Identification of ferroptosis-related molecular clusters and genes for diabetic osteoporosis based on the machine learning

BackgroundDiabetic osteoporosis exhibits heterogeneity at the molecular level. Ferroptosis, a controlled form of cell death brought on by a buildup of lipid peroxidation, contributes to the onset and development of several illnesses. The aim was to explore the molecular subtypes associated with ferroptosis in diabetic osteoporosis at the molecular level and to further elucidate the potential molecular mechanisms.MethodsIntegrating the CTD, GeneCards, FerrDb databases, and the microarray data of GSE35958, we identified ferroptosis-related genes (FRGs) associated with diabetic osteoporosis. We applied unsupervised cluster analysis to divide the 42 osteoporosis samples from the GSE56814 microarray data into different subclusters based on FRGs. Subsequently, FRGs associated with two ferroptosis subclusters were obtained by combining database genes, module-related genes of WGCNA, and differentially expressed genes (DEGs). Eventually, the key genes from FRGs associated with diabetic osteoporosis were identified using the least absolute shrinkage and selection operator (LASSO), Boruta, support vector machine recursive feature elimination (SVM ­ RFE), and extreme gradient boosting (XGBoost) machine learning algorithms. Based on ROC curves of external datasets (GSE56815), the model’s efficiency was examined.ResultsWe identified 15 differentially expressed FRGs associated with diabetic osteoporosis. In osteoporosis, two distinct molecular clusters related to ferroptosis were found. The expression results and GSVA analysis indicated that 15 FRGs exhibited significantly different biological functions and pathway activities in the two ferroptosis subclusters. Therefore, we further identified 17 FRGs associated with diabetic osteoporosis between the two subclusters. The results of the comprehensive analysis of 17 FRGs demonstrated that these genes were heterogeneous and had a specific interaction between the two subclusters. Ultimately, the prediction model had a strong foundation and excellent AUC values (0.84 for LASSO, 0.84 for SVM ­ RFE, 0.82 for Boruta, and 0.81 for XGBoost). IDH1 is a common gene to all four algorithms thus being identified as a key gene with a high AUC value (AUC = 0.698).ConclusionsAs a ferroptosis regulator, IDH1 is able to distinguish between distinct molecular subtypes of diabetic osteoporosis, which may offer fresh perspectives on the pathogenesis of the disease’s clinical symptoms and prognostic heterogeneity

A Systematic Analysis on DNA Methylation and the Expression of Both mRNA and microRNA in Bladder Cancer

Background: DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. Methodology/Principal Findings: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to "neurogenesis" and "cell differentiation" by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. Conclusions/Significance: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research

Underground Coal Mine Fingerprint Positioning Based on the MA-VAP Method

The access points (APs) in a coal mine wireless local area network (WLAN) are generally sparsely distributed. It can, with difficulty, satisfy the basic requirements of the fingerprint positioning based on Wi-Fi. Currently, the effectiveness of positioning is ensured by deploying more APs in an underground tunnel, which significantly increases system cost. This problem can be solved by using the Virtual Access Point (VAP) method that introduces virtual access points (VAPs), which can be virtually arranged in any part of the positioning area without installing actual access points. The drawback of the VAP method is that the generated received signal strength (RSS) value of a VAP is calculated based on the mapping of RSS value from only one corresponding access point (AP). This drawback does not consider the correlation between different AP signals and the generated RSS value of a VAP, which makes the modeling of fingerprint samples and real-time RSS collection incomplete. This study proposed a Multi-Association Virtual Access Point (MA-VAP) method takes into account the influence of multi-association. The multi-association coefficient is calculated based on the correlation between the RSS values of a VAP and multiple access points (APs). Then, the RSS value generated by a VAP is calculated using the multi-association function. The real-time collected RSS values from multiple APs related to this VAP are the input of the multi-association function. The influence of the number of VAPs and their arrangement on positioning accuracy is also analyzed. The experimental positioning results show that the proposed MA-VAP method achieves better positioning performance than the VAP method for the same VAP arrangement. Combined with the Weight K-Nearest Neighbors (WKNN) algorithm and Kernel Principal Component Analysis (KPCA) algorithm, the positioning error of the MA-VAP method of the error distance cumulative distribution function (CDF) at 90% is 4.5 m (with WKNN) and 3.5 m (with KPCA) in the environment with non-line-of-sight (NLOS) interference, and the positioning accuracy is improved by 10% (with WKNN) and 22.2% (with KPCA) compared with the VAP method. The MA-VAP method not only effectively solves the fingerprint positioning problem when APs are sparse deployed, but also improves the positioning accuracy

Research and Application of Underground WLAN Adaptive Radio Fingerprint Database

Fingerprint positioning based on WiFi in coal mines has received much attention because of the widespread application of WiFi. Fingerprinting techniques have developed rapidly due to the efforts of many researchers. However, the off-line construction of the radio fingerprint database is a tedious and time-consuming process. When the underground environments change, it may be necessary to update the signal received signal strength indication (RSSI) of all reference points, which will affect the normal working of a personnel positioning system. To solve this problem, an adaptive construction and update method based on a quantum-behaved particle swarm optimization–user-location trajectory feedback (QPSO–ULTF) for a radio fingerprint database is proposed. The principle of ULTF is that the mobile terminal records and uploads the related dataset in the process of user’s walking, and it forms the user-location track with RSSI through the analysis and processing of the positioning system server. QPSO algorithm is used for the optimal radio fingerprint match between the RSSI of the access point (AP) contained in the dataset of user-location track and the calibration samples to achieve the adaptive generation and update of the radio fingerprint samples. The experimental results show that the radio fingerprint database generated by the QPSO–ULTF is similar to the traditional radio fingerprint database in the statistical distribution characteristics of the signal received signal strength (RSS) at each reference point. Therefore, the adaptive radio fingerprint database can replace the traditional radio fingerprint database. The comparable results of well-known traditional positioning methods demonstrate that the radio fingerprint database generated or updated by the QPSO–ULTF has a good positioning effect, which can ensure the normal operation of a personnel positioning system

A Memory Structure with Different Control Gates

Memory is a key and fundamental component in integrated circuits (IC). A dominant volatile memory is the dynamic random access memory (DRAM) with one transistor and one capacitor, whose footprint is comparable to about two transistors. Memory structure needs further simplification according to IC's scaling-down requirement. However, most updated structures at present are still mainly limited in lab. Here, a memory structure with one transistor is demonstrated. The advantages of this new structure over conventional memory structures include the simplification of the structure by saving a capacitor space in DRAM, and thus the simplification of fabrication process. Typical characterization of the memory device is also performed, and very quick response time (approximate to 1 ns), which is faster than most present memories in the foundry, that is, 2 ns or more, is reported. Both simulation and experiments are performed to explain the memory working mechanism. The memory programming functions are implemented through the junction caused by control gate. This structure could be scaled down by using lithography processes in the foundry, which could ensure a fair reliability and enable immediate applications for information technology electronics as a potential alternative candidate for DRAM