The consistency of Anti-Toxocara IgG between the Aqueous Humor and Vitreous of Patients with Clinically Suspected Ocular Toxocariasis.

PURPOSE: To assess the consistencies of anti-Toxocara IgG (T-IgG) and Goldmann-Witmer coefficient (GWC) between paired aqueous humor (AH) and vitreous samples from patients with clinically-suspected ocular toxocariasis (OT). DESIGN: Inter-test reliability assessment. METHODS: A total of 47 patients with clinically-suspected OT who underwent vitrectomy were included. AH, vitreous and serum samples from each patient were collected and levels of specific T-IgG in them were detected. The association and agreement of T-IgG and GWC between AH and vitreous were evaluated. The area under the receiver operating characteristic curve (AUROC) was generated to assess the diagnostic performance of AH. RESULTS: The T-IgG levels and GWC values in vitreous were higher than those in AH (P = 0.023 and P = 0.029, respectively), but similar positivity rates in the T-IgG (P = 1.000) and GWC>3 (P = 1.000) were apparent between vitreous and AH. In addition, there was a positive correlations between the AH and vitreous T-IgG levels (rs = 0.944, P < 0.001) and the GWC values (rs = 0.455, P = 0.022). Moreover, the consistencies between AH and vitreous samples in their T-IgG and GWC positivity rates were almost perfect (both, κ = 0.915, 95% CI, 0.799-1.000) in both. The AUROC reached 0.991, with a 95% confidence interval of 0.971-1.000. The best cut-off value for accurate OT diagnosis was found at 1.434, yielding 96% sensitivity and 100% specificity. CONCLUSIONS: Our findings demonstrate that AH and vitreous samples had significant correlations and perfect agreements for both T-IgG and GWC, suggesting that the AH may serve as a proxy for vitreous to provide a safer, earlier, and more convenient screening of OT.

Myofibrillar protein lipoxidation in fish induced by linoleic acid and 4-hydroxy-2-nonenal: Insights from LC-MS/MS analysis.

The oxidation of fish lipids and proteins is interconnected. The LOX (lipoxygenase)-catalyzed LA (linoleic acid) oxidation system on MPs (myofibrillar proteins) was established in vitro, to investigate the impact of lipoxidation on the physicochemical properties of fish MPs. By detecting HNE (4-hydroxy-2-nonenal) concentration during LA oxidation, the HNE treatment system was established to investigate the role of HNE in this process. In addition, the site specificity of modification on MPs was detected utilizing LC-MS/MS. Both treatments could induce sidechain modification, increase particle size, and cause loss of nutritional value through the reduction in amino acid content of MPs. The HNE group is more likely to alter the MPs' surface hydrophobicity compared to the LA group. By increasing the exposure of modification sites in MPs, the HNE group has more types and number of modifications compared to the LA group. LA group mainly induced the modification of single oxygen addition on MPs instead, which accounted for over 50 % of all modifications. The LA group induced a more pronounced reduction in the solubility of MPs as compared to the HNE group. In conclusion, HNE binding had a high susceptibility to Lys on MPs. Protein aggregation, peptide chain fragmentation, and decreased solubility occurred in the LA group mainly induced by peroxide generated during lipid oxidation or the unreacted LA instead of HNE. This study fills in the mechanism of lipoxidation on protein oxidation in fish and sheds light on the HNE modification sites of MPs, paving the way for the development of oxidation control technology.

Improvement of Spatial Memory and Cognitive Function in Mice via the Intervention of Milk Fat Globule Membrane.

With the improvement of living standards, dietary interventions have become an appropriate approach to enhance memory and cognitive performance. The present study investigated the potential mechanisms of spatial memory and cognitive function improvement with the milk fat globule membrane (MFGM) intervention in mice. The Morris water maze experiment revealed that the trajectories of mice in group M were more disordered. Also, the immunohistochemical results demonstrated a significantly higher number of neurons in group M compared with group C, especially in the hippocampal dentate gyrus (DG) area. It is suggested that MFGM enhanced mice's spatial memory and cognition from macroscopic behavior and microscopic cytology, respectively. Meanwhile, 47 differentially expressed proteins (DEPs) were identified, including 20 upregulated and 27 downregulated proteins. Upregulated (Sorbs 2, Rab 39, and Cacna 1e) and downregulated (Hp and Lrg 1) DEPs may improve spatial memory and cognition in mice by promoting synapse formation and increasing neurotransmitter receptors. KEGG enrichment analysis of the DEPs identified seven signaling pathways that were significantly enriched (p < 0.05). One of these pathways was neuroactive ligand-receptor interactions, which are strongly associated with improved spatial memory and cognitive performance. These findings give some new insights and references to the potential mechanisms of spatial memory and cognitive enhancement by MFGM.

Protein oxidation affected the digestibility and modification sites of myofibrillar proteins from bighead carp fillets treated with hydroxyl radicals and endogenous oxidizing system.

This study aimed to investigate the effect of hydroxyl radical oxidizing system (HROS) and endogenous oxidizing system (EOS, i.e., frozen storage at -20 °C) on protein oxidation, digestive properties, and peptide modification of myofibrillar proteins (MPs) in bighead carp (Hypophthalmichthys nobilis) fillets. The oxidation degree increased with the frozen time and H2O2 concentration as evidenced by carbonyl group generation and sulfhydryl group loss in MPs. The digestibility of protein declined gradually during frozen storage, while it increased after treatment with 5 mM H2O2 compared with no H2O2 intervention. More modification numbers and types were observed in the EOS group than HROS in digested MPs peptides, which might be due to the complexity of the frozen fillet system such as the presence of lipid. The potential conversion of α-aminoadipic semialdehyde (AAS) to α-aminoadipic acids (AAA) was observed in HROS. Additionally, the myosin heavy chain was more susceptible to oxidation among all MPs by EOS oxidation.

Downregulation of angiogenic factors in aqueous humor associated with less intraoperative bleeding in PDR patients with NVG receiving conbercept: a randomized controlled trial.

BACKGROUND: To analyze the level changes of 28 cytokines in aqueous humor of patients with proliferative diabetic retinopathy (PDR) coexisting neovascular glaucoma (NVG) after intravitreal injection of conbercept (IVC), and to investigate whether these cytokines are associated with intraoperative bleeding (IOB). METHODS: Totally 34 eyes with NVG secondary to PDR were enrolled. Patients were randomized into two groups, and all of them underwent 25-gauge pars plana vitrectomy (PPV) combined with trabeculectomy. Group I, 18 eyes received IVC 3 days before PPV, and 100 µL aqueous humor was collected at the time of IVC pretreatment and 3 days later at the beginning of PPV respectively. Group II, 16 eyes received IVC after PPV, and 100 µL aqueous humor was collected only at the beginning of PPV. Aqueous humor from 19 eyes with age-matched cataract patients served as controls. Luminex bead-based multiplex array was used to measure the levels of 28 cytokines in aqueous humor. The baseline cytokine levels were compared among the three groups. All NVG patients were divided into IOB and non-bleeding (INB) groups. The cytokine levels of aqueous humor at the beginning of PPV were compared between group I and II, also between IOB and INB groups. IOB in NVG patients was graded according to vitreous bleeding amount. The correlation between cytokine levels and the grades of IOB were analyzed. RESULTS: Compared with controls, the baseline levels of 18 cytokines associated with inflammation and angiogenesis showed significantly increased in group I and group II (all, P < 0.0167). The IOB rate as well as the levels of IL-4, IL-22, Ang-2, PLGF and VEGF-A in group I were significantly lower than in group II (all, P < 0.05). The levels of IL-4, IL-22, Ang-2, PLGF and VEGF-A were significantly lower in INB group than in IOB group (all, P < 0.05). The levels of IL-4, Ang-2, PLGF and VEGF-A were positively correlated with the grades of IOB in NVG patients (all, rs > 0.4, P < 0.05). CONCLUSIONS: IVC 3 days before PPV combined with trabeculectomy reduces IOB in NVG patients, in which the downregulation of IL-4, Ang-2, PLGF and VEGF-A after IVC may be an underlying mechanism. TRIAL REGISTRATION: ChiCTR2100048118 , retrospectively registered on 2 July 2021.

Aqueous Level of ANGPTL4 Correlates with the OCTA Metrics of Diabetic Macular Edema in NPDR.

PURPOSE: To investigate the aqueous levels of angiogenic factors in nonproliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and to ascertain their association with optical coherence tomography angiography (OCTA) metrics. METHODS: This study enrolled 21 NPDR eyes with DME (NPDR/DME+), 17 NPDR eyes without DME (NPDR/DME-), and 16 diabetic eyes without retinopathy (DWR). Luminex bead-based multiplex array was used to measure the levels of 25 cytokines. OCTA system with a scan area of 3 × 3 mm was used to measure retinal thickness (RT), retinal volume (RV), superficial vessel density (SVD), deep vessel density (DVD), foveal avascular zone (FAZ) area, perimeter and acircularity index. RESULTS: The levels of ANGPTL4 were significantly different among the three groups (P < 0.05), in which NPDR/DME+ group had the highest level and NPDR/DME- group had a higher level than the DWR group (all, P < 0.0167). OCTA examination showed that, compared with DWR and NPDR/DME- group, RT and RV increased and the whole/parafoveal DVD decreased in NPDR/DME+ group (all, P < 0.05). Meanwhile, NPDR/DME- group had lower parafoveal DVD than the DWR group (P < 0.05). Correlation analysis showed that the levels of ANGPTL4 were positively correlated with foveal/parafoveal RT and RV and negatively correlated with whole/parafoveal DVD in NPDR patients (all, P < 0.05). As the influencing factor of RT, RV, and DVD, every additional 103 pg/ml of ANGPTL4 was associated with an increase in foveal and parafoveal RT of 4.299 µm and 3.598 µm, respectively. Every additional 106 pg/ml of ANGPTL4 was associated with an increase in foveal and parafoveal RV of 3.371 mm3 and 17.705 mm3, respectively. Every additional 104 pg/ml of ANGPTL4 was associated with a decrease in whole and parafoveal DVD of 1.705% and 1.799%, respectively. CONCLUSIONS: The level of ANGPTL4 in aqueous humor of NPDR patients with DME was significantly increased and ANGPTL4 might predict RT, RV, and parafoveal DVD of DME in NPDR patients.

Transcriptome and metabolite profiling analyses provide insight into volatile compounds of the apple cultivar 'Ruixue' and its parents during fruit development.

BACKGROUND: Aroma is one the most crucial inherent quality attributes of fruit. 'Ruixue' apples were selected from a cross between 'Pink Lady' and 'Fuji', a later ripening yellow new cultivar. However, there is little known about the content and composition of aroma compounds in 'Ruixue' apples or the genetic characters of 'Ruixue' and its parents. In addition, the metabolic pathways for biosynthesis of aroma volatiles and aroma-related genes remain poorly understood. RESULTS: Volatile aroma compounds were putatively identified using gas chromatography-mass spectrometry (GC-MS). Our results show that the profile of volatile compounds changes with ripening. Aldehydes were the dominant volatile compounds in early fruit development, with alcohols and esters increasing dramatically during maturation. On the basis of a heatmap dendrogram, these aroma compounds clustered into seven groups. In ripe fruit, esters and terpenoids were the main aroma volatiles in ripening fruit of 'Pink Lady' and 'Fuji' apples, and they included butyl 2-methylbutanoate; propanoic acid, hexyl ester; propanoic acid, hexyl ester; hexanoic acid, hexyl ester; acetic acid, hexyl ester and (Z, E)-α-farnesene. Interestingly, aldehydes and terpenoids were the dominant volatile aroma compounds in ripening fruit of 'Ruixue', and they mainly included hexanal; 2-hexenal; octanal; (E)-2-octenal; nonanal and (Z, E)-α-farnesene. By comparing the transcriptome profiles of 'Ruixue' and its parents fruits during development, we identified a large number of aroma-related genes related to the fatty acid, isoleucine and sesquiterpenoid metabolism pathways and transcription factors that may volatile regulate biosynthesis. CONCLUSIONS: Our initial study facilitates a better understanding of the volatile compounds that affect fruit flavour as well as the mechanisms underlying differences in flavour between 'Ruixue' and its parents.

Diabetes onset at an earlier age and high HbA1c levels as risk factors of diabetic retinopathy.

AIM: To assess the effect of age at diabetes onset and uncontrollable high HbA1c levels on the development of diabetic retinopathy (DR) among Chinese type 2 diabetes mellitus (DM) patients. METHODS: This was a cross-sectional survey of diabetic patients in Subei district, China. Data covering physical measurements, fasting blood-glucose (FBG), glycosylated hemoglobin (HbA1c), blood lipid, urinary albumin/creatinine ratio (UACR), ocular fundus examination, and diabetes treatment records were collected. An independent sample t-test were used to analyze differences. A Logistic regression analysis was applied to study the independent risk factors of DR. RESULTS: A total of 1282 patients with type 2 DM were enrolled, and 191 cases had DR (14.9%). The age at diabetes onset, education level, alcohol consumption, HbA1c level, UACR level, and hypoglycemic drugs were independent influencing factors for DR. The older the onset of diabetes, the less likely to develop DR (OR: 0.958, 95%CI: 0.942-0.975, P=0.000). Patients were then divided in terms of age at diabetes onset as follows: <50y, 50-59y, 60-69y, and ≥70y. Compared with diabetes onset age <50y, 50-59y (OR: 0.463, 95%CI: 0.306-0.699, P=0.000), 60-69y (OR: 0.329, 95%CI: 0.203-0.535, P=0.000) and ≥70y (OR: 0.232, 95%CI: 0.094-0.577, P=0.002) were at a lower risk of DR. The prevalence of DR was highest in patients with diabetes onset age <50y (29.5%, P<0.05). The HbA1c level (8.67±1.97)% and proportion of insulin injection (52.5%) in patients with diabetes onset <40y were higher than in patients with older diabetes onset age (P<0.05). CONCLUSION: Diabetes onset at an earlier age and uncontrollable high HbA1c level could be independent risk factors for DR.

Case Report: Vitreous Amyloidosis Caused by a TTR Lys55Asn Mutation With Intraoperative Suprachoroidal Hemorrhage.

We report a vitreous amyloidosis patient with white vitreous opacities (footplates) adhering to the posterior lens capsule. A positive Congo-red stain and transthyretin (TTR) Lys55Asn mutation confirmed the diagnosis of vitreous amyloidosis. Optical coherence tomography (OCT) revealed fern-like material adhering to the the posterior pole retinal surface in both eyes. Visual acuity significantly improved after the first vitrectomy, but vitreous opacities recurred 4 years later. The patient appeared to have aggravated sensorimotor neuropathy and severe autonomic dysfunction at the same time. He developed intraoperative suprachoroidal hemorrhage during the second vitrectomy.

IL-6-induced acetylation of E2F1 aggravates oxidative damage of retinal pigment epithelial cell line.

Oxidative damage in retinal pigment epithelial cells (RPE) is considered to be a crucial pathogenesis of age-related macular degeneration (AMD). Although dysregulation of the DNA repair system has been found in RPE cells of AMD patients, the detailed molecular mechanisms of this dysregulation and their relationship with the intraocular microenvironment of AMD patients remain unclear. Here, we established an RPE model of H2O2-induced oxidative stress and found that Sirtuin 1 (Sirt1)-mediated deacetylation of E2F transcription factor 1 (E2F1) was required for oxidation resistance in RPE cells. Moreover, E2F1 induced the expression of the chromatin-binding protein, high mobility group AT-Hook 1 (HMGA1), which promoted the transcription of glucose 6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, to increase NADPH level for antioxidant defense. Interrupting the E2F1/HMGA1/G6PD regulatory axis increased reactive oxygen species (ROS) levels, DNA damage, and apoptosis in RPE cells under oxidative stress. Notably, interleukin 6 (IL-6), an inflammatory cytokine that is known to be upregulated in the intraocular fluid of AMD patients, induced phosphorylation (S47) of Sirt1 by activating PI3K/AKT/mTOR signaling, thereby inhibiting Sirt1 activity and increasing the acetylation of E2F1. Specific inhibitors of PI3K/AKT/mTOR signaling decreased DNA damage and ROS while increasing NADPH in RPE cells. Collectively, our findings demonstrate that IL-6-induced acetylation of E2F1 impairs the antioxidant capacity of RPE cells by disturbing the pentose phosphate pathway, which elucidates a relationship between the intraocular microenvironment and RPE oxidative damage in AMD and provides a possible therapeutic target for AMD.

Abnormally expressed JunB transactivated by IL-6/STAT3 signaling promotes uveal melanoma aggressiveness via epithelial-mesenchymal transition.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and it carries a high risk of metastasis and mortality. Various proinflammatory cytokines have been found to be significantly increased in the aqueous humor or vitreous fluid of UM patients; however, the role of these cytokines in UM metastasis remains elusive. In the present study, we found that long-term interleukin (IL)-6 exposure promoted the migration and invasion of UM cells, diminished cell-cell adhesion, and enhanced focal adhesion. Moreover, IL-6 treatment decreased the membranous epithelial marker TJP1 and increased the cytoplasmic mesenchymal marker Vimentin. Further investigation demonstrated that JunB played a critical role in IL-6-induced UM epithelial-mesenchymal transition (EMT). In UM cells, the expression of JunB was significantly up-regulated during the IL-6-driven EMT process. Additionally, JunB induction occurred at the transcriptional level in a manner dependent on phosphorylated STAT3, during which activated STAT3 directly bound to the JunB promoter. Importantly, the knockdown of STAT3 prevented the IL-6-induced EMT phenotype as well as cell migration and invasion, whereas JunB overexpression recovered the attenuated aggressiveness of UM cells. Similarly, with IL-6 stimulation, the stable overexpression of JunB strengthened the migratory and invasive capabilities of UM cells and induced the EMT-promoting factors (Snail, Twist1, matrix metalloproteinase (MMP)-2, MMP-14, and MMP-19). Analysis of The Cancer Genome Atlas (TCGA) database indicated that JunB was positively correlated with IL-6 and STAT3 in UM tissues. The present study proposes an IL-6/STAT3/JunB axis leading to UM aggressiveness by EMT, which illustrates the negative side of inflammatory response in UM metastasis.

Refractive error among urban preschool children in Xuzhou, China.

The prevalence of refractive errors in urban preschool children in Xuzhou, China remains unknown. Children attending twelve randomly selected kindergartens participated in this study. Visual acuity, ocular alignment, cover-uncover test, cycloplegic refraction, slit-lamp and funduscopy were performed under a standardized testing environment. Cycloplegic streak retinoscopy was performed for all subjects. The mean spherical equivalent (SE) refractive error was the main outcome measure. Emmetropia was defined as refractive status between +1.75 diopters (D) and -0.75D. Myopia, hyperopia, astigmatism and anisometropia were defined as SE < -0.50D, SE > +2.0 D, cylindrical error > 1.0 D and SE difference ≥ 1 D between fellow eyes, respectively. Out of 2349 eligible children, 2255 (96%) children completed a refractive examination. Of the 2255 children, the mean SE of right eyes was +1.14 ± 0.95 diopters (D). Mean SE of the right eyes did not decline with age (r = -0.01; P = 0.56). The majority (86.6%) of children were emmetropia. The prevalence of myopia and hyperopia was 0.9% and 14.3%, respectively. The mean astigmatism for the right eyes was 0.87 ± 0.62 D. The prevalence of With-the-rule, against the rule and oblique astigmatism was 93.8%, 4.7% and 1.5%, respectively. The mean anisometropia between two eyes was 0.14 ± 0.38 D. The most common type of refractive error was hyperopia (14.3%), followed by astigmatism (8.8%), anisometropia (3.2%), and myopia (0.9%). The refractive status in this population of urban Xuzhou preschool children was stable and there was no evidence of a myopic refractive shift over this age range in our cross-sectional study.

[Specific causes of death among 381 AIDS patients who died in hospitals].

OBJECTIVE: In this study, researchers investigated the demographic and clinical characteristics of AIDS patients who died in hospitals, analyzed the specific causes of death, and looked for the correlation between specific cause of death and their clinical characteristics. METHODS: Data of clinical characteristics of patients and their specific causes AIDS of death who died in the seven hospitals from 2009 to 2010 were collected retrospectively. All the specific causes of death were classified according to the Cause of Death (CoDe) project protocol. Univariate analysis and multivariate logistic regression analysis were used to find the association between some categorical variables and the risk for AIDS patients died from AIDS related illnesses. RESULTS: Clinical characteristics and the cause of death of the 381 deceased in seven hospitals in this study were collected. 82.4% were male, with priority as 30-45 years old. 123 (32.3%) death patients had received ART before death. In all death cases, the cause of death of 252 patients (66.1%) were due to AIDS related diseases, with opportunistic infections the most (92.4%). Tubercle bacillus, infection of Penicillium marneffei and Pneumocystis jiroveci were the three leading causes of opportunistic infection deaths. Of 129 patients who died of non-AIDS related disease, non-AIDS infection (29.5%), hepatitis (22.5%), and non-AIDS malignancy(10.1%)were the first three causes of death. The cause of death in patients who had injecting drug use behavior within one year, had not received ART or not long enough, with opportunistic infections, without hepatitis, with the last low CD4 cell counts before death etc. were tend to due to AIDS related disease. CONCLUSION: Opportunistic infections, non-AIDS related infections and hepatitis were the three leading causes of death in this study. The duration of time on ART had impact on the patient's cause of death. The HIV infected patients who had received ART before death had more risk to die of non-AIDS related disease, compared to patients who had not. The longer time they had accessed to ART, the less likely they would die on non-AIDS related illnesses.

[Oblique nuclear chopping and nuclear extraction by binding procedure for cataract extraction].

OBJECTIVE: To investigate the effects of oblique nuclear chopping and nuclear extraction by binding procedure (ONCNEB) in cataract extraction. METHODS: Extracapsular cataract extraction by ONCNEB with foldable IOL implantation was performed in 86 senile cataract cases (97 eyes) by using a line-shaped cataract nuclear chopping apparatus developed by the authors. RESULTS: In 97 eyes treated with ONCNEB, there was posterior capsular rupture in 1 eye; anterior chamber hemorrhage in 2 eyes; elevated intraocular pressure in 6 eyes; mild corneal edema in 8 eyes which subsided within 5 days. Corrected visual acuity > or = 0.5 was obtained in 78 eyes (80.41%) one week and 91 eyes (93.81%) three months after the operation. Corrected visual acuity was > or = 1.0 in 66 eyes (68.04%) three months after the operation. Mean astigmatism one week and three months postoperatively showed not significant difference as compared with preoperative astigmatism. CONCLUSION: The ONCNEB can solve the problem of implanting foldable IOL through a small incision. This procedure is relatively simple and safe.