CircDCAF8 promotes the progression of hepatocellular carcinoma through miR-217/NAP1L1 Axis, and induces angiogenesis and regorafenib resistance via exosome-mediated transfer.

BACKGROUND: Circular RNAs (circRNAs), which are a new type of single-stranded circular RNA, have significant involvement in progression of many diseases, including tumors. Currently, multiple circRNAs have been identified in hepatocellular carcinoma (HCC). Our study aims to investigate the function and mechanism of circDCAF8 in HCC. METHODS: The expression of circDCAF8 (hsa_circ_0014879) in HCC and para-carcinoma tissue samples was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The biological function of circDCAF8 in HCC was confirmed by experiments conducted both in vitro and in vivo. And the relationship between circDCAF8, miR-217 and NAP1L1 was predicted by database and verified using qRT-PCR, RNA-binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Exosomes isolated from HCC cells were utilized to assess the connection of exosomal circDCAF8 with HCC angiogenesis and regorafenib resistance. RESULTS: CircDCAF8 is upregulated in HCC tissues and cell lines, and is linked to an unfavourable prognosis for HCC patients. Functionally, circDCAF8 was proved to facilitate proliferation, migration, invasion and Epithelial-Mesenchymal Transformation (EMT) in HCC cells. Animal examinations also validated the tumor-promoting characteristics of circDCAF8 on HCC. Besides, exosomal circDCAF8 promoted angiogenesis in HUVECs. Mechanistically, circDCAF8 interacted with miR-217 and NAP1L1 was a downstream protein of miR-217. CircDCAF8 promoted NAP1L1 expression by sponging miR-217. In addition, exosomes may transfer circDCAF8 from regorafenib-resistant HCC cells to sensitive cells, where it would confer a resistant phenotype. CONCLUSION: CircDCAF8 facilitates HCC proliferation and metastasis via the miR-217/NAP1L1 axis. Meanwhile, circDCAF8 can promote angiogenesis and drive resistance to regorafenib, making it a viable therapeutic target for HCC patients.

Liquid-phase scanning electron microscopy for single membrane protein imaging.

Liquid-phase electron microscopy is highly desirable for observing biological samples in their native liquid state at high resolution. We developed liquid imaging approaches for biological cells using scanning electron microscopy. Novel approaches included scanning transmission electron imaging using a liquid-cell apparatus (LC-STEM), as well as correlative cathodoluminescence and electron microscopy (CCLEM) imaging. LC-STEM enabled imaging at a ∼2 nm resolution and excellent contrast for the precise recognition of localization, distribution, and configuration of individually labeled membrane proteins on the native cells in solution. CCLEM improved the resolution of fluorescent images down to 10 nm. Liquid SEM technologies will bring unique and wide applications to the study of the structure and function of cells and membrane proteins in their near-native states at the monomolecular level.

Pan-Cancer Analysis of IGF-1 and IGF-1R as Potential Prognostic Biomarkers and Immunotherapy Targets.

AIM: Insulin-like growth factor-1 receptor (IGF-1R) is one of the main members of the tyrosine protein kinase receptor family. This receptor binds insulin-like growth factor-1 (IGF-1) with a high affinity. IGF-1 is a member of a family of proteins involved in mediating growth and development. However, the correlations of IGF-1 and IGF-1R to prognosis and tumor-infiltrating lymphocytes in different cancers remain unclear. METHOD: This research comprehensively analyzed the expression pattern of IGF-1 and IGF-1R and the influence of IGF-1 and IGF-1R on clinical significance in prognosis prediction among 33 types of malignancies using The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) databases. The correlation between IGF-1, IGF-1R, and cancer immunity was explored. RESULTS: IGF-1 and IGF-1R displayed inconsistent gene expression levels among diverse cancer cell lines. Typically, high expression level of IGF-1 and IGF-1R was detected in most malignant tumors. High expression of IGF-1 was closely bound up with the unfavorable overall survival (OS) for patients in BLCA, CHOL, and LAML upon Cox and Kaplan-Meier analyses. While high expression of IGF-1R was closely bound up with the unfavorable overall survival (OS) for patients in BLCA, LIHC, and LUAD. Furthermore, high expression level of IGF-1 and IGF-1R were closely connected with high degrees of tumor infiltrates, including CD4+ T cell, dendritic cells, and macrophages. In addition, we found that IGF-1 was commonly positively correlated with the expression of gene markers including LAIR1, ICOS, CD40LG, CTLA4, CD48, CD28, CD200R1, HAVCR2, and CD86. Whereas, IGF-1R was commonly positively correlated with the expression of gene markers including NRP1 and CD276. More importantly, IGF-1 and IGF-1R expression were correlated with tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT) of different types of cancers. CONCLUSIONS: The impact of high IGF-1 and IGF-1R on prognosis and immune infiltrates differs across cancer types. Anti-IGF-1R therapy may inhibit tumor growth and contribute to immunotherapy in LIHC and KIRC.

Intermediate stage hepatocellular carcinoma: Comparison of the value of inflammation-based scores in predicting progression-free survival of patients receiving transarterial chemoembolization.

CONTEXT AND AIMS: The identification of inflammation-related prognostic heterogeneity in intermediate-stage hepatocellular carcinoma (HCC) can reveal more effective first-line treatments. Our study aimed to compare the intermediate-stage HCC patients' different inflammation-based scores in predicting their progression-free survival (PFS) after transarterial chemoembolization (TACE). MATERIALS AND METHODS: We analyzed retrospectively a total of 128 intermediate-stage HCC patients who received first-line TACE treatment. We used the Cox-proportional hazards modeling to identify the independent prognostic factors. We compared the inflammation-based scores abilities to predict the PFS through the time-dependent receiver operating characteristic curves and area under the curves. RESULTS: The multivariate analysis showed that tumor size and platelet-to-lymphocyte ratio (PLR) were the independent prognostic factors for PFS (P < 0.05). The PLR predicted the intermediate-stage HCC patients' PFS receiving the TACE treatment better than other inflammation-based scores (e.g., the neutrophil-to-lymphocyte ratio, the Glasgow Prognostic Score (GPS), the modified GPS, the Prognostic Index, the Prognostic Nutritional Index, the lymphocyte-to-monocyte ratio, and the systemic immune-inflammation index) (P < 0.05). An easy-to-use novel inflammation score based on tumor size - PLR-size score significantly improved the PFS prediction performance (P < 0.05). CONCLUSIONS: As a first-line treatment, TACE was not well suitable for all intermediate-stage HCC patients, while the PLR was a better inflammation-based score than others. Tumor size should be regarded as an essential variable in affecting intermediate-stage HCC patients' first-line treatment strategies.

Microwave ablation versus sorafenib for intermediate-Stage Hepatocellular carcinoma with transcatheter arterial chemoembolization refractoriness: a propensity score matching analysis.

Purpose: To compared the benefits of sorafenib with microwave ablation (MWA) in intermediate-stage hepatocellular carcinoma (HCC) patients with tumor size ≤7 cm and tumor number ≤5 after Transcatheter Arterial Chemoembolization (TACE) failure.Methods: A retrospective, single-center study was conducted using a one-to-one propensity score matching (PSM) analysis and involved 52 intermediate-stage HCC patients with absence of evidence of intrahepatic vascular invasion and extrahepatic metastasis after TACE failure and underwent treatment with MWA or sorafenib between 2007 and 2019. The overall survival (OS) and progression-free survival (PFS) were evaluated by the Kaplan-Meier method. The factors with OS and PFS were determined by Cox regression.Results: Of the 52 patients included in our study, 30 (57.7%) underwent MWA and 22 (42.3%) received sorafenib. After PSM, 22 pairs were enrolled into different groups for further analysis. Patients in the MWA-group had a significantly longer median PFS than patients in the sorafenib-group on both before (median, 9.3 vs. 2.8 months, p = .001) and after PSM (median, 9.0 vs. 2.8 months, p = .006). They also had a significantly longer median OS than patients in the sorafenib-group on before (median, 48.8 vs. 16.6 months, p = .001) and after PSM (median, Not reached vs. 16.6 months, p = .001). Besides, Cox regression analysis showed that the treatment and age were the independent prognostic factors of OS and PFS (p＜0.05).Conclusions: MWA was superior to sorafenib in improving survival for intermediate-stage hepatocellular carcinoma (HCC) patients with tumor size ≤7 cm and tumor number ≤5 after TACE failure.Key PointsCompared with sorafenib, microwave ablation may be a more reasonable alternative treatment for intermediate-stage hepatocellular carcinoma (HCC) patients with tumor size ≤7 cm and tumor number ≤5 after TACE refractoriness.The treatment (MWA vs sorafenib) and the age of patients were the independent prognostic factors of OS and PFS.

Analyses of fracture line distribution in intra-articular distal radius fractures.

PURPOSE: To assess the association between the fracture line distribution and the location of comminution in intra-articular distal radius fractures by building fracture mapping. PATIENTS/METHODS: Forty cases with intra-articular fractures of distal radius were enrolled in the current prospective clinical study. Fracture lines and comminution zones were identified by reduced three-dimensional computed tomography reconstructions and then graphically superimposed onto a standard template to create two-dimensional fracture maps, followed by the conversion into heating maps. Based on qualitative descriptive fracture mapping analyses, the patterns of intra-articular distal radius fractures were determined. RESULTS: It was observed that the highest fracture line intensity was located as an inverted "T" shape zone in the dorsal aspect of the joint with high incidence of fractures and the prominently intense color in heat mapping. The keystone projected area, the radial styloid process and the metacarpal radial side articular surface were found to be the least involved parts of the fracture. According to the mapping of the number and distribution of fracture lines, a new classification method for intra-articular fractures of the distal radius was redefined. Different surgical approaches and internal fixation techniques were proposed for different types. In this paper, we retrospectively compared the preoperative X-ray findings between different types. Based on the preoperative X-ray prediction, the distal intra-articular radius fractures were classified, so as to develop effective surgical strategies. In this study, a new surgical approach was attempted, but due to the lack of evidence-based evidence, long-term postoperative complications and hand function should be further evaluated. CONCLUSION: This study redefines a new method for the classification of intra-articular fractures of the distal radius, which allows doctors to have a clearer understanding of the characteristics of distal radius fractures. Moreover, the application value in fracture diagnosis is more significant, and the best surgical approach is selected for different types.

Enhanced contrast separation in scanning electron microscopes via a suspended-thin sample approach.

A suspended-thin-sample (STS) approach for signal selection and contrast separation is developed in scanning electron microscopes with commonly used primary beam energies and traditional detectors. Topography contrast, electron channeling contrast and composition contrast are separated and largely enhanced from suspended thin samples of several hundred nanometers in thickness, which is less than the escape depth of backscattered electrons. This imaging technique enables to detect relatively pure secondary electron and elastic backscattered electron singles, whereas suppress multiple inelastic scattering effects. The provided contrast features are different from those of bulk samples, which are largely mixed with inelastic scattering effects. The STS imaging concept and method could be expected to have more applications in distinguishing materials of nanostructures, multilayers, compounds and composites, as well as in SEM-based electron backscatter diffraction, cathodoluminesence, and x-ray microanalysis.

Acute transverse myelitis following vaccination against H1N1 influenza: a case report.

H1N1 vaccination is currently safe, and only rare acceptable side-effects have been reported. Here we describe for the first time a serious adverse event, i.e., acute transverse myelitis, following H1N1 vaccination in China. After the standard treatment with methylprednislone, the patient recovered completely.

Distinguishing crystallographic misorientations of lanthanum zirconate epilayers on nickel substrates by electron backscatter diffraction.

Electron backscatter diffraction (EBSD) was used for distinguishing crystallographic orientations and local lattice misfits of a La(2)Zr(2)O(7) (LZO) buffer layer epitaxially grown on a cube textured Ni-5.%W (Ni-W) substrate for a YBCO superconductor film. Orientation data were obtained from the LZO epilayer using low energy primary electrons (5keV) and from the Ni-W substrate by increasing the voltage to 15keV. In-plane and out-of-plane orientations of the LZO epilayer were revealed with respect to its Ni-W substrate. A strong {100} 〈011〉 rotated-cube texture in the LZO epilayer was formed on the {100} 〈001〉 cube-textured Ni-W substrates. LZO and Ni in-plane crystallographic axes are related by an expected 45° rotation. The step-misorientations and the local misfit strains between the LZO epilayer and the substrate were also analyzed.

Charge compensation by in-situ heating for insulating ceramics in scanning electron microscope.

With a steady temperature increase under high vacuum (HV) in an environmental scanning electronic microscope, we observed charge-free characterization and fine secondary electron (SE) images in focus for insulating ceramics (alumina (Al2O3), aluminum nitride (AlN), pure magnesium silicate (Mg2SiO4)). The sample current I(sc) increased from -8.18 x 10(-13) to 2.76 x 10(-7)A for Al2O3 and -9.28 x 10(-12) to 2.77 x 10(-6)A for AlN with the temperature increased from 298 to 633K. The surface conductance sigma increased from 5.6 x 10(-13) to 5.0 x 10(-11)/Omega for Al2O3 and 1.1 x 10(-12) to 1.0 x 10(-7)/Omega for AlN with the temperature increased from 363 to 593K. The SE image contrast obtained via heating approach in high vacuum with an Everhart-Thornley SE-detector was better than that via conventional approach of electron-ion neutralization in low vacuum (LV) with a gaseous SE-detector. The differences of compensation temperatures for charge effects indicate dielectric and thermal properties, and band structures of insulators. The charge compensation mechanisms of heating approach mainly relate to accelerated release of trapped electrons on insulating surface and to increase of electron emission yield by heating.

Charging compensation of alumina samples by using an oxygen microinjector in the environmental scanning electron microscope.

A gas microinjector system was set up in an environmental scanning electron microscope (ESEM) to create an oxygen atmosphere around the alumina samples for the charging compensation under a pressure between 2 x 10(-5) Pa approximately 2 x 10(-2) Pa. At low pressures, the skirt effect of the electron scattering can be degraded, which results in improvement of the imaging contrast and increase of the signal/noise ratio. The sample current (I(SC)) and the Duane-Hunt limit were measured to evaluate the charging effect.