RNF125 is a ubiquitin-protein ligase that promotes p53 degradation.

BACKGROUND/AIMS: Although early studies show that Mdm2 is the primary E3 ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data suggests that p53 ubiquitination and degradation are more complex than once thought. Here, we investigated the role of RNF125, a non-Mdm2 ubiquitin-protein ligase, in the regulation of p53. METHODS AND RESULTS: RNF125 physically interacted with p53 in exogenous/endogenous co-immunoprecipitation (IP) and GST-pull down assay, and a C72/75A mutation of RNF125 did not interfere with this interaction. Expression of RNF125 decreased the level of p53 in a dose-dependent manner, whereas knockdown of RNF125 by RNA interference increased the level of p53. As shown by Western blotting and ubiquitin assay, RNF125 ubiquitinated p53 and targeted it for proteasome degradation. Furthermore, RNF125 repressed p53 functions including p53-dependent transactivation and growth inhibition. CONCLUSION: Our data suggest that RNF125 negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation.

(K, Na, Li)(Nb, Ta)O3:Mn lead-free single crystal with high piezoelectric properties.

Lead-free single crystal, (K, Na, Li)(Nb, Ta)O3:Mn, was successfully grown using top-seeded solution growth method. Complete matrix of dielectric, piezoelectric and elastic constants for [001]C poled single crystal was determined. The piezoelectric coefficient d33 measured by the resonance method was 545 pC/N, which is almost three times that of its ceramic counterpart. The values measured by the Berlincourt meter ( [Formula: see text]) and strain-field curve ( [Formula: see text]) were even higher. The differences were assumed to relate with the different extrinsic contributions of domain wall vibration and domain wall translation during the measurements by different approaches, where the intrinsic contribution (on the order of 539 pm/V) was supposed to be the same. The crystal has ultrahigh electromechanical coupling factor (k33 ~ 95%) and high ultrasound velocity, which make it promising for high frequency medical transducer applications.

Genetic association between cyclin D1 polymorphism and breast cancer susceptibility.

Cyclin D1 polymorphism has been reported to be associated with risk of breast cancer, but the published studies have yielded controversial results. This study was undertaken to derive a precise risk estimate for the cyclin D1 polymorphism associated with breast cancer risk. We performed a search of EMBASE, PubMed, and Web of Science. In total, data from 18 publications were pooled and the association was assessed by odds ratios (ORs) with 95 % confidence intervals (CIs). This analysis showed that there was no obvious association between the cyclin D1 polymorphism and breast cancer risk in any of the analyzed genetic model. We found the same negative association in stratified analyses by ethnicity, source of controls, and sample size. Our meta-analysis provides an estimate that the presence of cyclin D1 polymorphism may not confer susceptibility to breast cancer.

ERCC1 and BRCA1 mRNA expressions are associated with clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy.

We conducted a perspective study to investigate whether the expression of excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group G (XPG), breast cancer 1 (BRCA1), and ribonucleotide reductase M1 (RRM1) is correlated with clinical outcome of non-small cell lung cancer (NSCLC). Patients with histologically confirmed inoperable stages IIIB and IV NSCLC were collected and followed up until January 2012. Relative cDNA quantification for ERCC1, XPG, BRCA1, and RRM1 was performed using a fluorescence-based, real-time detection method. Cox regression analysis indicated that a high level of ERCC1 was associated with shorter overall survival (OS) and progression-free survival (PFS) times when compared with low expression, with adjusted hazard ratios (HRs) (95% confidence interval (CI)) of 2.25 (1.18-4.39) and 2.63 (1.33-5.25), respectively. High expression of BRCA1 was correlated with shorter OS and PFS times when compared with low expression, and the adjusted HRs (95% CI) were 3.29 (1.72-6.39) and 5.94 (2.80-13.06), respectively. Moreover, we found a significant correlation between BRCA1 expression and age (χ(2) = 4.14, P = 0.04) and stage (χ(2) = 5.26, P = 0.02). Our results suggest that ERCC1 and BRCA1 mRNA expressions are associated with PFS and OS in advanced NSCLC patients treated with platinum-based chemotherapy.

Flexible Sensor for Real-Time Monitoring of Motion Artifacts in Magnetic Resonance Imaging.

In recent years, magnetic resonance imaging has been widely used in the medical field. During the scan, if the human body moves, then there will be motion artifacts on the scan image, which will interfere with the diagnosis and only be found after the end of the scan sequence, resulting in a waste of manpower and resources. However, there is a lack of technology that halts scanning once motion artifacts arise. Here, we designed a real-time monitoring sensor (RMS) to dynamically perceive the movement of the human body and to pause in time when the movement exceeds a certain amplitude. The sensor has an array structure that can accurately sense the position of the human body in real time. The selection of the RMS ensures that there is no additional interference with the scanning results. Based on this design, the RMS can achieve the monitoring function of motion artifact generation.

Probing Hyperbolic Shear Polaritons in ß-Ga2O3 Nanostructures Using STEM-EELS.

Phonon polaritons, quasiparticles arising from strong coupling between electromagnetic waves and optical phonons, have potential for applications in subdiffraction imaging, sensing, thermal conduction enhancement, and spectroscopy signal enhancement. A new class of phonon polaritons in low-symmetry monoclinic crystals, hyperbolic shear polaritons (HShPs), have been verified recently in ß-Ga2O3 by free electron laser (FEL) measurements. However, detailed behaviors of HShPs in ß-Ga2O3 nanostructures still remain unknown. Here, by using monochromatic electron energy loss spectroscopy in conjunction with scanning transmission electron microscopy, the experimental observation of multiple HShPs in ß-Ga2O3 in the mid-infrared (MIR) and far-infrared (FIR) ranges is reported. HShPs in various ß-Ga2O3 nanorods and a ß-Ga2O3 nanodisk are excited. The frequency-dependent rotation and shear effect of HShPs reflect on the distribution of EELS signals. The propagation and reflection of HShPs in nanostructures are clarified by simulations of electric field distribution. These findings suggest that, with its tunable broad spectral HShPs, ß-Ga2O3 is an excellent candidate for nanophotonic applications.

The Clinicopathological Significance and Prognostic Value of Androgen Receptor in Endometrial Carcinoma: A Meta-Analysis.

Background: The role of androgen receptor (AR) in evaluating the prognosis of patients with endometrial cancer (EC) remains controversial. Here, we performed a meta-analysis to assess whether AR expression improves EC survival outcomes. Methods: We searched related articles published before August 2021 in PubMed, EMBASE, and Web of Science. The association between AR expression and patient prognosis was estimated with hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs). The review is registered on PROSPERO, registration number: CRD42021268591. Results: Ten studies including 1,485 patients were enrolled in the meta-analysis. The results showed that AR expression in EC tissues was associated with a better survival in crude analyses (HR = 1.63, 95% CI = 1.32-2.02, P < 0.001). However, no significant relation was found after the adjustment of the confounding factors (HR = 1.68, 95% CI = 0.75-3.75, P = 0.205). In subgroup analyses, grade 1-2 disease, stage I-II disease, negative lymph node status, and lack of the lymphovascular invasion were more common in AR-positive groups (OR = 0.47, 0.48, 0.37, and 0.57; 95% CI = 0.45-0.62, 0.35-0.65, 0.24-0.56, and 0.37-0.89). Furthermore, AR expression was more common in endometrioid cancers (OR = 2.39, 95% CI = 1.79-3.20). Conclusions: AR expression is significantly associated favorable characteristics including low-grade disease, early-stage disease, negative lymph node status, and lack of the lymphovascular invasion and a specific histology-endometrioid cancer. However, AR is not an independent prognostic factor.

Derivation, Comprehensive Analysis, and Assay Validation of a Pyroptosis-Related lncRNA Prognostic Signature in Patients With Ovarian Cancer.

Background: Pyroptosis is regulated by long non-coding RNAs (lncRNAs) in ovarian cancer (OC). Therefore, a comprehensive analysis of pyroptosis-related lncRNAs (PRLs) in OC is crucial for developing therapeutic strategies and survival prediction. Methods: Based on public database raw data, mutations in the landscape of pyroptosis-related genes (PRGs) in patients with OC were investigated thoroughly. PRLs were identified by calculating Pearson correlation coefficients. Cox and LASSO regression analyses were performed on PRLs to screen for lncRNAs participating in the risk signature. Furthermore, receiver operating characteristic (ROC) curves, Kaplan-Meier survival analyses, decision curve analysis (DCA) curves, and calibration curves were used to confirm the clinical benefits. To assess the ability of the risk signature to independently predict prognosis, it was included in a Cox regression analysis with clinicopathological parameters. Two nomograms were constructed to facilitate clinical application. In addition, potential biological functions of the risk signature were investigated using gene function annotation. Subsequently, immune-related landscapes and BRCA1/2 mutations were compared in different risk groups using diverse bioinformatics algorithms. Finally, we conducted a meta-analysis and in-vitro assays on alternative lncRNAs. Results: A total of 374 patients with OC were randomized into training and validation cohorts (7:3). A total of 250 PRLs were selected from all the lncRNAs. Subsequently, a risk signature (DICER1-AS1, MIR600HG, AC083880.1, AC109322.1, AC007991.4, IL6R-AS1, AL365361.1, and AC022098.2) was constructed to distinguish the risk of patient survival. The ROC curve, K-M analysis, DCA curve, and calibration curve indicated excellent predictive performance for determining overall survival (OS) based on the risk signature in each cohort (p < 0.05). The Cox regression analysis indicated that the risk signature was an independent prognostic factor for OS (p < 0.05). Moreover, significant differences in the immune response and BRCA1 mutations were identified in different groups distinguished by the risk signature (p < 0.05). Interestingly, in-vitro assays showed that an alternative lncRNA (DICER1-AS1) could promote OC cell proliferation. Conclusion: The PRL risk signature could independently predict overall survival and guide treatment in patients with OC.

[Human parasitology teaching in the 21st century].

Multimedia techniques were applied in parasitological teaching and experimental practices. In order to strengthen the practical ability of the undergraduate students, reform was conducted including a prioritization of the teaching content, use of series micro-slides and video show, etc.

Effects of silencing the ATP-binding cassette protein E1 gene by electroporation on the proliferation and migration of EC109 human esophageal cancer cells.

In the present study, the gene expression of ATP-binding cassette protein E1 (ABCE1) in the EC109 human esophageal cancer cell line was silenced using electroporation to examine the effect if the ABCE1 gene on the growth migration and cell cycle of cancer cells. The small interference (si)RNA sequence of ABCE1 was designed and synthesized to transfect the EC109 cells by electroporation. The mRNA and protein expression levels of ABCE1 were then detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The analysis of the cell cycle and apoptosis was performed using flow cytometry. The effect of silencing the ABCE1 gene on the proliferation, migration and invasive ability of the EC109 human esophageal cancer cells were assessed using a Cell counting kit-8 (CCK-8) and with proliferation, wound-healing and cell invasion assays. The mRNA and protein expression levels of ABCE1 were significantly lower in the experimental group compared with the control group (P<0.05). The apoptotic rate of the experimental group was markedly higher than the control group and blank group (P<0.01). The CCK-8 proliferation assay revealed that, compared with the control and blank groups, the proliferation of the EC109 cells in the experimental group was significantly inhibited (P<0.05). The wound healing assay revealed that the migration capacity of the cells in the experimental group was significantly decreased (P<0.05). The Transwell chamber assay demonstrated that the invasive ability of the EC109 cells in the experimental group was significantly decreased (P<0.01). These results revealed that ABCE1 is closely associated with cell proliferation, invasion and migration in esophageal cancer and silencing the ABCE1 gene by electroporation can significantly reduce the proliferation, invasion and migration capacity of EC109 cells in vitro.

Temperature dependence of dielectric and electromechanical properties of (K,Na)(Nb,Ta)O3 single crystal and corresponding domain structure evolution.

Domain structures and their evolution with temperature in the [001] C oriented (K,Na)(Nb,Ta)O3 (KNNT) single crystal have been studied before and after poling by polarizing light microscopy. The results indicate that the KNNT crystal is difficult to be completely poled by the room temperature poling process. The domain structure is rather stable in the orthorhombic phase, but exhibits substantial changes near the phase transition temperatures TO-T and TC. Narrower stripe domains are formed during both the orthorhombic-tetragonal and tetragonal-cubic phase transition processes, no intermediate phases were found during the phase transitions. The temperature dependence of the dielectric and piezoelectric properties were measured, and the influence of domain structures on the dielectric and electromechanical properties were quantified.

The role of the rs1544410 polymorphism of vitamin D receptor gene in breast cancer susceptibility.

This study was devised to investigate the genetic effect modification of the BsmI polymorphism associated with the susceptibility to breast cancer. Case-control studies of the BsmI polymorphism and breast cancer were searched. A total of 17 eligible publications were included in our final analysis. Pooled ORs and 95 % CIs were obtained by means of fixed effects model. The general and stratified analyses according to ethnicity showed that the association between the BsmI polymorphism and the risk of breast cancer was not statistically significant. However, the subgroup of the hospital-based studies was found to confer protection against the disease (ORBBvs.bb = 0.83, 95 % CI = 0.71-0.97, P h = 0.571; OR BBvs.Bb+bb = 0.86, 95 % CI = 0.74-1.00, P h = 0.903; OR allele B vs. allele b = 0.92, 95 % CI = 0.86-0.99, P h = 0.337). Our results suggested that the presence of the BsmI polymorphism may contribute to the susceptibility of breast cancer. It is necessary that future large-scale studies should be conducted to further confirm the association between the BsmI polymorphism and breast cancer risk.

Complete set of material constants of single domain (K, Na)(Nb, Ta)O3 single crystal and their orientation dependence.

A self-consistent complete set of dielectric, piezoelectric, and elastic constants for single domain Ta modified (K, Na)NbO3 (KNN) crystal was determined. This full set constant for single domain KNN-based crystals allowed the prediction of orientation dependence of the longitudinal dielectric, piezoelectric, elastic coefficients, and electromechanical coupling factors. The maximum piezoelectric and electromechanical properties were found to exist near [001] C . In addition, material constants of [001] C poled domain engineered single crystal with 4 mm symmetry were experimentally measured and compared with the calculated values. Based on this, extrinsic contribution to the piezoelectricity was estimated to be ∼20%.

Growth and properties of Li, Ta modified (K,Na)NbO3 lead-free piezoelectric single crystals.

Li, Ta modified (K,Na)NbO3 single crystals with the size of 18 mm × 18 mm × 10 mm were successfully grown by top-seeded solution growth method, with orthorhombic-tetragonal phase transition temperature ~79 °C and Curie temperature ~276 °C. The electromechanical coupling factors k33 and kt were found to be ~88% and ~65%, respectively. The piezoelectric coefficient d33 for the [001]c poled crystals reached 255 pC/N. In addition, the electromechanical coupling factor exhibited high stability over the temperature range of -50 °C to 70 °C, making these lead free crystals good candidates for electromechanical applications.

miR-218 is downregulated and directly targets SH3GL1 in childhood medulloblastoma.

An increasing number of studies have suggested that microRNAs (miRNAs) are aberrantly expressed in numerous types of tumors and that a deregulation in miRNA expression may lead to carcinogenesis. Although miR­218 has been demonstrated to be downregulated in several types of cancer, including medulloblastoma (MB), its involvement in MB is unclear. In the present study, the expression of miR­218 and SH3GL1 were assessed in four MB cell lines and normal cerebellum by qPCR. The ectopic expression of miR­218 induced by lentiviral transfection in MB cells on proliferation was evaluated by MTT assay, and cell migration and invasion were determined by transwell assays. Analysis of the target protein expression and related protein expression was determined by western blot analysis. The targeting of SH3GL1 by miR­218 was identified using a luciferase reporter assay. The results demonstrated that miR­218 was significantly downregulated in MB cell lines. MiR­218 significantly inhibited SH3GL1 mRNA and protein expression and reduced the luciferase activity of a SH3GL1 3' untranslated region­based reporter. Furthermore, overexpression of miR­218 induced by transfection with lentivirus significantly suppressed MB cell growth, migration and invasion in vitro. Small interfering RNA­mediated SH3GL1 downregulation partially phenocopied the effect of miR­218 overexpression in the MB cell lines. The results indicated that miR­218 was significantly downregulated in MB cancer cell lines. Furthermore, miR­218 functioned as a tumor suppressor by regulating SH3GL1 expression in MB cancer cells.

Complete set of elastic, dielectric, and piezoelectric constants of [011]C poled rhombohedral Pb(In0.5Nb0.5)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3:Mn single crystals.

Mn modified rhombohedral Pb(In0.5Nb0.5)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 (PIN-PMN-PT:Mn) single crystals poled along [011]C crystallographic direction exhibit a "2R" engineered domain configuration, with macroscopic mm2 symmetry. The complete sets of material constants were determined using combined resonance and ultrasonic methods, and compared to [001]C poled PIN-PMN-PT:Mn crystals. The thickness shear piezoelectric coefficient d15 and electromechanical coupling factor k15 were found to be on the order of ∼3000 pC/N and 0.92, respectively, with longitudinal piezoelectric coefficient d33 and coupling factor k33 being on the order of ∼1050 pC/N and 0.90. Of particular importance is that PIN-PMN-PT:Mn single crystals exhibited high mechanical quality factor Q33 ∼ 1000, comparable to "hard" PZT8 ceramics, which can also be confirmed by the low extrinsic contribution, being ≤2% from the Rayleigh analysis.

Elastic, dielectric and piezoelectric characterization of single domain PIN-PMN-PT: Mn crystals.

Mn modified 0.26Pb(In(1/2)Nb(1/2))O(3)-0.42Pb(Mg(1/3)Nb(2/3))O(3)-0.32PbTiO(3) (PIN-PMN-PT:Mn) single crystals with orthorhombic perovskite crystal structure were polarized along [011] direction, resulting in the single domain state "1O." The complete set of material constants was determined using the combined resonance and ultrasonic methods. The thickness shear piezoelectric coefficient d(15) and electromechanical coupling factor k(15) were found to be on the order of 3100 pC/N and 94%, respectively, much higher than longitudinal d(33) ∼ 270 pC/N and k(33) ∼ 70%. Using the single domain data, the rotated value of d(33)* along [001] direction was found to be 1230 pC/N, in agreement with the experimentally determined d(33) value of 1370 pC/N, conferring extrinsic contributions being about 10%, which was also confirmed using the Rayleigh analysis. In addition, the mechanical quality factors Q(m) were evaluated for different "1O" vibration modes, where the longitudinal Q(m) was found to be ∼1200, much higher than the value for "4O" crystals, ∼300.

Predictive role of GSTs on the prognosis of breast cancer patients with neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the predictive value of GST gene polymorphisms with regard to prognosis of breast cancer patients receiving neoadjuvant chemotherapy. METHODS: A total of 159 patients were included in our study between January 2005 and January 2007. All the patients were followed up until January 2012. Genotyping was based upon the duplex polymerase-chain-reaction with the PCR-CTPP method. RESULTS: Patients with null GSTM1 and GSTP1 Val/Val genotypes had significantly had better response rates to chemotherapy when compared with non-null GSTM1 and GSTP1 Ile/ Ile genotypes (OR=1.96 and OR=2.14, respectively). Patients with the GSTM1 null genotype had a longer average survival time and significantly lower risk of death than did those with non-null genotypes (HR=0.66). Similarly, those carrying the GSTP1 Val/Val genotype had 0.54- fold the risk of death of those with GSTP1 Ile/ Ile (HR=0.54). CONCLUSION: A significant association was found between GSTM1 and GSTP1 gene polymorphisms and clinical outcomes in breast cancer cases.

Radiosensitivity enhancement by arsenic trioxide in conjunction with hyperthermia in the EC-1 esophageal carcinoma cell line.

OBJECTIVE: To explore the effect on radiosensitivity of arsenic trioxide (As203) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line. METHOD: Inhibition of EC-1 cell proliferation at different concentrations of As203 was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of IC50 value and choice of 20% of the IC50 as the experimental drug concentration. Blank control, As203, hyperthermia, radiotherapy group, As203 + hyperthermia, As203 + radiotherapy, hyperthermia + radiotherapy and As203 + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle. RESULTS: As203 exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an IC50 of 18.7 µmol/L. After joint therapy of As203 + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the G2/M phase, and as the ratio of cells in G0/G1 and S phases decreased, cell death became more pronounced. CONCLUSION: As203 and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, As203 and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.