Neuroprotective effects and mechanisms of action of artemisinin in retinal ganglion cells in a mouse model of traumatic optic neuropathy.

Introduction: Traumatic optic neuropathy is known to be a critical condition that can cause blindness; however, the specific mechanism underlying optic nerve injury is unclear. Recent studies have reported that artemisinin, considered vital in malaria treatment, can also be used to treat neurodegenerative diseases; however, its precise role and mechanism of action remain unknown. Therefore, in this study, we aimed to investigate the impact and probable mechanism of action of artemisinin in retinal ganglion cells (RGCs) in a mouse model of traumatic optic neuropathy induced by optic nerve crush (ONC). Methods: ONC was induced in the left eye of mice by short-term clamping of the optic nerve; oral artemisinin was administered daily. The neuroprotective effect of the drug was assessed using Tuj-1 staining in RGCs. In addition, the inflammatory response and the expression levels of phosphorylated tau protein and tau oligomers were observed using RT-qPCR, TUNEL assay, and fluorescence staining to investigate the underlying mechanisms. Results: Artemisinin increased the survival rate of RGCs 14 days after ONC. Artemisinin significantly reduced the levels of inflammatory factors such as CXCL10, CXCR3, and IL-1ß in the retina and decreased the apoptosis of RGCs. Moreover, downregulation of the phosphorylation of tau proteins and the expression of tau oligomers were observed after artemisinin treatment. Conclusion: Our results suggest that artemisinin can increase the survival rate of RGCs after ONC and reduce their apoptosis. This effect may be achieved by inhibiting the inflammatory response it triggers and downregulating tau protein phosphorylation and tau oligomer expression. These findings suggest the potential application of artemisinin as a therapeutic agent for neuropathy.

Substrate Stiffness Modulates Stemness and Differentiation of Rabbit Corneal Endothelium Through the Paxillin-YAP Pathway.

Purpose: To explore the role of substrate stiffness and the mechanism beneath corneal endothelial cells' (CECs') stemness maintenance and differentiation. Methods: CECs were divided into central zone (8 mm trephined boundary) and peripheral zone (8 mm trephined edge with attached limbal). Two zones were analyzed by hematoxylin-eosin staining and scanning electron microscopy for anatomic structure. The elastic modulus of Descemet's membrane (DM) was analyzed by atomic force microscopy. Compressed type I collagen gels with different stiffness were constructed as an in vitro model system to test the role of stiffness on phenotype using cultured rabbit CECs. Cell morphology, expression and intracellular distribution of Yes-associated protein (YAP), differentiation (ZO-1, Na+/K+-ATPase), stemness (FOXD3, CD34, Sox2, Oct3/4), and endothelial-mesenchymal transition (EnMT) markers were analyzed by immunofluorescence, quantitative RT-PCR, and Western blot. Results: The results showed that the peripheral area of rabbit and human DM is softer than the central area ex vivo. Using the biomimetic extracellular matrix collagen gels in vitro model, we then demonstrated that soft substrate weakens the differentiation and EnMT in the culture of CECs. It was further proved by the inhibitor experiment that soft substrate enhances stemness maintenance via inhibition of paxillin-YAP signaling, which was activated on a stiff substrate. Conclusions: Our findings confirm that substrate stiffness modulates the stemness maintenance and differentiation of CECs and suggest a potential strategy for CEC-based corneal tissue engineering.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

Regulating Crystal Orientation in VO2 for Aqueous Zinc Batteries with Enhanced Pseudocapacitance.

Although aqueous zinc batteries have attracted extensive interest, they are limited by relatively low rate capabilities and poor cyclic stability of cathodes. The crystal orientation of the cathode is one important factor influencing electrochemical properties. However, it has rarely been investigated. Herein, VO2 cathodes with different crystal orientations are developed via tuning the number of hydroxyl groups in polyol, such as using glycerol, erythritol, xylitol, or mannitol. The polyols serve as a reductant as well as a structure-directing agent through a hydrothermal reaction. Xylitol-derived VO2 shows a (110)-orientated crystalline structure and ultrathin nanosheet morphology. Such features greatly enhance the pseudocapacitance to 76.1% at a scan rate of 1.0 mV s-1, which is significantly larger than that (61.6%) of the (001)-oriented VO2 derived from glycerol. The corresponding aqueous zinc batteries exhibit a high energy storage performance with a reversible specific capacity of 317 mAh g-1 at 0.5 A g-1, rate ability of 220 mAh g-1 at 10 A g-1, and capacity retention of 81.0% at 10 A g-1 over 2000 cycles. This work demonstrates a facile method for tailoring VO2 crystal orientations, offers an understanding of the Zn2+ storage mechanism upon different VO2 facets, and provides a novel method to develop cathode materials toward advanced aqueous zinc batteries.

High-Performance Engineered Composites Biofabrication Using Fungi.

Various natural polymers offer sustainable alternatives to petroleum-based adhesives, enabling the creation of high-performance engineered materials. However, additional chemical modifications and complicated manufacturing procedures remain unavoidable. Here, a sustainable high-performance engineered composite that benefits from bonding strategies with multiple energy dissipation mechanisms dominated by chemical adhesion and mechanical interlocking is demonstrated via the fungal smart creative platform. Chemical adhesion is predominantly facilitated by the extracellular polymeric substrates and glycosylated proteins present in the fungal outer cell walls. The dynamic feature of non-covalent interactions represented by hydrogen bonding endows the composite with extensive unique properties including healing, recyclability, and scalable manufacturing. Mechanical interlocking involves multiple mycelial networks (elastic modulus of 2.8 GPa) binding substrates, and the fungal inner wall skeleton composed of chitin and ß-glucan imparts product stability. The physicochemical properties of composite (modulus of elasticity of 1455.3 MPa, internal bond strength of 0.55 MPa, hardness of 82.8, and contact angle of 110.2°) are comparable or even superior to those of engineered lignocellulosic materials created using petroleum-based polymers or bioadhesives. High-performance composite biofabrication using fungi may inspire the creation of other sustainable engineered materials with the assistance of the extraordinary capabilities of living organisms.

Experimentally validated design principles of heteroatom-doped-graphene-supported calcium single-atom materials for non-dissociative chemisorption solid-state hydrogen storage.

Non-dissociative chemisorption solid-state storage of hydrogen molecules in host materials is promising to achieve both high hydrogen capacity and uptake rate, but there is the lack of non-dissociative hydrogen storage theories that can guide the rational design of the materials. Herein, we establish generalized design principle to design such materials via the first-principles calculations, theoretical analysis and focused experimental verifications of a series of heteroatom-doped-graphene-supported Ca single-atom carbon nanomaterials as efficient non-dissociative solid-state hydrogen storage materials. An intrinsic descriptor has been proposed to correlate the inherent properties of dopants with the hydrogen storage capability of the carbon-based host materials. The generalized design principle and the intrinsic descriptor have the predictive ability to screen out the best dual-doped-graphene-supported Ca single-atom hydrogen storage materials. The dual-doped materials have much higher hydrogen storage capability than the sole-doped ones, and exceed the current best carbon-based hydrogen storage materials.

Robust Micro-Sized and Defect-Rich Carbon-Carbon Composites as Advanced Anodes for Potassium-Ion Batteries.

Pitch-derived carbon (PC) anode features the merits of low-cost, rich edge-defect sites, and tunable crystallization degree for potassium ion batteries (PIBs). However, gaining the PC anode with both rich edge-defect sites and robust structure remains challenging. Herein, micro-sized and robust PC/expanded-graphite (EG) composites (EGC) with rich edge-defect sites are massively synthesized via melting impregnation and confined pyrolysis. The PC is in situ encapsulated in micro-sized EG skeleton with robust chemical bonds between PC and EG after thermal treatment, endowing the structural stability as micro-sized carbon-carbon composites. The confinement effect originating from EG skeleton could suppress the crystallization degree of the PC and contribute rich edge-defect sites in EGC composites. Additionally, the EG skeleton inside EGC could form continuous electronic conduction nets and establish low-tortuosity carbonaceous electrodes, facilitating rapid electron/ion migration. While applied in PIBs, the EGC anode delivers a reversible capacity that up to 338.5 mAh g-1 at 0.1 A g-1 , superior rate performance of 127.5 mAh g-1 at 5.0 A g-1 , and long-term stability with 204.8 mAh g-1 retain after 700 cycles at 1.0 A g-1 . This novel strategy highlights an interesting category of heterogeneous carbon-carbon composite materials to keep pace with the demand for the future PIBs industry.

Rechargeable Aqueous Zinc-Halogen Batteries: Fundamental Mechanisms, Research Issues, and Future Perspectives.

Aqueous zinc-halogen batteries (AZHBs) have emerged as promising candidates for energy storage applications due to their high security features and low cost. However, several challenges including natural subliming, sluggish reaction kinetics, and shuttle effect of halogens, as well as dendrite growth of the zinc (Zn) anode, have hindered their large-scale commercialization. In this review, first the fundamental mechanisms and scientific issues associated with AZHBs are summarized. Then the research issues and progresses related to the cathode, separator, anode, and electrolyte are discussed. Additionally, emerging research opportunities in this field is explored. Finally, ideas and prospects for the future development of AZHBs are presented. The objective of this review is to stimulate further exploration, foster the advancement of AZHBs, and contribute to the diversified development of electrochemical energy storage.

Amniotic membrane transplantation combined with conjunctival flap covering surgery for the treatment of corneal perforations in fungal keratitis.

Purpose: To investigate the efficiency of amniotic membrane transplantation (AMT) combined with conjunctival flap covering surgery (CFCS) for patients with corneal perforations in fungal keratitis (FK). Methods: In this non-comparative, retrospective case series, 16 participants of corneal perforation in FK were successfully treated by a combination of multilayer AMT and bipedicle conjunctival flap with partial tenon's capsule. Corneal healing, recurrence of FK, visual acuity, and relevant complications were reported as outcome measures. Results: Sixteen patients (13 male, 3 female) had a mean age of 58.8 ± 10.3 (range 29-72) years. The mean diameter of corneal perforation was 1.9 ± 0.7 (range 0.5-2.8) mm. Corneal perforations healed and all the patients preserved their eyeballs. During the 11.0 ± 4.4 (range 6-18) months of follow-up, there was no recurrence of FK in any of these cases. Visual acuity improved in 15 eyes (93.8 %) and remained unchanged in 1 patient (6.3 %) who had no light perception when first admitted. All 6 patients who accepted secondary keratoplasty showed improved best corrected visual acuity of more than 4 lines. The most frequently found fungi were Aspergillus species (6 of 16, 37.5 %) and Fusarium species (4 of 16, 25.0 %), followed by 1 Scedosporium apiospermum (1 of 16, 6.3 %). Conclusions: Combination AMT with CFCS is a safe and effective surgery for patients with corneal perforations in FK, particularly where eye banks and fresh corneas are not available. This surgery could preserve the integrity of the eyeball and avoid the recurrence of FK. Besides, it provides a greater opportunity for further optical keratoplasty.

Isolation and Culture of Human Meibomian Gland Ductal Cells.

Purpose: Hyperkeratinization of meibomian gland (MG) ducts is currently recognized as the primary pathologic mechanism of meibomian gland dysfunction (MGD). This research figured out a method to isolate the MG ducts and established a novel system to culture the human meibomian gland ductal cells (HMGDCs) for investigating the process of MGD. Methods: The MG ducts were obtained from the eyelids of recently deceased donors and subjected to enzymatic digestion. The acini were then removed to isolate independent ducts. These MG ducts were subsequently cultivated on Matrigel-coated wells and covered with a glass plate to obtain HMGDCs. The HMGDCs were further cultivated until passage 2, and when they reached 60% confluence, they were treated with IL-1ß and rosiglitazone for a duration of 48 hours. Immunofluorescence staining and Western blot techniques were employed to identify ductal cells and analyze the effects of IL-1ß on HMGDCs in an in vitro setting. Results: Ophthalmic micro-forceps and insulin needles can be employed for the purpose of isolating ducts. Within this particular culture system, the rapid expansion of HMGDCs occurred in close proximity to the duct tissue. MG ducts specifically expressed keratin 6 (Krt6) and hardly synthesized lipids. Furthermore, the expression of Krt6 was significantly higher (P < 0.0001) in HMGDCs compared to human meibomian gland cells. Upon treatment with IL-1ß, HMGDCs exhibited an overexpression of keratin 1, which was effectively blocked by the administration of rosiglitazone. Conclusions: The present study successfully isolated human MG ducts and cultured HMGDCs, providing a valuable in vitro model for investigating the mechanism of MGD. Additionally, the potential therapeutic efficacy of rosiglitazone in treating hyperkeratinization of ducts in patients with MGD was identified.

Mitophagy and mitochondrion-related expression profiles in response to physiological and pathological hypoxia in the corneal epithelium.

To study the mitochondrial and cellular responses to physiological and pathological hypoxia, corneal epithelial cells were preconditioned under 21% O2, 8% O2 or 1% O2. The cell survival rate, mitochondrial fluorescence and mitophagy flux were quantified using flow cytometry. After RNA sequencing, gene set enrichment analysis (GSEA) was performed. When the oxygen level decreased from 21% to 8%, mitochondrial fluorescence decreased by 45% (p < 0.001), accompanied by an 80% increase in mitophagy flux (p < 0.001). When the oxygen level dropped to 1%, the cell survival rate and mitochondrial fluorescence decreased, while mitophagy flux further increased (each p < 0.001). Comparison of 1% O2 vs. 21% O2 revealed enrichment of the HYPOXIA hallmark. Most of the significantly enriched mitochondrion-related gene sets were involved in apoptosis. The corresponding foremost leading edge genes belonged to the BCL-2 family. Corneal epithelial cell fate decisions under hypoxia may involve noncanonical pathways of mitophagy.

Differential expression of antimicrobial peptides in human fungal keratitis.

AIM: To analyze a series of antimicrobial peptides (AMPs) in corneal tissue from individuals with fungal keratitis (FK) during the active phase of the fungus infection and after healing. METHODS: Patients undergone lamellar keratoplasty for the treatment of severe FK or corneal scar had their corneal buttons sampled. Quantitative real-time polymerase chain reaction (PCR) was used to ascertain the gene expression of human beta-defensin (HBD)-1, -2, -3, -9, S100A7, 8, 9, and LL-37. RESULTS: All AMPs' messenger ribonucleic acid (mRNA) expression was considerably elevated in all samples (n=12). In contrast to controls, where HBD-2, -3, and S100A7 mRNAs were expressed at very low levels, it was discovered that HBD-1, -9, S100A8, S100A9, and LL-37 were constitutively expressed in all healed samples (n=4). HBD-1, -2 -3, S100A7, and LL-37 mRNAs were significantly increased in all active FK samples (n=8). The levels of HBD-9, S100A8, and S100A9 mRNAs were moderately upregulated in all active FK samples. Subgroup comparison showed that HBD-2 was significantly increased in Fusarium keratitis samples (n=5), and LL-37 mRNAs were significantly enhanced in Aspergillus keratitis samples (n=3). Whereas there was not significantly increased of HBD-1, -3, -9, S100A7, 8, 9 mRNA in Aspergillus keratitis samples compared with Fusarium keratitis samples. CONCLUSION: AMPs expression is increased in active FK, but not all AMPs are equally expressed. HBD-2 and LL-37 expression levels are the highest, showing some specificity of AMP expression related to FK. Human AMPs, particularly HBD-2 may play a significant role in Fusarium keratitis and LL-37 might be the key player in Aspergillus keratitis.

Conjunctival Limbal Autograft Combined with Amnion-Assisted Conjunctival Epithelial Redirection for Unilateral Total Limbal Stem Cell Deficiency after Severe Chemical Burn.

(1) Background: To evaluate the efficacy of conjunctival limbal autograft (CLAU) combined with the amnion-assisted conjunctival epithelial redirection (ACER) procedure for patients with unilateral total limbal stem cell deficiency (LSCD) caused by severe chemical burn. (2) Methods: A retrospective interventional case series of unilateral total LSCD after chemical burn who underwent CLAU combined with ACER surgery between September 2021 and July 2023 was collected. Outcome measures included epithelialization of the cornea with donor limbus-derived epithelium, best corrected visual acuity (BCVA), and complications. (3) Results: Nine males and one female were included in this study. The mean age was 40.9 ± 9.63 (range, 26 to 55) years. The average duration between injury and CLAU combined with the ACER procedure was 7.67 ± 3.97 (range, 4 to 18) months. All patients achieved corneal epithelialization and improved BCVA. Postoperative complications occurred in four cases, including delayed corneal epithelial healing in one case, delayed amniotic membrane dissolution and detachment in two cases, and recurrence of symblepharon in one case. No complications were noted in the healthy donor eyes. (4) Conclusions: CLAU combined with ACER is a safe and effective treatment for unilateral total LSCD caused by severe chemical burn. This combined surgery restores visual function for patients with corneal blindness caused by chemical burn, reducing the burden on the families and society.

Mycelium Composite with Hierarchical Porous Structure for Thermal Management.

High-performance porous materials with a low carbon footprint provide sustainable alternatives to petroleum-based lightweight foams and can help meet carbon neutrality goals. However, these materials generally face a trade-off between thermal management capabilities and structural strength. Here, a mycelium composite with a hierarchical porous structure, including both macro- and microscale pores, produced from multiple and advanced mycelial networks (elastic modulus of 1.2 GPa) binding loosely distributed sawdust is demonstrated. The morphological, biological, and physicochemical properties of the filamentous mycelium and composites are discussed in terms of how they are influenced by the mycelial system of the fungi and the way they interact with the substrate. The composite shows a porosity of 0.94, a noise reduction coefficient of 0.55 at a frequency range of 250-3000 Hz (for a 15 mm thick sample), a thermal conductivity of 0.042 W m-1  K-1 , and an energy absorption of 18 kJ m-3 at 50% strain. It is also hydrophobic, repairable, and recyclable. It is expected that the hierarchical porous structural composite with excellent thermal and mechanical properties can make a significant impact on the future development of highly sustainable alternatives to lightweight plastic foams.

Two-step strategy-conjunctival flap covering surgery combined with secondary deep anterior lamellar keratoplasty for the treatment of high-risk fungal keratitis.

AIM: To investigate whether the two-step strategy [conjunctival flap covering surgery (CFCS) combined with secondary deep anterior lamellar keratoplasty (DALK)] is effective for patients with high-risk fungal keratitis (FK). METHODS: In this noncomparative, retrospective case series, 10 subjects (6 males, 4 females) with a mean age of 56.5±7.1 (range 47-72)y with high-risk FK undergone the two-step strategy were included. Reported outcome measures were healing of the corneal ulcer, recurrence of FK, reject reaction, improvement in best corrected visual acuity (BCVA) and relevant complications. RESULTS: The average diameter of corneal infiltrates was 7.50±0.39 mm, ranging from 6.94 to 8.13 mm. The mean depth of corneal infiltrates was 422.4±77.1 µm, ranging from 350 to 535 µm. The mean corneal thickness was 597.4±117.3 µm, ranging from 458 to 851 µm. Hypopyon and endothelial plaques were presented in all patients. The period between the two steps was 3.65±0.9 (ranging from 3 to 5)mo. The graft diameter was 7.75±0.39 mm. At the last follow-up (average 9.25±3.39, ranging from 5.5 to 17mo), no fungal recurrence or graft rejection appeared, and all patients showed improvement of BCVA. One patient suffered from liver function impairment due to oral voriconazole for 4wk and recovered spontaneously after 1wk of drug withdrawal. CONCLUSION: The two-step strategy is safe and effective in the treatment of high-risk FK by transforming intentional therapeutic penetrating keratoplasty during acute infection to later optical DALK. It is a practical strategy, especially in areas lacking fresh donor corneas and eye bank services.

The inhibition of p38 MAPK blocked inflammation to restore the functions of rat meibomian gland epithelial cells.

Meibomian glands (MGs) are vital for ocular surface health. However, the roles of inflammation in the progression of meibomian gland dysfunction (MGD) are largely unknown. In this study, the roles of the inflammation factor interleukin-1ß (IL-1ß) via the p38 mitogen-activated protein kinases (MAPK) signaling pathway on rat meibomian gland epithelial cells (RMGECs) were explored. Eyelids from adult rat mice at 2 months and 2 years of age were stained with specific antibodies against IL-1ß to identify inflammation levels. RMGECs were exposed to IL-1ß and/or SB203580, a specific inhibitor of p38 MAPK signaling pathway, for 3 days. Cell proliferation, keratinization, lipid accumulation, and matrix metalloproteinases 9 (MMP9) expression were evaluated by MTT assay, polymerase chain reaction (PCR), immunofluorescence staining, apoptosis assay, lipid staining, and Western blot analyses. We found that IL-1ß was significantly higher in the terminal ducts of MGs in rats with age-related MGD than in young rats. IL-1ß inhibited cell proliferation, suppressed lipid accumulation and peroxisome proliferator activator receptor γ (PPARγ) expression, and promoted apoptosis while activating the p38 MAPK signaling pathway. Cytokeratin 1 (CK1), a marker for complete keratinization, and MMP9 in RMGECs were also up-regulated by IL-1ß. SB203580 effectively diminished the effects of IL-1ß on differentiation, keratinization, and MMP9 expression by blocking IL-1ß-induced p38 MAPK activation, although it also inhibited cell proliferation. The inhibition of the p38 MAPK signaling pathway blocked IL-1ß-induced differentiation reduction, hyperkeratinization, and MMP9 overexpression of RMGECs, which provides a potential therapy for MGD.

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves' Ophthalmopathy.

Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves' ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.

Ductal Hyperkeratinization and Acinar Renewal Abnormality: New Concepts on Pathogenesis of Meibomian Gland Dysfunction.

Meibomian gland dysfunction (MGD) is a functional and morphological disorder of the meibomian glands which results in qualitative or quantitative alteration in meibum secretion and is the major cause of evaporative dry eye (EDE). EDE is often characterized by tear film instability, increased evaporation, hyperosmolarity, inflammation, and ocular surface disorder. The precise pathogenesis of MGD remains elusive. It has been widely considered that MGD develops as a result of ductal epithelial hyperkeratinization, which obstructs the meibomian orifice, halts meibum secretion, and causes secondary acinar atrophy and gland dropout. Abnormal self-renewal and differentiation of the acinar cells also play a significant role in MGD. This review summarizes the latest research findings regarding the possible pathogenesis of MGD and provides further treatment strategies for MGD-EDE patients.

Characteristics of In Vitro Culture and In Vivo Confocal Microscopy in Patients with Fungal Keratitis in a Tertiary Referral Hospital in Central China.

PURPOSE: To investigate the characteristics of in vitro culture and in vivo confocal microscopy (IVCM) in patients with fungal keratitis (FK) presented in a tertiary referral hospital in central China. METHODS: In this noncomparative retrospective study, patients with the diagnosis of FK between October 2021 and November 2022 were reviewed. An IVCM and fungal culture (corneal scraping specimens) were performed, and the characteristics were analyzed. RESULTS: During October 2021 and November 2022, 85 patients were diagnosed with FK. From 63 culture-positive cases, 8 species of fungus were identified. The proportions of isolated fungal species were Fusarium and Aspergillus equally accounting for 33.3% (21 of 63), Alternaria 9.5% (6 of 63), Curvularia 6.3% (4 of 63), Scedosporium apiospermum 6.3% (4 of 63), Paecilomyces lilacinus 3.2% (2 of 63), Exserohilum 3.2% (2 of 63), and Candida 4.8% (3 of 63), respectively. In positive culture cases, IVCM was found to be positive for hyphae or spores in 61 of 63 patients (96.8%). Different fungal species had a variety of cultural characteristics and IVCM manifestations. CONCLUSIONS: In a tertiary referral hospital in central China, Fusarium species, Aspergillus species, and Alternaria species were the 3 most common isolated fungal pathogens, and the proportion of Aspergillus species was significantly higher than that in other regions of China. Careful lesion depth examination by IVCM and OCT should be taken before lamellar keratoplasty to avoid postoperative recurrence. Identifying the IVCM image and culture characteristics will facilitate rapid diagnosis and proper treatment, but IVCM cannot yet replace fungal cultures to distinguish between different fungal species.