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.

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.

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.

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.

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.

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.

The Association between Myopia and Primary Open-Angle Glaucoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies identified myopia as a risk factor for primary open-angle glaucoma (POAG). However, recent studies have shown different results, and the definitive relationship between myopia and POAG remains controversial. OBJECTIVES: The aim of this study was to investigate the relationship between myopia and POAG. METHODS: Published articles were searched from PubMed, Embase, and Scopus databases between 1970 and 2020. A pooled analysis of the odds ratios (ORs) was performed using a random-effects model. RESULTS: Data on the association between myopia and POAG were obtained from 16 cross-sectional studies, and the pooled OR was 2.26 (95% confidence interval [CI], 1.77-2.89, p < 0.001) in random-effects model (I2 = 86%; p < 0.01). For the relationship of myopia and POAG progression, data from 7 longitudinal cohort studies were included, and the pooled OR was 0.85 (95% CI, 0.73-0.99, p = 0.042) in the random-effects model (I2 = 88%; p < 0.01). CONCLUSION: Our findings demonstrated that myopia may be a risk factor associated with POAG and a possible protective factor for POAG progression. It may be due to myopia with the presence of a lamina cribrosa defect, slowing down the visual field loss and also POAG progression. Further research for underlying mechanisms is still needed.

Endophilin A2 regulates calcium-activated chloride channel activity via selective autophagy-mediated TMEM16A degradation.

TMEM16A Ca2+-activated chloride channel (CaCC) plays an essential role in vascular homeostasis. In this study we investigated the molecular mechanisms underlying downregulation of TMEM16A CaCC activity during hypertension. In cultured basilar artery smooth muscle cells (BASMCs) isolated from 2k2c renohypertesive rats, treatment with angiotensin II (0.125-1 µM) dose-dependently increased endophilin A2 levels and decreased TMEM16A expression. Similar phenomenon was observed in basilar artery isolated from 2k2c rats. We then used whole-cell recording to examine whether endophilin A2 could regulate TMEM16A CaCC activity in BASMCs and found that knockdown of endophilin A2 significantly enhanced CaCC activity, whereas overexpression of endophilin A2 produced the opposite effect. Overexpression of endophilin A2 did not affect the TMEM16A mRNA level, but markedly decreased TMEM16A protein level in BASMCs by inducing ubiquitination and autophagy of TMEM16A. Ubiquitin-binding receptor p62 (SQSTM1) could bind to ubiquitinated TMEM16A and resulted in a process of TMEM16A proteolysis in autophagosome/lysosome. These data provide new insights into the regulation of TMEM16A CaCC activity by endophilin A2 in BASMCs, which partly explains the mechanism of angiotensin-II-induced TMEM16A inhibition during hypertension-induced vascular remodeling.

Silica nanomaterials induce organ injuries by Ca2+-ROS-initiated disruption of the endothelial barrier and triggering intravascular coagulation.

BACKGROUND: The growing use of silica nanoparticles (SiNPs) in many fields raises human toxicity concerns. We studied the toxicity of SiNP-20 (particle diameter 20 nm) and SiNP-100 (100 nm) and the underlying mechanisms with a focus on the endothelium both in vitro and in vivo. METHODS: The study was conducted in cultured human umbilical vein endothelial cells (HUVECs) and adult female Balb/c mice using several techniques. RESULTS: In vitro, both SiNP-20 and SiNP-100 decreased the viability and damaged the plasma membrane of cultured HUVECs. The nanoparticles also inhibited HUVECs migration and tube formation in a concentration-dependent manner. Both SiNPs induced significant calcium mobilization and generation of reactive oxygen species (ROS), increased the phosphorylation of vascular endothelial (VE)-cadherin at the site of tyrosine 731 residue (pY731-VEC), decreased the expression of VE-cadherin expression, disrupted the junctional VE-cadherin continuity and induced F-actin re-assembly in HUVECs. The injuries were reversed by blocking Ca2+ release activated Ca2+ (CRAC) channels with YM58483 or by eliminating ROS with N-acetyl cysteine (NAC). In vivo, both SiNP-20 and SiNP-100 (i.v.) induced multiple organ injuries of Balb/c mice in a dose (range 7-35 mg/kg), particle size, and exposure time (4-72 h)-dependent manner. Heart injuries included coronary endothelial damage, erythrocyte adhesion to coronary intima and coronary coagulation. Abdominal aorta injury exhibited intimal neoplasm formation. Lung injuries were smaller pulmonary vein coagulation, bronchiolar epithelial edema and lumen oozing and narrowing. Liver injuries included multifocal necrosis and smaller hepatic vein congestion and coagulation. Kidney injuries involved glomerular congestion and swelling. Macrophage infiltration occurred in all of the observed organ tissues after SiNPs exposure. SiNPs also decreased VE-cadherin expression and altered VE-cadherin spatial distribution in multiple organ tissues in vivo. The largest SiNP (SiNP-100) and longest exposure time exerted the greatest toxicity both in vitro and in vivo. CONCLUSIONS: SiNPs, administrated in vivo, induced multiple organ injuries, including endothelial damage, intravascular coagulation, and secondary inflammation. The injuries are likely caused by upstream Ca2+-ROS signaling and downstream VE-cadherin phosphorylation and destruction and F-actin remodeling. These changes led to endothelial barrier disruption and triggering of the contact coagulation pathway.

Zn(II)-curcumin solid dispersion impairs hepatocellular carcinoma growth and enhances chemotherapy by modulating gut microbiota-mediated zinc homeostasis.

Zinc(II) complexes of curcumin display moderate cytotoxicity towards cancer cells at low micromolar concentrations. However, the clinical use of zinc(II) complexes is hampered by hydrolytic insolubility and poor bioavailability and their anticancer mechanisms remain unclear. Here, we investigated the efficacy and mechanism of action of a polyvinylpyrrolidone (PVP-k30)-based solid dispersion of Zn(II)-curcumin (ZnCM-SD) against hepatocellular carcinoma (HCC) in vitro and in vivo. In vitro assays revealed ZnCM-SD not only reduced the viability of HepG2 cells and SK-HEP1 cells in a dose-dependent manner, but also potently and synergistically enhanced cell growth inhibition and cell death in response to doxorubicin by regulating cellular zinc homeostasis. ZnCM-SD was internalized into the cells via non-specific endocytosis and degraded to release curcumin and Zn2+ ions within cells. The anticancer effects also occur in vivo in animals following the oral administration of ZnCM-SD, without significantly affecting the weight of the animals. Interestingly, ZnCM-SD did not reduce tumor growth or affect zinc homeostasis in HepG2-bearing mice after gut microbiome depletion. Moreover, administration of ZnCM-SD alone or in combination with doxorubicin significantly attenuated gut dysbiosis and zinc dyshomeostasis in a rat HCC model. Notably, fecal microbiota transplantation revealed the ability of ZnCM-SD to regulate zinc homeostasis and act as a chemosensitizer for doxorubicin were dependent on the gut microbiota. The crucial role of the gut microbiota in the chemosensitizing ability of ZnCM-SD was confirmed by broad-spectrum antibiotic treatment. Collectively, ZnCM-SD could represent a simple, well-tolerated, safe, effective therapy and function as a novel chemosensitizing agent for cancer.

Ca2+/Calmodulin-Dependent Protein Kinase II γ-Dependent Serine727 Phosphorylation Is Required for TMEM16A Ca2+-Activated Cl- Channel Regulation in Cerebrovascular Cells.

BACKGROUND: TMEM16A is a critical component of Ca2+-activated chloride channels (CaCCs) and mediates basilar arterial smooth muscle cell (BASMC) proliferation in hypertensive cerebrovascular remodeling. CaMKII is a negative regulator of CaCC, and four CaMKII isoforms (α, ß, γ and δ) are expressed in vasculature; however, it is unknown which and how CaMKII isoforms affect TMEM16A-associated CaCC and BASMC proliferation.Methods and Results:Patch clamp and small interfering RNA (siRNA) knockdown of different CaMKII isoforms revealed that only CaMKIIγ inhibited native Ca2+-activated chloride currents (ICl.Ca) in BASMCs. The TMEM16A overexpression evoked TMEM16A Cl-current and inhibited angiotensin II (Ang II)-induced proliferation in BASMCs. The co-immunoprecipitation and pull-down assay indicated an interaction between CaMKIIγ and TMEM16A protein. TMEM16A Cl-current was modulated by CaMKIIγ phosphorylation at serine residues in TMEM16A. Serine525 and Serine727 in TMEM16A were mutated to alanine, and only mutation at Ser727 (S727A) reversed the CaMKIIγ inhibition of the TMEM16A Cl-current. Phosphomimetic mutation S727D markedly decreased TMEM16A Cl-current and reversed TMEM16A-mediated suppression of BASMC proliferation, mimicking the inhibitory effects of CaMKIIγ on TMEM16A. A significant increase in CaMKIIγ isoform content was observed in parallel to the decrease of TMEM16A and ICl.Cain basilar artery proliferative remodeling in Ang II-infused mice. CONCLUSIONS: Serine 727 phosphorylation in TMEM16A by CaMKIIγ provides a new mechanism for regulating TMEM16A CaCC activity and Ang II-induced BASMC proliferation.

Five-year incidence and progression of myopic maculopathy in a rural Chinese adult population: the Handan Eye Study.

PURPOSE: To determine the cumulative five-year incidence and progression of myopic maculopathy in a rural Chinese adult population. METHODS: The Handan Eye Study was a population-based longitudinal study. In 2006, 6830 subjects aged 30+ years participated in this study (baseline). Five years later, 5394 subjects (follow-up rate: 85.3%) took part in the follow-up study. Participants had a detailed eye examination, including visual acuity, standardized refraction and fundus photography according to a similar protocol at both baseline and follow-up. Myopic maculopathy was defined as any of the following signs: diffuse chorioretinal atrophy, patchy chorioretinal atrophy, macular atrophy, lacquer cracks and myopic choroidal neovascularization at the posterior pole. Parapapillary atrophy was assessed separately. RESULTS: Of 5394 participants, 5078 (10 021 eyes) had gradable fundus photographs. Over the five years, four participants (five eyes) developed new myopic maculopathy, with an eye-specific incidence of 0.05% (95% CI, 0.02-0.10%). Among the 51 eyes with myopic maculopathy at baseline, the progression occurred in 18 eyes (35.3%), with new signs of patchy chorioretinal atrophy in 11 eyes (21.6%), diffuse chorioretinal atrophy in seven eyes (13.7%), lacquer cracks in three eyes (6.9%), macular atrophy in three eyes (6.9%) and myopic choroidal neovascularization in two eyes (3.9%). By multivariable analysis, female gender (OR, 9.14; p = 0.004) and higher educational level (OR, 8.24; p = 0.004) were associated with a higher risk of progression of myopic maculopathy, whereas lower myopia at baseline (OR, 0.79; p < 0.0001) and hypertension (OR, 0.21; p = 0.017) were associated with a reduced risk. CONCLUSIONS: The five-year incidence of myopic maculopathy was 0.05% in rural Chinese adults aged 30+ years. The progression rate in participants with myopic maculopathy was 35.3%, indicating the importance of regular follow-up for these patients.

Five-year refractive changes in a rural Chinese adult population and its related factors: the Handan Eye Study.

IMPORTANCE: Provision of refractive changes is important to predict eye care needs for aging population. BACKGROUND: To provide 5-year refractive changes in a rural Chinese adult population. DESIGN: Population-based longitudinal study. PARTICIPANTS: At baseline, 6830 subjects aged 30+ years took part in the Handan Eye Study. A total of 5394 of the 6323 survivors (85.3%) participated in the 5-year follow-up. METHODS: Ocular examinations including standardized refraction were performed according to the same protocol at both baseline and follow-up. MAIN OUTCOME MEASURES: Change in spherical equivalent (SE; sphere + 1/2 cylinder) and astigmatism. RESULTS: A total of 3970 right eyes were available for refraction analysis. The 5-year change in SE for all subjects was +0.17 diopters (D), and was -0.21D, +0.14D, +0.40D and +0.08D for subjects aged 30-39, 40-49, 50-59, and 60-69 years, respectively. By binary regression analysis, myopic shift was associated with severe nuclear opacity, longer axil length, diabetes and large change of lens power, while hyperopic shift was associated with older age and ocular hypertension at baseline. There was a mean change of 0.18D in the against-the-rule astigmatism. CONCLUSIONS AND RELEVANCE: There was a myopic shift for those 30-39 years old and a hyperopic shift from 40 to 69 years old in a rural Chinese adult population. Those with severe nuclear opacity, longer axil length, diabetes and large change of lens power tended to have a myopic shift, while those being older and having ocular hypertension at baseline were prone to have a hyperopic shift. There was also an increase in against-the-rule astigmatism in this population.

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.

A new vector for identification of prokaryotes and their variable-size genomes.

A large number of prokaryotes have been produced, so how to provide a means to describe and distinguish them accurately is becoming a key issue of prokaryotic taxonomy. We proposed an efficient algorithm to filter out most genome fragments that are horizontally transferred, and extracted a new genome vector (GV). To highlight the power of GV, we applied it to identify prokaryotes and their variable-size genome fragments. The result indicated that the new vector as species tags can accurately identify genome fragments as short as 3,000 bp at species level.

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.

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.

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.