;~lasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

Persistent activation of Survivin and its overexpression contribute to the formation, progression and metastasis of several different tumor types. Therefore, Survivin is an ideal target for RNA interference mediated-growth inhibition. Blockade of Survivin using specific short hairpin RNAs （shRNA） can significantly reduce prostate tumor growth. RNA interference does not fully ablate target gene expression, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Survivin-specific shRNA, we employed a combinatorial expression of Survivin-specific shRNA and gene associated with retinoid-interferon-induced mortality-19 （GRIM-19）. Then, the GRIM-19 coding sequences and Survivin-specific shRNAs were used to create a dual expression plasmid vector and were carried by an attenuated strain of Salmonella enteric serovar typhimurium （S. typhimurium） to treat prostate cancer in vitro and in vivo. We found that the co-expressed Survivin-specific shRNA and GRIM-19 synergistically and more effectively inhibited prostate tumor proliferation and survival, when compared with treatment with either single agent alone in vitroand in vivo. This study has provided a novel cancer gene therapeutic approach for prostate cancer.

Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo

DNA vector-based Stat3-specific RNA interference （si-Stat3） blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BIJ6 mice. CaCl2-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Star3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGFand cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling （TUNEL） assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% （P〈0.01）. Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis （up to 42%, P〈0.01）. The Stat3 downstream genes Bcl-2, VEGFand cyclin DI were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.

Novel esophageal squamous cell carcinoma bone metastatic clone isolated by scintigraphy, X ray and micro PET/CT

AIM: To establish a Chinese esophageal squamous cell carcinoma (ESCC) cell line with high bone metastasis potency using 99mTc-methylene diphosphonate (99mTc-MDP) micro-pinhole scintigraphy, X ray and micro-positron emission tomography/computed tomography (PET/CT) for exploring the mechanism of occurrence and development in esophageal cancer.

High temperature stress–strain curves of MnS and their applications in finite element simulation

A novel method for testing stress–strain curves of non-metallic materials was presented.The high temperature stress-strain curves of MnS were preliminarily obtained and corrected to account for the influence of friction.Using the finite element method,the influence of deformation parameters on the deformation evolution of MnS inclusions was investigated based on the experimental reference data.The corresponding physical experiment was designed for comparative analysis.The results indicate that the experimental high-temperature deformation data of MnS are highly reliable.In the process of matrix deformation,the shapes of MnS inclusions change from spherical to ellipsoidal and even to lamellar.There are some differences in the morphological deformation of MnS inclusions located at different positions.With the increase in the initial size of MnS inclusions,the risk of failing the inclusion-flaw inspection increases and the forging quality further deteriorates.

Is XMRV a causal virus for prostate cancer？

The potential association between xenotropic murine leukaemia virus-related gammaretrovirus （XMRV） and prostate cancer （PCa） has been documented since 2006, It is important for furthering our understanding of the biological mechanisms of PCa to ascertain whether this association is causal. To summarize the available information on the epidemiological and laboratory findings of the association, we conducted a literature search of the PubMed electronic database （from March 2006 to February 2011） to identify relevant published studies that examined the association between XMRV and PCa, Although several studies showed the positive association between XMRV and PCa, more recent studies did not support this conclusion, The positive findings might be due to contamination of human samples, Further studies are needed to clarify this association,

High-temperature fracture behavior of MnS inclusions based on GTN model

The influence of the MnS plastic inclusion on the accumulation of internal damage was considered, and the Gurson– Tvergaard–Needleman (GTN) model was calibrated based on the finite element inverse method and image analysis method using ABAQUS and GTN models. The modified GTN damage model was used to simulate the initiation and propagation of cracks in an as-cast 304 stainless steel with MnS inclusions at 900 C. The simulation results agreed well with the experimental results, indicating that the model can be effectively applied to examine the high-temperature fracture behavior of MnS inclusions. The simulation and high-temperature tensile test results revealed that MnS inclusions increased the number of holes initiation and the probability of hole polymerization, reduced the crack propagation resistance, accelerated the occurrence of material fracture behavior, and were closely related to the stress state at high temperatures. When the stress triaxiality was low, the plastic strain in the metal matrix was high, and the MnS plastic inclusions accelerated the polymerization of the pores, making metal fracture failure more likely. On the other hand, when the stress triaxiality was high, the stress state in the metal matrix was biased to the tensile state, the plastic strain in the metal matrix was low, and the influence of MnS plastic inclusions on the fracture behavior was not evident.

Prediction of Critical Conditions for Dynamic Recrystallization in 316LN Austenitic Steel

Hot compression experiments conducted on a Gleeble-3500thermo-mechanical simulator and metallographic observation tests were employed to study the critical conditions of dynamic recrystallization（DRX）of 316 LN austenitic stainless steel.The true stress-true strain curves of 316 LN were obtained at deformation temperatures ranging from 900℃to 1 200℃and strain rates ranging from 0.001s-1 to 10s-1.Based on the above tests,the critical conditions of DRX were determined and compared with those obtained from work-hardening theory and the Cingara-McQueen flow stress model.Furthermore,the microstructure was observed to validate the calculated results.The ratio of critical strain to peak strain（εc/εp）for 316 LN was determined,and the quantitative relationship between the critical strain and the deformation parameters of 316 LN was elucidated.The results demonstrated that the onset of DRX corresponds to the constant normalized strain hardening rate（Γ）,namely,the critical strain hardening rateΓcfor316LN is equal to 0.65.

Flow Stress Behaviors and Microstructure Evolution of 300M High Strength Steel under Isothermal Compression

The compressive deformation behaviors of 300M high strength steel were investigated over a wide range of temperatures （850- 1200 C） and strain rates （0. 001- 10 s^- 1 ） on a Gleeble-3800 thermo-mechanical simulator. The measured flow stress was modified by the corrections of the friction and the temperature compensations, which nicely reflect negative effects of the friction and temperature on the flow stress. The corrected stress-strain curves were the dynamic recrystallization type on the conditions of higher deformation temperature and lower strain rate. Flow stress increases with the increase of strain rate at the same deformation temperature and strain. By contrast, flow stress decreases with the increase of temperature at the same strain rate and strain. Dependence of the peak stress on temperature and strain rate for 300M steel is described by means of the conventional hyperbolic sine equation. By re gression analysis, the activation energy （Q） in the whole range of deformation temperature is determined to be 367. 562 kJ/mol. The effects of the temperature and the strain rate on mierostructural evolution are obvious. With the increase of the deformation temperature and the decrease of the strain rate, the original austenite grain sizes of 300M steel increase. At the same time, the corrected flow stress curves more accurately determine the evolution of the microstrueture.

Self-assembly of Amphiphilic Linear Diblock Rod-Coil Molecules by Hydrogen Bond and π-π Stacking Interactions

Aromatic amphiphilic molecules（1） consisting of three biphenyl groups linked together with ether bonds as a rigid rod segment and poly（ethylene oxide） with the number of repeating units of 17 as a coil segment were synthesized, and their self-assembly behavior in the bulk state and aqueous solution was investigated. In bulk, molecules 1 self-assembled into 1-D lamellar structure in the solid state or smectic A phase in the liquid crystalline phase via the cooperative effects of ？-？ stacking, micro-phase separation and hydrogen bond interactions. In dilute aqueous solutions, molecules 1 were observed to selfassemble into cylindrical micelles owned uniform diameter and length of hundreds of nanometers.

Formation Mechanism of Inclusion Defects in Large Forged Pieces

Nonmetallic inclusions mixed into large forged metal objects destroy the continuity in the metal and affect the quality of the forged product.Research on how inclusions affect the plastic deformation of a matrix shows the significance of the formation mechanism of inclusion defects.For upset forging,the nonlinear finite element model was shown to be appropriate for the ingot hot-forging process by comparing the results with experiments involving plastic and hard inclusions inserted into the forged piece.The high-temperature stress-strain curves of MnS plastic inclusions were obtained experimentally.The results show how,during upsetting,the morphology of MnS plastic inclusions varies from spherical to ellipsoidal,until finally becoming flat in shape.The larger the inclusion is,the larger the degree of deformation of the inclusion is,and large inclusions enhance the risk of the final product failing to pass inspection for inclusion flaws.Strain significantly concentrates in the matrix near a hard inclusion.When the hard inclusion reaches a certain size,conical fractures form on both sides of the inclusion.To pass inclusion-flaw inspection and close hole defects to the extent possible,the flat-anvil upsetting is recommended.Finally,the inclusiondeformation state obtained by finite element simulation is verified experimentally.