three-year follow-up period, the subjects' left eye ECD decreased from the baseline at 24 months and the right eye ECD decreased from the baseline at 27 months ( P<0.05). The CCT results in the subjects showed that CCT became thinner at 1 month after wearing the lens ( P<0.05), but the follow-up CCT showed a stable trend. CONCLUSION: After three years of long-term follow-up, no serious corneal complications occurred in children/adolescents with moderate and low myopia after long-term wearing of ortho-k lens. The corneal ECD of both eyes started decreasing 24 months after wearing the ortho-k lenses and the CCT decreased 1 month after wearing the lenses.

[Motion-in-depth Perception and Static Stereopsis of Patients with Strabismics].

OBJECTIVE: To determine the role of motion-in-depth perception and static stereopsis in strabismics, and factors associated with the perception of motion-in-depth. METHODS: A total of 84 strabismic patients (including 57 intermittent exotropes, 12 constant exotropes and 15 esotropes) and 16 normal controls were recruited. Binocular fusion ability, static stereopsis and motion-in-depth perception were tested using the computer-generated stereoscopic stimuli. The correlations between these tests were analyzed. RESULTS: There was a significant correlation between motion-in-depth perception and static stereopsis in strabismics. Only patients with static stereopsis demonstrated the perception of motion-in-depth. A positive correlation was found between motion-in-depth perception thresholds and static stereopsis in intermittent exotropes. All participants in the control group had motion-in-depth perception and static stereopsis. The participants with stereopsis had significantly lower thresholds than those with strabismus (P<0.01). The perception of motion-in-depth varied with the type of strabismus: 87.7% of the intermittent exotropes exhibited motion-in-depth perception, whereas none of the constant strabismics were able to pass the motion-in-depth perception tests. The perception of motion-in-depth was correlated with the presence of binocular fusion. CONCLUSIONS: Motion-in-depth perception is correlated with static stereopsis in strabismics. The perception of motion-in-depth varies with the type of strabismus: only intermittent exotropes have the perception of motion-in-depth.

A mouse model for X-linked Alport syndrome induced by Del-ATGG in the Col4a5 gene.

Alport syndrome (AS) is an inherited glomerular basement membrane (GBM) disease leading to end-stage renal disease (ESRD). X-linked AS (XLAS) is caused by pathogenic variants in the COL4A5 gene. Many pathogenic variants causing AS have been detected, but the genetic modifications and pathological alterations leading to ESRD have not been fully characterized. In this study, a novel frameshift variant c.980_983del ATGG in the exon 17 of the COL4A5 gene detected in a patient with XLAS was introduced into a mouse model in by CRISPR/Cas9 system. Through biochemical urinalysis, histopathology, immunofluorescence, and transmission electron microscopy (TEM) detection, the clinical manifestations and pathological alterations of Del-ATGG mice were characterized. From 16 weeks of age, obvious proteinuria was observed and TEM showed typical alterations of XLAS. The pathological changes included glomerular atrophy, increased monocytes in renal interstitial, and the absence of type IV collagen α5. The expression of Col4a5 was significantly decreased in Del-ATGG mouse model. Transcriptomic analysis showed that differentially expressed genes (DEGs) accounted for 17.45% (4,188/24003) of all genes. GO terms indicated that the functions of identified DEGs were associated with cell adhesion, migration, and proliferation, while KEGG terms found enhanced the degradation of ECM, amino acid metabolism, helper T-cell differentiation, various receptor interactions, and several important pathways such as chemokine signaling pathway, NF-kappa B signaling pathway, JAK-STAT signaling pathway. In conclusion, a mouse model with a frameshift variant in the Col4a5 gene has been generated to demonstrate the biochemical, histological, and pathogenic alterations related to AS. Further gene expression profiling and transcriptomic analysis revealed DEGs and enriched pathways potentially related to the disease progression of AS. This Del-ATGG mouse model could be used to further define the genetic modifiers and potential therapeutic targets for XLAS treatment.