An Enhanced Lemaitre Model and Fracture Map for Cr5 Alloy Steel during High-Temperature Forming Process.

To effectively control and predict crack defects in the high-temperature forming process of Cr5 alloy steel, based on the traditional Lemaitre damage model, a new high-temperature damage model of Cr5 alloy steel was proposed which considered the change of material elastic modulus with temperature, the influence of material hydrostatic pressure as well as temperature and strain rate on material damage. Because Cr5 alloy steels are usually forged at high temperatures, tensile testing is an important method to study the damage behaviour of materials. Through the high-temperature tensile test and elastic modulus measurement test of the Cr5 alloy steel, the stress-strain curves and the relationship curves of the elastic modulus value with the temperature of Cr5 alloy steel under different temperatures and strain rates were obtained. A new high-temperature damage model of Cr5 alloy steel was built by introducing the Zener-Hollomon coefficient considering the influence of temperature and strain rate. The established high-temperature damage model was embedded in Forge® finite element software through the program's secondary development method to numerically simulate the experimental process of Cr5 alloy steel. Comparing the difference between the displacement-load curves of the numerical simulation and the actual test of the tensile process of the experimental samples, the correlation coefficient R2 is 0.987 and the difference between the experimental value and the simulated value of the tensile sample elongation at break is 1.28%. The accuracy of the high-temperature damage model of Cr5 alloy steel established in this paper was verified. Finally, the high-temperature damage map of Cr5 alloy steel was constructed to analyse the variation law of various damage parameters with the temperature and strain rate of the high-temperature damage model of Cr5 alloy steel.

Biosorption of sterols from tobacco waste extract using living and dead of newly isolated fungus Aspergillus fumigatus strain LSD-1.

Sterols are verified to be able to produce polycyclic aromatic hydrocarbons during its pyrolysis. In this study, a kind of Aspergillus fumigatus (LSD-1) was isolated from cigar leaves, and the biosorption effects on the stigmasterol, ß-sitosterol, campesterol, cholesterol, and ergosterol by using living and dead biomass of LSD-1 were investigated. The results showed that both living and dead biomass could efficiently remove these sterols in aqueous solution and tobacco waste extract (TWE). Interestingly, compared with the living biomass of LSD-1, the dead biomass of LSD-1 not only kept a high adsorption efficiency but also did not produce ergosterol. Overall, dead biomass of LSD-1 was a more suitable biosorbent to sterols in TWE. Furthermore, Brunner-Emmet-Teller (BET), Fourier transformed infrared spectrometer (FTIR) and scanning electron microscope (SEM) analysis were used to explore the biosorption process of living and dead biomass and their differences, suggesting that the biosorption of sterols was a physical process.

Polyphyllin G exhibits antimicrobial activity and exerts anticancer effects on human oral cancer OECM-1 cells by triggering G2/M cell cycle arrest by inactivating cdc25C-cdc2.

Plant natural products have long been considered to be important sources of bioactive molecules. A large number of antimicrobial and anticancer agents have been isolated form plants. In the present study we evaluated the antimicrobial and anticancer activity of a plant derived secondery metabolite, Polyphyllin G. The results of antibacterial assays showed that Polyphyllin G prevented the growth of both Gram-positive and Gram-negative bacteria with minimum inhibitory concentrations (MICs) ranging from 13.1 to 78 µg/ml. Antifungal activity measured as inhibition of mycelium growth ranged between 38.32 and 56.50%. Further Polyphyllin G was also evaluated against a panel of cancer cell lines. The IC50 of Polyphyllin G ranged from 10 to 65 µM. However the IC50 of Polyphyllin G was found to be comparatively high (120 µM) against the normal FR2 cancer cell line. The lowest IC50 of 10 µM was found against the oral cancer cell line OECM-1. Therefore further studies were carried out on this cell line only. Our results indicated that Polyphyllin G induced cell arrest in oral cancer OECM-1 cells by inactivation of cdc25C-cdc22 via ATM-Chk 1/2 stimulation. Therefore, we propose that Polyphyllin G might prove a lead molecule in the management of oral cancers and at the same time may prevent the growth of opportunistic microbes.

Risk factors for dislocation after revision total hip arthroplasty: A systematic review and meta-analysis.

BACKGROUND: No formal systematic review or meta-analysis was performed up to now to summarize the risk factors of dislocation after revision total hip arthroplasty(THA). AIMS: The present study aimed to quantitatively and comprehensively conclude the risk factors of dislocation after revision total hip arthroplasty. METHODS: A search was applied to CNKI, Embase, Medline, and Cochrane central database (all up to October 2016). All studies assessing the risk factors of dislocation after revision THA without language restriction were reviewed, and qualities of included studies were assessed using the Newcastle-Ottawa Scale. Data were pooled and a meta-analysis completed. RESULTS: A total of 8 studies were selected, which altogether included 4656 revision THAs. 421 of them were cases of dislocation occurred after surgery, suggesting the accumulated incidence of 9.04%. Results of meta-analyses showed that age at surgery (standardized mean difference -0.222; 95% CI -0.413-0.031), small-diameter femoral heads (≤28 mm) (OR 1.451; 95%CI 1.056-1.994), history of instability (OR 2.739; 95%CI 1.888-3.974), number of prior revisions ≥ 3 (OR, 2.226; 95% CI, 1.569-3.16) and number of prior revisions ≥ 2 (OR 1.949; 95% CI 1.349-2.817), acetabular components with elevated rim liner were less likely to develop dislocation after revision THA (OR 0.611; 95% CI 0.415-0.898). CONCLUSIONS: Related prophylaxis strategies should be implemented in patients involved with above-mentioned risk factors to prevent dislocation after revision THA.

Sesamin inhibits lipopolysaccharide-induced proliferation and invasion through the p38-MAPK and NF-κB signaling pathways in prostate cancer cells.

Sesamin, a lipid-soluble lignan, is one of the major constituents of sesame. Previous studies have reported that sesamin induces growth inhibition in human cancer cells, particularly prostate cancer cells. In the present study, we mainly explored the mechanism underlying the protective effect of sesamin on prostate cancer cell proliferation and invasion induced by lipopolysaccharide (LPS). We found that the proliferation of PC3 cells, as determined using the MTT assay, and the expression of cyclin D1, COX-2, Bcl-2 and survivin proteins elevated by LPS were distinctly inhibited by sesamin in a dose-dependent manner. Meanwhile, the ability of PC3 cell invasion, as determined using the Transwell assay and the expression of matrix metalloproteinase 9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) proteins increased by LPS were obviously reduced by sesamin in a dose-dependent manner. In addition, the accumulation of TGF-α and interleukin-6 (IL-6) production induced by LPS in the culture supernatant was found to be decreased dose-dependently with sesamin pretreatment in PC3 cells using the enzyme-linked immunosorbent assay (ELISA) kit. Furthermore, phosphorylation of the p38 protein and nuclear factor (NF)-κB activity in the PC3 cells were enhanced by LPS and further inhibited with sesamin, SB203580 pretreatment or p38-siRNA transfection, respectively. Sesamin or SB203580 pretreatment obviously inhibited PC3 cells-derived tumor growth induced by LPS in vivo. Taken together, these results suggest that the potential ability of sesamin to downregulate the secretion of cytokines and the expression of cell proliferative- and invasive-related gene products induced by LPS was shown to be via the p38 mitogen-activated protein kinase (p38-MAPK) and NF-κB signaling pathways, which may be one of the mechanisms of the anticancer activity of this sesamin agent in prostate cancer cells.

EGFR inhibitor-driven endoplasmic reticulum stress-mediated injury on intestinal epithelial cells.

AIMS: The aim of this study is to understand the underlying mechanisms regulating the adverse effect of diarrhea caused by epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). MAIN METHODS: We comparatively examined the effects of two EGFR-TKIs, gefitinib and icotinib, on intestinal epithelial cells (IEC-6). Cell proliferation was measured using MTT analysis. Expression of multiple cytokines was assayed by real-time PCR. Cell cycle and apoptosis of IEC were evaluated using flow cytometry. Protein levels were determined by Western blot. KEY FINDINGS: These two EGFR-TKIs exerted cytotoxicity to inhibit proliferation and induce apoptosis in IEC-6 cells. These effects are due to the ability of these EGFR-TKIs to cause cell cycle arrest at G0/G1 by regulating the expression of cyclin D1 and p27. In addition, gefitinib and icotinib significantly suppressed the levels of cell adhesion molecules while increasing the expression of the proinflammatory cytokines interleukin (IL)-6 and IL-25. Finally, these EGFR-TKIs triggered an endoplasmic reticulum (ER) stress response, characterized by the activation of the RNA dependent protein kinase-like ER kinase (PERK) pathway and the transcriptional induction of XBP-1 signaling, resulting in ER-mediated cell death. Moreover, gefitinib exerted more cytotoxicity than icotinib on IEC-6 cells. SIGNIFICANCE: Because diarrhea is a common adverse event occurring in patients receiving small-molecular EGFR-TKI chemotherapy, the results of this study are clinically significant. The finding that icotinib exerts less cytotoxic activity than gefitinib on IEC-6 cells indicates its usefulness as a less toxic treatment option for non-small-cell lung cancer.

Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer.

Nonresolving inflammation in the intestine predisposes individuals to the development of colitis-associated cancer (CAC). Inflammasomes are thought to mediate intestinal homeostasis, and their dysregulation contributes to inflammatory bowel diseases and CAC. However, few agents have been reported to reduce CAC by targeting inflammasomes. Here we show that the small molecule andrographolide (Andro) protects mice against azoxymethane/dextran sulfate sodium-induced colon carcinogenesis through inhibiting the NLRP3 inflammasome. Administration of Andro significantly attenuated colitis progression and tumor burden. Andro also inhibited NLRP3 inflammasome activation in macrophages both in vivo and in vitro, as indicated by reduced expression of cleaved CASP1, disruption of NLRP3-PYCARD-CASP1 complex assembly, and lower IL1B secretion. Importantly, Andro was found to trigger mitophagy in macrophages, leading to a reversed mitochondrial membrane potential collapse, which in turn inactivated the NLRP3 inflammasome. Moreover, downregulation of the PIK3CA-AKT1-MTOR-RPS6KB1 pathway accounted for Andro-induced autophagy. Finally, Andro-driven inhibition of the NLRP3 inflammasome and amelioration of murine models for colitis and CAC were significantly blocked by BECN1 knockdown, or by various autophagy inhibitors. Taken together, our findings demonstrate that mitophagy-mediated NLRP3 inflammasome inhibition by Andro is responsible for the prevention of CAC. Our data may help guide decisions regarding the use of Andro in patients with inflammatory bowel diseases, which ultimately reduces the risk of CAC.

Andrographolide sulfonate ameliorates experimental colitis in mice by inhibiting Th1/Th17 response.

Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting condition of inflammation involves overproduction of pro-inflammatory cytokines and excessive functions of inflammatory cells. However, current treatments for IBD may have potential adverse effects including steroid dependence, infections and lymphoma. Therefore new therapies for the treatment of IBD are desperately needed. In the present study, we aimed to examine the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on murine experimental colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Andrographolide sulfonate was administrated through intraperitoneal injection to mice with TNBS-induced colitis. TNBS-induced body weight loss, myeloperoxidase activity, shortening of the colon and colonic inflammation were significantly ameliorated by andrographolide sulfonate. Both the mRNA and protein levels of pro-inflammatory cytokines were reduced by andrographolide sulfonate administration. Moreover, andrographolide sulfonate markedly suppressed the activation of p38 mitogen-activated protein kinase as well as p65 subunit of nuclear factor-κB (NF-κB). Furthermore, CD4(+) T cell infiltration as well as the differentiation of Th1 (CD4(+)IFN-γ(+)) and Th17 (CD4(+)IL17A(+)) subset were inhibited by andrographolide sulfonate. In summary, these results suggest that andrographolide sulfonate ameliorated TNBS-induced colitis in mice through inhibiting Th1/Th17 response. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders.

LKB1 suppresses proliferation and invasion of prostate cancer through hedgehog signaling pathway.

Activation of the hedgehog (Hh) signaling pathway has been implicated in the development of many human malignancies. Hh signaling target genes, such as patched (PTCH), smoothened (SMO) and sonic hedgehog (SHH), are markers of Hh signaling activation in most Hh-associated tumors. The protein kinase LKB1 has been shown to slow proliferation and induce cell-cycle arrest in many cell lines. However, the function of LKB1 in prostate cancer development remains largely unclear. In this study, the expression of LKB1 in human prostate cancer tissue samples and prostate cancer cell lines was detected, and the effects of LKB1 on prostate cancer cell proliferation and invasion were evaluated. Moreover, the influence of LKB1 on target genes of the Hh signaling pathway was analyzed. The results indicated that knockdown of LKB1 expression by RNA interference promoted cell proliferation, colony formation and invasion. Meanwhile, we observed that LKB1 siRNA increased the expression of factors related to Hh signaling reporter activity in prostate cancer cells, including PTCH, SMO and SHH. These findings suggest that LKB1 is a putative tumor suppressor gene in prostate cancer, and that LKB1 is negatively correlated with the expression of Hh signaling related transcription factors. Our results suggest that LKB1 may inhibit tumorigenesis by regulating the Hh signaling pathway in certain cancers.

Loss of SHP-2 activity in CD4+ T cells promotes melanoma progression and metastasis.

The Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2) has been reported to have both tumor-promoting and tumor-suppressing roles in tumorigenesis. However, the role of SHP-2 in tumor immunity remains unclear. Here we observed progressively lower levels of phosphorylated SHP-2 in tumor-associated CD4(+) T cells during melanoma development in a murine model. Similarly, the levels of phosphorylated SHP-2 in the CD4(+) T cells of human melanoma specimens revealed a decrease paralleling cancer development. The CD4(+) T cell-specific deletion of SHP-2 promoted melanoma metastasis in mice. Furthermore, SHP-2 deficiency in CD4(+) T cells resulted in the increased release of inflammatory cytokines, especially IL-6, and the enhanced accumulation of tumor-promoting myeloid-derived suppressor cells (MDSCs) in tumor-bearing mice. An IL-6-neutralizing antibody reduced MDSC accumulation and inhibited tumor growth in CD4(+) T-cell-specific SHP-2-knockout mice. Our results suggest that SHP-2 in CD4(+) T cells plays an important role in preventing melanoma progression and metastasis.