Strain coupling of ferroelastic domains and misfit dislocations in [101]-oriented ferroelectric PbTiO3 films.

High-index perovskite ferroelectric thin films possess excellent dielectric permittivity, piezoelectric coefficient, and exotic ferroelectric switching properties. They also exhibit complications in the ferroelastic domains, misfit dislocations, and strain-relaxation behaviors. Exploring the relationship of the ferroelastic domains and misfit dislocations may be of benefit for promoting the high-quality growth of these thin films. Here, the strain field of the ferroelastic domains and misfit dislocations in [101]-oriented PbTiO3/(La, Sr)(Al, Ta)O3 epitaxial thin films were investigated by advanced aberration-corrected (scanning) transmission electron microscopy (TEM) combined with geometry phase analysis (GPA). Two types of misfit dislocations with projected Burgers vectors of a[001] or a[100] on the (010) plane were elucidated, whose strain fields included in-plane strain and lattice rotation coupled with the c domains above them. Besides, it was demonstrated that the coupling was kept inside the PbTiO3 films when the film thickness was increased. Furthermore, the polarization rotation was observed in both narrow c domains and around the misfit dislocation cores, which may be attributed to the flexoelectric effect. These results are expected to provide useful information for understanding the nucleation and propagation mechanism of ferroelastic domains and for further modifying the growth of high-index ferroelectric thin films.

Polar meron lattice in strained oxide ferroelectrics.

A topological meron features a non-coplanar structure, whose order parameters in the core region are perpendicular to those near the perimeter. A meron is half of a skyrmion, and both have potential applications for information carrying and storage. Although merons and skyrmions in ferromagnetic materials can be readily obtained via inter-spin interactions, their behaviour and even existence in ferroelectric materials are still elusive. Here we observe using electron microscopy not only the atomic morphology of merons with a topological charge of 1/2, but also a periodic meron lattice in ultrathin PbTiO3 films under tensile epitaxial strain on a SmScO3 substrate. Phase-field simulations rationalize the formation of merons for which an epitaxial strain, as a single alterable parameter, plays a critical role in the coupling of lattice and charge. This study suggests that by engineering strain at the nanoscale it should be possible to fabricate topological polar textures, which in turn could facilitate the development of nanoscale ferroelectric devices.

Inhibition of miR-126 protects chondrocytes from IL-1ß induced inflammation via upregulation of Bcl-2.

OBJECTIVES: The aim of this study was to investigate the role of miR-126 in the development of osteoarthritis, as well as the potential molecular mechanisms involved, in order to provide a theoretical basis for osteoarthritis treatment and a novel perspective for clinical therapy. METHODS: Human chondrocyte cell line CHON-001 was administrated by different doses of interleukin (IL)-1ß to simulate inflammation. Cell viability, migration, apoptosis, IL-6, IL-8, and tumour necrosis factor (TNF)-α expression, as well as expression of apoptosis-related factors, were measured to assess inflammation. miR-126 expression was measured by quantitative polymerase chain reaction (qPCR). Cells were then transfected with miR-126 inhibitor to assess the effect of miR-126 on IL-1ß-injured CHON-001 cells. Expression of B-cell lymphoma 2 (Bcl-2) and the activity of mitogen-activated protein kinase (MAPK) / Jun N-terminal kinase (JNK) signaling pathway were measured by Western blot to explore the underlying mechanism through which miR-126 affects IL-1ß-induced inflammation. RESULTS: After IL-1ß administration, cell viability and migration were suppressed while apoptosis was enhanced. Expression of IL-6, IL-8, and TNF-α were all increased, and miR-126 was upregulated. In IL-1ß-administrated CHON-001 cells, miR-126 inhibitor suppressed the effect of IL-1ß on cell viability, migration, apoptosis, and inflammatory response. Bcl-2 expression was negatively regulated with miR-126 in IL-1ß-administrated cells, and thus affected expressions of phosphorylated MAPK and JNK. CONCLUSION: IL-1ß-induced inflammatory markers and miR-126 was upregulated. Inhibition of miR-126 decreased IL-1ß-induced inflammation and cell apoptosis, and upregulated Bcl-2 expression via inactivating the MAKP/JNK signalling pathway.Cite this article: C. D. Yu, W. H. Miao, Y. Y. Zhang, M. J. Zou, X. F. Yan. Inhibition of miR-126 protects chondrocytes from IL-1ß induced inflammation via upregulation of Bcl-2. Bone Joint Res 2018;7:414-421. DOI: 10.1302/2046-3758.76.BJR-2017-0138.R1.

[The expression and association of CD14(+) HLA-DR(Low/-) myeloid-derived suppressor cell-like cells and interleukin-1ß in ovarian cancer].

Objective: To analyze the percentage of CD14(+) HLA-DR(Low/-) myeloid-derived suppressor cell-like cell subtypes(MDSCs) and interleukin-1ß(IL-1ß) concentration in peripheral blood and ascites of ovarian cancer patients, and to explore their association with clinicopathological characteristics. Methods: Blood samples of 31 patients and ascites of 5 patients in Qilu Hospital of Shandong University from January 2016 to December 2016 were collected. Blood samples of 20 healthy volunteers with matched age were collected as control. The percentages of CD14(+) HLA-DR(Low/-) cell subtypes in CD14(+) monocytes were collected by flow cytometry and their phenotypes were analyzed. qRT-PCR was used to analyze the expression of immunosuppression factors in this subtype. ELISA was used to analyze IL-1ß concentration in peripheral blood and ascites of ovarian cancer patients and healthy controls. The correlation between CD14(+) HLA-DR(Low/-) cell percentage and IL-1ß concentration was explored. The association between CD14(+) HLA-DR(Low/-) cell percentage, IL-1ß concentration and clinicopathological characteristics were analyzed. Results: The percentage of CD14(+) HLA-DR(Low/-) cells in CD14(+) monocytes of peripheral blood of healthy controls was (2.30±0.49)%, and the percentage in ovarian cancer patients was (3.74±0.95)%, with statistical significance (t=6.96, P<0.01). This cell subset showed similar phenotypes and factor expression with monocytic MDSCs. The percentage of CD14(+) HLA-DR(Low/-) cells in peripheral blood ascites of ovarian cancer patients was (16.60±7.35)%, significantly higher than those in peripheral bloods (4.03±0.94)%(t=3.87, P<0.05). The concentration of IL-1ß in peripheral blood of healthy controls was[3.88(0.41, 7.07)]ng/L, and the concentration in ovarian cancer patients was (12.77±3.52) ng/L, with statistical significance (Z=-4.93, P<0.01). IL-1ß concentration in ascites of ovarian cancer patients was (62.17±23.05) ng/L, significantly higher than that in peripheral bloods (12.65±3.93) ng/L(t=5.20, P<0.01). IL-1ß concentration was correlated with CD14(+) HLA-DR(Low/-) cell percentage in ovarian cancer patients (R(2)=0.36 in peripheral blood, P<0.01; R(2)=0.68 in ascites, P<0.05), but not in healthy controls (R(2)=0.02, P>0.05). The percentage of CD14(+) HLA-DR(Low/-) cells and IL-1ß concentration were associated with metastasis and FIGO stage of ovarian cancer. Conclusion: The elevated percentage of CD14(+) HLA-DR(Low/-) cells and IL-1ß concentration might involve in the development of ovarian cancer.

Identification of the transactivation domain of the human FHL3.

Four and a half LIM domain protein 3 (FHL3) has the transactivation and repressor activity, and plays important roles in regulating the expression levels of various genes. In this study, FHL3 was proved to possess the auto-activation ability when constructed into the pGBKT7 plasmid (a GALA DNA-binding domain (BD) cloning vector of the yeast two-hybrid system) and transformed into yeast Y190 cells. To determine the transactivation domain of FHL3, five mutants were constructed by sequentially deleting each LIM domain of FHL3 and then inserting them into the pGBKT7 plasmid. After being transformed into yeast Y190 cells, expression levels of the mutants were identified by Western blot analysis. The beta-galactosidase assay showed that the mutant without the fourth LIM domain (LIM4) lost the auto-activation ability. Further investigations on the mutants with deleted first or second zinc finger of LIM4 confirmed that the second zinc finger motif in LIM4 was responsible for the auto-activation of FHL3.

High rates of ras codon 61 mutation in thyroid tumors in an iodide-deficient area.

Using polymerase chain reaction and sequence-specific oligonucleotide hybridization, the frequency of three ras oncogene mutations (N-ras, Ha-ras, and K-ras) in thyroid tumors (25 adenomas, 16 follicular carcinomas, and 22 papillary carcinomas) was investigated in both iodide-deficient and iodide-sufficient areas. The ras oncogene mutation rate was significantly higher in the iodide-deficient area, being 85 versus 17% in the adenomas, and 50 versus 10% in the follicular carcinomas. No mutations were found in papillary carcinomas. The most common mutation site was Ha-ras codon 61 with Gln----Arg substitution. Two ras mutations at codon 61 (Gln----Lys in N-ras and Gln----Arg in Ha-ras) were found in a microfollicular adenoma specimen from Eastern Hungary. We conclude that dietary iodine may modulate ras oncogene mutations, and that in the iodide-deficient area, ras oncogene activation may play a more important role in the initiation and/or maintenance of follicular tumors. Additional factors are, however, necessary to initiate carcinogenesis.