Discrimination of indoor versus outdoor environmental state with machine learning algorithms in myopia observational studies.

BACKGROUND: Wearable smart watches provide large amount of real-time data on the environmental state of the users and are useful to determine risk factors for onset and progression of myopia. We aim to evaluate the efficacy of machine learning algorithm in differentiating indoor and outdoor locations as collected by use of smart watches. METHODS: Real time data on luminance, ultraviolet light levels and number of steps obtained with smart watches from dataset A: 12 adults from 8 scenes and manually recorded true locations. 70% of data was considered training set and support vector machine (SVM) algorithm generated using the variables to create a classification system. Data collected manually by the adults was the reference. The algorithm was used for predicting the location of the remaining 30% of dataset A. Accuracy was defined as the number of correct predictions divided by all. Similarly, data was corrected from dataset B: 172 children from 3 schools and 12 supervisors recorded true locations. Data collected by the supervisors was the reference. SVM model trained from dataset A was used to predict the location of dataset B for validation. Finally, we predicted the location of dataset B using the SVM model self-trained from dataset B. We repeated these three predictions with traditional univariate threshold segmentation method. RESULTS: In both datasets, SVM outperformed the univariate threshold segmentation method. In dataset A, the accuracy and AUC of SVM were 99.55% and 0.99 as compared to 95.11% and 0.95 with the univariate threshold segmentation (p < 0.01). In validation, the accuracy and AUC of SVM were 82.67% and 0.90 compared to 80.88% and 0.85 with the univariate threshold segmentation method (p < 0.01). In dataset B, the accuracy and AUC of SVM and AUC were 92.43% and 0.96 compared to 80.88% and 0.85 with the univariate threshold segmentation (p < 0.01). CONCLUSIONS: Machine learning algorithm allows for discrimination of outdoor versus indoor environments with high accuracy and provides an opportunity to study and determine the role of environmental risk factors in onset and progression of myopia. The accuracy of machine learning algorithm could be improved if the model is trained with the dataset itself.

CircGLIS3 inhibits thyroid cancer invasion and metastasis through miR-146b-3p/AIF1L axis.

PURPOSE: Studies have shown that circRNA is involved in the occurrence and development of human cancers. However, it remains unclear that the contribution of circRNA in thyroid carcinoma and its role in the process of tumorigenesis. METHODS: The expression profile of circRNA-miRNA-mRNA in thyroid carcinoma was detected by RNA sequencing and verified by qRT-PCR. The characteristics of circGLIS3 were verified by RNase R and actinomycin assays, subcellular fractionation, and fluorescence in situ hybridization. The functions of circGLIS3 and AIF1L were detected by wound healing, transwell, 3D culture and Western blot. RNA Immunoprecipitation (RIP), RNA pulldown and dual-luciferase reporter assays were used to verify the target genes of circGLIS3 and downstream miRNAs. Functional rescue experiments were performed by transfecting miRNA mimics or siRNA of target genes. Finally, metastatic mouse models were used to investigate circGLIS3 function in vivo. RESULTS: In this study, we discovered a novel circRNA (has_circ_0007368, named as circGLIS3) by RNA sequencing. CircGLIS3 was down-regulated in thyroid carcinoma tissues and cells line, and was negatively associated with malignant clinical features of thyroid carcinoma. Functional studies found that circGLIS3 could inhibit the migration and invasion of thyroid carcinoma cells, and was related to the EMT process. Mechanistically, circGLIS3 can upregulate the expression of the AIF1L gene by acting as a miR-146b-3p sponge to inhibit the progression of thyroid carcinoma. CONCLUSION: Our study identified circGLIS3 as a novel tumor suppressor in thyroid cancer, indicating the potential of circGLIS3 as a promising diagnostic and prognostic marker for thyroid cancer.

Biosynthesis and Detection of Domoic Acid from Diatom Pseudo-nitzschia: A Review.

The domoic acid (DA) produced by certain species of the marine pennate diatom genus Pseudo-nitzschia is highly neurotoxic and can induce nerve excitability and neurotoxicity by binding with ionotropic glutamate receptors, causing amnesic shellfish poisoning in humans who consume seafood contaminated with DA. In recent years, poisoning of humans caused by DA has occurred around the world, which has attracted increasing attention, and studies on DA production by Pseudo-nitzschia have become the hotpot. This article reviews the progress in the biosynthesis of DA by the typical diatom Pseudo-nitzschia, in which the metabolic pathway of the biosynthesis of DA and its precursors, i.e., geranyl pyrophosphate and L-glutamate, and the various environmental factors affecting DA production including temperature, light intensity, nutrients, trace metals, and alien bacteria are discussed. The detection methods of DA (including bioassays, enzyme linked immunosorbent assays, high performance liquid chromatography, capillary electrophoresis and biosensors), as well as the morphology and toxigenicity of Pseudo-nitzschia are also presented.

STRA6 Promotes Thyroid Carcinoma Progression via Activation of the ILK/AKT/mTOR Axis in Cells and Female Nude Mice.

BACKGROUND: Metastasis has emerged to be an important cause for poor prognosis of thyroid carcinoma (TC) and its molecular mechanisms are not fully understood. STRA6 is a multifunctional membrane protein widely expressed in embryonic and adult tissues. The function and mechanism of STRA6 in TC remain elusive. OBJECTIVE: We aimed to explore the role of STRA6 in TC progression and provide a therapeutic target for TC. METHODS: The expression and clinicopathological relevance of STRA6 were explored in TC. Stable STRA6-knockdown TC cells were established and used to determine the biological function of STRA6 in vitro and in vivo. RNA sequencing and co-immunoprecipitation were performed to unveil the molecular mechanism of STRA6 in TC progression. The potential of STRA6 as a therapeutic target was evaluated by lipid nanoparticles (LNPs) containing siRNA. RESULTS: STRA6 was upregulated in TC and correlated with aggressive clinicopathological features, including extrathyroidal extension and lymph node metastasis, which contributed to the poor prognosis of TC. STRA6 facilitated TC progression by enhancing proliferation and metastasis in vitro and in vivo. Mechanistically, STRA6 could interact with integrin-linked kinase (ILK) and subsequently activate the protein kinase B/mechanistic target of rapamycin (AKT/mTOR) signaling pathway. We further unveiled that STRA6 reprogrammed lipid metabolism through SREBP1, which was crucial for the metastasis of TC. Moreover, STRA6 siRNA delivered by LNPs significantly inhibited cell growth in xenograft tumor models. CONCLUSIONS: Our study demonstrates the critical roles of STRA6 contributing to TC progression via the ILK/AKT/mTOR axis, which may provide a novel prognostic marker as well as a promising therapeutic target for aggressive TC.

Genetic alterations in cfDNA of benign and malignant thyroid nodules based on amplicon-based next-generation sequencing.

BACKGROUND: Circulating cell-free DNA (cfDNA) serves as a biomarker in multiple malignant diseases. However, controversy still surrounds the role of cfDNA detection in the diagnosis and monitoring of papillary thyroid carcinoma (PTC). This study set out to identify the role of cfDNA detection in distinguishing between benign and malignant thyroid nodules. METHODS: Tissue, blood cell, and plasma samples were collected from 10 patients with benign nodules and 10 patients with malignant nodules. The DNA isolated from these samples was subject to PCR-based amplification using primers designed for 50 proto-oncogenes and tumor suppressor genes. PCR products were sequenced using Illumina technology, and the mutations were detected with varScan among sequencing data for each sample and comparative analysis was carried out. RESULTS: Through amplicon sequencing, we found one non-synonymous somatic mutation in the benign nodules and three in the malignant nodules. Among these four mutations, BRAFV600E mutation was detected in the tissue samples of 8 out of the 10 PTC patients, but it was not detected in the benign nodules. However, no BRAFV600E mutation was detected in cfDNA. Further differential analysis of cfDNA indicated that some genes had more mutations in benign patients than in malignant patients, such as MET and IDH, and some genes had more mutations in malignant patients, such as PIK3CA and EZH2. CONCLUSIONS: We found that BRAFV600E mutation was a credible disease-related mutation in PTC; however, it could not be detected in cfDNA. Moreover, there was a large difference in mutation gene distribution between benign and malignant thyroid nodules.

TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion.

BACKGROUND: Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) promoting demethylation in cells. However, the expression pattern and biologic significance of TET in papillary thyroid carcinoma (PTC) remain unclear. This study aimed to elucidate the biological functions of TET1 and the miRNA and mRNA expression levels in PTC cells with downregulated TET1. METHODS: The expression of the TET family in 49 PTC tissues and corresponding tumor-adjacent tissues, as well as PTC cell lines (BCPAP, K1, and TPC-1) and the normal thyroid epithelial cell line (Nthy-ori 3-1), were detected using quantitative real-time polymerase chain reaction. The 5hmC level was detected in PTC tissues and cell lines using immunohistochemistry and dot blot assay, respectively. After silencing the TET1 gene with siRNAs in BCPAP and TPC-1 cells, cell proliferation was detected using EdU assay. Transwell assay was used to investigate cell migration and invasion. miRNA and mRNA expression arrays were conducted in TET1-depleted BCPAP cells. RESULTS: The expression level of TET1 decreased in PTC tissues and cell lines and was consistent with the reduction in the 5hmC level. The knockdown of the TET1 gene with siRNAs in BCPAP and TPC-1 cells, cell proliferation was detected using EdU assay. Transwell assay was used to investigate cell migration and invasion. miRNA and mRNA expression arrays were conducted in TET1-depleted BCPAP cells. WNT4, FZD4, CDK6, MCF2L, and EDN1 was upregulated as potential target genes of dysregulated miRNAs. CONCLUSION: The study showed that TET1 dysfunction inhibited the migration and invasion of BCPAP cells and might have a potential role in the pathogenesis of PTC.

Enhancer-Driven lncRNA BDNF-AS Induces Endocrine Resistance and Malignant Progression of Breast Cancer through the RNH1/TRIM21/mTOR Cascade.

Epigenomic alterations can give rise to various tumor-promoting properties, including therapeutic resistance of cancer cells. Here, we identify an lncRNA, BDNF-AS, whose overexpression is specifically driven by a MEF2A-regulated enhancer in endocrine-resistant and triple-negative breast cancer (TNBC). High levels of BDNF-AS in breast cancer tissues not only feature endocrine resistance in hormone receptor (HR)-positive patients but also correlate with poor outcomes in both HR-positive and TNBC patients. Mechanistically, BDNF-AS acts as a molecular scaffold to promote RNH1 protein degradation via TRIM21-mediated ubiquitination of RNH1 at K225. Subsequently, BDNF-AS abolishes RNH1-regulated and RISC-mediated mTOR mRNA decay, therefore sustaining the activation of mTOR signaling. Importantly, mTOR inhibitor, but not PI3K inhibitor, could reverse tamoxifen resistance induced by the overexpression of BDNF-AS. These results point toward a master regulatory role of an enhancer-activated cascade of BDNF-AS/RNH1/TRIM21/mTOR in endocrine resistance and malignant progression of breast cancer.

miR-3619-3p promotes papillary thyroid carcinoma progression via Wnt/ß-catenin pathway.

BACKGROUND: It is well known that the dysregulation of microRNAs (miRNAs) has been identified in papillary thyroid carcinoma (PTC), but their roles in the progression and metastasis of PTC remain unclear. MicroRNA-3619-3p (miR-3619-3p) is associated with cancer progression as an oncogene which is predicted to target at the Wnt/ß-catenin signaling pathway. Our study aimed to investigate the role of miR-3619-3p on PTC cell migration and invasion, as well as the underlying mechanisms. METHODS: The expression of miR-3619-3p in 36 PTC tissues and corresponding tumor-adjacent tissues, as well as 3 PTC cell lines (BCPAP, K1, TPC-1) and the normal thyroid epithelial cell line (N-thy-ori 3-1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between miR-3619-3p expression and clinicopathologic status of PTC patients was analyzed. Migration, invasion, and wound healing, were used to evaluate the role of miR-3619-3p in PTC. The activation of ß-catenin and the possible molecular pathway were detected by western blotting. RESULTS: The expression of miR-3619-3p in PTC tissues was significantly higher than the corresponding tumor-adjacent tissues (P<0.01), and its high expression positively correlated with extrathyroidal invasion, multicentricity, and cervical lymph node metastasis. Moreover, the miR-3619-3p was also up-regulated in PTC cell lines when compared to N-thy-ori 3-1. MiR-3619-3p enhanced the capabilities of migration and invasion in PTC cell lines. Furthermore, miR-3619-3p activated Wnt/ß-catenin pathway via maintaining the mRNA stability of ß-catenin. CONCLUSIONS: miR-3619-3p promoted PTC cell migration and invasion as an oncogene via activating the Wnt/ß-catenin pathway through increasing the stability of ß-catenin.

MicroRNA-222 Promotes Invasion and Metastasis of Papillary Thyroid Cancer Through Targeting Protein Phosphatase 2 Regulatory Subunit B Alpha Expression.

BACKGROUND: Increasing evidence indicates that microRNA dysfunction is involved in the pathogenesis and progression of cancer. MicroRNA-222 (miR-222) is upregulated in papillary thyroid carcinoma (PTC). However, the role of miR-222 in invasion and metastasis of PTC remains unknown. This study investigated the function of miR-222 and its underlying mechanism in the progression of PTC. METHODS: The expression of miR-222 was detected by quantitative reverse transcription polymerase chain reaction, and its correlation with various clinical characteristics was analyzed. The role of miR-222 in PTC cell migration ability was assessed with Transwell® assays and wound-healing assays in both TPC-1 and K1 cells. By using bioinformatics analyses and dual-luciferase 3'-UTR reporter assays, the study identified the direct target of miR-222 and the downstream pathways of PTC. Further, the study confirmed the role of miR-222 in promoting PTC distant metastasis in vivo by injecting TPC-1 cells into nude mice. RESULTS: This study confirmed that miR-222 was upregulated in PTC tissues compared to adjacent thyroid tissues and that it correlated with aggressive cancer phenotypes. The results indicate that ectopic miR-222 enhanced cell migration and invasion of thyroid cancer cells in vitro and distant pulmonary metastases in vivo. Protein phosphatase 2 regulatory subunit B alpha (PPP2R2A), a tumor suppressor, was identified as a direct target of miR-222 through the 3'-UTR of PPP2R2A. Restoring PPP2R2A expression led to the attenuation of migration and invasion in miR-222-overexpressing thyroid cancer cells. Moreover, we found that miR-222 promoted invasion and metastasis partly through the AKT signaling pathway. CONCLUSIONS: Taken together, the results suggest that miR-222 promotes tumor invasion and metastasis in thyroid cancer by targeting PPP2R2A. Thus, miR-222 could serve as a potential diagnostic biomarker, as well as an attractive therapeutic tool for thyroid cancer.