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Indoor air quality is a critical factor influencing athletic performance, particularly in professional sports settings, yet its impact remains underexplored. This study utilizes a panel dataset from 2516 Chinese Basketball Association (CBA) matches across 20 cities in China between 2014 and 2019. We integrate daily air pollution metrics with player efficiency ratings (PER) to investigate the effects of air quality on individual performance. We find that a 10% increase in the air quality index (AQI) corresponds to a 1.4223 decrease in PER, indicating a strong negative effect of poor air quality on player productivity. Different pollutants have varying effects, with some exacerbating the decline in both overall performance and precision in tasks. Notably, older players and international players exhibit greater resilience to air pollution. These insights contribute to the development of a comprehensive index for assessing work efficiency under varying air quality conditions and suggest targeted strategies to mitigate the negative impacts of air pollution in competitive athletic settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The capsular tension ring is a novel assistant tool for cataract surgery; however, controversy exists in its co-implantation. The potential for hyperopic or myopic shift resulting from the co-implantation of the capsular tension ring and intraocular lens remains unclear. This study aimed to determine the postoperative refractive prediction error and the direction of refractive shift in cataract patients who underwent capsular tension ring co-implantation., Methods: We conducted a systematic review and meta-analysis,searching electronic databases for studies of individuals diagnosed with cataracts receiving surgery with or without capsular tension ring implantation. Systematic searches were performed based on five databases: PubMed, Cochrane Library, Web of Science, Medline, and China National Knowledge Infrastructure. The primary outcome was the mean arithmetic refractive prediction error. Secondary outcomes were mean absolute refractive prediction error and the number of eyes within a certain refractive prediction error range. We applied a fixed-effectsmodel to pool effect sizes across trials using weighted mean differences (WMD) and risk ratios (RR) with their 95% confidence intervals (95% CI). Statistical heterogeneity scores were assessed with the I 2 statistic., Results: A total of 407 affected eyes were included in eight independent clinical studies. Meta-analysis suggested significant differences both in short-term (≤1 month) co-implantation (WMD = 0.16, p  < .001, 95% CI: -0.13 ~ 0.19) and long-term (≥3 months) co-implantation between the capsular tension ring co-implantation group and the control group (WMD = 0.19, p  < .001, 95% CI: 0.15 ~ 0.23). However, no significant difference was observed in the high myopia subgroup whether capsular tension ring co-implantation (WMD = 0.03, p  = .083, 95% CI: -0.27 ~ 0.34). Heterogeneity was not found among the studies., Conclusion: Compared to simple intraocular lens implantation, capsular tension ring co-implantation is more susceptible to developing hyperopic shifts in non-myopic cataract patients, probably related to anterior chamber depth. It requires careful consideration by clinicians when determining the target diopter preoperatively. However, interpretation is limited, because there is a lack of studies available for analysis. There still needs to be additional studies to expand the evidence base.

Purpose: To evaluate the effect of 0.01% atropine combined with orthokeratology (OK) lens on axial elongation in schoolchildren with myopia., Methods: Sixty children aged 8-12 years with spherical equivalent refraction (SER) from -1.00D to -4.00D in both eyes were enrolled in this randomized, double-masked, placebo-controlled, cross-over trial. Children who had been wearing OK lenses for 2 months were randomly assigned into combination group (combination of OK lens and 0.01% atropine) for 1 year followed by control group (combination of OK lens and placebo) for another 1 year or vice versa. This trial was registered in the Chinese Clinical Trial Registry (Number: ChiCTR2000033904, 16/06/2020). The primary outcome was changes in axial length (AL). Data of right eyes were analyzed., Results: There were statistically significant differences in the changes in AL between combination and control groups after generalized estimating equation model adjusting for age and baseline SER ( p  = 0.001). The mean axial elongation difference between combination and control groups was 0.10 mm in the first year (0.10 ± 0.13 mm vs. 0.20 ±0.15 mm; p  = 0.01), and 0.09 mm in the second year (0.22 ± 0.10 mm vs. 0.13 ± 0.14 mm; p  = 0.01), respectively. The mean axial elongation difference of two groups in the first year was similar to that in the second year during the cross-over treatment., Conclusion: In central Mainland China in myopic children, the treatment of combination therapy is more effective than single OK lens in controlling axial elongation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Yu, Gao, Sun, Pang, Li, Wang, Zhang and Fu.)

Purpose: Danio rerio zebrafish constitute a popular model for studying lens development and congenital cataracts. However, the specific deletion of a gene with a Cre/LoxP system in the zebrafish lens is unavailable because of the lack of a lens-Cre-transgenic zebrafish. This study aimed to generate a transgenic zebrafish line in which Cre recombinase was specifically expressed in the lens., Methods: The pTol2 cryaa :Cre-polyA- cryaa :EGFP (enhanced green fluorescent protein) plasmid was constructed and co-injected with Tol2-transposase into one-to-two-cell-stage wild-type (WT) zebrafish embryos. Whole-mount in situ hybridization (ISH), tissue section, hematoxylin and eosin staining, a Western blot, a split-lamp observation, and a grid transmission assay were used to analyze the Cre expression, lens structure, and lens transparency of the transgenic zebrafish., Results: In this study, we generated a transgenic zebrafish line, zTg( cryaa :Cre- cryaa :EGFP), in which Cre recombinase and EGFP were driven by the lens-specific cryaa promoter. zTg( cryaa :Cre- cryaa :EGFP) began to express Cre and EGFP specifically in the lens at the 22 hpf stage, and this ectopic Cre could efficiently and specifically delete the red fluorescent protein (RFP) signal from the lens when zTg( cryaa :Cre- cryaa :EGFP) embryos were injected with the loxP -flanked RFP plasmid. The overexpression of Cre and EGFP did not impair zebrafish development or lens transparency. Accordingly, this zTg( cryaa :Cre- cryaa :EGFP) zebrafish line is a useful tool for gene editing, specifically with zebrafish lenses., Conclusions: We established a zTg( cryaa :Cre- cryaa :EGFP) zebrafish line that can specifically express an active Cre recombinase in lens tissues. This transgenic zebrafish line can be used as a tool to specifically manipulate a gene in zebrafish lenses., (Copyright © 2024 Molecular Vision.)

In some vertebrates and invertebrates, semen release factors affecting female physiology and behavior. Here, we report that semen delivered to females is potentially beneficial for promoting oocyte development in a viviparous teleost, Sebastes schlegelii . 88% of mated ovaries develop normally and give birth to larval fish, whereas 61% of non-mated ovaries are arrested in the previtellogenic stage. Semen's significant role (p < 0.0001) in promoting oocyte development may involve remodeling follicular cells and regulating the expression of the extracellular matrix, which facilitates cell communication. Furthermore, the ovarian response to semen may influence the brain, affecting hormone release, follicular cell development and steroid production, and crucial for oocyte growth. This mechanism, which could potentially delay maternal investment in offspring until male genetic input occurs to avoid energy wastage, has not been previously described in teleosts. These findings enhance our understanding of ovarian development in viviparous fish, with broader implications for reproductive biology., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Compound drought and heatwaves (CDH) have garnered increasing attention because concurrent extreme events can exacerbate the harmful impacts caused by univariate extremes. However, various severities in CDH events and their relationships with sea surface temperature (SST) variations in China remain little understood. Here, we accurately identify CDH events and multi-aspect of characteristics using the standardized precipitation evapotranspiration index (SPEI) and the excess heat factor (EHF) during the extended summer (May-September) of 1961-2017. The evolution of multifaceted characteristics of CDH and their association with SST variation are further explored. The results suggest that the number, frequency, duration and intensity of regional CDH events show heterogeneous spatial patterns, with a significant increasing trend. A consistent abrupt transition in CDH characteristics averaged over China occurred in the period of 1993-1996. Mild and moderate CDHs occur more commonly in Northwest and North China, whereas severe CDHs are mainly found in central and eastern regions. Mild and moderate CDHs are more susceptible to SST modes than severe CDH, and there are strong positive correlations between mild and moderate CDH characteristics and SST variations in the northwest and northern regions. Compared to El Niño-Southern Oscillation (ENSO), Indian Ocean Dipole (IOD) plays a dominant role in the intensifications of mild and moderate CDH events. Regionally, the northwest and north have experienced longer, more frequent and severe CDH events during the positive phase of IOD. These findings reveal the divergent evolutions in CDH characteristics with various severities and inconsistent impacts of different SST modes on the compound events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

SARS-Cov-2 infection, which has caused the COVID-19 global pandemic, triggers cellular senescence. In this study, we investigate the role of the SARS-COV-2 spike protein (S-protein) in regulating the senescence of RPE cells. The results showed that administration or overexpression of S-protein in ARPE-19 decreased cell proliferation with cell cycle arrest at the G1 phase. S-protein increased SA-β-Gal positive ARPE-19 cells with high expression of P53 and P21, senescence-associated inflammatory factors (e.g., IL-1β, IL-6, IL-8, ICAM, and VEGF), and ROS. Elimination of ROS by N-acetyl cysteine (NAC) or knocking down p21 by siRNA diminished S-protein-induced ARPE cell senescence. Both administrated and overexpressed S-protein colocalize with the ER and upregulate ER-stress-associated BIP, CHOP, ATF3, and ATF6 expression. S-protein induced P65 protein nuclear translocation. Inhibition of NF-κB by bay-11-7082 reduced S-protein-mediated expression of senescence-associated factors. Moreover, the intravitreal injection of S-protein upregulates senescence-associated inflammatory factors in the zebrafish retina. In conclusions, the S-protein of SARS-Cov-2 induces cellular senescence of ARPE-19 cells in vitro and the expression of senescence-associated cytokines in zebrafish retina in vivo likely by activating ER stress, ROS, and NF-κb. These results may uncover a potential association between SARS-cov-2 infection and development of AMD., (© 2023. The Author(s).)

This study aims to evaluate the efficacy of 0.01% atropine eye drops in preventing myopia shift and myopia onset in premyopic children. A prospective, randomized, double-masked, placebo-controlled, and crossover trial was conducted over 13 months. Sixty premyopic children aged 6-12 years with cycloplegic spherical equivalent refraction (SER) >  - 0.75 D and ≤  + 0.50 D in both eyes were assigned in a 1:1 ratio to receive one drop of 0.01% atropine or placebo once nightly for 6 months (period 1), followed by a 1-month recovery period. Then, the 0.01% atropine group was crossed over to the placebo group, and the latter was crossed over to the 0.01% atropine group for another 6 months (period 2). The primary outcomes were changes in SER and axial length (AL), and the secondary outcomes were the proportion of myopia onset (SER ≤  - 0.75D) and fast myopic shift (change in SER ≤  - 0.25D) in the two periods. Generalized estimating equation (GEE) model performed a statistically significant treatment effect of 0.01% atropine compared with placebo (p SER  = 0.02, p AL  < 0.001), with a mean SER and AL difference of 0.20D (- 0.15 ± 0.26D vs. - 0.34 ± 0.34D) and 0.11 mm (0.17 ± 0.11 mm vs. 0.28 ± 0.14 mm) in period 1, and 0.17D (- 0.18 ± 0.24D vs. - 0.34 ± 0.31D) and 0.10 mm (0.15 ± 0.15 mm vs. 0.24 ± 0.11 mm) in period 2. The GEE model showed that the proportion of myopia onset (p = 0.004) and fast myopic shift (p = 0.009) was significantly lower in the 0.01% atropine group than that in the placebo group. The period effect was not statistically significant (all p > 0.05). A total of 0.01% atropine significantly prevented myopic shift, axial elongation, and myopia onset in premyopic schoolchildren in central Mainland China., Conclusion: Within the limits of only two consecutive 6-month observation period, 0.01% atropine eye drops effectively prevented myopic shift, axial elongation, and myopia onset in premyopic children., Trial Registration: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000034760). Registered 18 July 2020., What Is Known: • Minimal studies on interventions for pre-myopia, despite the International Myopia Institute stating that preventing myopia is an "even more valuable target" for science and practice than reducing progression after onset., What Is New: • A total of 0.01% atropine eye drops may safely and effectively reduce the proportion of myopia onset and fast myopic shift in premyopic schoolchildren., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Conductance-photosynthesis (G s -A) models, accompanying with light use efficiency (LUE) models for calculating carbon assimilation, are widely used for estimating canopy stomatal conductance (G s ) and transpiration (T c ) under the two-leaf (TL) scheme. However, the key parameters of photosynthetic rate sensitivity (g su and g sh ) and maximum LUE (ϵ msu and ϵ msh ) are typically set to temporally constant values for sunlit and shaded leaves, respectively. This may result in T c estimation errors, as it contradicts field observations., Methods: In this study, the measured flux data from three temperate deciduous broadleaved forests (DBF) FLUXNET sites were adopted, and the key parameters of LUE and Ball-Berry models for sunlit and shaded leaves were calibrated within the entire growing season and each season, respectively. Then, the estimations of gross primary production (GPP) and T c were compared between the two schemes of parameterization: (1) entire growing season-based fixed parameters (EGS) and (2) season-specific dynamic parameters (SEA)., Results: Our results show a cyclical variability of ϵ msu across the sites, with the highest value during the summer and the lowest during the spring. A similar pattern was found for g su and g sh , which showed a decrease in summer and a slight increase in both spring and autumn. Furthermore, the SEA model (i.e., the dynamic parameterization) better simulated GPP, with a reduction in root mean square error (RMSE) of about 8.0 ± 1.1% and an improvement in correlation coefficient (r) of 3.7 ± 1.5%, relative to the EGS model. Meanwhile, the SEA scheme reduced T c simulation errors in terms of RMSE by 3.7 ± 4.4%., Discussion: These findings provide a greater understanding of the seasonality of plant functional traits, and help to improve simulations of seasonal carbon and water fluxes in temperate forests., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jin, Liu, Hou, Cai, Zhang, Wang, Fang, Huang, Yong and Ren.)

The dysfunction of CRALBP, a key regulator of the visual cycle, is associated with retinitis punctata albescens characterized by night vision loss and retinal degeneration. In this paper, we find that the expression of CRALBP is regulated by heat shock protein 90 (HSP90). Inhibition of HSP90α or HSP90β expression by using the CRISPR-Cas9 technology downregulates CRALBP's mRNA and protein expression in ARPE-19 cells by triggering the degradation of transcription factor SP1 in the ubiquitin-proteasome pathway. SP1 can bind to CRALBP's promoter, and inhibition of SP1 by its inhibitor plicamycin or siRNA downregulates CRALBP's mRNA expression. In the zebrafish, inhibition of HSP90 by the intraperitoneal injection of IPI504 reduces the thickness of the retinal outer nuclear layer and Rlbp1b mRNA expression. Interestingly, the expression of HSP90, SP1, and CRALBP is correlatedly downregulated in the senescent ARPE-19 and Pig primary RPE cells in vitro and in the aged zebrafish and mouse retinal tissues in vivo. The aged mice exhibit the low night adaption activity. Taken together, these data indicate that the HSP90-SP1 is a novel regulatory axis of CRALBP transcriptional expression in RPE cells. The age-mediated downregulation of the HSP90-SP1-CRALBP axis is a potential etiology for the night vision reduction in senior people., (© 2023 Federation of American Societies for Experimental Biology.)

Capsular residual lens epithelial cells (CRLEC) undergo differentiation to fiber cells for lens regeneration or tansdifferentiation to myofibroblasts leading to posterior capsular opacification (PCO) after cataract surgery. The underlying regulatory mechanism remains unclear. Using human lens epithelial cell lines and the ex vivo cultured rat lens capsular bag model, we found that the lens epithelial cells secrete HSP90α extracellularly (eHSP90) through an autophagy-associated pathway. Administration of recombinant GST-HSP90α protein or its M-domain induces the elongation of rat CRLEC cells with concomitant upregulation of the crucial fiber cell transcriptional factor PROX1and its downstream targets, β- and γ-crystallins and structure proteins. This regulation is abolished by PROX1 siRNA. GST-HSP90α upregulates PROX1 by binding to LRP1 and activating LRP1-AKT mediated YAP degradation. The upregulation of GST-HSP90α on PROX1 expression and CRLEC cell elongation is inhibited by LRP1 and AKT inhibitors, but activated by YAP-1 inhibitor (VP). These data demonstrated that the capsular residue epithelial cells upregulate and secrete eHSP90α, which in turn drive the differentiation of lens epithelial cell to fiber cells. The recombinant HSP90α protein is a potential novel differentiation regulator during lens regeneration., (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Glabridin is a prenylated isoflavonoid with considerable anticancer property. Reactive oxygen species (ROS) have evolved as regulators of many cellular signaling pathways in prostate cancer (PC). However, the role of ROS signaling in the anticancer activity of glabridin has not been investigated. Here, we attempted to evaluate the effect of glabridin on PC and the involvement of ROS signaling. Intracellular ROS and mitochondrial ROS (mitoROS) production in PC cell lines, DU-145 and LNCaP, were measured by H2DCFDA and MitoSOX Red staining, respectively. MTT assay was used to analyze the cellular viability. EdU staining assay was conducted to analyze the cell proliferation. To analyze apoptotic rate, TUNEL assay was performed. Caspase-3 activity was detected to reflect cell apoptosis. Western blot was carried out to detect the expression levels of Akt and p-Akt. We found that intracellular ROS and mitoROS levels were dose-dependently upregulated after glabridin treatment in both DU-145 and LNCaP cells, which was reversed by the treatment of ROS inhibitor, N-acetyl-L-cysteine (NAC). Glabridin inhibited the cell viability and reduced the number of EdU-positive DU-145 and LNCaP cells, which were respectively proved by MTT assay and EdU staining assay. Glabridin promoted cell death with increased apoptotic rate and caspase-3 activity in DU-145 and LNCaP cells. The effects of glabridin on cell proliferation and apoptosis were reversed by NAC. Moreover, glabridin suppressed the ratio of p-Akt/Akt, while NAC mitigated the decreased p-Akt/Akt ratio. In addition, the effects of glabridin on cell proliferation and apoptosis were also attenuated by Akt activator, SC79. Collectively, our results demonstrated that glabridin suppressed proliferation and induced apoptosis in PC cells via regulating ROS-mediated PI3K/Akt pathway. These findings suggested that glabridin might hold a promising prospective as a therapeutic agent against PC., (© 2022 Wiley Periodicals LLC.)

Oxidative stress damage to the lens is a key factor in most cataracts. Forkhead box O 4 (FOXO4), a member of the forkhead box O family, plays a pivotal role in oxidative stress. FOXO4 is upregulated in lens of age-related cataract patients, but its role in cataract has not been elucidated. Herein, we investigated the role and mechanism of FOXO4 during oxidative stress damage in lens epithelial cells. H 2 O 2 treatment enhanced FOXO4 expression in HLEpiC cells. Short hairpin RNAs mediated FOXO4 silence aggravated H 2 O 2 -induced cell apoptosis. In addition, upon H 2 O 2 exposure, silencing of FOXO4 reduced SOD and CAT activities, as well as increased intracellular MDA and ROS levels. FOXO4 silencing also inhibited Nrf2 nuclear translocation, followed by reducing the expressions of Nrf2-governed antioxidant genes HO-1 and NOQ-1. Exogenous overexpression of FOXO4 was also involved in this study and exhibited opposite effects of FOXO4-silencing. Mechanistically, FOXO4 directly bound the promoter of TRIM25 and regulated its transcription, thereby activating the Nrf2 signaling. Taken together, in the condition of oxidative stress, the expression of FOXO4 showed a compensatory upregulation and it exhibited an anti-oxidative effect by modulating the transcription of TRIM25, thus activating the Nrf2 signaling. The FOXO4/TRIM25/Nrf2 axis may be associated with the pathological mechanisms of cataract., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Diabetic retinopathy (DR) is a common microvascular complication leading to a high blindness rate among patients with diabetes. Ferroptosis is a type of cell death caused by the accumulation of iron-dependent lipid peroxides. Studies have shown that ferroptosis plays an important role in DR. The rat model of DR was constructed and treated with Ferrostatin-1 (Ferr-1). Haematoxylin and eosin (HE) were used to detect the degree of retinopathy. Oxidative stress levels were detected by ELISA. Perl's staining was used to detect iron deposition in retinal tissues. Ferritin levels were measured by ELISA. The expression of GPX4 was detected by immunohistochemistry (IHC). GSH/GSSG kit was used to detect the content and proportion of reduced/oxidized glutathione. Western blot was used to detect the expression of ferroptosis-related proteins. TUNEL assay was used to detect cell apoptosis. The expression of GSDMD was detected by fluorescence in situ hybridization (FISH). Western blot was used to detect the expression of apoptosis and pyroptosis-related proteins. Then, high glucose (HG)-induced retinal epithelial cell line ARPE-19 was treated by Erastin (ferroptosis activator) and Ferr-1. CCK-8, ELISA, western blot, flow cytometry, and immunofluorescence (IF) staining were used to detect oxidative stress levels, ferroptosis and cell damage. The mechanism was further explored by adding ferroptosis agonist Erastin. In vitro and in vivo results showed that oxidative stress was increased in DR model, resulting in ferroptosis and tissue or cell damage. After administration of Ferr-1, the antioxidant capacity was improved, ferroptosis levels were reduced and tissue or cell damage was alleviated. In vitro results showed that Ferr-1 reversed the impacts of Erastin on oxidative stress, ferroptosis, and cell damage in HG-induced ARPE-19 cells. Ferr-1 alleviated tissue and cell damage by improving the antioxidant capacity of the Xc - -GPX4 system., (© 2022. The Author(s).)

Objectives: To determine the diagnostic accuracy of ultrasound (US), CT and their combination in detecting cervical lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC)., Methods: Medline (via PubMed), Web of Science, Embase were searched to identify studies published till 5 December 2021 that used US and CT to detect CLNM in patients with PTC. The primary outcomes were sensitivity, specificity and diagnostic ORs in neck-level-based (lymph nodes are analysed by neck level) or patient-based (lymph nodes are analysed by patient) analysis. Secondary outcomes were sensitivity, specificity and DORs in the central and lateral compartments., Results: Fourteen studies (6167 patients with 11 601 neck lymph nodes) met the inclusion criteria. Based on the neck-level-based analysis, the pooled sensitivity, specificity and DORs were 0.35 (95% CI 0.34 to 0.37), 0.95 (95% CI 0.94 to 0.95) and 13.94 (95% CI 9.34 to 20.82) for US, were 0.46 (95% CI 0.44 to 0.47), 0.88 (95% CI 0.87 to 0.89) and 7.24 (95% CI 5.46 to 9.62) for CT, were 0.51 (95% CI 0.49 to 0.52), 0.85 (95% CI 0.84 to 0.86), 6.01 (95% CI 3.84 to 9.40) for the combination of US and CT. In the patient-based analysis, the pooled estimates of sensitivity, specificity and DOR were 0.41 (95% CI 0.36 to 0.46), 0.92 (95% CI 0.89 to 0.94) and 7.56 (95% CI 4.08 to 14.01) for US, were 0.49 (0.44 to 0.54), 0.91 (0.89 to 0.94), 9.40 (5.79 to 15.27) for CT, and were 0.64 (95% CI 0.57 to 0.71), 0.83 (95% CI 0.77 to 0.88), 8.59 (95% CI 5.37 to 13.76) for the combination of US and CT., Discussion: These findings suggest US, with a DOR almost twice that of CT in the neck-level-based analysis, was superior to CT in detecting CLNM in patients with PTC, especially in the lateral compartment. The combination of US and CT increased the sensitivity from 41%-49% for the individual modalities to 64% for combined modalities in the patient-based analysis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The effect of interventional time for 3% Diquafosol reatment in post-cataract surgery has not been well established. A meta-analysis was performed to evaluate the improvement of ocular surface condition in post-cataract surgery patients who received 3% DQS for various treatment durations., Methods: Studies were performed based on 5 databases: PubMed, Cochrane Library, Web of Science, Embase, and China National Knowledge Infrastructure. Data on changes in Schirmer's test, tear breakup time (TBUT), corneal staining score, and OSDI score were collected for meta-analysis., Results: A total of 621 affected eyes from 9 independent clinical studies were included. 6 studies conducted Schirmer's test after the application of 3% DQS. Meta-analysis showed that the difference between 3% DQS and control groups was not statistically significant for short-term application (less than or equal to 1 month) (WMD ​= ​0.14, P  ​= ​0.27, 95% CI:-0.11 to 0.39), but was statistically different for long-term application (longer than or equal to 3 months) (WMD ​= ​0.76, P  ​= ​0.03, 95% CI:0.08 to 1.45). For the corneal fluorescence staining score, the data from 6 studies indicated that the improvement was statistically significant for short-term application (WMD ​= ​-0.40, P <0.00001, 95% CI:-0.72 to -0.08) and but not long-term application (WMD ​= ​-0.21, P  ​= ​0.26, 95% CI:-0.57 to 0.15). For TBUT, the data from 9 studies indicated that both short-term and long-term application showed significant improvement (WMD ​= ​1.70, P <0.00001, 95% CI:1.38 to 2.03; WMD ​= ​1.52, P <0.00001, 95% CI:1.09 to 1.95). Similar results were observed in data from 5 studies with OSDI scores, where both short-term and long-term application showed statistically significant improvements (WMD ​= ​-5.41, P <0.00001, 95% CI: -7.02 to -3.81; WMD ​= ​-6.10, P <0.00001, 95% CI:-8.52 to -3.67)., Conclusions: The application of 3% DQS in post-operative cataract patients has a positive effect on improving the ocular surface conditions. Short-term application resulted in lower corneal staining scores, prolonged TBUT, and improved OSDI scores. Long-term application improved Schirmer's test results, TBUT, and subjective symptoms., Key Messages: The updated article suggests that 3% Diquafosol is less effective in the short term after cataract surgery, and that application over three months can improve the patient's ocular surface condition., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc. on behalf of Zhejiang University Press.)

Background: The aim of this study was to identify the increased value of integrating computed tomography (CT) radiomics analysis with the radiologists' diagnosis and clinical factors to preoperatively diagnose cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) patients., Methods: A total of 178 PTC patients were randomly divided into a training ( n = 125) and a test cohort ( n = 53) with a 7:3 ratio. A total of 2553 radiomic features were extracted from noncontrast, arterial contrast-enhanced and venous contrast-enhanced CT images of each patient. Principal component analysis (PCA) and Pearson's correlation coefficient (PCC) were used for feature selection. Logistic regression was employed to build clinical-radiological, radiomics and combined models. A nomogram was developed by combining the radiomics features, CT-reported lymph node status and clinical factors., Results: The radiomics model showed a predictive performance similar to that of the clinical-radiological model, with similar areas under the curve (AUC) and accuracy (ACC). The combined model showed an optimal predictive performance in both the training (AUC, 0.868; ACC, 86.83%) and test cohorts (AUC, 0.878; ACC, 83.02%). Decision curve analysis demonstrated that the combined model has good clinical application value., Conclusions: Embedding CT radiomics into the clinical diagnostic process improved the diagnostic accuracy. The developed nomogram provides a potential noninvasive tool for LNM evaluation in PTC patients.

Objective: To evaluate 18 F-fluorodeoxyglucose positron emission tomography ( 18 FDG PET) and clinical parameters to differentiate rheumatoid arthritis (RA) and polymyalgia rheumatic (PMR). Patients and Methods . This retrospective study evaluated 54 patients with suspected RA ( n  = 23) and PMR ( n  = 31) who underwent 18 F-FDG PET/CT before treatment. The complete diagnosis was based on each classification criterion and at least followed up for 6 months. Demographic and clinical data were also collected. Semiquantitative analysis (maximum standardized uptake value, SUVmax) of abnormal 18 F-FDG uptake was undertaken at 17 musculoskeletal sites, and two scoring systems (mean reference (liver/control) scores) were evaluated. The differential diagnostic efficacy of each independent parameter was evaluated using the receiver operating characteristic (ROC) curve. Integrated discriminatory improvement (IDI) and bootstrap tests were used to evaluate the improvement in diagnostic efficacy using a combination of multiple parameters., Results: The ROC curve analysis of SUVmax indicated that the interspinous ligament showed the highest discriminative diagnostic value (sensitivity, 64.5%; specificity, 78.3%; area under the curve (AUC), 0.764; positive predictive value, 0.800; negative predictive value, 0.621). The combined model with the rheumatoid factor (RF) and metabolic parameters of 18 F-FDG PET resulted in the highest AUC of 0.892 and showed significant reclassification by IDI (IDI, 9.51%; 95% confidence interval: 0.021-0.175; P  = 0.013). According to the bootstrap test, compared with RF alone, the combination of RF and metabolic parameters showed an improvement in ROC and was statistically significant ( P  = 0.017)., Conclusions: The combination of 18 F-FDG PET metabolic and clinical parameters can further improve the differential diagnosis of RA and PMR., Competing Interests: Yanmei Wang was employed by GE Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2022 Guanyun Wang et al.)

Genetic mutations in HSF4 cause congenital cataracts. HSF4 exhibits both positive and negative regulation on the transcription of heat shock and non-heat shock proteins during lens development, and its activity is regulated by posttranslational modifications. Biotin is an essential vitamin that regulates gene expression through protein biotinylation. In this paper, we report that HSF4b is negatively regulated by biotinylation. Administration of biotin or ectopic bacterial biotin ligase BirA increases HSF4b biotinylation at its C-terminal amino acids from 196 to 493. This attenuates the HSF4b-controlled expression of αB-crystallin in both lens epithelial cells and tested HEK293T cells. HSF4b interacts with holocarboxylase synthetase (HCS), a ubiquitous enzyme for catalyzing protein biotinylation in mammal. Ectopic HA-HCS expression downregulates HSF4b-controlled αB-crystallin expression. Lysine-mutation analyses indicate that HSF4b/K444 is a potential biotinylation site. Mutation K444R reduces the co-precipitation of HSF4b by streptavidin beads and biotin-induced reduction of αB-crystallin expression. Mutations of other lysine residues such as K207R/K209R, K225R, K288R, K294R and K355R in HSF4's C-terminal region do not affect HSF4's expression level and the interaction with streptavidin, but they exhibit distinct regulation on αB-crystallin expression through different mechanisms. HSF4/K294R leads to upregulation of αB-crystallin expression, while mutations K207R/K209R, K225R, K288R, K255R and K435R attenuate HSF4's regulation on αB-crystallin expression. K207R/K209R blocks HSF4 nuclear translocation, and K345R causes HSF4 destabilization. Taken together, the data reveal that biotin maybe a novel factor in modulating HSF4 activity through biotinylation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Purpose: The purpose of this study was to explore the therapeutic role of heat shock protein 90 (Hsp90) in wound healing of injury cornea epithelium., Methods: The right eye of C57BL/6N male mice were performed the debridement wounds in the center of the cornea using an algerbrush II blade. The injured area was determined by staining the cornea with fluorescein sodium and measured with image-J. Immunoblotting, ELISA and immunochemistry were used for determining protein expression. The quantitation PCR was performed to measure mRNA expression., Results: Hsp90α is upregulated at both the mRNA and protein levels, and is secreted extracellularly into the corneal stroma and tear film during the healing process after corneal injury in mice. This upregulation is associated with activation of HSF1. Administration of recombinant exogenous Hsp90α (eHsp90α) speeds up wound healing of injured corneal epithelium. The eHsp90α binds to low-density lipoprotein (LDL)-related protein-1 (LRP-1) on the corneal epithelial cells and increases phosphorylation of AKT at S473, which is associated with proliferation and migration corneal epithelial cells in vitro or vivo. Inhibition of AKT by its inhibitor LY294002 abolishes eHsp90α-induced migration and proliferation of corneal epithelial cells., Conclusion: Hsp90α is upregulated and secreted after corneal injury and acts to promote the healing process. Recombinant Hsp90α may be a promising therapeutic drug candidate for corneal injury.

Skeletal myoblasts are activated satellite cells capable of proliferation and differentiation. Studies on mammalian myoblast differentiation and myogenesis could be carried out in vitro thanks to the availability of mouse myoblast cell line C2C12. Lacking of muscle cell line hinders the studies of teleost fish myogenesis. Here, we established a continuous skeletal muscle cell line from juvenile rockfish (Sebastes schlegelii) muscle using explant method and subcultured more than 50 passages for over 150 days. Stable expression of myoblast-specific marker, MyoD (myoblast determination protein) and the potential of differentiation into multi-nucleated skeletal myotubes upon induction suggested the cell line were predominately composed of myoblasts. Transcriptome analysis revealed a total of 4375 genes differentially expressed at four time points after the switch to differentiation medium, which were mainly involved in proliferation and differentiation of myoblasts. KIF22 (kinesin family member 22) and POLA1 (DNA polymerase alpha 1) were identified as the key genes involved in fish myoblast proliferation whereas MYL3 (myosin light chain 3) and TNNT2 (troponin T2) were determined as the crucial genes responsible for differentiation. In all, the continuous myoblasts cultured in this study provided a cell platform for future studies on marine fish myoblast differentiation and myogenesis. The molecular process of myoblast differentiation revealed in this study will open a window into the understanding of indeterminate muscle growth of large teleost., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Genetic mutations in heat shock factor 4 (Hsf4) is associated with both congenital and age-related cataracts. Hsf4 regulates lens development through its ability to both activate and inhibit transcription. Previous studies suggested Hsf4 is involved in modulating cellular senescence depending on p21 cip1 and p27 kip1 expression in MEF cells. Here, we found that Hsf4 acts as a suppressor of p21 cip1 expression and plays an anti-senescence role during lens development. Knocking out Hsf4 facilitated UVB-induced cellular senescence in mouse lens epithelial cells (mLECs). p21 cip1 was upregulated at both the mRNA and protein levels in HSF4 -/- mLECs under control and UVB-treated conditions, and knockdown of p21 cip1 by siRNA alleviated UVB-induced cellular senescence. HSF4 directly bound to the p21 cip1 promoter and increased H3K27m3 levels at the p21 cip1 proximal promoter region by recruiting the methyltransferase EZH2. In animal models, p21 cip1 was gradually upregulated in wild-type mouse lenses with increasing age, while Hsf4 levels decreased. We generated a Hsf4 mutant mice line (Hsf4 del-42 ) which displayed obvious congenital cataract phenotype. The expression of p21 cip1 and senescence-associated cytokines were induced in the cataractous lenses of Hsf4 del-42 mice. H3K27m3 and EZH2 levels decreased in p21 cip1 promoters in the lenses of Hsf4 del-42 mice. The SA-β-Gal activities were positive in lens epithelia of aged Hsf4 null zebrafish compared to wild-type lenses. p21 cip1 and senescence-associated cytokines levels were also upregulated in lenses of Hsf4 null zebrafish. Accordingly, we propose that HSF4 plays a protective role in lens epithelial cells against cellular senescence during lens development and aging, partly by fine-tuning p21 cip1 expression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We developed an effective nanoparticle-biomaterial in alleviating diabetic retinopathy (DR), hyaluronic acid (HA)-CeO₂, composed mainly of CeO₂ and HA. To demonstrate its anti-DR capacity, retinal cells from a B6/J mouse model were used to compare the efficiency of PEI-CeO₂ and HA-CeO₂. We investigated the transport performance, histolysis, immune cell infiltration, angiogenesis, and hyperemia induced by the transport system. The structural integrity, microvascular apoptosis, and superoxide and peroxide concentrations in the retina were measured to evaluate the clinical efficacy of CeO₂. The infiltration efficiency of HA-CeO₂ was higher than that of PEI-CeO₂. Lower levels of foreign body reaction were evident for HA-CeO₂ with less histolysis, immune cell infiltration, angiogenesis, and hyperemia. The clinical efficacy of HA-CeO₂ in terms of preservation of retinal structure and lowering of microvascular apoptosis and superoxide and peroxide concentrations was superior to those of PEI-CP. HA-CeO₂ was shown to have significant antioxidation and anti-vascular injury capacity in a mouse model, and may be a potential compound nanodrug for DR treatment in the future.

Parkinson's disease is a common chronic disease that affects a large number of people. In the real world, however, Parkinson's disease can result in a loss of physical performance, which is classified as a movement disorder by clinicians. Parkinson's disease is currently diagnosed primarily through clinical symptoms, which are highly dependent on clinician experience. As a result, there is a need for effective early detection methods. Traditional machine learning algorithms filter out many inherently relevant features in the process of dimensionality reduction and feature classification, lowering the classification model's performance. To solve this problem and ensure high correlation between features while reducing dimensionality to achieve the goal of improving classification performance, this paper proposes a recurrent neural network classification model based on self attention and motion perception. Using a combination of self-attention mechanism and recurrent neural network, as well as wearable inertial sensors, the model classifies and trains the five brain area features extracted from MRI and DTI images (cerebral gray matter, white matter, cerebrospinal fluid density, and so on). Clinical and exercise data can be combined to produce characteristic parameters that can be used to describe movement sluggishness. The experimental results show that the model proposed in this paper improves the recognition performance of Parkinson's disease, which is better than the compared methods by 2.45% to 12.07%., Competing Interests: All the authors do not have any possible conflicts of interest., (Copyright © 2021 Baojuan Ma et al.)

The senescence of retinal pigment epithelial (RPE) cells is associated with age-related macular degeneration (AMD), a leading cause of blindness in the world. HSP90 is a predominant chaperone that regulates cellular homeostasis under divergent physio-pathological conditions including senescence. However, the role of HSP90 in senescent RPE cells still remains unclear. Here, we reported that HSP90 acts as a senomorphic target of senescent RPE cells in vitro . Using H 2 O 2 -induced senescent ARPE-19 cells and replicative senescent primary RPE cells from rhesus monkey, we found that HSP90 upregulates the expression of IKKα, and HIF1α in senescent ARPE-19 cells and subsequently controls the induction of distinct senescence-associated inflammatory factors. Senescent ARPE-19 cells are more resistant to the cytotoxic HSP90 inhibitor IPI504 (IC50 = 36.78 μM) when compared to normal ARPE-19 cells (IC50 = 6.16 μM). Administration of IPI504 at 0.5-5 μM can significantly inhibit the induction of IL-1β, IL-6, IL-8, MCP-1 and VEGFA in senescent ARPE-19 and the senescence-mediated migration of retinal capillary endothelial cells in vitro . In addition, we found that inhibition of HSP90 by IPI504 reduces SA-β-Gal's protein expression and enzyme activity in a dose-dependent manner. HSP90 interacts with and regulates SA-β-Gal protein stabilization in senescent ARPE-19 cells. Taken together, these results suggest that HSP90 regulates the SASP and SA-β-Gal activity in senescent RPE cells through associating with distinctive mechanism including NF-κB, HIF1α and lysosomal SA-β-Gal. HSP90 inhibitors (e.g. IPI504) could be a promising senomorphic drug candidate for AMD intervention.

Sports injuries will have an impact on the consistency and systemicity of the training process, as well as athlete training and performance improvement. Many talented athletes have had their careers cut short due to sports injuries. Preventing sports injuries is the best way for basketball players to reduce sports injuries. Many coaches and athletes on sports teams, on the other hand, are unaware of the importance of sports injury prevention. They only realize that the body's sports functions are abnormal when it suffers from sports injuries. As a result, this paper proposes a gray theory neural network-based athlete injury prediction model. First, from the standpoint of a single model, the improved unequal interval model is used to predict sports injury by optimizing the unequal interval model in gray theory. The findings show that it is a good predictor of sports injuries, but it is a poor predictor of the average number of injuries. Following that, in order to overcome the shortcomings of a single model, a gray neural network combination model was used. A combination model of the unequal time interval model and BP neural network was determined and established. The prediction effect is significantly improved by combining the gray neural network mapping model and the coupling model to predict the two characteristics of sports injuries. Finally, simulation experiments show that the proposed method is effective., Competing Interests: All the authors do not have any possible conflicts of interest., (Copyright © 2021 Fengyan Zhang et al.)

Myosins are important eukaryotic motor proteins that bind actin and utilize the energy of ATP hydrolysis to perform a broad range of functions such as muscle contraction, cell migration, cytokinesis, and intracellular trafficking. However, the characterization and function of myosin is poorly studied in teleost fish. In this study, we identified 60 myosin family genes in a marine teleost, black rockfish ( Sebastes schlegelii ), and further characterized their expression patterns. myosin showed divergent expression patterns in adult tissues, indicating they are involved in different types and compositions of muscle fibers. Among 12 subfamilies, S. schlegelii myo2 subfamily was significantly expanded, which was driven by tandem duplication events. The up-regulation of five representative genes of myo2 in the skeletal muscle during fast-growth stages of juvenile and adult S. schlegelii revealed their active role in skeletal muscle fiber synthesis. Moreover, the expression regulation of myosin during the process of myoblast differentiation in vitro suggested that they contribute to skeletal muscle growth by involvement of both myoblast proliferation and differentiation. Taken together, our work characterized myosin genes systemically and demonstrated their diverse functions in a marine teleost species. This lays foundation for the further studies of muscle growth regulation and molecular mechanisms of indeterminate skeletal muscle growth of large teleost fishes.

Objective: Numerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia., Methods: We compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson's correlation revealed the relationship among total score of DM and clinical and neuropsychological data., Results: Compared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study., Conclusions: Our findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.

Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1 + macrophages/microglia and CD4 + T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs). Moreover, MAT treatment promoted Akt phosphorylation and shifted the Bcl-2/Bax ratio back towards an antiapoptotic one, which could be a mechanism for its therapeutic effect in the ON model. Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.

The accessibility of urban fire services is a critical indicator in evaluating fire services and optimizing fire resource allocation. However, previous studies have mainly concentrated on measuring the spatial accessibility of fire services, and little, if any, consideration has been paid to exploring the spatiotemporal dynamics of the accessibility of urban fire services. Therefore, we used real-time travel time to extend an existing spatial accessibility method to measure the spatiotemporal accessibility of fire services in a case study of Nanjing, China. The results show that (1) the overall accessibility of fire incidents and fire stations in Nanjing, China, is uneven, with relatively high accessibility in the southwest and northeast of the city center; (2) the number of fire incidents with low-level accessibility apparently increases in rush hours (i.e., 07:00-09:00 and 17:00-19:00 h) in the southeast and north of the city center, and the fire incidents with medium-level and high-level accessibility easily change to lower levels under the influence of traffic congestion, with fire incidents with medium-level accessibility being affected the most; (3) the accessibility of fire stations changes over time with an obvious W pattern, with lower accessibility during rush hours than at other times, and several fire stations in the city center present an asymmetric W pattern; (4) the accessibility decline ratio for fire stations in rush hours is greater in the city center than in urban suburbs, and the decline ratios are strongly related to the travel time increase and the percent increase in uncovered fire incidents during rush hours. The results and findings demonstrate that our method can be used to explore the spatiotemporal dynamics of the accessibility of fire services, and so can guide policymakers in improving fire services.

Background/objective: Although lots of long non-coding RNAs (lncRNAs) have been demonstrated to be involved in carcinogenesis, the functions of numerous of lncRNAs remain unknown. Bioinformatics online database showed that lncRNA LOC100132707 was highly expressed in metastatic melanoma tissues, and its expression predicted a lower overall survival rate in melanoma patients. However, LOC100132707 function in uveal melanoma (UM) progression still remains unclear. In the present study, we aimed to elucidate the role and molecular mechanisms underlying LOC100132707 in UM., Methods: RT-PCR was used to detect the levels of LOC100132707 in UM cells. Cell migration, invasion and tumorigenesis were tested by using the transwell chamber assay and in vivo assay., Results: LOC100132707 expression in metastatic UM cell line MM28 was significantly higher than that of the non-metastatic UM cell lines, MP38, MP46 and MP65, as well as the expressions of LOC100132707-related genes, including XRN1, PARP14, JAK2, DDX60, BUB1 and SAMD9L. LOC100132707 downregulation significantly repressed cell migration and invasion abilities, whereas overexpressing JAK2 rescued these effects. Consistently, upregulation of LOC100132707 induced significant increases in cell migration and invasion abilities via upregulating JAK2. In addition, silencing of LOC100132707 significantly repressed the in vivo tumor formation ability in UM cells., Conclusion: This study reveals that silence of LOC100132707 represses the migration of UM via downregulating JAK2. The LOC100132707/JAK2 axis might serve as a potent target for the prevention and treatment of UM metastasis., Competing Interests: The authors declare that they have no conflicts of interest., (© 2020 Qi et al.)

Diabetic retinopathy (DR) is the leading cause of decreased vision and blindness globally. The aim of this study was to understand the role of physcion 8-O-β-glucopyranoside (PG) in high glucose (HG)-induced DR and to investigate whether lncRNA NORAD/miR-125/STAT3 signalling was the underlying mechanism involved in DR. To this end, the serum levels of NORAD, miR-125, and STAT3 were determined in patients with DR. The APRE-19 cells were subjected to HG treatment to construct the cell model of DR. HG-disposed APRE-19 cell injury was assessed by detecting cell viability, apoptosis, concentrations of pro-inflammatory cytokines including TNF-α and IL-1β, and ROS generation. Moreover, the effect of PG on HG-disposed APRE-19 cell injury was investigated. NORAD was then overexpressed to investigate the combined effects of NORAD overexpression and PG on HG-disposed APRE-19 cell injury. Furthermore, the regulatory relationship between NORAD and miR-125 as well as miR-125 and STAT3 was investigated. The expression levels of NORAD and STAT3 were significantly increased in the serum of DR patients, while the miR-125 expression was decreased. The HG treatment-induced injury to APRE-19 cells, which were alleviated by PG treatment. Moreover, PG alleviated HG-disposed injury to ARPE-19 cells by decreasing NORAD. NORAD negatively regulated miR-125 expression and the combined effects of NORAD and PG on HG-disposed ARPE-19 cell injury were reversed by miR-125 overexpression. Furthermore, STAT3 was confirmed as a target gene of miR-125. Our results show that PG exerts protective roles in HG-disposed DR via regulating lncRNA NORAD/miR-125/STAT3 signalling. NORAD/miR-125/STAT3 axis may provide a novel perspective for target therapy of DR.

Objective: Human uveal melanoma (UM) is a common ocular malignant tumor with a high risk of metastasis. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are correlated with the development of UM. Here, we aimed to determine the biological significance of lncRNA growth arrest-specific transcript 5 (GAS5) in UM., Methods: The expression levels of GAS5 and microRNA-21 (miR-21) in UM tissues and cells were detected by qRT-PCR analysis. CCK-8 assay was performed to investigate the viability of UM cells after cell transfections, and the migration and invasion of UM cells were determined by transwell assay. The protein expression levels were detected by Western blot assay. The relationship between miR-21 and GAS5 in UM cells was confirmed by bioinformatics prediction and luciferase report assay., Results: Our experiments demonstrated that GAS5 was markedly downregulated in UM cells and clinical specimens. Overexpression of GAS5 inhibited, whereas knockdown of GAS5 promoted the viability, migration, and invasion of UM cells. The epithelial-to-mesenchymal transition (EMT) process of UM cells was also suppressed by upregulating of GAS5 and enhanced by downregulating of GAS5. Additionally, as a competitive endogenous RNA (ceRNA), GAS5 directly binded to the oncogenic miR-21 in UM cells, and overexpression of miR-21 attenuated the EMT-suppressing effect of GAS5., Conclusion: Taken together, our findings suggest that GAS5/miR-21 axis is implicated in the pathogenesis of UM and might serve as a potential therapeutic target., Competing Interests: The authors report no funding and no conflicts of interest for this work., (© 2020 Qi et al.)

The present work has investigated the value of computed tomography (CT) features in the diagnosis of papillary thyroid tumors in the incidental thyroid nodules (ITNs). In the 82 enrolled patients, 101 thyroid nodules were incidentally found by the neck CT scanning, among which 49 were histologically confirmed to be papillary thyroid carcinoma (PTC) while the other 52 were nodular goiter (NG). The tumor location, size, shape, tiny calcification, cystic change, and signs of an irregular ring, marginal defects, and enhanced blurring were all depicted by CT features. Both univariate and multivariate analyses were employed to identify independent predictors of PTC. The univariate analysis of PTC and NG showed that four CT features were statistically significant, including tiny calcification and signs of an irregular ring, marginal defects, and enhanced blurring. Furthermore, the multivariate logistic regression model indicated that signs of an irregular ring, marginal defects, and enhanced blurring were strongly correlated with PTC, of which the odds ratio (OR) was 27.374 (95% CI: 5.871∼127.636), 28.587 (95% CI: 4.139∼197.460), and 4.315 (95% CI: 0.858∼21.694), respectively. In the predictive model of PTC, the value of sensitivity, specificity, accuracy, and Youden index was 87.8%, 94.2%, 91.1%, and 0.82 with a likelihood ratio of 15.1. Therefore, the signs of an irregular ring, marginal defects, and enhanced blurring may be helpful in the diagnosis of PTC in incidentally found thyroid nodules., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Fengyan Zhang et al.)

Diabetic retinopathy (DR) is progressive damage to the retina and it's caused by damage to the blood-retinal barrier. Quercetin has pleiotropic action like anti-oxidant, regulation cell cycle &vascular integrity, and preventive effect of neuroinflammation. The present study is designed to investigate the nano-formulation of quercetin (NQ) in a zebrafish model of DR. The DR was developed by a single intraperitoneal injection of streptozotocin (STZ; 350 mg/kg). The acceleration of retinopathy was made on 7 days of diabetic zebrafish by intravitreal injection of STZ (20 μL of 7 % w/v of STZ stock solution). The treatment of NQ (5 and 10 mg/kg; i.p.) was administered for 21 consecutive days. The reference control i.e., dexamethasone (DEX, 10 mg/kg; i.p.) was also administered for 21 consecutive days. The sign of DR was assessed by eyeball/body weight ratio, eyeball weight, optomotor response (OMR), startle response (SR), phototactic response (PTR), and escape response (ER). Furthermore, the biochemical changes like plasma glucose and homocysteine (HCY) levels; and eye retinal tissue lipid peroxidation, reduced glutathione (GSH), and arginase reductase (AR) activity levels were assessed. The NQ found to attenuate the effect of STZ induced DR along with the regulation of biochemical abnormalities. And, it also comparable with reference drug treatment i.e., DEX treated group. Hence, NQ can be used for the treatment of diabetic associated retinopathy and neurosensory disorder visits anti-hyperglycemic, regulation of homocysteine pathway, reduction of lipid peroxidation, and free radical scavenging actions., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Over the years, microRNA-20b-3p (miR-20b-3p) has been found to play an essential role in human diseases; we aimed to investigate the effect of miR-20b-3p on the progression of diabetic retinopathy (DR). The DR rat models were established by streptozotocin injection and treated with miR-20b-3p mimics, silenced, or overexpressed thioredoxin-interacting protein (TXNIP). Afterward, the expression of miR-20b-3p and TXNIP, visual function, inflammatory factors, microvascular injury, vascular permeability, cell apoptosis, and angiogenesis in rats' retinal tissues were assessed. The target relation between miR-20b-3p and TXNIP was confirmed by dual luciferase reporter gene assay. MiR-20b-3p was poorly expressed while TXNIP was highly expressed in DR rats' retinal tissues. Elevated miR-20b-3p and inhibited TXNIP promoted the visual function, and restricted the inflammatory reaction, microvascular injury, vascular permeability, cell apoptosis, and angiogenesis in DR rats, thereby decelerating the development of DR. Furthermore, TXNIP was targeted by miR-20b-3p. We have found in this study that elevated miR-20b-3p could repress the levels of inflammatory factors by inhibiting TXNIP, thus attenuating the pathology of retina in DR rats, which provided new candidates for DR treatment., (© 2020 International Union of Biochemistry and Molecular Biology.)

Purpose: To determine the effect of decorin on oxidative stress and apoptosis of human lens epithelial (HLE) cells under high glucose condition., Methods: HLE cell line (HLEB3) was incubated in normal glucose (5.5 mM) or high glucose (60 mM) medium. Decorin (50 nM) was applied 2 hours before high glucose medium was added. Apoptosis detection was executed by flow cytometry and western blotting (analysis of bcl-2 and bax). Oxidative stress level was measured by the generation of reactive oxygen species (ROS), glutathione peroxidase (GSH) and superoxide dismutase (SOD). P38 mitogen-activated protein kinase (MAPK) phosphorylation, the expression of p22phox of HLE cells and human lens anterior capsules were detected by western blotting. Small interfering RNA transfection to p22phox and p38 MAPK was also carried out on HLEB3., Results: High glucose caused HLE cells oxidative stress and apoptosis exhibiting the increase of apoptotic cells and ROS production and decrease of bcl-2/bax ratio, GSH/GSSG ration and SOD activity. P22phox and phospho-p38 MAPK were upregulated in high glucose treated HLEB3 cells. Knocking down p22phox or p38 by siRNAs can reduce high glucose induced cell apoptosis and oxidative stress level. Silencing p22phox by siRNA can downregulate the phosphorylation of p38 MAPK. Decorin can inhibit the apoptosis, oxidative stress level and the induction of p22phox and phospho-p38 of HLEB3 induced by high glucose. Furthermore, the expression of p22phox and p38 were found significantly increased in lens anterior capsules of diabetic cataract patients compared to that of normal age-related cataract patients., Conclusions: Results showed that p22phox-p38 pathway may be participated in high glucose induced lens epithelial cell injury, decorin may inhibit the high glucose induced apoptosis and oxidative stress injury by suppressing this pathway in part., Competing Interests: The authors have declared that no competing interests exist.

The accurate role of ANRIL in cataract is poorly understood. We aimed to reveal the effects of ANRIL on H 2 O 2 -treated HLECs, SRA01/04, as well as the regulatory mechanisms. Oxidative stress model of HLECs was induced by H 2 O 2 . Cell injury was evaluated according to cell proliferation, apoptosis and DNA damage using CCK-8 assay/flow cytometry and TUNEL assays/γH2AX staining. Expressions of ANRIL and miR-21 in HLECs were determined by RT-qPCR. The effects of miR-21, miR-34a and miR-122-5p inhibition as well as AMPK and β-catenin on HLECs with ANRIL overexpression and H 2 O 2 stimulation were analyzed. In vivo experiment was performed via RT-qPCR. H 2 O 2 repressed proliferation and induced apoptosis or DNA damage in HLECs. Those alterations induced by H 2 O 2 were attenuated by ANRIL overexpression. MiR-21 was positively regulated by ANRIL, and both of them were repressed in H 2 O 2 -induced HLECs and cataract patient tissues. Inhibition of miR-21 but not miR-34a or miR-122-5p reversed the effects of ANRIL on H 2 O 2 -treated HLECs. Phosphorylation of AMPK and expression of β-catenin were increased by ANRIL via regulating miR-21. AMPK and β-catenin affected beneficial function of ANRIL-miR-21 axis.Therefore, lncRNA ANRIL attenuated H 2 O 2 -induced cell injury in HELCs via up-regulating miR-21 via the activation of AMPK and β-catenin.

Background: Germline mutations in heat shock factor 4 (HSF4) cause congenital cataracts. Previously, we have shown that HSF4 is involved in regulating lysosomal pH in mouse lens epithelial cell in vitro. However, the underlying mechanism remains unclear., Methods: HSF4-deficient mouse lens epithelial cell lines and zebrafish were used in this study. Immunoblotting and quantitative RT-PCR were used for expression analysis. The protein-protein interactions were tested with GST-pull downs. The lysosomes were fractioned by ultracentrifugation., Results: HSF4 deficiency or knock down of αB-crystallin elevates lysosomal pH and increases the ubiquitination and degradation of ATP6V1A by the proteasome. αB-crystallin localizes partially in the lysosome and interacts solely with the ATP6V1A protein of the V1 complex of V-ATPase. Furthermore, αB-crystallin can co-precipitate with mTORC1 and ATP6V1A in GST pull down assays. Inhibition of mTORC1 by rapamycin or siRNA can lead to dissociation of αB-crystallin from the ATP6V1A and mTORC1complex, shortening the half-life of ATP6V1A and increasing the lysosomal pH. Mutation of ATP6V1A/S441A (the predicted mTOR phosphorylation site) reduces its association with αB-crystallin. In the zebrafish model, HSF4 deficiency reduces αB-crystallin expression and elevates the lysosomal pH in lens tissues., Conclusion: HSF4 regulates lysosomal acidification by controlling the association of αB-crystallin with ATP6V1A and mTOR and regulating ATP6V1A protein stabilization., General Significance: This study uncovers a novel function of αB-crystallin, demonstrating that αB-crystallin can regulate lysosomal ATP6V1A protein stabilization by complexing to ATP6V1A and mTOR. This highlights a novel mechanism by which HSF4 regulates the proteolytic process of organelles during lens development., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To identify multidetector computed tomography (MDCT) findings of surgically confirmed adhesive internal hernias (IHs)., Methods: Two gastrointestinal radiologists performed blinded, independent, and retrospective reviews of MDCT findings from a consecutive cohort of 35 adhesive IH and 41 adhesive small-bowel obstruction cases that had undergone surgery within 48 hours after MDCT. Univariate statistical analyses were performed to assess CT signs of adhesive IHs and CT findings of intestinal necrosis in patients presenting with adhesive IHs., Results: Dislocated cluster of the intestine (P = 0.005), 2 transitional zones (P = 0.002), and presence of fat in the center sign (P = 0.001) were key CT outcomes that were significantly associated with adhesive IHs. Additionally, intramural hemorrhage was found the MDCT feature indicative of intestinal necrosis (P = 0.028)., Conclusions: This study illustrates specific MDCT findings of IHs, and these observations may help guide early clinical management of the condition.

Retinoblastoma (RB) is the most common intraocular malignancy in infants and children. S-phase kinase-associated protein 2 (SKP2) has been unmasked as an oncogene in a great many of carcinomas. The biologic function and the detailed molecular mechanism of SKP2 in RB need to be better understood. In this study, real-time quantitative polymerase chain reaction and Western blot showed the ectopic expression of SKP2 in RB tissues and cell lines. Loss of function assays showed the attenuated cell proliferation in RB as a result of SKP2 knockdown. In addition, bioinformatics analysis predicted the interaction between SKP2 and miR-422a. Luciferase reporter assay and Pearson's correlation analysis validated the negative correlation between miR-422a and SKP2. MiR-422a overexpression led to a decline of SKP2 expression and cell growth in RB. The binding capacity between miR-422a and circ&#95;ODC1 was also predicted by bioinformatics analysis. Pearson's correlation analysis and luciferase reporter assay confirmed that circ&#95;ODC1 is negatively correlated with miR-422a. Silencing circ&#95;ODC1 resulted in a rise in miR-422a expression and RB cell growth. Moreover, reduced cell growth was restored by SKP2 overexpression. In a word, SKP2, induced by circ&#95;ODC1 and miR-422a, promotes RB proliferation. Our new findings in this research might expedite the discovery of novel prognostic markers and therapeutic targets of RB., (© 2019 Wiley Periodicals, Inc.)

Posterior capsule opacification (PCO) is a common complication of cataract surgery, resulting from a combination of proliferation, migration, epithelial-mesenchymal transition (EMT) of residual capsular epithelial cells and fibrosis of myofibroblasts. HSP90 is known to regulate the proteostasis of cells under pathophysiological conditions. The role of HSP90 in PCO formation, however, is not clear. To do this, the lens epithelial cell lines and an ex vivo cultured rat capsular bag model were used to study the role of HSP90 in PCO formation. The expression of protein and mRNA was measured by immunoblotting and quantitative RT-PCR, and cell apoptosis was measured by TUNEL(TdT-mediated dUTP nick-end labeling). The cell proliferation was measured by cell viability assays. The results showed that 17-AAG (Tanespimycin), an inhibitor of HSP90, suppresses the proliferation of immortalized lens epithelial cell lines HLE-B3, SRA01/04, and mLEC, with IC 50 values of 0.27, 0.27, and 0.49 μM, respectively. In an ex vivo cultured rat capsular model, the capsular residual epithelial cells resisted the stress of the capsulorhexis surgery and took 3-6 days to completely overlay the capsular posterior wall. During this process, heat shock factor 1 and its downstream targets HSP90, HSP25, αB-crystallin, and HSP40 were upregulated. Treatment with 17-AAG inhibited the viability of capsular residual epithelial cells and induced the cells apoptosis, characterized by increases in ROS levels, apoptotic DNA injury, and the activation of caspases 9 and 3. HSP90 participated in regulating both EGF receptor (EGFR) and TGF receptor (TGFR) signaling pathways. HSP90 was found to interact with the EGFR, such that inhibition of HSP90 by 17-AAG destabilized the EGFR protein and suppressed p-ERK1/2 and p-AKT levels. 17-AAG also inhibited the TGF-β-induced phosphorylation of SMAD2/3 and ERK1/2 and the decrease in E-cadherin and ZO-1 expression. Accordingly, these data suggest that the induction of HSP90 protects capsular residual epithelial cells against capsulorhexis-induced stress and participates in regulating the processes of proliferation, EMT and migration of rat capsular residual epithelial cells, at least partly, through the EGFR and TGFR signaling pathways. Treatment with 17-AAG suppresses PCO formation and is therefore a potential therapeutic candidate for PCO prevention., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aberrant expression of microRNAs plays an important role in the pathogenesis and progression of retinoblastoma. MiR-25, a member of the miR-106b˜25 cluster, has been reported to be abnormally expressed in retinoblastoma, but the exact role of it remains unclear. In our study, we found that miR-25-3p was upregulated in retinoblastoma tissues and cell lines. Enforced expression of miR-25-3p in retinoblastoma cell line WERI-RB-1 increased cell growth, colony formation, anchorage-independent growth, cell migration and invasion in vitro and tumor xenograft growth in vivo. In contrast, inhibited miR-25-3p expression in retinoblastoma cell line Y79 suppressed cell growth, colony formation, anchorage-independent growth, cell migration and invasion. Through luciferase reporter assay, we found that phosphatase and tensin homolog (PTEN) was a direct target of miR-25-3p. This was verified by western blot that miR-25-3p overexpression suppressed PTEN and activated Akt signaling. In addition, miR-25-3p was found to promote epithelial-mesenchymal transition (EMT) of WERI-RB-1 cells through PTEN/Akt pathway. Western blot analysis revealed that miR-25-3p overexpression increased Vimentin and Snail expression, and suppressed E-cadherin expression, but this could be reversed by restoring PTEN. Moreover, LY294002 treatment or restoring PTEN expression abolished the effects of miR-25-3p on cell invasion, colony formation and anchorage-independent growth in vitro and tumor xenograft growth in vivo. Taken together, our results suggested that miR-25-3p promotes malignant transformation of retinoblastoma cells by suppressing PTEN., (Copyright © 2019. Published by Elsevier Masson SAS.)

Purpose : Previous studies have revealed that microRNA-665 (miR-665) is dysregulated in a variety of human cancers. However, little is known regarding its expression profiles and functions in retinoblastoma (RB). Therefore, the aims of our study were to evaluate miR-665 expression in RB and determine the precise roles of miR-665 in the progression of RB. Patients and methods : Herein, RT-qPCR was used to determine miR-665 expression levels in RB tissues and cell lines, and a series of functional experiments were performed to explore the influence of miR-665 on RB cell proliferation, colony formation, apoptosis, migration, and invasion as well as tumor growth. The molecular mechanisms underlying the tumor-suppressive action of miR-665 in RB were also explored. Results : We found that miR-665 was markedly reduced in RB tissues and cell lines and that lower miR-665 expression was strongly associated with tumor size, TNM stage, and differentiation in patients with RB. Exogenous expression of miR-665 suppressed cell proliferation, colony formation, migration, and invasion, and induced cell apoptosis in RB cells, while silencing miR-665 expression had the opposite effects. In addition, upregulation of miR-665 decreased the tumor growth of RB cells in vivo. High-mobility group box 1 ( HMGB1 ) was identified as a direct target of miR-665 in RB cells, and decreasing the expression of HMGB1 simulated the regulatory effects of miR-665 overexpression in RB cells, while knockdown of HMGB1 expression counteracted the miR-665-mediated antitumor effects in RB cells. Moreover, miR-665 was shown to regulate the Wnt/β-catenin signaling pathway by targeting HMGB1 in vitro and in vivo. Conclusion : Taken together, our in vitro and in vivo results suggest that miR-665 acts as a tumor-suppressive miRNA in RB by directly targeting HMGB1 and inactivating the Wnt/β-catenin pathway. Hence, this miRNA is a candidate prognostic biomarker and therapeutic target in patients with RB., Competing Interests: The authors report no conflicts of interest for this work.

Corneal neovascularization (CRNV) is a prevalence eye disorder that affects the transparency and refraction properties of eyes. To explore the correlation between the level of Angiotensin II (Ang II) and corneal angiogenesis, the rat model of CRNV was established using alkali-burn, while the human umbilical vein endothelial cells (HUVECs) were stimulated using VEGF to induce the CRNV cells in vitro. RNA immunoprecipitation (RIP) and RNA pull-down were performed to validate the relationship between MIAT and miR-1246. The expression of MIAT and Ang II was increased, while miR-1246 was decreased in CRNV rat model. VEGF stimulation significantly promoted cell proliferation and migration of HUVECs, knockdown of MIAT dramatically reversed the effects of VEGF, while cells co-transfected with miR-1246 inhibitor obviously abolished the effect of VEGF+si-MIAT, however, enalaprilat abolished the effects of VEGF+si-MIAT+miR-1246 inhibitor. MIAT directly regulated the expression of miR-1246. In conclusion, VEGF stimulation promoted cell proliferation and migration of HUVECs mainly through regulating MIAT/miR-1246/ACE.

Dysfunction of HSF4 is associated with congenital cataracts. HSF4 transcription activity is turned on and regulated by phosphorylation during early postnatal lens development. Our previous data suggested that mutation HSF4b/S299A can upregulate HSF4 transcription activity in vitro, but the biological significance of posttranslational modification on HSF4/S299 during lens development remains unclear. Here, we found that the mutation HSF4/S299A can upregulate the expression of HSP25 and alpha B-crystallin at both protein and mRNA levels in mouse the lens epithelial cell line, but HSF4/S299D does not. Using the rabbit polyclonal antibody against phospho-S299 of HSF4, we found that EGF and ectopic expression of MEK1 can increase the phosphorylation of HSF4/S299 and induce HSF4 sumoylation, and these effects are inhibited by U0126. ERK1/2 can phosphorylate the S299 in HSF4/wt but not in HSF4/S299A in the in vitro kinase assay. Functionally, ectopic MEK1 can inhibit HSF4-controled alpha B-crystallin expression but has less effect on HSF4/S299A. EGF can upregulate phospho-HSF4/S299 and downregulate alpha B-crystallin expression in P3 mouse lens, and this downregulation is suppressed by U0126. During mouse lens development, phosphorylation of HSF4/S299 is downregulated in P3 lens and upregulated in P7 and P14 lens. However, in 2 months old lens, both phosphorylation of HSF4/S299 and total HSF4 protein are decreased. Interestingly, ERK1/2 activity is lower in P3 lens than in P7 and P14 lens, which is in line with the phosphorylation of HSF4/S299. Taken together, our data demonstrate that HSF4/299 is a phosphorylation target of MEK1-ERK1/2, and phosphorylation of S299 is responsible for tuning down HSF4 transcription activity during postnatal lens development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A method for the determination of the content of olive oil in olive blend oil by headspace gas chromatography-mass spectrometry (SH-GC/MS) was established. The amount of the sample, the heating temperature, the heating time, the amount of injection, the injection mode and the chromatographic column were optimized. The characteristic compounds of olive oil were found by chemometric method. A sample of 1.0 g was placed in a 20 mL headspace flask, and heated at 180℃ for 2700 s. Then, 1.0 mL headspace gas was taken into the instrument. An HP-88 chromatographic column was used for the separation and the analysis was performed by GC/MS. The results showed that the linear range was 0-100%(olive oil content). The linear correlation coefficient ( r 2 ) was more than 0.995, and the limits of detection were 1.26%-2.13%. The deviations of olive oil contents in the olive blend oil were from -0.65% to 1.02%, with the relative deviations from -1.3% to 6.8% and the relative standard deviations from 1.18% to 4.26% ( n =6). The method is simple, rapid, environment friendly, sensitive and accurate. It is suitable for the determination of the content of olive oil in olive blend oil.

Interfacial materials play a critical role in photoelectric conversion properties as well as the anomalous hysteresis phenomenon of the perovskite solar cells (PSCs). In this article, a water-soluble polythiophene PTEBS was employed as a cathode interfacial material for PSCs. Efficient energy level aligning and improved film morphology were obtained due to an ultrathin coating of PTEBS. Better ohmic contact between the perovskite layer and the cathode also benefits the charge transport and extraction of the device. Moreover, less charge accumulation at the interface weakens the polarization of the perovskite resulting in a relatively quick response of the modified device. The ITO/PTEBS/CH 3 NH 3 PbI 3 /spiro-MeOTAD/Au cells by an all low-temperature process achieved power conversion efficiencies of up to 15.4% without apparent hysteresis effect. Consequently, the utilization of this water-soluble polythiophene is a practical approach for the fabrication of highly efficient, large-area, and low-cost PSCs and compatible with low-temperature solution process, roll-to-roll manufacture, and flexible application.