Fundus Tessellation and Parapapillary Atrophy, as Ocular Characteristics of Spontaneously High Myopia in Macaques: The Non-Human Primates Eye Study.

Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.

40-Hz optogenetic stimulation rescues functional synaptic plasticity after stroke.

Evoked brain oscillations in the gamma range have been shown to assist in stroke recovery. However, the causal relationship between evoked oscillations and neuroprotection is not well understood. We have used optogenetic stimulation to investigate how evoked gamma oscillations modulate cortical dynamics in the acute phase after stroke. Our results reveal that stimulation at 40 Hz drives activity in interneurons at the stimulation frequency and phase-locked activity in principal neurons at a lower frequency, leading to increased cross-frequency coupling. In addition, 40-Hz stimulation after stroke enhances interregional communication. These effects are observed up to 24 h after stimulation. Our stimulation protocol also rescues functional synaptic plasticity 24 h after stroke and leads to an upregulation of plasticity genes and a downregulation of cell death genes. Together these results suggest that restoration of cortical dynamics may confer neuroprotection after stroke.

Identification and validation of key biomarkers and potential therapeutic targets for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is a prevalent cause of blindness worldwide, resulting in degeneration of retinal ganglion cells and permanent damage to the optic nerve. However, the underlying pathogenetic mechanisms of POAG are currently indistinct, and there has been no effective nonsurgical treatment regimen. The objective of this study is to identify novel biomarkers and potential therapeutic targets for POAG. The mRNA expression microarray datasets GSE27276 and GSE138125, as well as the single-cell high-throughput RNA sequencing (scRNA-seq) dataset GSE148371 were utilized to screen POAG-related differentially expressed genes (DEGs). Functional enrichment analyses, protein-protein interaction (PPI) analysis, and weighted gene co-expression network analysis (WGCNA) of the DEGs were performed. Subsequently, the hub genes were validated at a single-cell level, where trabecular cells were annotated, and the mRNA expression levels of target genes in different cell clusters were analyzed. Immunofluorescence and quantitative real-time PCR (qPCR) were performed for further validation. DEGs analysis identified 43 downregulated and 32 upregulated genes in POAG, which were mainly enriched in immune-related pathways, oxidative stress, and endoplasmic reticulum (ER) stress. PPI networks showed that FN1 and DUSP1 were the central hub nodes, while GPX3 and VAV3 were screened out as hub genes through WGCNA and subsequently validated by qPCR. Finally, FN1, GPX3, and VAV3 were determined to be pivotal core genes via single-cell validation. The relevant biomarkers involved in the pathogenesis of POAG, may serve as potential therapeutic targets. Further studies are necessary to unveil the mechanisms underlying the expression variations of these genes in POAG.

Multimodal Analysis on Clinical Characteristics of the Advanced Stage in Myopic Traction Maculopathy.

INTRODUCTION: Here we investigate the clinical features of foveal detachment (FD), full-thickness macular hole (MH), and macular hole retinal detachment (MHRD) in myopic traction maculopathy (MTM). METHODS: In the retrospective observational case series, 314 eyes of 198 patients with myopic retinoschisis in Beijing Tongren Hospital were enrolled. We recorded gender, age, and axial length and evaluated fundus characteristics using optical coherence tomography. Epiretinal membranes (ERMs), vitreoretinal traction, and paravascular abnormalities (PVAs) were used to describe the vitreoretinal interface condition. Different retinoschisis layers (inner, middle, and outer retinoschisis) and the location with a range of outer retinoschisis were evaluated to reveal the retinal condition. Five patterns of the scleral shape: dome-shaped, sloped toward the optic nerve, symmetrical or asymmetrical around the fovea, and irregular were assessed to show retina-sclera condition. We regarded the FD, full-thickness MH, and MHRD as the advanced stage in MTM. Multivariate logistic regression assessed significant factors for the advanced stage with odds ratios (OR) and 95% confidence intervals (CI). RESULTS: There were 76 eyes with FD, 6 eyes with full-thickness MH, and 7 eyes with MHRD. The mean age was 52.9 ± 12.3 years. On univariate analysis, the eyes with the advanced stage were older and had higher rates of ERMs, PVAs, middle retinoschisis, outer retinoschisis, and irregular sclera shape. The number of retinoschisis layers and the grade of outer retinoschisis were higher in eyes with the advanced stage. After multivariate logistic regression, ERMs (OR 1.983; 95% CI 1.093-3.595; P = 0.024), middle retinoschisis (OR 2.967; 95% CI 1.630-5.401; P < 0.001), and higher grades of outer retinoschisis (OR 2.227; 95% CI 1.711-2.898; P < 0.001) remained associated with the advanced stage. CONCLUSION: ERMs, middle retinoschisis, and more extensive outer retinoschisis were significant characteristics of the advanced stage in MTM.

Feasibility Study of Combining Hyperspectral Imaging with Deep Learning for Chestnut-Quality Detection.

The rapid detection of chestnut quality is a critical aspect of chestnut processing. However, traditional imaging methods pose a challenge for chestnut-quality detection due to the absence of visible epidermis symptoms. This study aims to develop a quick and efficient detection method using hyperspectral imaging (HSI, 935-1720 nm) and deep learning modeling for qualitative and quantitative identification of chestnut quality. Firstly, we used principal component analysis (PCA) to visualize the qualitative analysis of chestnut quality, followed by the application of three pre-processing methods to the spectra. To compare the accuracy of different models for chestnut-quality detection, traditional machine learning models and deep learning models were constructed. Results showed that deep learning models were more accurate, with FD-LSTM achieving the highest accuracy of 99.72%. Moreover, the study identified important wavelengths for chestnut-quality detection at around 1000, 1400 and 1600 nm, to improve the efficiency of the model. The FD-UVE-CNN model achieved the highest accuracy of 97.33% after incorporating the important wavelength identification process. By using the important wavelengths as input for the deep learning network model, recognition time decreased on average by 39 s. After a comprehensive analysis, FD-UVE-CNN was deter-mined to be the most effective model for chestnut-quality detection. This study suggests that deep learning combined with HSI has potential for chestnut-quality detection, and the results are encouraging.

[Distribution Characteristics and Risk Assessment of Microplastics in Water of Different Functional Parks in Guilin].

The water environment capacity of urban parks is small, and their self-purification ability is poor. They are also more likely to be affected by microplastics (MPs), which cause an imbalance of the water micro-ecosystem. Based on the functional characteristics of parks (comprehensive park, community park, and ecological park), this study investigated the distribution characteristics of MPs in the water of Guilin parks through spot sampling, microscopic observation, and Fourier transform infrared spectroscopy. In addition, the pollution risk index and the pollution load index were used to evaluate the pollution risk of MPs.The results showed that the abundances of MPs in the park surface water and sediments ranged from 104.67-674.44 n·m-3 and 95.57-877.78 n·kg-1, respectively. There were four main shape types of MPs:fragments, fibers, films, and particles. MPs were dominated by fragments and fibers with small sizes (<1 mm). The polymers of MPs were polyethylene and polyethylene terephthalate. There were significant differences in the abundance of MPs in the water of different functional parks, and the abundance of MPs in comprehensive parks was the highest. The abundance of MPs in park water was closely related to the function of the park and the number of people entering the park. The pollution risk of MPs in the surface water of Guilin parks was low, whereas the pollution risk of MPs in sediments was relatively high. The results of this study indicated that tourism was an important source of MPs pollution in the water of Guilin City parks. The pollution risk of MPs in the water of Guilin City parks was mild. However, the pollution risk of MPs accumulated in small freshwater waters of urban parks requires continued attention.

NF-κB Activator 1 downregulation in macrophages activates STAT3 to promote adenoma-adenocarcinoma transition and immunosuppression in colorectal cancer.

BACKGROUND: Adenoma-adenocarcinoma transition is a key feature of colorectal cancer (CRC) occurrence and is closely regulated by tumor-associated macrophages (TAMs) and CD8+ T cells. Here, we investigated the effect of the NF-κB activator 1 (Act1) downregulation of macrophages in the adenoma-adenocarcinoma transition. METHODS: This study used spontaneous adenoma-developing ApcMin/+, macrophage-specific Act1-knockdown (anti-Act1), and ApcMin/+; anti-Act1 (AA) mice. Histological analysis was performed on CRC tissues of patients and mice. CRC patients' data retrieved from the TCGA dataset were analyzed. Primary cell isolation, co-culture system, RNA-seq, and fluorescence-activated cell sorting (FACS) were used. RESULTS: By TCGA and TISIDB analysis, the downregulation of Act1 expression in tumor tissues of CRC patients negatively correlated with accumulated CD68+ macrophages in the tumor. Relative expression of EMT markers in the tumor enriched ACT1lowCD68+ macrophages of CRC patients. AA mice showed adenoma-adenocarcinoma transition, TAMs recruitment, and CD8+ T cell infiltration in the tumor. Macrophages depletion in AA mice reversed adenocarcinoma, reduced tumor amounts, and suppressed CD8+ T cell infiltration. Besides, macrophage depletion or anti-CD8a effectively inhibited metastatic nodules in the lung metastasis mouse model of anti-Act1 mice. CRC cells induced activation of IL-6/STAT3 and IFN-γ/NF-κB signaling and the expressions of CXCL9/10, IL-6, and PD-L1 in anti-Act1 macrophages. Anti-Act1 macrophages facilitated epithelial-mesenchymal-transition and CRC cells' migration via CXCL9/10-CXCR3-axis. Furthermore, anti-Act1 macrophages promoted exhaustive PD1+ Tim3+ CD8+ T cell formation. Anti-PD-L1 treatment repressed adenoma-adenocarcinoma transition in AA mice. Silencing STAT3 in anti-Act1 macrophages reduced CXCL9/10 and PD-L1 expression and correspondingly inhibited epithelial-mesenchymal-transition and CRC cells' migration. CONCLUSIONS: Act1 downregulation in macrophages activates STAT3 that promotes adenoma-adenocarcinoma transition via CXCL9/10-CXCR3-axis in CRC cells and PD-1/PD-L1-axis in CD8+ T cells.

The PPN and motor control: Preclinical studies to deep brain stimulation for Parkinson's disease.

The pedunculopontine nucleus (PPN) is the major part of the mesencephalic locomotor region, involved in the control of gait and locomotion. The PPN contains glutamatergic, cholinergic, and GABAergic neurons that all make local connections, but also have long-range ascending and descending connections. While initially thought of as a region only involved in gait and locomotion, recent evidence is showing that this structure also participates in decision-making to initiate movement. Clinically, the PPN has been used as a target for deep brain stimulation to manage freezing of gait in late Parkinson's disease. In this review, we will discuss current thinking on the role of the PPN in locomotor control. We will focus on the cytoarchitecture and functional connectivity of the PPN in relationship to motor control.

Design, methodology, and preliminary results of the non-human primates eye study.

PURPOSE: To describe the normative profile of ophthalmic parameters in a healthy cynomolgus monkey colony, and to identify the characteristic of the spontaneous ocular disease non-human primates (NHP) models. METHODS: The NHP eye study was a cross-sectional on-site ocular examination with about 1,000 macaques held in Guangdong Province, southeastern China. The NHPs (Macaca fascicularis, cynomolgus) in this study included middle-aged individuals with a high prevalence of the ocular disease. The NHP eye study (NHPES) performed the information including systematic data and ocular data. Ocular examination included measurement of intraocular pressure (IOP), anterior segment- optical coherence tomography (OCT), slit-lamp examination, fundus photography, autorefraction, electroretinography, etc. Ocular diseases included measurement of refractive error, anisometropia, cataract, pterygium, etc. RESULTS: A total of 1148 subjects were included and completed the ocular examination. The average age was 16.4 ± 4.93 years. Compared to the male participants, the females in the NHPES had shorter axial length and the mean Average retinal nerve fiber layer (RNFL) thickness (except for the nasal quadrants). The mean IOP, anterior chamber depth, lens thickness, axial length, central corneal thickness, choroid thickness and other parameters were similar in each group. CONCLUSION: The NHPES is a unique and high-quality study, this is the first large macaque monkey cohort study focusing on ocular assessment along with comprehensive evaluation. Results from the NHPES will provide important information about the normal range of ophthalmic measurements in NHP.

Retinal nerve fibre layer thickness measured with SD-OCT in a population-based study: the Handan Eye Study.

PURPOSE: To examine the normative profile of retinal nerve fibre layer (RNFL) thickness and ocular parameters based on spectral-domain optical coherence tomography (SD-OCT) and its associations with related parameters among the Chinese population. METHODS: This population-based cohort Handan Eye Study (HES) recruited participants aged≥30 years. All subjects underwent a standardised ophthalmic examination. Peripapillary RNFL thickness was obtained using SD-OCT. Mixed linear models were adopted to evaluate the correlation of RNFL thickness with ocular parameters as well as systemic factors. R V.3.6.1 software was used for statistical analysis. RESULTS: 3509 subjects (7024 eyes) with the average age of 55.54±10.37 were collected in this analysis. Overall mean RNFL thickness measured was 113.46±10.90 µm, and the thickest quadrant of parapapillary RNFL was the inferior quadrant, followed by the superior quadrant, the nasal quadrant and the temporal quadrant. In the multivariate linear regression model, thinner RNFL thickness was remarkable association with male (p<0.001), older age (p<0.001), increased body mass index (>30, p=0.018), absence of diabetes (p=0.009), history of cataract surgery (p=0.001), higher intraocular pressure (p=0.007), lower spherical equivalent (p<0.001) and increased axial length (p=0.048). CONCLUSIONS: In non-glaucoma individuals, this difference of RNFL thickness in Chinese population should be noted in making disease diagnoses. Meanwhile, multiple ocular and systemic factors are closely related to the thickness of RNFL. Our findings further emphasise the need to demonstrate ethnic differences in RNFL thickness and the specificity of associated ocular and systemic factors, as well as to develop better normative databases worldwide. TRIAL REGISTRATION NUMBER: HES was registered in Chinese Clinical Trial Registry website, and the registry number was ChiCTR-EOC-17013214.

Mapping the T cell epitopes of the M-type transmembrane phospholipase A2 receptor in primary membranous nephropathy.

The M-type phospholipase A2 receptor (PLA2R) is the major autoantigen of primary membranous nephropathy (MN). Despite many studies on B-cell epitopes recognized by antibodies, little is known about T-cell epitopes. Herein, we synthesized 123 linear peptides, each consisting of 15-22 amino acids with 8-12 amino acid overlaps, across ten domains of PLA2R. Their binding capacity to risk (DRB1∗1501, DRB1∗0301) and protective (DRB1∗0901, DRB1∗0701) HLA molecules was then assessed by flow cytometry. Proliferation of CD4+ T cells from patients with anti-PLA2R positive MN was analyzed after peptide stimulation. Cytokines produced by activated peripheral blood mononuclear cells were measured by cytometric bead arrays. We identified 17 PLA2R peptides that bound to both DRB1∗1501 and DRB1∗0301 molecules with high capacity. Some of these peptides showed decreased binding to heterozygous DRB1∗1501/0901 and DRB1∗0301/0701. Ten of the 17 peptides (CysR1, CysR10, CysR12, FnII-3, CTLD3-9, CTLD3-10, CTLD3-11, CTLD5-2-1, CTLD7-1 and CTLD7-2) induced significant proliferation of CD4+ T cells from patients with MN than cells from healthy individuals. Upon activation by these peptides, peripheral blood mononuclear cells from patients with MN produced higher levels of pro-inflammatory cytokines, predominantly IL-6, TNF-α, IL-10, IL-9 and IL-17. Thus, we mapped and identified ten peptides in the CysR, FnII, CTLD3, CTLD5, and CTLD7 domains of PLA2R as potential T-cell epitopes of MN. These findings are a first step towards developing peptide-specific immunotherapies.

Effect of refractive status on retinal nerve fiber layer thickness in Chinese Population.

PURPOSE: To evaluate the relationship between retinal nerve fiber layer (RNFL) thickness and other related parameters measured by spectral-domain optical coherence tomography and the refractive error of eyes. METHODS: A total of 5394 subjects were enrolled in this population-based cohort study, who were divided into three groups by refractive state after they underwent a standardized ophthalmic examination: emmetropia (the absolute value should range from 0 to 0.5 D), low-moderate myopia (the absolute value of myopic error should range from 0.5 to 6 D), and high myopia (the absolute value of myopic error should be over than 6 D). R 3.6.1 software was adopted for statistical analysis. RESULTS: Two thousand five hundred fifty-two subjects (4548 eyes) were collected in this study, with an average age of 53.14 ± 10.64 years. There were significant differences among groups in average central corneal curvature, spherical equivalent, and axial length (P < 0.001). The measurements of average retinal nerve fiber layer (RNFL) were 113.95 ± 10.62 µm, 112.97 ± 11.59 µm, and 101.88 ± 15.67 µm, respectively, in the emmetropia, low-moderate, and high myopia groups (P < 0.001). Meanwhile, there was a decreasing trend of cup area, cup volume, disc area, and rim area in the high myopia group compared with the emmetropia group (P < 0.001). CONCLUSION: The measurements of RNFL thickness vary greatly with refractive error, and this study indicated that it is of great significance for the accurate diagnosis of glaucoma to establish an individualized RNFL thickness database.

Macular thickness and its associated factors in a Chinese rural adult population: the Handan Eye Study.

PURPOSE: To describe the normal macular thickness and assess its associations. METHODS: The Handan Eye Follow-up Study was conducted between 2012 and 2013. Macular thickness was scanned by spectral-domain optical coherence tomography (OCT). The built-in software generated a retinal thickness (RT) map, which was divided into three regions (central, internal and external regions) and nine quadrants (one in central and four in internal and external regions each). RESULTS: For 5394 subjects in the Handan Eye Follow-up Study, 4793 received OCT examination, 2946 of whom (accounting for 61.46% of the total subjects, mean age 58.91±10.95, 55.6% were women) were included for analysis. The mean RT in central macula, inner and outer rings were (237.38 µm±23.05 µm), (309.77 µm±18.36 µm) and (278.29 µm±14.38 µm), respectively (overall difference, p＜0.001). In inner ring, the RT in temporal was thinnest, followed by nasal, superior and inferior. In outer ring, the RT in superior was thinnest, with the next subfields being temporal, inferior and nasal, respectively. The RT in central macula, inner and outer rings were significantly thicker in men than in women. Multivariate linear regression analysis showed that in central macula, RT increased in subjects younger than 60 years and thinned above the age of 60. In inner and outer rings, RT thinned along with age (p＜0.001). CONCLUSIONS: This study finds that RT in central macula is the thinnest, followed by the outer ring, the RT in the inner ring is the thickest. Age and gender are related to RT. These associated factors need to be considered when explaining RT.

Outdoor time influences VIPR2 polymorphism rs2071623 to regulate axial length in Han Chinese children.

Clinical relevance: Identification of individuals with a higher risk of developing refractive error under specific gene and environmental backgrounds, especially myopia, could enable more personalized myopic control advice for patients. Background: Refractive error is a common disease that affects visual quality and ocular health worldwide. Its mechanisms have not been elaborated, although both genes and the environment are known to contribute to the process. Interactions between genes and the environment have been shown to exert effects on the onset of refractive error, especially myopia. Axial length elongation is the main characteristic of myopia development and could indicate the severity of myopia. Thus, the purpose of the study was to investigate the interaction between environmental factors and genetic markers of VIPR2 and their impact on spherical equivalence and axial length in a population of Han Chinese children. Methods: A total of 1825 children aged 13~15 years in the Anyang Childhood Eye Study (ACES) were measured for cycloplegic autorefraction, axial length, and height. Saliva DNA was extracted for genotyping three single-nucleotide polymorphisms (SNPs) in the candidate gene (VIPR2). The median outdoor time (2 h/day) was used to categorize children into high and low exposure groups, respectively. Genetic quality control and linear and logistic regressions were performed. Generalized multifactor dimensional reduction (GMDR) was used to investigate gene-environment interactions. Results: There were 1391 children who passed genetic quality control. Rs2071623 of VIPR2 was associated with axial length (T allele, ß=-0.11 se=0.04 p=0.006), while SNP nominally interacted with outdoor time (T allele, ß=-0.17 se=0.08 p=0.029). Rs2071623 in children with high outdoor exposure had a significant interaction effect on axial length (p=0.0007, ß=-0.19 se=0.056) compared to children with low outdoor exposure. GMDR further suggested the existence of an interaction effect between outdoor time and rs2071623. Conclusions: Rs2071623 within VIPR2 could interact with outdoor time in Han Chinese children. More outdoor exposure could enhance the protective effect of the T allele on axial elongation.

Identification of the Optimal Model for the Prediction of Diabetic Retinopathy in Chinese Rural Population: Handan Eye Study.

Background: To identify an optimal model for diabetic retinopathy (DR) prediction in Chinese rural population by establishing and comparing different algorithms based on the data from Handan Eye Study (HES). Methods: Five algorithms, including multivariable logistic regression (MLR), classification and regression trees (C&RT), support vector machine (SVM), random forests (RF), and gradient boosting machine (GBM), were used to establish DR prediction models with HES data. The performance of the models was assessed based on the adjusted area under the ROC curve (AUROC), sensitivity, specificity, and accuracy. Results: The data on 4752 subjects were used to build the DR prediction model, and among them, 198 patients were diagnosed with DR. The age of the included subjects ranged from 30 to 85 years old, with an average age of 50.9 years (SD = 3.04). The kappa coefficient of the diagnosis between the two ophthalmologists was 0.857. The MLR model revealed that blood glucose, systolic blood pressure, and body mass index were independently associated with the development of DR. The AUROC obtained by GBM (0.952), RF (0.949), and MLR (0.936) was similar and statistically larger than that of CART (0.682) and SVM (0.765). Conclusions: The MLR model exhibited excellent prediction performance and visible equation and thus was the optimal model for DR prediction. Therefore, the MLR model may have the potential to serve as a complementary screening tool for the early detection of DR, especially in remote and underserved areas.

Salt-Sensitive Ileal Microbiota Plays a Role in Atrial Natriuretic Peptide Deficiency-Induced Cardiac Injury.

Atrial natriuretic peptide (ANP) activity deficiency contributes to salt-sensitive hypertension in humans and mice. However, the role of ileal microbiota in salt sensitivity in ANP deficiency-related cardiac injury has not been investigated yet. This study used ANP-/- mice to analyze the role of the salt-sensitive ileal microbiome on cardiac injury. ANP-/- mice showed an increase in blood pressure (BP), the heart weight/body weight (HW/BW) ratio, and cardiac hypertrophy compared with wild-type (WT) mice. ANP deficiency did not impact the histological structure but reduced occludin expression in the ileum. Antibiotics significantly relieved BP and cardiac hypertrophy in ANP-/- mice. A high-salt diet (HSD) increased BP, the HW/BW ratio, and cardiac hypertrophy/fibrosis in WT and ANP-/- mice, and an HSD treatment in ANP-/- mice exacerbated these cardiac parameters. The HSD markedly decreased muscularis layer thickening, villus length, and numbers of Paneth and goblet cells in the ileum of WT and ANP-/- mice. Furthermore, the HSD increased the level of TLR4 and IL-1ß in ANP-/- mice ileum compared with WT mice. Antibiotics reduced the HW/BW ratio, cardiac hypertrophy/fibrosis, and the level of TLR4 and IL-1ß in the ileum, and rescued the muscularis layer thickening, villus length, and numbers of Paneth and goblet cells in the ileum of HSD-ANP-/- mice. Importantly, ANP deficiency induced the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum on the NSD diet, which was only observed in HSD-induced WT mice but not in WT mice on the NSD. Besides, the HSD significantly enhanced the sum of the percentage of the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum of ANP-/- mice. Ileal microbiota transfer (IMT) from ANP-/- mice to healthy C57BL/6J mice drove Lactobacillus johnsonii and Lactobacillus reuteri colonization in the ileum, which manifested an increase in BP, the HW/BW ratio, cardiac hypertrophy, and ileal pathology compared with IMT from WT mice. The HSD in C57BL/6J mice with IMT from ANP-/- mice drove the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum and further exacerbated the cardiac and ileal pathology. Our results suggest that salt-sensitive ileal microbiota is probably related to ANP deficiency-induced cardiac injury.

Catalpol protects AC16 cells from hypoxia/reoxygenation injury by regulating the miR-22-3p/DPP4 axis.

Catalpol (CA) is widely used in the protection of cardiomyocytes. Nevertheless, the mechanism of CA in alleviating ischemia-reperfusion-induced injury of cardiomyocytes remains unclear. Human cardiomyocyte AC16 cells were subjected to hypoxia/reoxygenation (H/R) injury. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were applied to detect tumor necrosis factor-alpha (TNF-α) mRNA, interleukin-6 (IL-6) mRNA, interleukin-1beta (IL-1ß) mRNA, microRNA-22-3p (miR-22-3p), dipeptidyl peptidase 4 (DPP4) mRNA, and DPP4 protein expressions. The cell viability and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Lactate dehydrogenase (LDH) and creatine kinase (CK-MB) were examined by enzyme-linked immunosorbent assay (ELISA) kits. A dual-luciferase reporter gene assay was performed to confirm the binding sequence between miR-22-3p and DPP4 mRNA 3'-untranslated region (3'UTR). CA promoted the viability and reduced cell apoptosis of AC16 cells and repressed the release of inflammatory cytokines TNF-α, IL-6, and IL-1ß, and inhibited the leakage of myocardial injury markers LDH and CK-MB. Furthermore, CA enhanced the expression of miR-22-3p in cardiomyocytes, and DPP4 was validated to be the target gene of miR-22-3p. The inhibition of miR-22-3p and augmentation of DPP4 reversed the above effects of CA. CA protects A16 cells from H/R injury by regulating the miR-22-3p/DPP4 axis.

New loci for refractive errors and ocular biometric parameters in young Chinese Han adults.

Myopia has become a major public health issue with an increasing prevalence. There are still individuals who experience similar environmental risk factors and, yet, remain non-myopic. Thus, there might be genetic factors protecting people from myopia. Considering the opposite ocular characteristics of primary angle closure glaucoma (PACG) to myopia and possible common pathway between them, we propose that certain risk genes for PACG might act as a protective factor for myopia. In this study, 2,678 young adults were genotyped for 37 targeted single nucleotide polymorphisms. Compared with emmetropia, rs1401999 (allele C: OR=0.795, P=0.03; genotype in dominant model: OR=0.759, P=0.02) and rs1258267 (allele A: OR=0.824, P=0.03; genotype in dominant model: OR=0.603, P=0.01) were associated with low to moderate myopia and high myopia, respectively. Genotype under recessive model of rs11024102 was correlated with myopia (OR=1.456, P=0.01), low to moderate myopia (OR=1.443, P=0.02) and high myopia (OR=1.453, P=0.02). However, these associations did not survive Bonferroni correction. Moreover, rs1401999, rs1258267, and rs11024102 showed associations with certain ocular biometric parameters in different groups. Our study suggests that ABCC5, CHAT and PLEKHA7 might be associated with refractive errors by contributing to the regulation of ocular biometry, in terms of uncorrected results and their biological functions.

Clinical Spectrum of Uveitis Induced by Herpes Simplex Virus with Posterior Pole Involvement at Initial Presentation: A Case Series and Literature Review.

PURPOSE: To report four cases of herpes simplex virus-induced uveitis with posterior pole involvement at initial presentation. CASE PRESENTATIONS: In case 1, the posterior pole initially showed dense vitreous hemorrhage from the optic disc, multiple subretinal lesions around the optic disc, and retinal arterial sheath prior to retinal necrosis. In case 2, the posterior pole presented with optic disc edema, retinal venous tortuosity, and arterial sheathing around the optic disc prior to the peripheral retinal necrosis. In case 3 diagnosed with posterior herpetic uveitis, the posterior pole showed retinal arterial sheath and macular structural abnormities. In case 4, the posterior pole demonstrated optic disc swelling, along with perivascular retinal hemorrhage 4 days prior to peripheral retinal necrosis. CONCLUSIONS: Posterior pole involvement might occur either solely or before the development of peripheral retinal necrosis in patients with herpes simplex virus-induced acute retinal necrosis with and without prior central nervous system herpetic virus infection.