;~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.

羟基磷灰石纳米粒子携带Si-Star3质粒抑制小鼠前列腺癌生长的体外研究

DNA质粒介导的Stat3特异性RNA干扰呵以阻断Stat3信号并抑制前列腺肿瘤的生长。然而，抗肿瘤效心依赖于si—Stat3质粒的传递效率。本研究揭示了羟基磷灰石携带Stat3siRNA质粒对小鼠前列腺癌生长的影响。采用RM-1瘤块种植C57BL／6小鼠。CaCl2修饰的径基磷灰石携带si-Stat3质粒瘤体注射，测量肿瘤体积并绘制生长曲线，检测肿瘤组织学变化。采用RT-PCR和Westernblot分析Stat3展因与蛋白的表达变化，及pTyr—Stat3，Bcl-2，Bax，Caspase3，VEGF和cyclinD1蛋白的表达变化。采用免疫组织化学和TUNEL检测细胞凋亡。移植RM1瘤块C57BL／6小鼠，羟基磷灰石纳米粒子携带si-Stat3组与对照组相比较，显著抑制了肿瘤的生长，抑制率达到74％（P〈0．01）。在si-Stat3组肿瘤组织中，Stat3的表达水平显著下调，同时，肿瘤细胞的凋亡显著增加，凋亡指数达42％（P〈0．01）。肿垴组织中Stat3下游基因Bcl-2，VEGF和cyclinD1的表达水平也出现明显下调，同时Bax蛋白的表达增加和Caspase3的活性增强。这些结果表明，羟基磷灰石纳米粒子可以携带RNA干扰质粒进入肿瘤细胞内。

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 using99mTc-methylene diphosphonate(99mTcMDP)micro-pinhole scintigraphy,X ray and micropositron emission tomography/computed tomography(PET/CT)for exploring the mechanism of occurrence and development in esophageal cancer.METHODS:The cells came from a BALB/c nu/nu immunodeficient mouse,and oncogenic tumor tissue was from a surgical specimen from a 61-year-old male patient with ESCC.The cell growth curve was mapped and analysis of chromosome karyotype was performed.Approximately 1×106oncogenic cells were injected into the left cardiac ventricle of immunodeficient mice.The bone metastatic lesions of tumor-bearing mice were detected by99mTc-MDP scintigraphy,micro-PET/CT and X-ray,and were resected from the mice under deep anesthesia.The bone metastatic cells in the lesions were used for culture and for repeated intracardiac inoculation.This in vivo/in vitro experimental metastasis study was repeated for four cycles.All of the suspicious bone sites were confirmed by pathology.Real-time polymerase chain reaction was used to compare the gene expression in the parental cells and in the bone metastatic clone.RESULTS:The surgical specimen was implanted subcutaneously in immunodeficient mice and the tumorigenesis rate was 100%.First-passage oncogenic cells were named CEK-Sq-1.The chromosome karyotype analysis of the cell line was hypotriploid.The bone metastasis rate went from 20%with the first-passage oncogenic cells via intracardiac inoculation to 90%after four cycles.The established bone metastasis clone named CEK-Sq-1BM had a high potential to metastasize in bone,including mandible,humerus,thoracic and lumbar vertebrae,scapula and femur.The bone metastasis lesions were successfully detected by micro-pinhole bone scintigraphy,micro-PET/CT,and X-ray.The sensitivity,specificity and accuracy of the micro-pinhole scintigraphy,X-ray,and micro-PET/CT imaging examinations were:89.66%/32%/80%,88.2%/100%/89.2%,and 88.75%/77.5%/87.5%,respectively.Some gene expression difference was found between parental and bone metastasis cells.CONCLUSION:This newly established Chinese ESCC cell line and animal model may provide a useful tool for the study of the pathogenesis and development of esophageal carcinoma.

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,

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.

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.

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.