Characterization of Trap States in AlGaN/GaN MIS-High-Electron-Mobility Transistors under Semi-on-State Stress.

Devices under semi-on-state stress often suffer from more severe current collapse than when they are in the off-state, which causes an increase in dynamic on-resistance. Therefore, characterization of the trap states is necessary. In this study, temperature-dependent transient recovery current analysis determined a trap energy level of 0.08 eV under semi-on-state stress, implying that interface traps are responsible for current collapse. Multi-frequency capacitance-voltage (C-V) testing was performed on the MIS diode, calculating that interface trap density is in the range of 1.37×1013 to 6.07×1012cm-2eV-1 from EC-ET=0.29 eV to 0.45 eV.

Semaphorin 6D as an independent predictor for better prognosis in clear cell renal cell carcinoma.

INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) is the most common type of RCC and is associated with poor survival. However, the mechanisms underlying its development have not been thoroughly investigated. Semaphorin 6D (SEMA6D) is differentially expressed in various cancers, including lung adenocarcinoma and colorectal cancer. However, the role and mechanism of SEMA6D in ccRCC remain unexplored. MATERIALS AND METHODS: We obtained 25 pairs of ccRCC tissue samples and 57 urine samples from patients with ccRCC and 52 urine samples from healthy volunteers. We performed RNA sequencing and compared the results with data from The Cancer Genome Atlas database to identify our gene of interest, SEMA6D. To verify the differential expression of SEMA6D, we used real-time quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. Finally, we conducted in vitro proliferation, migration and invasion experiments. RESULTS: SEMA6D expression was significantly lower in ccRCC tissue compared to that in normal tissue. Comparative analysis of our results with data from online databases revealed that the expression level of SEMA6D in ccRCC tissue correlated with the clinical stage and pathological grade of ccRCC. Furthermore, higher SEMA6D expression was associated with improved quality of life of patients with ccRCC. In addition, the diagnostic value of SEMA6D was confirmed using data from two Gene Expression Omnibus ccRCC databases. The results showed that SEMA6D can be used as a predictor for ccRCC diagnosis, with an area under the curve of 0.9642. CONCLUSION: SEMA6D may serve as a diagnostic and prognostic biomarker for ccRCC.

Ubiquitin-specific peptidase 2 inhibits epithelial-mesenchymal transition in clear cell renal cell carcinoma metastasis by downregulating the NF-κB pathway.

Clear cell renal cell carcinoma, the most common type of renal cancer, is associated with poor survival. Ubiquitin-specific peptidase 2 regulates the molecular mechanisms of cancer cells. However, its mechanism in clear cell renal cell carcinoma remains unclear. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry were performed to assess ubiquitin-specific peptidase 2 expression in human clear cell renal cell carcinoma samples. Ubiquitin-specific peptidase 2 was weakly expressed in clear cell renal cell carcinoma samples and associated with poor patient outcomes. Ubiquitin-specific peptidase 2 inhibition promoted clear cell renal cell carcinoma cell proliferation, migration, and invasion. Ubiquitin-specific peptidase 2 overexpression inhibited clear cell renal cell carcinoma cell proliferation, migration, and invasion in vitro and in vivo. RNA-sequencing showed significant changes in the epithelial-mesenchymal transition-related pathways following ubiquitin-specific peptidase 2 knockdown. Western blotting was performed to detect the protein expression levels. Expression of p-nuclear factor-κB p65, N-cadherin, Vimentin, and Snail, which were markedly increased, as well as E-cadherin, which was decreased following ubiquitin-specific peptidase 2 knockdown. Rescue experiments using the nuclear factor-κB inhibitor BAY 11-7082 revealed that the migration and invasion abilities and the expression of epithelial-mesenchymal transition pathway proteins were inhibited in both the short hairpin RNA (shRNA) for ubiquitin-specific peptidase 2 and shRNA for negative control groups. Ubiquitin-specific peptidase 2 is a potential biomarker to distinguish clear cell renal cell carcinoma patients from healthy individuals. Ubiquitin-specific peptidase 2-mediated inhibition of epithelial-mesenchymal transition in clear cell renal cell carcinoma cells is dependent on the nuclear factor-κB pathway.

Feedback activation of NF-KB signaling leads to adaptive resistance to EZH2 inhibitors in prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) is the most common malignant tumor in developed countries, which has seriously threatened men's lifestyle and quality of life. The up-regulation of EZH2 is associated with advanced PCa and poor prognosis, making it a promising therapeutic target. However, the EZH2 inhibitors-based treatment is basically ineffective against PCa, which limits its clinical application. METHODS: Microarray data (GSE107779) from LNCaP cells treated with either siRNA against EZH2 or a EZH2 inhibitor EPZ6438 was analyzed by Limma R package. Western blot, real-time PCR and luciferase reporter assays were used to determine the EZH2-SOX9-TNFRSF11A axis and the activity of NF-κB signaling in PCa cells. CCK-8 assay was used to determine the viability of PCa cells following various treatments. RESULTS: Genetic ablation or pharmacological inhibition of EZH2 leads to feedback activation of NF-κB signaling in PCa cells. EZH2-dependent SOX9 expression regulates the activation of NF-κB signaling. TNFRSF11A, also known as receptor activator of NF-κB (RANK), is a downstream target of SOX9 in PCa cells. SOX9 recognizes two putative SOX9 response elements in the promoter region of TNFRSF11A gene to drive TNFRSF11A expression and downstream NF-κB signaling activation. Suppression of the NF-κB signaling by either TNFRSF11A silencing or BAY11-7082 treatment rendered PCa cells to EZH2 inhibitors. CONCLUSION: Collectively, our finding reveals a EZH2-SOX9-TNFRSF11A axis in the regulation of activity of NF-κB signaling in PCa cells and suggests that a combination of EZH2 inhibitors and BAY11-7082 would be an effective approach for the treatment of PCa patients in the future.

Direct Sequencing of tRNA by 2D-HELS-AA MS Seq Reveals Its Different Isoforms and Dynamic Base Modifications.

Post-transcriptional modifications are intrinsic to RNA structure and function. However, methods to sequence RNA typically require a cDNA intermediate and are either not able to sequence these modifications or are tailored to sequence one specific nucleotide modification only. Interestingly, some of these modifications occur with <100% frequency at their particular sites, and site-specific quantification of their stoichiometries is another challenge. Here, we report a direct method for sequencing tRNAPhe without cDNA by integrating a two-dimensional hydrophobic RNA end-labeling strategy with an anchor-based algorithm in mass spectrometry-based sequencing (2D-HELS-AA MS Seq). The entire tRNAPhe was sequenced and the identity, location, and stoichiometry of all eleven different RNA modifications was determined, five of which were not 100% modified, including a 2'-O-methylated G (Gm) in the wobble anticodon position as well as an N2, N2-dimethylguanosine (m22G), a 7-methylguanosine (m7G), a 1-methyladenosine (m1A), and a wybutosine (Y), suggesting numerous post-transcriptional regulations in tRNA. Two truncated isoforms at the 3'-CCA tail of the tRNAPhe (75 nt with a 3'-CC tail (80% abundance) and 74 nt with a 3'-C tail (3% abundance)) were identified in addition to the full-length 3'-CCA-tailed tRNAPhe (76 nt, 17% abundance). We discovered a new isoform with A-G transitions/editing at the 44 and 45 positions in the tRNAPhe variable loop, and discuss possible mechanisms related to the emergence and functions of the isoforms with these base transitions or editing. Our method revealed new isoforms, base modifications, and RNA editing as well as their stoichiometries in the tRNA that cannot be determined by current cDNA-based methods, opening new opportunities in the field of epitranscriptomics.

Compact polarization-entangled photon-pair source based on a dual-periodically-poled Ti:LiNbO3 waveguide.

We present an experimental realization of a compact and reliable way to build a nondegenerate polarization-entangled photon-pair source based on a dual-periodically-poled $ {\rm Ti}:{{\rm LiNbO}_3} $Ti:LiNbO3 waveguide, which is in the telecommunication window and compatible with the fiber quantum networks. The dual-periodic structure allows two inherently concurrent quasiphase-matching spontaneous parametric down-conversion processes pumped by a single laser beam, hence enabling our source to be compact and stable. We show that our source has a high brightness of $ B = 1.22{\rm } \times {\rm }{10^7}\;{\rm pairs}/(\rm s \times mW \times nm) $B=1.22×107pairs/(s×mW×nm). With quantum state tomography, we estimate an entanglement fidelity of $ 0.945 \pm 0.003 $0.945±0.003. A violation of Clauser-Horne-Shimony-Holt inequality with $ S = 2.75 \pm 0.03 $S=2.75±0.03 is also demonstrated.

LncRNA-LET inhibits cell growth of clear cell renal cell carcinoma by regulating miR-373-3p.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with a poor prognosis. LncRNA-LET is a long non-coding RNA (lncRNA) that is down-regulated in ccRCC tissues. However, its role in ccRCC development and progress is unclear. METHODS: LncRNA-LET expression was detected in ccRCC tissues and ccRCC cells using quantitative real-time PCR. The overexpression and knockdown experiments were performed in ccRCC cells and xenograft mouse model to evaluate role of lncRNA-LET. Cell cycle, apoptosis and JC-1 assays were conducted via flow cytometer. The protein levels were measured through western blot analysis and the interaction between lncRNA-LET and miR-373-3p was identified via luciferase reporter assay. RESULTS: LncRNA-LET expression was lower in ccRCC tissues than that in the matched adjacent non-tumor tissues (n = 16). In vitro, lncRNA-LET overexpression induced cell cycle arrest, promoted apoptosis and impaired mitochondrial membrane potential, whereas its knockdown exerted opposite effects. Moreover, we noted that lncRNA-LET may act as a target for oncomiR miR-373-3p. In contrast to lncRNA-LET, miR-373-3p expression was higher in ccRCC tissues. The binding between lncRNA-LET and miR-373-3p was validated. Two downstream targets of miR-373-3p, Dickkopf-1 (DKK1) and tissue inhibitor of metalloproteinase-2 (TIMP2), were positively regulated by lncRNA-LET in ccRCC cells. MiR-373-3p mimics reduced lncRNA-LET-induced up-regulation of DKK1 and TIMP2 levels, and attenuated lncRNA-LET-mediated anti-tumor effects in ccRCC cells. In vivo, lncRNA-LET suppressed the growth of ccRCC xenograft tumors. CONCLUSION: These findings indicate that lncRNA-LET plays a tumor suppressive role in ccRCC by regulating miR-373-3p.