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Epithelial–mesenchymal transition (EMT) is an initiating event in tumor cell invasion and metastasis. It has been shown to occur in resistance to a range of cancer therapies, including tamoxifen. MicroRNAs (miRNAs) have been associated with EMT as well as resistance to standard therapies. To investigate the role of miRNAs in the development of resistance to tamoxifen as well as accompanying EMT-like properties, we established a tamoxifen-resistant (TamR) model by continually exposing MCF-7 breast cancer cells to tamoxifen. In addition to the molecular changes known to be involved in acquired tamoxifen resistance, TamR cells displayed mesenchymal features and had increased invasiveness. Genome-wide miRNA microarray analysis revealed that miRNA-375 was among the top downregulated miRNAs in resistant cells. Re-expression of miR-375 was sufficient to sensitize TamR cells to tamoxifen and partly reversed EMT. A combination of mRNA profiling, bioinformatics analysis and experimental validation identified metadherin (MTDH) as a direct target of miR-375. Knockdown of MTDH partially phenocopied the effects of miR-375 on the sensitivity to tamoxifen and the reversal of EMT. We observed an inverse correlation between the expression of miR-375 and its target MTDH in primary breast cancer samples, implying the pathological relevance of targeting. Finally, tamoxifen-treated patients with higher expression of MTDH had a shorter disease-free survival and higher risk of relapse. As most cancer-related deaths occur because of resistance to standard therapies and metastasis, re-expression of miR-375 or targeting MTDH might serve as potential therapeutic approaches for the treatment of TamR breast cancer.

Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.

The elliptic lattice KdV system, discovered in 2003, is an extension of the lattice potential KdV equation associated with an elliptic curve. This is a rather complicated three-component system on the quad lattice, which contains the moduli of the elliptic curve as parameters. In this paper, we investigate this system further and, among other results, derive a two-component multiquartic form of the system on the quad lattice. Furthermore, we construct an elliptic Yang–Baxter map and study the associated continuous and semidiscrete systems. In particular, we derive the so-called “generating PDE” for this system, comprising a six-component system of second-order PDEs, which can be considered to constitute an elliptic extension of the Ernst equations of General Relativity.

The genes encoding microRNAs of the human miR-200 family map to fragile chromosomal regions and are frequently downregulated upon tumor progression. Although having been reported to regulate epithelial-to-mesenchymal transition and transforming growth factor-beta-driven cell invasion, the role of the miR-200 family in EGF-driven breast cancer cell invasion, viability, apoptosis and cell cycle progression is still unknown. In particular, there is no study comparing the roles of the two clusters of this miRNA family. In this study, we show for the first time that miR-200 family members differentially regulate EGF-driven invasion, viability, apoptosis and cell cycle progression of breast cancer cells. We showed that, all miR-200 family members regulate EGF-driven invasion, with the miR-200bc/429 cluster showing stronger effects than the miR-200a/141 cluster. Furthermore, expression of the miR-200a/141 cluster results in G1 arrest supported by increased p27/Kip1 and decreased cyclin dependent kinase 6 expression. In contrast, expression of the 200bc/429 cluster decreases G1 population and increases G2/M phase, in line with the observed reduction of p27/Kip1 and upregulation of the inhibitory phosphorylation of Cdc25C, respectively. To test the hypothesis that phenotypical differences observed between the two clusters are caused by differential targeting spectrums, we performed genome-wide microarray profiling in combination with gain-of-function studies. This identified phospholipase C gamma 1 (PLCG1), which was downregulated only by the miR-200bc/429 cluster, as a potential candidate contributing to these phenotypical differences. Luciferase reporter assays validated PLCG1 as a direct functional target of miR-200bc/429 cluster, but not of miR-200a/141 cluster. Finally, loss of PLCG1 in part mimicked the effect of miR-200bc/429 overexpression in viability, apoptosis and EGF-driven cell invasion of breast cancer cells. Our results suggest that the miR-200 family has a tumor-suppressor function by negatively regulating EGF-driven cell invasion, viability and cell cycle progression in breast cancer.

Solving the indoor positioning problem can effectively improve work and life efficiency. Outdoors, navigation and positioning mainly rely on satellites to provide global positioning and road network topology to constrain the direction of travel. Therefore, to achieve good indoor navigation and positioning, two things are needed: 1) continuous position acquisition and 2) an indoor road network. Since the indoor environment is relatively stable, the geodetic coordinates of key indoor nodes can be obtained in advance through measurement methods and control points can be set up. Inertial navigation is stable and autonomous, and when combined with control points, it can achieve stable position acquisition. QR codes are rich in information, low in cost, and easy to deploy. They can be used as nodes to construct an indoor road network or as control points. This study proposes an indoor road network map construction method that can achieve local accuracy and global consistency in large indoor scenes. In this indoor road network map, node information includes the position and posture of the QR code. When a machine passes through a node position, it can obtain its absolute position and direction in the geodetic coordinate system by taking a picture of the node’s QR code and combining it with IMU fusion positioning. Through map edge information, indoor navigation and path planning can be achieved.

The microbial production of 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae under micro-aerobic conditions was investigated in this study. The experimental results of batch fermentation showed that the final concentration and yield of 1,3-PD on glycerol under micro-aerobic conditions approached values achieved under anaerobic conditions. However, less ethanol was produced under microaerobic than anaerobic conditions at the end of fermentation. The batch micro-aerobic fermentation time was markedly shorter than that of anaerobic fermentation. This led to an increment of productivity of 1,3-PD. For instance, the concentration, molar yield, and productivity of 1,3-PD of batch micro-aerobic fermentation by K. pneumoniae DSM 2026 were 17.65 g/l, 56.13%, and 2.94 g l(-1) h(-1), respectively, with a fermentation time of 6 h and an initial glycerol concentration of 40 g/l. Compared with DSM 2026, the microbial growth of K. pneumoniae AS 1.1736 was slow and the concentration of 1,3-PD was low under the same conditions. Furthermore, the microbial growth in fed-batch fermentation by K. pneumoniae DSM 2026 was faster under micro-aerobic than anaerobic conditions. The concentration, molar yield, and productivity of 1,3-PD in fed-batch fermentation under micro-aerobic conditions were 59.50 g/l, 51.75%, and 1.57 g l(-1) h(-1), respectively. The volumetric productivity of 1,3-PD under microaerobic conditions was almost twice that of anaerobic fed-batch fermentation, at 1.57 and 0.80 g l(-1) h(-1), respectively.

Objective Controversy remains existed whether chemoradiotherapy (CRT), especially neoadjuvant chemoradiotherapy (neoadjuvant CRT) achieves a significant benefit in resectable pancreatic cancer (PC) treatment. In this meta-analysis, we aimed to clarify the benefits of CRT and neoadjuvant CRT in resectable PC. Methods Eligible trials were identified from MEDLINE, EMBASE, Cochrane center, China National Knowledge Internet and Wanfang database since their inception to July 31, 2013. Only patients with resectable PC, who underwent tumor resection and received CRT and/or neoadjuvant CRT, were enrolled. The treatment outcomes were overall survival (OS) and progression-free survival (PFS). Hazard ratio (HR) with a 95 % confidence interval (CI) was used to measure the pooled effect according to a fixed-effects model. The statistical heterogeneity between trials was detected by χ 2 and I 2 test. Sensitivity analyses were also carried out. Results A total of 28 studies were identified as relevant, but only 17 studies with a total of 3,088 patients were included in the comparison between CRT versus non-CRT, and a total number of three studies with 189 patients included in the comparison between neoadjuvant CRT versus postoperative CRT. The comparison between CRT and non-CRT showed that the overall pooled HR for death was 0.96 (95 % CI 0.89–1.03; P  = 0.28). The HR for progress was 0.83 (95 % CI 0.68–1.03, P  = 0.09). Comparison between neoadjuvant CRT and adjuvant CRT revealed a pooled HR of 0.93 (95 % CI 0.69–1.25; P  = 0.62). Conclusions This meta-analysis showed that CRT showed no significant effect on OS and PFS when compared to non-CRT. Neoadjuvant CRT showed no significant effect over postoperative adjuvant CRT.

Biotransformation of piceid in Polygonum cuspidatum to resveratrol by Aspergillus oryzae was investigated in this study. Resveratrol is widely used in medicine, food, and cosmetic because of its pharmacological properties. However, it has a much lower content in plants compared with its glucoside piceid, which has a much lower bioavailability. Traditionally, the aglycone is acquired by acid or enzymatic hydrolysis of its glucoside, but the violent condition and the acid pollution in hydrolytic reaction and the high cost of the enzyme limit their industrial development. In this paper, fermentation of P. cuspidatum by A. oryzae was successfully performed, during which, piceid was converted to resveratrol with the highest yield of trans-resveratrol 1.35%, 3.6 times higher than that obtained from raw herb by microwave-assisted extraction. Scale-up production was also performed and the yield of trans-resveratrol was 3.1 times higher after 24 h incubation. Therefore, biotransformation is a better method to increase the yield of resveratrol because of its high yield and mild conditions.

Optical property parameters play an important role in ocean colour studies. As a key variable, the absorption coefficient is of great significance for calculating the content of each component in water and simulating the physical, chemical and biological properties of water. The inversion algorithms mainly include empirical model, semi-analytical model and neural network model. In this study, we focused on the QAA_V6, which is the newest version of Quasi-Analytical Algorithm (QAA). It is necessary to test the QAA_V6 model in different conditions. IOCCG data set is used to verify the accuracy of QAA_V6. Additionally, MODIS data of case 1 waters and case 2 waters were selected. After extraction and matching, the data was finally imported into QAA_V6 model to calculate the absorption coefficient with a R2 of 0.999 in both case 1 waters and case 2 waters, thus the QAA_V6 model showed a high accuracy and robust applicability in the inversion of inherent optical properties. Subsequently, it can be further verified for the waters in more complicated areas, providing a firm foundation for implementing QAA into the research of ocean colour remote sensing.

Highway engineering quality inspection and evaluation is a key link in highway engineering construction project quality control, and efficient and effective is essential to quality inspection and evaluation. Combined with the quality inspection and assessment standards, a standardized standard library was formed, and the engineering division was improved to achieve refined engineering division and rationalized engineering division. Through the quality assessment and quality rectification, the whole process of assessment is completed, and the QR code visualization technology is used to match the quality inspection table to realize the information management of the quality inspection data and complete the system research and development. Finally, according to the specific engineering application, the efficiency of bridge engineering quality inspection and evaluation is improved, the evaluation data is effectively managed, and the system functions are fully verified.