Pain perception, aqueous humour cytokines, and miosis response following first and second eye femtosecond laser-assisted cataract surgery: A randomised, prospective, intraindividual study.

BACKGROUND: To compare pain perception, pupil behaviours, and cytokine levels during first-eye and second-eye femtosecond laser-assisted cataract surgery (FLACS) and determine which is better regarding a short or long interval for bilateral FLACS. METHODS: Notably, 96 eyes of 48 patients with bilateral cataracts underwent the first surgeries in the left or right eye, according to a random sequence. They were further randomised into 2- and 6-week subgroups based on surgery intervals. Pupil size was measured from captured images, and pain perception was assessed using a visual analog scale (VAS). Aqueous humour prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, and IL-8 levels were also quantitatively analysed. All patients were followed for 1 week to evaluate changes in endothelial cell density (ECD), central corneal thickness (CCT), and macular central subfield thickness (CST). RESULTS: Ocular pain was significantly higher in patients who underwent second-eye FLACS. First tear break-up time was negatively correlated with VAS score. MCP-1 levels were significantly higher in patients who underwent second-eye FLACS, and VAS scores were positively correlated with MCP-1 levels across all patients. There were no differences between sequential FLACS in miosis, PGE2, IL-6, IL-8 levels and changes in postoperative ECD, CCT, and CST. Patients who underwent second-eye FLACS after 6 weeks showed more CCT, CST, and MCP-1 changes than baseline. CONCLUSION: Second-eye FLACS causes more pain and upregulated MCP-1. There was no difference between sequential FLACS in PGE2 levels, miosis, and postoperative inflammation. Furthermore, first-eye FLACS triggered a sympathetic irritation, particularly after a 6-week interval.

Prediction of postoperative mortality in older surgical patients by clinical frailty scale: A systematic review and meta-analysis.

AIMS: To systematically evaluate the predictive efficacy of clinical frailty scale (CFS) for postoperative mortality older surgical patients, and to evaluate the prevalence of frailty in the included studies. DESIGN: A systematic review and meta-analysis of observational studies was conducted, utilizing the MOOSE guidelines for the evaluation of both. Quality assessment of the articles was also performed. DATA SOURCES: The protocol was registered (CRD42023423552). Relevant English and Chinese language studies published until October 20th, 2023 were retrieved from PubMed, Web of Science, Embase, Medline, CINAHL,Cochrane, WAN FANG DATA, VIP Information, CNKI, and SinoMed databases. REVIEW METHODS: Study were included in which frailty was measured by the CFS and postoperative mortality was reported for older surgery patients. A meta-analysis to predict postoperative mortality and frailty prevalence was performed using STATA 17.0 software. RESULTS: Sixteen cohort studies were included (5,864 participants) from 1,513 records. All studies' Newcastle-Ottawa Scale (NOS) scores were above 6 points. It was found that the prevalence of surgical frailty in the older was 0.36(CI 0.20-0.52). Patients assessed as frail by the CFS were associated with higher all-cause mortality (OR:4.01; CI 2.59-6.23). Subgroup analysis shows that frailty was associated with1-month mortality (OR:3.85; CI 1.11-13.45) and 1-year mortality (OR:4.43; CI 2.18-8.99). CONCLUSIONS: The prevalence of frailty is high in older surgical patients, and CFS can effectively predict the mortality of older surgical patients with frailty.

Achieving dendrite-free growth of Zn anode by electrodepositing on zincophilic gold-furnished mesh for aqueous zinc-ion batteries.

Here, we report a gold-furnished mesh as the current collector for Zn electrodeposition, which is used as the anode in aqueous zinc-ion batteries. The anode exhibits excellent cycling performance without obvious dendrite growth, and the full cell shows an outstanding specific capacity and long-term durability, surpassing those of bare Zn.

Millimeter-wave high-wavenumber scattering diagnostic developments on EAST and NSTX-U.

A pioneering 4-channel, high-k poloidal, millimeter-wave collective scattering system has been successfully developed for the Experimental Advanced Superconducting Tokamak (EAST). Engineered to explore high-k electron density fluctuations, this innovative system deploys a 270 GHz mm-wave probe beam launched from Port K and directed toward Port P (both ports lie on the midplane and are 110° part), where large aperture optics capture radiation across four simultaneous scattering angles. Tailored to measure density fluctuations with a poloidal wavenumber of up to 20 cm-1, this high-k scattering system underwent rigorous laboratory testing in 2023, and the installation is currently being carried out on EAST. Its primary purpose lies in scrutinizing ion and electron-scale instabilities, such as the electron temperature gradient (ETG) mode, by furnishing measurements of the kθ (poloidal wavenumber) spectrum. This advancement significantly bolsters the capacity to probe high-k electron density fluctuations within the framework of EAST. Beam tracing and data interpretation modules developed for both EAST and NSTX-U high-k scattering diagnostics are described.

Lens autophagy protein ATG16L1: a potential target for cataract treatment.

Rationale: Cataract is the leading cause of blindness and low vision worldwide, yet its pathological mechanism is not fully understood. Although macroautophagy/autophagy is recognized as essential for lens homeostasis and has shown potential in alleviating cataracts, its precise mechanism remains unclear. Uncovering the molecular details of autophagy in the lens could provide targeted therapeutic interventions alongside surgery. Methods: We monitored autophagic activities in the lens and identified the key autophagy protein ATG16L1 by immunofluorescence staining, Western blotting, and transmission electron microscopy. The regulatory mechanism of ATG16L1 ubiquitination was analyzed by co-immunoprecipitation and Western blotting. We used the crystal structure of E3 ligase gigaxonin and conducted the docking screening of a chemical library. The effect of the identified compound riboflavin was tested in vitro in cells and in vivo animal models. Results: We used HLE cells and connexin 50 (cx50)-deficient cataract zebrafish model and confirmed that ATG16L1 was crucial for lens autophagy. Stabilizing ATG16L1 by attenuating its ubiquitination-dependent degradation could promote autophagy activity and relieve cataract phenotype in cx50-deficient zebrafish. Mechanistically, the interaction between E3 ligase gigaxonin and ATG16L1 was weakened during this process. Leveraging these mechanisms, we identified riboflavin, an E3 ubiquitin ligase-targeting drug, which suppressed ATG16L1 ubiquitination, promoted autophagy, and ultimately alleviated the cataract phenotype in autophagy-related models. Conclusions: Our study identified an unrecognized mechanism of cataractogenesis involving ATG16L1 ubiquitination in autophagy regulation, offering new insights for treating cataracts.

An elastomer with in situ generated pure zwitterionic surfaces for fibrosis-resistant implants.

Polymeric elastomers are widely utilized in implantable biomedical devices. Nevertheless, the implantation of these elastomers can provoke a robust foreign body response (FBR), leading to the rejection of foreign implants and consequently reducing their effectiveness in vivo. Building effective anti-FBR coatings on those implants remains challenging. Herein, we introduce a coating-free elastomer with superior immunocompatibility. A super-hydrophilic anti-fouling zwitterionic layer can be generated in situ on the surface of the elastomer through a simple chemical trigger. This elastomer can repel the adsorption of proteins, as well as the adhesion of cells, platelets, and diverse microbes. The elastomer elicited negligible inflammatory responses after subcutaneous implantation in rodents for 2 weeks. No apparent fibrotic capsule formation was observed surrounding the elastomer after 6 months in rodents. Continuous subcutaneous insulin infusion (CSII) catheters constructed from the elastomer demonstrated prolonged longevity and performance compared to commercial catheters, indicating its great potential for enhancing and extending the performance of various implantable biomedical devices by effectively attenuating local immune responses. STATEMENT OF SIGNIFICANCE: The foreign body response remains a significant challenge for implants. Complicated coating procedures are usually needed to construct anti-fibrotic coatings on implantable elastomers. Herein, a coating-free elastomer with superior immunocompatibility was achieved using a zwitterionic monomer derivative. A pure zwitterionic layer can be generated on the elastomer surface through a simple chemical trigger. This elastomer significantly reduces protein adsorption, cell and bacterial adhesion, and platelet activation, leading to minimal fibrotic capsule formation even after six months of subcutaneous implantation in rodents. CSII catheters constructed from the PQCBE-H elastomer demonstrated prolonged longevity and performance compared to commercial catheters, highlighting the significant potential of PQCBE-H elastomers for enhancing and extending the performance of various implantable biomedical devices.

Association between glaucoma and stroke: A bidirectional mendelian randomization study.

Purpose: Observational studies have reported positive associations between glaucoma and stroke; however, controversial results exist. Importantly, the nature of the relationship remains unknown since previous studies were not designed to test causality. Therefore, we aimed to investigate the possible causal relationships between glaucoma and stroke. Methods: Our two-sample Mendelian randomization (MR) encompassed multi-ethnic large-scale genome-wide association studies with more than 20000 cases and 260000 controls for glaucoma, and more than 80000 cases and 630000 controls for stroke. Individual effect estimates for each SNP were combined using the inverse-variance weighted (IVW) method. To avoid potential pleiotropic effects, we adjusted the main results by excluding genetic variants associated with metabolic factors. The weighted median and MR-Egger methods were also used for the sensitivity analysis. Results: Our MR analysis revealed that glaucoma and its subtypes, including primary open-angle glaucoma and primary angle-closure glaucoma, exhibited no causal role in relation to any stroke (AS), any ischemic stroke (AIS), large-artery atherosclerotic stroke (LAS), small-vessel stroke (SVS), or cardioembolic stroke (CES) across MR analyses (all P â€‹> â€‹0.05). The null associations remained robust even after adjusting for metabolic-related traits and were consistent in both the European and Asian populations. Furthermore, reverse MR analyses also did not indicate any significant causal effects of AS, AIS, LAS, or CES on glaucoma risk. Conclusions: Evidence from our series of causal inference approaches using large-scale population-based MR analyses did not support causal effects between glaucoma and stroke. These findings suggest that the relationship of glaucoma management and stroke risk prevention should be carefully evaluated in future studies. In turn, stroke diagnosis should not be simply applied to glaucoma risk prediction.

Rosmarinic acid-grafted gelatin nanogels for efficient diquafosol delivery in dry eye disease therapy.

Dry eye disease (DED) is a prevalent ocular disorder characterized by unstable tear film condition with loss of aqueous or mucin, excessive oxidative stress, and inflammation, leading to discomfort and potential damage to the ocular surface. Current DED therapies have shown restricted therapeutic effects such as frequent dosing and temporary relief with potential unwanted side effects, urgently necessitating the development of innovative efficient therapeutic approaches. Herein, we developed rosmarinic acid (RosA) conjugated gelatin nanogels loading diquafosol sodium (DQS), DRGNG, for simultaneous ROS-scavenging and mucin-secreting DED treatment. Mechanically, DRGNG suppressed the ROS production, reduced inflammatory factors, and prompted mucin secretion in vitro and in vivo. The whole transcriptome RNA sequencing in vitro further provided a detailed analysis of the upregulation of anti-oxidant, anti-inflammatory, and mucin-promotion pathways. Therapeutically, both in evaporative DED and aqueous deficient DED models, the dual-functional DRGNG could prolong the retention time at the ocular surface, efficiently suppress the oxidative stress response, reverse ocular surface morphology, and recover tear film homeostasis, thus alleviating the DED when the dosage is halved compared to the commercial Diquas®. Our findings contribute to developing innovative therapies for DED and offer insights into the broader applications of nanogels in ocular drug delivery and oxidative stress-related conditions.

Irisin attenuates acute glaucoma-induced neuroinflammation by activating microglia-integrin αVß5/AMPK and promoting autophagy.

Neuroinflammation, characterized by microglial activation and the release of multiple inflammatory mediators, is a key factor in acute glaucomatous injury leading to retinal ganglion cell (RGC) death and ultimately irreversible vision loss. Irisin, a novel exercise-induced myokine, has demonstrated anti-inflammatory activity in ischemia/reperfusion injuries across multiple organs and has displayed a significant neuroprotective role in experimental stroke disease models. This study examined the protective impact of irisin and investigated its potential mechanism involved in this process utilizing an acute ocular hypertension (AOH)-induced retinal injury model in mice and a microglia inflammation model induced by lipopolysaccharide (LPS). There was a transient downregulation of irisin in the retina after AOH injury, with parallel emergence of retinal neuroinflammation and RGC death. Irisin attenuated retinal and optic nerve damage and promotes the phenotypic conversion of microglia from M1 to M2. Mechanistically, irisin significantly upregulated the expression of integrin αVß5, p-AMPK, and autophagy-related markers. Integrin αVß5 was highly expressed on microglia but hardly expressed on RGC. The integrin αVß5 inhibitor cilengitide, the AMPK inhibitor dorsomorphin, and the autophagy inhibitor 3-Methyladenine (3-MA) blocked the neuroprotective effects of irisin. Our results suggest irisin attenuates acute glaucoma-induced neuroinflammation and RGC death by activating integrin αVß5/AMPK in microglia and promoting autophagy. It should be considered a potential neuroprotective therapy for acute glaucoma.

Global incidence and prevalence of malignant orbital tumors.

Purpose: Aims to provide an overview of the contemporary epidemiology of malignant orbital tumors by analyzing population-based incidence patterns across various regions worldwide. Methods: In this article, we retrieved orbital malignancy data from the MEDLINE database and analyzed the incidence and prevalence of orbital malignancies worldwide. We performed the literature search by searching on the Mesh terms for malignant orbital tumors ("orbital", "tumor", "lymphoma", "malignant", "cancer", "incidence", and "epidemiology"). All included studies were published between 1993 and 2023 and were written in English. Results: Ocular or ophthalmic lymphoma most frequently occurred in the orbit, with a prevalence ranging from 47% to 54%. The incidence of malignant orbital tumors was increasing in the USA (2.0 per million (1981-1993), Netherlands (0.86 (1981-1985) to 2.49 (2001-2005) per million) and South Korea (0.3-0.8 per million (1999-2016)), respectively. Ophthalmic lymphoma which includes orbit lymphoma was increasing in Canada (0.17-1.47 per million (1992-2010)), Denmark (0.86 per million (1981-1985) to 2.49 per million (2001-2005)), respectively. Conclusions: The predominant primary malignant orbital tumor in adults was lymphoma. Ocular or ophthalmic lymphoma most frequently occured in the orbit. The limited data available suggested an increasing trend in the incidence of malignant orbital tumors in each country included, which were mainly attributed to the increase in lymphoma. Generally, incidence rates were found to increase with advancing age, with no difference between males and females.

Truncation mutations of CRYGD gene in congenital cataracts cause protein aggregation by disrupting the structural stability of γD-crystallin.

Congenital cataracts, a prevalent cause of blindness in children, are associated with protein aggregation. γD-crystallin, essential for sustaining lens transparency, exists as a monomer and exhibits excellent structural stability. In our cohort, we identified a nonsense mutation (c.451_452insGACT, p.Y151X) in the CRYGD gene. To explore the effect of truncation mutations on the structure of γD-crystallin, we examined the Y151X and T160RfsX8 mutations, both located in the Greek key motif 4 at the cellular and protein level in this study. Both truncation mutations induced protein misfolding and resulted in the formation of insoluble aggregates when overexpressed in HLE B3 and HEK 293T cells. Moreover, heat, UV irradiation, and oxidative stress increased the proportion of aggregates of mutants in the cells. We next purified γD-crystallin to estimate its structural changes. Truncation mutations led to conformational disruption and a concomitant decrease in protein solubility. Molecular dynamics simulations further demonstrated that partial deletion of the conserved domain within the Greek key motif 4 markedly compromised the overall stability of the protein structure. Finally, co-expression of α-crystallins facilitated the proper folding of truncated mutants and mitigated protein aggregation. In summary, the structural integrity of the Greek key motif 4 in γD-crystallin is crucial for overall structural stability.

Celastrol regulates the oligomeric state and chaperone activity of αB-crystallin linked with protein homeostasis in the lens.

Protein misfolding and aggregation are crucial pathogenic factors for cataracts, which are the leading cause of visual impairment worldwide. α-crystallin, as a small molecular chaperone, is involved in preventing protein misfolding and maintaining lens transparency. The chaperone activity of α-crystallin depends on its oligomeric state. Our previous work identified a natural compound, celastrol, which could regulate the oligomeric state of αB-crystallin. In this work, based on the UNcle and SEC analysis, we found that celastrol induced αB-crystallin to form large oligomers. Large oligomer formation enhanced the chaperone activity of αB-crystallin and prevented aggregation of the cataract-causing mutant ßA3-G91del. The interactions between αB-crystallin and celastrol were detected by the FRET (Fluorescence Resonance Energy Transfer) technique, and verified by molecular docking. At least 9 binding patterns were recognized, and some binding sites covered the groove structure of αB-crystallin. Interestingly, αB-R120G, a cataract-causing mutation located at the groove structure, and celastrol can decrease the aggregates of αB-R120G. Overall, our results suggested celastrol not only promoted the formation of large αB-crystallin oligomers, which enhanced its chaperone activity, but also bound to the groove structure of its α-crystallin domain to maintain its structural stability. Celastrol might serve as a chemical and pharmacological chaperone for cataract treatment.

Chromosome-level genome assembly of the cereal cyst nematode Heterodera flipjevi.

As an economically important plant parasitic nematode (PPN), Heterodera filipjevi causes great damage on wheat, and now it was widely recorded in many countries. While multiple genomes of PPNs have been published, high-quality genome assembly and annotation on H. filipjevi have yet to be performed. This study presents a chromosome-scale genome assembly and annotation for H. filipjevi, utilizing a combination of Illumina short-read, PacBio long-read, and Hi-C sequencing technologies. The genome consists of 9 pseudo-chromosomes that contain 134.19 Mb of sequence, with a scaffold N50 length of 11.88 Mb. In total, 10,036 genes were annotated, representing 75.20% of the total predicted protein-coding genes. Our study provides the first chromosome-scale genome for H. filipjevi, which is also the inaugural high-quality genome of cereal cyst nematodes (CCNs). It provides a valuable genomic resource for further biological research and pest management of cereal cyst nematodes disease.

Personalized treatment approaches in intraocular cancer.

Background: Intraocular malignant tumors represent a severe disease that threatens vision as well as life. To better extend the life of the patient, preserve visual function, and maintain ocular aesthetics, selecting the appropriate timing and methods of treatment becomes crucial. Main text: With the continuous advancement of medical technology, the techniques and methods for treating intraocular malignant tumors are constantly evolving. While surgery was once considered the optimal method to prolong patient survival and prevent local recurrence, the discovery and application of various treatments such as radiotherapy, laser therapy, chemotherapy, cryotherapy, and monoclonal antibodies have led to a greater diversity of treatment options. This diversity offers more possibilities to develop personalized treatment plans, and thereby maximize patient benefit. This article reviews the various treatment methods for intraocular malignant tumors, including indications for treatment, outcomes, and potential complications. Conclusions: Differentiating small intraocular malignant tumors from pigmented lesions is challenging, and ongoing monitoring with regular follow-up is required. Small to medium-sized tumors can be treated with radiotherapy combined with transpupillary thermotherapy. Depending on the tumor's distance from the optic disc, surgery with partial resection may be considered for distant tumors, while proximal tumors may require complete enucleation. Systemic chemotherapy has been widely applied to patients with retinal tumors, lymphomas, and intraocular metastatic cancers, but has limited efficacy in patients with choroidal melanoma. Antagonists of Vascular Endothelial Growth Factor (Anti-VEGF) drugs can improve patient vision and quality of life, while the efficacy of immunotherapy and molecular targeted therapy is still under research.

Challenges in cataract surgery after penetrating keratoplasty managed using femtosecond laser: A series of 3 case reports.

INTRODUCTION: Cataract surgery in patients after penetrating keratoplasty (PKP) is often challenging because of changes in corneal structure induced by PKP and primary corneal disease. Femtosecond laser-assisted cataract surgery offers several advantages over conventional phacoemulsification, and has been widely used in complicated cataract surgery. CASE REPORT: We report the use of femtosecond laser-assisted cataract surgery in 3 challenging cases after penetrating keratoplasty. Case 1 involved a patient with hard nuclear grade IV° cataract. After surgery, his corrected distance visual acuity (CDVA) improved from 20/400 to 20/25, and the endothelial cell loss (ECL) % was 12.05 % at 3 months postoperatively. The rotation of the toric IOL in Case 1 was 2°. Case 2 involved a patient with severe nuclear cataract and an endothelial cell density of 837 cells/mm2. After surgery, the CDVA improved from 20/100 to 20/40. The ECL% was 4.06% at 1 week postoperatively. Case 3 was a 91-year-old woman with a short axis length of 21.35 mm and an endothelial cell density number of 1238 cells/mm2. After surgery, the CDVA improved from light perception to 20/133, and the ECL% was 26.09% at 1 week postoperatively; ECL% was 2.67% at 1 month post-operation. The corneal grafts were transparent. CONCLUSION: Femtosecond laser-assisted cataract surgery seems to be an effective, predictable, and safe approach for challenging patients after PKP, and improves visual recovery and optimal refractive outcomes.

Development of a Menglà virus minigenome and comparison of its polymerase complexes with those of other filoviruses.

Ebola virus (EBOV) and Marburg virus (MARV), members of the Filoviridae family, are highly pathogenic and can cause hemorrhagic fevers, significantly impacting human society. Bats are considered reservoirs of these viruses because related filoviruses have been discovered in bats. However, due to the requirement for maximum containment laboratories when studying infectious viruses, the characterization of bat filoviruses often relies on pseudoviruses and minigenome systems. In this study, we used RACE technology to sequence the 3'-leader and 5'-trailer of Menglà virus (MLAV) and constructed a minigenome. Similar to MARV, the transcription activities of the MLAV minigenome are independent of VP30. We further assessed the effects of polymorphisms at the 5' end on MLAV minigenome activity and identified certain mutations that decrease minigenome reporter efficiency, probably due to alterations in the RNA secondary structure. The reporter activity upon recombination of the 3'-leaders and 5'-trailers of MLAV, MARV, and EBOV with those of the homologous or heterologous minigenomes was compared and it was found that the polymerase complex and leader and trailer sequences exhibit intrinsic specificities. Additionally, we investigated whether the polymerase complex proteins from EBOV and MARV support MLAV minigenome RNA synthesis and found that the homologous system is more efficient than the heterologous system. Remdesivir efficiently inhibited MLAV as well as EBOV replication. In summary, this study provides new information on bat filoviruses and the minigenome will be a useful tool for high-throughput antiviral drug screening.

Ocular RNA nanomedicine: engineered delivery nanoplatforms in treating eye diseases.

Ocular disorders remain a major global health challenge with unmet medical needs. RNA nanomedicine has shown significant therapeutic benefits and safety profiles in patients with complex eye disorders, already benefiting numerous patients with gene-related eye disorders. The effective delivery of RNA to the unique structure of the eye is challenging owing to RNA instability, off-target effects, and ocular physiological barriers. Specifically tailored RNA medication, coupled with sophisticated engineered delivery platforms, is crucial to guide and advance developments in treatments for oculopathy. Herein we review recent advances in RNA-based nanomedicine, innovative delivery strategies, and current clinical progress and present challenges in ocular disease therapy.

Characterization of mechanical stress in the occurrence of cortical opacification in age-related cataracts using three-dimensional finite element model of the human lens and RNA-seq.

Cataract is the leading cause of blindness across the world. Age-related cataract (ARC) is the most common type of cataract, but its pathogenesis is not fully understood. Using three-dimensional finite element modeling combining experimental biotechnology, our study demonstrates that external forces during accommodation cause mechanical stress predominantly in lens cortex, basically matching the localization of opacities in cortical ARCs. We identified the cellular senescence and upregulation of PIEZO1 mRNA in HLECs under mechanical stretch. This mechano-induced senescence in HLECs might be mediated by PIEZO1-related pathways, portraying a potential biomechanical cause of cortical ARCs. Our study updates the fundamental insight towards cataractogenesis, paving the way for further exploration of ARCs pathogenesis and nonsurgical treatment.

A UV-related risk analysis in ophthalmic malignancies: Increased UV exposure may cause ocular malignancies.

Purpose: To explore the role of ultraviolet radiation (UVR) in the occurrence and development of various ocular malignancies. Methods: In this article, we retrieved ocular malignancy data from the Global Cancer Observatory (GCO) and performed correlation analysis with the global UV index and sunshine duration. We searched for associated studies using the following databases: Embase, Pubmed, Cochrane Library, and Google Scholar. We conducted the literature by searching the Mesh terms denoting an exposure of interest ("UV radiation", "ultraviolet rays", and "ocular malignancies", All studies included are published until December 30, 2023 without language restrictions. Results: The mechanisms and epidemiological statistics of UVR on the onset and progression of eyelid malignancies are the most studied and clear. The role of UVR in conjunctival melanoma is similar to that in eyelid melanoma. The relationship between uveal melanoma and UVR is controversial, however, it may have at least a certain impact on its prognosis. UVR causes ocular surface squamous neoplasia by further activating HPV infection. Conclusions: UVR is a decisive risk factor for ocular malignancies, but the incidence of ultraviolet-induced tumors is also affected by many other factors. A correct and comprehensive understanding of the mechanisms of UVR in the pathogenesis of ocular malignant tumors can provide patients with more effective and selective immune regulation strategies.

Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune-Epithelial Crosstalk.

Dry eye disease (DED) affects a substantial worldwide population with increasing frequency. Current single-targeting DED management is severely hindered by the existence of an oxidative stress-inflammation vicious cycle and complicated intercellular crosstalk within the ocular microenvironment. Here, a nanozyme-based eye drop, namely nanoceria loading cyclosporin A (Cs@P/CeO2), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). In vitro studies showed that the dual-functional Cs@P/CeO2 not only inhibits cellular reactive oxygen species production, sequentially maintaining mitochondrial integrity, but also downregulates inflammatory processes and repolarizes macrophages. Moreover, using flow cytometric and single-cell sequencing data, the in vivo therapeutic effect of Cs@P/CeO2 was systemically demonstrated, which rebalances the immune-epithelial communication in the corneal microenvironment with less inflammatory macrophage polarization, restrained oxidative stress, and enhanced epithelium regeneration. Collectively, our data proved that the antioxidative and anti-inflammatory Cs@P/CeO2 may provide therapeutic insights into DED management.