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Abstract Background Anthocyanins are water-soluble flavonoids in plants, which give plants bright colors and are widely used as food coloring agents, nutrients, and cosmetic additives. There are several limitations for traditional techniques of collecting anthocyanins from plant tissues, including species, origin, season, and technology. The benefits of using engineering microbial production of natural products include ease of use, controllability, and high efficiency. Results In this study, ten genes encoding enzymes involved in the anthocyanin biosynthetic pathway were successfully cloned from anthocyanin-rich plant materials blueberry fruit and purple round eggplant rind. The Yeast Fab Assembly technology was utilized to construct the transcriptional units of these genes under different promoters. The transcriptional units of PAL and C4H, 4CL and CHS were fused and inserted into Chr. XVI and IV of yeast strain JDY52 respectively using homologous recombination to gain Strain A. The fragments containing the transcriptional units of CHI and F3H, F3’H and DFR were inserted into Chr. III and XVI to gain Strain B1. Strain B2 has the transcriptional units of ANS and 3GT in Chr. IV. Several anthocyanidins, including cyanidin, peonidin, pelargonidin, petunidin, and malvidin, were detected by LC-MS/MS following the predicted outcomes of the de novo biosynthesis of anthocyanins in S. cerevisiae using a multi-strain co-culture technique. Conclusions We propose a novel concept for advancing the heterologous de novo anthocyanin biosynthetic pathway, as well as fundamental information and a theoretical framework for the ensuing optimization of the microbial synthesis of anthocyanins.

Abstract Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure. Intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor. Here we show that using the RNA interference tool CasRx based on shH10 adenovirus-associated virus can reduce the expression of the aqueous humor circulation related genes Rock1 and Rock2, as well as aquaporin 1 and β2 adrenergic receptor in female mice. This significantly reduced intraocular pressure in female mice and provided protection to the retina ganglion cells, ultimately delaying disease progression. In addition, we elucidated the mechanisms by which the knockdown of Rock1 and Rock2, or aquaporin 1 and β2 adrenergic receptor in female mice, reduces the intraocular pressure and secures the retina ganglion cells by single-cell sequencing.

Abstract Purpose The present study aimed to investigate the clinical characteristics and lung function impairment in young people diagnosed with chronic obstructive pulmonary disease (COPD). Patients and methods We retrospectively enrolled patients with COPD who underwent symptom assessment and comprehensive pulmonary function tests at the First Affiliated Hospital of Guangzhou Medical University between August 2017 and March 2022. The patients were categorized into two groups based on age: a young COPD group (aged 20–50 years) and an old COPD group (aged > 50 years). Results A total of 1282 patients with COPD were included in the study, with 76 young COPD patients and 1206 old COPD patients. Young COPD patients exhibited a higher likelihood of being asymptomatic, lower rates of smoking, and a lower smoking index compared to old COPD patients. Although young COPD patients had higher median post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) (1.4 vs.1.2 L, P = 0.019), diffusing capacity of the lung for carbon monoxide (DLCO) (7.2 vs. 4.6, P 120%) between two groups. Surprisingly, the prevalence of reduced DLCO was found to be 71.1% in young COPD, although lower than in old COPD (85.2%). Conclusion Young COPD showed fewer respiratory symptoms, yet displayed a similar severity distribution by GOLD categories. Furthermore, a majority of them demonstrated lung hyperinflation and reduced DLCO. These results underscore the importance of a comprehensive assessment of lung function in young COPD patients.

Abstract Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5’-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Abstract General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp3)−C(sp3) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles. The utility of this methodology has been demonstrated by late-stage functionalization of drug molecules, asymmetric synthesis of bioactive molecules, natural products and functional materials, and identification of a class of molecules exhibiting anti-apoptosis activities in UVB-irradiated HaCaT cells. Ligands play a vital role in controlling the reaction regioselectivity. Changing the ligand from bi-dentate L6 to tridentate L12 enables CoH-catalyzed Markovnikov hydroalkylation. Mechanistic studies disclose that the anti-Markovnikov hydroalkylation involves a migratory insertion process while the Markovnikov hydroalkylation involves a MHAT process.

Abstract Background Protein arginine methyltransferase 6 (PRMT6) plays a crucial role in various pathophysiological processes and diseases. Glioblastoma (GBM; WHO Grade 4 glioma) is the most common and lethal primary brain tumor in adults, with a prognosis that is extremely poor, despite being less common than other systemic malignancies. Our current research finds PRMT6 upregulated in GBM, enhancing tumor malignancy. Yet, the specifics of PRMT6’s regulatory processes and potential molecular mechanisms in GBM remain largely unexplored. Methods PRMT6’s expression and prognostic significance in GBM were assessed using glioma public databases, immunohistochemistry (IHC), and immunoblotting. Scratch and Transwell assays examined GBM cell migration and invasion. Immunoblotting evaluated the expression of epithelial-mesenchymal transition (EMT) and Wnt-β-catenin pathway-related proteins. Dual-luciferase reporter assays and ChIP-qPCR assessed the regulatory relationship between PRMT6 and YTHDF2. An in situ tumor model in nude mice evaluated in vivo conditions. Results Bioinformatics analysis indicates high expression of PRMT6 and YTHDF2 in GBM, correlating with poor prognosis. Functional experiments show PRMT6 and YTHDF2 promote GBM migration, invasion, and EMT. Mechanistic experiments reveal PRMT6 and CDK9 co-regulate YTHDF2 expression. YTHDF2 binds and promotes the degradation of negative regulators APC and GSK3β mRNA of the Wnt-β-catenin pathway, activating it and consequently enhancing GBM malignancy. Conclusions Our results demonstrate the PRMT6-YTHDF2-Wnt-β-Catenin axis promotes GBM migration, invasion, and EMT in vitro and in vivo, potentially serving as a therapeutic target for GBM.

Abstract Funduscopic diseases, including diabetic retinopathy (DR) and age‐related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti‐vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next‐generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally.

The generator, which combines convolutional neural network (CNN) and Transformer as its core modules, serves as the primary model for the handwriting font generation network and demonstrates effective performance. However, there are still problems with insufficient feature extraction in the overall structure of the font, the thickness of strokes, and the curvature of strokes, resulting in subpar detail in the generated fonts. To solve the problems, we propose a method for constructing a handwritten font generation model based on Pyramid Squeeze Attention, called PSA-HWT. The PSA-HWT model is divided into two parts: an encoder and a decoder. In the encoder, a multi-branch structure is used to extract spatial information at different scales from the input feature map, achieving multi-scale feature extraction. This helps better capture the semantic information and global structure of the font, aiding the generation model in understanding fine-grained features such as the shape, thickness, and curvature of the font. In the decoder, it uses a self-attention mechanism to capture dependencies across various positions in the input sequence. This helps to better understand the relationship between the generated strokes or characters and the handwritten font being generated, ensuring the overall coherence of the generated handwritten text. The experimental results on the IAM dataset demonstrate that PSA-HWT achieves a 16.35% decrease in Fréchet inception distance (FID) score and a 13.09% decrease in Geometry Score (GS) compared to the current advanced methods. This indicates that PSA-HWT generates handwritten fonts of higher quality, making it more practically valuable.

Abstract Corneal neovascularization (CNV) is a common clinical finding seen in a range of eye diseases. Current therapeutic approaches to treat corneal angiogenesis, in which vascular endothelial growth factor (VEGF) A plays a central role, can cause a variety of adverse side effects. The technology of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 can edit VEGFA gene to suppress its expression. CRISPR offers a novel opportunity to treat CNV. This study shows that depletion of VEGFA with a novel CRISPR/Cas9 system inhibits proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Importantly, subconjunctival injection of this dual AAV‐SpCas9/sgRNA‐VEGFA system is demonstrated which blocks suture‐induced expression of VEGFA, CD31, and α‐smooth muscle actin as well as corneal neovascularization in mice. This study has established a strong foundation for the treatment of corneal neovascularization via a gene editing approach for the first time.

Summary: Glioblastoma (GBM) is characterized by aggressive growth, invasiveness, and poor prognosis. Elucidating the molecular mechanisms underlying GBM is crucial. This study explores the role of Sm-like protein 14 homolog A (LSM14A) in GBM. Bioinformatics and clinical tissue samples analysis demonstrated that overexpression of LSM14A in GBM correlates with poorer prognosis. CCK8, EdU, colony formation, and transwell assays revealed that LSM14A promotes proliferation, migration, and invasion in GBM in vitro. In vivo mouse xenograft models confirmed the results of the in vitro experiments. The mechanism of LSM14A modulating GBM cell proliferation was investigated using mass spectrometry, co-immunoprecipitation (coIP), protein half-life, and methylated RNA immunoprecipitation (MeRIP) analyses. The findings indicate that during the G1/S phase, LSM14A stabilizes DDX5 in the cytoplasm, regulating CDK4 and P21 levels. Furthermore, METTL1 modulates LSM14A expression via mRNA m7G methylation. Altogether, our work highlights the METTL1-LSM14A-DDX5 pathway as a potential therapeutic target in GBM.

Abstract Background To evaluate the intraobserver repeatability and interobserver reproducibility of a newly developed dynamic real-time visualization 25 kHz swept-source optical coherence tomography (SS-OCT) based biometer (ZW-30, TowardPi Medical Technology Ltd, China) and compare its agreement with another SS-OCT based biometer (IOLMaster 700, Carl Zeiss Meditec AG, Jena, Germany). Methods Eighty-two healthy right eyes were enrolled in this prospective observational study. Measurements were repeated for three times using the ZW-30 and IOLMaster 700 in a random order. Obtained parameters included axial length (AL), central corneal thickness (CCT), aqueous depth (AQD), anterior chamber depth (ACD), lens thickness (LT), mean keratometry (Km), astigmatism magnitude (AST), vector J0, vector J45, and corneal diameter (CD). The within-subject standard deviation (Sw), test–retest (TRT) variability, coefficient of variation (CoV), and intraclass correlation coefficient (ICC) were adopted to assess the intraobserver repeatability and interobserver reproducibility. The double-angle plot was also used to display the distribution of AST. To estimate agreement, Bland–Altman plots were used. Results For the intraobserver repeatability and interobserver reproducibility, the Sw, TRT and CoV for all parameters were low. Meanwhile, the ICC values were all close to 1.000, except for the J45 (ICC = 0.887 for the intraobserver repeatability). The double-angle plot showed that the distribution of AST measured by these two devices was similar. For agreement, the Bland–Altman plots showed narrow 95% limits of agreements (LoAs) for AL, CCT, AQD, ACD, LT, Km AST, J0, J45, and CD (− 0.02 mm to 0.02 mm, − 7.49 μm to 8.08 μm, − 0.07 mm to 0.04 mm, − 0.07 mm to 0.04 mm, − 0.07 mm to 0.08 mm, − 0.16 D to 0.30 D, − 0.30 D to 0.29 D, − 0.16 D to 0.16 D, − 0.23 D to 0.13 D, and − 0.39 mm to 0.10 mm, respectively). Conclusions The newly dynamic real-time visualization biometer exhibited excellent intraobserver repeatability and interobserver reproducibility. The two devices both based on the SS-OCT principle had similar ocular parameters measurement values and can be interchanged in clinical practice.

Abstract Background Corneal cross-linking (CXL) using riboflavin and ultraviolet-A light (UVA) is a treatment used to prevent progression of keratoconus. This ex vivo study assesses the impact on CXL effectiveness, as measured by tissue enzymatic resistance and confocal microscopy, of including a pre-UVA corneal surface rinse with balanced salt solution (BSS) as part of the epithelium-off treatment protocol. Methods Sixty-eight porcine eyes, after epithelial debridement, were assigned to six groups in three experimental runs. Group 1 remained untreated. Groups 2–6 received a 16-min application of 0.1% riboflavin/Hydroxypropyl methylcellulose (HPMC) drops, after which Group 3 was exposed to 9 mW/cm2 UVA for 10 min, and Groups 4–6 underwent corneal surface rinsing with 0.25 mL, 1 mL or 10 mL BSS followed by 9 mW/cm2 UVA exposure for 10 min. Central corneal thickness (CCT) was recorded at each stage. Central 8.0 mm corneal buttons from all eyes were subjected to 0.3% collagenase digestion at 37 °C and the time required for complete digestion determined. A further 15 eyes underwent fluorescence confocal microscopy to assess the impact of rinsing on stromal riboflavin concentration. Results Application of riboflavin/HPMC solution led to an increase in CCT of 73 ± 14 µm (P

Abstract Background In the context of increasing population aging, ongoing drug-resistant pathogens and the COVID-19 epidemic, the changes in the epidemiological and clinical characteristics of patients with pneumonia remain unclear. This study aimed to assess the trends in hospitalization, case fatality, comorbidities, and isolated pathogens of pneumonia-related adult inpatients in Guangzhou during the last decade. Methods We retrospectively enrolled hospitalized adults who had doctor-diagnosed pneumonia in the First Affiliated Hospital of Guangzhou Medical University from January 1, 2013 to December 31, 2022. A natural language processing system was applied to automatically extract the clinical data from electronic health records. We evaluated the proportion of pneumonia-related hospitalizations in total hospitalizations, pneumonia-related in-hospital case fatality, comorbidities, and species of isolated pathogens during the last decade. Binary logistic regression analysis was used to assess predictors for patients with prolonged length of stay (LOS). Results A total of 38,870 cases were finally included in this study, with 70% males, median age of 64 (53, 73) years and median LOS of 7.9 (5.1, 12.8) days. Although the number of pneumonia-related hospitalizations showed an upward trend, the proportion of pneumonia-related hospitalizations decreased from 199.6 per 1000 inpatients in 2013 to 123.4 per 1000 in 2021, and the case fatality decreased from 50.2 per 1000 in 2013 to 23.9 per 1000 in 2022 (all P

Abstract Background To assess repeatability and reproducibility of corneal epithelium thickness (ET) measured by a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in keratoconus (KC) population at different stages, as well as to determine the progression limits for evaluating KC progression. Methods A total of 149 eyes were enrolled in this study, with 29 eyes in the forme fruste keratoconus (FFKC) group, 34 eyes in the mild KC group, 40 eyes in the moderate KC group, and 46 eyes in the severe KC group. Employing the within-subject standard deviation (Sw), test-retest variability (TRT), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) to evaluate intraoperator repeatability and interoperator reproducibility. Results The repeatability and reproducibility of MS-39 in patients with KC were acceptable, according to ICC values ranging from 0.732 to 0.954. However, patients with more severe KC and progressive peripheralization of the measurement points had higher TRTs but a thinning trend. The current study tended to set the cut-off values of mild KC, moderate KC, and severe KC to 4.9 µm, 5.2 µm, and 7.4 µm for thinnest epithelium thickness (TET). When differences between follow-ups are higher than those values, progression of the disease is possible. As for center epithelium thickness (CET), cut-off values for mild KC, moderate KC, and severe KC should be 2.8 µm, 4.4 µm, and 5.3 µm. This might be useful in the follow-up and diagnosis of keratoconus. Conclusions This study demonstrated that the precision of MS-39 was reduced in measuring more severe KC patients and more peripheral corneal points. In determining disease progression, values should be differentiated between disease-related real changes and measurement inaccuracies. Due to the large difference in ET measured by MS-39 between various stages of disease progression, it is necessary to accurately grade KC patients to avoid errors in KC clinical decision-making.

Background The prevalence, Medicaid use and mortality risk associated with low forced expiratory volume in 1 s (FEV1) among young adults aged 20–35 years are not well understood, despite its potential implications for the development of chronic pulmonary disease and overall prognosis.Methods A retrospective cohort study was conducted among young adults aged 20–35 years old, using data from the National Health and Nutrition Examination Survey, National Death Index and Centers for Medicare & Medicaid Services. Participants were categorised into a low FEV1 group (pre-bronchodilator FEV1%pred

Abstract Introduction The aim of this work is to evaluate the intraobserver repeatability and interobserver reproducibility of corneal power measurements obtained with a swept-source optical coherence tomographer (CASIA 2, Tomey, Japan) in healthy subjects. Methods A total of 67 right eyes from 67 healthy subjects were enrolled. Two experienced observers measured each eye three times consecutively with the CASIA 2. Corneal power values were recorded as simulated keratometry, anterior, posterior, and total corneal power. Parameters were flattest keratometry (K f), steepest keratometry (K s), mean keratometry (K m), astigmatism magnitude, astigmatism power vectors J 0 and J 45. Intraobserver repeatability and interobserver reproducibility of the CASIA 2 were assessed by the within-subject standard deviation (S w), test–retest repeatability (TRT), coefficients of variation (CoV), and intraclass correlation coefficients (ICCs). Double-angle plots were used for astigmatism vector analysis. Results The CASIA 2 had high repeatability for all corneal power values, with S w values ≤ 0.17 diopters (D), TRT ≤ 0.46 D, and ICCs ranging from 0.866 to 0.998. Interobserver reproducibility was also high, showing all S w values ≤ 0.10 D, TRT ≤ 0.27 D, and ICCs ≥ 0.944. The reproducibility of the average of three consecutive measurements (S w 0.01–0.10 D, TRT 0.03–0.27 D, ICC 0.944–0.998) was higher than the reproducibility of single measurements (S w 0.01–0.17 D, TRT 0.03–0.47 D, ICC 0.867–0.996). Conclusions The CASIA 2 showed high intraobserver repeatability and interobserver reproducibility for anterior, posterior, and total corneal power measurements in 6.0-mm diameter area. In addition, we suggest that using the average of three consecutive measurements can improve reproducibility between observers, compared to single measurements only.

Abstract Introduction This study evaluated the differences and agreement between a new Scheimpflug camera (Scansys) and a swept-source anterior segment optical coherence tomographer (CASIA 2) for measurements of the anterior segment of the eye in normal subjects. Methods This prospective study included 84 eyes from 84 normal adult subjects who underwent three consecutive measurements with the Scansys and the CASIA 2 in random order. The mean keratometry (Km), astigmatism magnitude (AST), J 0, and J 45 vectors for both anterior and posterior corneal surfaces, central corneal thickness (CCT), thinnest corneal thickness (TCT), and anterior chamber depth (ACD) were obtained by both devices. The difference between these two devices was assessed using paired t test and violin plots. Bland–Altman plots and 95% limits of agreement (LoAs) were used to evaluate agreement. Results No statistically significant differences between the two devices were found for the anterior AST, anterior J 45, and posterior J 45 (P > 0.05). The remaining parameters were statistically significant (P ≤ 0.05), but the differences not clinically significant. The violin plots showed that the distribution and probability density of the measured parameters were similar for both devices. Bland–Altman plots revealed high agreement for the measured parameters between the Scansys and CASIA 2, with narrow 95% LoAs. Conclusions In terms of assessing parameters for the anterior segment, our study indicated that Scansys and CASIA 2 generally showed significant agreement. The two devices used in this study’s assessment of all the parameters can be used interchangeably in refractive analysis.

Abstract Background To develop a novel machine learning-based intraocular lens (IOL) power calculation formula for highly myopic eyes. Methods A total of 1828 eyes (from 1828 highly myopic patients) undergoing cataract surgery in our hospital were used as the internal dataset, and 151 eyes from 151 highly myopic patients from two other hospitals were used as external test dataset. The Zhu-Lu formula was developed based on the eXtreme Gradient Boosting and the support vector regression algorithms. Its accuracy was compared in the internal and external test datasets with the Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO) 2.0, Kane, Pearl-DGS and Radial Basis Function (RBF) 3.0 formulas. Results In the internal test dataset, the Zhu-Lu, RBF 3.0 and BUII ranked top three from low to high taking into account standard deviations (SDs) of prediction errors (PEs). The Zhu-Lu and RBF 3.0 showed significantly lower median absolute errors (MedAEs) than the other formulas (all P

Abstract Introduction Phoropters are widely accepted for clinical use in refraction examination and visual function assessment. This study assessed the reliability of the new Inspection Platform of Visual Function (IPVF) in comparison with the conventional equipment phoropter (TOPCON VT-10) in visual function assessment. Methods This prospective study enrolled 80 eyes of 80 healthy subjects. The horizontal phoria at distance and near (Phoria_D and Phoria_N, respectively) was measured with the von Graefe method, negative/positive relative accommodation (NRA/PRA) was measured with the positive/negative lens method, and accommodative amplitude (AMP) was measured with the minus lens method. Data of three consecutive measurements with each instrument were evaluated using the intraclass correlation coefficient (ICC) for repeatability, and the agreement of the two instruments was evaluated using a Bland–Altman plot. Results The ICCs of the three consecutive measurements for phoria, NRA/PRA, and AMP using the IPVF instrument were high (0.87–0.96), indicating high repeatability. The ICCs of the three consecutive measurements using the phoropter were high (0.914–0.983) for phoria, NRA, and AMP, indicating high repeatability, while that of PRA was 0.732 (between 0.4 and 0.75), indicating acceptable repeatability. The 95% limits of agreement of phoria, NRA/PRA, and AMP were narrow, indicating good agreement between the two instruments. Conclusion The repeatability of both instruments was high, and the IPVF instrument was slightly better in terms of PRA repeatability than the phoropter. The agreement of phoria, NRA/PRA, and AMP measured by the new IPVF instrument and phoropter was also satisfactory.

Background Chronic obstructive pulmonary disease (COPD) has been considered a disease of the elderly, but it could also occur in young people aged 20–50 years. However, the characteristics and prognosis of COPD in such young people remain unclear.Methods Our retrospective cohort study was based on the National Health and Nutrition Examination Survey (NHANES). Participants who 20–50 years old at baseline and completed the pulmonary function test were enrolled in our study cohort. These participants were followed up to 31 December 2019. The sample weight and Taylor Linearization Procedures were adapted to make representative estimations of prevalence and baseline characteristics. The weighted logistic regression model was used to assess the risk factors. The propensity score method and Cox proportional hazard models were applied to calculate the risk of mortality.Results The weighted prevalence of COPD in young people in the USA was 1.64% and it increased with age, with a higher prevalence in males than females (2.59% vs 0.72%, p

Abstract Introduction The aim of this study was to evaluate the measurements of corneal higher-order aberrations (HOAs) obtained by a new anterior segment optical coherence tomography (OCT) technique combined with a Placido topographer (the MS-39 device) in eyes with prior small-incision lenticule extraction (SMILE) and compare them to the measurements obtained by a Scheimpflug camera combined with a Placido topographer (the Sirius device). Methods A total of 56 eyes (56 patients) were included in this prospective study. Corneal aberrations were analyzed for the anterior, posterior, and total cornea surfaces. Within-subject standard deviation (S w), test–retest repeatability (TRT), and intraclass correlation coefficient (ICC) were used to assess the intraobserver repeatability and interobserver reproducibility. The differences were evaluated by paired t-test. Bland–Altman plots and 95% limits of agreement (95% LoA) were used to evaluate the agreement. Results High repeatability was observed for anterior and total corneal parameters, with S w value 0.893, but not trefoil. For the posterior corneal parameters, ICCs varied from 0.088 to 0.966. Regarding interobserver reproducibility, all S w values were ≤ 0.04 and TRT ≤ 0.11. ICCs ranged from 0.846 to 0.989, from 0.432 to 0.972, and from 0.798 to 0.985 for the anterior, total, and posterior corneal aberrations parameters, respectively. The mean difference in all aberrations was ≤ 0.05 μm. All parameters showed a narrow 95% LoA. Conclusion The MS-39 device achieved high precision in both anterior and total corneal measurements; the precision of posterior corneal higher-order RMS, astigmatism II, coma, and trefoil was lower. The two technologies used by the MS-39 and Sirius devices can be used interchangeably for measuring corneal HOAs after SMILE.

Abstract Background To assess agreement of measurements between a new optical low coherence reflectometry (OLCR) biometer (SW-9000, Suoer, Tianjin, China) and a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in healthy subjects. Methods A total of 66 right eyes from 66 healthy subjects were enrolled in this prospective study. Three consecutive measurements were randomly obtained with both devices by the same experienced operator to assess agreement. Bland-Altman plots and 95% limits of agreement (LoA) were used to verify the agreement between the devices. Results are presented as mean ± standard deviation (SD). Results The SD-OCT/Placido tomographer showed high agreement with the OLCR biometer for all parameters included in this study. The mean differences of central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), mean keratometry (Km) and corneal diameter (CD) were 2.21 ± 2.67 μm (P

Abstract Purpose To systematically compare and rank ocular measurements with optical and ultrasound biometers based on big data. Methods PubMed, Embase, the Cochrane Library and the US trial registry ( www.ClinicalTrial.gov ) were used to systematically search trials published up to October 22nd, 2020. We included comparative studies reporting the following parameters measured by at least two devices: axial length (AL), flattest meridian keratometry (Kf), steepest meridian keratometry (Ks), mean keratometry (Km), astigmatism (AST), astigmatism vectors J0 and J45, anterior chamber depth (ACD), aqueous depth (AQD), central corneal thickness (CCT), corneal diameter (CD) and lens thickness (LT). A network-based big data analysis was conducted using STATA version 13.1. Results Across 129 studies involving 17,181 eyes, 12 optical biometers and two ultrasound biometers (with both contact and immersion techniques) were identified. A network meta-analysis for AL and ACD measurements found that statistically significant differences existed when contact ultrasound biometry was compared with the optical biometers. There were no statistically significant differences among the four swept-source optical coherence tomography (SS-OCT) based devices (IOLMaster 700, OA-2000, Argos and ANTERION). As for Ks, Km and CD, statistically significant differences were found when the Pentacam AXL was compared with the IOLMaster and IOLMaster 500. There were statistically significant differences for CCT when the OA-2000 was compared to Pentacam AXL, IOLMaster 700, Lenstar, AL-Scan and Galilei G6. Conclusion For AL and ACD, contact ultrasound biometry obtains the lower values compared with optical biometers. The Pentacam AXL achieves the lowest values for keratometry and CD. The smallest value for CCT measurement is found with the OA-2000.

Abstract Practice of tumor-targeted suicide gene therapy is hampered by unsafe and low efficient delivery of plasmid DNA (pDNA). Using HIV-Tat-derived peptide (Tat) to non-covalently form Tat/pDNA complexes advances the delivery performance. However, this innovative approach is still limited by intracellular delivery efficiency and cell-cycle status. In this study, Tat/pDNA complexes were further condensed into smaller, nontoxic nanoparticles by Ca2+ addition. Formulated Tat/pDNA-Ca2+ nanoparticles mainly use macropinocytosis for intercellular delivery, and their macropinocytic uptake was persisted in mitosis (M-) phase and highly activated in DNA synthesis (S-) phase of cell-cycle. Over-expression or phosphorylation of a mitochondrial chaperone, 75-kDa glucose-regulated protein (GRP75), promoted monopolar spindle kinase 1 (MPS1)-controlled centrosome duplication and cell-cycle progress, but also driven cell-cycle-dependent macropinocytosis of Tat/pDNA-Ca2+ nanoparticles. Further in vivo molecular imaging based on DF (Fluc-eGFP)-TF (RFP-Rluc-HSV-ttk) system showed that Tat/pDNA-Ca2+ nanoparticles exhibited highly suicide gene therapy efficiency in mouse model xenografted with human ovarian cancer. Furthermore, arresting cell-cycle at S-phase markedly enhanced delivery performance of Tat/pDNA-Ca2+ nanoparticles, whereas targeting GRP75 reduced their macropinocytic delivery. More importantly, in vivo targeting GRP75 combined with cell-cycle or macropinocytosis inhibitors exhibited distinct suicide gene therapy efficiency. In summary, our data highlight that mitochondrial chaperone GRP75 moonlights as a biphasic driver underlying cell-cycle-dependent macropinocytosis of Tat/pDNA-Ca2+ nanoparticles in ovarian cancer.

ObjectiveThis study aimed to test the inter-examiner and intra-examiner reliability of macular vascular density (VD) measurement of retinal and choriocapillaris plexuses in healthy children using optical coherence tomography angiography (OCTA).Materials and methodsNinety-two school children were prospectively recruited. Macular OCTA images (6 × 6 mm2) were obtained thrice by two examiners using the RTVue-XR Avanti OCT system. The coefficient of variation (COV), intraclass correlation coefficient (ICC), and Bland–Altman plots were used to evaluate the repeatability and reproducibility.ResultsNinety participants aged 6–15 years were enrolled; two participants were excluded because of low-quality images. In the retina, the reproducibility and repeatability of VD became poorer from superficial to deep retinal capillary plexus (superficial: COV = 4.61–11.11%; intermediate: COV = 7.73–14.15%; deep: COV = 14.60–32.28%). For both reproducibility and repeatability, the ICC ranged from moderate to high (superficial plexus: ICC = 0.570–0.976; intermediate plexus: ICC = 0.720–0.968; deep plexus: ICC = 0.628–0.954). In the choroid, the inter-examiner reproducibility and intra-examiner repeatability of the VD measurement of choriocapillaris were excellent in the macula, fovea, parafovea, and perifovea (COV = 1.00–6.10%; ICC = 0.856–0.950). The parameters of the foveal avascular zone (FAZ) also showed significant reproducibility and repeatability (COV = 0.01–0.21%; ICC = 0.743–0.994).ConclusionThe VD measurements of the choriocapillaris and FAZ parameters using OCTA showed excellent inter-examiner and intra-examiner reliability in school children. The reproducibility and repeatability of the VD of three retinal capillary plexuses depended on the depth of the retinal capillary plexus.

ABSTRACT: A safe, convenience, and effective vaccine for controlling avian influenza virus infection is crucial in scale poultry production. Yeasts are considered useful vaccine vehicles for the delivery of antigens, which has been used to protect human and animal health. We report here the development of H9N2 strain hemagglutinin (HA)-based recombinant protein vaccines (rH9HA) and DNA-RNA-combined vaccine (rH9-DNA-RNA) in Saccharomyces cerevisiae for the first time. The immunogenicity assay indicated that both rH9HA and rH9-DNA-RNA could induce robust production of serum IgG, mucosal sIgA, and cellular immune responses. The reshape and diversification of gut microbiota and an enriched Lactobacillus, Debaryomyces were observed after oral immunization with rH9HA or rH9-DNA-RNA yeast vaccine, which might contribute to modulate the intestinal mucosal immunity and antiviral process. Oral immunized birds with either rH9HA or rH9-DNA-RNA were effectively protected from H9N2 virus challenge. Our findings suggested that yeast-derived H9N2 HA-based recombinant protein vaccines and DNA-RNA-combined nucleic acid vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of avian influenza vaccines to achieve good protection effect.

IntroductionProphylactic vaccination is regarded as the most effective means to control avian flu infection. Currently, there is a need for a universal vaccine that provides broad and long-lasting protection against influenza virus. Meanwhile, although yeast-based vaccines have been used in clinic, studies are still required to further understand the molecular mechanism of yeast-based vaccines under physiological conditions.MethodsWe generated a yeast-based vaccine against influenza hemagglutinin (HA) of H5, H7 and H9 using surface displaying technology and evaluated the protective efficacy of chickens after exposure to H9N2 influenza virus.ResultsOral yeast vaccine provided less clinical syndrome, reduced viral loading and alleviated airway damage significantly. Compared to the commercial inactivated vaccine, yeast vaccine stimulated the activation of splenic NK and APCs cells and boosted TLR7-IRF7-IFN signaling in spleen. Meanwhile, γδ T cells in the bursa of Fabricius were activated and the innate lymphoid cells (ILCs) in the bursa of Fabricius promoted the CILPs to differentiate to ILC3 cells in oral yeast birds. Moreover, the reshaped gut microbiota and a suppressed Th17-IL17-mediated inflammation in intestine was observed in oral yeast chickens, which might facilitate the recovery of intestinal mucosal immunity upon virus infection. Collectively, our findings suggest that oral yeast based multivalent bird flu vaccines provide an attractive strategy to update host defense function via reshapes of multi-systemic immune homeostasis.

IntroductionThe H5N8 influenza virus is a highly pathogenic pathogen for poultry and human. Vaccination is the most effective method to control the spread of the virus right now. The traditional inactivated vaccine, though well developed and used widely, is laborious during application and more interests are stimulated in developing alternative approaches.MethodsIn this study, we developed three hemagglutinin (HA) gene-based yeast vaccine. In order to explore the protective efficacy of the vaccines, the gene expression level in the bursa of Fabricius and the structure of intestinal microflora in immunized animals were analyzed by RNA seq and 16SrRNA sequencing, and the regulatory mechanism of yeast vaccine was evaluated.ResultsAll of these vaccines elicited the humoral immunity, inhibited viral load in the chicken tissues, and provided partial protective efficacy due to the high dose of the H5N8 virus. Molecular mechanism studies suggested that, compared to the traditional inactivated vaccine, our engineered yeast vaccine reshaped the immune cell microenvironment in bursa of Fabricius to promote the defense and immune responses. Analysis of gut microbiota further suggested that oral administration of engineered ST1814G/H5HA yeast vaccine increased the diversity of gut microbiota and the increasement of Reuteri and Muciniphila might benefit the recovery from influenza virus infection. These results provide strong evidence for further clinical use of these engineered yeast vaccine in poultry.

Infectious bursal disease (IBD), as a highly infectious immunosuppressive disease, causes severe economic losses in the poultry industry worldwide. Saccharomyces cerevisiae is an appealing vehicle used in oral vaccine formulations to safely and effectively deliver heterologous antigens. It can elicit systemic and mucosal responses. This study aims to explore the potential as oral an vaccine for S. cerevisiae expressing the capsid protein VP2 of IBDV. We constructed the recombinant S. cerevisiae, demonstrated that VP2 was displayed on the cell surface and had high immunoreactivity. By using the live ST1814G/Aga2-VP2 strain to immunize the mice, the results showed that recombinant S. cerevisiae significantly increased specific IgG and sIgA antibody titers, indicating the potential efficacy of vaccine-induced protection. These results suggested that the VP2 protein-expressing recombinant S. cerevisiae strain was a promising candidate oral subunit vaccine to prevent IBDV infection.

Heat waves, particularly humid heat waves that occur together with high temperatures and humidity, pose a severe hazard to human health in the context of global warming. In this work, daily observations from more 1500 sites are used to define dry and humid heat waves in a warm season (May to September) and assess their spatiotemporal characteristics during 1960–2015. Dry heat waves are identified with daily maximum temperatures, while humid heat waves are identified based on the wet bulb temperature, derived from both temperature and humidity. We compare dry and humid heat waves from various aspects based on multiple heat wave indices, including their frequency, duration, and intensity. Results suggest that the occurrence of both dry and humid heat wave days in China is higher in the southern than in the northern part of China, due to the higher air temperature and humidity therein. Compared to dry heat waves, humid heat waves are of higher amplitude but shorter duration. The long-term trend analysis shows that the occurrence of both dry and humid heat waves has increased overall over the last 50 years, with an especially rapid increase in the last 20 years, which may be related to China’s rapid warming since the late 1980s. The future projections with multiple global climate models indicate that China will experience more frequent, stronger, and longer-duration dry and humid heat waves in the future, under both intermediate and high-emission pathways.

ImportanceOptical coherence tomography angiography (OCTA) has been widely applied into children, however, few studies have assessed the repeatability and reproducibility of papillary and peripapillary VD in healthy children.ObjectiveTo assess the precision of papillary and peripapillary vascular density (VD) measurements using optical coherence tomography angiography (OCTA) and analyze the effects of the signal strength index (SSI) and axial length (AL) on precision estimates.Design, setting, and participantsThis was a prospective observational study. Seventy-eight children aged 6–16 years underwent 4.5 × 4.5 mm OCTA (RTVue XR Avanti) disc scans: two scans by one examiner (repeatability) and two additional scans by another examiner (reproducibility). Within-subject standard deviation (Sw), test-retest reproducibility (TRT), within-subject coefficient of variation (CoV), intraclass correlation coefficient (ICC), and Bland–Altman analysis were performed.Main outcomes and measuresIn repeatability measurement, the fluctuation ranges (minimum to maximum) of VD between intraexaminer A/B in Sw, TRT, CoV, and ICC were (1.05–2.17)% / (1.16–2.32)%, (2.9–6)% / (3.21–6.44)%, (1.9–4.47)% / (2.08–5)%, and (0.588–0.783)% / (0.633–0.803)%, respectively. In reproducibility measurement, the fluctuation ranges of VD in Sw, TRT, CoV, and ICC were 1.11–2.13%, 3.07–5.91%, 1.99–4.41%, and 0.644–0.777%, respectively. VD was negatively correlated with SSI in most sectors of the peripapillary (e.g., inferior nasal, temporal inferior, temporal superior, superior temporal, and superior nasal). AL was positively correlated with inferior temporal VD and negatively correlated with superior nasal VD.Conclusion and relevanceOptical coherence tomography angiography showed moderate-to-good repeatability and reproducibility for papillary and peripapillary perfusion measurements in healthy children. The SSI value affects most of the peripapillary VD, while AL affects only the temporal inferior and nasal superior peripapillary VD.

ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV) is a serious threat to the global swine industry. As a typical immunosuppressive virus, PRRSV has developed a variety of complex mechanisms to escape the host innate immunity. In this study, we uncovered a novel immune escape mechanism of PRRSV infection. Here, we demonstrate for the first time that the endoplasmic reticulum (ER)-resident N-acetyltransferase Nat9 is an important host restriction factor for PRRSV infection. Nat9 inhibited PRRSV proliferation in an acetyltransferase activity-dependent manner. Mechanistically, glycoprotein 5 (GP5) of PRRSV was identified as interacting with Nat9 and being N-terminally acetylated by it, which generates a GP5 degradation signal, promoting the K27-linked-ubiquitination degradation of GP5 to decrease virion assembly. Meanwhile, the expression of Nat9 was inhibited during PRRSV infection. In detail, two transcription factors, ETV5 and SP1, were screened out as the key transcription factors binding to the core promoter region of Nat9, and the PRRSV nonstructural protein 1β (Nsp1β), Nsp4, Nsp9, and nucleocapsid (N) proteins were found to interfere significantly with the expression of ETV5 and SP1, thereby regulating the transcription activity of Nat9 and inhibiting the expression of Nat9. The findings suggest that PRRSV decreases the N-terminal acetylation of GP5 to support virion assembly by inhibiting the expression of Nat9. Taken together, our findings showed that PRRSV has developed complex mechanisms to inhibit Nat9 expression and trigger virion assembly. IMPORTANCE To ensure efficient replication, a virus must hijack or regulate multiple host factors for its own benefit. Understanding virus-host interactions and the molecular mechanisms of host resistance to PRRSV infection is necessary to develop effective strategies to control PRRSV. The N-acetyltransferase Nat9 plays important roles during virus infection. Here, we demonstrate that Nat9 exhibits an antiviral effect on PRRSV proliferation. The GP5 protein of PRRSV is targeted specifically by Nat9, which mediates GP5 N-terminal acetylation and degradation via a ubiquitination-dependent proteasomal pathway. However, PRRSV manipulates the transcription factors ETV5 and SP1 to inhibit the expression of Nat9 and promote virion assembly. Thus, we report a novel function of Nat9 in PRRSV infection and elucidate a new mechanism by which PRRSV can escape the host innate immunity, which may provide novel insights for the development of antiviral drugs.

Abstract The wake‐up phenomenon widely exists in hafnia‐based ferroelectric capacitors, which causes device parameter variation over time. Crystallization at a higher temperature has been reported to be effective in eliminating wake‐up, but high temperature may yield the monoclinic phase or generate more oxygen vacancies. In this work, a unidirectional annealing method is proposed for the crystallization of Hf0.5Zr0.5O2 (HZO) superlattice ferroelectrics, which involves heating from the Pt/ZrO2 interface side. It is demonstrated that 600 °C annealing only leads to a moderate content of monoclinic phase in HZO, and the TiN/HZO/Pt capacitor exhibits wake‐up free nature and a switchable remnant polarization value of 27.4 µC cm−2. On the other hand, heating from the TiN/HfO2 side, or using 500 °C annealing temperature, could yield ferroelectric devices that require a wake‐up process. The special configuration of Pt/ZrO2 is verified by comparative studies with several other superlattice structures and HZO solid‐state solutions. It is discovered that heating from the Pt/HfO2 side at 600 °C leads to high leakage current and a memristor behavior. The mechanisms of ferroelectric phase stabilization and memristor formation have been discussed. The unidirectional heating method can also be useful for other hafnia‐based ferroelectric devices.

Wolbachia induced cytoplasmic incompatibility (CI) is caused by linked pairs of genes named cifA and cifB. Here, authors show that the residues at interfaces of the CidA-CidB complex is crucial for their binding and contribute to the diversity of CI.

Abstract Background To evaluate the precision of corneal higher-order aberrations measurements after small incision lenticule extraction (SMILE) using the Sirius Scheimpflug-Placido topographer (CSO, Italy). Methods Seventy-five eyes from 75 postoperative subjects were included in this prospective study. Three consecutive corneal aberrometric measurements were obtained with the Scheimpflug-Placido topographer by two experienced operators to assess intra- and inter-observer reproducibility. The within-subject standard deviation (Sw), test-retest repeatability (TRT) and the intraclass correlation coefficient (ICC) were calculated. Results For intraobserver repeatability of anterior and total corneal aberrations, all ICCs were more than 0.922, except for trefoil (0.722 to 0.768). The ICCs of total root mean square (RMS), coma Z (3, ± 1), and spherical aberration Z (4, 0) were over 0.810 while higher-order RMS, trefoil Z (3, ± 3), and astigmatism II Z (4, ± 2) were below 0.634 for posterior corneal surface aberrations. All Sw values for all types of aberrations were equal to or below 0.07 μm. Regarding interobserver reproducibility, all TRT values were no more than 0.12 μm, 0.05 μm, and 0.11 μm for anterior, posterior, and total corneal aberrations, respectively. The ICC values ranged from 0.875 to 0.989, from 0.686 to 0.976 and over 0.834 for anterior, posterior, and total corneal aberrations, respectively. Conclusions The repeatability of measurements of anterior and total corneal aberrations with the Sirius system in corneas after SMILE surgery was high, except for trefoil. There was some variability in posterior corneal aberrometric measurements. High reproducibility of corneal aberrometric measurements was observed between measurements of both examiners, except for trefoil, with poor to moderate reproducibility.

Cell-penetrating peptides (CPPs), developed for more than 30 years, are still being extensively studied due to their excellent delivery performance. Compared with other delivery vehicles, CPPs hold promise for delivering different types of drugs. Here, we review the development process of CPPs and summarize the composition and classification of the CPP-based delivery systems, cellular uptake mechanisms, influencing factors, and biological barriers. We also summarize the optimization routes of CPP-based macromolecular drug delivery from stability and targeting perspectives. Strategies for enhanced endosomal escape, which prolong its half-life in blood, improved targeting efficiency and stimuli-responsive design are comprehensively summarized for CPP-based macromolecule delivery. Finally, after concluding the clinical trials of CPP-based drug delivery systems, we extracted the necessary conditions for a successful CPP-based delivery system. This review provides the latest framework for the CPP-based delivery of macromolecular drugs and summarizes the optimized strategies to improve delivery efficiency.

Abstract Background Current treatment options for glioma are limited, and the prognosis of patients with glioma is poor as the available drugs show low therapeutic efficacy. Furthermore, the molecular mechanisms associated with glioma remain poorly understood. METTL1 mainly catalyzes the formation of N(7)-methylguanine at position 46 of the transfer RNA sequence, thereby regulating the translation process. However, the role of METTL1 in glioma has not been studied to date. The purpose of this study was to analyze the expression and prognosis of METTL1 in glioma, and to explore the potential analysis mechanism. Methods Data from five publicly available databases were used to analyze METTL1 expression across different tumor types and its differential expression between carcinoma and adjacent normal tissues. The expression of METTL1 in glioma was further validated using real-time polymerase chain reaction and immunohistochemistry. Meanwhile, siRNA was used to knockdown METTL1 in U87 glioma cells, and the resultant effect on glioma proliferation was verified using the Cell Counting Kit 8 (CCK8) assay. Furthermore, a nomogram was constructed to predict the association between METTL1 expression and the survival rate of patients with glioma. Results METTL1 expression increased with increasing glioma grades and was significantly higher in glioma than in adjacent noncancerous tissues. In addition, high expression of METTL1 promoted cell proliferation. Moreover, METTL1 expression was associated with common clinical risk factors and was significantly associated with the prognosis and survival of patients with glioma. Univariate and multivariate Cox regression analyses revealed that METTL1 expression may be used as an independent prognostic risk factor for glioma. Furthermore, results of functional enrichment and pathway analyses indicate that the mechanism of METTL1 in glioma is potentially related to the MAPK signaling pathway. Conclusions High METTL1 expression is significantly associated with poor prognosis of patients with glioma and may represent a valuable independent risk factor. In addition, high expression of METTL1 promotes glioma proliferation and may regulate mitogen-activated protein kinase (MAPK) signaling pathway. Thus, METTL1 may be a potential biomarker for glioma. Further investigations are warranted to explore its clinical use.

Purpose: To investigate the relationship between corneal biomechanical and ocular biometric parameters, and to explore biomechanical asymmetry between anisometropic eyes using the corneal visualization Scheimpflug technology device (Corvis ST).Methods: 180 anisometropic participants were included. Participants were divided into low (1.00≤△Spherical equivalent (SE) < 2.00D), moderate (2.00D≤△SE < 3.00D) and high (△SE ≥ 3.00D) anisometropic groups. Axial length (AL), keratometry, anterior chamber depth (ACD) and corneal biomechanical parameters were assessed using the OA-2000 biometer, Pentacam HR and Corvis ST, respectively.Results: The mean age of participants was 16.09 ± 5.64 years. Stress-Strain Index (SSI) was positively correlated with SE (r = 0.501, p < 0.001) and negatively correlated with AL (r = -0.436, p < 0.001). Some other Corvis ST parameters had weak correlation with SE or AL. Corneal biomechanical parameters except for time of first applanation (A1T), length of second applanation (A2L), deformation amplitude (DA), first applanation stiffness parameter (SPA1) and ambrosia relational thickness-horizontal (ARTh) were correlated with ametropic parameters (SE or AL) in multiple regression analyses. A1T, velocity of first applanation (A1V), time of second applanation (A2T), A2L, velocity of second applanation (A2V), corneal curvature radius at highest concavity (HCR), peak distance (PD), DA, deformation amplitude ratio max (2 mm) (DAR), SPA1, integrated radius (IR), and SSI showed significant differences between fellow eyes (p < 0.05). There was no significant difference in asymmetry of corneal biomechanics among the three groups (p > 0.05). Asymmetry of some biomechanical parameters had weak correlation with asymmetry of mean corneal curvatures and ACD. However, asymmetry of corneal biomechanical parameters was not correlated with asymmetry of SE or AL (p > 0.05).Conclusion: More myopic eyes had weaker biomechanical properties than the contralateral eye in anisometropia. However, a certain linear relationship between anisometropia and biomechanical asymmetry was not found.

ObjectiveTo establish a normative database for the vascular density (VD) in macular, disc, and peripapillary regions in healthy myopic children and to evaluate associated ocular features with optical coherence tomography angiography (OCTA).MethodsThis was an observational, prospective and cross-sectional study. 776 Chinese healthy myopic children (375 boys and 401 girls) were enrolled, mean (±SD) age 9.84 ± 1.98 (range 6–16) years. En-face angiogram OCTA was performed on 6 mm × 6 mm retinal and 4.5 mm × 4.5 mm disc regions. VD measurements in the macular retina were segmented into the four regions: superficial capillary plexus (SCP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and choriocapillaris (CC). Correlations between macular, disc, and peripapillary VD and possible influencing factors [age, gender, axial length (AL), spherical equivalent refraction (SER), right/left eye, and signal strength index (SSI)] were assessed by Pearson’s correlation and multivariate regression analysis.ResultsFor macular scans, the corrected VD in the ICP region was (48.25 ± 4.24)% for the whole macular retina. The macular ICP VD in most sections was lower than the SCP, DCP, and CC (all P < 0.001). The corrected VD in CC was (72.96 ± 4.42)% for the whole macular retina. The macular CC VD in every section was all higher than the SCP, ICP, and DCP (all P < 0.001). The size of foveal avascular zone (FAZ) and foveal VD 300 (FD-300) was 0.28 mm2± 0.10 mm2 and (58.43 ± 4.17)% respectively. For disc scans, the corrected VD was (58.04 ± 2.73)% for the whole disc area. Both AL and SER were strongly correlated with ICP, DCP, and CC VD in all regions (all P < 0.01). Larger SSI was correlated with a lower VD in the SCP and ICP, and a higher VD in DCP and CC (all P < 0.01).ConclusionVascular density values provide large scale normative data on macular, disc, and peripapillary vascular parameters in a large sample of healthy myopic children with OCTA measured in the four different retinal plexuses and regions. The VD in different regions had various influencing factors; mainly a close correlation with AL and SSI.

In this study, a one-step electrochemical aptasensor was developed to detect the biomarker vascular endothelial growth factor (VEGF), an important protein in the pathogenesis of many retinal diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. The aptamer has a good affinity and can rapidly identify and capture VEGF based on its unique structure. We designed a VEGF aptasensor based on the aptamer recognition and complex metallo nanoenzyme particles as an electron exchange center and bridge between capture DNA and electrode. The aptamers maintained the hairpin structure to avoid nonspecific surface adsorption and expose the capture sequence outwards when the target was inexistent. Conversely, the aptamers opened the hairpin structure to release space to accomplish binding between VEGF and DNA, resulting in increased impedance. The performance of the electrochemical aptasensor is detected by electrochemical impedance spectroscopy (EIS). The limit of detection by EIS was as low as 8.2 pg ml−1, and the linear range was 10 pg ml−1–1 μg ml−1. The electrochemical aptasensor also showed high specificity and reproducibility.

PurposeThis study aimed to compare the efficacy and safety of corneal refractive therapy (CRT) lenses and vision shaping treatment (VST) lenses for myopia control in children.MethodsMedical records of 1,001 children (2,002 eyes) who had been fitted with orthokeratology lenses for over 1.5 years were retrospectively reviewed. We collected the clinical data of four types of orthokeratology (OK) lenses available: one CRT lens (brand: CRT) and three VST lenses (brands: Euclid, Alpha, and Hiline) over 1.5 years. Results were compared and analyzed using a one-way ANOVA and Pearson's chi-square test.ResultsAxial length elongation in the CRT lens group was 0.13 ± 0.02 mm faster than that in the Euclid lens, 0.1 ± 0.02 mm faster in the Alpha lens, and 0.08 ± 0.02 mm faster in the Hiline lens over the 1.5-year period (all P < 0.05). Among the subjects, 37.3% of them using the CRT lens experienced more than 1 D of refractive growth, compared with 20.2–30.8% of subjects wearing the three groups of VST lenses (all P < 0.05). A lower incidence of total adverse events was found with the CRT lenses compared with the VST lenses (P < 0.05), especially corneal staining. No difference was found in axial length elongation, refraction growth, and incidence of adverse events among the three types of VST lenses (all P > 0.05).ConclusionsCompared with the VST lenses, CRT lenses demonstrated a weaker effect on myopia control but with a better safety profile. Different types of VST lenses had similar efficacy and safety in the context of controlling myopia progression.

A recent study showed that patients with coronavirus disease 2019 (COVID-19) have gastrointestinal symptoms and intestinal flora dysbiosis. Yeast probiotics shape the gut microbiome and improve immune homeostasis. In this study, an oral candidate of yeast-derived spike protein receptor-binding domain (RBD) and fusion peptide displayed on the surface of the yeast cell wall was generated. The toxicity and immune efficacy of oral administration were further performed in Institute of Cancer Research (ICR) mice. No significant difference in body weights, viscera index, and other side effects were detected in the oral-treated group. The detectable RBD-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and more complex microbiota were detected from oral administration mice compared with those of the control group. Interestingly, the recombinant yeast was identified in female fetal of the high-dose group. These results revealed that the displaying yeast could fulfill the agent-driven immunoregulation and gut microbiome reconstitution. The findings will shed light on new dimensions against SARS-CoV-2 infection with the synergistic oral agents as promising non-invasive immunization and restoring gut flora.

Abstract Background To compare the difference in central corneal thickness (CCT) measurements in normal eyes between a rotating Scheimpflug camera combined with a Placido-disk corneal topographer (Sirius, CSO, Italy) and ultrasound pachymetry (USP). Methods A systematic literature search was conducted for relevant studies published on PubMed, Medline, EMBASE, and the Cochrane Library and ClinicalTrials.gov from inception to August 1st, 2019. Primary outcome measures were CCT measurements between Sirius and USP. A random effects model was used to pool CCT measurements. Results A total of twelve studies involving 862 eyes were included in this meta-analysis. The meta-analysis found CCT measurements between Sirius and USP to be statistically significantly different (P

In recent years, hafnia-based ferroelectrics have attracted enormous attention due to their capability of maintaining ferroelectricity below 10 nm thickness and excellent compatibility with microelectronics flow lines. However, the physical origin of their ferroelectricity is still not fully clear, although it is commonly attributed to a polar Pca 2 _1 orthorhombic phase. The high-temperature paraelectric phases (the tetragonal phase or the cubic phase) do not possess a soft mode at the Brillouin zone center, thus the ferroelectric distortion has to be explained in terms of trilinear coupling among three phonon modes in the tetragonal phase. It is necessary to explore new materials with possible ferroelectricity due to the polar Pca 2 _1 phase, which in turn should be very helpful in evaluating the microscopic theory for ferroelectric hafnia. In this work, based on the idea of the Materials Genome Engineering, a series of hafnia-like ferroelectrics have been found, exemplified by LaSeCl, LaSeBr, LuOF and YOF, which possess adequate spontaneous polarization values and also relatively favorable free energies for the polar phase. Their common features and individual differences are discussed in detail. In particular, a promising potential ferroelectric material, Pca 2 _1 phase LuOF, is predicted and recommended for further experimental synthesis and investigation.

PurposeTo evaluate measurement precision and to compare the Pentacam AXL (Oculus Optikgeräte, Wetzlar, German), a new optical biometer based on Scheimpflug imaging and partial coherence interferometry (PCI) with that of the OA-2000 biometer (Tomey, Nagoya, Japan), which combines swept-source optical coherence tomography (SS-OCT) and Placido-disk topography.MethodsAxial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), mean keratometry (Km), astigmatism vectors J0, J45, and corneal diameter (CD) were measured in triplicate by two technical operators. Within-subject standard deviation (Sw), repeatability and reproducibility (2.77 Sw), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) were used to assess the Pentacam AXL intra-observer repeatability and inter-observer reproducibility. Paired t-test and Bland-Altman plots were used to determine the agreement between the two biometers.ResultsThe new optical biometer had high intra-observer repeatability [all parameters evaluated had low CoV (0.88)]. Inter-observer reproducibility was also excellent, with high ICC (>0.95) and low CoV (

Abstract Background To investigate the biomechanical properties of the cornea in myopic eyes using corneal visualization Scheimpflug technology (Corvis ST). The relationships between the biomechanical properties of the cornea and the degree of myopia were also investigated. Methods 265 eyes of 265 subjects were included. Based on spherical equivalent (SE) in diopters (D), participants were divided into four groups: low myopia/control (SE: − 0.50 to − 3.00D), moderate myopia (SE: − 3.00 to − 6.00D), high myopia (SE: − 6.00 to − 10.00D) and severe myopia (SE greater than − 10.00D). Axial length (AL), anterior segment parameters, and corneal biomechanical properties were obtained with the Lenstar LS900, Pentacam HR and Corvis ST, respectively. Results Mean (±SD) SE was − 7.29 ± 4.31D (range: − 0.63 to − 25.75D). Mean AL was 26.31 ± 1.82 mm (range: 21.87 to 31.94 mm). Significant differences were detected within the four groups in terms of six corneal biomechanical parameters: deformation amplitude (DA), time from start until second applanation (A2-time), length of flattened cornea at the second applanation (A2-length), corneal velocity during the first and second applanation (A2-velocity), time from start to highest concavity (HC-time), and central curvature at highest concavity (HC radius). AL was positively associated with DA whereas negatively associated with A1-velocity and A2-length. SE was positively associated with A2-time, HC-time and A2-velocity, whereas negatively associated with DA. IOP was positively associated with four corneal biomechanical parameters and negatively associated with three parameters. Conclusions Eyes with severe myopia showed greater DA, lesser A2 time, HC time, and faster A2-velocity compared to low to high myopia. This suggests the cornea becomes weaker and more deformable with elongation of axial length with corresponding increases in myopia. DA, A2-time and A2-velocity could be useful corneal biomechanical indicators in patients with myopia.

Abstract Purpose To assess the repeatability and reproducibility of swept-source optical coherence tomography (SS-OCT) and Scheimpflug system and evaluate the agreement between the two systems in measuring multiple corneal regions in children. Methods Pachymetric and keratometric maps for both systems were evaluated. Central, midperipheral and peripheral corneal thickness (CT), keratometry and astigmatism power vectors were recorded. The three outcomes yielded by the same observer were used to assess intraobserver repeatability. The differences in the mean values provided by each observer were used to evaluate interobserver reproducibility. Within-subject standard deviation, test-retest repeatability (TRT) and coefficient of variation (CoV) were used to analyze the intraobserver repeatability and interobserver reproducibility. Paired T-test and Bland-Altman were used to appraise interdevice agreement. Results Seventy-eight eyes of 78 children were included. The CoV was ≤2.12 and 1.10%, respectively, for repeatability and reproducibility. TRT and CoV were lower for central and paracentral CT measurements than for peripheral measurements. The SS-OCT device generated higher precision when acquiring CT data, whereas Scheimpflug system showed higher reliability when measuring corneal keratometry. Although the CT readings measured using SS-OCT were significantly thinner than Scheimpflug device (P

Abstract The 2019 novel coronavirus disease (COVID-19) has now swept through the continents and poses a global threat to public health. Several investigations have been conducted to identify whether COVID-19 can be transmitted through the ocular route, and the conclusion is that it is a potential route but remains uncertain. Due to the face-to-face communication with patients, frequent exposure to tears and ocular discharge, and the unavoidable use of equipment which requires close proximity, ophthalmologists carry a high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on 33 articles published by Chinese scholars, guidelines and clinical practice experience in domestic hospitals, we have summarized the Chinese experience through the lens of ophthalmology, hoping to make a contribution to protecting ophthalmologists and patients around the world.

Abstract Background To evaluate the effect of orthokeratology on precision of measurements in children using a new swept-source optical coherence tomography (SS-OCT) optical biometer (OA-2000), and agreement between its measurements and those provided by the commonly used IOLMaster based on partial coherence interferometry (PCI). Methods This study recruited fifty-one eyes of 51 normal children (8–16 years). An operator took measurements with the two biometers. Then, a second operator took measurements with the SS-OCT biometer. After orthokeratology was performed for one month, the same operators repeated the same procedures. Axial length (AL), mean keratometry (Km) at 2.5 mm and 3.0 mm diameters (Km2.5 and Km3.0), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT) and corneal diameter (CD) were analyzed. Results With the SS-OCT optical biometer, the test-retest repeatability of AL measurements was 0.95. The 95% limits of agreement of difference between the two devices for CD parameter were up to 1.53 mm. After orthokeratology, the fluctuation ranges of difference for Km3.0 measurement was 1.11 times higher than before orthokeratology, while the absolute values of difference for AL, Km2.5, ACD and CD measurements were comparable. Conclusions Before and after orthokeratology, the SS-OCT biometer showed high repeatability and reproducibility for all measurements. Wearing orthokeratology contact lenses affected the agreement between SS-OCT and PCI biometers for Km3.0 measurements. The CD measurement showed poor agreement between the two devices.