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Steel slag has been used widely as an aggregate in road application, but it could pose a contamination risk for the environment due to considerable heavy metals (HMs). To explore the leaching behavior and contamination risk of HMs from steel slag and its asphalt mixture is of great significance. In this study, the physical-chemical features, batch leaching test and semi-dynamic test were conducted to determine the mobility capability and leaching characteristics of HMs. The results show that steel slag presents a low pollution risk in short-term leaching, whereas the cumulative release mass of Cd, Ni, As and Pb are more than or approach the limits, which indicates that steel slag exhibits environment impacts to a certain extent. Steel slag covered with asphalt binder results in As and Cu reduced by 3.64% and 4.83%. Diffusion is the main controlling mechanism of HMs in asphalt mixture and the mobility capability of most HMs were classed as "low mobility" (LI > 8). Asphalt stripping off can aggravate the release potential of HMs from asphalt mixture, but the pollution risk remains controllable. [ABSTRACT FROM AUTHOR]

Lung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. Brassica nigra (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previously exhibited significant anticancer activities against several cancer types. In the present study, we have investigated various cellular and molecular mechanisms of anticancer effects of an ethanolic extract of B. nigra seeds against A549 and H1299 human non-small cell lung cancer cell lines. B. nigra extract showed a substantial growth-inhibitory effect as it reduced the viability and clonogenic survival of A549 and H1299 cells in a concentration-dependent manner. B. nigra extract induced cellular apoptosis in a time- and concentration-dependent fashion as evidenced from increased caspase-3 activity. Furthermore, treatment of both A549 and H1299 cells with B. nigra extract alone or in combination with camptothecin induced DNA double-strand breaks as evidenced by upregulation of γH2A histone family member X, Fanconi anemia group D2 protein, Fanconi anemia group J protein, ataxia-telangiectesia mutated and Rad3-related protein. Based on cell cycle analysis, B. nigra extract significantly arrested A549 and H1299 cells at S and G2/M phases. Additionally, B. nigra extract suppressed the migratory and invasive properties of both cell lines, downregulated the expression of matrix metalloproteinase-2 (MMP2), MMP9, and Snail and upregulated the expression of E-cadherin at mRNA and protein levels. Taken together, these findings indicate that B. nigra seed extract may have an important anticancer potential against human lung cancer which could be mediated through simultaneous and differential regulation of proliferation, apoptosis, DNA damage, cell cycle, migration, and invasion. [ABSTRACT FROM AUTHOR]

Artemisia annua L. has been reported to show anti-cancer activities. Here, we determined whether polyphenols extracted from Artemisia annua L. (pKAL) exhibit anti-cancer effects on radio-resistant MDA-MB-231 human breast cancer cells (RT-R-MDA-MB-231 cells), and further explored their molecular mechanisms. Cell viability assay and colony-forming assay revealed that pKAL inhibited cell proliferation on both parental and RT-R-MDA-MB-231 cells in a dose-dependent manner. The anti-proliferative effects of pKAL on RT-R-MDA-MB-231 cells were superior or similar to those on parental ones. Western blot analysis revealed that expressions of cluster of differentiation 44 (CD44) and Oct 3/4, matrix metalloproteinase-9 (MMP-9) and signal transducer and activator of transcription-3 (STAT-3) phosphorylation were significantly increased in RT-R-MDA-MB-231 cells compared to parental ones, suggesting that these proteins could be associated with RT resistance. pKAL inhibited the expression of CD44 and Oct 3/4 (CSC markers), and β-catenin and MMP-9 as well as STAT-3 phosphorylation of RT-R-MDA-MB-231. Regarding upstream signaling, the JNK or JAK2 inhibitor could inhibit STAT-3 activation in RT-R-MDA-MB-231 cells, but not augmented pKAL-induced anti-cancer effects. These findings suggest that c-Jun N-terminal kinase (JNK) or Janus kinase 2 (JAK2)/STAT3 signaling are not closely related to the anti-cancer effects of pKAL. In conclusion, this study suggests that pKAL exhibit anti-cancer effects on RT-R-MDA-MB-231 cells by suppressing CD44 and Oct 3/4, β-catenin and MMP-9, which appeared to be linked to RT resistance of RT-R-MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

An externally bonded fiber reinforced polymer (FRP) plate (or sheet) is now widely used in strengthening bending members due to its outstanding properties, such as a high strength to weight ratio, easy operating, corrosion and fatigue resistance. However, the concrete member strengthened by this technology may have a problem with the adhesion between FRP and concrete. This kind of debonding failure can be broadly classified into two modes: (a) plate end debonding at or near the plate end, and (b) intermediate crack-induced debonding (intermediate crack-induced (IC) debonding) near the loading point. The IC debonding, unlike the plate end debonding, still needs a large amount of investigation work, especially for the interface under fatigue load. In this paper, ten single shear pull-out tests were carried out under a static or fatigue load. Different load ranges and load levels were considered, and the debonding growth process was carefully recorded. The experimental results indicate that the load range is one of the main parameters, which determines the debonding growth rate. Moreover, the load level can also play an important role when loaded with the same load range. Finally, a new prediction model of the fatigue debonding growth rate was proposed, and has an excellent agreement with the experimental results. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the shear capacity performance for eight deep beams with HTRB600 reinforced high strength concrete under concentrated load to enable a better understanding of the effects of shear span–depth ratio, longitudinal reinforcement ratio, vertical stirrup ratio and in order to improve design procedures. The dimension of eight test specimens is 1600 mm × 200 mm × 600 mm. The effective span to height ratio l0/h is 2.0, the shear span–depth ratio λ is 0.3, 0.6 and 0.9, respectively. In addition, the longitudinal reinforcement ratio ρs is set to 0.67%, 1.05%, 1.27%, and the vertical stirrup ratio is taken to be 0%, 0.25%, 0.33%, 0.5%. Through measuring the strain of steel bar, the strain of concrete and the deflection of mid-span, the characteristics of the full process of shear capacity, the failure mode and the load deflection deformation curve were examined. The test results showed that the failure mode of deep beams with small shear span–depth ratio is diagonal compression failure, which is influenced by the layout and quantity of web reinforcement. The diagonal compression failure could be classified into two forms: crushing-strut and diagonal splitting. With decreasing of shear span–depth ratio and increasing longitudinal reinforcement ratio, the shear capacity of deep beams increases obviously, while the influence of vertical web reinforcement ratio on shear capacity is negligible. Finally, the shear capacity of eight deep beams based on GB 50010-2010 is calculated and compared with the calculation results of ACI 318-14, EN 1992-1-1:2004 and CSA A23.3-04, which are based on strut-and-tie model. The obtained results in this paper show a very good agreement with GB50010-2010 and ACI 318-14, while the results of EN 1992-1-1:2004 and CSA A23.3-04 are approved to be conservative. [ABSTRACT FROM AUTHOR]

Previous studies have shown that small-molecule BCL-2 inhibitors can have a synergistic interaction with ABCG2 substrates in chemotherapy. Venetoclax is a potent and selective BCL-2 inhibitor, approved by the FDA in 2016 for the treatment of patients with chronic lymphocytic leukemia (CLL). This study showed that, at a non-toxic concentration, venetoclax at 10 µM significantly reversed multidrug resistance (MDR) mediated by wild-type ABCG2, without significantly affecting MDR mediated by mutated ABCG2 (R482G and R482T) and ABCB1, while moderate or no reversal effects were observed at lower concentrations (0.5 to 1 µM). The results showed that venetoclax increased the intracellular accumulation of chemotherapeutic agents, which was the result of directly blocking the wild-type ABCG2 efflux function and inhibiting the ATPase activity of ABCG2. Our study demonstrated that venetoclax potentiates the efficacy of wild-type ABCG2 substrate drugs. These findings may provide useful guidance in combination therapy against wild-type ABCG2-mediated MDR cancer in clinical practice. [ABSTRACT FROM AUTHOR]

Tivantinib, also known as ARQ-197, is a potent non-ATP competitive selective c-Met inhibitor currently under phase 3 clinical trial evaluation for liver and lung cancers. In this study, we explored factors that may lead to tivantinib resistance, especially in regards to its interaction with ATP-binding cassette super-family G member 2 (ABCG2). ABCG2 is one of the most important members of the ATP-binding cassette (ABC) transporter family, a group of membrane proteins that play a critical role in mediating multidrug resistance (MDR) in a variety of cancers, including those of the liver and lung. Tivantinib received a high score in docking analysis, indicating a strong interaction between tivantinib and ABCG2, and an ATPase assay indicated that tivantinib stimulated ABCG2 ATPase activity in a concentration-dependent manner. An MTT assay showed that ABCG2 overexpression significantly desensitized both the cancer cells and ABCG2 transfected-HEK293 cells to tivantinib and that this drug resistance can be reversed by ABCG2 inhibitors. Furthermore, tivantinib upregulated the protein expression of ABCG2 without altering the cell surface localization of ABCG2, leading to increased resistance to substrate drugs, such as mitoxantrone. Altogether, these data demonstrate that tivantinib is a substrate of ABCG2, and, therefore, ABCG2 overexpression may decrease its therapeutic effect. Our study provides evidence that the overexpression of ABCG2 should be monitored in clinical settings as an important risk factor for tivantinib drug resistance. [ABSTRACT FROM AUTHOR]

The overexpression of ABC transporters induced by anticancer drugs has been found to be the main cause of multidrug resistance. It is actually also a strategy by which cancer cells escape being killed. Tetrandrine is a natural product extracted from the stem of Tinospora crispa. In this study, tetrandrine showed synergistic cytotoxic activity in combinational use with chemotherapeutic drugs, such as Doxorubicin, Vincristine, and Paclitaxel, in both drug-induced and MDR1 gene-transfected cancer cells that over-expressed ABCB1/P-glycoprotein. Tetrandrine stimulated P-glycoprotein ATPase activity, decreased the efflux of [3H]-Paclitaxel and increased the intracellular accumulation of [3H]-Paclitaxel in KB-C2 cells. Furthermore, SW620/Ad300 and KB-C2 cells pretreated with 1 μM tetrandrine for 72 h decreased P-glycoprotein expression without changing its cellular localization. This was demonstrated through Western blotting and immunofluorescence analysis. Interestingly, down-regulation of P-glycoprotein expression was not correlated with gene transcription, as the MDR1 mRNA level exhibited a slight fluctuation in SW620/Ad300 and KB-C2 cells at 0, 24, 48, and 72 h treatment time points. In addition, molecular docking analysis predicted that tetrandrine had inhibitory potential with the ABCB1 transporter. Our results suggested that tetrandrine can antagonize MDR in both drug-selected and MDR1 gene-transfected cancer cells by down regulating the expression of the ABCB1 transporter, followed by increasing the intracellular concentration of chemotherapeutic agents. The combinational therapy using tetrandrine and other anticancer drugs could promote the treatment efficiency of drugs that are substrates of ABCB1. [ABSTRACT FROM AUTHOR]

The WRKY family is one of the largest transcription factor (TF) families in plants and plays central roles in modulating plant stress responses and developmental processes, as well as secondary metabolic regulations. Lotus (Nelumbo nucifera) is an aquatic crop that has significant food, ornamental and pharmacological values. Here, we performed an overview analysis of WRKY TF family members in lotus, and studied their functions in environmental adaptation and regulation of lotus benzylisoquinoline alkaloid (BIA) biosynthesis. A total of 65 WRKY genes were identified in the lotus genome and they were well clustered in a similar pattern with their Arabidopsis homologs in seven groups (designated I, IIa-IIe, and III), although no lotus WRKY was clustered in the group IIIa. Most lotus WRKYs were functionally paired, which was attributed to the recently occurred whole genome duplication in lotus. In addition, lotus WRKYs were regulated dramatically by salicilic acid (SA), jasmonic acid (JA), and submergence treatments, and two lotus WRKYs, NnWRKY40a and NnWRKY40b, were significantly induced by JA and promoted lotus BIA biosynthesis through activating BIA biosynthetic genes. The investigation of WRKY TFs for this basal eudicot reveals new insights into the evolution of the WRKY family, and provides fundamental information for their functional studies and lotus breeding. [ABSTRACT FROM AUTHOR]

Jointly using spatial and spectral information has been widely applied to hyperspectral image (HSI) classification. Especially, convolutional neural networks (CNN) have gained attention in recent years due to their detailed representation of features. However, most of CNN-based HSI classification methods mainly use patches as input classifier. This limits the range of use for spatial neighbor information and reduces processing efficiency in training and testing. To overcome this problem, we propose an image-based classification framework that is efficient and straightforward. Based on this framework, we propose a multiscale spatial-spectral CNN for HSIs (HyMSCN) to integrate both multiple receptive fields fused features and multiscale spatial features at different levels. The fused features are exploited using a lightweight block called the multiple receptive field feature block (MRFF), which contains various types of dilation convolution. By fusing multiple receptive field features and multiscale spatial features, the HyMSCN has comprehensive feature representation for classification. Experimental results from three real hyperspectral images prove the efficiency of the proposed framework. The proposed method also achieves superior performance for HSI classification. [ABSTRACT FROM AUTHOR]

P-glycoprotein (P-gp), which is encoded by the ATP-binding cassette (ABC) transporter subfamily B member 1 (ABCB1) gene, is one of the most pivotal ABC transporters that transport its substrates across the cell membrane. Its overexpression is one of the confirmed causes of multidrug resistance (MDR), which results in the failure of cancer treatment. Here, we report that checkpoint kinase (Chk) 1 inhibitor MK-8776, a drug candidate in clinical trial, can restore the sensitivity of chemotherapeutics that are substrates of P-gp in KB-C2, SW620/Ad300 cells and human embryonic kidney (HEK)293/ABCB1 cells that overexpress P-gp. MK-8776 remarkably enhanced the cellular [3H]-paclitaxel accumulation and suppressed the efflux function of P-gp without reducing its expression and affecting its cellular localization in cancer cells. Furthermore, MK-8776 (0–40 μM) stimulated the activity of ATPase in P-gp, which was 4.1-fold greater than the control. In addition, MK-8776 formed a cation–π bond and π–π interaction with key residues of the substrate-binding site in P-gp, as indicated by computer-aided molecular docking study. Our study indicated that MK-8776 may significantly enhance the sensitivity of chemotherapeutics that are substrates of P-gp, providing important information for its application in the reversal of MDR. [ABSTRACT FROM AUTHOR]

We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage. However, whether it has the ability to exert antitumor activity in other cancer cells and what is the exact molecular mechanism for its antiproliferation effect remained to be determined. In the present study, compound-7g exhibited strong activity in suppressing proliferation and growth of glioblastoma cells. The inhibitor selectively downregulated F-box protein SKP2 expression and upregulated cell cycle inhibitor p27, and then resulted in G1 cell cycle arrest. Mechanism analysis revealed that compound-7g also provokes the down-regulation of E2F-1, which acts as a transcriptional factor of SKP2. Further results indicated that compound-7g induced an increase of LC3B-II and p62, which causes a suppression of fusion between autophagosome and lysosome. Moreover, compound-7g mediated autophagic flux blockage promoted accumulation of ubiquitinated proteins and then led to endoplasmic reticulum stress. Our study thus demonstrated that pharmacological inactivation of E2F-1-SKP2-p27 axis is a promising target for restricting cancer progression. [ABSTRACT FROM AUTHOR]

Material properties at elevated temperatures are important factors in the fire safety design and numerical analysis of concrete members strengthened with fiber reinforced polymer (FRP) composites. Most of the previous research mainly focused on tensile strength and elastic modulus in conventional steady state temperature tests. However, the transient state test method is more realistic for strengthening concrete structures. At the same time, the coefficient of thermal expansion of FRP composites is also one of the important factors affecting concrete members at elevated temperatures. This paper presents a detailed experimental investigation on the longitudinal thermal expansion deformation, and the mechanical properties of carbon FRP (CFRP) tendons with 8 mm diameter in the steady state and transient state. The results indicate that longitudinal deformation of CFRP tendons is negative at high temperature; in addition, the transient state test results of CFRP tendons are slightly higher than the steady state test results. The final part of this paper assesses the accuracy of different empirical models. Furthermore, a new equation calculating the properties of CFRP composites at elevated temperatures is presented with the numerical fitting technique, which is in good agreement with the experimental results. [ABSTRACT FROM AUTHOR]

Seven known sesquiterpene coumarins and a new sesquiterpene coumarin, anatolicin (8), were isolated from the dichloromethane extract of the roots of Heptaptera anatolica. Structures of these compounds were elucidated based on their spectral properties. While some of these sesquiterpene coumarins showed modest cytotoxic activity against COLO205, KM12, A498, UO31, and TC32 cancer cell lines, selective cytotoxicity of anatolicin (8) and 14′-acetoxybadrakemin (7) were observed at nanomolar level against the UO31 kidney cancer cell line. [ABSTRACT FROM AUTHOR]

The phytochemical oxyresveratrol has been shown to exert diverse biological activities including prevention of obesity. However, the exact reason underlying the anti-obese effects of oxyresveratrol is not fully understood. Here, we investigated the effects and mechanism of oxyresveratrol in adipocytes and high-fat diet (HFD)-fed obese mice. Oxyresveratrol suppressed lipid accumulation and expression of adipocyte markers during the adipocyte differentiation of 3T3-L1 and C3H10T1/2 cells. Administration of oxyresveratrol in HFD-fed obese mice prevented body-weight gains, lowered adipose tissue weights, improved lipid profiles, and increased glucose tolerance. The anti-obese effects were linked to increases in energy expenditure and higher rectal temperatures without affecting food intake, fecal lipid content, and physical activity. The increased energy expenditure by oxyresveratrol was concordant with the induction of thermogenic genes including Ucp1, and the reduction of white adipocyte selective genes in adipose tissue. Furthermore, Foxo3a was identified as an oxyresveratrol-induced gene and it mimicked the effects of oxyresveratrol for induction of thermogenic genes and suppression of white adipocyte selective genes, suggesting the role of Foxo3a in oxyresveratrol-mediated anti-obese effects. Taken together, these data show that oxyresveratrol increases energy expenditure through the induction of thermogenic genes in adipose tissue and further implicates oxyresveratrol as an ingredient and Foxo3a as a molecular target for the development of functional foods in obesity and metabolic diseases. [ABSTRACT FROM AUTHOR]

Ginsenosides from Panax ginseng (Korean ginseng) are unique triterpenoidal saponins that are considered to be responsible for most of the pharmacological activities of P. ginseng. However, the various linkage positions cause different pharmacological activities. In this context, we aimed to synthesize new derivatives of ginsenosides with unusual linkages that show enhanced pharmacological activities. Novel α-glycosylated derivatives of ginsenoside F1 were synthesized from transglycosylation reactions of dextrin (sugar donor) and ginsenoside F1 (acceptor) by the successive actions of Toruzyme®3.0L, a cyclodextrin glucanotransferase. One of the resultant products was isolated and identified as (20S)-3β,6α,12β-trihydroxydammar-24ene-(20-O-β-D-glucopyranosyl-(1→2)-α-D-glucopyranoside) by various spectroscopic characterization techniques of fast atom bombardment-mass spectrometry (FAB-MS), infrared spectroscopy (IR), proton-nuclear magnetic resonance (1H-NMR), 13C-NMR, gradient heteronuclear single quantum coherence (gHSQC), and gradient heteronuclear multiple bond coherence (gHMBC). As expected, the novel α-glycosylated ginsenoside F1 (G1-F1) exhibited increased solubility, lower cytotoxicity toward human dermal fibroblast cells (HDF), and higher tyrosinase activity and ultraviolet A (UVA)-induced inhibitory activity against matrix metalloproteinase-1 (MMP-1) than ginsenoside F1. Since F1 has been reported as an antiaging and antioxidant agent, the enhanced efficacies of the novel α-glycosylated ginsenoside F1 suggest that it might be useful in cosmetic applications after screening. [ABSTRACT FROM AUTHOR]

Fucoidans have been reported to exert anticancer effects with simultaneous low toxicity against healthy tissue. That correlation was observed in several cancer models, however, it has never been investigated in head and neck cancer before. To magnify the efficacy of conventional therapy, the administration of agents like fucoidan could be beneficial. The aim of this study was to evaluate the anticancer effect of Fucus vesiculosus (FV) extract alone and with co-administration of cisplatin in head and neck squamous cell carcinoma (HNSCC) in vitro. MTT assay results revealed an FV-induced inhibition of proliferation in all tested cell lines (H103, FaDu, KB). Flow cytometric cell cycle analysis showed an FV-induced, dose-dependent arrest in either S/G2 phase (H103, FaDu) or G1 arrest (KB). Furthermore, a dose-dependent gain in apoptotic fraction was observed. Western blot analysis confirmed the induction of apoptosis. A significant dose-dependent increase in reactive oxygen species (ROS) production was revealed in the H103 cell line, while FaDu cells remained unresponsive. On the contrary, an HPV-positive cell line, KB, demonstrated a dose-dependent decrease in ROS synthesis. Moreover, fucoidan enhanced the response to cisplatin (synergistic effect) in all cell lines with the HPV-positive one (KB) being the most sensitive. These results have been confirmed by flow-cytometric apoptosis analysis. In conclusion, we confirmed that fucoidan exhibits anticancer properties against HNSCC, which are manifested by the induction of apoptosis, regulation of ROS production, cell cycle arrest, and inhibition of proliferation. [ABSTRACT FROM AUTHOR]

Calcium plays an important role in plant growth, development, and response to environmental stimuli. Copines are conserved plasma membrane-localized calcium-binding proteins which regulate plant immune responses and development. In this study, we found that copine proteins BON2 and BON3, the paralogs of BON1, physically interact with calcium pumps ACA8 and ACA10 in Arabidopsis. Notably, ACA9, the closest homologue of ACA8 and ACA10 functioning in pollen tube growth, interacts with all three copines. This is consistent with the protein–protein interactions between the two protein families, the aca8, aca10, aca8/aca10, bon1/2/3 mutants as well as aca9 mutant exhibited defects on pollen germination and seed production. Taken together, plasma membrane-localized interacting calcium pumps and copines coordinately control pollen tube growth, likely through manipulating calcium efflux. [ABSTRACT FROM AUTHOR]