Search

Background Osteosarcoma (OS) is a tumour with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extraterminal domain (BET) and histone deacetylases (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. Methods Cell proliferation, migration, invasion, colony formation, and sphere-forming assays were performed with the two inhibitors alone or in combination to evaluate their suppressive effect on the malignant properties of OS cells. Apoptosis and the cell cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumours was also examined in a nude mouse xenograft model. Results The combined therapy of OTX015/WT-161 synergistically inhibited growth, migration, and invasion and induced apoptosis, resulting in G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibited the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration revealed that the synergistic downregulation of β-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be critical for the synergistic effect. Finally, the results of an in vivo assay showed that tumour xenografts were significantly decreased after treatment with the OTX015/WT-161 combination compared with OTX015 or WT-161 alone. Conclusions Our findings in this study demonstrated that OTX015 and WT-161 had synergistic anticancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS.

Thin-walled structures are of great importance in automotive crashworthiness design, because of their high crash energy absorption capability and their high potential for light weighting. To identify the best compromise between these two requirements, numerical optimization is needed. Size and shape optimization is relatively well explored while topology optimization for crash is still an open issue. Hence, this paper proposes an approach based on hybrid cellular automata (HCA) for crashworthiness topology optimization with a special focus on thin-walled structures. First approaches have been published, e.g. Duddeck et al. (Struct Multidiscip Optim 54(3):415---428, 2016), using a simple rule to define the target mass for the inner loop of the HCA. To improve the performance, a modified scheme is proposed here for the outer optimization loop, which is based on a bi-section search with limited length. In the inner loop, hybrid updating rules are used to redistribute the mass and a mass correction technique is proposed to make the real mass converge to the target mass strictly. The efficiency and correctness of the proposed method is compared with LS-OPT for axial crash case. Two different methods of defining the target mass in the outer loop are studied, the proposed bi-section search with limited length shows its advantage in two types of three-point bending crash optimization cases. Another advantage of this method is that it requires no significantly increasing number of evaluations when the number of design variables increases. This is demonstrated by applying this method to a crashworthiness optimization problem with 380 design variables.

Although topology optimization is well established in most engineering fields, it is still in its infancy concerning highly non-linear structural applications like vehicular crashworthiness. One of the approaches recently proposed and based on Hybrid Cellular Automata is modified here such that it can be applied for the first time to thin-walled structures. Classical methods based on voxel techniques, i.e., on solid three-dimensional volume elements, cannot derive structures made from thin metal sheets where the main energy absorption mode is related to plastic buckling, folding and failure. Because the main components of car structures are made from such thin-walled beams and panels, a special approach using SFE CONCEPT was developed, which is presented in this paper.

Due to its high packaging strain and shape memory effect, elastic memory composite (EMC) has considerable potential application in future deployable space structures. Buckling of the reinforcing fibers is the primary deformation mechanism of such a new class of functional materials to realize a higher folding strain than that of conventional fiber reinforced composites. In this paper, the orientation of buckling direction of the reinforcing fibers in EMC laminate will be theoretically analyzed to better understand such deformation mechanism. The results reveal that the bucking protruding from the edge produces the lower energy needed for EMC laminate.

Heavy metal contents (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in 99 pairs of soil-rice plant samples were evaluated from the downwind directions of a large thermal power plant in Shaoguan City, Guangdong Province, China. Results indicate that there is a substantial buildup of As, Cd, Cu, Pb, and Zn in the predominant wind direction of the power plant. The significant correlations between S and heavy metals in paddy soil suggest that the power plant represents a source of topsoil heavy metals in Shaoguan City due to sulfur-rich coal burning emissions. Elevated Cd concentrations were also found in rice plant tissues. Average Cd (0.69 mg kg(-1)) and Pb (0.39 mg kg(-1)) contents in rice grain had exceeded their maximum permissible limits (both were 0.2 mg kg(-1)) in foods of China (GB2762-2005). The enrichment of Cd and Pb in rice grain might pose a potential health risk to the local residents.

To study the treatment outcomes of brain-only metastases from small-cell lung cancer (SCLC) at initial diagnose treated by chemotherapy with concurrent brain and thoracic radiotherapy (RT). From Jan 2004 to Jan 2009, 36 treatment-naïve SCLC patients with brain-only metastases in Sun yat-sen University were enrolled. Treatment contained initial EP chemotherapy with concurrent whole-brain radiotherapy (WBRT). EP regimen consisted of etoposide 100 mg/m(2) IV d1-3, cisplatin 80 mg/m(2) IV d1, repeated every 3 weeks. WBRT with total dose of 30 Gy in 10 fractions was started within 1 week from the beginning of chemotherapy followed by thoracic RT including 2 Gy once daily to a total dose of 60 Gy. Treatment responses were evaluated after 3 cycles of chemotherapy. EP regimen was given totally 6 cycles for no tumor progression. Thirty-four patients were evaluable. All of the 20 CNS symptomatic patients experienced symptoms relief. Objective responses in the brain and primary thoracic lesions were observed in 26 (76.5%, 16CR + 10PR) and 29 (85.3%, 23CR + 6PR) patients, respectively. The median survival time (MST) was 19.2 months, and the 1-and 2-year overall survival rates (OS) were 70.6 and 29.4%, respectively, in all patients. Patients with CR response had the longest MST of 21.9 months and 1-and 2-year OS of 93.8 and 43.8%, respectively. Treatment toxicity profiles were acceptable. The treatment strategy of concurrent chemotherapy with brain and thoracic RT might achieve promising survival outcomes comparable to limited-stage SCLC in initially diagnosed SCLC with brain-only metastases.

The concentrations, distribution and sources of 16 polycyclic aromatic hydrocarbons (PAHs) were determined in 30 agricultural soil and 16 vegetable samples collected from subtropical Shunde area, an important manufacturing center in China. The total PAHs ranged from 33.7 to 350 microg/kg in soils, and 82 to 1,258 microg/kg in vegetables. The most abundant individual PAHs are phenanthrene, fluoranthene, chrysene, pyrene and benzo(b)fluoranthene for soil samples, and anthracene, naphthalene, phenanthrene, pyrene and chrysene for vegetable samples. Average vegetable-soil ratios of total PAHs were 2.20 for leafy vegetables and 1.27 for fruity vegetables. Total PAHs in vegetable samples are not significantly correlated to those in corresponding soil samples. Principal component analyses were conducted to distinguish samples on basis of their distribution in each town, soil type and vegetable specie. Relatively abundant soil PAHs were found in town Jun'an, Beijiao, Chencun, Lecong and Ronggui, while abundant vegetable PAHs were observed in town Jun'an, Lecong, Xingtan, Daliang and Chenchun. The highest level of total PAHs were found in vegetable soil, followed by pond sediment and "stacked soil" on pond banks. The PAHs contents in leafy vegetables are higher than those in fruity vegetables. Some PAH compound ratios suggest the PAHs derived from incomplete combustion of petroleum, coal and refuse from power generation and ceramic manufacturing, and paint spraying on furniture, as well as sewage irrigation from textile industries. Soil PAHs contents have significant logarithmic correlation with total organic carbon, which demonstrates the importance of soil organic matter as sorbent to prevent losses of PAHs.