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Background: Nasopharyngeal carcinoma (NPC) is a deadly cancer, mainly presenting in southeast and east Asia. Long noncoding RNAs (lncRNAs) play essential roles in cancer progression. Exosomes are critical for intercellular communication. Thus, the aim of this study was to identify the functional lncRNAs in NPC and its relevant mechanisms. Methods: Data from public databases were utilized to screen for functional lncRNAs in NPC. Functional and mechanical experiments were performed to determine the role of lncRNAs in NPC and its relative molecular mechanisms. Exosomes derived from NPC cells were isolated to determine their function in tumor-associated macrophages. Results: LncRNA TP73-AS1 was increased in NPC cells and tissues and was associated with a poor prognosis. TP73-AS1 overexpression promoted proliferation, colony formation, and DNA synthesis of NPC cells while TP73-AS1 knockdown showed opposite roles. TP73-AS1 could directly bind with miR-342-3p. MiR-342-3p overexpression attenuated the effect of TP73-AS1 in NPC cells. Furthermore, TP73-AS1 was transferred by exosomes to promote M2 polarization of macrophages. Lastly, exosomal TP73-AS1 enhanced the motility and tube formation of macrophages. Conclusions: Together, this study suggests that TP73-AS1 promotes NPC progression through targeting miR-342-3p and exosome-based communication with macrophages and that TP73-AS1 might be an emerging biomarker for NPC. [ABSTRACT FROM AUTHOR]

Background: Laryngeal cancer has the highest mortality rate among head and neck tumours. RNA N6-methyladenosine (m6A) is the most plentiful and variable in mammalian mRNA. Yet, the m6A regulatory mechanism underlying the carcinogenesis or progression of LSCC remains poorly understood. Methods: The m6A RNA methylation quantification kit was used to detect tissue methylation levels. m6A microarray analysis, mRNA transcriptomic sequencing (mRNA-seq), and proteomics were used to determine RBM15, TMBIM6, and IGF2BP3. Immunohistochemical (IHC), quantitative real-time PCR (qRT-PCR) and Western blot were used to investigate RBM15, TMBIM6, and IGF2BP3 expression in tissue samples and cell lines. The biological effects of RBM15 were detected both in vitro and in vivo. The combination relationship between RBM15/IGF2BP3 and TMBIM6 was verified by RNA immunoprecipitation (RIP) assay, Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNase Mazf, and luciferase report assay. RNase Mazf was used to determine the methylation site on TMBIM6 mRNA. Hoechst staining assay was used to confirm the apoptotic changes. The actinomycin D verified TMBIM6 stability. Results: The global mRNA m6A methylation level significantly increased in LSCC patients. RBM15, as a "writer" of methyltransferase, was significantly increased in LSCC and was associated with unfavorable prognosis. The knockdown of RBM15 reduced the proliferation, invasion, migration, and apoptosis of LSCC both in vitro and in vivo. The results were reversed after overexpressing RBM15. Mechanically, TMBIM6 acted as a downstream target of RBM15-mediated m6A modification. Furthermore, RBM15-mediated m6A modification of TMBIM6 mRNA enhanced TMBIM6 stability through IGF2BP3-dependent. Conclusion: Our results revealed the essential roles of RBM15 and IGF2BP3 in m6A methylation modification in LSCC, thus identifying a novel RNA regulatory mechanism. [ABSTRACT FROM AUTHOR]

As the critical components of tumor microenvironment, cancer-associated fibroblasts (CAFs) support the development of various type of cancers, including laryngeal squamous cell carcinoma (LSCC), but the detailed molecular mechanisms by which cancer-associated fibroblasts interact with LSCC cells to facilitate its progression have not been fully uncovered. In the present study, by analyzing the contents from normal fibroblasts (NFs) and cancer-associated fibroblasts-derived extracellular vesicles (EVs) with Real-Time qPCR analysis, we found that the tumor-initiating LncRNA TUC338 was significantly upregulated in the cancer-associated fibroblasts-derived extracellular vesicles, compared to the normal fibroblasts-secreted extracellular vesicles. Further experiments confirmed that cancer-associated fibroblasts-derived extracellular vesicles promoted cell proliferation, colony formation abilities, epithelial-mesenchymal transition (EMT) and tumorigenesis of LSCC cells via delivering LncRNA TUC338. The mechanical experiments verified that LncRNA TUC338 was stabilized by METTL3/YTHDF1-mediated N6-methyladenosine (m6A) modifications, and elevated LncRNA TUC338 sponged miR-8485 to upregulate chromobox homolog 2 (CBX2) in LSCC cells in a competing endogenous RNA mechanisms-dependent manner. Moreover, our rescue experiments evidenced that cancer-associated fibroblasts-derived LncRNA TUC338-containing extracellular vesicles-induced supportive effects in LSCC aggressiveness were all abrogated by overexpressing miR-8485 and silencing CBX2. Collectively, this study is the first to identify a novel m6A/LncRNA TUC338/miR-8485/CBX2 axis in CAFs-EVs-mediated LSCC development, and to show its potential as a diagnostic biomarker for LSCC. • CAFs-derived extracellular vesicles enhanced cancer aggressiveness of LSCC via delivering TUC338. • METTL3/YTHDF1-mediated m6A modifications are essential for sustaining the stability and expression of TUC338. • TUC338 upregulated CBX2 via sponging miR-8485 in a ceRNA-dependent manner. • TUC338-EVs promoted LSCC progression through modulating the miR-8485/CBX2 axis. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate patient safety culture in secondary hospitals of Heilongjiang, Northeast China, and explore the implications of patient safety culture and practices through the perspectives of various healthcare workers. Methods: A cross-sectional survey using the Safety Attitude Questionnaire (SAQ) was conducted to ascertain the status of patient safety culture in nine secondary hospitals across the six dimensions of the SAQ. Among the 900 staff members who were invited to participate, 665 completed the questionnaire. Descriptive statistics were used to calculate the general means and standard deviations of the patient safety culture dimensions and other numerical variables, and F-test and a multivariate regression analysis were used to statistically analyze the differences in perceptions of safety culture considering the differences in demographic characteristics. All statistical analyses were performed using SPSS v. 22.0. Results: The respondents rated job satisfaction as the highest among all six dimensions of the SAQ, followed in order by teamwork climate, working conditions, and stress recognition (the lowest). There were significant differences among the dimensions of patient safety culture and other factors, such as gender, age, job position, and education. Compared with previous studies, teamwork climate and working conditions scores were quite high, while stress recognition score was very low. We also found differences in patient safety culture by demographic characteristics. Conclusions: The findings revealed the patient safety culture attitudes of healthcare workers in secondary hospitals of Heilongjiang, and provided baseline data for related future research. This evidence may also help government health policymakers and hospital administrators understand related challenges and develop strategies to improve patient safety culture in secondary hospitals of China and perhaps also in other developing countries. [ABSTRACT FROM AUTHOR]

miRNAs regulate gene expression and are key mediators of tumourigenesis. miR-129 has diverse effects in tumours, but its role in laryngeal squamous cell carcinoma (LSCC) remains unknown. This article focuses on the role of miR-129-5p in LSCC. We show miR-129-5p is upregulated in primary LSCC tumours and correlated with advanced disease. Down-regulating miR-129-5p suppressed cell proliferation and migration, and caused cell cycle arrest in Hep-2 cell lines. Downregulation of miR-129-5p alone is sufficient to induce apoptosis both in vivo and in vitro. Moreover, the growth of LSCC xenograft exposed to miR-129-5p antisense oligonucleotides (ASO) in BALB/c mice was markedly inhibited. In addition, we found that miR-129-5p targeted adenomatous polyposis coli (APC) to release inhibition of Wnt signalling causing cell growth and tumourigenesis. Our results suggest miR-129-5p functions as an oncogene in LSCC by repressing APC and is a potential therapeutic target for LSCC. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a subtype of head and neck cancer with dismal prognosis and high relapse rate. The role of long non-coding RNAs (lncRNAs) in NPC has become a research hotspot in recent years. This study aimed to interrogate the function and mechanism of lncRNA MSC antisense RNA 1 (MSC-AS1) in NPC. Methods: MSC-AS1 level in NPC tissues and cells were detected by RT-qPCR. Function of MSC-AS1 in NPC cells was assessed by CCK-8, EdU, TUNEL, caspase-3 activity, and transwell invasion assay. Interaction of microRNA-524-5p (miR-524-5p) with MSC-AS1 and nuclear receptor subfamily 4 group A member 2 (NR4A2) was determined by RIP and luciferase reporter assays. Results: MSC-AS1 was upregulated in NPC tissues and cells. Functional assays indicated that MSC-AS1 exacerbated cell proliferation, hindered apoptosis, and facilitated invasion and epithelial-to-mesenchymal transition (EMT) in NPC. Mechanistically, MSC-AS1 sequestered miR-524-5p to upregulate NR4A2 expression in NPC cells. Finally, NR4A2 was conformed as an oncogene in NPC, and overexpressed NR4A2 could restore MSC-AS1 knockdown-mediated inhibition on NPC progression. Conclusions: Our study firstly showed that lncRNA MSC-AS1 aggravated NPC progression by sponging miR-524-5p to increase NR4A2 expression, indicating MSC-AS1 as a novel target for the lncRNA-targeted therapy in NPC. [ABSTRACT FROM AUTHOR]

When the non-standard customized brush roller tool is used for robotic grinding of large-scale components, the clamping and positioning error of the brush roller at the end of the robot is extremely easy to cause misalignment at the brush roller-workpiece contact interface, which will affect the machining accuracy and surface quality. In order to ensure the parallel contact between the brush roller and the workpiece surface during the machining process, a calculation model of the angular misalignment at the brush roller-workpiece contact interface is proposed based on the elastic contact force perception, and then the accurate positioning of the robot end brush roller is realized by a fast compensation method. Firstly, according to the geometric force relationship between the brush roller and the workpiece, as well as the determined brush roller material property parameters, the estimation model of angular misalignment is established. Secondly, both the axial force and normal torque at the time of initial contact detected by the force-controlled sensor are regarded as the input parameters in the model. Furthermore, the calculated brush roller-workpiece contact offset is used as the geometric error compensation amount, and the brush roller is deflected to achieve error compensation by the robot RAPID program control command. The finite element simulation results are compared with the theoretical calculation values, and the average relative error is 15.1%. The experiment on robotic grinding and brushing of high-speed rail body indicates that the compensated angle can be reduced to 0.024° from an average of 0.179° before compensation, coupled with uniform material removal depth. The proposed method can significantly improve the contour accuracy of large-scale components. [ABSTRACT FROM AUTHOR]

The near-β Ti-55531 (Ti-5Al-5Mo-5V-3Cr-1Zr, wt%) alloy with thin-wall structures were manufactured by laser melting deposition (LMD), and followed by the post-processing of electroshocking treatment (EST). The microstructure evolution before and after EST were characterized via using the scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) and X-ray diffraction (XRD). The results showed that the microstructure of as-deposited specimen was mainly composed of short columnar grains and equiaxed grains, showing a unique structure of alternating short columnar grains-equiaxed grains-short columnar grains. The results of EBSD showed that EST could reduce the orientation concentration and weaken the texture of β phase. XRD results indicated that the α phase content slightly increased after EST. The micro-strain and lattice constant of β phase were changed after EST, which were probably ascribed to the precipitation of α, the generation of crystal defects on α/β interface, and the decrease of texture intensity. The results of mechanical properties indicated that EST could increase the microhardness, the yield strength and the tensile strength, which were due to the variation of microstructure. All results show that EST is an effective approach for optimizing the microstructure and improving the mechanical properties of LMD near-β titanium alloy. [Display omitted] • LMD Ti-55531 shows a unique structure of alternating columnar-equiaxed-columnar grains. • EST can alleviate the orientation concentration and weaken the texture of β phase. • More α tends to precipitate inside β after EST, due to the thermal and athermal effects of EST. • Variation of micro-strain and lattice constant are ascribed to the precipitation of α and decrease of texture intensity. • EST can optimize microstructure and improve mechanical properties of LMD near-β titanium alloy. [ABSTRACT FROM AUTHOR]

In this work, ultrasonic shot peening (USP) was performed for a CrMnFeCoNi high-entropy alloy with an equal atomic ratio to improve the mechanical performance at room temperature. The microstructure evolution and mechanical properties of the CrMnFeCoNi high-entropy alloy under different USP durations were studied. The effects of USP-induced grain refinement, phase transformation, strengthening, and fracture morphologies were analyzed. The results indicated that a certain thickness of compressive residual stress layer with nanocrystalline was formed on the surface of the alloy. After USP, the phase was transformed from the FCC phase to the mixed dual phases FCC+BCC. The alloy exhibited a strength-ductility balance, with hardness and strength enhanced significantly, while elongation to failure remained at around 30%. Additionally, the sample before USP exhibited a typical ductile fracture, while after USP, it was transformed into a mixed fracture of dimple and quasi-cleavage or cleavage. The crack initiated from the sub-surface rather than the initial surface, and then propagated to the interior structure after coming into contact with the surface strengthening layer, effectively delaying the failure of the material. It was demonstrated that the ultrasonic shot peening treatment is a general and efficient physical strengthening method for high-entropy alloy at room temperature. • Ultrasonic shot peening (USP) process was applied on the CrMnFeCoNi high-entropy alloy. • Surface grain refinement from the microscale to the nanoscale. • Phase transformation from the FCC phase to the mixed dual phases FCC+BCC. • The surface mechanical properties were improved and a strength–ductility balance was achieved after USP. [ABSTRACT FROM AUTHOR]

Background: To investigate the effect of DACH1 over-expression on proliferation and invasion of laryngeal squamous cell carcinoma (LSCC). Methods: The 120 cases of LSCC tumors and 114 adjacent non-neoplastic tissues were collected to detect the expression of DACH1 by immunohistochemistry. The changes of DACH1 expression from each group were assessed and correlated to the clinical parameters of the patients. Plasmid-DACH1 was transfected into Hep-2 cells to up-regulate the expression of DACH1C. Real-time PCR, Western blot, CCK8 and transwell assay were used to verify the cell proliferation and invasion after plasmid-DACH1 transfection. Results: The results indicated that DACH1 was downregulated in LSCC tissues as compared to corresponding adjacent non-neoplastic tissues. Decreased expression of DACH1 was found in the tumors upraglottic tumor, lymph node metastases, T3–4 stage and advanced clinical stage. In Hep-2 cells, transfection with plasmid-DACH1 could suppress cell proliferation, invasion and induce G1 phase extension in cell cycle. Conclusions: DACH1 may act as a tumor suppressor gene and could be a potential target for therapeutic intervention of LSCC. [ABSTRACT FROM AUTHOR]