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The damage behavior of limestone rock masses containing calcite mineral filling under uniaxial compression experimental conditions is unclear, and the fracture mechanism of the rock masses needs to be further explored. In this study, uniaxial compression tests were conducted on limestone rock specimens containing veined calcite by combining acoustic emission and digital image correlation techniques. The effects of veined calcite on the generation and development of cracks on the surface of the specimens until the formation of macroscopic penetration and the strength properties of the rock mass were analyzed. The results showed that the transversely distributed veined calcite caused significant stress concentrations in the rock specimens. The longitudinally distributed veined calcite caused cracks in the specimens or influenced the expansion path of the longitudinal principal cracks. The final damage pattern of the specimens didn’t differ significantly from that of conventional rock masses due to the presence of veined calcite. The presence of the veined calcite had effect on the uniaxial compressive capacity of the rock, but the load variation process of the specimen with time still conformed to the load variation pattern during the uniaxial compressive test of conventional rocks. [ABSTRACT FROM AUTHOR]

A significant challenge in conventional heat-shrinkable polymers is to produce controllable microstructures. Here we report that the polymer material fabricated by three-dimensional (3D) printing technique has a heat-shrinkable property, whose initial microstructure can undergo a spontaneous pattern transformation under heating. The underlying mechanism is revealed by evaluating internal strain of the printed polymer from its fabricating process. It is shown that a uniform internal strain is stored in the polymer during the printing process and can be released when heated above its glass transition temperature. Furthermore, the internal strain can be used to trigger the pattern transformation of the heat-shrinkable polymer in a controllable way. Our work provides insightful ideas to understand a novel mechanism on the heat-shrinkable effect of printed material, but also to present a simple approach to fabricate heat-shrinkable polymer with a controllable thermo-structural response. [ABSTRACT FROM AUTHOR]

Post-ischemic activation of NMDA receptors (NMDARs) has been linked to NMDAR subunit-specific signaling that mediates pro-survival or pro-death activity. Although extensive studies have been performed to characterize the role of GluN2A and GluN2B following ischemia, there is less understanding regarding the regulation of GluN2C. Here, we show that GluN2C expression is increased in acute hippocampal slices in response to ischemia. Strikingly, GluN2C knockout mice, following global cerebral ischemia, exhibit greater neuronal death in the CA1 area of the hippocampus and reduced spatial working memory compared to wild-type mice. Moreover, we find that GluN2C-expressing hippocampal neurons show marked resistance to NMDA-induced toxicity and reduced calcium influx. Using both in vivo and in vitro experimental models of ischemia, we demonstrate a neuroprotective role of GluN2C, suggesting a mechanism by which GluN2C is upregulated to promote neuronal survival following ischemia. These results may provide insights into development of NMDAR subunit-specific therapeutic strategies to protect neurons from excitotoxicity. [ABSTRACT FROM AUTHOR]

Western wheatgrass (Pascopyrum smithii Rydb.) is an important cool-season forage and turfgrass. However, due to seed dormancy and poor seedling vigor, it is difficult to develop high seed yield production systems, and assessing these components in response to seed yield. Based on multifactor orthogonally designed field experimental plots under various field management regimes, the effects of numbers of fertile tillers m−2 (Y1), spikelets/fertile tiller (Y2), florets/spikelet (Y3), seed numbers/spikelet (Y4), and seed weight (Y5) on seed yield (Z) were determined over three successive years. Correlation analysis indicated that fertile tillers (Y1) was the most important seed yield component. And the biggest contribution of those five yield component is fertile tillers (Y1), followed by seed numbers/spikelet (Y4), spikelets/fertile tiller (Y2), florets/spikelet (Y3) and seed weight (Y5), respectively. By using ridge regression analysis, we have developed an accurate model of seed yield with its five components. Finally, the results of synergism and antagonism among these yield components on seed yield showed that fertile tillers and seed numbers/spikelet had an antagonistic effect on seed yield. Therefore, selection for high seed yield by direct selection for large values of fertile tillers and seed numbers/spikelet would be the most effective breeding strategy for western wheatgrass. [ABSTRACT FROM AUTHOR]

Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11.7 months. Cox analysis showed that PS 0-1, recurrent disease, EGFR mutations, or EGFR-TKI treatment were associated with improved OS. In patients with EGFR-activating mutations, Cox analysis showed that patients with adenocarcinoma, recurrent disease, or EGFR-TKI treatment had significantly longer survival. Patients with EGFR-activating mutations who received EGFR-TKI therapy had a median OS of 24.3 months, which was significantly longer than those who had not received EGFR-TKI therapy (10.8 months). Patients with wild-type EGFR had a median OS of 9.7 months and Cox analysis showed that PS score and disease type were independent predictors. EGFR-TKI therapy is an independently prognostic factor for NSCLC with mutated EGFR. A more effective therapy is needed for patients with wild-type EGFR. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is refractory to chemotherapies, necessitating novel effective agents. The lysosome inhibitor Bafilomycin A1 (BafA1) at high concentrations displays cytotoxicity in a variety of cancers. Here we show that BafA1 at nanomolar concentrations suppresses HCC cell growth in both 2 dimensional (2D) and 3D cultures. BafA1 induced cell cycle arrest in the G1 phase and triggered Cyclin D1 turnover in HCC cells in a dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) dependent manner. Notably, BafA1 induced caspase-independent cell death in HCC cells by impairing autophagy flux as demonstrated by elevated LC3 conversion and p62/SQSTM1 levels. Moreover, genetic ablation of LC3 significantly attenuated BafA1-induced cytotoxicity of HCC cells. We further demonstrate that pharmacological down-regulation or genetic depletion of p38 MAPK decreased BafA1-induced cell death via abolishment of BafA1-induced upregulation of Puma. Notably, knockdown of Puma impaired BafA1-induced HCC cell death, and overexpression of Puma enhanced BafA1-mediated HCC cell death, suggesting a role for Puma in BafA1-mediated cytotoxicity. Interestingly, pharmacological inhibition of JNK with SP600125 enhanced BafA1-mediated cytotoxicity both in vitro and in xenografts derived from HCC cells. Taken together, our data suggest that BafA1 may offer potential as an effective therapy for HCC. [ABSTRACT FROM AUTHOR]