MiR-125a-5p regulates the radiosensitivity of laryngeal squamous cell carcinoma via HK2 targeting through the DDR pathway.

Objective: To determine the function of miR-125a-5p in laryngeal squamous cell carcinoma (LSCC), its correlation with radiation sensitivity, and the underlying regulatory mechanism. Materials and methods: We conducted the analysis on the correlation between miR-125a-5p and head and neck squamous cell carcinoma (HNSCC) using data obtained from The Cancer Genome Atlas (TCGA). The putative gene targeted by miR-125a-5p has been identified as HK2, while the expression levels of miR-125a-5p and HK2 were measured in laryngeal cancer tissues and cells using RT-PCR. MiR-125a-5p and HK2 were introduced into the lentiviral vector and the vector was used to transfect AMC-HN-8 cells. The roles of miR-125a-5p and HK2 in LSCC and on radiosensitivity were determined by evaluating cell growth, examining colony formation, analyzing flow cytometry, and utilizing the single hit multi-target model. Western blotting was used to measure H2AX and rH2AX levels in the DNA damage response (DDR) pathway. The validation of the interaction between miR-125a-5p and HK2 was conducted through the dual-luciferase assay. To further confirm the association between miR-125a-5p and HK2, as well as its influence on radiosensitivity, rescue experiments were performed. Results: The expression of miR-125a-5p is downregulated in LSCC, while upregulating its expression could suppress cell growth, induce apoptosis, and enhance radiosensitivity. Additionally, HK2 exhibited high expression in LSCC and the biological function was opposite to miR-125a-5p. Western blotting analysis revealed that miR-125a-5p increased rH2AX levels and decreased H2AX levels, conversely, HK2 had the opposite effect on miR-125a-5p. These findings suggested that HK2 may serve as the target gene of miR-125a-5p. The double luciferase assay confirmed the binding of HK2 to miR-125a-5p, and rescue trials confirmed the role of miR-125a-5p in regulating the effects and radiation sensitivity of LSCC by targeting HK2 via the DDR pathway. Conclusion: By targeting HK2 and impacting the DDR pathway, miR-125a-5p has been found to inhibit cellular proliferation, enhance apoptosis, and heighten radiosensitivity in LSCC.

Roll-to-Roll Manufactured Polyetherimide Nanocomposite With Different Diameters of SiO2 Nanoparticles Exhibiting Improved High-Temperature Dielectric Energy Storage Performance.

To enhance the high-temperature energy storage performance of the polymer-based dielectric film, inorganic nanofillers with large band gaps are much more effective and have been widely adopted. However, the impact of nanoparticle diameters on the dielectric properties of polymer nanocomposites has been less studied. Herein, silicon dioxide nanoparticles (SiO2-NPs) with varying diameters (20, 60, 120, 200 nm) prepared by the sol-gel method are incorporated in the PEI matrix to form PEI/SiO2 nanocomposites. The characterization results reveal a distinct correlation between the dielectric properties of polyetherimide (PEI) composites and the diameters of SiO2-NPs. Leakage current density analysis and breakdown strength simulations indicate that SiO2-NPs with smaller diameters generate more deep traps that impede the transport of charge carriers, especially under high temperatures. Notably, PEI/20 nm-SiO2 exhibits a high discharged energy density of 4.4 J cm-3 with an efficiency of 90% at 150 °C. Furthermore, PEI/SiO2 films with 10 µm in thickness are manufactured by a large-scale solution casting process. The continuously prepared PEI/20 nm-SiO2 film exhibits a discharged energy density of 3.2 J cm-3 with an efficiency of 90% at 150 °C. This study not only provides a strategy for the design of high-performance dielectric polymer composites but also offers a large-scale high-temperature dielectric film for practical use.

MiR-125 family improves the radiosensitivity of head and neck squamous cell carcinoma.

BACKGROUND: MiRNAs can affect the radiosensitization of head and neck squamous cell carcinoma (HNSCC). We aimed to analyze the function of miR-125 family members in HNSCC using The Cancer Genome Atlas (TCGA) and determine their effect on radiation in laryngeal squamous cell cancer (LSCC). METHODS: First, we systematically analyzed the role of the miR-125 family in HNSCC using the TCGA database and found that miR-125a-5p is associated with radiotherapy. We then performed comprehensive enrichment analysis of miR-125a-5p and predicted target genes. Then, we performed transfection, cell proliferation assays, reverse transcription polymerase chain reaction, apoptosis assays, micronucleus tests, and western blotting on hep-2 cells selected with puromycin. RESULTS: MiR-125 family members exhibited significantly different expression in HNSCC. They were significantly associated with tumor-node-metastasis staging, clinical stages, and histological grades. Radiation therapy had a statistically effect on miR-125 family members, except miR-125a-3p. Moreover, miR-125a-5p was related to overall survival in LSCC. Thus, we predicted 110 target genes and seven hub genes of miR-125a-5p. The proliferation rate of cells transfected with lentivirus vector expressing miR-125a-5p was significantly reduced compared to the other groups. The radiation effect was enhanced in cells transfected with miR-125a-5p. The ratio of apoptotic cells transfected and exposed to X-rays (10 Gy) was distinctly higher than that of the Ad-control group. Western blotting analysis revealed that miR-125a-5p upregulated the apoptotic regulators P53 and rH2AX. Thus, miR-125a-5p may increase radiosensitivity in LSCC via upregulation of pro-apoptotic genes. CONCLUSIONS: MiR-125 family members could be prognostic biomarkers of HNSCC and improve HNSCC sensitivity to radiotherapy by activating P53. Upregulating miR-125a-5p via lentivirus vectors may be a novel strategy to strengthen the effect of radiotherapy on LSCC.

Distinct role of histone chaperone Asf1a and Asf1b during fertilization and pre-implantation embryonic development in mice.

BACKGROUND: Asf1 is a well-conserved histone chaperone that regulates multiple cellular processes in different species. Two paralogous genes, Asf1a and Asf1b exist in mammals, but their role during fertilization and early embryogenesis remains to be investigated further. METHODS: We analyzed the dynamics of histone chaperone Asf1a and Asf1b in oocytes and pre-implantation embryos in mice by immunofluorescence and real-time quantitative PCR, and further investigated the role of Asf1a and Asf1b during fertilization and pre-implantation development by specific Morpholino oligos-mediated knock down approach. RESULTS: Immunofluorescence with specific antibodies revealed that both Asf1a and Asf1b were deposited in the nuclei of fully grown oocytes, accumulated abundantly in zygote and 2-cell embryonic nuclei, but turned low at 4-cell stage embryos. In contrast to the weak but definite nuclear deposition of Asf1a, Asf1b disappeared from embryonic nuclei at morula and blastocyst stages. The knockdown of Asf1a and Asf1b by specific Morpholino oligos revealed that Asf1a but not Asf1b was required for the histone H3.3 assembly in paternal pronucleus. However, knockdown of either Asf1a or Asf1b expression decreased developmental potential of pre-implantation embryos. Furthermore, while Asf1a KD severely reduced H3K56 acetylation level and the expression of Oct4 in blastocyst stage embryos, Asf1b KD almost eliminated nuclear accumulation of proliferating cell marker-PCNA in morula stage embryos. These results suggested that histone chaperone Asf1a and Asf1b play distinct roles during fertilization and pre-implantation development in mice. CONCLUSIONS: Our data suggested that both Asf1a and Asf1b are required for pre-implantation embryonic development. Asf1a regulates H3K56ac levels and Oct4 expression, while Asf1b safeguards pre-implantation embryo development by regulating cell proliferation. We also showed that Asf1a, but not Asf1b, was necessary for the assembly of histone H3.3 in paternal pronuclei after fertilization.

Investigation of Electrical Properties of BiFeO3/LDPE Nanocomposite Dielectrics with Magnetization Treatments.

The purpose of this paper is to study the effect of nano-bismuth ferrite (BiFeO3) on the electrical properties of low-density polyethylene (LDPE) under magnetic-field treatment at different temperatures. BiFeO3/LDPE nanocomposites with 2% mass fraction were prepared by the melt-blending method, and their electrical properties were studied. The results showed that compared with LDPE alone, nanocomposites increased the crystal concentration of LDPE and the spherulites of LDPE. Filamentous flake aggregates could be observed. The spherulite change was more obvious under high-temperature magnetization. An agglomerate phenomenon appeared in the composite, and the particle distribution was clear. Under high-temperature magnetization, BiFeO3 particles were increased and showed a certain order, but the change for room-temperature magnetization was not obvious. The addition of BiFeO3 increased the crystallinity of LDPE. Although the crystallinity decreased after magnetization, it was higher than that of LDPE. An AC test showed that the breakdown strength of the composite was higher than that of LDPE. The breakdown strength increased after magnetization. The increase of breakdown strength at high temperature was less, but the breakdown field strength of the composite was higher than that of LDPE. Compared with LDPE, the conductive current of the composite was lower. So, adding BiFeO3 could improve the dielectric properties of LDPE. The current of the composite decayed faster with time. The current decayed slowly after magnetization.

MicroRNA­98/PTEN/AKT pathway inhibits cell proliferation and malignant progression of hypopharyngeal carcinoma by MTDH.

Laryngeal carcinoma is one of the most common tumors concerning otorhinolaryngology head and neck surgery, however, the pathogenesis of laryngeal carcinoma remains unclear. MicroRNAs (miRNAs) have been reported to play vital roles in the pathogenesis of laryngeal carcinoma Herein, the present study was designed to explore the function and mechanism of miRNA­98 in hypopharyngeal carcinoma. In brief, qRT­PCR, MTT assay, western blot analysis, Transwell assay and luciferase reporter assay were performed. Based on the results, miRNA­98 expression was downregulated in patients with hypopharyngeal carcinoma. Downregulation of miRNA­98 promoted cell growth and migration, and decreased the apoptotic rate of hypopharyngeal carcinoma cells. Overexpression of miRNA­98 increased the apoptotic rate, and inhibited cell growth and migration of hypopharyngeal carcinoma cells. Moreover, luciferase reporter assays revealed that MTDH is a direct target of miRNA­98 and overexpression of miRNA­98 induced the protein expression of PTEN and suppressed that of PI3K and p­Akt. si­MTDH attenuated the anticancer effects of miRNA­98 on hypopharyngeal carcinoma via the PTEN/AKT pathway. To the best of our knowledge, the present study confirmed for the first time that miRNA­98 inhibits hypopharyngeal carcinoma cell proliferation and induces apoptosis via the PTEN/AKT pathway by MTDH.