Temperature-Induced Internal Stress Influence on Specimens in Indentation Tests.

The factors affecting the internal stress of specimens during indentation tests were investigated by finite element analysis (FEA) modelling. This was carried out to gain a qualitative understanding of the test errors introduced by the temperature environment during the indentation process. In this study, the influence of thermal expansion of fixed stage on upper specimen (currently neglected in temperature indentation) was explored in detail. Technical issues associated with the parameters of the specimen (such as thickness, width, and elastic modulus) and external conditions (such as stage and glue) were identified and addressed. The test error of the calculated hardness and elastic modulus of the specimen reached up to more than 3% simultaneously at -196 °C (temperature of liquid nitrogen). Based on these considerations, the preferred operation conditions were identified for testing in specific temperature environment. These results can guide experiments aimed at obtaining precise mechanical parameters.

Dexmedetomidine protects high-glucose induced apoptosis in human retinal pigment epithelial cells through inhibition on p75(NTR).

BACKGROUND: In both human patients and animals, diabetic condition of high blood glucose induced significant apoptotic responses in retinal pigment epithelial (RPE) cells. In this work, we used an in vitro culture model of human ARPE-19 cells to evaluate whether dexmedetomidine (DEX) may protect high d-glucose (DG)-induced diabetic apoptosis. METHODS: ARPE-19 cells were incubated with DG in vitro to induce apoptosis. Cells were also pre-incubated with different concentrations of DEX prior to DG treatment. The apoptotic injury by DG, and possible protection by DEX were evaluated using a TUNEL assay. Western blot assay was used to evaluate DEX-associated signaling pathway proteins, including Casp-3, precursor of the nerve growth factor (proNGF) and p75 neurotrophin receptor (p75(NTR)). Moreover, p75(NTR) was overexpressed in ARPE-19 cells, to assess its mechanistic role in DEX-mediated protection on DG-induced apoptosis. RESULTS: In ARPE-19 culture, DG induced significant apoptosis, which was protected by pre-incubation of DEX, in a concentration-dependent manner. DG-induce apoptosis was associated with protein upregulation of Casp-3, proNGF and p75(NTR). Among them, Casp-3 and p75(NTR) were inversely reduced by DEX pre-incubation, but not proNGF. In ARPE-19 cells, p75(NTR) overexpression was shown to reverse the protective effect of DEX on DG-induced apoptosis. CONCLUSION: DEX was proven to have protective effect on DG-induced RPE apoptosis, possible through inhibition on p75(NTR) and its associated signaling pathways.

Novel and functional DNA sequence variants within the GATA6 gene promoter in ventricular septal defects.

Congenital heart disease (CHD) is the most common birth defect in humans. Genetic causes and underlying molecular mechanisms for isolated CHD remain largely unknown. Studies have demonstrated that GATA transcription factor 6 (GATA6) plays an essential role in the heart development. Mutations in GATA6 gene have been associated with diverse types of CHD. As GATA6 functions in a dosage-dependent manner, we speculated that changed GATA6 levels, resulting from DNA sequence variants (DSVs) within the gene regulatory regions, may mediate the CHD development. In the present study, GATA6 gene promoter was genetically and functionally analyzed in large groups of patients with ventricular septal defect (VSD) (n=359) and ethnic-matched healthy controls (n=365). In total, 11 DSVs, including four SNPs, were identified in VSD patients and controls. Two novel and heterozygous DSVs, g.22169190A>T and g.22169311C>G, were identified in two VSD patients, but in none of controls. In cultured cardiomyocytes, the activities of the GATA6 gene promoter were significantly reduced by the DSVs g.22169190A>T and g.22169311C>G. Therefore, our findings suggested that the DSVs within the GATA6 gene promoter identified in VSD patients may change GATA6 levels, contributing to the VSD development as a risk factor.

[Effects of intrauterine cigarette smoking exposure on expression of 3-mercaptopyruvate sulfurtransferase in medulla oblongata of neonatal rats].

OBJECTIVE: To investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of neonatal rats and effects of intrauterine cigarette exposure on its expression. METHODS: Sprague Dawley pregnant rats were randomly divided into 2 groups, control group and cigarette smoke exposure group (n = 8). 3MST mRNA and protein expression in medulla oblongata of neonatal rats were analysed by RT-PCR and Western blot, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of neonatal rats was investigated with immunohistochemical technique. RESULTS: The RT-PCR and Western blot analyses showed that 3MST mRNA and protein were expressed in the medulla oblogata of neonatal rats and intrauterine cigarette exposure promoted their expression (P < 0.05). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in control group of the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N, Amb and FN, but not NTS, were significantly increased in cigarette smoke exposure group (P < 0.05). CONCLUSIONS: 3MST exists in the neurons of medullary respiratory nuclei of neonatal rats and its expression can be up-regulated by intrauterine cigarette exposure, suggesting that the 3MST-H2S pathway may be involved in protection of medullary respiratory centers against injury induced by intrauterine cigarette exposure.

The anti-apoptotic effect of hydrogen sulfide attenuates injuries to the medullary respiratory centers of neonatal rats subjected to in utero cigarette smoke exposure.

H2S may serve as an important neuroprotectant. The present experiments were performed to determine whether H2S could attenuate the injuries sustained by the medullary respiratory centers of neonatal rats that were subjected to cigarette smoke exposure (CS) in utero. Pregnant SD rats were divided into 4 exposure groups: control, CS, CS+NaHS (donor of H2S) and NaHS. Hypoxia decreased the burst frequencies of the hypoglossal rootlets of the medullary slices in CS neonatal rats, and NaHS offset the hypoxia-induced respiratory suppression. Nissl staining indicated that NaHS alleviated the injuries that were sustained by neurons after CS in utero. NaHS also decreased the number of TUNEL-positive neurons and the expression of activated caspase-3 protein in the medulla oblongata of CS neonatal rats. Furthermore, NaHS promoted Bcl-2 protein expression and reduced Bax protein and mRNA expression in the medulla oblongata of CS neonatal rats. Therefore, the present study indicates that the anti-apoptotic effect of H2S protects rat medullary respiratory centers from injuries that would otherwise be sustained from in utero CS exposure.