Recalled age of myopia onset may predict risk of high adult myopia in Chinese adults.

INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.

Unraveling the ecological mechanisms of Aluminum on microbial community succession in epiphytic biofilms on Vallisneria natans leaves: Novel insights from microbial interactions.

The extensive use of aluminum (Al) poses an escalating ecological risk to aquatic ecosystems. The epiphytic biofilm on submerged plant leaves plays a crucial role in the regulation nutrient cycling and energy flow within aquatic environments. Here, we conducted a mesocosm experiment aimed at elucidating the impact of different Al concentrations (0, 0.6, 1.2, 2.0 mg/L) on microbial communities in epiphytic biofilms on Vallisneria natans. At 1.2 mg/L, the highest biofilms thickness (101.94 µm) was observed. Al treatment at 2.0 mg/L significantly reduced bacterial diversity, while micro-eukaryotic diversity increased. Pseudomonadota and Bacteroidota decreased, whereas Cyanobacteriota increased at 1.2 mg/L and 2.0 mg/L. At 1.2 and 2.0 mg/L. Furthermore, Al at concentrations of 1.2 and 2.0 mg/L enhanced the bacterial network complexity, while micro-eukaryotic networks showed reduced complexity. An increase in positive correlations among microbial co-occurrence patterns from 49.51% (CK) to 57.05% (2.0 mg/L) was indicative of augmented microbial cooperation under Al stress. The shift in keystone taxa with increasing Al concentration pointed to alterations in the functional dynamics of microbial communities. Additionally, Al treatments induced antioxidant responses in V. natans, elevating leaf reactive oxygen species (ROS) content. This study highlights the critical need to control appropriate concentration Al concentrations to preserve microbial diversity, sustain ecological functions, and enhance lake remediation in aquatic ecosystems.

Revealing the response characteristics of periphyton biomass and community structure to sulfamethoxazole exposure in aquaculture water: The perspective of microbial network relationships.

The widespread application of sulfonamide antibiotics in aquaculture has raised concerns about their adverse environmental impacts. Periphyton plays a crucial role in the aquatic ecosystem. In this study, we examined sulfamethoxazole (SMX) effects on the community structure and interactions of periphyton in simulated aquaculture water. Our findings indicated that the total biomass of periphyton decreased, while the biomass of periphytic algae and the secretion of extracellular polymeric substances (EPS) increased at 0.7 × 10-3 mg/L. Under higher SMX concentrations (5 mg/L and 10 mg/L), periphyton growth was severely inhibited, the microbial community structure of periphyton were sharply altered, characterized by the cyanobacteria growth suppression and decrease in the diversity index of community. Furthermore, elevated SMX concentrations (5 mg/L and 10 mg/L) increased the ratio of negative relationships from 45.4% to 49.4%, which suggested that high SMX concentrations promoted potential competition among microbes and disrupted the microbial food webs in periphyton. The absolute abundance of sul1 and sul2 genes in T2 and T3 groups were 2-3 orders of magnitude higher than those in control group after 30 days of SMX exposure, which elevated the risk of resistance gene enrichment and dissemination in the natural environment. The study contributes to our understanding of the detrimental effects of antibiotic pollution, which can induce changes in the structure and interaction relationship of microbial communities in aquaculture water.

An interpretable model predicts visual outcomes of no light perception eyes after open globe injury.

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.

[Characteristics of Phytoplankton Communities and Key Impact Factors in Three Types of Lakes in Wuhan].

To reveal the characteristics and key impact factors of phytoplankton communities in different types of lakes, sampling surveys for phytoplankton and water quality parameters were conducted at 174 sampling sites in a total of 24 lakes covering urban, countryside, and ecological conservation areas of Wuhan in spring, summer, autumn, and winter 2018. The results showed that a total of 365 species of phytoplankton from nine phyla and 159 genera were identified in the three types of lakes. The main species were green algae, cyanobacteria, and diatoms, accounting for 55.34%, 15.89%, and 15.07% of the total number of species, respectively. The phytoplankton cell density varied from 3.60×106-421.99×106 cell·L-1, chlorophyll-a content varied from 15.60-240.50 µg·L-1, biomass varied from 27.71-379.79 mg·L-1, and the Shannon-Wiener diversity index varied from 0.29-2.86. In the three lake types, cell density, Chla, and biomass were lower in EL and UL, whereas the opposite was true for the Shannon-Wiener diversity index. NMDS and ANOSIM analysis showed differences in phytoplankton community structure (Stress=0.13, R=0.048, P=0.2298). In addition, the phytoplankton community structure of the three lake types had significant seasonal characteristics, with chlorophyll-a content and biomass being significantly higher in summer than in winter (P<0.05). Spearman correlation analysis showed that phytoplankton biomass decreased with increasing N:P in UL and CL, whereas the opposite was true for EL. Redundancy analysis (RDA) showed that WT, pH, NO3-, EC, and N:P were the key factors that significantly affected the variability in phytoplankton community structure in the three types of lakes in Wuhan (P<0.05).

Fabrication of a core-shell porphyrin-based magnetic covalent organic framework for effective extraction of PCPs in a wide polarity range.

A novel porphyrin-based magnetic covalent organic framework (PCOF) was first reported by using a facile synthetic procedure. The Fe3O4@NH2@PCOF nanospheres were utilized to effectively extract personal care products in a wide polarity range (log Kow values from 1.96 to 7.60). The successful magnetic solid-phase extraction (MSPE) of target analytes could be ascribed to the sufficient oxygen-, nitrogen- and phenyl-containing functional groups of the COF layer, which are demonstrated to be of good compatibility with pollutants exhibiting different polarities by using molecular dynamics simulations, independent gradient model analysis and various characterizations. The MSPE extraction efficiency was enhanced by optimizing key parameters. The findings indicated that the method had a wide linearity range (1-500 ng mL-1 for parabens and UV filters) and low detection limits (0.4-0.9 ng mL-1 for parabens and 0.2-0.6 ng mL-1 for UV filters). The accuracy was reflected by recoveries ranging from 74% to 114%. Satisfactory intra- and inter-day precisions from 3.0% to 9.8% and 0.5%-9.1% were obtained. Overall, the proposed MSPE-HPLC method is accurate and reliable for identifying parabens as well as UV filters in wastewater and swimming pool water. The potential of the method for evaluating human exposure risk was unfolded.

Inhibition of ferroptosis promotes retina ganglion cell survival in experimental optic neuropathies.

Retinal ganglion cell (RGC) death is a hallmark of traumatic optic neuropathy, glaucoma, and other optic neuropathies that result in irreversible vision loss. However, therapeutic strategies for rescuing RGC loss still remain challenging, and the molecular mechanism underlying RGC loss has not been fully elucidated. Here, we highlight the role of ferroptosis, a non-apoptotic form of programmed cell death characterized by iron-dependent lethal lipid peroxides accumulation, in RGC death using an experimental model of glaucoma and optic nerve crush (ONC). ONC treatment resulted in significant downregulation of glutathione peroxidase 4 (GPx4) and system xc(-) cystine/glutamate antiporter (xCT) in the rat retina, accompanied by increased lipid peroxide and iron levels. The reduction of GPx4 expression in RGCs after ONC was confirmed by laser-capture microdissection and PCR. Transmission electron microscopy (TEM) revealed alterations in mitochondrial morphology, including increased membrane density and reduced mitochondrial cristae in RGCs after ONC. Notably, the ferroptosis inhibitor ferrostatin-1 (Fer-1) significantly promoted RGC survival and preserved retinal function in ONC and microbead-induced glaucoma mouse models. In addition, compared to the apoptosis inhibitor Z-VAD-FMK, Fer-1 showed better effect in rescuing RGCs death in ONC retinas. Mechanistically, we found the downregulation of GPx4 mainly occurred in the mitochondrial compartment, accompanied by increased mitochondrial reactive oxygen species (ROS) and lipid peroxides. The mitochondria-selective antioxidant MitoTEMPO attenuated RGC loss after ONC, implicating mitochondrial ROS and lipid peroxides as major mechanisms in ferroptosis-induced RGC death in ONC retinas. Notably, administering Fer-1 effectively prevented the production of mitochondrial lipid peroxides, the impairment of mitochondrial adenosine 5'-triphosphate (ATP) production, and the downregulation of mitochondrial genes, such as mt-Cytb and MT-ATP6, in ONC retinas. Our findings suggest that ferroptosis is a major form of regulated cell death for RGCs in experimental glaucoma and ONC models and suggesting targeting mitochondria-dependent ferroptosis as a protective strategy for RGC injuries in optic neuropathies.

One-pot fabrication of functional magnetic adsorbent for efficient capture of mercury species in aqueous samples prior to HPLC analysis.

Efficient extraction is a vital step in mercury speciation. In this context, using 4-vinylbenzeneboronic acid and 9-vinylanthracene as functional monomers, a new magnetic adsorbent was fabricated according to one-pot hydrothermal approach. Various characterization results prove the as-prepared adsorbent presented abundant functional groups and saturation magnetism. Combining with magnetic solid phase extraction (MSPE), the adsorbent exhibited satisfactory entrapment performance towards different mercury species which had been pre-coordinated with dithizone to form metal-organic coordination. A series of parameters influencing the extraction performance were inspected in detail. Under the most beneficial conditions, sensitive and reliable approach to quantify trace methylmercury, ethylmercury, phenylmercury and inorganic mercury in aqueous samples was developed by the combination of HPLC/DAD. Limits of detection and precision located in the ranges of 0.012-0.074 µg/L and 2.5-9.8%, respectively. Recoveries with low, medium and high fortified contents in actual waters varied from 79.8 to 119%. Confirmatory experiments were performed to evidence the accuracy and reliability of established approach. In addition, a possible mechanism was suggested based on the chemical nature of analytes, extraction conditions and characterization results.

SARS-CoV-2 tetrameric RBD protein blocks viral infection and induces potent neutralizing antibody response.

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy and calls for the development of safe treatments and effective vaccines. The receptor-binding domain in the spike protein (SRBD) of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that dimeric SRBD-Fc and tetrameric 2xSRBD-Fc fusion proteins bind ACE2 with different affinity and block SARS-CoV-2 pseudoviral infection. Immunization of mice with SRBD-Fc fusion proteins elicited high titer of RBD-specific antibodies with robust neutralizing activity against pseudoviral infections. As such, our study indicates that the polymeric SRBD-Fc fusion protein can serve as a treatment agent as well as a vaccine for fighting COVID-19.

Generation of a homozygous P4HA2 knockout human embryonic stem cell line (FDCHDPe012-A) by CRISPR/Cas9 system.

Prolyl 4-hydroxylase subunit alpha-2(P4HA2) is associated with autosomal dominant high myopia. A significant reduction of P4HA2 protein expression has been observed in fibroblast cells of high myopia patients with inherited P4HA2 mutations. To explore the function of P4HA2 in cases of high myopia, we generated a P4HA2-KO hES cell line (FDCHDPe012-A) efficiently through CRISPR/Cas9 system. We confirmed the presence of a 5-bp biallelic deletion, causing a frameshift and premature P4HA2 translation termination. The FDCHDPe012-A presented morphology of typical stem cells expressed pluripotent genes, possessed a normal parental karyotype, and could differentiate into three germ layers.

Correction of Beta-Thalassemia IVS-II-654 Mutation in a Mouse Model Using Prime Editing.

Prime editing was used to insert and correct various pathogenic mutations except for beta-thalassemia variants, which disrupt functional beta-globin and prevent hemoglobin assembly in erythrocytes. This study investigated the effect of gene correction using prime editor version 3 (PE3) in a mouse model with the human beta-thalassemia IVS-II-654 mutation (C > T). The T conversion generates a 5' donor site at intron 2 of the beta-globin gene resulting in aberrant splicing of pre-mRNA, which affects beta-globin expression. We microinjected PE3 components (pegRNA, nick sgRNA, and PE2 mRNA) into the zygotes from IVS-II-654 mice to generate mutation-edited mice. Genome sequencing of the IVS-II-654 site showed that PE3 installed the correction (T > C), with an editing efficiency of 14.29%. Reverse transcription-PCR analysis showed that the PE3-induced conversion restored normal splicing of beta-globin mRNA. Subsequent comprehensive phenotypic analysis of thalassemia symptoms, including anemic hematological parameters, anisocytosis, splenomegaly, cardiac hypertrophy, extramedullary hematopoiesis, and iron overload, showed that the corrected IVS-II-654 mice had a normal phenotype identical to the wild type mice. Off-target analysis of pegRNA and nick sgRNA additionally showed the genomic safety of PE3. These results suggest that correction of beta-thalassemia mutation by PE3 may be a straightforward therapeutic strategy for this disease.

Sports and Myopia: An Investigation on the Prevalence and Risk Factors of Myopia in Young Sports-Related Groups in Tianjin, China.

Objective: To explore the relationship between sports and the prevalence of myopia in young sports-related groups in Tianjin, China. Methods: In this cross-sectional study, a cluster sampling method was used to survey professional athletes in Tianjin, students at Tianjin University of Sport, and Tianjin Vocational College of Sports. All participants completed epidemiological questionnaires and ophthalmic examinations. Multivariable logistic regression models were used to explore the potential risk factors of myopia. Results: This study recruited 1401 participants. The prevalence of myopia was 50.18%. The prevalence of low, moderate, and high myopia were 52.63%, 37.41%, and 9.96%, respectively. There were no sex-related differences in the prevalence of myopia. The odds of having myopia was 1.788 times higher in the indoor sports group than the outdoor sports group (the adjusted odds ratio [OR], 95% confidence interval [CI], 1.391-2.297). Training time of more than 4 h/d (4-6 h/d: OR, 0.539; 95% CI, 0.310-0.938; >6 h/d: OR, 0.466; 95% CI, 0.257-0.844) resulted in a lower risk of myopia. Participants who often used the electronic screen (OR, 1.406; 95% CI, 1.028-1.923) and/or had a family history of myopia (OR, 2.022; 95% CI, 1.480-2.763) were more likely to suffer from myopia. Conclusions: Outdoor sports do not necessarily guarantee to insulate against myopia. Youngsters engaged in outdoor sports had a lower prevalence of myopia than those participating in indoor sports. Electronic screen use, training time, and family history of myopia were also associated with the prevalence of myopia in young sports-related groups.

Lysozyme Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Inflammation in Human Corneal Epithelial Cells.

Purpose: The purpose of this study was to investigate the effects of lysozyme, an antimicrobial enzyme found in tears that protects the eye against pathogens, on pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through corneal epithelial cells. Methods: The expression of the angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease (TMPRSS2) in human corneal epithelial cells (HCECs) was measured by RT-PCR and Western blotting. The altered expression of the pro-inflammatory molecules induced by spike protein and lysozyme was analyzed by RT-PCR. Cell toxicity was tested by CCK8 assay. The cell entry of SAR-CoV-2 in HCECs and primary rabbit corneal epithelial cells (RbCECs) was detected by luciferase assay. Results: ACE2 and TMPRSS2 were highly expressed in HCECs. The spike proteins of SARS-CoV-2 stimulated a robust inflammatory response in HCECs, characterized by increased secretion of pro-inflammatory molecules, including IL-6, TNF-α, iNOS, and MCP-1, and pretreatment with lysozyme in HCECs markedly decreased the production of proinflammatory molecules induced by spike proteins. In addition, the inflammatory cytokine TNF-α enhanced the entry of SARS-CoV-2 into HCECs, which can be mitigated by pretreatment with lysozyme. Conclusions: In this study, we analyzed the susceptibility of human corneal epithelial cells to SARS-CoV-2 infection and suggested the protective effects of lysozyme on SARS-CoV-2 infection.

Prime Editor 3 Mediated Beta-Thalassemia Mutations of the HBB Gene in Human Erythroid Progenitor Cells.

Recently developed Prime Editor 3 (PE3) has been implemented to induce genome editing in various cell types but has not been proven in human hematopoietic stem and progenitor cells. Using PE3, we successfully installed the beta-thalassemia (beta-thal) mutations in the HBB gene in the erythroid progenitor cell line HUDEP-2. We inserted the mCherry reporter gene cassette into editing plasmids, each including the prime editing guide RNA (pegRNA) and nick sgRNA. The plasmids were electroporated into HUDEP-2 cells, and the PE3 modified cells were identified by mCherry expression and collected using fluorescence-activated cell sorting (FACS). Sanger sequencing of the positive cells confirmed that PE3 induced precise beta-thal mutations with editing ratios from 4.55 to 100%. Furthermore, an off-target analysis showed no unintentional edits occurred in the cells. The editing ratios and parameters of pegRNA and nick sgRNA were also analyzed and summarized and will contribute to enhanced PE3 design in future studies. The characterization of the HUDEP-2 beta-thal cells showed typical thalassemia phenotypes, involving ineffective erythropoiesis, abnormal erythroid differentiation, high apoptosis rate, defective alpha-globin colocalization, cell viability deterioration, and ROS resisting deficiency. These HUDEP-2 beta-thal cells could provide ideal models for future beta-thal gene therapy studies.

Multi-Omics Analysis in ß-Thalassemia Using an HBB Gene-Knockout Human Erythroid Progenitor Cell Model.

ß-thalassemia is a hematologic disease that may be associated with significant morbidity and mortality. Increased expression of HBG1/2 can ameliorate the severity of ß-thalassemia. Compared to the unaffected population, some ß-thalassemia patients display elevated HBG1/2 expression levels in their red blood cells. However, the magnitude of up-regulation does not reach the threshold of self-healing, and thus, the molecular mechanism underlying HBG1/2 expression in the context of HBB-deficiency requires further elucidation. Here, we performed a multi-omics study examining chromatin accessibility, transcriptome, proteome, and phosphorylation patterns in the HBB homozygous knockout of the HUDEP2 cell line (HBB-KO). We found that up-regulation of HBG1/2 in HBB-KO cells was not induced by the H3K4me3-mediated genetic compensation response. Deletion of HBB in human erythroid progenitor cells resulted in increased ROS levels and production of oxidative stress, which led to an increased rate of apoptosis. Furthermore, in response to oxidative stress, slower cell cycle progression and proliferation were observed. In addition, stress erythropoiesis was initiated leading to increased intracellular HBG1/2 expression. This molecular model was also validated in the single-cell transcriptome of hematopoietic stem cells from ß-hemoglobinopathy patients. These findings further the understanding of HBG1/2 gene regulatory networks and provide novel clinical insights into ß-thalassemia phenotypic diversity.

Reactivation of γ-globin expression using a minicircle DNA system to treat ß-thalassemia.

Reactivation of fetal hemoglobin by editing the B-cell lymphoma/leukemia 11A (BCL11A) erythroid enhancer is an effective gene therapy for ß-thalassemia. Using the CRISPR/Cas9 system, fetal γ-globin expression can be robustly reactivated to mitigate the clinical course of ß-thalassemia. In our study, we found that the transfection efficiencies of CD34+ hematopoietic stem/progenitor cells (HSPCs) were significantly and negatively correlated with the length of plasmids and greatly affected by the linearization of plasmids. Furthermore, the transgene expression of minicircles (MC) without plasmid backbone sequences was better both in vitro and in vivo compared with conventional plasmids. Thus, MC DNA was used to deliver the cassette of Staphylococcus aureus Cas9 (SaCas9) into HSPCs, and a single-guide RNA targeting the erythroid enhancer region of BCL11A was selected. After electroporation with MC DNA, an evident efficiency of gene editing and reactivation of γ-globin expression in erythroblasts derived from unsorted HSPCs was acquired. No significant off-target effects were found by deep sequencing. Furthermore, fragments derived from lentiviral vectors, but not MC DNA, were highly enriched in promoter, exon, intron, distal-intergenic, and cancer-associated genes, indicating that MC DNA provided a relatively safe and efficient vector for delivering transgenes. The developed MC DNA vector provided a potential approach for the delivery of SaCas9 cassette and the reactivation of γ-globin expression for ameliorating syndromes of ß-thalassemia.

Epidemiology of Sports-Related Eye Injuries Among Athletes in Tianjin, China.

Purpose: To investigate the incidence, characteristics, and risk factors of sports-related eye injuries among athletes in Tianjin, China. Methods: A cross-sectional study was carried out from March 2018 to October 2018. In this study, the athletes from Tianjin University of Sports, Tianjin Vocational College of Sports, and Tianjin provincial sports teams were selected for general investigation. In total, 1,673 athletes were invited and 1,413 participated in the study (response rate of 84.5%). Results: In total, 1,413 athletes were enrolled; 151 had suffered from sports-related eye injuries, with an incidence of 10.7% (95% CI: 9.1-12.0%). Handball (38.5%) was the sport with the highest incidence of eye injuries, followed by water polo (36.4%) and diving (26.7%). Overall, 42.4% of the athletes were injured by ball and 22.5% of injuries came from teammates. The eye injuries usually occurred during training (64.2%) and competitions (14.6%). Adnexa wound (51.7%) was the most common type of injury. About 11.9% of the athletes with eye injuries had the impaired vision; 66.7% failed to see doctors on time. The athletes <18 years of age had a higher risk of eye injuries (odds ratio [OR] =1.60, 95% CI: 1.06-2.40). The athletes with lower family income (<1,000 RMB) were at risk population for sports-related eye injuries (OR = 3.91, 95% CI: 2.24-6.82). Training >4 h a day increased the risk of eye injuries (OR = 2.21, 95% CI: 1.42-3.43). Conclusion: The incidence of sports-related eye injuries among athletes was 10.7% in Tianjin, China. Handball, water polo, and diving were the most common activities of injury. Age, family income, and training time were the risk factors for sports-related eye injuries.

Association of cigarette smoking with retinal thickness and vascular structure in an elderly Chinese population.

BACKGROUND: To explore the association of cigarette smoking with retinal thickness and vascular structure in an elderly Chinese population. METHODS: This cross-sectional study enrolled employees and retirees aged over 50 years at Tianjin University of Sport from October 2020 to December 2020. Information on smoking status and lifestyle was obtained using a detailed questionnaire. All participants underwent full ophthalmic examination. OCTA image was acquired. Vascular and the thickness parameters in central fovea and peripapillary parameters were automatically calculated. Multiple linear regression analyses were utilized to assess the association of smoking with retinal thickness and vascular structure after controlling potential confounders. RESULTS: Compared with non-smoking adults, current smokers (ß=-36.78; P = 0.01) and ever smokers (ß=-35.45; P = 0.00) tended to have thinner macular fovea. Cigarettes daily, pack-years of smoking and CSI were negatively related to macular thickness (cigarettes daily: ß=-1.43; pack-years: ß=-14.73; CSI: ß=-14.70), while they were positively associated with the circumference (cigarettes daily: ß=0.03; pack-years: ß=0.30; CSI: ß=0.31) and the area of FAZ (cigarettes daily: ß=0.01; pack-years: ß=0.07). CONCLUSIONS: Cigarette smoking seems associated with decreased macular fovea thickness and elevated circumference and area of the FAZ compared to non-smokers. Our data add to evidence of smoking on retinal thickness and the microvascular system in the macular area.

Identifying Mitochondrial-Related Genes NDUFA10 and NDUFV2 as Prognostic Markers for Prostate Cancer through Biclustering.

Prostate cancer is currently associated with higher morbidity and mortality in men in the United States and Western Europe, so it is important to identify genes that regulate prostate cancer. The high-dimension gene expression profile impedes the discovery of biclusters which are of great significance to the identification of the basic cellular processes controlled by multiple genes and the identification of large-scale unknown effects hidden in the data. We applied the biclustering method MCbiclust to explore large biclusters in the TCGA cohort through a large number of iterations. Two biclusters were found with the highest silhouette coefficient value. The expression patterns of one bicluster are highly similar to those found by the gene expression profile of the known androgen-regulated genes. Further gene set enrichment revealed that mitochondrial function-related genes were negatively correlated with AR regulation-related genes. Then, we performed differential analysis, AR binding site analysis, and survival analysis on the core genes with high phenotypic contribution. Among the core genes, NDUFA10 showed a low expression value in cancer patients across different expression profiles, while NDUFV2 showed a high expression value in cancer patients. Survival analysis of NDUFA10 and NDUFV2 demonstrated that both genes were unfavorable prognostic markers.

Inferring Cell Subtypes and LncRNA Function by a Cell-Specific CeRNA Network in Breast Cancer.

Single-cell RNA sequencing is a powerful tool to explore the heterogeneity of breast cancer. The identification of the cell subtype that responds to estrogen has profound significance in breast cancer research and treatment. The transcriptional regulation of estrogen is an intricate network involving crosstalk between protein-coding and non-coding RNAs, which is still largely unknown, particularly at the single cell level. Therefore, we proposed a novel strategy to specify cell subtypes based on a cell-specific ceRNA network (CCN). The CCN was constructed by integrating a cell-specific RNA-RNA co-expression network (RCN) with an existing ceRNA network. The cell-specific RCN was built based on single cell expression profiles with predefined reference cells. Heterogeneous cell subtypes were inferred by enriching RNAs in CCN to the estrogen response hallmark. Edge biomarkers were identified in the early estrogen response subtype. Topological analysis revealed that NEAT1 was a hub lncRNA for the early response subtype, and its ceRNAs could predict patient survival. Another hub lncRNA, DLEU2, could potentially be involved in GPCR signaling, based on CCN. The CCN method that we proposed here facilitates the inference of cell subtypes from a network perspective and explores the function of hub lncRNAs, which are promising targets for RNA-based therapeutics.