HNF1A induces glioblastoma by upregulating EPS8 and activating PI3K/AKT signaling pathway.

Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.

USP10 promotes the progression of triple-negative breast cancer by enhancing the stability of TCF4 protein.

Investigating the role of ubiquitin-specific peptidase 10 (USP10) in triple-negative breast cancer (TNBC). Analyzed USP10 expression levels in tumors using public databases. Detected USP10 mRNA and protein levels in cell lines. Examined USP10 expression in tumor tissues from breast cancer patients. Conducted USP10 knockdown experiments and analyzed changes in cell proliferation and metastasis. Confirmed protein-protein interactions with USP10 through mass spectrometry, Co-IP, and fluorescence experiments. Assessed impact of USP10 on transcription factor 4 (TCF4) ubiquitination and validated TCF4's influence on TNBC cells. We initially identified a pronounced overexpression of USP10 across multiple tumor types, including TNBC. Subsequently, we observed a conspicuous upregulation of USP10 expression levels in breast cancer cell lines compared to normal breast epithelial cells. However, upon subsequent depletion of USP10 within cellular contexts, we noted a substantial attenuation of malignant proliferation and metastatic potential in TNBC cells. In subsequent experimental analyses, we elucidated the physical interaction between USP10 and the transcription factor TCF4, whereby USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC. Collectively, this study demonstrates that USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC.

Landscape of Alternative Splicing Events Related to Prognosis and Immune Infiltration in Glioma: A Data Analysis and Basic Verification.

Background: Glioma is a prevalent primary brain cancer with high invasiveness and typical local diffuse infiltration. Alternative splicing (AS), as a pervasive transcriptional regulatory mechanism, amplifies the coding capacity of the genome and promotes the progression of malignancies. This study was aimed at identifying AS events and novel biomarkers associated with survival for glioma. Methods: RNA splicing patterns were collected from The Cancer Genome Atlas SpliceSeq database, followed by calculating the percentage of splicing index. Expression profiles and related clinical information of glioma were integrated based on the UCSC Xena database. The AS events in glioma were further analyzed, and glioma prognosis-related splicing factors were identified with the use of bioinformatics analysis and laboratory techniques. Further immune infiltration analysis was performed. Results: Altogether, 9028 AS events were discovered. Upon univariate Cox analysis, 425 AS events were found to be related to the survival of patients with glioma, and 42 AS events were further screened to construct the final prognostic model (area under the curve = 0.974). Additionally, decreased expression of the splicing factors including Neuro-Oncological Ventral Antigen 1 (NOVA1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), heterogeneous nuclear ribonucleoprotein L-like protein (HNRNPLL), and RNA-Binding Motif Protein 4 (RBM4) contributed to the poor survival in glioma. The immune infiltration analysis demonstrated that AS events were related to the proportion of immune cells infiltrating in glioma. Conclusions: It is of great value for comprehensive consideration of AS events, splicing networks, and related molecular subtype clusters in revealing the underlying mechanism and immune microenvironment remodeling for glioma, which provides clues for the further verification of related therapeutic targets.

Plasma miRNA-506 as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma.

BACKGROUND MicroRNAs (miRNAs) are responsible for regulating proliferation, differentiation, apoptosis, invasion, and metastasis in tumor cells. miRNA-506 is abnormally expressed in multiple tumors, indicating that it might be oncogenic or tumor-suppressive. However, little is known about the association between miRNA-506 expression and esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS We examined the expression of miRNA-506 in the plasma of ESCC patients using quantitative real-time polymerase chain reaction (qRT-PCR) to determine the association between miRNA-506 expression and clinicopathological features of ESCC. ROC curves were produced for ESCC diagnosis by plasma miRNA-506 and the area under curve was calculated to explore its diagnostic value. RESULTS Average miRNA-506 expression levels were remarkably higher in the plasma of ESCC patients than in healthy volunteers (P<0.001). The expression of miRNA-506 in the plasma was closely associated with lymph node status (P=0.004), TNM stage (P=0.031), and tumor length (P<0.001). According to ROC curves, the area under the curve for plasma miRNA-506 was 0.835, indicating statistical significance for ESCC diagnosis by plasma miRNA-506 (P<0.001). Kaplan-Meier analysis showed that patients with high miRNA-506 expression had significantly shorter survival time than those with low miRNA-506 expression. Cox regression analysis demonstrated that T stage, N stage, tumor length, and miRNA-506 expression levels were significantly correlated with prognosis in ESCC patients. CONCLUSIONS miRNA-506 can serve as an important molecular marker for diagnosis and prognostic prediction of ESCC.

Detection of Circulating Tumor Cells by Fluorescent Immunohistochemistry in Patients with Esophageal Squamous Cell Carcinoma: Potential Clinical Applications.

BACKGROUND Circulating tumor cells (CTCs) are tumor cells that leave the primary tumor site and enter the bloodstream, where they can spread to other organs; they are very important in the diagnosis, treatment, and prognosis of malignant tumors. However, few studies have investigated CTCs in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the CTCs in blood of ESCC patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS CTCs were acquired by a negative enrichment method that used magnetic activated cell sorting (MACSTM). Fluorescent immunohistochemistry (IHC) was used to identify the CTCs. Then, the positive CTC patients with ESCC were analyzed, after which the relationship between CTCs and clinicopathologic features was evaluated. RESULTS In the present study, 62 out of 140 (44.3%) patients with ESCC were positive for CTCs. The positive rate of CTCs was significantly related with stage of ESCC patients (P=0.013). However, there was no relationship between CTC status and age, sex, smoking tumor history, tumor location, differentiation of tumor, lymphatic invasion, or lymph venous invasion (P>0.05). Kaplan-Meier analysis showed that patients positive for CTCs had significantly shorter survival time than patients negative for CTCs. Multivariate analysis demonstrated that stage and CTC status were significant prognostic factors for patients with ESCC. CONCLUSIONS CTCs positivity is an independent prognostic biomarker that indicates a worse prognosis for patients with ESCC.

[The Enhancement Research of Magnetic Stirring with Laser Irradiation Aqueous Solution on ICP Source Radiation].

At present, the way to introduce the sample into the inductively coupled plasma atomic emission spectrometry (ICP-AES) light source is still in the form of solution. In order to improve the treatment effect of the aqueous solution and change its physical properties, the surface tension and viscosity under different experimental conditions were measured with magnetic stirring combined with laser irradiation. . The treated samples were introduced into the inductively coupled plasma (ICP) to measure the spectral line intensity, signal-to-background ratio, excitation temperature and electron density emitted by the ICP source. The experimental results showed that: when the magnetic stirrer rotate speed was 1 197 r·min-1, the laser power density was 0.227 6 W·cm-2 and irradiation for 15 min, the surface tension and viscosity of the solution were decreased by 27.85% and 8.66% respectively than those of the untreated solution. As to the element spectral lines of As 188.980 nm, Cd 214.439 nm, Cr 267.716 nm, Cu 324.754 nm, Hg 253.652 nm and Pb 220.353nm: the intensity was enhanced 32.07%, 65.36%, 18.27%, 32.29%, 19.38% and 54.28%; the signal-to-background ratio increased by 25.13%, 60.97%, 18.18%, 27.69%, 21.11% and 48.93%, respectively. The enhancement of the plasma radiation was explained to a certain extent by measuring the excitation temperature and electron density of the plasma. The processing method of the aqueous solution can effectively improve the spectral intensity and signal-to-background ratio of the ICP. Compared with the laser irradiation aqueous solution separately, this method significantly shortened the processing time, improve the efficiency. This method is simple, with no secondary pollution in the treatment of the sample solution, convenient popularization and use.

[Enhancement effect of double-beam laser processed aqueous solution on ICP emission spectrum].

In order to change the physical properties of aqueous solution and improve the radiation intensity of the ICP emission spectrum, the effects of different laser power density and irradiation time on the surface tension and viscosity of aqueous solution were investigated by using near infrared laser at 976 nm and CO2 laser at 10. 6 µm to irradiate aqueous solution orthogonally, then the enhancement of ICP spectral intensity with processed solution was discussed. The results showed that the surface tension and viscosity of aqueous solution reduced by 42. 13% and 14. 03% compared with the untreated, and the atomization efficiency increased by 51.26% at the laser power density 0. 265 7 W . cm-2 of 976 nm and 0. 206 9 W . cm-2 of CO2 laser with 40 min irradiation time. With the optimized aqueous solution introduced into the ICP source, the spectral line intensity of sample elements As, Cd, Cr, Hg and Pb was enhanced by 46.29%, 94. 65%, 30. 76%, 33.07% and 94. 58% compared to the untreated aqueous solution, while the signal-to-background ratio increased by 43. 84%, 85. 35%, 28. 71%, 34. 37% and 90. 91%, respectively. Plasma temperature and electron density also increased by 5. 94% and 1. 18% respectively. It is obvious that the method of double-beam laser orthogonal irradiation on solution can reduce the surface tension and viscosity of aqueous solution significantly, and raise the radiationintensity of ICP source, and will provide a better condition for detecting the trace heavy metal elements in water samples.

[Study of self-absorption effect on laser-induced metal plasma].

In order to reduce the effect of the spectral line self-absorption on the analysis result in the laser induced plasma and enhance the qualities of spectrum, the spectral information was recorded by the spectral analysis system consisting of a modular multifunctional grating spectrometer and a CCD detector etc., and the electron temperature and electron density of the plasma were measured with the spectroscopic methods. A plane mirror device was used to constraint the laser plasma, and a reasonable explanation was got through comparing the linear evolution under different experimental conditions and measuring the temperature, electronic density and sample evaporation. The result shows that when an appropriate plane mirror device was used to constraint the laser plasma, the axial temperature of the plasma increased and the radial distribution of the plasma becomes uniform; the electron density increased dramatically; however, obviously sample evaporation decreased, which may be the reasons for being able to effectively reduce the level of self-absorption spectral lines. Therefore, the plane mirror device could reduce the self-absorption effect in the laser-induced plasma. This makes it possible to choose a sensitive line that acts as analysis line in the quantitative analysis of the major elements. In other words, this promotes the measurement precision in the laser-induced break-down spectroscopy.

[Enhancement effect of laser-processed aqueous solution on ICP source radiation].

To enhance the intensity of inductively coupled plasma-atomic emission spectrum and improve the detection level of trace heavy metal elements, the surface tension and viscosity of the aqueous solution processed by near-infrared laser at wave-length of 976 nm were studied in the present paper. The influences of the treated solution on the spectral line intensity and signal-to-background ratio of the ICP source were observed. The results showed that when the laser irradiation time was 60 min and the power density was 0.329 6 W x cm(-2), the surface tension and viscosity of the solution decreased by 36.73% and 9.73% respectively compared to the untreated solution. Under the optimum conditions, the aqueous solution treated by the laser irradiation was introduced into the ICP source. By measuring the intensity of emission spectrum of the sample elements, the spectral line intensity of Cd, Cr, Cu, Hg, and Pb was enhanced by about 73.52%, 22.97%, 33.86%, 24.44% and 65.59% compared to the untreated solution, while the signal-to-background ratio increased by 76.03%, 21.74%, 32.17%, 22.68% and 65.32%, respectively. Spectral line intensity and signal-to-background ratio of the ICP source were significantly improved so that the foundation was established for reducing the analysis detection limits. Further more, the surface tension and viscosity of the processed aqueous solution remain the same within 30 minutes standing time with the stable physical properties. This simple and easy method of laser-processed aqueous solution helps improve the detection capabilities of ICP spectrometry.

Relationships between genetic polymorphisms in inflammation-related factor gene and the pathogenesis of nasopharyngeal cancer.

Our study aims to discuss the association between inflammation-related factors such as single nucleotide polymorphisms (SNPs) with susceptibility and recurrence in nasopharyngeal carcinoma. We used Taqman real-time polymerase chain reaction (PCR) to characterize the genetic variation of five SNPs in 194 nasopharyngeal carcinoma patients and 231 healthy subjects. All statistical analysis is performed with statistical product and service solutions v13.0; odds ratio (OR) value and 95 % confidence interval (CI) were calculated. There is no relationship between TGFß1 -869 T/C, IL-6 -634C/G, TGFß1 -509C/T, IL1 -511C/T and nasopharyngeal carcinoma susceptibility. Both single factor and multiple factors analysis showed that IL1a -889 T/T genotype is significantly associated with nasopharyngeal carcinoma in decreasing the risk of nasopharyngeal carcinoma. A highly significant association was found between IL1a -889 T/T genotype and protective genotype as defined by various pathological types. This is more obvious in the protective genotype of the non-keratin-type squamous carcinoma undifferentiated type. We also discovered that genotype G/G and C/G + G/G of IL6 -634 gene are associated with reduced recurrence of nasopharyngeal carcinoma. IL1a -889 gene polymorphism and susceptibility is related to nasopharyngeal carcinoma and can potentially decrease the risk of nasopharyngeal carcinoma in the Han Chinese population in north China. IL1-889 TT genotype is protective genotype for nasopharyngeal carcinoma. We have provided evidence that the GG genotype of the IL6 -634 gene is associated with recurrent risk of nasopharyngeal carcinoma. The G allele is the protective gene of nasopharyngeal carcinoma recurrence.

[Synthesis and upconversion luminescence properties of BaIn6 Y2O13 : Yb3+, Er3+].

BaIn6 Y2O13 phosphors with different doping concentrations of Yb3+ and Er3+ were prepared via the high temperature solid-state reaction method. XRD data showed that BaIn6 Y2O13 phosphors belong to hexagonal system and the introduction of doping agent Yb3+ and Er3+ did not change the lattice structure of the host. The upconversion emission spectrum and power were measured by 971 nm LD laser with different excitation powers and the energy efficiencies of the samples were calculated. The obtained data showed that the ratio of green power to red power kept decreasing with the increase in doping agent concentration when the excitation density remains constant, increasing with the increase in the excitation density at the same concentration of doping agent. The analyses revealed that the former was attributed to the increasing cross relaxation between Er3+ ions, while the latter came from the raise of the energy transfer between Yb3+ and Er3+ ions and the excited state absorption of Er3+ ions due to the higher excitation density. With the increase in the excitation density, at the beginning the green luminescence power was proportional to the square of the excitation power, which agrees with the reported result. The maximum values of the fluorescence efficiencies of the samples were obtained as 0.38% (the doping concentrations of Yb3+ and Er3+ are 3%, 1%)and 0.06% (the doping concentrations of Yb3+ and Er3+ are 9%, 3%). It can be attributed to the long lifetime of 4 I13/2 energy level so it can gather a large number of electrons and reduce the population of ground state, resulting in lower pump efficiency.

[Preparation and up-conversion luminescence dynamic process of Yb3+/ Er3+ co-doped BaGd2ZnO5].

Yb3+/Er3+ co-doped BaGd2 ZnO5 phosphors were prepared by using the sol-gel method. The up-conversion luminescence powers and efficiencies were measured under different excitation densities. The obtained data showed that the green luminescence power was proportional to the second-order of that of the excitation power under the lower excitation density and linearly in the higher one. The up-conversion mechanism under different excitation power was described by a rate equation. Yb3+/ Er3+ co-doped BaGd2 ZnO5 was excited by 971 nm LD laser with a square wave signal modulation and the rise and decay processes of green up-conversion luminescence were measured. In a low excitation condition, the rate equation of the energy level 4S3/2 for Er3+ ions was used to fit the green rise and decay processes in order to fix the relevant parameters, and confirm that the population of 4S3/2 energy level of Er3+ ion mainly came from the energy transfer from Yb3+ to Er3+.

[Progress in the method of laser ablation solid sample introduction to inductively coupled plasma source].

On the basis of consulting the home and abroad literatures in recent years, the research progress in the method of laser ablation solid sampling to the inductively coupled plasma source and its application in the analysis of material compositions are described. The present paper emphatically reviewed the influence of the laser-beam properties (output wavelength, pulse duration, repetition frequency, energy density) and atmosphere gases (helium and argon) on the sample ablation process, and discussed the functions of the laser ablation chamber, aerosol transmission pipelines, and sample introduction devices improved in the process of the evaporated material transferring to the inductively coupled plasma source. Getting small uniform aerosol particles and transporting the ablated materials to the inductively coupled plasma source efficiently and steadily are the key points to make laser ablation solid sampling technique more perfect, and the elements fractionation and evaporation deposition are important influence factors for the analysis performance. As a practical example, the application of laser ablation solid sampling inductively coupled plasma atomic emission spectrometry/mass spectrometry in the analysis of metal, glass, organic substance, and other samples was also discussed. The accuracy, precision, detection limits, and sensitivity of the analysis method were briefly reviewed.

[Study of enhancement effect of laser-induced crater on plasma radiation].

Single pulses exported from high-energy neodymium glass laser were used to act on the same position of soil sample surface repeatedly, and the plasma emission spectra generated from sequential laser pulse action were collected by spectral recording system. The experimental results show that the laser-induced soil plasma radiation was enhanced continuously under the confinement effect of the crater walls, and the line intensities and signal-to-background ratios both had different improvements along with increasing the number of acting pulses. The photographs of the plasma image and crater appearance were taken to study the plasma shape, laser-induced crater appearance, and the mass of the ablated sample. The internal mechanism behind that laser-induced crater enhanced plasma radiation was researched. Under the sequential laser pulse action, the forming plasma as a result enlarges gradually first, leading to distortion at the trail of plasma plume, and then, its volume diminishes slowly. And also, the color of the plasma changes from buff to white gradually, which implies that the temperature increases constantly. The laser-induced crater had a regular shape, that is, the diameter increased from its bottom to top gradually, thus forming a taper. The mass of the laser-ablated substance descends along with increasing the amount of action pulse. Atomization degree of vaporized substance was improved in virtue of the crater confinement effect, Fresnel absorption produced from the crater walls reflection, and the inverse bremsstrahlung, and the plasma radiation intensity was enhanced as a result.

[Optics heterodyne detection of the autoionization state of barium].

The autoionization state of barium was observed by optics heterodyne between three-photon resonant nondegenerated six-wave mixing (NSWM) and two-photon resonant nondegenerated four-wave mixing (NFWM). In this way, optics heterodyne spectrum of 6p(3/2) 19d autoionization state of barium was measured. The suppression and enhancement of the NFWM signal was observed which was caused by the quantum interference between NFWM and NSWM. Our method is a pure nonlinear optic technique. It has the advantages of excellent spatial signal resolution and simple optical alignment. Here two-photon resonant NFWM is used as local oscillation, while three-photon resonant NSWM signal is used as signal beam. Detection of autoionization states of Ba was achieved by changing the frequency of signal beam. The phase matching condition of this technique is not so stringent and can be achieved over a very wide frequency range, which is very difficult in the general six-wave mixing. Furthermore, the signal is coherent light. Optics heterodyne spectrum is a Doppler-free spectroscopy when the incident lasers have narrow bandwidths.