A highly distorted ultraelastic chemically complex Elinvar alloy.

The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various industrial applications, from actuators and medical devices to high-precision instruments1,2. The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys3-including gum metals4,5 and strain glass alloys6,7-may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation3. Recently, chemically complex alloys, such as 'high-entropy' alloys8, have attracted tremendous research interest owing to their promising properties9-15. In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10-4) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported.

MIIP inhibits malignant progression of hepatocellular carcinoma through regulating AKT.

OBJECTIVE: This study was aimed to investigate the expression characteristics of MIIP in hepatocellular carcinoma (HCC), and to further explore whether it can inhibit the malignant progression of this disease via regulating AKT expression. PATIENTS AND METHODS: Real-time quantitative PCR (qRT-PCR) was performed to examine the expression of MIIP in tumor and paracancerous tissue specimens of 39 patients with HCC, and to analyze the interplay between MIIP expression and clinical indicators and prognosis of HCC patients. At the same time, in HCC cell lines, the expression of MIIP was further verified using qRT-PCR. In addition, MIIP overexpression and knockdown models were constructed using lentivirus in HCC cell lines (Bel-7402 and Hep3B), and the influence of MIIP on the biological function of HCC cells was analyzed through CCK-8 and transwell migration assays. Finally, luciferase reporting assay and cell reverse experiments were applied to further explore the potential molecular mechanism and the interaction between MIIP and AKT. RESULTS: The results of qRT-PCR showed that the expression level of MIIP in HCC tissue samples was remarkably lower than that in adjacent ones, with a statistically significant difference. Compared with patients with high expression of MIIP, patients with low MIIP expression had a higher occurrence of distant metastasis and a lower overall survival rate. Similarly, compared with control group, the proliferation and migration ability of HCC cells in MIIP knockdown group (sh-MIIP) was remarkably enhanced, while the opposite result was observed in MIIP overexpression group. In addition, qRT-PCR results also revealed that AKT and MIIP were negatively correlated in HCC tissues. At the same time, the results of luciferase reporter gene assay demonstrated that MIIP can be targeted by AKT through certain binding site. Additionally, cell reverse experiment found that there might exist a mutual regulation between MIIP and AKT, thereby jointly regulating the malignant progression of HCC. CONCLUSIONS: MIIP expression is remarkably decreased both in HCC tissues and cell lines; meanwhile, the low expression of MIIP is positively correlated with the occurrence of distant metastasis and poor prognosis of patients with HCC. In addition, MIIP may be able to inhibit the malignant progression of HCC by modulating AKT expression.

Controlled synthesis of nanostructured glassy and crystalline high entropy alloy films.

High entropy alloy (HEA) based thin films have been attracting increasing research interest recently because of their unique mechanical/physical properties. However, the physical mechanisms that govern the formation of the atomic structure in HEA thin films are not clear yet. In this work, we synthesized a series of FeCoNiNb0.5 HEA thin films via direct current magnetron sputtering with carefully controlled processing parameters. Through a systematical study by x-ray diffraction and transmission electron microscopy, we demonstrated that the atomic structure of the HEA thin films of the same composition could exhibit different nanostructures and metastable phases, including amorphous and metastable crystalline phases. In addition, we also developed a physical model which sheds quantitative insights into the thermodynamics and kinetics for the phase selection in our HEA thin films. Our current work could pave a way for a controlled synthesis of a variety of nanostructured chemically complex alloy thin films for future structural and functional applications.

Overexpression of miR-145-5p alleviated LPS-induced acute lung injury.

Acute lung injury (ALI) is a disease with high incidence and no effective therapeutic treatments. miR- 145-5p has been reported to be aberrantly expressed in lung injury tissues, suggesting a potential role in the progression and development of ALI. To validate this hypothesis and explore the underlying mechanism, a mouse model of ALI was established using lipopolysaccharide (LPS). Hematoxylin and eosin (Hand E) staining verified the successful establishment of mouse model with ALI. Levels of interleukin (IL)-1ß, IL- 6, tumor necrosis factor α (TNF-α) and myeloperoxidase (MPO) were detected by both enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Mouse type II alveolar epithelial cells (AT II) were isolated and treated with LPS. miR-145-5p was significantly down-regulated both in mice with acute lung injury and LPS-induced AT II cells. Dual luciferase assays confirmed miR-145-5p could target and regulate Toll Like Receptor 4 (TLR4). Further analysis showed that miR-145-5p overexpression decreased the expression levels of IL-1ß, IL-6 and TNF-α in LPS-induced AT II cells. miR-145-5p overexpression also blocked the LPS-induced activation of nuclear factor kappa B (NF-κB) pathway and reactive oxygen species (ROS) accumulation in AT II cells. Finally, in ALI mouse model, miR-145-5p overexpression alleviated lung tissue injury, decreased the expression levels of IL-1ß, IL-6 and TNF-α and reduced MPO activity. In conclusion, miR-145-5p participated in the progression and development of ALI by decreasing the production of pro-inflammatory cytokines, inhibiting NF-κB pathway and suppressing ROS accumulation, shedding light on miR-145-5p as a potential therapeutic target for the treatment of ALI.

[Expression and significance of STAT6 in solitary fibrous tumor].

Objective: To study the clinicopathologic features, the differential diagnosis and the expression of STAT6 in solitary fibrous tumor (SFT). Methods: Eighty cases of SFT were evaluated. The expression of STAT6, CD34, CD99 and bcl-2 protein was studied in these cases and in other groups of soft tissue tumors by immunohistochemical EnVision method. The results were analyzed and relevant literature were reviewed. Results: The expression rate of STAT6 in SFT was 97.5% (78/80) and that in other soft tissue tumors was 3.3% (3/90). The difference was significant (P<0.05). The expression rates of CD34, CD99 and bcl-2 were 88.8% (71/80), 76.3% (61/80) and 75.0% (60/80) in SFT, respectively, which were significantly different from STAT6 expression rate (P<0.05). Conclusions: The expression of STAT6 in SFT has high sensitivity (97.5%) and specificity (96.7%). The expression of STAT6 in SFT is higher than that of CD34, CD99 and bcl-2. STAT6 may be a useful marker for clinical diagnosis of SFT.

[Pulmonary epithelioid hemangioendothelioma: a clinicopathologic analysis of six cases].

OBJECTIVE: To investigate the clinicopathologic characteristics, differential diagnosis and prognosis of pulmonary epithelioid hemangioendotheliomas (PEHs). METHODS: The clinical symptoms and imaging findings of 6 cases of PEHs were investigated and pathologic analyses including histomorphologic and immunohistochemical studies were performed. RESULTS: Clinical symptoms of the patients were nonspecific and insidious. The typical radiological manifestation was characterized by multiple small pulmonary nodules. The pathological findings were well-demarcated hypocellular hyalinized nodules with more cellularity at the periphery of the nodule. The neoplastic cells showed mild nuclear atypia and prominent eosinophilic cytoplasm with vacuoles, attempting to form primitive vasculature. Immunohistochemically, tumor cells were positive to CD31, CD34 and ERG. Follow-up data from 8 months to 5 years showed no tumor progression, except for the development of bone metastases in one case at 6 months. CONCLUSIONS: PEHs are uncommon vascular tumors with low-intermediate malignancy. Using H&E and immunohistochemistry, the final pathological diagnosis can be made and misdiagnosed as a benign fibrotic nodule or other malignant tumors can be avoided. The most effective treatment is surgical resection, if necessary, combined with chemotherapy or radiotherapy.

[Spatial analysis and prediction of severe fever with thrombocytopenia syndrome in Zhejiang province, 2011-2015].

Objective: To understand the distribution of the severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang province, and predict the incidence and the probability of SFTS outbreak. Methods: Based on the cases of SFTS from 2011-2015, software ArcGIS 10.0 was used to analyze the spatial distribution, Moran's I and Getis-Ord Gi were used to analyze the spatial autocorrelation. The incidence trend was explored by trend surface analysis, and the prediction was made by Kriging interpolation. Results: The incidence of SFTS increased and the distribution expanded in Zhejiang from 2011 to 2015, the seasonal and the demographic characteristics of SFTS were similar to the previous research; there were regional clustering of the cases (P<0.001); a downward trend was observed from northeast to southwest in terms of incidence of SFTS; the second-order disjunctive Kriging interpolation based on circular model and the indicator Kriging interpolation based on exponential model had higher prediction accuracy, the probabilities of outbreak in Anji, Daishan and Tiantai were high, the prediction deviation of inland was less than that of edge area. Conclusion: The prediction of SFTS by Kriging interpolation had high accuracy, the incidence of SFTS was higher and the distribution of SFTS was larger than the results of surveillance, the risk areas for epidemic were Anji, Daishan, Ninghai,Tiantai, Sanmen and Linhai.

The role of nisin in fuel ethanol production with Saccharomyces cerevisiae.

AIMS: To investigate the effects of nisin on lactobacilli contamination of yeast during ethanol fermentation and to determine the appropriate concentration required to control the growth of selected lactobacilli in a YP/glucose media fermentation model. METHODS AND RESULTS: The lowest concentration of nisin tested (5 IU ml(-1) ) effectively controlled the contamination of YP/glucose media with 10(6) CFU ml(-1) lactobacilli. Lactic acid yield decreased from 5.0 to 2. 0 g l(-1) and potential ethanol yield losses owing to the growth and metabolism of Lactobacillus plantarum and Lactobacillus brevis were reduced by 11 and 7.8%, respectively. Approximately, equal concentrations of lactic acid were produced by Lact. plantarum and Lact. brevis in the presence of 5 and 2 IU ml(-1) nisin, respectively, thus demonstrating the relatively higher nisin sensitivity of Lact. brevis for the strains in this study. No differences were observed in the final ethanol concentrations produced by yeast in the absence of bacteria at any of the nisin concentrations tested. CONCLUSIONS: Metabolism of contaminating bacteria was reduced in the presence of 5 IU ml(-1) nisin, resulting in reduced lactic acid production and increased ethanol production by the yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteriocins represent an alternative to the use of antibiotics for the control of bacterial contamination in fuel ethanol plants and may be important in preventing the emergence of antibiotic-resistant contaminating strains.

Construction of the industrial ethanol-producing strain of Saccharomyces cerevisiae able to ferment cellobiose and melibiose.

The gene mel1, encoding alpha-galactosidase in Schizosaccharomyces pombe, and the gene bgl2, encoding and beta-glucosidase in Trichoderma reesei, were isolated and co-expressed in the industrial ethanol-producing strain of Saccharomyces cerevisiae. The resulting strains were able to grow on cellobiose and melibiose through simultaneous production of sufficient extracellular alpha-galactosidase and beta-glucosidase activity. Under aerobic conditions, the growth rate of the recombinant strain GC 1 co-expressing 2 genes could achieve 0.29 OD600 h(-1) and a biomass yield up to 7.8 g l(-1) dry cell weight on medium containing 10.0 g l(-1) cellobiose and 10.0 g l(-1) melibiose as sole carbohydrate source. Meanwhile, the new strain of S. cerevisiae CG 1 demonstrated the ability to directly produce ethanol from microcrystalline cellulose during simultaneous saccharification and fermentation process. Approximately 36.5 g l(-1) ethanol was produced from 100 g of cellulose supplied with 5 g l(-1) melibose within 60 h. The yield (g of ethanol produced/g of carbohydrate consumed) was 0.44 g/g, which corresponds to 88.0% of the theoretical yield.

Mannan-modified adenovirus as a vaccine to induce antitumor immunity.

Tumor vaccine is a useful strategy for cancer therapy. However, priming of the immune system requires the relevant antigen to be presented by antigen-presenting cells (APCs). Here, we employed telomerase reverse transcriptase as a model antigen to explore the feasibility of using mannan-modified adenovirus as a tumor vaccine. We found that tumor immunogene therapy with the vaccine was effective at protective antitumor immunity in mice. The antigen-specific cytotoxic T lymphocytes were found in in vitro cytotoxicity assay. The elevation of the killing activity could be abrogated by anti-CD8 or anti-major histocompatibility complex-I antibodies. Adoptive transfer of purified CD8+ cells, and CD4+ cells to a less extent, was effective at antitumor activity. In vivo antitumor activity could be abrogated by depleting CD4+ T lymphocytes. A possible explanation for the antitumor effects may be the antigen was transferred to APCs in the presence of mannan. These observations provide insights into the design of novel vaccine strategies and might be important for the future application of antigens identified in other diseases.

Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen.

Overcoming immune tolerance of the growth factors associated with tumor growth should be a useful approach to cancer therapy by active immunity. We used vascular endothelial growth factor (VEGF) as a model antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a single xenogeneic homologous gene, targeting the growth factors associated with angiogenesis. To test this concept, we constructed a plasmid DNA encoding Xenopus homologous VEGF (XVEGF-p) and control vectors. We found that immunogene tumor therapy with a vaccine based on XVEGF was effective at both protective and therapeutic antitumor immunity in several tumor models in mice. VEGF-specific autoantibodies in sera of mice immunized with XVEGF-p could be found in Western blotting analysis and ELISA assay. The purified immunoglobulins were effective at the inhibition of VEGF-mediated endothelial cell proliferation in vitro, and at antitumor activity and the inhibition of angiogenesis by adoptive transfer in vivo. The elevation of VEGF in the sera of the tumor-bearing mice could be abrogated with XVEGF-p immunization. The antitumor activity and production of VEGF-specific autoantibodies, significantly elevated IgG1 and IgG2b, could be abrogated by the depletion of CD4(+) T lymphocytes. The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factors associated with tumor growth in a cross reaction with single xenogeneic homologous gene and may be of importance in the further exploration of the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.

Blood pressure is associated with body mass index in both normal and obese children.

Obesity is associated with elevated blood pressure (BP) both in adults and children. Childhood obesity has become a severe health problem, especially during the last few decades. So far there has not been any large-scale study specifically focusing on the association between obesity and BP in early life. The aim of this study is to examine systematically the association between obesity and BP in preschool Chinese children in mainland China. In 1996, measurements of weight, height, and BP values were collected in a nationwide, case-control study of 748 boys and 574 girls who ranged in age from 0.1 to 6.9 years in 8 cities in mainland China. One obese child and 1 nonobese child were matched for gender and age. The BP differences of the mean-matched pair were approximately 5 mm Hg for systolic blood pressure (SBP) and approximately 4 mm Hg for diastolic blood pressure (DBP) (P<0.05); a higher value was noted in obese children. The BP value of 19.4% children in the obese group and 7.0% children in the nonobese group was higher than the 95th percentile value (P<0.0001), which is defined as high BP by the Task Force on Blood Pressure Control in Children. Both SBP and DBP were significantly (P<0.05) positively related to body mass index (BMI) values (P<0.05) for children in obese and nonobese groups after adjustment for age, gender, and height. To be specific, an increase of 1 BMI unit was associated with, on average, an increase of 0.56 mm Hg and 0.54 mm Hg in SBP and DBP, respectively, for obese children. In nonobese children, the increase in SBP and DBP was 1.22 mm Hg and 1.20 mm Hg, respectively. An increase in the BMI is conclusively associated with elevated SBP and DBP in nonobese children. Furthermore, an increase in the adjusted BMI was associated with an increase in SBP and DBP in obese and nonobese children.

Risk factors of obesity in preschool children in China: a population-based case--control study.

OBJECTIVE: To identify the risk factors of obesity in preschool children in China. DESIGN: A nationwide case-control study in eight cities in China. SUBJECTS: A total of 748 boys and 574 girls (age 0.1 - 6.9 y), including the obese and non-obese. One obese child was matched with one non-obese child by sex and age. MEASUREMENTS: Weight, height and other measurements were taken for all the subjects. The information on child activity, feeding pattern and family background was collected by our study team from the parents and the kindergarten teacher. RESULTS: Birth weight > or =4.0 kg, high eating speed, obesity among the child's relatives > or =25%, mother's body mass index (BMI) > 25 kg/m2 and father's BMI > 25 kg/m2 were identified as the major significant (P < 0.05) risk factors of obesity in preschool children in China. CONCLUSION: Family history of obesity, high birth weight and eating speed were identified as the risk factors of obesity in preschool children in China. Our results show the need for family therapy as part of an intervention program for childhood obesity, which includes behavior modification.