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Purpose: Osteoarthritis (OA) is the most common joint disease worldwide and is the primary cause of disability and chronic pain in older adults.Ferroptosis is a type of programmed cell death characterized by aberrant iron metabolism and reactive oxygen species accumulation; however, its role in OA is not known. Methods: To identify ferroptosis markers co-expressed in articular cartilage and synovium samples from patients with OA, in silico analysis was performed.Signature genes were analyzed and the results were evaluated using a ROC curve prediction model.The biological function, correlation between Signature genes, immune cell infiltration, and ceRNA network analyses were performed. Signature genes and ferroptosis phenotypes were verified through in vivo animal experiments and clinical samples. The expression levels of non-coding RNAs in samples from patients with OA were determined using qRT-PCR. ceRNA network analysis results were confirmed using dual-luciferase assays. Results: JUN, ATF3, and CDKN1A were identified as OA- and ferroptosis-associated signature genes. GSEA analysis demonstrated an enrichment of these genes in immune and inflammatory responses, and amino acid metabolism. The CIBERSORT algorithm showed a negative correlation between T cells and these signature genes in the cartilage, and a positive correlation in the synovium. Moreover, RP5-894D12.5 and FAM95B1 regulated the expression of JUN, ATF3, and CDKN1A by competitively binding to miR-1972, miR-665, and miR-181a-2-3p. In vivo, GPX4 was downregulated in both OA cartilage and synovium; however, GPX4 and GSH were downregulated, while ferrous ions were upregulated in patient OA cartilage and synovium samples, indicating that ferroptosis was involved in the pathogenesis of OA. Furthermore, JUN, ATF3, and CDKN1A expression was downregulated in both mouse and human OA synovial and cartilage tissues. qRT-PCR demonstrated that miR-1972, RP5-894D12.5, and FAM95B1 were differentially expressed in OA tissues. Targeted interactions between miR-1972 and JUN, and a ceRNA regulatory mechanism between RP5-894D12.5, miR-1972, and JUN were confirmed by dual-luciferase assays. Conclusion: This study identified JUN, ATF3, and CDKN1A as possible diagnostic biomarkers and therapeutic targets for joint synovitis and OA. Furthermore, our finding indicated that RP5-894D12.5/miR-1972/JUN was a potential ceRNA regulatory axis in OA, providing an insight into the connection between ferroptosis and OA. [ABSTRACT FROM AUTHOR]

Simple Summary: Growing evidence shows that the dynamic interactions between tumor-associated macrophages and lactate play an important role in sustaining a tumor niche; however, the relationship between lactate and tumor-associated macrophages in colorectal cancer has not been fully studied. In this study, we found that lactate produced by CRC could induce M2 polarization by activating the AKT-ERK pathway. After polarization, M2 macrophages secreted abundant CCL8 and accelerated tumor progression and metastasis through the CCR5/mTORC1 pathway. This mutual interaction between macrophages and tumor cells may be central to formulate the inhibitory niche of TME and maintain the malignancy of a tumor. Targeting the CCL8/CCR5/mTORC1 pathway is a promising target for future tumor treatment. Tumor-associated macrophages (TAMs) play a pivotal role in shaping the tumor microenvironment. Lactic acid (LA) has been identified as an influential factor in promoting immune escape and tumor progression. However, the mechanisms through which LA modulates TAMs in colorectal cancer (CRC) remain poorly understood. We used qRT-PCR to quantify the expression of LA-related genes (LDHA and LAMP2) in CRC tumor tissues and adjacent nontumor tissues (n = 64). The biological effects and mechanisms of LA on macrophages and tumors were evaluated via qRT-PCR, Western blot, RNA-seq, wound healing assay, colony formation assay in vitro, and allograft mouse tumor models in vivo. We found the expression of LDHA and LAMP2 was highly elevated in the tumor regions and positively associated with a poor clinical stage of CRC. A high concentration of LA was generated under hypoxia; it could promote tumor progression and metastasis with the involvement of macrophages. The inhibition of LA release impaired this protumor phenomenon. Mechanically, LA induced M2 macrophages through the AKT/ERK signaling pathway; subsequently, M2 macrophages secreted CCL8 and facilitated the proliferation and metastasis of CRC cells by activating the CCL8/CCR5/mTORC1 axis. This effect was inhibited by the antagonist or knockdown of CCR5. In conclusion, lactate-induced CCL8 in TAMs accelerated CRC proliferation and metastasis through the CCL8/CCR5/mTORC1 axis. [ABSTRACT FROM AUTHOR]

The dissolution of supercritical carbon dioxide (ScCO2) in water forms a ScCO2–H2O system, which exerts a transformative influence on the physicochemical characteristics of coal and significantly impacts the CO2-driven enhanced coalbed methane (CO2-ECBM) recovery process. Herein, the effect of ScCO2–H2O treatment on the physicochemical properties of coal was simulated in a high-pressure reactor. The migration of major elements, change in the pore structure, and change in the CH4 adsorption capacity of coal after the ScCO2–H2O treatment were detected using plasma emission spectroscopy, the low-temperature liquid nitrogen adsorption method, and the CH4 adsorption method, respectively. The results show that (1) the ScCO2–H2O treatment led to mineral reactions causing a significant migration of constant elements in the coal. The migration of Ca ions was the most significant, with an increase in their concentration in treated water from 0 to 16–970 mg·L−1, followed by Na, Mg, and K. Al migrated the least, from 0 to 0.004–2.555 mg·L−1. (2) The ScCO2–H2O treatment increased the pore volume and pore-specific surface area (SSA) of the coal via the dissolution and precipitation of minerals in the coal pores. The total pore volume increased from 0.000795–0.011543 to 0.001274–0.014644 cm3·g−1, and the total pore SSA increased from 0.084–3.332 to 0.400–6.061 m2·g−1. (3) Changes in the CH4 adsorption capacity were affected by the combined effects of a mineral reaction and pore structure change. The dissolved precipitates of the minerals in the coal pores after the ScCO2–H2O treatment caused elemental migration, which not only decreased the mineral content in the coal pores but also increased the total pore volume and total pore SSA, thus improving the CH4 adsorption capacity of the coal. This study provides theoretical support for CO2 sequestration and ECBM recovery. [ABSTRACT FROM AUTHOR]

In this work, the effect of in situ SiNx grown with different carrier gas on the structural and electrical properties of the SiNx/AlGaN/GaN MIS-HEMTs is studied. It was found that the growth rate of SiNx grown with N2 as carrier gas (N2-SiNx) is more sensitive to different growth conditions, while the growth rate of SiNx grown with H2 as carrier gas (H2-SiNx) is very stable due to the inhibiting effects of H2 carrier gas on the SiH4–NH3 forward reactions. More importantly, a continuous and smooth SiNx growth at the initial stage can be realized with H2 carrier gas due to its faster surface migration, leading to a decent surface morphology and sharp interface of H2-SiNx. As a result, the SiNx passivated device with H2 as carrier gas shows improved performance compared to that with N2 as carrier gas, featuring ultra-low interface-state density of 2.8 × 1010 cm−2 eV−1, improved on- and off-state current, reduced threshold voltage shift, and mitigated current collapse, especially after long-term electrical stress. These results not only elaborate on the growth mechanisms of in situ SiNx with different carrier gases but also highlight the advances of H2 as carrier gas for in situ SiNx growth, providing an effective strategy to tailor the passivation schemes for GaN-based devices. [ABSTRACT FROM AUTHOR]

Epilepsy is a disease caused by abnormal discharges in the central nervous system. Automatic detection and accurate identification of epileptic seizures based on electroencephalography (EEG) are significant in the clinical diagnosis and treatment of epilepsy. In this paper, we first decompose the patient's EEG signal into multiple intrinsic modal functions (IMFs) using empirical modal decomposition, then compute the mean, standard deviation, fluctuation index, and sample entropy of IMF1, and finally classify them using a fusion algorithm of support vector machine and K‐nearest neighbor optimized by particle swarm algorithm. The results of validation using the epileptic EEG data set from Bonn University show that the auto‐detection and fast recognition method proposed in this paper can achieve a high seizure accuracy recognition rate (≥95%) with only a small number of training samples, which has a good clinical application value. [ABSTRACT FROM AUTHOR]

In this work, we comprehensively studied the correlation between the electrical characteristics and the gate width (${W}_{G}$) of GaN-based HEMTs. On the one hand, as ${W}_{G}$ is scaled down from 100 $\mu \text{m}$ down to $3~\mu \text{m}$ , the devices exhibit five-times-enhanced on-state drain current density and largely reduced on-resistance, thanks to the increased electron mobility and mitigated self-heating effects in the narrow- ${W}_{G}$ channels. On the other hand, the devices with a wider ${W}_{G}$ exhibit reduced off-state leakage current and enhanced breakdown voltage, thanks to a decreased electric field and increased Schottky barrier height. Further temperature-dependent characterization reveals that the ${W}_{G}$ -modulation behavior on both on- and off-state device properties is still effective at a high temperature of 150°C. These experimental results can provide a straightforward approach for effective channel modulation and device optimization of GaN-based power devices of the future. [ABSTRACT FROM AUTHOR]

In this work, we investigated the temperature-dependent photodetection behavior of a high-performance AlGaN/GaN-based ultraviolet phototransistor (UVPT) operating under 265 nm illumination. As the temperature continuously rises from room temperature to 250 °C, the photocurrent of a device increases in the beginning but suffers from degradation afterwards. This can be explained by the competing process between the generation and recombination rate of photo-induced carriers in the UVPT at room and high temperatures. Intriguingly, we found that the optimal operating temperature for our UVPT is around 50 °C, featuring a high peak responsivity of 1.52 × 105 A/W under a light intensity of 45 μW/cm2. Furthermore, the photoresponse time of our UVPT is also highly temperature-dependent, exhibiting the shortest rise time of 50 ms at 100 °C while the decay time is monotonically reduced as the temperature rises to 250 °C. Notably, our AlGaN/GaN-based UVPTs exhibit ultra-high responsivity at high temperatures, which have outperformed those earlier reported UV photodetectors in the form of different device architectures, highlighting the great potential of such device configurations for harsh environment applications. [ABSTRACT FROM AUTHOR]

Background. Although accumulating evidence suggested that a molecular signature panel may be more effective for the prognosis prediction than routine clinical characteristics, current studies mainly focused on colorectal or colon cancers. No reports specifically focused on the signature panel for rectal cancers (RC). Our present study was aimed at developing a novel prognostic signature panel for RC. Methods. Sequencing (or microarray) data and clinicopathological details of patients with RC were retrieved from The Cancer Genome Atlas (TCGA-READ) or the Gene Expression Omnibus (GSE123390, GSE56699) database. A weighted gene coexpression network was used to identify RC-related modules. The least absolute shrinkage and selection operator analysis was performed to screen the prognostic signature panel. The prognostic performance of the risk score was evaluated by survival curve analyses. Functions of prognostic genes were predicted based on the interaction proteins and the correlation with tumor-infiltrating immune cells. The Human Protein Atlas (HPA) tool was utilized to validate the protein expression levels. Results. A total of 247 differentially expressed genes (DEGs) were commonly identified using TCGA and GSE123390 datasets. Brown and yellow modules (including 77 DEGs) were identified to be preserved for RC. Five DEGs (ASB2, GPR15, PRPH, RNASE7, and TCL1A) in these two modules constituted the optimal prognosis signature panel. Kaplan-Meier curve analysis showed that patients in the high-risk group had a poorer prognosis than those in the low-risk group. Receiver operating characteristic (ROC) curve analysis demonstrated that this risk score had high predictive accuracy for unfavorable prognosis, with the area under the ROC curve of 0.915 and 0.827 for TCGA and GSE56699 datasets, respectively. This five-mRNA classifier was an independent prognostic factor. Its predictive accuracy was also higher than all clinical factor models. A prognostic nomogram was developed by integrating the risk score and clinical factors, which showed the highest prognostic power. ASB2, PRPH, and GPR15/TCL1A were predicted to function by interacting with CASQ2/PDK4/EPHA67, PTN, and CXCL12, respectively. TCL1A and GPR15 influenced the infiltration levels of B cells and dendritic cells, while the expression of PRPH was positively associated with the abundance of macrophages. HPA analysis supported the downregulation of PRPH, RNASE7, CASQ2, EPHA6, and PDK4 in RC compared with normal controls. Conclusion. Our immune-related signature panel may be a promising prognostic indicator for RC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis and high mortality. To identify key genes associated with HCC and the underlying mechanisms, we performed weighted correlation network analysis (WGCNA) of potential key genes of HCC. We identified 17 key genes closely related to HCC by yellow module combined with PPI analysis. Verification of the role of these genes revealed that SPC25 knockdown results in a significant decrease in proliferation and metastasis of HCC cells and increased protein levels of components of the p53 pathway in vitro. In summary, we identified that SPC25 is a potential tumor‐promoting factor in HCC and may act via the p53 pathway. [ABSTRACT FROM AUTHOR]

PINX1 (Pin2/TRF1 interacting protein X1, an intrinsic telomerase inhibitor and putative tumor suppressor gene) may represent a novel prognostic tumor biomarker. However, the results of previous studies are inconsistent and the prognostic value of PINX1 remains controversial. Therefore, we conducted a meta-analysis to determine whether PINX1 expression is associated with overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), recurrence-free survival (RFS), and clinicopathological characteristics in patients with malignant tumors. A systematic search was performed in the PubMed, Web of Science, and Embase databases in April 2018. Quality assessment was performed according to the modified Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95.0% confidence intervals (CIs) were calculated to determine the relationship between PINX1 expression and OS, DSS, DFS/RFS, and clinicopathological characteristics. Due to the heterogeneity across the included studies, subgroup and sensitivity analyses were performed. Fixed-effects models were used when the heterogeneity was not significant and random-effects models were used when the heterogeneity was significant. Fourteen studies of 16 cohorts including 2,624 patients were enrolled. Low PINX1 expression was associated with poor OS (HR: 1.51, 95.0% CI: 1.03–2.20; P = 0.035) and DFS/RFS (HR: 1.78, 95.0% CI: 1.28–2.47; P = 0.001) but not DSS (HR: 0.80, 95.0% CI: 0.38–1.67; P = 0.548). Low PINX1 expression was also associated with lymphatic invasion (OR: 2.23, 95.0% CI: 1.35–3.70; P = 0.002) and advanced tumor-node-metastasis stage (OR: 2.43, 95.0% CI: 1.29–4.57; P = 0.006). No significant associations were observed between low PINX1 expression and sex, depth of invasion, grade of differentiation, and distant metastasis. Low PINX1 expression was associated with poor OS and DFS/RFS and lymphatic invasion and advanced tumor-node-metastasis stage, suggesting that PINX1 expression may be a useful predictor of prognosis in patients with malignant tumors. [ABSTRACT FROM AUTHOR]

Mammalian-enabled ( MENA) protein is an actin-regulatory protein that influences cell motility and adhesion. It is known to play a role in tumorigenicity of hepatocellular carcinoma ( HCC) but the underlying molecular mechanism remains unknown. This study aimed to investigate the oncogenic potential of MENA and its capacity to regulate cancer stem cell ( CSC)-like phenotypes in HCC cells. Real-time- PCR and western blot were used to assess mRNA and protein levels of target genes in human HCC tissue specimens and HCC cell lines, respectively. Stable MENA-overexpressing HCC cells were generated from HCC cell lines. Transwell cell migration and colony formation assays were employed to evaluate tumorigenicity. Ectopic expression of MENA significantly enhanced cell migration and colony-forming ability in HCC cells. Overexpression of MENA upregulated several hepatic progenitor/stem cell markers in HCC cells. A high MENA protein level was associated with high mRNA levels of MENA, CD133, cytokeratin 19 ( CK19), and epithelial cell adhesion molecule (Ep CAM) in human HCC tissues. Overexpression of MENA enhanced epithelial-to-mesenchymal transition ( EMT) markers, extracellular signal-regulated kinases ( ERK) phosphorylation, and the level of β-catenin in HCC cells. This study demonstrated that overexpression of MENA in HCC cells promoted stem cell markers, EMT markers, and tumorigenicity. These effects may involve, at least partially, the ERK and β-catenin signaling pathways. [ABSTRACT FROM AUTHOR]

There is increasing evidence that circular RNA (circ RNA) are involved in cancer development, but the regulation and function of human circ RNA remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular ( circ ZKSCAN1) forms of RNA in human hepatocellular carcinoma ( HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1 mRNA and circ ZKSCAN1 was significantly lower ( P < 0.05) in the HCC samples compared with that in matched adjacent nontumorous tissues by reverse transcription PCR ( RT- PCR). The low expression level of ZKSCAN1 was only associated with tumor size ( P = 0.032), while the cir ZKSCAN1 levels varied in patients with different tumor numbers ( P < 0.01), cirrhosis ( P = 0.031), vascular invasion ( P = 0.002), or microscopic vascular invasion ( P = 0.002), as well as with the tumor grade ( P < 0.001). Silencing both ZKSCAN1 mRNA and circ ZKSCAN1 promoted cell proliferation, migration, and invasion. In contrast, overexpression of both forms of RNA repressed HCC progression in vivo and in vitro. Silencing or overexpression of both forms of RNA did not interfere with each other. RNA-seq revealed a very different molecular basis for the observed effects; ZKSCAN1 mRNA mainly regulated cellular metabolism, while circ ZKSCAN1 mediated several cancer-related signaling pathways, suggesting a nonredundant role for ZKSCAN1 mRNA and circ RNA. In conclusion, our results revealed two post-translational products ( ZKSCAN1 mRNA and circ ZKSCAN1) that cooperated closely with one another to inhibit growth, migration, and invasion of HCC. cir ZKSCAN1 might be a useful marker for the diagnosis of HCC. [ABSTRACT FROM AUTHOR]