Fibronectin binds integrin α5ß1 to regulate macular neovascularization through the Wnt/ß-catenin signaling pathway.

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the macula. The formation of macular neovascularization (MNV) and subretinal fibrosis of AMD is the most classic cause of the loss of vision in older adults worldwide. While the underlying causes of MNV and subretinal fibrosis remain elusive, the common feature of many common retinal diseases is changes the proportions of protein deposition in extracellular matrix (ECM) when compared to normal tissue. In ECM, fibronectin (FN) is a crucial component and plays a pivotal part not only in fibrotic diseases but also in the process of angiogenesis. The study aims to understand the role of ligand FN and its common integrin receptor α5ß1 on MNV, and to understand the molecular mechanism involved. To study this, the laser-induced MNV mouse model and the rhesus macaque choroid-retinal endothelial cell line (RF/6A) chemical hypoxia mode were established, and the FN-α5ß1 expression levels were detected by immunohistochemistry (IHC) and quantitative real-time PCR analysis (qRT-PCR). Fibronectin expression was silenced using small interfering RNA (siRNA) targeting FN. The tube formation and vitro scratch assays were used to assess the ability to form blood vessels and cell migration. To measure the formation of MNV, immunofluorescence, and Western blot assays were used. These results revealed that the expressions of FN and integrin α5ß1 were distinctly increased in the laser-induced MNV mouse model and in the RF/6A cytochemically induced hypoxia model, and the expression tendency was identical. After the use of FN siRNA, the tube formation and migration abilities of the RF/6A cells were lower, the ability of endothelial cells to proliferate was confined and the scope of damage caused by the laser in animal models was significantly cut down. In addition, FN gene knockdown dramatically inhibited the expression of Wnt/ß-catenin signal. The interaction of FN with the integrin receptor α5ß1 in the constructed model, which may act through the Wnt/ß-catenin signaling pathway, was confirmed in this study. In conclusion, FN may be a potential new molecular target for the prevention and treatment of subretinal fibrosis and MNV.

Abnormal platelet parameters in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Platelet dysfunction plays a critical role in the pathogenesis of inflammatory bowel disease (IBD). Despite clinical observations indicating abnormalities in platelet parameters among IBD patients, inconsistencies persist, and these parameters lack standardization for diagnosis or clinical assessment. METHODS: A comprehensive search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases for relevant articles published up to December 16th, 2023. A random-effects model was employed to pool the weighted mean difference (WMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) between IBD patients and healthy controls, and subgroup analyses were performed. RESULTS: The meta-analysis included 79 articles with 8,350 IBD patients and 13,181 healthy individuals. The results revealed significantly increased PLT and PCT levels (WMD: 69.910, 95% CI: 62.177, 77.643 109/L; WMD: 0.046%, 95% CI: 0.031%, 0.061%), and decreased MPV levels (WMD: -0.912, 95% CI: -1.086, -0.739 fL) in IBD patients compared to healthy individuals. No significant difference was found in PDW between the IBD and control groups (WMD: -0.207%, 95% CI: -0.655%, 0.241%). Subgroup analysis by disease type and disease activity showed no change in the differences for PLT, PCT, and MPV in the ulcerative colitis and Crohn's disease groups, as well as the active and inactive groups. Notably, the active group exhibited significantly lower PDW levels than the control group (WMD: -1.138%, 95% CI: -1.535%, -0.741%). CONCLUSIONS: Compared with healthy individuals, IBD patients display significantly higher PLT and PCT and significantly lower MPV. Monitoring the clinical manifestations of platelet abnormalities serves as a valuable means to obtain diagnostic and prognostic information. Conversely, proactive measures should be taken to prevent the consequences of platelet abnormalities in individuals with IBD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023493848.

Characteristics of China's coal mine methane emission sources at national and provincial levels.

Methane (CH4) is the second most abundant greenhouse gas. China is the largest CH4 emitter in the world, with coal mine methane (CMM) being one of the main anthropogenic contributions. Thus, there is an urgent need for comprehensive estimates and strategies for reducing CMM emissions in China. However, the development of effective strategies is currently challenged by a lack of information on temporal variations in the contributions of different CMM sources and the absence of provincial spatial analysis. Here, considering five sources and utilization, we build a comprehensive inventory of China's CMM emissions from 1980 to 2022 and quantify the contributions of individual sources to the overall CMM emissions at the national and provincial levels. Our results highlight a significant shift in the source contributions of CMM emissions, with the largest contributor, underground mining, decreasing from 89% in 1980 to 69% in 2022. Underground abandoned coal mines, which were ignored or underestimated in past inventories, have become the second source of CMM emissions since 1999. From 2011 to 2022, we identified Shanxi, Guizhou, and Shaanxi as the three largest CMM-emitting provinces, while the Emissions Database for Global Atmospheric Research (EDGAR) v8 overestimated emissions from Inner Mongolia, ranking it third. Notably, we observed a substantial decrease (exceeding 1 Mt) in CMM emissions in Sichuan, Henan, Liaoning, and Hunan between 2011 and 2022, which was not captured by EDGAR v8. To develop targeted CMM emission reduction strategies at the provincial level, we classified 31 provinces into four groups based on their CMM emission structures. In 2022, the number of provinces with CMM emissions mainly from abandoned coal mines has exceeded that of provinces with mainly underground mines, which requires attention. This study reveals the characteristics of the source of CMM emissions in China and provides emission reduction directions for four groups of provinces.

Structural characteristics and drivers of greenhouse gas emissions at county-level and long-time scales: A case study of the Anji County, China.

To achieve carbon neutrality, the Chinese government needs to gain a comprehensive understanding of the sources and drivers of greenhouse gas (GHG) emissions, particularly at the county level. Anji County in eastern China is a typical example of an industrial transformation from quarrying to a low-carbon economy. This study analyzed the decoupling types and structural characteristics of GHG emissions and the driving factors of carbon dioxide (CO2) emissions in the Anji from 2006 to 2019, and explored the differences between county-level and provincial-level or city-level results. It was observed that energy-related activities are the main source of GHG emissions in Anji and that economic development is the driving factor behind the increasing CO2 emissions. However, industrial transformation and upgradation coupled with the alternative use of clean energy limit the growth of GHG emissions. This study details the GHG emissions of county during the industrial transformation stage and provides corresponding policy recommendations for county governments.

Thymoquinone attenuates inflammation in C. Albicans keratitis by activating Nrf2/HO-1 signaling pathway and reducing fungal load.

PURPOSE: This study aims to investigate the anti-inflammatory and antifungal properties of thymoquinone (TQ) and elucidate its mechanism of action in the context of C. albicans keratitis. METHODS: Various methods were employed to identify a safe and effective concentration of TQ with antifungal properties, including the determination of the minimum inhibitory concentration (MIC), the cell counting kit-8 (CCK-8) test, and the Draize experiment. The severity of fungal keratitis (FK) was assessed through clinical ratings and slit-lamp imaging. Fungus burden was determined using plate counting and periodic acid Schiff (PAS) staining. Neutrophil infiltration and activity were investigated through immunofluorescence staining (IFS), myeloperoxidase (MPO) analysis, and hematoxylin and eosin (HE) staining. To explore the anti-inflammatory effects of TQ and its mechanism of action, we employed RT-PCR, ELISA, and western blot techniques. RESULTS: TQ effectively controlled fungal growth at a concentration of 50 µg/mL while preserving the integrity of mouse corneas. Human corneal epithelial cells (HCECs) remained unaffected by TQ at concentrations ≤ 3.75 µg/mL. Treatment with TQ led to significant improvements in clinical scores, fungal burden, neutrophil infiltration, and the expression of inflammatory factors compared to the DMSO group. Moreover, TQ demonstrated the ability to reduce the levels of inflammatory factors in HCECs stimulated by C. albicans. Additionally, TQ enhanced the expressions of Nrf2 and HO-1 in mouse corneas. The downregulation of cytokines induced by TQ was reversed upon pretreatment with inhibitors of Nrf2 or HO-1. CONCLUSION: TQ exhibits a protective effect in the context of C. albicans keratitis through multiple mechanisms, including inhibition of C. albicans growth, reduction of neutrophil recruitment, activation of the Nrf2/HO-1 pathway, and limitation of the expression of pro-inflammatory factors.

Inhibition of AIF-1 alleviates laser-induced macular neovascularization by inhibiting endothelial cell proliferation via restrained p44/42 MAPK signaling pathway.

Age-related macular degeneration (AMD) is a leading blinding disease worldwide, and macular neovascularization (MNV) is a common complication encountered in the advanced stages of AMD. While the underlying causes of MNV remain elusive, aberrant multiplication of choroidal endothelial cells (CECs) and increased vascular endothelial growth factor (VEGF) are thought to play significant roles in the occurrence and development of MNV. Allograft inflammatory factor-1(AIF-1) is a crucial regulatory factor of vascular tubular structure formation and growth, involving the proliferation and migration of vascular endothelial cells and various tumor cells. This study aimed to understand how AIF-1 effects the proliferation of CECs and the subsequent progression of MNV. To study this, a mouse MNV model was established through laser injury, and the AIF-1 expression levels were then measured using western blot and immunohistochemistry. AIF-1 siRNA was intravitreally injected to silence AIF-1 gene expression. Western blot and choroidal flat mount were performed to measure the progression of MNV and proliferation of the CECs. These results showed that the protein expression of AIF-1 was significantly elevated in the laser-induced mouse MNV model, and the expression trend was consistent with VEGF. The protein level of AIF-1 was significantly decreased after the intravitreal injection of AIF-1 siRNA, the damage range of laser lesions was significantly reduced, and the proliferation of endothelial cells was inhibited. Knockdown of the AIF-1 gene significantly inhibited the expression of mitogen-activated protein kinase p44/42 in MNV lesions. In summary, this research demonstrates that AIF-1 promoted MNV progression by promoting the proliferation of CECs and that silencing AIF-1 significantly ameliorates MNV progression in mouse models, which may act through the p44/42 MAPK signaling pathway. AIF-1 could be a new potential molecular target for MNV.

Evaluation of vitrectomy combined preoperative intravitreal ranibizumab and postoperative intravitreal triamcinolone acetonide for proliferative diabetic retinopathy.

BACKGROUND: To explore the treatment efficacy of the combination of preoperative intravitreal ranibizumab (IVR) and postoperative intravitreal triamcinolone acetonide (IVTA) in patients undergoing pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). METHODS: A retrospective comparative study was performed on 128 eyes of 128 patients who had PDR and underwent PPV. Patients who received a single PPV were assigned to Group A. Those who received PPV with preoperative IVR were assigned to Group B. Patients in Group C underwent PPV combined preoperative IVR and postoperative IVTA. Intraoperative findings, changes in mean best-corrected visual acuity (BCVA) and postoperative adverse events, were retrospectively evaluated at 6-month follow-up. RESULTS: The incidences of iatrogenic breaks, severe intraoperative bleeding, using long-term internal tamponade agents, recurrent vitreous hemorrhage (VH), and duration of surgery were statistically significantly less in Group B and Group C than in Group A. The postoperative BCVA was statistically significantly better in Groups B and Group C than in Group A, respectively, at 1 month after surgery. The mean 3-month postoperative visual acuity was better in Group C. The incidence of high intraocular pressure (IOP) was significantly higher in Group C at the first postoperative week. There were no statistically significant differences in the incidence of exudative retinal detachment and choroidal detachment among the three groups. CONCLUSION: In patients undergoing PPV for PDR, preoperative IVR significantly reduced the occurrence of intraoperative and postoperative complications, and the combination of preoperative IVR and postoperative IVTA can better improve the postoperative visual outcome.

Role of PTX3 in corneal epithelial innate immunity against Aspergillus fumigatus infection.

Pentraxin3 (PTX3), a member of long pentraxin family, plays a non-redundant role in human humoral innate immunity. However, whether PTX3 is expressed by corneal epithelial cells and its role during corneal fungi infection has not yet been investigated. To identify the presence of PTX3 in cornea, the possible mechanisms involved in its expression, and also the effects on corneal anti-fungi innate immune response, clinic human corneal tissues and cultured human corneal epithelial cells (HCECs) were resorted. PTX3 mRNA and protein were detected in corneal samples and cultured HCECs, which was significantly up-regulated after exposing to Aspergillus fumigatus (A. fumigatus). Pretreated with specific inhibitors, only Syk contributed to the regulation of PTX3 expression in Dectin-1/Syk signal axis. Furthermore, among the MAPK members (p38 MAPK, ERK1/2 and JNK), only ERK1/2 and JNK were responsible for A. fumigatus induced PTX3 production. Blocking of endogenous PTX3 by siRNA down-regulated the production of IL-1ß at both mRNA and protein levels. Meanwhile, blocking of PTX3 also inhibited the phosphorylation of ERK1/2 and JNK, but not p38 MAPK. These findings demonstrate that PTX3 is expressed in human corneal epithelial cells and Syk, ERK1/2, JNK signaling pathways play an important role in the regulation of PTX3 induction. PTX3 plays a proinflammatory role in corneal epithelial anti-fungi immune response by affecting the production of IL-1ß and activation of some proinflammatory signaling pathways (ERK1/2 and JNK).

Effect of incision on visual outcomes after implantation of a trifocal diffractive IOL.

BACKGROUND: To evaluate visual acuity, corneal astigmatism and corneal higher-order aberrations (HOAs) after implantation of trifocal diffractive IOLs operated with either a corneal steep-axis incision or 135° incision. METHOD: This prospective study enrolled patients randomly assigned to different groups. According to preoperative corneal astigmatism, 101 eyes of 77 patients were assigned into group A1 (0 ~ 0.50 D) or A2 (0.51 ~ 1.00 D) with a corneal steep-axis incision or group B1 (0 ~ 0.50 D) or B2 (0.51 ~ 1.00 D) with a 135° incision. Visual acuity, corneal astigmatism and corneal higher-order aberrations (HOAs) were followed-up for 3 months. RESULTS: Corneal astigmatism in group A2 significantly decreased 3 months after surgery (P < 0.01) and was significantly lower than that in group B2 1 day, 2 weeks, 1 month, and 3 months postoperatively (all values of P < 0.01). The following parameters were better in group A2 than in group B2: uncorrected intermediate visual acuity (UIVA) at 1 day, 2 weeks, 1 month, and 3 months (P = 0.00, 0.00, 0.01, 0.01, respectively);uncorrected distance visual acuity (UDVA) at 1 day and 2 weeks (P = 0.00, 0.01); and uncorrected near visual acuity (UNVA) at 1 day, 2 weeks, and 1 month postoperatively (P = 0.00, 0.01, 0.02, respectively). CONCLUSIONS: After a corneal steep-axis incision, patients with preoperative corneal astigmatism of 0.51 D to 1.00 D exhibited reduced corneal astigmatism and achieved better UIVA and early postoperative UDVA/UNVA. TRIAL REGISTRATION: Retrospectively Registered Trials ISRCTN10086721 , 23/06/2018.

A retrospective analysis of eleven cases of invasive rhino-orbito-cerebral mucormycosis presented with orbital apex syndrome initially.

BACKGROUND: Rhino-orbito-cerebral mucormycosis(ROCM) is an invasive fungal infection that usually occurs in immunocompromised patients and sometimes presents as orbital apex syndrome(OAS) initially. It is rapidly fatal without an early diagnosis and treatment. We report the cases of invasive ROCM presenting with OAS initially in order to raise the attention of clinicians. METHODS: We retrospectively investigated eleven cases of invasive ROCM presenting initially with OAS admitted between January 2006 and December 2013. We analyzed clinical features, results of laboratory and radiological examinations, nasal endoscopy, aggressive surgical excision and debridement, and medical management outcomes of each case. RESULTS: A total of eleven cases of invasive ROCM with OAS as an initial sign were presented. Mucormycosis was accompanied by type II diabetes mellitus in nine cases, renal transplant in one case, and injury caused by traffic accident in one case. Anterior rhinoscopy revealed palatine or nasal necrotic lesions in all patients, and transethmoidal optic nerve decompression was carried out in three patients at the same time. CT scan revealed rhino-orbital-cerebral involvement in every patient. All patients were given intravenous amphotericin B. Nine patients underwent surgical debridement of necrotic tissue. Three patients survived. CONCLUSIONS: ROCM is a severe, emergent and fatal infection requiring multidisciplinary management. It may often present with OAS initially. For ophthalmologist, mucormycosis must be considered in immunocompromised patients presenting with OAS initially, and anterior rhinoscopy is imperative before hormonotherapy, even in the cases absent of ketoacidosis induced by diabetes mellitus.

Protein tyrosine phosphatase 1B regulates the activity of retinal pigment epithelial cells.

PURPOSE: To determine whether protein tyrosine phosphatase 1B (PTP1B) is expressed in rat retinal pigment epithelium (RPE) cells, to evaluate whether inhibition of PTP1B contributes to initiation of RPE cells into an active state, and to investigate the signaling pathways involved in this process. METHODS: Rat retinas were detached by trans-scleral injection of 1.4% sodium hyaluronate into the subretinal space. Immunocytochemistry evaluated the expression of PTP1B in RPE cells located at normal and detached retinas. From the cultured RPE cells treated with TCS-401, cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetracolium bromide assay, and the protein expression levels of cyclin A and cyclin D1 were determined. The effect of TCS-401 on cell differentiation was confirmed by immunostaining for α-smooth muscle actin and by western blot. Cell migration activity and PTP1B signaling mechanism were determined. Migration Assay was used to evaluate cell migration activity. PTP1B signaling mechanism was determined by use of PD98059 and LY294002. RESULTS: PTP1B was expressed in the RPE layer of the normal retina. After retinal detachment, weak immunolabeling of PTP1B was seen in the RPE cells. TCS-401 promoted the proliferation and expression of cyclin A and cyclin D1 in RPE cells. TCS-401 induced RPE cells to differentiate toward better contractility and motility. A migration assay proved that inhibiting PTP1B improved the migratory activity of RPE cells. TCS-401 activated extracellular signal-regulated kinase (Erk) and protein kinase B (Akt) phosphorylation. Pretreatment with PD98059 and LY294002 abolished TCS-401-induced activation of Erk, Akt, cell proliferation, and cell migration. CONCLUSIONS: PTP1B may be involved in regulating the active state of RPE cells. The inhibition of PTP1B promoted the proliferation, myofibroblast differentiation, and migration of RPE cells, and MEK/Erk and PI3K/Akt signaling pathways played important roles in the proliferation and migration process.

Role of Dectin-1 in the innate immune response of rat corneal epithelial cells to Aspergillus fumigatus.

BACKGROUND: To observe Dectin-1 expression in fungal keratitis on rat models and to determine the role of Dectin-1 in innate immune response to Aspergillus fumigatus. METHODS: Wistar rats were randomly divided into control, fungal keratitis and pretreatment (pretreated with Laminarin) groups. Samples were used for conducting immunohistochemical staining and real-time PCR to observe expression of cytokines like CCL2, CCL3, CXCL1, CXCL2, IL-1ß, TNF-α, IL-6, IL-10. RESULTS: After fungal stimulations, all 7 inflammatory factors, except IL-10, increased with different levels. After 4 h of fungal stimulations, IL-1ß, IL-6, CCL2, CXCL1 and CXCL2 of pretreatment groups were significantly (p < 0.05) lower than fungal groups, while the other 3 cytokines had no significant changes. After 8 h of fungal stimulations, IL-6 and CXCL1 of pretreatment groups were still significantly (p < 0.05) lower than fungal groups. DISCUSSION: With progress of fungus stimulation, expression of IL-1ß,CXCL1 ,CXCL2,MCP-1 gradually increased, whilepretreated with Laminarin to block Dectin-1, these expression decreased, indicating that Dectin-1 maypromote immune reaction through them. IL-10 decreased in fungal group because of itsimmunosuppressive effect at 4h, and it began to increase at 8h to suppress Th1 inflammation response inorder to avoid excessive tissue damage. CONCLUSION: Dectin-1 in early period of innate immune responses in rat fungal keratitis might work through IL-1ß, IL-6, CCL2, CXCL1, CXCL2 to recruit neutrophils and macrophages to participate anti-fungal immunity.

The role of Syk signaling in antifungal innate immunity of human corneal epithelial cells.

BACKGROUND: Fungal keratitis is a kind of intractable and sight-threatening diseases. Spleen-tyrosine kinase (Syk) is a non-receptor tyrosine kinase, which plays an important role in the signaling pathway of the receptors. In the current study, we investigate the expression and function of Syk in human corneal epithelial cells with Aspergillus fumigatus (A. fumigatus) infection. METHODS: Cultured telomerase-immortalized human corneal epithelial cells (THCEs) were treated with A. fumigatus hyphae with or without treatment of Syk inhibitors. Activation of Syk and the role of Syk in regulating inflammatory cytokines and chemokines expression were evaluated. The mRNA expression was determined by real time PCR, and protein activation was measured by western blotting. RESULTS: Syk protein was detected in THCEs, and its activation was enhanced after treatment of A. fumigatus hyphae. Expression of inflammatory cytokines (IL-1ß and IL-6) and chemokines (IL-8 and CXCL1) mRNA were significantly increased after stimulation of A. fumigatus hyphae in THCEs. Activation of Syk and expression of IL-1ß, IL-6, IL-8 and CXCL1 by A. fumigatus hyphae were blocked by Syk inhibitors. CONCLUSION: These findings demonstrate that normal human corneal epithelial cells produce Syk, and Syk activation plays an important role in regulating A. fumigatus hyphae-induced inflammatory responses in THCEs.

Progranulin Protects against Aspergillus fumigatus Keratitis by Attenuating the Inflammatory Response through Enhancing Autophagy.

Fungal keratitis (FK) is a severe corneal condition caused by pathogenic fungi and is associated with the virulence of fungi and an excessive tissue inflammatory response. Progranulin (PGRN), functioning as a multifunctional growth factor, exerts a pivotal influence on the regulation of inflammation and autophagy. The aim of our research was to analyze the role of PGRN in Aspergillus fumigatus (A. fumigatus) keratitis. We found that PGRN expression was increased in the mouse cornea with A. fumigatus keratitis. In our experiments, corneas of mice with FK were treated with 100 ng/mL of PGRN. In vitro, RAW 264.7 cells were treated with 10 ng/mL of PGRN before A. fumigatus stimulation. The findings suggested that PGRN effectively alleviated corneal edema and decreased the expression of pro-inflammatory cytokines in mice. In stimulated RAW 264.7 cells, PGRN treatment suppressed the expression of pro-inflammatory cytokines IL-6 and TNF-α but promoted the expression of the anti-inflammatory cytokines IL-10. PGRN treatment significantly upregulated the expression of autophagy-related proteins LC3, Beclin-1, and Atg-7. 3-Methyladenine (3-MA, autophagy inhibitor) reversed the regulation of inflammatory cytokines by PGRN. In addition, our study demonstrated that PGRN also enhanced phagocytosis in RAW 264.7 cells. In summary, PGRN attenuated the inflammatory response of A. fumigatus keratitis by increasing autophagy and enhanced the phagocytic activity of RAW 264.7 cells. This showed that PGRN had a protective effect on A. fumigatus keratitis.

Role of Inhibiting Inflammation of LC3-Associated Phagocytosis in Dry Eye Disease.

PURPOSE: To confirm the expression and investigate the role of LC3-associated phagocytosis (LAP) in dry eye disease (DED). METHODS: The DED model of mice was established by scopolamine subcutaneous injection in a low-humidity environment chamber. Tear secretion test and corneal fluorescein sodium staining were used to evaluate the severity of DED. Expression levels of Rubicon, microtubule-associated protein light chain 3-II (LC3-II), Beclin-1 and autophagy-related gene-7 (Atg-7) in corneas of mice with DED were tested by western blot. Cell Counting Kit-8 (CCK-8) assay was used to detect the effects of different concentrations of hypertonic solutions on the proliferation activity of human corneal epithelial cells (HCECs). The expression levels of Dectin-1, IL-6 and IL-1ß in HCECs after stimulation with different concentrations of hypertonic solutions were tested. The expressions of Rubicon, LC3-II, Beclin-1 and ATG-7 in HCECs were detected by reverse transcription polymerase chain reaction (RT-PCR). After being pretreated with 10 µM si-Rubicon, the severity of the disease was documented by corneal fluorescein sodium staining. And the expression levels of IL-6 and IL-1ß were also tested by RT-PCR. RESULTS: Compared with the normal control group, the corneal fluorescein sodium staining scores and tear secretion were significantly reduced. Rubicon, LC3-II, Beclin-1 and ATG-7 were significantly elevated. CCK-8 showed that the 400 and 450 mOsM hypertonic solutions did not affect the proliferation activity of HCECs. The expression of Dectin-1, IL-1ß and IL-6 were elevated after stimulation with 450 mOsM solution. LC3-II, Rubicon, ATG-7 and Beclin-1 increased after stimulation with 450 mOsM hyperosmolar solution in HCECs. Corneal fluorescein staining showed that si-Rubicon increased the severity of DED in mice. Moreover, the mRNA expressions of inflammatory factors IL-1ß and IL-6 in the cornea of mice were significantly increased. CONCLUSION: DED increased the expression of proteins associated with LAP. LAP could play an anti-inflammatory effect in DED.

CCl4 emissions in eastern China during 2021-2022 and exploration of potential new sources.

According to the Montreal Protocol, the production and consumption of ozone-layer-depleting CCl4 for dispersive applications was globally phased out by 2010, including China. However, continued CCl4 emissions were disclosed, with the latest CCl4 emissions unknown in eastern China. In the current study, based on the atmospheric measurements of ~12,000 air samples taken at two sites in eastern China, the 2021-2022 CCl4 emissions are quantified as 7.6 ± 1.7 gigagrams per year. This finding indicates that CCl4 emissions continued after being phased out for dispersive uses in 2010. Subsequently, our study identifies potential industrial sources (manufacture of general purpose machinery and manufacture of raw chemical materials, and chemical products) of CCl4 emissions.

Global methyl halide emissions from biomass burning during 2003-2021.

Methyl halides (CH3Cl, CH3Br, and CH3I) are ozone-depleting substances. Biomass burning (BB) is an important source of methyl halides. The temporal variations and global spatial distribution of BB methyl halide emissions are unclear. Thus, global methyl halide emissions from BB during 2003-2021 were estimated based on satellite data. A significant decreasing trend (p < 0.01) in global methyl halide emissions from BB was found between 2003 and 2021, with CH3Cl emissions decreasing from 302 to 220 Gg yr-1, CH3Br emissions decreasing from 16.5 to 11.7 Gg yr-1, and CH3I emissions decreasing from 8.9 to 6.1 Gg yr-1. From a latitudinal perspective, the northern high-latitude region (60-90° N) was the only latitude zone with significant increases in BB methyl halide emissions (p < 0.01). Based on an analysis of the drivers of BB methyl halide emissions, emissions from cropland, grassland, and shrubland fires were more correlated with the burned area, while BB emissions from forest fires were more correlated with the emissions per unit burned area. The non-BB emissions of CH3Cl increased from 4749 Gg yr-1 in 2003 to 4882 Gg yr-1 in 2020, while those of CH3Br decreased from 136 Gg yr-1 in 2003 to 118 Gg yr-1 in 2020 (global total CH3I emissions are not available). The finding indicates that global CH3Cl and CH3Br emissions from sources besides BB increased and decreased during 2003-2020. Based on our findings, not only searching for unknown sources is important, but also re-evaluating known sources is necessary for addressing methyl halide emissions.

Characteristics and source apportionment of some halocarbons in Hangzhou, eastern China during 2021.

In recent years, eastern China has been identified as an important contributor to national and global emissions of halocarbons, some of which are ozone depletion substances (ODSs) that delay the recovery of the stratospheric ozone layer. However, the most recent characteristics and sources of halocarbons in eastern China remain unclear. Thus, hourly atmospheric observations of halocarbons were conducted in Hangzhou throughout 2021. The results showed that methylene chloride (CH2Cl2) was the most abundant halocarbon (2207 (25 %-75 % quantile: 1116-2848) ppt; parts per trillion) followed by chloromethane (CH3Cl) (912 (683-1043) ppt), and 1,2-dichloroethane (CH2ClCH2Cl) (596 (292-763) ppt). Then, backward trajectory and potential source contribution function (PSCF) analysis show that the emission hot spots of halocarbons were concentrated in adjacent cities in Zhejiang and neighboring provinces in eastern China. Moreover, based on positive matrix factorization (PMF) analysis, industrial emission (38.7 %), solvent usage (32.6 %), and the refrigeration sector and biomass burning (23.7 %) were the main sources of halocarbons (observed in this study). This study reveals high concentrations and potential sources of halocarbons in eastern China, which are important for studying the recovery of the ozone layer.

Candidalysin amplifies the immune inflammatory response in Candida albicans keratitis through the TREM-1/DAP12 pathway.

Candidalysin is a fungal peptide toxin secreted by Candida albicans hyphae during invasion into epithelial cells. In Candida albicans-infected mucosa, candidalysin causes epithelial cell damage and activates downstream inflammatory responses, especially the release of inflammatory cytokines. However, the role of candidalysin in Candida albicans corneal keratitis remains unexplored. Moreover, it remains unclear whether candidalysin regulates the inflammatory response through the TREM-1/DAP12 pathway in Candida albicans corneal keratitis. In this study, we determined the expression pattern of TREM-1 in a mouse model of Candida albicans corneal keratitis and investigated the molecular mechanism underlying the inflammatory response regulation by candidalysin. The corneal keratitis model was established in C57BL/6 mice. In the GF9 group, mice were pretreated and then treated with the TREM-1 inhibitor GF9; in the candidalysin group, mice were treated with peptide candidalysin; and in the PD98059 group, mice were pretreated with the ERK inhibitor PD98059. Slit-lamp photography, clinical scoring, PCR, western blotting and immunofluorescence assay were performed to observe disease response and GF9 therapeutic efficacy. Pretreatment with candidalysin or PD98059 was performed before Candida albicans infection. GF9 treatment reduced the expression of TREM-1 and cytokines in the infected mouse cornea, whereas candidalysin treatment increased the expression of TREM-1, p-ERK, and cytokines, and this increase was inhibited by GF9. The candidalysin-induced increment of TREM-1, p-ERK, and cytokines was inhibited by PD98059 pretreatment. These data suggest that candidalysin can initiate inflammatory response in Candida albicans corneal keratitis through the TREM-1/DAP12 pathway and can regulate cytokine expression by enhancing ERK phosphorylation.