Glucocorticoids promote lung metastasis of pancreatic cancer cells through enhancing cell adhesion, migration and invasion.

Glucocorticoids (GCs) are the important stress hormones and widely prescribed as drugs. Although stress has been suggested as a promoter of tumor progression, the direct influence of GCs on metastasis of tumor is not fully understood. Metastasis is a major cause of death in pancreatic cancer patients. In the present study, we investigated the effect of GCs on progression of pancreatic cancer and elucidated the underlying mechanism. It was found that GCs significantly promote cell adhesion, migration, and invasion of pancreatic cancer cells in vitro and their lung metastasis in vivo. Further mechanistic studies showed that GCs notably up-regulate the expression of a trans-membrane glycoprotein, mucin 1 (MUC1) and increase the activation of AKT. Inhibiting MUC1 expression not only attenuates the activation of AKT, but also significantly reduces the promoting effects of GCs on cell adhesion, migration, invasion, and lung metastasis of pancreatic cancer cells. Moreover, GCs not only significantly up-regulate expression of Rho-associated kinase 1/2 (ROCK1/2) and matrix metalloproteinase 3 and 7 (MMP3/7), but also activate ROCK2, which are also involved in the pro-migratory and pro-invasive effects of GCs in pancreatic cancer cells. Taken together, our findings reveal that GCs promote metastasis of pancreatic cancer cells through complex mechanism. MUC1-PI3K/AKT pathway, ROCK1/2 and MMP3/7 are involved in the promoting effect of GCs on cell migration, invasion and metastasis in pancreatic cancer cells. These results suggest the importance of reducing stress and GCs administration in patients with pancreatic cancer to avoid an increased risk of cancer metastasis.

Suppressing the Loss of Polymer-Based Dielectrics for High Power Energy Storage.

Polymer-based dielectrics have received intensive interest from academic community in the field of high-power energy storage owing to their superior flexibility and fast charge-discharge ability. Recently, how to suppress the loss of polymer-based dielectrics has been increasingly recognized as a critical point to attain a high charge-discharge efficiency in the film capacitors. Some achievements are made in analyzing the source of loss and suppressing loss via Edison's trial and error method. In this review, the significance of suppressing loss in polymer-based dielectrics is firstly emphasized. Then, different sources of loss are discussed carefully and an in-depth analysis of the related measurements is presented. Next, recent research results in suppressing loss are summarized and discussed in detail according to different strategies. Finally, the challenges and opportunities in the loss suppression research for the rational design of high-efficiency polymer-based dielectrics are proposed.

Flexible and Stretchable Capacitive Sensors with Different Microstructures.

Recently, sensors that can imitate human skin have received extensive attention. Capacitive sensors have a simple structure, low loss, no temperature drift, and other excellent properties, and can be applied in the fields of robotics, human-machine interactions, medical care, and health monitoring. Polymer matrices are commonly employed in flexible capacitive sensors because of their high flexibility. However, their volume is almost unchanged when pressure is applied, and they are inherently viscoelastic. These shortcomings severely lead to high hysteresis and limit the improvement in sensitivity. Therefore, considerable efforts have been applied to improve the sensing performance by designing different microstructures of materials. Herein, two types of sensors based on the applied forces are discussed, including pressure sensors and strain sensors. Currently, five types of microstructures are commonly used in pressure sensors, while four are used in strain sensors. The advantages, disadvantages, and practical values of the different structures are systematically elaborated. Finally, future perspectives of microstructures for capacitive sensors are discussed, with the aim of providing a guide for designing advanced flexible and stretchable capacitive sensors via ingenious human-made microstructures.

Soft, tough, and fast polyacrylate dielectric elastomer for non-magnetic motor.

Dielectric elastomer actuators (DEAs) with large electrically-actuated strain can build light-weight and flexible non-magnetic motors. However, dielectric elastomers commonly used in the field of soft actuation suffer from high stiffness, low strength, and high driving field, severely limiting the DEA's actuating performance. Here we design a new polyacrylate dielectric elastomer with optimized crosslinking network by rationally employing the difunctional macromolecular crosslinking agent. The proposed elastomer simultaneously possesses desirable modulus (~0.073 MPa), high toughness (elongation ~2400%), low mechanical loss (tan δm = 0.21@1 Hz, 20 °C), and satisfactory dielectric properties ([Formula: see text] = 5.75, tan δe = 0.0019 @1 kHz), and accordingly, large actuation strain (118% @ 70 MV m-1), high energy density (0.24 MJ m-3 @ 70 MV m-1), and rapid response (bandwidth above 100 Hz). Compared with VHBTM 4910, the non-magnetic motor made of our elastomer presents 15 times higher rotation speed. These findings offer a strategy to fabricate high-performance dielectric elastomers for soft actuators.

The ABA-induced soybean ERF transcription factor gene GmERF75 plays a role in enhancing osmotic stress tolerance in Arabidopsis and soybean.

BACKGROUND: Ethylene-responsive factors (ERFs) play important roles in plant growth and development and the response to adverse environmental factors, including abiotic and biotic stresses. RESULTS: In the present study, we identified 160 soybean ERF genes distributed across 20 chromosomes that could be clustered into eight groups based on phylogenetic relationships. A highly ABA-responsive ERF gene, GmERF75, belonging to Group VII was further characterized. Subcellular localization analysis showed that the GmERF75 protein is localized in the nucleus, and qRT-PCR results showed that GmERF75 is responsive to multiple abiotic stresses and exogenous hormones. GmERF75-overexpressing Arabidopsis lines showed higher chlorophyll content compared to WT and mutants under osmotic stress. Two independent Arabidopsis mutations of AtERF71, a gene homologous to GmERF75, displayed shorter hypocotyls, and overexpression of GmERF75 in these mutants could rescue the short hypocotyl phenotypes. Overexpressing GmERF75 in soybean hairy roots improved root growth under exogenous ABA and salt stress. CONCLUSIONS: These results suggested that GmERF75 is an important plant transcription factor that plays a critical role in enhancing osmotic tolerance in both Arabidopsis and soybean.

The Roles of GmERF135 in Improving Salt Tolerance and Decreasing ABA Sensitivity in Soybean.

Abscisic acid (ABA) mediates various abiotic stress responses, and ethylene responsive factors (ERFs) play vital role in resisting stresses, but the interaction of these molecular mechanisms remains elusive. In this study, we identified an ABA-induced soybean ERF gene GmERF135 that was highly up-regulated by ethylene (ET), drought, salt, and low temperature treatments. Subcellular localization assay showed that the GmERF135 protein was targeted to the nucleus. Promoter cis-acting elements analysis suggested that numerous potential stress responsive cis-elements were distributed in the promoter region of GmERF135, including ABA-, light-, ET-, gibberellin (GA)-, and methyl jasmonate (MeJA)-responsive elements. Overexpression of GmERF135 in Arabidopsis enhanced tolerance to drought and salt conditions. In addition, GmERF135 promoted the growth of transgenic hairy roots under salt and exogenous ABA conditions. These results suggest that soybean GmERF135 may participate in both ABA and ET signaling pathways to regulate the responses to multiple stresses.

Up-regulation of Rho-associated kinase 1/2 by glucocorticoids promotes migration, invasion and metastasis of melanoma.

Although glucocorticoids (GCs) regulate proliferation, differentiation and apoptosis of tumor cells, their influence on metastasis of tumor cells is poorly understood. Melanoma is a type of skin cancers with high metastasis. We investigated the effect of GCs on metastasis of melanoma cells and its mechanism. We found that GCs significantly promoted the adhesion, migration, invasion of melanoma cells in vitro and lung metastasis in experimental melanoma metastasis mice. Dexamethasone (Dex), a synthetic GC, did not change the RhoA, RhoB and RhoC signalings, but significantly increased the expression and activity of Rho-associated kinase 1/2 (ROCK1/2). The effect of Dex was to increase ROCK1/2 stability mediated by glucocorticoid receptor. Inhibiting ROCK1/2 activity with Y-27632, a ROCK1/2 inhibitor abrogated the pro-migration and pro-metastasis effects of GCs in vitro and in vivo, indicating that ROCK1/2 mediated the pro-metastasis effects of GCs. Activation of PI3K/AKT also contributed to the pro-migration and pro-invasion effects of Dex partially through up-regulating ROCK1/2 expression. Additionally, Dex also down-regulated the expression of tissue inhibitors of matrix metalloproteinase-2. Taken together, our findings provide new data to understand the possible promoting roles and mechanisms of GCs in melanoma metastasis.

[The application of CRISPR-Cas9 gene editing technology in viral infection diseases].

The RNA-guided Cas9 nuclease from microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system has been used to facilitate efficient genome engineering in eukaryotic cells. The specific targeted genome is recognized and cut by gRNA-directed CRISPR/Cas9 complex, specifically by the endonuclease Cas9. The targeted gene locus could be repaired either by homology-directed repair or nonhomologous end joining, thus achieving a desired editing outcome. Viruses infect cells through specific receptors, and then the viral genome is transcribed, replicated and translated to complete its life cycle. As a result, some DNA virus and retrovirus genomes are integrated into the cellular genome. Gene therapy is a new trend to treat viral infected diseases. Given its designable sequence-specific editing of the targeted genome, CRISPR/Cas9 has tremendous potential in treating persistent and latent viral infections. In this review, we summarize the mechanism and progresses of CRISPR/Cas9, and also highlight its therapeutic application in infectious diseases.

Correlation between activation of PI3K/AKT/mTOR pathway and prognosis of breast cancer in Chinese women.

BACKGROUND: Abnormal activation of PI3K/AKT/mTOR (PAM) pathway, caused by PIK3CA mutation, KRAS mutation, PTEN loss, or AKT1 mutation, is one of the most frequent signaling abnormalities in breast carcinoma. However, distribution and frequencies of mutations in PAM pathway are unclear in breast cancer patients from the mainland of China and the correlation between these mutations and breast cancer outcome remains to be identified. METHODS: A total of 288 patients with invasive ductal breast cancer were recruited in this study. Mutations in PIK3CA (exons 4, 9 and 20), KRAS (exon 2) and AKT1 (exon 3) were detected using Sanger sequencing. PTEN loss was measured by immunohistochemistry assay. Correlations between these genetic aberrations and clinicopathological features were analyzed. RESULTS: The frequencies of PIK3CA mutation, KRAS mutation, AKT1 mutation and PTEN loss were 15.6%, 1.8%, 4.4% and 35.3%, respectively. However, except for PTEN loss, which was tied to estrogen receptor (ER) status, these alterations were not associated with other clinicopathological features. Survival analysis demonstrated that PIK3CA mutation, PTEN loss and PAM pathway activation were not associated with disease-free survival (DFS). Subgroup analysis of patients with ER positive tumors revealed that PIK3CA mutation more strongly reduced DFS compared to wild-type PIK3CA (76.2% vs. 54.2%; P = 0.011). PIK3CA mutation was also an independent factor for bad prognosis in ER positive patients. CONCLUSIONS: AKT1, KRAS and PIK3CA mutations and PTEN loss all exist in women with breast cancer in the mainland China. PIK3CA mutation may contribute to the poor outcome of ER positive breast carcinomas, providing evidence for the combination of PI3K/AKT/mTOR inhibitors and endocrine therapy.

Two wheat glutathione peroxidase genes whose products are located in chloroplasts improve salt and H2O2 tolerances in Arabidopsis.

Oxidative stress caused by accumulation of reactive oxygen species (ROS) is capable of damaging effects on numerous cellular components. Glutathione peroxidases (GPXs, EC 1.11.1.9) are key enzymes of the antioxidant network in plants. In this study, W69 and W106, two putative GPX genes, were obtained by de novo transcriptome sequencing of salt-treated wheat (Triticum aestivum) seedlings. The purified His-tag fusion proteins of W69 and W106 reduced H2O2 and t-butyl hydroperoxide (t-BHP) using glutathione (GSH) or thioredoxin (Trx) as an electron donor in vitro, showing their peroxidase activity toward H2O2 and toxic organic hydroperoxide. GFP fluorescence assays revealed that W69 and W106 are localized in chloroplasts. Quantitative real-time PCR (Q-RT-PCR) analysis showed that two GPXs were differentially responsive to salt, drought, H2O2, or ABA. Isolation of the W69 and W106 promoters revealed some cis-acting elements responding to abiotic stresses. Overexpression of W69 and W106 conferred strong tolerance to salt, H2O2, and ABA treatment in Arabidopsis. Moreover, the expression levels of key regulator genes (SOS1, RbohD and ABI1/ABI2) involved in salt, H2O2 and ABA signaling were altered in the transgenic plants. These findings suggest that W69 and W106 not only act as scavengers of H2O2 in controlling abiotic stress responses, but also play important roles in salt and ABA signaling.

[Mixed infection and risk factors in children with severe adenovirus pneumonia].

OBJECTIVE: To investigate the mixed infection and analyze risk factors in children with severe adenovirus pneumonia. METHODS: A retrospective analysis was performed on the clinical data of 756 children with adenovirus pneumonia between June 2009 and June 2011. Pathogens and risk factors were studied in 216 severe cases. RESULTS: Of the 216 severe cases, 138 (63.9%) were aged from 6 months to 2 years, and 161 (74.5%) developed the disease in the winter and spring; 177 (81.9%) were affected by 1-4 pathogens besides adenovirus, including 74 cases (34.3%) infected with one pathogen as an addition. A total of 334 pathogen strains were identified from the respiratory secretions and sera of the 216 cases. Of them, 163 (48.8%) were bacterial strains, dominated by Gram-negative bacteria (124 strains), 108 (32.3%) were viral strains, and 40 (12.0%) were fungal strains. Multivariate logistic regression analysis indicated that congenital heart disease, congenital airway abnormalities, nutritional anemia, recurrent pulmonary infection, and surgical history were the independent risk factors for severe adenovirus pneumonia in children, with odds ratios of 3.3, 11.1, 7.2, 14.3 and 12.9 respectively (P<0.05). CONCLUSIONS: Severe adenovirus pneumonia is mostly seen in children aged from 6 months to 2 years and occurs frequently in the winter and spring. Many cases are also infected with other pathogens, most commonly Gram-negative bacteria. Congenital heart disease, congenital airway abnormalities, nutritional anemia, recurrent pulmonary infection and surgical history are the independent risk factors for severe adenovirus pneumonia in children.

Up-regulation of stomatin expression by hypoxia and glucocorticoid stabilizes membrane-associated actin in alveolar epithelial cells.

Stomatin is an important lipid raft-associated protein which interacts with membrane proteins and plays a role in the membrane organization. However, it is unknown whether it is involved in the response to hypoxia and glucocorticoid (GC) in alveolar epithelial cells (AEC). In this study we found that hypoxia and dexamethasone (dex), a synthetic GC not only up-regulated the expression of stomatin alone, but also imposed additive effect on the expression of stomatin in A549 cells, primary AEC and lung of rats. Then we investigated whether hypoxia and dex transcriptionally up-regulated the expression of stomatin by reporter gene assay, and found that dex, but not hypoxia could increase the activity of a stomatin promoter-driven reporter gene. Further deletion and mutational studies demonstrated that a GC response element (GRE) within the promoter region mainly contributed to the induction of stomatin by dex. Moreover, we found that hypoxia exposure did not affect membrane-associated actin, but decreased actin in cytoplasm in A549 cells. Inhibiting stomatin expression by stomatin siRNA significantly decreased dense of peripheral actin ring in hypoxia or dex treated A549 cells. Taken all together, these data indicated that dex and/or hypoxia significantly up-regulated the expression of stomatin in vivo and in vitro, which could stabilize membrane-associated actin in AEC. We suppose that the up-regulation of stomatin by hypoxia and dex may enhance the barrier function of alveolar epithelia and mediate the adaptive role of GC to hypoxia.

[Effect of clinical pathway management on pediatric pneumonia].

OBJECTIVE: To investigate effect of clinical pathway management on pediatric pneumonia. METHOD: Data were colleted from children hospitalizated with bronchial pneumonia, bronchiolitis, mycoplasma pneumonia in Center of Respiratory Disorders in Children's Hospital of Chongqing Medical University from January 2011 to December 2012. According to implement of clinical pathway management, all patients were divided into pathway management group (n = 405) and non-pathway management group (n = 503). Length of stay, costs of hospitalization, clinical effect and use of antibiotics were compared in these two groups. RESULT: In pathway management group, average length of stay of children with bronchial pneumonia and bronchiolitis was (6.1 ± 1.6) d and (6.2 ± 1.5) d respectively. While in non-pathway management group, length of stay was (7.2 ± 1.9) d and (7.3 ± 1.5) d (P = 0.000). There was no significant difference in length of stay between these two groups of children with mycoplasma pneumonia [ (6.9 ± 1.8) d vs.(7.7 ± 2.5) d] (P = 0.198). Costs of auxiliary tests in pathway management group was slightly higher than that in non-pathway management group. While other costs in pathway management group were significantly lower than those in non-pathway management group. Total costs of hospitalization of patients with these three diseases in pathway management group and non-pathway management group were ¥(4609 ± 1225) vs ¥ (5629 ± 1813) , ¥ (5006 ± 1250) vs. ¥ (5686 ± 1337), ¥ (4946 ± 1259) vs. ¥ (6488 ± 3032) respectively. There was a significant difference (P < 0.05). Percentages of antibiotics use in two groups were 70.9% vs.99.4%, 45.7% vs.93.4% and 96.2% vs.100.0%. Antibiotics related indicators such as mean number of day of use, ratio of combination and grade of antibiotics were significantly higher in pathway management group compared to non-pathway management group (P < 0.01). There was no significant difference in other indicators like clinical effect and unscheduled readmission in 30 days between two groups (P > 0.05). CONCLUSION: Clinical pathway management can regulate medical behaviors through reduction of medical costs, avoidance of excessive laboratory tests and therapy, and regulation of antibiotic use.