A novel near infrared spectroscopy analytical strategy for soil nutrients detection based on the DBO-SVR method.

Soil is the basis of agricultural production and accessing accurate information on soil nutrients is essential. Traditional methods of soil composition detection, which are based on chemical analysis, are characterized by being costly and polluting. Spectroscopic analysis has proven to be a rapid, non-destructive and effective technique for predicting soil properties in general and potassium, phosphorus and organic matter in particular. However, previous research on soils has rarely combined optimization algorithms with machine learning techniques, which has led to suboptimal model accuracy and convergence speed. In this study, a total of 184 soil samples were collected from three cities of Linhai, Yueqing and Longyou County, Zhejiang Province, China. After measuring pH values, alkali-hydrolyzable nitrogen (SAN), available phosphorus (SAP), available potassium (SAK) and soil organic matter (SOM) contents, along with their corresponding spectroscopic measurements, nine pretreatment methods and their combinations are adopted. A novel assessment model, integrating support vector machine and dung beetle optimization algorithm (DBO-SVR), is proposed to predict pH values and SAN, SAP, SAK, SOM content. Meanwhile, the DBO algorithm is compared with three mainstream optimization algorithms (particle swarm optimization (PSO), whale optimization algorithm (WOA) and grey wolf optimizer (GWO)). Results showed that the DBO-SVR model was shown best performance with Rp, RMSEP and RPD of 0.9842, 0.1306, 5.6485 respectively for prediction of pH value, with Rp, RMSEP and RPD of 0.8802, 15.0574 mg/kg and 2.0508, respectively for assessment of SAN content, with Rp, RMSEP and RPD of 0.9790, 12.8298 mg/kg, and 4.5132, respectively for assessment of SAP content, with Rp, RMSEP and RPD of 0.8677, 22.5107 mg/kg, and 1.9546, respectively for assessment of SAK content, and with Rp, RMSEP and RPD of 0.9273, 2.6427g/kg , and 2.1821, respectively for assessment of SOM content. This study demonstrates that the combination of near-infrared (NIR) spectroscopy and the DBO-SVR algorithm is capable of predicting soil nutrient composition with greater accuracy and efficiency.

The application of approaches in detecting ferroptosis.

Ferroptosis is a regulatory cell death (RCD) caused by iron-dependent lipid peroxidation, which is the backbone of regulating various diseases such as tumor, nervous system diseases and so on. Despite ferroptosis without specific detection methods currently, there are numerous types of detection technology commonly used, including flow cytometry, cell activity assay, microscopic imaging, western blotting, quantitative polymerase chain reaction (qPCR). In addition, ferroptosis could be detected by quantifying oxygen-free radicals reactive oxygen species (ROS), the lipid metabolite (malondialdehyde ((MDA)), related pathways and observing mitochondrial damage. In the face of numerous detection methods, how to choose appropriate detection methods based on experimental purposes has become a problem that needs to be solved at present. In this review, we summarized the commonly used detection methods of the critical substances in the process of ferroptosis, in the hope of facilitating the comprehensive study of ferroptosis, with a view to providing a guidance for subsequent related research.

Impaired glycine neurotransmission causes adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. Because of this, treatment of AIS is limited to bracing and/or invasive surgery after onset. Preonset diagnosis or preventive treatment remains unavailable. Here, we performed a genetic analysis of a large multicenter AIS cohort and identified disease-causing and predisposing variants of SLC6A9 in multigeneration families, trios, and sporadic patients. Variants of SLC6A9, which encodes glycine transporter 1 (GLYT1), reduced glycine-uptake activity in cells, leading to increased extracellular glycine levels and aberrant glycinergic neurotransmission. Slc6a9 mutant zebrafish exhibited discoordination of spinal neural activities and pronounced lateral spinal curvature, a phenotype resembling human patients. The penetrance and severity of curvature were sensitive to the dosage of functional glyt1. Administration of a glycine receptor antagonist or a clinically used glycine neutralizer (sodium benzoate) partially rescued the phenotype. Our results indicate a neuropathic origin for "idiopathic" scoliosis, involving the dysfunction of synaptic neurotransmission and central pattern generators (CPGs), potentially a common cause of AIS. Our work further suggests avenues for early diagnosis and intervention of AIS in preadolescents.

Learnable Graph Convolutional Network With Semisupervised Graph Information Bottleneck.

Graph convolutional network (GCN) has gained widespread attention in semisupervised classification tasks. Recent studies show that GCN-based methods have achieved decent performance in numerous fields. However, most of the existing methods generally adopted a fixed graph that cannot dynamically capture both local and global relationships. This is because the hidden and important relationships may not be directed exhibited in the fixed structure, causing the degraded performance of semisupervised classification tasks. Moreover, the missing and noisy data yielded by the fixed graph may result in wrong connections, thereby disturbing the representation learning process. To cope with these issues, this article proposes a learnable GCN-based framework, aiming to obtain the optimal graph structures by jointly integrating graph learning and feature propagation in a unified network. Besides, to capture the optimal graph representations, this article designs dual-GCN-based meta-channels to simultaneously explore local and global relations during the training process. To minimize the interference of the noisy data, a semisupervised graph information bottleneck (SGIB) is introduced to conduct the graph structural learning (GSL) for acquiring the minimal sufficient representations. Concretely, SGIB aims to maximize the mutual information of both the same and different meta-channels by designing the constraints between them, thereby improving the node classification performance in the downstream tasks. Extensive experimental results on real-world datasets demonstrate the robustness of the proposed model, which outperforms state-of-the-art methods with fixed-structure graphs.

FireFace: Leveraging Internal Function Features for Configuration of Functions on Serverless Edge Platforms.

The emerging serverless computing has become a captivating paradigm for deploying cloud applications, alleviating developers' concerns about infrastructure resource management by configuring necessary parameters such as latency and memory constraints. Existing resource configuration solutions for cloud-based serverless applications can be broadly classified into modeling based on historical data or a combination of sparse measurements and interpolation/modeling. In pursuit of service response and conserving network bandwidth, platforms have progressively expanded from the traditional cloud to the edge. Compared to cloud platforms, serverless edge platforms often lead to more running overhead due to their limited resources, resulting in undesirable financial costs for developers when using the existing solutions. Meanwhile, it is extremely challenging to handle the heterogeneity of edge platforms, characterized by distinct pricing owing to their varying resource preferences. To tackle these challenges, we propose an adaptive and efficient approach called FireFace, consisting of prediction and decision modules. The prediction module extracts the internal features of all functions within the serverless application and uses this information to predict the execution time of the functions under specific configuration schemes. Based on the prediction module, the decision module analyzes the environment information and uses the Adaptive Particle Swarm Optimization algorithm and Genetic Algorithm Operator (APSO-GA) algorithm to select the most suitable configuration plan for each function, including CPU, memory, and edge platforms. In this way, it is possible to effectively minimize the financial overhead while fulfilling the Service Level Objectives (SLOs). Extensive experimental results show that our prediction model obtains optimal results under all three metrics, and the prediction error rate for real-world serverless applications is in the range of 4.25∼9.51%. Our approach can find the optimal resource configuration scheme for each application, which saves 7.2∼44.8% on average compared to other classic algorithms. Moreover, FireFace exhibits rapid adaptability, efficiently adjusting resource allocation schemes in response to dynamic environments.

Prmt5 deficiency inhibits CD4+ T-cell Klf2/S1pr1 expression and ameliorates EAE disease.

BACKGROUND: Protein arginine methyltransferase 5 (Prmt5) is the main type II methyltransferase, catalyzes protein arginine residue symmetric dimethylation, and modulates normal cellular physiology and disease progression. Prmt5 inhibition or deletion in CD4+ T cells has been reported to ameliorate experimental autoimmune encephalomyelitis (EAE), but the detailed molecular mechanisms have not yet been elucidated. METHODS: EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG35-55) in T cells Prmt5 conditional knockout (CD4-cre-Prmt5fl/fl, Prmt5cko) and Prmt5fl/fl (WT) mice. Flow cytometry, single-cell RNA sequencing, ATAC sequencing and chromatin immunoprecipitation assay (ChIP) approaches were used to explore the detail mechanisms. RESULTS: We find that Prmt5cko mice are resistant to EAE; infiltrating inflammatory CD4+ T cells in the central nervous system (CNS) are greatly reduced. However, in Prmt5cko mice, T cells in the spleen show much more proliferation and activation properties, the total number of CD4+ T cells in the spleen is not reduced, and the percentage of Rora+ CD4+ T cells is elevated. Also, CD4+ T cells express lower levels of S1pr1 and Klf2 than WT mice, which may influence pathogenic CD4+ T-cell egress from the spleen and migration to the CNS. Moreover, the single-cell ATAC sequence and ChIP assay reveal that the transcription factor Klf2 is enriched at the S1pr1 promoter and that Klf2 motif activity is reduced in Prmt5cko mice. CONCLUSIONS: Our study delineates the undiscovered role of Prmt5 in T-cell biology in which Prmt5 may inhibit Klf2-S1pr1 pathway to ameliorate EAE disease. Controlling T-cell Prmt5 expression may be helpful for the treatment of autoimmune diseases.

Prmt5 deficient mouse B cells display RNA processing complexity and slower colorectal tumor progression.

Protein arginine methyltransferase 5 (Prmt5) is essential for normal B-cell development; however, the roles of Prmt5 in tumor-infiltrating B cells in tumor therapy have not been well elucidated. Here, we revealed that CD19-cre-Prmt5fl/fl (Prmt5cko) mice showed smaller tumor weights and volumes in the colorectal cancer mouse model; B cells expressed higher levels of Ccl22 and Il12a, which attracted T cells to the tumor site. Furthermore, we used direct RNA sequencing to comprehensively profile RNA processes in Prmt5 deletion B cells to explore underline mechanisms. We found significantly differentially expressed isoforms, mRNA splicing, poly(A) tail lengths, and m6A modification changes between the Prmt5cko and control groups. Cd74 isoform expressions might be regulated by mRNA splicing; the expression of two novel Cd74 isoforms was decreased, while one isoform was elevated in the Prmt5cko group, but the Cd74 gene expression showed no changes. We observed Ccl22, Ighg1, and Il12a expression was significantly increased in the Prmt5cko group, whereas Jak3 and Stat5b expression was decreased. Ccl22 and Ighg1 expression might be associated with poly(A) tail length, Jak3, Stat5b, and Il12a expression might be modulated by m6A modification. Our study demonstrated that Prmt5 regulates B-cell function through different mechanisms and supported the development of Prmt5-targeted antitumor treatments.

MRI characteristics of lumbosacral dural arteriovenous fistulas.

Background and purpose: Spinal dural arteriovenous fistulas located in the lumbosacral region are rare and present with nonspecific clinical signs. The purpose of this study was to find out the specific radiologic features of these fistulas. Methods: We retrospectively reviewed the clinical and radiological data of 38 patients diagnosed with lumbosacral spinal dural arteriovenous fistulas in our institution from September 2016 to September 2021. All patients underwent time-resolved contrast-enhanced three-dimensional MRA and DSA examinations, and were treated with either endovascular or neurosurgical strategies. Results: Most of the patients (89.5%) had motor or sensory disorders in both lower limbs as the first symptoms. On MRA, the dilated filum terminale vein or radicular vein was seen in 23/30 (76.7%) patients with lumbar spinal dural arteriovenous fistulas and 8/8 (100%) patients with sacral spinal dural arteriovenous fistulas. T2W intramedullary abnormally high signal intensity areas were found in all lumbosacral spinal dural arteriovenous fistula patients, with involvement of the conus present in 35/38 (92.1%) patients. The "missing piece sign" in the intramedullary enhancement area was seen in 29/38 (76.3%) patients. Conclusion: Dilatation of the filum terminale vein or radicular vein is powerful evidence for diagnosis of lumbosacral spinal dural arteriovenous fistulas, especially for sacral spinal dural arteriovenous fistulas. T2W intramedullary hyperintensity in the thoracic spinal cord and conus, and the missing-piece sign could be indicative of lumbosacral spinal dural arteriovenous fistula.

A deep learning approach for anterior cruciate ligament rupture localization on knee MR images.

Purpose: To develop and evaluate a deep learning-based method to localize and classify anterior cruciate ligament (ACL) ruptures on knee MR images by using arthroscopy as the reference standard. Methods: We proposed a fully automated ACL rupture localization system to localize and classify ACL ruptures. The classification of ACL ruptures was based on the projection coordinates of the ACL rupture point on the line connecting the center coordinates of the femoral and tibial footprints. The line was divided into three equal parts and the position of the projection coordinates indicated the classification of the ACL ruptures (femoral side, middle and tibial side). In total, 85 patients (mean age: 27; male: 56) who underwent ACL reconstruction surgery under arthroscopy were included. Three clinical readers evaluated the datasets separately and their diagnostic performances were compared with those of the model. The performance metrics included the accuracy, error rate, sensitivity, specificity, precision, and F1-score. A one-way ANOVA was used to evaluate the performance of the convolutional neural networks (CNNs) and clinical readers. Intraclass correlation coefficients (ICC) were used to assess interobserver agreement between the clinical readers. Results: The accuracy of ACL localization was 3.77 ± 2.74 and 4.68 ± 3.92 (mm) for three-dimensional (3D) and two-dimensional (2D) CNNs, respectively. There was no significant difference in the ACL rupture location performance between the 3D and 2D CNNs or among the clinical readers (Accuracy, p < 0.01). The 3D CNNs performed best among the five evaluators in classifying the femoral side (sensitivity of 0.86 and specificity of 0.79), middle side (sensitivity of 0.71 and specificity of 0.84) and tibial side ACL rupture (sensitivity of 0.71 and specificity of 0.99), and the overall accuracy for sides classifying of ACL rupture achieved 0.79. Conclusion: The proposed deep learning-based model achieved high diagnostic performances in locating and classifying ACL fractures on knee MR images.

PD-L1+CD8+ T cells enrichment in lung cancer exerted regulatory function and tumor-promoting tolerance.

Immunotherapy targeting checkpoint blockade to rescue T cells from exhaustion has become an essential therapeutic strategy in treating cancers. Till now, little is known about the PD-L1 graphic pattern and characteristics in CD8+ T cells. We combined cytometry by time-of-flight (CyTOF) and imaging mass cytometry (IMC) approaches to analyze CD8+ T cells from primary lung cancers and discovered that PD-L1+CD8+ T cells were enriched in tumor lesions, spatially localized with PD-1+CD8+ T cells. Furthermore, PD-L1+CD8+ T cells exerted regulatory functions that inhibited CD8+ T cells proliferation and cytotoxic abilities through the PD-L1/PD-1 axis. Moreover, tumor-derived IL-27 promotes PD-L1+CD8+ T cells development through STAT1/STAT3 signaling. Single-cell RNA sequencing data analysis further clarified PD-L1+CD8+ T cells elevated in the components related to downregulation of adaptive immune response. Collectively, our data demonstrated that PD-L1+CD8+ T cells enriched in lung cancer engaged in tolerogenic effects and may become a therapeutic target in lung cancer.

PRMT5 Deficiency Enforces the Transcriptional and Epigenetic Programs of Klrg1+CD8+ Terminal Effector T Cells and Promotes Cancer Development.

Protein arginine methyltransferase 5 (PRMT5) participates in the symmetric dimethylation of arginine residues of proteins and contributes to a wide range of biological processes. However, how PRMT5 affects the transcriptional and epigenetic programs involved in the establishment and maintenance of T cell subset differentiation and roles in antitumor immunity is still incompletely understood. In this study, using single-cell RNA and chromatin immunoprecipitation sequencing, we found that mouse T cell-specific deletion of PRMT5 had greater effects on CD8+ than CD4+ T cell development, enforcing CD8+ T cell differentiation into Klrg1+ terminal effector cells. Mechanistically, T cell deficiency of PRMT5 activated Prdm1 by decreasing H4R3me2s and H3R8me2s deposition on its loci, which promoted the differentiation of Klrg1+CD8+ T cells. Furthermore, effector CD8+ T cells that transited to memory precursor cells were decreased in PRMT5-deficient T cells, thus causing dramatic CD8+ T cell death. In addition, in a mouse lung cancer cell line-transplanted tumor mouse model, the percentage of CD8+ T cells from T cell-specific deletion of PRMT5 mice was dramatically lost, but CD8+Foxp3+ and CD8+PDL1+ regulatory T cells were increased compared with the control group, thus accelerating tumor progression. We further verified these results in a mouse colon cancer cell line-transplanted tumor mouse model. Our study validated the importance of targeting PRMT5 in tumor treatment, because PRMT5 deficiency enforced Klrg1+ terminal CD8+ T cell development and eliminated antitumor activity.

Interleukin 32 Promotes Foxp3+ Treg Cell Development and CD8+ T Cell Function in Human Esophageal Squamous Cell Carcinoma Microenvironment.

Proinflammatory cytokine interleukin 32 (IL-32) is involved in infectious diseases and cancer, but what subtypes of immune cells express IL-32 and its roles in tumor microenvironment (TME) have not been well discussed. In this study, we applied bioinformatics to analyze single-cell RNA sequencing data about tumor-infiltrating immune cells from esophageal squamous cell carcinoma (ESCC) TME and analyzed IL-32 expression in different immune cell types. We found CD4+ regulatory T cells (Treg cells) express the highest level of IL-32, while proliferating T and natural killer cells expressed relatively lower levels. Knocking down of IL-32 reduced Foxp3 and interferon gamma (IFNγ) expressions in CD4+ and CD8+ T cells, respectively. IL-32 was positively correlated with Foxp3, IFNG, and GZMB expression but was negatively correlated with proliferation score. IL-32 may have a contradictory role in the TME such as it promotes IFNγ expression in CD8+ T cells, which enhances the antitumor activity, but at the same time induces Foxp3 expression in CD4+ T cells, which suppresses the tumor immune response. Our results demonstrate different roles of IL-32 in Treg cells and CD8+ T cells and suggest that it can potentially be a target for ESCC cancer immunosuppressive therapy.

PRMT5 Inhibition Promotes PD-L1 Expression and Immuno-Resistance in Lung Cancer.

Protein arginine transferase 5 (PRMT5) has been implicated as an important modulator of tumorigenesis as it promotes tumor cell proliferation, invasion, and metastasis. Studies have largely focused on PRMT5 regulating intrinsic changes in tumors; however, the effects of PRMT5 on the tumor microenvironment and particularly immune cells are largely unknown. Here we found that targeting PRMT5 by genetic or pharmacological inhibition reduced lung tumor progression in immunocompromised mice; however, the effects were weakened in immunocompetent mice. PRMT5 inhibition not only decreased tumor cell survival but also increased the tumor cell expression of CD274 in vitro and in vivo, which activated the PD1/PD-L1 axis and eliminated CD8+T cell antitumor immunity. Mechanistically, PRMT5 regulated CD274 gene expression through symmetric dimethylation of histone H4R3, increased deposition of H3R4me2s on CD274 promoter loci, and inhibition of CD274 gene expression. Targeting PRMT5 reduced this inhibitory effect and promoted CD274 expression in lung cancer. However, PRMT5 inhibitors represent a double-edged sword as they may selectively kill cancer cells but may also disrupt the antitumor immune response. The combination of PRMT5 inhibition and ani-PD-L1 therapy resulted in an increase in the number and enhanced the function of tumor-infiltrating T cells. Our findings address an unmet clinical need in which combining PRMT5 inhibition with anti-PD-L1 therapy could be a promising strategy for lung cancer treatment.

Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment.

Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME. Transcriptional profiling coupled with T cell receptor (TCR) sequencing reveal lineage connections in T cell populations. CD8 T cells show continuous progression from pre-exhausted to exhausted T cells. While exhausted CD4, CD8 T and NK cells are major proliferative cell components in the TME, the crosstalk between macrophages and Tregs contributes to potential immunosuppression in the TME. Our results indicate several immunosuppressive mechanisms that may be simultaneously responsible for the failure of immuno-surveillance. Specific targeting of these immunosuppressive pathways may reactivate anti-tumor immune responses in ESCC.

BACH2 regulates the function of human CD4+ CD45RA- Foxp3l ° cytokine-secreting T cells and promotes B-cell response in systemic lupus erythematosus.

Although CD4+ CD45RA- Foxp3l ° cytokine-secreting T cells (Fr.III cells) have been reported to be increased in systemic lupus erythematosus (SLE), their function and effects on response of B cells are still unclear. Here, we dissect how BACH2 regulates Fr.III cells function and promotes B-cell response in active SLE patients. We measured cytokines and BACH2 expression, and found that Fr.III cells from SLE patients produce much more inflammatory cytokines and were more able to promote B- cell proliferation, IgG, IgA, and TNF-α production than controls in a co-culture system. Fr.III cells expressed high levels of ICOS and CD154, but a low level of Tfr and BACH2, BACH2 expression was negatively correlated with SLE Disease Activity Index. Overexpressed of BACH2 in Fr.III cells, decreased cytokines expression and reduced B-cell response. Furthermore, we identified a reduction of H3K27ac level binding at the BACH2 locus in the SLE Fr.III cells and SLE serum stimulation decreased H3K27ac binding at the BACH2 locus, which could be restored using trichostatin A (TSA). In conclusion, BACH2 was associated with SLE disease activity, regulated the function of Fr.III cells, and promoted B-cells response. Targeting BACH2 may be a new immune intervention therapy of SLE.

Elucidation of the more myopic eye in anisometropia: the interplay of laterality, ocular dominance, and anisometropic magnitude.

This study reveals how, in a myopic anisometrope, the odds of an eye being more myopic are related to laterality, ocular dominance, and magnitude of anisometropia. In 193 subjects, objective refraction was performed with cycloplegia. Sighting, motor, and sensory dominance were determined with the hole-in-the-card test, convergence near-point test, continuous flashing technique, respectively. Multiple logistic regression was used for probability analysis. Seventy percent of the subjects had a right eye that was more myopic, while 30% of them had a more myopic left eye. When the right eye was the sensory dominant eye, the probability of the right eye being more myopic increased to 80% if the anisometropia was less than 3.0 D, and decreased below 70% if anisometropia was beyond 3.0 D. When the left eye was the sensory dominant eye, the probability of the left eye being more myopic increased to above 40% if the anisometropia was less than 4.0 D and decreased below 30% if the anisometropia was beyond 4.0 D. Therefore, between the two eyes of anisometropes, laterality tilts the chance of being more myopic to the right. Being the sensory dominant eye increases an eye's probability of being more myopic by another 10% if the magnitude of anisometropia is moderate.

Preliminary study on visual recognition under low visibility conditions caused by artificial dynamic smog.

AIM: To quantitatively evaluate the effect of a simulated smog environment on human visual function by psychophysical methods. METHODS: The smog environment was simulated in a 40×40×60 cm3 glass chamber filled with a PM2.5 aerosol, and 14 subjects with normal visual function were examined by psychophysical methods with the foggy smog box placed in front of their eyes. The transmission of light through the smog box, an indication of the percentage concentration of smog, was determined with a luminance meter. Visual function under different smog concentrations was evaluated by the E-visual acuity, crowded E-visual acuity and contrast sensitivity. RESULTS: E-visual acuity, crowded E-visual acuity and contrast sensitivity were all impaired with a decrease in the transmission rate (TR) according to power functions, with invariable exponents of -1.41, -1.62 and -0.7, respectively, and R2 values of 0.99 for E and crowded E-visual acuity, 0.96 for contrast sensitivity. Crowded E-visual acuity decreased faster than E-visual acuity. There was a good correlation between the TR, extinction coefficient and visibility under heavy-smog conditions. CONCLUSION: Increases in smog concentration have a strong effect on visual function.

Hypothalamic DNA methylation in rats with dihydrotestosterone-induced polycystic ovary syndrome: effects of low-frequency electro-acupuncture.

NEW FINDINGS: What is the central question of this study? What is the role of hypothalamic DNA methylation in the development of polycystic ovary syndrome (PCOS) and the response to electro-acupuncture treatment. What is the main finding and its importance? Global DNA methylation and expression of DNA methyltransferases (DNMTs) were increased in PCOS-like rats, and electro-acupuncture (EA) decreased global DNA methylation and DNMT3b expression. Pyrosequencing showed that the DNA methylation of some PCOS candidate genes was changed in the PCOS and PCOS+EA groups, suggesting that hypothalamic DNA methylation plays an important role in the development of PCOS and in mediating the effects of electro-acupuncture treatment. ABSTRACT: Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine disease of unknown aetiology. Recently, epigenetic studies focusing on DNA methylation in PCOS have received much attention, but the mechanisms are still unclear. In the present study, we used the 5α-dihydrotestosterone-induced PCOS-like rat model and treated the rats with electro-acupuncture (EA). Rats were randomly divided into four groups - controls, diet-induced obesity, PCOS and PCOS+EA. We examined the reproductive, metabolic and behavioural phenotypes, validated the effect of EA, and explored the role of hypothalamic DNA methylation by analysing the methylation of global DNA and selected candidate genes. The PCOS rats presented with reproductive dysfunctions such as lack of regular oestrous cyclicity, metabolic disorders such as increased body weight and insulin resistance, and depression and anxiety-like behaviours. EA improved the reproductive functions, decreased body weight and improved experimental depressive behaviour. Furthermore, global DNA methylation and the expression of DNA methyltransferases (DNMTs) were increased in PCOS rats compared to the control group, and EA decreased the global DNA methylation and the expression of DNMT3b. In addition, pyrosequencing showed that the DNA methylation of certain CpG sites in targeted genes (Plcg1, Camk2b, Esr2 and Pgr) was increased in the PCOS group, but the DNA methylation of Camk2b and Ar was decreased after EA treatment. These results indicate that hypothalamic DNA methylation might be correlated with the development of PCOS and that EA has an effect on hypothalamic DNA methylation in PCOS rats.

The Associations among Metamorphopsia, Orientation Discrimination Threshold, and Retinal Layer Thickness in Patients with Idiopathic Epiretinal Membrane.

PURPOSE: To explore the association among the metamorphopsia identified by Amsler grid test, orientation discrimination threshold (ODT), and retinal layer thickness in patients with idiopathic epiretinal membrane (ERM). METHODS: A total of 48 ERM patients were divided into a fovea-spared (FS) group (n = 12) and a fovea-involved (FI) group (n = 36). A total of 23 visually normal people served as controls. Metamorphopsia was first assessed with an Amsler grid. The ODT was quantified with groups of briefly displayed short line segments. Inner and outer retinal layer thickness (IRLT and ORLT) was measured with spectral domain optical coherence tomography. RESULTS: A total of 12 patients with ERM (1 in FS and 11 in FI) reported abnormalities in the Amsler grid test. The ODT values were significantly elevated in patients in both FS (7.48 ± 1.94°, p < 0.001) and FI groups (10.14 ± 2.28°, p < 0.001) when compared to normal (4.22 ± 0.80). Receiver operating characteristic (ROC) analyses of ODT to distinguish Amsler positive and negative patients yielded an area under the curve (AUC) of 0.829. The IRLT was significantly thicker (386.6 ± 95.1 µm vs. 127.5 ± 17.6 in normal) and ORLT were significantly thinner (88.11 ± 8.24 vs. 94.39 ± 5.66 in normal) in the FI group. ROC analyses to distinguish Amsler positive and negative patients yield an AUC of 0.917 using IRLT and 0.719 using ORLT. ODT correlated tightly with the thicker IRLT in both the FS and FI groups, and with the thinner ORLT in the FI group. CONCLUSIONS: In patients with ERM, ODT reflects functional changes that are not detected by the Amsler grid test and correlates with changes in inner retina layer thickness well.

Balanced Eyes See Stereopsis More Quickly, but Not More Finely.

Purpose: To quantify ocular sensory dominance and investigate its relationship to stereopsis. Method: A total of 69 subjects participated in the study. Ocular dominance was measured by a continuous flashing technique, with the tested eye viewing a Gabor patch increasing in contrast, and the fellow eye viewing a Mondrian noise decreasing in contrast. In each trial, the log ratio of Mondrian to Gabor's contrasts was recorded as a subject first detected the Gabor. We collected 50 trials for each eye and an interocular difference was analyzed with a rank-sum test. The z-value was used as the ocular dominance index (ODI) to quantify the degree of ocular dominance. A subject with ODI ≥ 2 was categorized as having a clear ocular dominance, and a subject with ODI < 2 was considered as having balanced eyes (unclear dominance). The stereoacuity was measured with random dot patterns with durations varying from 50 to 1000 ms. The best achievable stereoacuity (Dmin) and the integration time needed to acquire that (Tmin) were calculated. Results: A total of 30 subjects had balanced eyes and 39 had clear ocular dominance. Tmin was significantly longer in subjects with clear ocular dominance than in subjects with balanced eyes (180.18 vs. 121.17 ms, P < 0.01). Tmin was positively correlated with ODI (P < 0.01). However, Dmin in subjects with clear dominance was not different from that in subjects with balanced eyes (40.60 vs. 35.73 arcsec, P = 0.18). Conclusions: Ocular dominance is not associated with how fine the stereoacuity is, but rather how quickly the best stereoacuity is acquired.