Characterization of distinct circular RNA signatures in solid tumors.

BACKGROUND: Circular RNAs (circRNAs) are differentially expressed between normal and cancerous tissues, contributing to tumor initiation and progression. However, comprehensive landscape of dysregulated circRNAs across cancer types remains unclear. METHODS: In this study, we conducted Ribo-Zero transcriptome sequencing on tumor tissues and their adjacent normal samples including glioblastoma, esophageal squamous cell carcinoma, lung adenocarcinoma, thyroid cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. CIRCexplorer2 was employed to identify circRNAs and dysregulated circRNAs and genes were determined by DESeq2 package. The expression of hsa_circ_0072309 (circLIFR) was measured by reverse transcription and quantitative real-time PCR, and its effect on cell migration was examined by Transwell and wound healing assays. The role of circLIFR in tumor metastasis was evaluated via mouse models of tail-vein injection and spleen injection for lung and liver metastasis, respectively. RESULTS: Distinct circRNA expression signatures were identified among seven types of solid tumors, and the dysregulated circRNAs exhibited cancer-specific expression or shared common expression signatures across cancers. Bioinformatics analyses indicated that aberrant expression of host genes and/or RNA-binding proteins contributed to circRNA dysregulation in cancer. Finally, circLIFR was experimentally validated to be downregulated in six solid tumors and to significantly inhibit cell migration in vitro and tumor metastasis in vivo. CONCLUSIONS: Our results provide a comprehensive landscape of differentially expressed circRNAs in solid tumors and highlight that circRNAs are extensively involved in cancer pathogenesis.

RNA-Seq profiling of circular RNA in human lung adenocarcinoma and squamous cell carcinoma.

Emerging evidences demonstrate that circular RNAs (circRNAs) are abnormally expressed in tumors and could serve as prognostic markers for cancers. However, the expression patterns and clinical implications of circRNAs in non-small cell lung cancer (NSCLC) remain obscure. In this study, we profiled circRNA expressions in 10 pairs of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) after ribosomal RNA-depletion and RNase R digestion to enrich circRNAs. Combining five circRNA computational programs, we found that LUAD and LUSC not only share common expression patterns, but also exhibit distinct circRNA expression signatures. Moreover, the Receiver Operating Characteristic (ROC) curve analysis indicated that hsa_circ_0077837 and hsa_circ_0001821 could serve as potential biomarkers for both LUAD and LUSC, while hsa_circ_0001073 and hsa_circ_0001495 could be diagnostic/subtyping marker for LUAD and LUSC, respectively. Therefore, our findings highlight the important diagnostic potential of circRNAs in NSCLC.

The effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in primary premature ejaculation: a pilot study.

Background: Penile hypersensitivity is not the whole penis, but rather only a part of the penis. Though local anesthetic can prolong intravaginal ejaculation latency time by reducing penile hypersensitivity, the effect on the hypersensitive and nonsensitive areas of penis is still unclear. Aim: The study aimed to explore whether the effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in premature ejaculation. Methods: Penile neurophysiological tests were performed on 290 patients with primary premature ejaculation. The sensory threshold, latency, and amplitude were recorded before and after the topical application of a local anesthetic (lidocaine cream) on the penis. Outcomes: Local anesthetics increased the sensory thresholds of hypersensitive and nonsensitive areas of the penis without difference but only prolonged the latency of the hypersensitive areas. Results: According to the neurophysiological results, 149 of 290 patients with primary premature ejaculation had normal penile sensitivity and 141 had penile hypersensitivity. While penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive, and may be that only a part of the penis is hypersensitive, and we examined the following hypersensitivities: glans hypersensitivity only (14 cases), shaft hypersensitivity only (77 cases), and whole penis hypersensitivity (50 cases). Local anesthetics (lidocaine cream) increased the sensory thresholds of hypersensitive and nonsensitive areas of the penis without difference (P < .001) but only prolonged the latency of the hypersensitive areas (P < .001), and the latency of the nonsensitive areas was not different (P > .05). Clinical Implications: The present discovery implies that it is possible to improve ejaculation by applying local anesthetics externally to the hypersensitive areas of the penis to reduce the afferent local sensory signals, and improve intravaginal ejaculation latency time through accurately decreasing penile sensibility. Strengths & Limitations: This is the first large-sample study to explore the difference of local anesthetics' effects on the hypersensitive and nonsensitive areas of the penis by means of neurophysiological methods in premature ejaculation. Our study exclusively examines alterations in penile evoked potential following electrical stimulation, which may not entirely encompass shifts in penile receptivity during sexual activity. Conclusion: The effects of local anesthetics on the same penis varied with penile sensitivity, and can only prolong the latency of hypersensitive area of the penis. The effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in premature ejaculation.

The sensitivity difference between the glans penis and penile shaft in primary premature ejaculation.

The penis is a vital organ of perception that transmits perceived signals to ejaculation-related centers. The penis consists of the glans penis and penile shaft, which differ considerably in both histology and innervation. This paper aims to investigate whether the glans penis or the penile shaft is the main source of sensory signals from the penis and whether penile hypersensitivity affects the whole organ or only part of it. The thresholds, latencies, and amplitudes of somatosensory evoked potentials (SSEPs) were recorded in 290 individuals with primary premature ejaculation using the glans penis and penile shaft as the sensory areas. The thresholds, latencies, and amplitudes of SSEPs from the glans penis and penile shaft in patients were significantly different (all P < 0.0001). The latency of the glans penis or penile shaft was shorter than average (indicating hypersensitivity) in 141 (48.6%) cases, of which 50 (35.5%) cases were sensitive in both the glans penis and penile shaft, 14 (9.9%) cases were sensitive in the glans penis only, and 77 (54.6%) cases were sensitive in the penile shaft only (P < 0.0001). There are statistical differences in the signals perceived through the glans penis and the penile shaft. Penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive. We classify penile hypersensitivity into three categories, namely, glans penis, penile shaft, and whole-penis hypersensitivity, and we propose the new concept of penile hypersensitive zone.

Magnetic anisotropy and ferroelectric-driven magnetic phase transition in monolayer Cr2Ge2Te6.

Monolayer Cr2Ge2Te6 (ML-CGT) has attracted broad interest due to its novel electronic and magnetic properties. However, there are still controversies on the origin of its intrinsic magnetism. Here, by exploring the electronic and magnetic properties of ML-CGT, we find that the magnetic shape anisotropy (MSA) is vital for establishing the long-range ferromagnetism, except for the contribution from magnetocrystalline anisotropy energy (MCA). Electronic band analysis, combined with atomic- and orbital-resolved magnetic anisotropy from a second-order perturbation theory, further reveals that the MCA of ML-CGT is mainly originated from hybridized Te-py and -pz orbitals. The MSA from magnetic Cr atoms in ML-CGT is larger than MCA, resulting in an in-plane magnetic anisotropy. Noticeably, by constructing a heterostructure (HTS) with ferroelectric Sc2CO2, CGT undergoes an in-plane to out-of-plane spin reorientation via ferroelectric polarization switching, accompanied with an electronic property transition from semiconductor to half-metal. The Curie temperature of CGT/Sc2CO2 HTS can be enhanced to 92.4 K under the ferroelectric polarization, which is much higher than that of pristine ML-CGT (34.7 K). These results not only clarify the contradiction of magnetic mechanism of ML-CGT in previous experimental and theoretical works, but also open the door for realizing nonvolatile magnetic memory devices based on a multifunctional ferromagnetic/ferroelectric HTS.

CircRNAs in lung cancer - Biogenesis, function and clinical implication.

Lung cancer is the leading cause of malignancy-related incidence and mortality worldwide. Molecular mechanisms underlying tumorigenesis and development of lung cancer are still warranted to be elucidated. Previous studies have shown that non-coding RNAs are related to the tumorigenesis and progression of various cancers. However, the expression patterns and clinical implications of circRNAs in lung cancer remain obscure. CircRNAs are a special class of non-coding RNAs with stable covalently closed circular structures, high abundance and tissue/cell/development-specific expression patterns. Thus, circRNAs are a new frontier in lung cancer research. Therefore, in this review, we elucidated the biological function and mechanism of circRNAs, as well as the role of aberrant expressed circRNAs in proliferation, invasion, drug resistance and tumor microenvironment. Furthermore, we discussed that circRNAs may serve as potential clinical biomarkers for the diagnosis, prognosis and treatment of lung cancer.