Limb development genes underlie variation in human fingerprint patterns.

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.

Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis.

The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF-1α), ATP2A2, P53, α-SMA, Caspase-3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in vivo and in vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca2+ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca2+ channels in cells resulted in downregulation of HIF-1α, ATP2A2, P53, α-SMA, Caspase-3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca2+ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.

Genetic dissection of Meloidogyne incognita resistance genes based on VIGS functional analysis in Cucumis metuliferus.

The southern root-knot nematode, Meloidogyne incognita, is a highly serious plant parasitic nematode species that causes significant economic losses in various crops, including cucumber (Cucumis sativus L.). Currently, there are no commercial cultivars available with resistance to M. incognita in cucumber. However, the African horned melon (Cucumis metuliferus Naud.), a semi-wild relative of cucumber, has shown high resistance to M. incognita. In this study, we constructed an ultrahigh-density genetic linkage bin-map using low-coverage sequences from an F2 population generated through the cross between C. metuliferus inbred lines CM3 and CM27. Finally, we identified a QTL (quantitative trait locus, QTL3.1) with a LOD (logarithm of the odds) score of 3.84, explaining 8.4% of the resistance variation. Subsequently, by combining the results of qPCR (quantitative PCR) and VIGS (virus-induced gene silencing), we identified two genes, EVM0025394 and EVM0006042, that are potentially involved in the resistance to M. incognita in CM3. The identification of QTLs and candidate genes in this study serve as a basis for further functional analysis and lay the groundwork for harnessing this resistance trait.

Deep Learning Model for Grading and Localization of Lumbar Disc Herniation on Magnetic Resonance Imaging.

BACKGROUND: Methods for grading and localization of lumbar disc herniation (LDH) on MRI are complex, time-consuming, and subjective. Utilizing deep learning (DL) models as assistance would mitigate such complexities. PURPOSE: To develop an interpretable DL model capable of grading and localizing LDH. STUDY TYPE: Retrospective. SUBJECTS: 1496 patients (M/F: 783/713) were evaluated, and randomly divided into training (70%), validation (10%), and test (20%) sets. FIELD STRENGTH/SEQUENCE: 1.5T MRI for axial T2-weighted sequences (spin echo). ASSESSMENT: The training set was annotated by three spinal surgeons using the Michigan State University classification to train the DL model. The test set was annotated by a spinal surgery expert (as ground truth labels), and two spinal surgeons (comparison with the trained model). An external test set was employed to evaluate the generalizability of the DL model. STATISTICAL TESTS: Calculated intersection over union (IoU) for detection consistency, utilized Gwet's AC1 to assess interobserver agreement, and evaluated model performance based on sensitivity and specificity, with statistical significance set at P < 0.05. RESULTS: The DL model achieved high detection consistency in both the internal test dataset (grading: mean IoU 0.84, recall 99.6%; localization: IoU 0.82, recall 99.5%) and external test dataset (grading: 0.72, 98.0%; localization: 0.71, 97.6%). For internal testing, the DL model (grading: 0.81; localization: 0.76), Rater 1 (0.88; 0.82), and Rater 2 (0.86; 0.83) demonstrated results highly consistent with the ground truth labels. The overall sensitivity of the DL model was 87.0% for grading and 84.0% for localization, while the specificity was 95.5% and 94.4%. For external testing, the DL model showed an appreciable decrease in consistency (grading: 0.69; localization: 0.66), sensitivity (77.2%; 76.7%), and specificity (92.3%; 91.8%). DATA CONCLUSION: The classification capabilities of the DL model closely resemble those of spinal surgeons. For future improvement, enriching the diversity of cases could enhance the model's generalization. TECHNICAL EFFICACY: Stage 2.

Real-Time Compensation for SLD Light-Power Fluctuation in an Interferometric Fiber-Optic Gyroscope.

An interferometric fiber-optic gyroscope (IFOG) demodulates a rotation signal via interferometric light intensity. However, the working environments of IFOGs typically involve great uncertainty. Fluctuations in temperature, air pressure, electromagnetic field, and the power system all cause the power of the superluminescent diode (SLD) light source to fluctuate as well. In this invited paper, we studied the effects of SLD power fluctuation on the dynamic and static performance characteristics of a gyro system through the use of a light-power feedback loop. Fluctuations of 0.5 mA, 1 mA, and 5 mA in the SLD source entering the IFOG caused zero-bias stability to be 69, 135, and 679 times worse. We established an effective method to monitor power fluctuations of SLD light sources and to compensate for their effects without increasing hardware complexity or system cost. In brief, we established a real-time power-sensing and -compensating system. Experimental results showed that for every 0.1 mA increase in the fluctuation amplitude of the driving current, the zero-bias stability became 4 to 7 times worse, which could be reduced about 95% through the use of SLD power compensation.

A Novel Closed-Loop Control to Solve Light Source Power Fluctuations in the Fiber-Optic Gyroscope.

The performance of a gyroscope is directly affected by the fluctuations in the light source power (LSP) in an interferometric fiber-optic gyroscope (IFOG). Therefore, it is important to compensate for fluctuations in the LSP. When the feedback phase generated by the step wave completely cancels the Sagnac phase in real-time, the error signal of the gyroscope is linearly related to the differential signal of the LSP, otherwise, the error signal of the gyroscope is uncertain. Herein, we present two compensation methods to compensate for the error of the gyroscope when the error is uncertain, which are double period modulation (DPM) and triple period modulation (TPM). Compared with the TPM, DPM has better performance, but it increases the requirements for the circuit. TPM has lower requirements for the circuit and is more suitable for small fiber- coil applications. The experimental results show that, when the frequency of the LSP fluctuation is relatively low (1 kHz and 2 kHz), DPM and TPM do not differ significantly in terms of performance; both of them can achieve an improvement of about 95% in bias stability. When the frequency of the LSP fluctuation is relatively high (4 kHz, 8 kHz and 16 kHz), DPM and TPM can achieve about 95% and 88% improvement in bias stability, respectively.

Identification of differentially methylated cell types in epigenome-wide association studies.

An outstanding challenge of epigenome-wide association studies (EWASs) performed in complex tissues is the identification of the specific cell type(s) responsible for the observed differential DNA methylation. Here we present a statistical algorithm called CellDMC ( https://github.com/sjczheng/EpiDISH ), which can identify differentially methylated positions and the specific cell type(s) driving the differential methylation. We validated CellDMC on in silico mixtures of DNA methylation data generated with different technologies, as well as on real mixtures from epigenome-wide association and cancer epigenome studies. CellDMC achieved over 90% sensitivity and specificity in scenarios where current state-of-the-art methods did not identify differential methylation. By applying CellDMC to an EWAS performed in buccal swabs, we identified smoking-associated differentially methylated positions occurring in the epithelial compartment, which we validated in smoking-related lung cancer. CellDMC may be useful in the identification of causal DNA-methylation alterations in disease.

Ocular microbial diversity, community structure, and function at high altitude.

PURPOSE: To investigate the composition and function of ocular surface microbiome in healthy people from different altitudes. METHODS: Thirty-two healthy people living in a high altitude region and 30 sex- and age-matched individuals living in a low altitude region were enrolled. Samples were collected from the lower conjunctival sac of one randomly chosen eye for each participant. 16S rRNA sequencing was conducted to study the bacterial community composition and predict gene function using PICRUSt software. RESULTS: Microbial diversity and richness was significantly decreased in samples from highlanders as calculated by Abundance-based Coverage Estimator (ACE) index, Chao1 index, and observed-species index (all p < 0.01). Principle coordinate analysis (PCoA) suggested significantly distinct clustering of the conjunctival sac bacterial communities between two groups (p = 0.03), especially the dominant genera. The relative abundances of Corynebacterium, Staphylococcus, and Anaerococcus were significantly enriched in highlanders, while those of Pseudomonas and Massilia were significantly decreased as compared with lowlanders (p < 0.01). In the functional annotation analysis, we found that 74 gene pathways, mainly in metabolism, differed in abundance. Pathways related to immune system diseases and infectious diseases were also enriched in highlanders. CONCLUSION: The composition and function of ocular surface microbiome in highlanders were distinct from those of lowlanders and our study may provide a reference catalog of the healthy conjunctival microbiome in highlanders.

DZNep protects against retinal ganglion cell death in an NMDA-induced mouse model of retinal degeneration.

Epigenetic gene enhancer of zeste homolog-2 (Ezh2) is reported to be associated with ocular neurodegenerative diseases; however, its underlying mechanism is poorly understood. The present study aimed to determine the role of 3-deazaneplanocin A (DZNep), which inhibits the transcription of Ezh2 by reducing the trimethylation of histone 3 lysine 27 (H3K27me3), in a retinal ganglion cell (RGC) degeneration model. Retinal damage was caused by intravitreal injection of N-methyl-D-aspartate (NMDA). DZNep and the vehicle control were intravitreally applied immediately post-NMDA injection. The severity of retinal damage was evaluated by immunofluorescence and terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining, and retinal function was determined by electroretinogram (ERG). The transcriptome was examined by RNA sequencing and quantitative PCR (qPCR). Microglial cells were detected by immunohistochemistry. DZNep significantly prevented the cell death in the ganglion cell layer (GCL) and inner nuclear layer (INL) induced by NMDA. DZNep preserved the ERG b- and a-wave amplitudes and the b/a ratio in NMDA-treated mice. Moreover, RNA sequencing and qPCR revealed that neuroprotective genes were upregulated and played an important role in preserving retinal cells. In addition, DZNep inhibited the NMDA-induced activation of microglial cells. Our results suggest that H3K27me3 controls RGC survival at the transcriptional and epigenetic levels. The absence of H3K27me3 deposition upregulates neuroprotective genes to protect RGCs. Therefore, DZNep, which inhibits Ezh2 activity, could be a novel therapeutic treatment for ocular neurodegenerative diseases.

ebGSEA: an improved Gene Set Enrichment Analysis method for Epigenome-Wide-Association Studies.

MOTIVATION: The biological interpretation of differentially methylated sites derived from Epigenome-Wide-Association Studies (EWAS) remains a significant challenge. Gene Set Enrichment Analysis (GSEA) is a general tool to aid biological interpretation, yet its correct and unbiased implementation in the EWAS context is difficult due to the differential probe representation of Illumina Infinium DNA methylation beadchips. RESULTS: We present a novel GSEA method, called ebGSEA, which ranks genes, not CpGs, according to the overall level of differential methylation, as assessed using all the probes mapping to the given gene. Applied on simulated and real EWAS data, we show how ebGSEA may exhibit higher sensitivity and specificity than the current state-of-the-art, whilst also avoiding differential probe representation bias. Thus, ebGSEA will be a useful additional tool to aid the interpretation of EWAS data. AVAILABILITY AND IMPLEMENTATION: ebGSEA is available from https://github.com/aet21/ebGSEA, and has been incorporated into the ChAMP Bioconductor package (https://www.bioconductor.org). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

EpiDISH web server: Epigenetic Dissection of Intra-Sample-Heterogeneity with online GUI.

SUMMARY: It is well recognized that cell-type heterogeneity hampers the interpretation of Epigenome-Wide Association Studies (EWAS). Many tools have emerged to address this issue, including several R/Bioconductor packages that infer cell-type composition. Here we present a web application for cell-type deconvolution, which offers the functionality of our EpiDISH Bioconductor/R package in a user-friendly GUI environment. Users can upload their data to infer cell-type composition and differentially methylated cytosines in individual cell-types (DMCTs) for a range of different tissues. AVAILABILITY AND IMPLEMENTATION: EpiDISH web server is implemented with Shiny in R, and is freely available at https://www.biosino.org/EpiDISH/.

Combustibility analysis of high-carbon fine slags from an entrained flow gasifier.

The fine slag produced from the entrained flow gasifier in coal chemical industry contains a high amount of unburned carbon content, which can reach more than 40%. The coal gasification fine slag is dissipated just by land filling which occupies a lot of land. Consequently, it causes the pollution of soil, water and wastes the combustible carbon in coal gasification fine slag. It is crucial to develop an environmental friendly and economical scheme for the utilization of coal gasification fine slag. To achieve this aim, it is significant to investigate the combustibility of coal gasification fine slag and then propose a comprehensive utilization technology. In this study, the physical and chemical properties of the raw bituminous coal and the produced coal gasification fine slag, including proximate and ultimate analysis, particle size distribution, ash composition, morphology, and specific area were investigated. The combustion and co-combustion characteristics of coal gasification fine slag were analyzed by a thermo-gravimetric analyzer. A drop tube furnace and a fluidized bed reactor were employed to test the combustibility of coal gasification fine slag in a pulverized furnace and a fluidized bed furnace, respectively. Results show that the carbon content in dried coal gasification fine slag is >40% with a heating value > 16 MJ kg-1. Further, thermo-gravimetric analyzer test showed that the combustion property of coal gasification fine slag is worse than that of anthracite and close to that of high ash coal, and there is a non-negligible synergistic effect for raw bituminous coal and coal gasification fine slag co-firing. The combustibility test in drop tube furnace and fluidized bed reactor showed that coal gasification fine slag can be well burned in a pulverized furnace requiring combustion temperature >900 °C and oxygen concentration >10 vol%. However, the fluidized bed furnace was not appropriate for high efficiency coal gasification fine slag burning, because the unburned carbon content of fly ash after coal gasification fine slag combustion is still >14%, even at 900 °C, 21% oxygen concentration and a low fluidization number. It is suggested that coal gasification fine slag will be better to burned it in a pulverized furnace rather than fluidized furnace.

[Correlation between childhood hypertension and passive smoking before and after birth].

OBJECTIVE: To investigate the association between environmental tobacco smoke( ETS) and blood pressure in children. METHODS: A cross-sectional study was conducted to study the effects of ETS and children's blood pressure among 1623 children aged 5 to 17 years, who were selected randomly from 10 primary and secondary schools in Shenyang from 2012-2013, Liaoning Province. The basic information of children was collected through questionnaires, including demographic characteristics, living environment, history of disease and passive smoking status. We also measured the height, weight and blood pressure of these children. Multiple Logistic regression analyses were used to determine whether ETS was associated with the risk of hypertension after adjustment for potential confounders. RESULTS: Nearly half of the participants( 37%, n = 600) had current ETS exposures, and in for 34% of the children( n = 514), their current ETS exposure was from tobacco use by their father. The adjusted odds ratios( a OR) for hypertension and ETS exposure in utero were 1. 59( 95% CI 1. 02-2. 48) in males and 2. 88( 95% CI 1. 82-4. 56) in females. Current ETS exposure( a OR = 2. 22, 95% CI 1. 47-3. 34) and current ETS exposure from the child's father( a OR = 2. 20, 95% CI 1. 46-3. 31), in addition different intensity of ETS exposure during workdays and during days off were associated with a higher rate of hypertension only in females. CONCLUSION: Prenatal and postnatal ETS exposure was significantly associated with increased odds of hypertension in children, especially in females.

[Effects of Histone Methyltransferase Inhibitors on the Survival, Apoptosis and Cell Cycle of Raji Cells].

OBJECTIVE: To determine the effects of three histone methylase inhibitors UNC1999, DZNep and GSK343 on the survival, apoptosis and cell cycle of non-hodgkin's lymphoma Raji cells. METHODS: PCR amplified 16 and 18 exons of enhancer of zeste homolog 2 ( EZH2) gene were detected. The expression of EZH2 in normal adult lymphocytes and Raji cells was detected by Western blot. The Raji cells were treated by UNC1999, DZNep and GSK343, followed by CCK-8 assays analyzing cell survival, flow cytometry detecting cell apoptosis and cell cycle, and Western blot detecting the expressions of EZH2 and H3K27 me3. RESULTS: The Sanger sequencing results showed that the Raji cells did not carry Y641 and A677 mutation sites of EZH2. The Western blot results showed high expressions of EZH2 in the Raji cells. The results of CCK-8 showed that UNC1999, DZNep and GSK343 inhibited cell survival, and the weakest effect was from DZNep. The flow cytometric assay showed that UNC1999, DZNep and GSK343 promoted apoptosis of the Raji cells, and the effect of UNC1999 was stronger than that of GSK343 and DZNep. The cell cycle was arrested at phase G 1/G 0 after treatment of the Raji cells with the three inhibitors, with UNC1999 triggering the most significant changes. The Western blot showed that UNC1999 and GSK343 inhibited the histone methylase activity of EZH2 and significantly reduced the expression of H3K27 me3. CONCLUSION: EZH2 inhibitors can inhibit cell survival, promote cell apoptosis and arrest cell cycle at phase G 1/G 0 of Raji cells through reducing the expression of H3K27me3. UNC1999 has a stronger effect than GSK343 and DZNep.

A comparison of reference-based algorithms for correcting cell-type heterogeneity in Epigenome-Wide Association Studies.

BACKGROUND: Intra-sample cellular heterogeneity presents numerous challenges to the identification of biomarkers in large Epigenome-Wide Association Studies (EWAS). While a number of reference-based deconvolution algorithms have emerged, their potential remains underexplored and a comparative evaluation of these algorithms beyond tissues such as blood is still lacking. RESULTS: Here we present a novel framework for reference-based inference, which leverages cell-type specific DNAse Hypersensitive Site (DHS) information from the NIH Epigenomics Roadmap to construct an improved reference DNA methylation database. We show that this leads to a marginal but statistically significant improvement of cell-count estimates in whole blood as well as in mixtures involving epithelial cell-types. Using this framework we compare a widely used state-of-the-art reference-based algorithm (called constrained projection) to two non-constrained approaches including CIBERSORT and a method based on robust partial correlations. We conclude that the widely-used constrained projection technique may not always be optimal. Instead, we find that the method based on robust partial correlations is generally more robust across a range of different tissue types and for realistic noise levels. We call the combined algorithm which uses DHS data and robust partial correlations for inference, EpiDISH (Epigenetic Dissection of Intra-Sample Heterogeneity). Finally, we demonstrate the added value of EpiDISH in an EWAS of smoking. CONCLUSIONS: Estimating cell-type fractions and subsequent inference in EWAS may benefit from the use of non-constrained reference-based cell-type deconvolution methods.

Dietary Selenium Deficiency or Excess Reduces Sperm Quality and Testicular mRNA Abundance of Nuclear Glutathione Peroxidase 4 in Rats.

Background: Glutathione peroxidase (GPX) 4 and selenoprotein P (SELENOP) are abundant, and several variants are expressed in the testis.Objective: We determined the effects of dietary selenium deficiency or excess on sperm quality and expressions of GPX4 and SELENOP variants in rat testis and liver.Methods: After weaning, male Sprague-Dawley rats were fed a Se-deficient basal diet (BD) for 5 wk until they were 9 wk old [mean ± SEM body weight (BW) = 256 ± 5 g]. They were then fed the BD diet alone (deficient) or with 0.25 (adequate), 3 (excess), or 5 (excess) mg Se/kg for 4 wk. Testis, liver, blood, and semen were collected to assay for selenoprotein mRNA and protein abundances, selenium concentration, GPX activity, 8-hydroxy-deoxyguanosine concentration, and sperm quality.Results: Dietary selenium supplementations elevated (P < 0.05) tissue selenium concentrations and GPX activities. Compared with those fed BD + 0.25 mg Se/kg, rats fed BD showed lower (P < 0.05) BW gain (86%) and sperm density (57%) but higher (P < 0.05) plasma 8-hydroxy-deoxyguanosine concentrations (189%), and nonprogressive sperm motility (4.4-fold). Likewise, rats fed BD + 5 mg Se/kg had (P = 0.06) lower BW gain and higher (1.9-fold) sperm deformity rates than those in the selenium-adequate group. Compared with the selenium-adequate group, dietary selenium deficiency (BD) or excess (BD + 3 or 5 mg Se/kg) resulted in 45-77% lower (P < 0.05) nuclear Gpx4 (nGpx4) mRNA abundance in the testis. Rats fed BD had lower (P < 0.05) mRNA levels of 2 Selenop variants in both testis and liver than those in the other groups. Testicular SELENOP was 155-170% higher (P < 0.05) in rats fed BD + 5 mg Se/kg and hepatic c/mGPX4 was 13-15% lower (P < 0.05) in rats fed BD than in the other groups.Conclusions: The mRNA abundance of rat testicular nGPX4 responded to dietary selenium concentrations in similar ways to sperm parameters and may be used as a sensitive marker to assess appropriate Se status for male function.

DNA Methylation Signatures in Vaginal Fluid Samples for Detection of Cervical and Endometrial Cancer.

OBJECTIVE: A noninvasive tool that allows individuals to be monitored who are at risk of developing a malignancy is an unmet need. Such a test would need to consist of a molecular signature that allows for gradual judgment to assess the efficacy of preventive strategies. Here we performed a proof-of-principle study to test whether a DNA methylation (DNAme) signature in fluid collected from the vagina is able to identify women with cervical or endometrial cancer. MATERIALS AND METHODS: DNA from vaginal fluid samples from 111 women (30, 8, 73 with endometrial cancer, cervical cancer, and benign gynecological conditions, respectively) were analyzed for DNAme using the Illumina 450k DNA methylation bead array assay, which allows the assessment of DNAme at more than 480.000 CpG sites. We developed a cervical and an endometrial cancer DNAme signature by comparing normal and cancerous cervical and endometrial samples from the publicly available The Cancer Genome Atlas data and developed deviation scores to assess the potential of discriminating cancer from a control sample using a vaginal fluid DNAme signature. RESULTS: More than 60% of variations in DNAme in our vaginal fluid cannot be explained by those clinical or technical factors that we were aware of. Both the cervical and the endometrial cancer DNAme signature resulted in receiver operating characteristic area under the curve between 0.75 and 0.83 to discriminate controls and the cancers for which the signature has been designed for. CONCLUSIONS: Whole DNAme signatures based on array technologies in body fluids are able to discriminate cancer cases from controls.

Topical administration of diminazene aceturate decreases inflammation in endotoxin-induced uveitis.

PURPOSE: Our previous study demonstrated that an intraperitoneal injection of Diminazene Aceturate (DIZE) attenuated uveitis by activating ocular angiotensin-converting enzyme 2 (ACE2). Here, we investigated the anti-inflammatory effects on the ocular anterior segment of a topical administration of a DIZE solution and explored the downstream target molecules involved in the anti-inflammatory mechanism after ACE2 activation. METHODS: Endotoxin-induced uveitis (EIU) in rats was induced by a subcutaneous injection of lipopolysaccharides (LPS, 200 µg) in 0.1 ml of sterile saline. DIZE (0.025, 0.05, or 0.1%) and dexamethasone (0.1%) solutions were applied topically (10 µl eyedrops) to both eyes 6X every two hours before and after LPS injection. The inflammation of the ocular anterior segment was observed and the clinical scores were evaluated 24 h after LPS injection. The total protein concentration and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the aqueous humor were determined. CD11b-positive cells adjacent to the iris ciliary body (ICB) were stained by immunohistochemistry. The mRNA levels of inflammatory cytokines and mediators, including IL-1ß, TNF-α, COX-2, and iNOS or NF-κB subunit p65 in the ICB, were analyzed by real time RT-PCR. The protein expression of NF-κB p65 and the phosphorylated protein of p38 MAPK were detected by western blotting. RESULTS: A topical administration of DIZE decreased clinical scores and the total protein concentration, as well as TNF-α and IL-6 levels in the aqueous humor. Meanwhile, the mRNA levels of inflammatory cytokines and mediators, including IL-1ß, TNF-α, COX-2, and iNOS in the ICB, were downregulated. DIZE reduced the recruitment of CD11b-positive cells adjacent to the ICB. Furthermore, DIZE downregulated the expressions of NF-κB subunit p65 at protein and mRNA levels and inhibited the phosphorylation of p38 MAPK protein in the ICB. CONCLUSIONS: A topical administration of DIZE suppressed ocular inflammation in EIU and decreased the levels of inflammatory cytokines. DIZE attenuated the activation of NF-κB and p38 MAPK in EIU, which may be associated with ACE2-mediated anti-inflammatory effects. Our data provided further evidence that DIZE may represent a novel class of drug for the management of ocular inflammation.

[Clinical characteristics of reticular pseudodrusen].

Reticular pseudodrusen (RPD) has recently been identified as a particular yellowish interlacing network of oval or round lesion in the fundus of aged retinal degeneration patients. RPD can be easily misdiagnosed as typical drusen. However, a large number of observations indicated that RPD and typical drusen are different in distribution, morphological features and pathophysiological processes. The diagnosis of RPD relies on multiple fundus examinations including fundus autofluorescence, infrared reflectance and spectral-domain optical coherence tomography. RPD may be associated with age-related macular degeneration, choroidal neovascularization and geographic atrophy, but the prevalence of RPD is found low in polypoidalchoroidalvasculopathycases. Differential diagnosis of RPD and drusen may affect the treatment and prognosis of these conditions. Thus a careful long-term follow-up is mandatory for these patients.