Research on Stacked Piezoelectric Cymbal Vibrator.

As demand for haptic feedback increases, piezoelectric materials have become one of the best candidate materials due to their small size, high electromechanical coupling coefficient, and fast response. A stacked piezoelectric cymbal vibrator is proposed based on the common cymbal-type transducer, which is composed of a piezoelectric stack to drive and a cymbal disk to amplify displacement. A coupling theoretical model between the piezoelectric stack and the cymbal-type structure is established. The longitudinal and radial displacements of the stacked piezoelectric cymbal vibrator are calculated in the low frequency range (<1000 Hz) by the theoretical model and the finite element method. The theoretical and numerical results are in good agreement. The results show that the radial displacement can be converted into longitudinal displacement and then effectively amplified by the cymbal disk with an amplification ratio of 30. The feature is conducive to its widespread application in the field of consumer electronics.

Benzo[a]pyrene-induced up-regulation of circ_0003552 via ALKBH5-mediated m6A modification promotes DNA damage in human bronchial epithelial cells.

Benzo [a]pyrene (B [a]P) is a widespread environmental chemical pollutant that has been linked to the development of various diseases. However, the specific mechanism of action remains unclear. In this study, human bronchial epithelial 16HBE and BEAS-2B cells were exposed to B [a]P at 0-32 µM to assess the DNA-damaging effects. B [a]P exposure resulted in elevated expression of γ-H2AX, a marker of DNA damage. The m6A RNA methylation assay showed that B [a]P exposure increased the extent of m6A modification and the demethylase ALKBH5 played an integral role in this process. Moreover, the results of the comet assay and Western blot analysis showed an increase in m6A modification mediated by ALKBH5 that promoted DNA damage. Furthermore, the participation of a novel circular RNA, circ_0003552, was assessed by high-throughput sequencing under the condition of high m6A modification induced by B [a]P exposure. In subsequent functional studies, an interference/overexpression system was created to confirm that circ_0003552 participated in regulation of DNA damage. Mechanistically, circ_0003552 had an m6A binding site that could regulate its generation. This study is the first to report that B [a]P upregulated circ_0003552 through m6A modification, thereby promoting DNA damage. These findings revealed that epigenetics played a key role in environmental carcinogen-induced DNA damage, and the quantitative changes it brought might provide an early biomarker for future medical studies of genetic-related diseases and a new platform for investigations of the interaction between epigenetics and genetics.

Long non-coding RNAs mediate the association between short-term PM2.5 exposure and circulating biomarkers of systemic inflammation.

Although short-term fine particulate matter (PM2.5) exposure is associated with systemic inflammation, the effect of lncRNA on these association remains unknown. This study aims to investigate whether the plasma lncRNA mediate the effect of short-term PM2.5 exposure on systemic inflammation. In this cross-sectional study, plasma Clara cell protein 16 (CC16), interleukin 6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and lncRNA expression levels were measured in 161 adults between March and April in 2018 in Shijiazhuang, China. PM2.5 concentrations were estimated 0-3 days prior to the examination date and the moving averages were calculated. Multiple linear regressions were used to evaluate the associations between PM2.5, the four biomarkers and lncRNA expression levels. Mediation analyses were performed to explore the potential roles of lncRNA expression in these associations. The median concentration of PM2.5 ranged from 39.65 to 60.91 mg/m3 across different lag days. The most significant effects on IL-6 and TNF-α per interquartile range increase in PM2.5 were observed at lag 0-3 days, with increases of 0.70 pg/mL (95% CI: 0.33, 1.07) and 0.21 pg/mL (95% CI: 0.06, 0.36), respectively. While the associations between PM2.5 and IL-8 (0.68 pg/mL, 95% CI: 0.34, 1.02) and CC16 (3.86 ng/mL, 95% CI: 1.60, 6.13) were stronger at lag 0 day. Interestingly, a negative association between PM2.5 and the expression of four novel lncRNAs (lnc-ACAD11-1:1, lnc-PRICKLE1-4:1, lnc-GPR39-7:2, and lnc-MTRNR2L12-3:6) were observed at each lag days. Furthermore, these lncRNAs mediated the effects of PM2.5 on the four biomarkers, with proportions of mediation ranged from 2.27% (95% CI: 1.19%, 9.82%) for CC16 to 35.60% (95% CI: 17.16%, 175.45%) for IL-6. Our findings suggested that plasma lncRNA expression mediat the acute effects of PM2.5 exposure on systematic inflammation. These highlight a need to consider circulating lncRNA expression as biomarkers to reduce health risks associated with PM2.5.

Design and Experimental Study of a Stepping Piezoelectric Actuator with Large Stroke and High Speed.

A stepping piezoelectric actuator is proposed with large stroke and high speed. The piezoelectric actuator consists of two symmetrical stators and a mover. The actuator can operate with a "double-drive, four-clamp" mode. The proposed actuator solves the problems of short stroke, low speed, and small load inherent in the currently published stepping piezoelectric actuators. By combining Workbench software with APDL language, finite element simulation and statics and dynamics analysis are carried out to guide the design of the actuator. The new piezoelectric simulation method can solve the difficulties regarding parameter setting and loading voltage on multiple interfaces for a complex piezoelectric model. Therefore, the novel method is helpful to develop the simulation of multilayer thin piezoelectric devices. The prototype of the actuator is developed and tested. Experimental results show that the actuator can run stably in the range of 0 to 600 Hz. The driving stroke is greater than 85 mm, the resolution can reach 535 nm, the maximum driving speed is 6.11 mm/s, and the maximum load is 49 N.

Design of GHz Mechanical Nanoresonator with High Q-Factor Based on Optomechanical System.

Micro-electromechanical systems (MEMS) have dominated the interests of the industry due to its microminiaturization and high frequency for the past few decades. With the rapid development of various radio frequency (RF) systems, such as 5G mobile telecommunications, satellite, and other wireless communication, this research has focused on a high frequency resonator with high quality. However, the resonator based on an inverse piezoelectric effect has met with a bottleneck in high frequency because of the low quality factor. Here, we propose a resonator based on optomechanical interaction (i.e., acoustic-optic coupling). A picosecond laser can excite resonance by radiation pressure. The design idea and the optimization of the resonator are given. Finally, with comprehensive consideration of mechanical losses at room temperature, the resonator can reach a high Q-factor of 1.17 × 104 when operating at 5.69 GHz. This work provides a new concept in the design of NEMS mechanical resonators with a large frequency and high Q-factor.

Bioinformatics analysis of the clinical significance of HLA class II in breast cancer.

Human leukocyte antigen (HLA) class II plays critical roles in antigen presentation and the initiation of immune responses. However, the correlation between the HLA class II gene expression level and the survival of patients with breast cancer is still under investigation. We analyzed microarray and RNA-Seq data of breast cancer from the cancer genome atlas (TCGA), genotype-tissue expression (GTEx) and Oncomine databases by using bioinformatics tools. The expression of the HLA-DQA1, HLA-DQA2, and HLA-DQB2 genes was significantly upregulated in breast cancer. Higher expression levels of HLA class II genes in breast cancer, especially HLA-DOB and HLA-DQB2, were significantly associated with better overall survival. Furthermore, the expression of HLA class II genes was more closely associated with survival in breast cancer than in other cancer types. CD48 coexpressed with both HLA-DOB and HLA-DQB2 was also positively associated with the overall survival of breast cancer patients. The results indicated that HLA class II and CD48 may enhance antitumor immunity, and their expression patterns may serve as potential prognostic biomarkers and therapeutic targets in breast cancer.

Butyrophilin-like 9 expression is associated with outcome in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent non-small cell lung cancer (NSCLC). Patients with LUAD have a poor 5-year survival rate. The use of immune checkpoint inhibitors (ICIs) for the treatment of LUAD has been on the rise in the past decade. This study explored the prognostic role of butyrophilin-like 9 (BTNL9) in LUAD. METHODS: Gene expression profile of buytrophilins (BTNs) was determined using the GEPIA database. The effect of BTNL9 on the survival of LUAD patients was assessed using Kaplan-Meier plotter and OncoLnc. Correlation between BTNL9 expression and tumor-infiltrating immune cells (TILs) was explored using TIMER and GEPIA databases. Further, the relationship between BTNL9 expression and drug response was evaluated using CARE. Besides, construction and evaluation of nomogram based on BTNL9 expression and TNM stage. RESULTS: BTNL9 expression was downregulated in LUAD and was associated with a poor probability of 1, 3, 5-years overall survival (OS). In addition, BTNL9 expression was regulated at epigenetic and post-transcriptional modification levels. Moreover, BTNL9 expression was significantly positively correlated with ImmuneScore and ESTIMATEScore. Furthermore, BTNL9 expression was positively associated with infiltration levels of B cells, CD4+ T cells, and macrophages. Kaplan-Meier analysis showed that BTNL9 expression in B cells and dendritic cells (DCs) was significantly associated with OS. BTNL9 expression was significantly positively correlated with CARE scores. CONCLUSIONS: These findings show that BTNL9 is a potential prognostic biomarker for LUAD. Low BTNL9 expression levels associated with low infiltration levels of naïve B cells, and DCs in the tumor microenvironment are unfavorable for OS in LUAD patients.

Retracted: Ferruginol Diterpenoid Selectively Inhibits Human Thyroid Cancer Growth by Inducing Mitochondrial Dependent Apoptosis, Endogenous Reactive Oxygen Species (ROS) Production, Mitochondrial Membrane Potential Loss and Suppression of Mitogen-Activated Protein Kinase (MAPK) and PI3K/AKT Signaling Pathways.

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. Reference: Guoqing Luo, Jingjing Zhou, Guanjie Li, Ningdong Hu, Xu Xia, Haibo Zhou: Ferruginol Diterpenoid Selectively Inhibits Human Thyroid Cancer Growth by Inducing Mitochondrial Dependent Apoptosis, Endogenous Reactive Oxygen Species (ROS) Production, Mitochondrial Membrane Potential Loss and Suppression of Mitogen-Activated Protein Kinase (MAPK) and PI3K/AKT Signaling Pathways.  Med Sci Monit 2019; 25:2935-2942. 10.12659/MSM.914348.

Ferruginol Diterpenoid Selectively Inhibits Human Thyroid Cancer Growth by Inducing Mitochondrial Dependent Apoptosis, Endogenous Reactive Oxygen Species (ROS) Production, Mitochondrial Membrane Potential Loss and Suppression of Mitogen-Activated Protein Kinase (MAPK) and PI3K/AKT Signaling Pathways.

BACKGROUND Thyroid cancer causes considerable mortality and morbidity across the globe. Owing to the unavailability of biomarkers and the adverse effects of existing drugs, there is an urgent need to develop efficient chemotherapy for the treatment of thyroid cancers. Plants have served as exceptional source of drugs for the treatment of lethal diseases. The purpose of this study was to evaluate the anticancer effects of ferruginol against thyroid cancer cells. MATERIAL AND METHODS We monitored the cell proliferation rate using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using 4',6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB), and annexin V/propidium iodide (PI) staining. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) levels were examined by fluorescence microscopy. Protein expressed was examined by western blotting. RESULTS We found that ferruginol exerted potent antiproliferative action against thyroid cancer cells, and an IC50 of 12 µM was observed for ferruginol against the MDA-T32 cell line. The toxic effects of ferruginol were less pronounced against normal cells. The anticancer effects of ferruginol were likely due to the induction of apoptosis which was also associated with upregulation of Bax and downregulation of Bcl-2. Ferruginol also caused ROS mediated alterations in the MMP of MDA-T32 cells. In MDA-T32 cells, ferruginol might also block the MAPK and PI3K/AKT signaling pathway, which is believed to be an important therapeutic target of anticancer drugs. CONCLUSIONS In conclusion, in view of the results of this study, it might be suggested that ferruginol might serve as an essential lead molecule for the treatment of thyroid cancer provided further in-depth studies especially studying ferruginol toxicological as well as in vivo studies are needed.

Prediction model of lymphovascular invasion based on clinicopathological factors in Chinese patients with invasive breast cancer.

The aim of this study was to evaluate the correlation between lymphovascular invasion (LVI) and tumor size, histological grade, and the expression statuses of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), Ki67, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, and P53 in invasive breast cancer, then establish a prediction model of LVI based on the associated clinicopathological factors.A total of 392 patients with primary invasive breast cancers were enrolled, and their paraffin-embedded tissues were manufactured into the tissue microarray. We evaluated the expression statuses of ER, PR, HER-2, Ki67, EGFR, VEGF, E-cadherin, and P53 based on immunohistochemistry, histological grade and LVI based on the hematoxylin and eosin stain, and tumor size.The positivity of LVI was significantly higher in the patients with HER-2 positive expression, Ki67 high expression, and tumor size >2 cm by Chi-square test. HER-2, Ki67, and tumor size were risk factors of LVI by multivariate analysis. The areas under the receiver operating curve of HER-2, Ki67, tumor size, and the combination of the 3 clinicopathological factors were 0.614 [P = .001, 95% confidence interval (CI): 0.544-0.683], 0.596 (P = .006, 95% CI: 0.529-0.662), 0.575 (P = .03, 95% CI: 0.510-0.641), and 0.670 (P < .001, 95% CI: 0.607-0.734), respectively.HER-2 positive expression, Ki67 high expression, and tumor size >2 cm were risk factors of LVI, whereas the power of the prediction model of LVI based on the 3 clinicopathological factors in invasive breast cancer was low.

Predictors of lymphovascular invasion identified from pathological factors in Chinese patients with breast cancer.

This study aimed to evaluate correlations between lymphovascular invasion (LVI) and the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), Ki-67, CK5/6, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, BCL11A and P53 in invasive breast cancer and to identify predictors of LVI based on these pathological factors. In all, 392 paraffin-embedded tissues from consecutive patients with primary operable invasive breast cancer were included. Immunohistochemistry (IHC) was retrospectively performed using a tissue microarray (TMA) of the paraffin-embedded tissues. LVI-positive rates were compared using the χ2 test. Correlations between pathological factors were assessed using Spearman's test. Binary logistic regression was employed in multivariate analyses of statistically significant factors. The results showed that LVI positivity was significantly higher in patients with HER-2-positive expression or high Ki-67 expression. HER-2 expression was weakly positively correlated with Ki-67 expression. HER-2-positive expression and high Ki-67 expression were found to be risk factors for LVI, and associations between LVI and other pathological factors were not significant. Therefore, HER-2-positive expression and high Ki-67 expression are predictors of LVI, whereas the expression of ER, PR, CK5/6, EGFR, VEGF, E-cadherin, BCL11A and P53 is not associated with LVI in invasive breast cancer.

RPN11 deubiquitinase promotes proliferation and migration of breast cancer cells.

The deubiquitinase enzyme RPN11 is involved in oncogenesis in various types of cancer. However, in breast cancer, the expression levels, prognostic relevance and biological function of RPN11 remains unclear. In the present study, RPN11 expression levels in breast cancer tissues and adjacent non­tumor tissues were determined by reverse transcription­quantitative polymerase chain reaction and immunohistochemical staining, and the association of RPN11 with clinicopathological features of breast cancer was evaluated. RPN11 expression was upregulated in breast cancer tissues compared with healthy tissues. Additionally, high expression levels of RPN11 may be an indicator of poor prognosis, as validated by a breast cancer cohort from the Gene Expression Omnibus database. Knockdown of RPN11 in MDA­MB­231 and T47D cells significantly reduced cell proliferation and enhanced G0/G1 arrest and apoptosis. Exogenous overexpression of RPN11 in MCF7 and Hs578T cells promoted cell growth and inhibited apoptosis. In addition, knockdown of RPN11 abrogated cell migration and reduced epithelial­mesenchymal transition. In conclusion, these findings suggested that RPN11 may function as an oncogene and its upregulation in breast cancer suggests that it may be a therapeutic target.