The use of the aquarium fishes Danio rerio and Poecilia reticulata as highly sensitive species for testing the carcinogenicity of chemical compounds

Aquarium fishes Danio rerio and Poecilia reticulata are recommended as test-objects for testing carcinogenic chemical agents. 30 compounds were tested for their action on these objects. The analysis of the incidence of induced tumors, period of their appearance and Iball index shows high sensitivity of the aquarium fishes to the carcinogenic action. Data are presented on the dynamics of experimental carcinogenesis, morphology of induced tumours, as well as on modifications of carcinogenesis (the role of environmental temperature, age, dose, exposition, etc.). Advantages and limitations of the "fish model" are compared with those found in the experiments carried on mammals.     

A study on the dynamic characteristics of the Korean Yi-dynasty bell type structure

The dynamic characteristics of the Korean Yi-dynasty bell type structure, including the acoustic effects, are analyzed both theoretically and experimentally. The numerical solutions of natural frequencies and mode shape for membrane and flexural behavior are obtained by using the NASTRAN program for the finite element method with plate shell elements of triangular and quadrilateral types. Test bells, A and B types similar to the Kap-Sa bell in Kong-Ju chosen among typical Korean Yi-dynasty bells, are manufactured on different scales to the original bell. To consider the effects of the variation of the structural dimension on the dynamic response, these bells are analyzed with respect to the variation of the thickness of the wall and the bottom rim and the asymmetric Dang-Jwas. The impact method with the Fast Fourier Transform Analyzer is adopted to experimentally assess the dynamic response. Results are in good agreement with the numerical solutions.     

Temperature dependence of high strain-rate impact fracture behaviour in highly filled polymeric composite and plasticized thermoplastic propellants

The effect of temperature and strain-rate on the fracture behaviour during high strain-rate ( 10³ sec^–1) impact of two highly filled polymeric composite propellants (containing segmented polyurethanes based on hydroxy-term inated polybutadiene (HTPB) or glycidyl azide polymer (GAP) filled with ammonium perchlorate (AP) particles) and a plasticized thermoplastic (cast double base (CDB) nitrocellulose-nitroglycerine) propellant have been examined over a wide temperature range encompassing the ittle-ductile transition. In the elastic region of the loaddisplacement curve, the yield stress and fracture toughness is highest for GAP/AP and lowest for HTPB/AP. In the elastic and post-yield ductile regions CDB is more fracture-resistant than GAP/AP and HTPB/AP over the temperature range –20 to 50° C, but below –40° C, where both CDB and GAP/AP are brittle, GAP/AP is more fracture-resistant than CDB (as observed in the elastic region). Although all the propellants are known to develop small cracks in the elastic and post-yield ductile regions of the load-displacement curve, the overall fracture behaviour is largely governed by viscoelastic properties (because the cracks close up in compression). The good mechanical properties of CDB, above the brittle-ductile transition temperature, can be attributed to the presence of a large-transition loss peak. In the composites, the fracture behaviour is also influenced to a lesser extent by the degree of filler-binder interactions. Dynamic mechanical analysis indicates that GAP/AP has a slightly higher degree of filler-binder interactions than HTPB/AP. A temperature-strain rate reduction has been obtained for the yield stress and the composite curve can be expressed by the equation _y =K ₁ +K ₂ log (ea _T ) whereK ₁ andK ₂ are constants anda _T is a shift factor.K ₂ is a material constant which reflects the temperature and strain-rate sensitivity.     

Molecular Docking Studies and Biological Evaluation of Berberine–Benzothiazole Derivatives as an Anti-Influenza Agent via Blocking of Neuraminidase

In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine–benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1–BBD14 compounds’ antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir.     

The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.     

Biocompatibility of surface treated pure titanium and titanium alloy by<Emphasis Type="Italic">in vivo</Emphasis> and<Emphasis Type="Italic">in vitro</Emphasis> test

In the present study, commercial pure Ti and Ti-6Al-4V alloy specimens with and without alkali and heat treatments were implanted in the abdominal connective tissue of mice. Conventional stainless steel 316L was also implanted for comparison. After three months, their biocompatibility was evaluated byin vitro andin vivo experiments. Surface structural changes of specimens due to the alkali treatment and soaking in Hank’s solution were analyzed by XRD, SEM, XPS and AES. An apatite layer, which accelerates the connection with bone, was formed more easily on the alkali treated specimens than the non-treated specimens. The number of macrophages, which is known to increase as the inflammatory reaction proceeds, was much lower for the alkali and heat treated specimens than for the others. The average thickness of the fibrous capsule formed around the implant was much thinner for the alkali and heat treated specimens than for the others.     

Simulated Microgravity Inhibits the Proliferation of Chang Liver Cells by Attenuation of the Major Cell Cycle Regulators and Cytoskeletal Proteins

Simulated microgravity (SMG) induced the changes in cell proliferation and cytoskeleton organization, which plays an important factor in various cellular processes. The inhibition in cell cycle progression has been considered to be one of the main causes of proliferation inhibition in cells under SMG, but their mechanisms are still not fully understood. This study aimed to evaluate the effects of SMG on the proliferative ability and cytoskeleton changes of Chang Liver Cells (CCL-13). CCL-13 cells were induced SMG by 3D clinostat for 72 h, while the control group were treated in normal gravity at the same time. The results showed that SMG reduced CCL-13 cell proliferation by an increase in the number of CCL-13 cells in G0/G1 phase. This cell cycle phase arrest of CCL-13 cells was due to a downregulation of cell cycle-related proteins, such as cyclin A1 and A2, cyclin D1, and cyclin-dependent kinase 6 (Cdk6). SMG-exposed CCL-13 cells also exhibited a downregulation of α-tubulin 3 and β-actin which induced the cytoskeleton reorganization. These results suggested that the inhibited proliferation of SMG-exposed CCL-13 cells could be associate with the attenuation of major cell cycle regulators and main cytoskeletal proteins.     

Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer

Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.     

Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis

Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation. The presence of USP29 effectively blocked polyubiquitination of Cdc25A and extended its half-life. CRISPR-Cas9-mediated knockdown of USP29 in HeLa cells resulted in cell cycle arrest at the G0/G1 phase. We also showed that USP29 knockdown hampered Cdc25A-mediated cell proliferation, migration, and invasion of cancer cells in vitro. Moreover, NSG nude mice transplanted with USP29-depleted cells significantly reduced the size of the tumors, whereas the reconstitution of Cdc25A in USP29-depleted cells significantly increased the tumor size. Altogether, our results implied that USP29 promoted cell cycle progression and oncogenic transformation by regulating protein turnover of Cdc25A.     

Material Design for 3D Multifunctional Hydrogel Structure Preparation

Hydrogels are recognized as one of the most promising materials for e-skin devices because of their unique applicable functionalities such as flexibility, stretchability, biocompatibility, and conductivity. Beyond the excellent sensing functionalities, the e-skin devices further need to secure a target-oriented 3D structure to be applied onto various body parts having complex 3D shapes. However, most e-skin devices are still fabricated in simple 2D film-type devices, and it is an intriguing issue to fabricate complex 3D e-skin devices resembling target body parts via 3D printing. Here, a material design guideline is provided to prepare multifunctional hydrogels and their target-oriented 3D structures based on extrusion-based 3D printing. The material design parameters to realize target-oriented 3D structures via 3D printing are systematically derived from the correlation between material design of hydrogels and their gelation characteristics, rheological properties, and 3D printing processability for extrusion-based 3D printing. Based on the suggested material design window, ion conductive self-healable hydrogels are designed and successfully applied to extrusion-based 3D printing to realize various 3D shapes.