Glioblastoma has highly invasive potential, which might result in poor prognosis and therapeutic failure. Hence, the key we study is to find effective therapies to repress migration and invasion. ...Sulforaphane (SFN) was demonstrated to inhibit cell growth in a variety of tumors. Here, we will further investigate whether SFN inhibits migration and invasion and find the possible mechanisms in human glioblastoma U87MG and U373MG cells.
First, the optimal time and dose of SFN for migration and invasion study were determined via cell viability and cell morphological assay. Further, scratch assay and transwell invasion assay were employed to investigate the effect of SFN on migration and invasion. Meanwhile, Western blots were used to detect the molecular linkage among invasion related proteins phosphorylated ERK1/2, matrix metalloproteinase-2 (MMP-2) and CD44v6. Furthermore, Gelatin zymography was performed to detect the inhibition of MMP-2 activation. In addition, ERK1/2 blocker PD98059 (25 µM) was integrated to find the link between activated ERK1/2 and invasion, MMP-2 and CD44v6.
The results showed that SFN (20 µM) remarkably reduced the formation of cell pseudopodia, indicating that SFN might inhibit cell motility. As expected, scratch assay and transwell invasion assay showed that SFN inhibited glioblastoma cell migration and invasion. Western blot and Gelatin zymography showed that SFN phosphorylated ERK1/2 in a sustained way, which contributed to the downregulated MMP-2 expression and activity, and the upregulated CD44v6 expression. These molecular interactions resulted in the inhibition of cell invasion.
SFN inhibited migration and invasion processes. Furthermore, SFN inhibited invasion via activating ERK1/2 in a sustained way. The accumulated ERK1/2 activation downregulated MMP-2 expression and decreased its activity and upregulated CD44v6. SFN might be a potential therapeutic agent by activating ERK1/2 signaling against human glioblastoma.
Abstract Estrogen excess in females has been linked to a diverse array of chronic and acute diseases. Emerging research shows that exposure to estrogen-like compounds such as bisphenol S leads to ...increases in 17 β -estradiol levels, but the mechanism of action is unclear. The aim of this study was to reveal the underlying signaling pathway-mediated mechanisms, target site and target molecule of action of bisphenol S causing excessive estrogen synthesis. Human ovarian granulosa cells SVOG were exposed to bisphenol S at environmentally relevant concentrations (1 μg/L, 10 μg/L, and 100 μg/L) for 48 h. The results confirms that bisphenol S accumulates mainly on the cell membrane, binds to follicle stimulating hormone receptor (FSHR) located on the cell membrane, and subsequently activates the downstream cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway, leading to enhanced conversion of testosterone to 17 β -estradiol. This study deepens our knowledge of the mechanisms of environmental factors in pathogenesis of hyperestrogenism.
The rice striped stem borer (SSB),
Chilo suppressalis
Walker, and the rice yellow stem borer (YSB),
Scirpophaga incertulas
Walker, are two of the most damaging pests of rice plant, whose relative ...crop damage has changed in recent years. Here, we carried out experiments and surveys to understand the potential impact of field flooding on populations of these species. YSB had a consistently higher mortality rate than SSB in overwintering populations. We show that SSB survived under submersion better than YSB, crawled more strongly than YSB, and escaped more effectively from a waterlogged environment than YSB. These differences may relate partly to the longer abdominal prolegs and thoracic legs of SSB than YSB. These factors likely explain why YSB has a higher mortality rate than SSB in overwintering populations and why the relative importance of YSB is declining in some areas. In addition, the flooding method provides an effective cultural practice for some crops. Our results uncover the reasons why flooding practice is more effective for YSB than SSB. The results also point to an effective control measure for YSB.
The non-linear multifactorial impacts on fuel-saving potential constrain the practical performance of the vehicular waste heat recovery system (WHRS). This study proposed a four-dimensional ...interaction-based appraisal approach to interpreting these impacts for enhancing WHRS’s in-vehicle performance. The interaction incorporates a heat exchanger, configuration, engine, and vehicle. The proposed approach comprises two successive steps, emphasizing evaluation under the rated (Step 1) and off-design (Step 2) heat source conditions. A case study of waste heat recovery from a passenger vehicle was conducted to evaluate the in-vehicle performance of a novel co-split system and two single-split ones (with/without a regenerator) through this approach. The novel system theoretically modifies vehicular performance but remains ambiguous concerning real-world behaviour, which is assessed and verified by the proposed approach. Two key factors determining vehicular performance were identified by Step 1, namely, net power output and engine backpressure. As the co-split system modified both factors, its fuel-saving potential could be increased by up to 20.3% compared with single-split systems. Also, the limiting factor for off-design performance was pinpointed by Step 2, namely, the mismatch between the heat source and working fluid, which led to the solution, i.e., the synergistic split regulation of the working fluid and heat source. An up to 8.8% improvement in net power output was achieved by the co-split system at off-design heat sources compared with fixed split ratios. Consequently, the approach enables holistic performance improvement of the vehicular WHRS under design/off-design heat source conditions.
The use of propranolol for the treatment of infantile hemangioma (IH) has been widely investigated in recent years. However, the underlying therapeutic mechanism of propranolol for the treatment of ...IH remains poorly understood. The aim of the present study was to investigate the expression of proteins regulated by cellular tumor antigen p53 (p53) in associated apoptosis pathways in IH endothelial cells (HemECs) treated with propranolol. Furthermore, the present study aimed to investigate the exact apoptotic pathway underlying the therapeutic effect of propranolol against IH. In the present study, HemECs were subcultured and investigated using an inverted phase contrast microscope, immunocytochemical staining and a scanning electron microscope (SEM). Experimental groups and blank control groups were prepared. All groups were subjected to drug treatment. A high p53 expression model of HemECs was successfully established via transfection, and a low p53 expression model of HemECs was established using pifithrin‑α. The apoptosis rate of each group was determined using Annexin V‑fluorescein isothiocyanate/propidium iodide double staining and flow cytometry. The expression levels of downstream proteins regulated by p53 tumour necrosis factor receptor superfamily member 6 (FAS), p53‑induced death domain‑containing protein (PIDD), death receptor 5 (DR5), BH3‑interacting domain death agonist (BID), apoptosis regulator BAX (BAX), p53 unregulated modulator of apoptosis (PUMA), phosphatidylinositol‑glycan biosynthesis class S protein (PIGS), and insulin‑like growth factor‑binding protein 3 (IGF‑BP3) were revealed in the experimental and control groups via western blotting. Microscopic observation revealed the growth of an adherent monolayer of cells, which were closely packed and exhibited contact inhibition. Immunocytochemical staining demonstrated increased expression of clotting factor VIII. SEM analysis revealed presence of Weibel‑Palade bodies. The results of the analyses verified that the cultured cells were HemECs. The staining of the samples resulted in a significantly increased rate of apoptosis in experimental groups compared with the blank control group. This result suggested that there is an association between p53 expression and the rate of apoptosis of propranolol‑treated HemECs. The results of the western blot analysis demonstrated an upregulation of BAX expression and a downregulation of IGF‑BP3 expression in the HemECs treated with propranolol. There were no significant differences in the expression levels of FAS, DR5, PIDD, BID, PUMA and PIGS between experimental and control groups. This result suggests that p53 has an important role in HemEC apoptosis. The results of the present study additionally suggest that the propranolol‑induced HemEC apoptosis pathway is a mitochondrial apoptosis pathway and is regulated by p53‑BAX signaling.
Previous work reveals that the adult Chinese citrus fly, Bactrocera minax (Enderlein), emerges from the ground in citrus orchards and presumably disperses to alternate food sources in neighboring ...shrubs and trees, where it stays and becomes reproductively mature, and then later returns to the orchard to lay eggs. We investigated the trajectories of early emerged adult Chinese citrus flies, which were tracked with portable harmonic radar in 2013, 2014, 2015, and 2016 in four different habitats in Hubei province of China that presumably provided food sources for adults. This study we investigated whether early emerged adult Chinese citrus flies migrate into forests. A total of 47 adults were tracked following release in a citrus orchard. Our results showed that a total of 33 adults released in a citrus orchard flew into the forest, and 14 adults that disappeared during the tracking process in the citrus orchard. A total of 10 adults (in 2014) that were tracked and released in the forest flew to the forest. Of the adult flies investigated, 54.5% flew directly into the forest, while the remaining 45.5% finally arrived in the forest after repeatedly adjusting their trajectories. When there were Castanea mollissima Blume (Fagaceae) in the surrounding forest, the proportion of frequency of adult landing on the plant represented 58.3% and 88.5% of landing on all species in 2014 and in 2015, respectively. We conclude that early emerged adult Chinese citrus flies in the mosaic-type citrus orchard of the hilly terrain landform dispersed into adjacent forest.
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•Early emerged adult B. minax in citrus orchard dispersed into adjacent forest.•B. minax usually recognize the host with constantly fine-tune in behavior.•Step length and index of straightness of adult were not related to experimental site.•Turning angle distribution for the adult directed into the forest
One new ent‐kaurane diterpenoid, 11β,16α‐dihydroxy‐ent‐kauran‐19‐oic acid (1), together with eight known analogues 2 – 9 were isolated from the aerial parts of Wedelia prostrata. One of the acidic ...diterpenoids, kaurenoic acid (3), was converted to seven derivatives, 10 – 16. All compounds were evaluated for their cytotoxic activity in vitro against human leukemia (K562), liver (HepG‐2), and stomach (SGC‐7901) cancer cell lines. Only four kaurenoic acid derivatives, 13 – 16, with 15‐keto and substitutions at C(19) position, exhibited notable cytotoxic activities on these tumor cell lines with IC50 value ranging from 0.05 to 3.71 μm. Compounds 10 – 12, with oxime on C(15) showed moderate inhibitory effects and compounds 1 – 9 showed no cytotoxicities on them. Structure–activity relationships were also discussed based on the experimental data obtained. The known derivative, 15‐oxokaurenoic acid 4‐piperdin‐1‐ylbutyl ester (17), induced typical apoptotic cell death in colon SW480 cells upon evaluation of the apoptosis‐inducing activity by flow‐cytometric analysis.
Bemisia tabaci (Hemiptera: Gennadius) is a notorious pest that is capable of feeding on >600 kinds of agricultural crops. Imidacloprid is critical in managing pest with sucking mouthparts, such as B. ...tabaci. However, the field population of B. tabaci has evolved resistance because of insecticide overuse. The overexpression of the detoxification enzyme cytochrome P450 monooxygenase is considered the main mechanism of imidacloprid resistance, but the mechanism underlying gene regulation remains unclear. MicroRNAs are a type of endogenous small molecule compounds that is fundamental in regulating gene expression at the post-transcriptional level. Whether miRNAs are related to the imidacloprid resistance of B. tabaci remains unknown. To gain deep insight into imidacloprid resistance, we conducted on miRNAs expression profiling of two B. tabaci Mediterranean (MED) strains with 19-fold resistance through deep sequencing of small RNAs. A total of 8 known and 1591 novel miRNAs were identified. In addition, 16 miRNAs showed significant difference in expression levels between the two strains, as verified by quantitative reverse transcription PCR. Among these, novel_miR-376, 1517, and 1136 significantly expressed at low levels in resistant samples, decreasing by 36.9%, 60.2%, and 15.6%, respectively. Moreover, modulating novel_miR-1517 expression by feeding with 1517 inhibitor and 1517 mimic significantly affected B. tabaci imidacloprid susceptibility by regulating CYP6CM1 expression. In this article, miRNAs related to imidacloprid resistance of B. tabaci were systematically screened and identified, providing important information for the miRNA-based technological innovation for this pest management.
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•A total of 8 known and 1591 novel miRNAs were identified in Bemisia tabaci populations.•The role of three miRNAs in imidacloprid resistance was verified.•Novel_miR-1517 mediates CYP6CM1 expression to regulate imidacloprid resistance.
This paper proposes an online maximum efficiency tracking control for a dual-motor drive system. The efficiency of each drive system is obtained by online measuring the input power and online ...estimating the output power. Two algorithms, including the steepest ascent algorithm and fuzzy logic algorithm are proposed to achieve maximum efficiency tracking. The proposed methods do not require any computations related to the copper and core losses of the motor and the switching and conduction losses of the inverter. In addition, the proposed drive system can have better efficiency and better flexibility and requires smaller power ratings of each motor and inverter, which are easily manufactured in industry. The control algorithms are executed by using two digital signal processors, type TMS 320-F2808, made by Texas Instruments Incorporated Company. A controller area network (CAN) bus is used as a communication tool. Several experimental results show the correctness and feasibility of the proposed method. The proposed method can be easily applied in industry because of its simplicity.
Glutamate uptake by transporters expressed in astrocytes combines with synaptic structure to regulate the time that synaptically released glutamate remains in the extracellular space and, ...consequently, the duration and location of postsynaptic receptor activation. Both factors change greatly in the rodent hippocampus during the second postnatal week when most synapses become established and begin to mature, processes that are influenced by synaptically released glutamate. Transporter expression increases, potentially speeding removal of synaptically released glutamate, whereas extracellular space decreases, thereby slowing dilution. We investigated whether these competing changes influence the glutamate concentration time course and postsynaptic responses in the CA1 region of the mouse hippocampus during this critical period of synaptic development. Our results suggest that the glutamate concentration time course remains relatively consistent over this period, although the primary mechanisms regulating glutamate clearance change. Before the second postnatal week, clearance of synaptically released glutamate depends primarily on diffusion into large extracellular spaces, whereas later in development it relies more on increased uptake capacity. Thus, increased transporter expression during this period accompanies structural changes in the neuropil, preserving a relatively consistent glutamate concentration time course and ensuring that postsynaptic receptor activation remains brief and primarily localized to receptors close to release sites.
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