AIM: To analyze the etiologies, disease course, clinical characteristics, and surgical management patterns of non-traumatic corneal perforation in China. METHODS: This multicenter, retrospective study reviewed medical records from patients with non-traumatic corneal perforation treated at 16 tertiary hospitals in China from 2019 to 2021. Data collected included demographics, etiology, disease duration, perforation location, visual acuity on admission, and surgical procedures. RESULTS: A total of 796 eyes from 791 patients were included, comprising 271 women (34.2%) and 520 men (65.7%), with a mean age of 58.4±15.6y (range, 0.38–92y). Infectious keratitis was the leading cause (62.6%), followed by postoperative complications (12.8%) and autoimmune diseases (8.7%). Fungal infections were more prevalent in rural areas, while autoimmune-related perforations were more common in females. Autoimmune cases more frequently presented with a chronic disease course and better visual acuity at admission compared to infectious causes (P<0.001). Among infectious causes, viral keratitis exhibited the highest proportion of chronic cases (65.7%). Perforation location varied significantly by etiology, with infectious cases predominantly central and autoimmune cases more often peripheral or limbal (P<0.001). Overall, 88.3% of eyes presented with poor visual acuity on admission. Most eyes (90.0%) required surgical intervention. Penetrating keratoplasty was the most common procedure, especially for central perforations, while lamellar keratoplasty was preferred for peripheral and autoimmune-related cases. CONCLUSION: This nationwide, multicenter study provides a comprehensive epidemiologic characterization of non-traumatic corneal perforation. Infectious keratitis was identified as the predominant etiology. Distinct patterns in disease progression, perforation location, and surgical intervention were observed across etiologic subgroups. These findings underscore the relevance of etiology-stratified assessment and support the need for tailored clinical management strategies.

To develop a deep learning-based computer-aided diagnostic model for the automated identification of corneal microneuromas from in vivo confocal microscopy (IVCM) images and to preliminarily assess its potential clinical utility in the context of diabetic corneal neuropathy. This retrospective diagnostic accuracy study was conducted at the Ophthalmology Center of Renmin Hospital of Wuhan University from August 2021 to December 2023. A total of 293 patients (358 eyes) underwent IVCM, yielding 4,554 corneal images, which were divided into a training set (3,542 images) and an internal test set (1,012 images). For external validation, an independent cohort of 87 patients (103 eyes) contributed 506 IVCM images from Wuhan Aier Hankou Eye Hospital. All images underwent standardized quality control and graded annotation by three senior corneal specialists prior to model development. The modeling pipeline included automated image-quality assessment and non-target-layer filtering, microneuroma detection, and microneuroma subtype classification. Model generalizability and potential clinical applicability were evaluated using the independent external dataset. The diagnostic model achieved an overall accuracy of 0.975 in image-quality screening. For identifying the presence or absence of microneuromas, the overall accuracy was 0.837 on the internal test set and 0.812 on the external test set. The accuracy range for the three morphological subtypes was 0.798-0.886. In the image-reading experiment, assistance from the model significantly improved the junior physicians' accuracy from 0.687 to 0.875 (P < 0.001) and increased their reading efficiency 2.2-fold, reducing the average reading time from 63.4 ± 15.2 s to 28.5 ± 6.8 s (t = 19.3, P < 0.001). These findings reflect model performance within the available datasets. We developed a deep learning-based system capable of automatically analyzing IVCM images to detect corneal microneuromas. The model demonstrated strong and consistent performance across internal and external datasets and substantially enhanced the diagnostic accuracy and efficiency of junior clinicians.

AIMS:Vascular endothelial growth factor (VEGF) drives corneal neovascularization (CorNV), yet no anti-VEGF eye drops are clinically available. We report phase I/IIa trials of KH906, a novel topical anti-VEGF agent. METHODS:Trial 1 was a phase I, open-label, dose-escalation study in healthy adults receiving KH906 at 0.1, 0.5, or 1.0 mg/mL. Trial 2 was a phase I, multicentre, open-label, dose-escalation study in patients with CorNV at the same doses. Trial 3 was a phase IIa, randomized, double-masked, placebo-controlled study assigning patients 1:1:1 to 0.5 mg/mL KH906, 1.0 mg/mL KH906, or placebo. Primary endpoints were safety, tolerability and pharmacokinetics (Trials 1 and 2) and safety, tolerability and efficacy (Trial 3). RESULTS:From 10 December 2018 to 16 June 2021, 18 healthy participants and 39 patients with CorNV were enrolled. One treatment-related adverse event occurred: a mild corneal epithelial defect in the 1.0-mg/mL group in Trial 3. No serious or other drug-related adverse events were observed. In Trial 2, KH906 reduced the CorNV area and vessel length. In Trial 3, at Day 28, mean changes in CorNV area were -1.2 (0.8), -1.6 (1.1) and -0.7 (1.1), and mean changes in CorNV length were -8.0 (7.3), -6.6 (5.9) and -1.7 (7.9), in the 0.5-mg/mL KH906, 1.0-mg/mL KH906 and placebo groups, respectively. The 1.0-mg/mL dose produced greater reduction of the CorNV area than lower doses, indicating a dose-response effect. CONCLUSIONS:KH906 appears safe and well tolerated and demonstrates preliminary efficacy in reducing CorNV, with higher doses showing greater effect, supporting further clinical development.

OBJECTIVES:To describe the demographic and clinical characteristics of inpatients with corneal blindness in China and identify independent risk factors. METHODS:This multicentre, retrospective, observational study was conducted by 16 clinical centres in 15 provincial-level administrative regions across China. Inpatients discharged with a primary diagnosis of corneal disease between January 1, 2019, and December 31, 2021, were included. The demographic and clinical characteristics of patients with corneal blindness were evaluated, and risk factors were identified via multivariate regression analysis. Regional variations in the corneal blindness and keratoplasty rates were also assessed. RESULTS:A total of 15,937 patients with corneal diseases were analysed; 9272 of these patients (58.18%) had corneal blindness. Most patients were male (6614 [71.33%]), with a median age of 55 years (IQR 45-66). The most common types of corneal blindness were keratitis (5141 [55.45%]) and corneal injury (3153 [34.01%]). Multivariate regression analysis revealed that male sex (aOR 1.171, 95% CI 1.081-1.268), older age (aOR 1.021, 95% CI 1.019-1.024), rural residence (aOR 1.348, 95% CI 1.254-1.448), lack of medical insurance (aOR 1.215, 95% CI 1.123-1.314), living in the western region (aOR 1.247, 95% CI 1.152-1.350) and having coexisting glaucoma (aOR 2.288, 95% CI 1.890-2.768) were risk factors for corneal blindness. The western region had the highest percentage of corneal blindness cases (p < 0.001, 61.23%) but the lowest percentage of keratoplasty cases (p < 0.001, 24.68%). CONCLUSIONS:The study on identifying risk factors for corneal blindness provides evidence for optimising clinical decision-making and may contribute to reducing the incidence of corneal blindness.

Precise drug target discovery is pivotal to mitigating the escalating costs and high attrition rates that characterize pharmaceutical research and development. Given that traditional single-omics methods often fail to elucidate the systemic complexity of human diseases, deep learning (DL)-enabled multi-omics integration has emerged as a transformative frontier. This review systematically summarizes the advancements in DL-driven multi-omics integration for drug target discovery. First, the multi-omics data foundation and integration strategies are delineated, followed by an exploration of the DL architectures utilized for processing such data. Subsequently, the efficacy of DL-driven multi-omics integration is examined regarding the identification of novel disease drivers, prediction of synthetic lethality interactions, and prioritization of therapeutic targets. Finally, addressing persistent challenges related to data sparsity, model interpretability, and target druggability and validation hurdles, emerging opportunities driven by Generative AI, Large Multimodal Models (LMMs), Explainable AI (XAI), and multidimensional feasibility assessment frameworks are discussed in the context of advancing precision medicine.

Photochromic ceramics attracted great interests of researchers due to the potential applications in anticounterfeiting, information storage and optical detector. However, the single color change and fixed photochromic absorption limited the further development in practical application. In this work, the Mo6+ was introduced into the typical KSr2Nb5O15 (KSN) photochromic ceramics, and the effects on the microstructures and photochromic properties were systematically investigated. The results showed that, introducing of Mo6+ into KSN ceramics simultaneously caused both Mo6+ substitution and formation of MoO3 secondary phase. And a competitive effect between these two variations in KSN host was existed and dynamically adjusted by the introducing concentration of Mo6+. Benefiting from these two variations, the distribution of carrier traps was optimized and the heterojunction structure between KSN and MoO3 phases was established. The photochromic contrast value of KSN host was enhanced over 60 %, and the photochromic color change aslo modulated, the color difference triangle Eab increased from 7.5 to 22.5. This work provided a novel strategy for controllable modulation about the photochromic properties of oxide ceramics both in photochromic contrast and absorption behavior.

With the development of related technology, the practical application scenarios put forward new requirements of multi-color and controllable modulation for inorganic photochromic materials. In this work, a novel inorganic photochromic MgNb2O6 ceramic has been proposed, exhibiting distinctly different photochromic behavior from KSr2Nb5O15 ceramics. Through in-situ compositing, MgNb2O6 secondary phases nucleated epitaxially within the KSr2Nb5O15 matrix, with interfacial KNbO3 transition layers (of about 1-2 nm thickness by AC-TEM) spontaneously forming at phase boundaries, which built the specific heterojunction structure. The central positions of photochromic absorption bands could be modulated from 426 nm to 495 nm, the related color-difference values (triangle Eab) covered from 3.95 to 16.40. This work provided a novel thought for the color modulation strategy of inorganic photochromic materials.

This review provides a systematic examination of recent advances in bismuth vanadate (BiVO4) photocatalyst research based on First-principles calculations. A particular focus is placed on elucidating the microscopic mechanisms underlying key aspects including crystal structure, facet effects, elemental doping, and heterojunction design. The role of Bi 6s2 lone pair electrons in monoclinic BiVO4 is clarified through density functional theory calculations, which show that these electrons induce a structural distortion and built-in electric field critical for visible-light absorption and charge separation. The review further reveals the anisotropic behavior of different exposed facets in carrier transport and surface reaction pathways. It elucidates, from an electronic structure perspective, how doping modulates band positions, defect states, and charge recombination dynamics. Additionally, the band alignment, charge transfer, and built-in field formation at heterojunction interfaces are analyzed, clarifying the theoretical foundations of enhanced photocatalytic performance in type-II, Z-scheme, and related heterostructures. This work establishes a coherent theoretical framework for the structure-property relationships in BiVO4 and demonstrates the predictive power of computational simulations in guiding the rational design of efficient photocatalysts.

Bismuth vanadate (BiVO4) is a promising photocatalytic material for water splitting and pollutant degradation due to its suitable band gap, good chemical stability, and environmental compatibility. Using first-principles calculations, we systematically investigate the multiscale properties of four BiVO4 polymorphs (sm, op, zt, and st-BiVO4). Results reveal that sm-BiVO4 exhibits superior photocatalytic potential, as structural distortion induces local polarization and lone pair electrons, which facilitate photogenerated carrier separation. This polymorph also demonstrates enhanced visible light absorption and stable surface adsorption. Thermodynamically, zt-BiVO4 is more stable, while mechanical analysis shows sm-BiVO4 possesses high hardness and modulus but lower ductility. This study elucidates the structure-performance relationship of BiVO4 from electronic, optical, adsorptive, thermodynamic, and mechanical perspectives, providing a theoretical basis for optimizing its photocatalytic applications.

Protein arginine methyltransferase 5 (PRMT5) is a histone methyltransferase crucial for cell proliferation, differentiation, and inflammation. However, the biological functions of PRMT5 and its underlying molecular mechanisms in corneal neovascularization (CNV) remain unclear. This study utilized corneal alkali burn and vascular endothelial growth factor (VEGF)-induced HUVEC models to examine the role of PRMT5 in CNV. We found that PRMT5 expression was significantly upregulated following corneal alkali burn. Experiments both in vitro and in vivo showed that PRMT5 knockdown or inhibition lowered pyroptosis-related protein expression and reduced cell death. PRMT5 interacts with the NACHT domain of NOD-like receptor family pyrin domain-containing 3 (NLRP3) via its Rossmann fold, catalyzing arginine methylation at the R490 and R504 residues through its methyltransferase activity. This process modulates inflammation and pyroptosis, thereby influencing the formation of CNV. In conclusion, our findings provide evidence that inhibiting PRMT5 can alleviate angiogenesis in CNV models by blocking NLRP3-mediated pyroptosis.

Purpose:This study aimed to explore the exosome-related gene network in herpes stromal keratitis (HSK) and to identify key molecular drivers, focusing on the role of secreted phosphoprotein 1 (SPP1) and investigating the therapeutic potential of ursolic acid (UA). Methods:Transcriptomic RNA sequencing was performed on corneal tissues from herpes simplex virus type 1 (HSV-1)-infected mice. Bioinformatics analyses included identification of differentially expressed genes (DEGs), immune cell infiltration assessment, exosome-related gene network construction, functional enrichment analyses, and compound-gene network creation. Immune infiltration findings were further validated using single-cell RNA sequencing and flow cytometry. Key findings were validated in a mouse HSK model using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry. The therapeutic effect and mechanism of UA were investigated through subconjunctival administration, with subsequent evaluation of corneal lesions, angiogenesis, fibrosis, and key signaling pathways. Results:Through analysis, 222 DEGs associated with exosomes were identified in HSK, and the exosome-related gene network revealed that the primary functional cluster was centered on the positive regulation of cell adhesion. Among the genes in the primary functional cluster, SPP1 emerged as a hub gene, demonstrating significant upregulation that correlated with clinical progression. SPP1 expression exhibited a shift from corneal epithelial cells under normal conditions to infiltrating immune cells, particularly neutrophils and monocytes, during HSK. In a mouse model, treatment with UA significantly reduced corneal opacity, vessel in-growth, and inflammatory cell infiltration. Mechanistically, UA downregulated SPP1 expression and subsequently inhibited the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Conclusions:These findings provide new insights into the exosome-related gene network and the mechanisms of HSK, while identifying UA as a promising candidate for therapeutic development.

ObjectivesIdentifying the amino acid in tears and plasma and investigating the correlation between amino acid concentrations and the presence of dry eye disease (DED) with ocular pain.Methods15 participants in the DED with ocular pain group, 19 in the DED group, and 16 in the control group were enrolled and underwent DED examinations. Evaluation parameters included the Ocular Surface Disease Index score, Numeric Rating Scale score, clinical ocular parameters, as well as measurements from in vivo laser confocal microscopy. Amino acid concentrations were analyzed using the Waters ACQUITY UPLC I-Class/Xevo TQ-S micro system.ResultsA total of 29 and 36 distinct amino acids were identified in tear fluid and plasma, respectively. The results showed significantly higher levels of methionine (MET) in tear fluid and 1-methyl-L-histidine (1-MEHIS) in plasma in people who developed DED with ocular pain compared to those who did not (p = 0.003, q-value = 0.044; p < 0.001, q-value < 0.001), with receiver-operating characteristic analysis yielding an AUC of 0.686 and 0.869.ConclusionMET in tear fluid and 1-MEHIS in plasma were significantly associated with DED with ocular pain, showing promise as potential biomarkers for DED with ocular pain. Further validation through large-scale studies is warranted.

Purpose:Effective management of corneal neovascularization (CoNV) remains challenging, and the role of epitranscriptomic regulation, particularly N5-methylcytosine (m5C) modification, in this process remain incompletely defined. This study investigated the function and mechanism of the RNA-binding protein YBX1 in CoNV following alkali burn (AB). Methods:An AB-induced CoNV model was generated using C57BL/6 mice. In vitro, human umbilical vein endothelial cells (HUVECs) underwent hypoxia/reoxygenation (H/R). Multi-omics approaches including transcriptome sequencing, RNA immunoprecipitation sequencing, and m5C methylated RNA immunoprecipitation sequencing were used to identify YBX1 targets and their modification status. Functional assays assessed angiogenesis, apoptosis, and reactive oxygen species (ROS). The therapeutic potential of the YBX1 inhibitor Soyasaponin II (SII) was evaluated in vivo. Results:YBX1 was upregulated following AB and H/R. YBX1 knockdown suppressed HUVEC migration, tube formation, and ROS production, while promoting apoptosis; these effects were rescued by HIF-1α overexpression. Mechanistically, YBX1 activated the JAK1/STAT3 pathway and recognizes m5C-modified sequences on STAT3 and VEGFA mRNAs, enhancing their stability. In vivo, subconjunctival injection of SII attenuated CoNV, reduced inflammation, and modulated macrophage polarization. Conclusions:Our study unveils a novel epitranscriptomic mechanism in which YBX1 drives CoNV by regulating the stability of m5C-modified STAT3 and VEGFA mRNAs, thereby activating the JAK1/STAT3/HIF-1α axis. Inhibition of YBX1 with SII effectively counteracts this pathway, highlighting YBX1 as an attractive candidate for intervention against sight-threatening CoNV.

The escalating global energy demand has rendered the development of advanced energy storage systems an imperative scientific challenge. Dielectric materials optimization serves as a critical pathway for achieving enhanced energy storage performance. Calcium copper titanate (CaCu3Ti4O12, CCTO) has garnered substantial research interest owing to its colossal dielectric permittivity and remarkable thermal/frequency stability. Nevertheless, the elevated dielectric loss tangent (tan delta) significantly constrains its technological implementation. The core-shell structural provides a viable strategy for dielectric loss mitigation in CCTO systems. This review systematically examines core-shell structural synthesis methodologies and the impact of structural optimization on the dielectric properties of CCTO. The internal barrier layer capacitor (IBLC) mechanism is elucidated through interfacial polarization analysis, along with a detailed analysis of the key role played by the selection and structural regulation of shell materials in enhancing performance. Finally, the potential applications of CCTO core-shell structures in electronic devices are explored, providing valuable insights for researchers in the field of dielectric materials.

With the global emphasis on green and sustainable development, sodium alginate-based hydrogels (SAHs), as a renewable and biocompatible environmental material, have garnered widespread attention for their research and application. This review summarizes the latest advancements in the study of SAHs, thoroughly discussing their structural characteristics, formation mechanisms, and current applications in various fields, as well as prospects for future development. Initially, the chemical structure of SA and the network structure of hydrogels are introduced, and the impact of factors such as molecular weight, crosslinking density, and environmental conditions on the hydrogel structure is explored. Subsequently, the formation mechanisms of SAHs, including physical and chemical crosslinking, are detailed. Furthermore, a systematic review of the applications of SAHs in tissue engineering, drug delivery, medical dressings, wastewater treatment, strain sensor, and food science is provided. Finally, future research directions for SAHs are outlined. This work not only offers researchers a comprehensive framework for the study of SAHs but also provides significant theoretical and experimental foundations for the development of new hydrogel materials.

To assess the incidence, cause and risk factors for unplanned readmission within 90 days after deep anterior lamellar keratoplasty (DALK). A multicentre cross-sectional study of 3603 eyes of 3588 patients after keratoplasty between January 1st, 2019, and September 30th, 2021 in 16 hospitals across China was performed. The demographic and clinical features between patients after DALK with 90-day unplanned readmission and those who did not have been compared. The risk factors of unplanned readmission were identified by a multivariable Cox regression model. Among 873 patients (878 eyes) after DALK, and the primary indications for DALK were keratitis (391 eyes, 44.53

A metal-free P-(g-C3N4/NCDs) photocatalytic composite was synthesized by modifying graphitic carbon nitride (g-C3N4) through a dual strategy of nitrogen-doped carbon quantum dots (NCDs) incorporation and protonation. Under light irradiation, the optimized catalyst achieved 99

With the growth of the global population and increasing concern for environmental issues, the development of sustainable and eco-friendly materials has become increasingly important. Starch, as a renewable resource, is one of the most abundant polysaccharides in nature, with the advantages of good biocompatibility, high biodegradability, and low cost. Starch-based hydrogels (SBHs) have attracted widespread attention due to their unique physical and chemical properties. This article provides a comprehensive review of the latest research progress in SBHs, discussing their main characteristics, formation mechanisms, diverse applications, and future development trends. First, it outlines the biocompatibility, degradability, water absorption and retention, environmental responsiveness, and mechanical strength of SBHs. Then, it elaborates in detail on the formation mechanisms of SBHs, including physical crosslinking (hydrogen bonding, electrostatic interactions, host-guest and coordination interactions), chemical crosslinking (such as initiators, heat, light, radiation, and click reactions), and synergistic effects. Subsequently, it analyzes the applications of SBHs in cutting-edge fields such as flexible sensors, medical dressings, drug delivery, tissue engineering, soil protection, wastewater treatment, and food packaging. Finally, it summarizes the challenges in current research and provides an outlook on future development trends, emphasizing the importance of further optimizing the performance of SBHs to meet broader industrial needs and environmental protection goals. This review not only provides a systematic theoretical framework for the study of SBHs but also charts a course for their innovative applications in the field of sustainable materials, playing a significant role in advancing the continuous development of this area.

Primary angle-closure glaucoma (PACG), characterized by angle closure (AC) with insidious and irreversible progression, requires precise assessment of AC mechanisms for accurate diagnosis and treatment. This study developed an artificial intelligence system, ACM-Assessor, to evaluate AC mechanisms in ultrasound biomicroscopy (UBM) images. A dataset of 8482 UBM images from 1160 patients was retrospectively collected. ACM-Assessor comprises models for pixel-to-physical spacing conversion, anterior chamber angle boundary segmentation, and scleral spur localization, along with three binary classification models to assess pupillary block (PB), thick peripheral iris (TPI), and anteriorly located ciliary body (ALCB). The integrated assessment model classifies AC mechanisms into pure PB, pure non-PB, multiple mechanisms (MM), and others. ACM-Assessor’s evaluation encompassed external testing (2266 images), human–machine competition and assisting beginners’ assessment (an independent test set of 436 images). ACM-Assessor achieved accuracies of 0.924 (PB), 0.925 (TPI), 0.947 (ALCB), and 0.839 (integrated assessment). In man–machine comparisons, the system’s accuracy was comparable to experts (p > 0.05). With model assistance, beginners’ accuracy improved by 0.117 for binary classification and 0.219 for integrated assessment. ACM-Assessor demonstrates expert-level accuracy and enhances beginners’ learning in UBM analysis.