Effect of 0.01% atropine combined with orthokeratology lens on axial elongation: a 2-year randomized, double-masked, placebo-controlled, cross-over trial.

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.

The generation and characterization of a transgenic zebrafish line with lens-specific Cre expression.

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.

Semen promotes oocyte development in Sebastesschlegelii elucidating ovarian development dynamics in live-bearing fish.

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.

Improvement of transpiration estimation based on a two-leaf conductance-photosynthesis model with seasonal parameters for temperate deciduous forests.

Introduction: Conductance-photosynthesis (Gs-A) models, accompanying with light use efficiency (LUE) models for calculating carbon assimilation, are widely used for estimating canopy stomatal conductance (Gs) and transpiration (Tc) under the two-leaf (TL) scheme. However, the key parameters of photosynthetic rate sensitivity (gsu and gsh) and maximum LUE (ϵmsu and ϵmsh) are typically set to temporally constant values for sunlit and shaded leaves, respectively. This may result in Tc 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 Tc 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 ϵmsu across the sites, with the highest value during the summer and the lowest during the spring. A similar pattern was found for gsu and gsh, 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 Tc 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.

Prevention of myopia shift and myopia onset using 0.01% atropine in premyopic children - a prospective, randomized, double-masked, and crossover trial.

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 (pSER = 0.02, pAL < 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.

The downregulation of HSP90-controlled CRALBP expression is associated with age-related vision attenuation.

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 HSP90ß 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.

SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway.

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-ß-Gal positive ARPE-19 cells with high expression of P53 and P21, senescence-associated inflammatory factors (e.g., IL-1ß, 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.

Extracellular HSP90 promotes differentiation of lens epithelial cells to fiber cells by activating LRP1-YAP-PROX1 axis.

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, ß- 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.

Ferrostatin-1 alleviates tissue and cell damage in diabetic retinopathy by improving the antioxidant capacity of the Xc--GPX4 system.

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.

FOXO4 mediates resistance to oxidative stress in lens epithelial cells by modulating the TRIM25/Nrf2 signaling.

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. H2O2 treatment enhanced FOXO4 expression in HLEpiC cells. Short hairpin RNAs mediated FOXO4 silence aggravated H2O2-induced cell apoptosis. In addition, upon H2O2 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.

The toxicity mechanism of glabridin in prostate cancer cells is involved in reactive oxygen species-dependent PI3K/Akt pathway: Integrated utilization of bioinformatic analysis and in vitro test validation.

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.

Diagnostic accuracy of ultrasound, CT and their combination in detecting cervical lymph node metastasis in patients with papillary thyroid cancer: a systematic review and meta-analysis.

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.

The Combination of 18F-Fluorodeoxyglucose Positron Emission Tomography Metabolic and Clinical Parameters Can Effectively Distinguish Rheumatoid Arthritis and Polymyalgia Rheumatic.

Objective: To evaluate 18F-fluorodeoxyglucose positron emission tomography (18FDG 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 18F-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 18F-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 18F-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 18F-FDG PET metabolic and clinical parameters can further improve the differential diagnosis of RA and PMR.

Radiomics Profiling Identifies the Value of CT Features for the Preoperative Evaluation of Lymph Node Metastasis in Papillary Thyroid Carcinoma.

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.

Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation.

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.

The Therapeutic Roles of Recombinant Hsp90α on Cornea Epithelial Injury.

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.

The effect of 3% diquafosol on the improvement of ocular surface post cataract surgery: A meta-analysis for time of intervention.

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 â€‹= â€‹0.14, P â€‹= â€‹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 â€‹= â€‹0.76, P â€‹= â€‹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 â€‹= â€‹-0.40, P <0.00001, 95% CI:-0.72 to -0.08) and but not long-term application (WMD â€‹= â€‹-0.21, P â€‹= â€‹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 â€‹= â€‹1.70, P <0.00001, 95% CI:1.38 to 2.03; WMD â€‹= â€‹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 â€‹= â€‹-5.41, P <0.00001, 95% CI: -7.02 to -3.81; WMD â€‹= â€‹-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.

Construction of Hyaluronic Acid-CeO2 Conjugated Composite Nanoparticles and Their Activity Efficiency in Diabetic Retinopathy Alleviation.

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.

Self-Attention-Guided Recurrent Neural Network and Motion Perception for Intelligent Prediction of Chronic Diseases.

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%.