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Due to high invasion and metastasis, hepatocellular carcinoma (HCC) is known as one of the most fatal carcinomas. We aim to further investigate regulatory mechanisms of invasion and metastasis to elucidate HCC pathogenesis and develop novel medications.Patient specimens were collected for assessing gene expression and correlation between gene expressions. The expression of Ki67 and E-cadherin in subcutaneous xenograft tumor were examined by immunohistochemistry staining. The expression of activating transcription factor 2 (ATF2), miR-548p and TUFT1 were determined using Real-time quantitative reverse transcription polymerase chain reaction. Epithelial-mesenchymal transition and PI3K/AKT signaling-associated markers were examined with western blot. The proliferation, migration and invasion were assessed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide, colony formation and transwell assays, respectively. Cell apoptosis was assessed via Annexin V and propidium iodide staining. Gene interaction was confirmed using chromatin immunoprecipitation and luciferase activity assays. Subcutaneous and intravenous xenograft mouse models were established for analyzing HCC growth and metastasis in vivo.ATF2 was up-regulated in HCC patients and cells. ATF2 promoted HCC cell proliferation, migration and invasion and inhibited cell apoptosis through directly targeting miR-548p and controlling its expression. miR-548p suppressed HCC cell proliferation, migration and invasion and enhanced cell apoptosis. miR-548p directly bound to the 3'UTR of TUFT1 to restrain its expression and subsequently suppress the PI3K/AKT signaling. ATF2 knock-down significantly suppressed the growth and metastasis of HCC.ATF2 accelerates HCC progression by promoting cell proliferation, migration, invasion and metastasis, which is dependent on regulating the miR-548p/TUFT1 axis.

Tumor-initiating cells (TICs) or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation, progression, metastasis, and drug resistance. It is hypothesized that gastrointestinal TICs (giTICs) might originate from cell-cell fusion. Here, we systemically evaluate the evidence that supports or opposes the hypothesis of giTIC generation from cell-cell fusion both in vitro and in vivo. We review giTICs that are capable of initiating tumors in vivo with 5000 or fewer in vivo fused cells. Under this restriction, there is currently little evidence demonstrating that giTICs originate from cell-cell fusion in vivo. However, there are many reports showing that tumor generation in vitro occurs with more than 5000 fused cells. In addition, the mechanisms of giTIC generation via cell-cell fusion are poorly understood, and thus, we propose its potential mechanisms of action. We suggest that future research should focus on giTIC origination from cell-cell fusion in vivo, isolation or enrichment of giTICs that have tumor-initiating capabilities with 5000 or less in vivo fused cells, and further clarification of the underlying mechanisms. Our review of the current advances in our understanding of giTIC origination from cell-cell fusion may have significant implications for the understanding of carcinogenesis and future cancer therapeutic strategies targeting giTICs.

Orchestrated control of multiple overlapping and sequential processes is required for the maintenance of epidermal homeostasis and the response to and recovery from a variety of skin insults. Previous studies indicate that membrane-associated serine protease matriptase and prostasin play essential roles in epidermal development, differentiation, and barrier formation. The control of proteolysis is a highly regulated process, which depends not only on gene expression but also on zymogen activation and the balance between protease and protease inhibitor. Subcellular localization can affect the accessibility of protease inhibitors to proteases and, thus, also represents an integral component of the control of proteolysis. To understand how membrane-associated proteolysis is regulated in human skin, these key aspects of matriptase and prostasin were determined in normal and injured human skin by immunohistochemistry. This staining shows that matriptase is expressed predominantly in the zymogen form at the periphery of basal and spinous keratinocytes, and prostasin appears to be constitutively activated at high levels in polarized organelle-like structures of the granular keratinocytes in the adjacent quiescent skin. The membrane-associated proteolysis appears to be elevated via an increase in matriptase zymogen activation and prostasin protein expression in areas of skin recovering from epidermal insults. There was no noticeable change observed in other regulatory aspects, including the expression and tissue distribution of their cognate inhibitors HAI-1 and HAI-2. This study reveals that the membrane-associated proteolysis may be a critical epidermal mechanism involved in responding to, and recovering from, damage to human skin.

The present empirical study investigated whether progressive visuospatial cues presented in a self-regulatory mode could assist learners in comprehending the operation of a mechanical system. In th...

The present empirical study was to examine whether progressive snowball-like cues can benefit learners in learning the operation of a mechanical system. In particular, this study investigated the e...

A novel package structure has been developed to fabricate quantum-dot (QD) white light-emitting diodes (WLEDs) by dispersing QDs into the backlight lens and integrating them with blue light-emitting diode to form white light. For this in-lens encapsulation structure, the luminous efficiency and lifetime of QD-WLEDs can reach 90 lm/W and 1000 h, which is 25 times longer than that of QD-WLEDs with on-chip encapsulation structure. Furthermore, a 32-inch prototype liquid crystal display TV shows a wide color gamut of 108% under the National Television Systems Committee standard with this in-lens encapsulation structure. The improvement performance should be attributed to providing a hermetic encapsulation environment preventing oxygen and water from reacting with the QDs and reducing the temperature of QDs due to in-lens package structure. Our results demonstrate that the in-lens solution can be a promising application in display backlight.

Background: Flowering plants (angiosperms) dominate most global ecosystems today, but their rapid Cretaceous diversification has remained poorly understood ever since Darwin referred to it as an ‘abominable mystery’. Although numerous Cretaceous fossil flowers have been discovered in recent years, most are represented by incomplete charcoalified fragments that do not preserve delicate structures such as complete petals and surface textures, which means that their similarity to living forms is often difficult to discern. The scarcity of information about the ecology of early angiosperms makes it difficult to test hypotheses about the drivers of their diversification. Among other factors, frequent fires in the Cretaceous have been postulated as having possibly facilitated the rise of angiosperms. However, to date no early fossil angiosperms displaying fire-adapted traits have been known, making the role of fire in shaping Cretaceous floras uncertain.Results: We report the discovery of two exquisitely preserved fossil flower species, one identical to the inflorescences of the extant crown eudicot genus Phylica and the other recovered as a sister group to Phylica, both preserved as inclusions in Cretaceous amber from northern Myanmar (~99 Ma). These specialized flower structures, named Phylica piloburmensis sp. nov. and Eophylica priscastellata gen. et sp. nov., were adapted to surviving frequent wildfires, providing the earliest evidence of fire-resistance in angiosperms. The fossils suggest that fire was a significant selective force in Cretaceous angiosperm floras and that adaptations to fire resistance in some eudicot clades have been conserved for at least 99 Ma. This morphological stasis encompasses a range of floral characters, including the production of ‘pseudo-flowers’, and characteristic fruit and pollen architecture. Given its morphological distinctiveness, the Eophylica-Phylica clade represents one of the first well-documented angiosperm ‘living fossil’ genera from the Cretaceous. Conclusion: Our study suggests that core eudicots with specialised flower morphology displaying hallmarks of fire resistance and identical to those of the extant south African genus Phylica, had originated by the mid-Cretaceous (~99 Ma). Palaeoenvironmental reconstructions indicate that these plants lived in conditions similar to those of present-day southern Africa where 70% of taxa survive frequent burning, and that fire resistance was probably widespread in the fire-prone Cretaceous. The results also provide new insights into the biogeographic origin of at least one element of the highly endemic Greater Cape Region biodiversity hotspot flora biota.

The rapid Cretaceous diversification of flowering plants remains Darwin's 'abominable mystery' despite numerous fossil flowers discovered in recent years. Wildfires were frequent in the Cretaceous and many such early flower fossils are represented by charcoalified fragments, lacking complete delicate structures and surface textures, making their similarity to living forms difficult to discern. Furthermore, scarcity of information about the ecology of early angiosperms makes it difficult to test hypotheses about the drivers of their diversification, including the role of fire in shaping flowering plant evolution. We report the discovery of two exquisitely preserved fossil flower species, one identical to the inflorescences of the extant crown-eudicot genus Phylica and the other recovered as a sister group to Phylica, both preserved as inclusions together with burned plant remains in Cretaceous amber from northern Myanmar (~99 million years ago). These specialized flower species, named Phylica piloburmensis sp. nov. and Eophylica priscastellata gen. et sp. nov., exhibit traits identical to those of modern taxa in fire-prone ecosystems such as the fynbos of South Africa, and provide evidence of fire adaptation in angiosperms.

While nearly all previous algorithms designed to solve simulation optimization problems have treated the outputs of simulation systems at a given design point (input parameter) as being independent of each other, this premise is flawed in that simulated outputs are generally correlated. We propose a decorrelation (DC) procedure that can effectively evaluate and remove the correlation of outputs of a simulation system. The proposed DC procedure is further integrated with STRONG, an improved framework of the well-known Response Surface Methodology (RSM), for tackling the simulation optimization problems with correlated outputs. This integration is particularly synergistic due to the fact that STRONG is a fully automated, response-surface-based procedure possessing appealing convergence properties and DC can take advantage of the concept of trust region as in STRONG to enable the removal of the correlation of outputs at the design points within the same trust region all at once. This is more efficient compared to the traditional approaches where a substantial number of observations are typically required for dealing with correlations. The resulting integrated method, which we call STRONG-DC, requires various adaptations so as to ensure the efficacy and efficiency of the overall framework. STRONG-DC preserves the desirable automation and convergence as STRONG, namely, it does not require human involvements and can be proved to achieve the truly optimal solution(s) with probability one (w.p.1) under reasonable conditions. Moreover, the effectiveness and efficiency of STRONG-DC are evaluated through extensive numerical analyses, along with a case study involving the well-known newsvendor problem.

BackgroundAlcohol-induced intestinal dysbiosis disrupts and inflammatory responses are essential in the development of alcoholic fatty liver disease (AFLD). Here, we investigated the effects of Fmo5 on changes in enteric microbiome composition in a model of AFLD and dissected the pathogenic role of Fmo5 in AFLD-induced liver pathology.MethodsThe expression profile data of GSE8006 and GSE40334 datasets were downloaded from the GEO database. The WGCNA approach allowed us to investigate the AFLD-correlated module. DEGs were used to perform KEGG pathway enrichment analyses. Four PPI networks were constructed using the STRING database and visualized using Cytoscape software. The Cytohubba plug-in was used to identify the hub genes. Western blot and immunohistochemistry assays were used to detect protein expression. ELISA assay was used to detect the levels of serum inflammatory cytokines. Lipid droplets in the cytoplasm were observed using Oil Red O staining. Apoptosis was detected using a TUNEL assay and flow cytometry analysis. ROS levels were detected using flow cytometry analysis. Nuclear translocation of NF-κB p65 was observed using immunofluorescence staining. Co-immunoprecipitation was used to detect the co-expression of PPARα and Fmo5 in L02 cells. 16S rDNA sequencing defined the bacterial communities in mice with AFLD.ResultsFmo5 is a key DEG and is closely associated with the gut microbiota and PPAR signaling pathway. Gut microbiome function in AFLD was significantly related to the PPAR signaling pathway. AFLD induced shifts in various bacterial phyla in the cecum, including a reduction in Bacteroidetes and increased Firmicutes. Fmo5 and PPARα co-expression in cell and animal models with AFLD, which decreased significantly. Silencing of Fmo5 and PPARα aggravated the functions of AFLD inducing apoptosis and inflammatory response, promoting liver injury, and activating the NF-κB signaling pathway in vivo and in vitro. The NF-κB inhibitor abolished the functions of silencing of Fmo5 and PPARα promoting AFLD-induced apoptosis, inflammatory response, and liver injury.ConclusionOur data indicated that the co-expression of Fmo5 and PPARα was involved in AFLD-related gut microbiota composition and alleviated AFLD-induced liver injury, apoptosis, and inflammatory response by inhibiting the nuclear translocation of NF-κB p65 to inhibit the NF-κB signaling pathway.

Background Herpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic HSV (oHSV) T-Vec. However, transcription regulatory sequence (TRS) and transcription regulatory factor (TRF) of HSV US12 are seldom reported. Methods Previously, our laboratory isolated a new HSV strain named HSV-1-LXMW from a male patient with oral herpes in Beijing, China. Firstly, the genetic tree was used to analyze its genetic relationship. The US12 TRS and TRF in HSV-1-LXMW were found by using predictive software. Secondly, the further verification by the multi-sequence comparative analysis shown that the upstream DNA sequence of HSV US12 gene contained the conserved region. Finally, the results of literature search shown that the expression of transcription factors was related to the tissue affinity of HSV-1 and HSV-2, so as to increase the new understanding of the transcriptional regulation of HSV biology and oncolytic virus (OVs) therapy. Results Here we reported the transcriptional regulation region sequence of our new HSV-1-LXMW, and its close relationship with HSV-1-CR38 and HSV-1-17. Importantly we identified eight different kinds of novel TRSs and TRFs of HSV US12 for the first time, and found they are conserved among HSV-1 (c-Rel, Elk-1, Pax-4), HSV-2 (Oct-1, CF2-II, E74A, StuAp) or both HSVs (HNF-4). The TRFs c-Rel and Oct-1 are biologically functional respectively in immune escape and viral replication during HSV infection. Conclusions Our findings have important implication to HSV biology, infection, immunity and oHSVs.

Orchestrated control of multiple overlapping and sequential processes is required for the maintenance of epidermal homeostasis and the response to and recovery from a variety of skin insults. Previous studies indicate that membrane-associated serine protease matriptase and prostasin play essential roles in epidermal development, differentiation, and barrier formation. The control of proteolysis is a highly regulated process, which depends not only on gene expression but also on zymogen activation and the balance between protease and protease inhibitor. Subcellular localization can affect the accessibility of protease inhibitors to proteases and, thus, also represents an integral component of the control of proteolysis. To understand how membrane-associated proteolysis is regulated in human skin, these key aspects of matriptase and prostasin were determined in normal and injured human skin by immunohistochemistry. This staining shows that matriptase is expressed predominantly in the zymogen form at the periphery of basal and spinous keratinocytes, and prostasin appears to be constitutively activated at high levels in polarized organelle-like structures of the granular keratinocytes in the adjacent quiescent skin. The membrane-associated proteolysis appears to be elevated via an increase in matriptase zymogen activation and prostasin protein expression in areas of skin recovering from epidermal insults. There was no noticeable change observed in other regulatory aspects, including the expression and tissue distribution of their cognate inhibitors HAI-1 and HAI-2. This study reveals that the membrane-associated proteolysis may be a critical epidermal mechanism involved in responding to, and recovering from, damage to human skin.

The purpose of this quasi-experimental study was to examine whether attention cueing can assist learners in learning the structure and functions of the brain. This study investigated the interactive effects of the experimental treatment and learners’ prior knowledge on their test results and cognitive load. Self-regulatory, mobile-phone-based animations depicting the brain comprised the instrument. A total of 55 English as a foreign language learners from two sections of a linguistics course were recruited. First, the participants’ prior knowledge concerning the functions of the brain was assessed. Next, they were randomly assigned into two modes—animation-only or animation-plus-cueing. Immediately, after the treatment period, the participants were administered retention, matching, organization, and transfer test along with cognitive load questionnaire. Experimental treatment and prior knowledge were the independent variables, while comprehension tests, cognitive load, and study time were the dependent variables. The results demonstrated that the learners in the cueing condition outperformed the non-cueing condition for matching and organization test, but not for transfer test. No differences were observed between the cueing and non-cueing condition concerning the cognitive load. The results stressed the importance of presenting relation cueing emphasizing cause–effect relationship on dynamic external representations can facilitate learners’ selection and organization of information so as to enhance general comprehension of external representations.

For the first time, the histerid genus Onthophilus Leach, 1817 is found from the mid-Cretaceous Burmese amber with a new species Onthophilus yingae sp. nov. The new species can be clearly assigned to the genus Onthophilus by sharing an identical set of characters with the extant species. As direct evidence, this new finding demonstrates the ancient origin of Onthophilus.

Well-crystallized bismuth oxides (Bi2O3) were synthesized through precipitation processes operating at room temperature. Two synthesis routes were used, which led to Bi2O3 products with completely different phase structures. The crystallization mechanisms of γ-Bi2O3 and δ-Bi2O3 in relation to the synthetic processes were discussed. The role of vanadium (V) ions and the doping limit on the structural modification were also investigated. The photocatalytic efficiencies of the V-modified γ-Bi2O3 and δ-Bi2O3 compared with TiO2 P25 powder were discussed.

Angiotensin-(1-7) [Ang-(1-7)] is a multifunctional bioactive angiotensin peptide which exerts a cardiovascular protective function mainly by opposing the effects of angiotensin II. We aimed to determine whether brain Ang-(1-7) regulates nitric oxide (NO) and neurotransmitter levels in the hypothalamic paraventricular nucleus (PVN), and influences sympathetic activity, blood pressure and cardiac hypertrophy in salt-sensitive hypertension. Dahl salt-sensitive rats receiving a high-salt (HS, 8% NaCl) or a normal-salt (NS, 0.3% NaCl) diet were treated with an intracerebroventricular (ICV) infusion of Ang-(1-7) for 6 weeks. Seven rats were measured in each group. In comparison with NS rats, HS rats exhibited significantly increased mean arterial pressure, plasma norepinephrine (NE) and cardiac hypertrophy. In addition, HS rats (compared to NS rats) had increased glutamate, NE and tyrosine hydroxylase (TH) expression, and reduced NO levels as well as reduced expression of γ-aminobutyric acid (GABA) and the 67 kDa isoform of glutamate decarboxylase (GAD67) in the PVN. Treatment with ICV infusion of Ang-(1-7) reversed these changes in the salt-sensitive hypertensive rats. The results suggest that the beneficial effects of brain Ang-(1-7) on salt-sensitive hypertension and cardiac hypertrophy are partly due to an elevation in the NO level and restoration of neurotransmitter balance in the PVN.

Background: Fine particulate matter (PM) air pollution is associated with numerous adverse health effects, including increased blood pressure (BP) and vascular dysfunction. Coarse PM substantially contributes to global air pollution, yet differs in characteristics from fine particles and is currently not regulated. However, the cardiovascular (CV) impacts of coarse PM exposure remain largely unknown. Objectives: Our goal was to elucidate whether coarse PM, like fine PM, is itself capable of eliciting adverse CV responses. Methods: We performed a randomized double-blind crossover study in which 32 healthy adults (25.9 ± 6.6 years of age) were exposed to concentrated ambient coarse particles (CAP; 76.2 ± 51.5 μg/m3) in a rural location and filtered air (FA) for 2 hr. We measured CV outcomes during, immediately after, and 2 hr postexposures. Results: Both systolic (mean difference = 0.32 mmHg; 95% CI: 0.05, 0.58; p = 0.021) and diastolic BP (0.27 mmHg; 95% CI: 0.003, 0.53; p = 0.05) linearly increased per 10 min of exposure during the inhalation of coarse CAP when compared with changes during FA exposure. Heart rate was on average higher (4.1 bpm; 95% CI: 3.06, 5.12; p < 0.0001) and the ratio of low-to-high frequency heart rate variability increased (0.24; 95% CI: 0.07, 0.41; p = 0.007) during coarse particle versus FA exposure. Other outcomes (brachial flow-mediated dilatation, microvascular reactive hyperemia index, aortic hemodynamics, pulse wave velocity) were not differentially altered by the exposures. Conclusions: Inhalation of coarse PM from a rural location is associated with a rapid elevation in BP and heart rate during exposure, likely due to the triggering of autonomic imbalance. These findings add mechanistic evidence supporting the biological plausibility that coarse particles could contribute to the triggering of acute CV events. Citation: Brook RD, Bard RL, Morishita M, Dvonch JT, Wang L, Yang HY, Spino C, Mukherjee B, Kaplan MJ, Yalavarthi S, Oral EA, Ajluni N, Sun Q, Brook JR, Harkema J, Rajagopalan S. 2014. Hemodynamic, autonomic, and vascular effects of exposure to coarse particulate matter air pollution from a rural location. Environ Health Perspect 122:624–630; http://dx.doi.org/10.1289/ehp.1306595

This quasi-experimental study examined whether or not attention cueing can benefit learners in learning the kinematic operation of a mechanical system. This study investigated the interaction effects of the dynamic and cued conditions on the test results as well as cognitive load. Self-regulatory, mobile-phone-based visualizations depicting the kinematics of a flushing cistern comprised the instrument. The participants consisted of 174 English as a foreign language (EFL) learners from four sections of a reading course. After assessing their backgrounds, they were randomly assigned to one of four experimental conditions—pictures only, pictures plus cueing, animation only, and animation plus cueing. Immediately, after administering the experimental treatment, the participants answered comprehension tests and a cognitive load questionnaire. The results demonstrated that visuospatial cues, particularly in static diagrams, ameliorated the learners' learning effectiveness by facilitating their local comprehension better than their global comprehension. While animation benefited the learners in terms of solving directions and troubleshooting problems, the static diagrams and animations complemented each other in helping the learners understand the different kinematic functions of a mechanical system. The static diagrams were beneficial in enhancing local comprehension, whereas the animations benefited the learners' global comprehension as indicated in the learners' transfer test results. The experimental results revealed that the effectiveness of animation and visual cueing depend on the subject matter and purpose of the tests.

Background: High ambient levels of ozone (O3) and fine particulate matter (PM2.5) are associated with cardiovascular morbidity and mortality, especially in people with preexisting cardiopulmonary diseases. Enhanced susceptibility to the toxicity of air pollutants may include individuals with metabolic syndrome (MetS). Objective: We tested the hypothesis that cardiovascular responses to O3 and PM2.5 will be enhanced in rats with diet-induced MetS. Methods: Male Sprague-Dawley rats were fed a high-fructose diet (HFrD) to induce MetS and then exposed to O3, concentrated ambient PM2.5, or the combination of O3 plus PM2.5 for 9 days. Data related to heart rate (HR), HR variability (HRV), and blood pressure (BP) were collected. Results: Consistent with MetS, HFrD rats were hypertensive and insulin resistant, and had elevated fasting levels of blood glucose and triglycerides. Decreases in HR and BP, which were found in all exposure groups, were greater and more persistent in HFrD rats compared with those fed a normal diet (ND). Coexposure to O3 plus PM2.5 induced acute drops in HR and BP in all rats, but only ND rats adapted after 2 days. HFrD rats had little exposure-related changes in HRV, whereas ND rats had increased HRV during O3 exposure, modest decreases with PM2.5, and dramatic decreases during O3 plus PM2.5 coexposures. Conclusions: Cardiovascular depression in O3- and PM2.5-exposed rats was enhanced and prolonged in rats with HFrD-induced MetS. These results in rodents suggest that people with MetS may be prone to similar exaggerated BP and HR responses to inhaled air pollutants. Citation: Wagner JG, Allen K, Yang HY, Nan B, Morishita M, Mukherjee B, Dvonch JT, Spino C, Fink GD, Rajagopalan S, Sun Q, Brook RD, Harkema JR. 2014. Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome. Environ Health Perspect 122:27–33; http://dx.doi.org/10.1289/ehp.1307085

High-density lipoprotein (HDL) particles perform numerous vascular-protective functions. Animal studies demonstrate that exposure to fine or ultrafine particulate matter (PM) can promote HDL dysfunction. However, the impact of PM on humans remains unknown.We aimed to determine the effect of exposure to coarse concentrated ambient particles (CAP) on several metrics of HDL function in healthy humans.Thirty-two adults (25.9 ± 6.6 years) were exposed to coarse CAP [76.2 ± 51.5 µg·m(-3)] in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Venous blood collected 2- and 20-h post-exposures was measured for HDL-mediated efflux of [(3)H]-cholesterol from cells and 20-h exposures for HDL anti-oxidant capacity by a fluorescent assay and paraoxonase activity. The changes [median (first, third quartiles)] between exposures among 29 subjects with available results were compared by matched Wilcoxon tests.HDL-mediated cholesterol efflux capacity did not differ between exposures at either time point [16.60% (15.17, 19.19) 2-h post-CAP versus 17.56% (13.43, 20.98) post-FA, p = 0.768 and 14.90% (12.47, 19.15) 20-h post-CAP versus 17.75% (13.22, 23.95) post-FA, p = 0.216]. HOI [0.26 (0.24, 0.35) versus 0.28 (0.25, 0.40), p = 0.198] and paraoxonase activity [0.54 (0.39, 0.82) versus 0.60 μmol·min(-1 )ml plasma(-1) (0.40, 0.85), p = 0.137] did not differ 20-h post-CAP versus FA, respectively.Brief inhalation of coarse PM from a rural location did not acutely impair several facets of HDL functionality. Whether coarse PM derived from urban sites, fine particles or longer term PM exposures can promote HDL dysfunction warrant future investigations.

The way of fault characteristic parameters fuzzy processing and optimizing the weights and thresholds of ANN by GA are studied. As a result, the convergent rate and convergent precision are greatly increased. Application to the fault diagnosis of a air blower system shows the new model overcomes the low learning rate and local optima of BP algorithm, and the fault diagnosis precision is effectively improved.

Dihydrodiol dehydrogenase (DDH) is frequently detected in cancer cells, and its overexpression correlates with drug resistance, the downregulation of DNA repair mechanisms, increased frequency of tumor recurrence, cancer cell metastasis and poor prognosis. The silencing of DDH expression using siRNA, on the other hand, reduces drug resistance and cancer cell mobility. These data suggest that DDH may be an oncogene-related protein. However, no specific DDH inhibitor has been identified to date. Thus, in this study, we used DDH as a target enzyme in a live-cell enzyme-linked immunosorbent assay to screen Chinese medicinal herb extracts (CMHEs) with the aim of identifying a DDH inhibitor. Using this method, we found 49 among 796 CMHEs that inhibited DDH expression. We selected three potential extracts, which had the highest activity against DDH, for further fractionation using high-performance liquid chromatography. The active ingredient was identified by immunoblot analysis. The function of the active ingredient was characterized by cell function analysis. Our results revealed that the CMHE-purified compounds targeted DDH, inducing autophagy and reducing DNA repair, which in turn enhanced the cytotoxic effects of the anticancer drugs and irradiation.

This study investigated the formation of bismuth oxide (Bi 2 O 3 ) crystals by an aqueous precipitation method using bismuth nitrate pentahydrate [Bi(NO 3 ) 3 ·5H 2 O] and NaOH. The phase evolution during NaOH titration was also studied. Basic bismuth nitrates were formed during NaOH titration. However, these nitrates dissolved and recrystallized into Bi 2 O 3 when the pH attained a critical range between 13 and 14. A second phase of Bi(OH) 3 was induced when the pH of the solution was over the critical pH range. The morphology of the Bi 2 O 3 crystal strongly depended on precipitation conditions. The NO 3 − ions favored the crystal growth along the [001] direction to obtain needle-like Bi 2 O 3 crystals. Conversely, NaOH tended to be absorbed on the (001) face and suppressed the preferred growth in the [001] direction because of the shielding effect. The crystal changed from needle-like to plate or polyhedral shape with increasing NaOH concentration. The optical absorption properties were also modified accordingly, resulting in the change of color from yellow to pale orange because of size and shape effects. Finally, Bi 2 O 3 crystals with plate and polyhedral morphologies were found to show relatively higher photocatalytic activity than the needle-like crystals due to the better development of the active crystal faces with suppression of the preferred crystal growth habit.

Cotton fiber is a type of natural fibers. Using natural fibers to fabricate textile can not only decrease the consumption of synthetic fibers, but also reduce the environmental pollution. This study aims to fabricate elastic knitted fabrics and evaluate their properties. Polyester (PET) filaments and rubber threads serve as the warp while cotton yarn serves as the weft for warp knitting. A crochet machine makes the warp and weft into warp knits with desirable stretchability, during which the amount (single/double) and the ply number (1-, 2-, and 3-ply) of the weft are further varied. The resulting warp knits are evaluated for water absorption, air permeability, and mechanical properties. As demonstrated by the experimental results, the warp knits with single 1-ply weft (S1) yield an optimal air permeability of 224.6 cm3/cm2/s and stiffness along the warp direction of 4.74cm. The warp knits with single 2-ply weft (S2) display an optimal tearing strength of 86N while the warp knits with double 3-ply weft (D3/3) has an optimal tensile strength of 708N.

Calcium channel blockade with nicardipine (NC) is an alternative to phenoxybenzamine (PB) preparation for resection of a pheochromocytoma. Intraoperative magnesium sulfate infusion (+MgSO(4)) is often used for its cardiovascular stabilizing properties. We hypothesized that preparation with NC would be similar clinically to PB for resection of a pheochromocytoma, and MgSO(4) infusion would not affect intraoperative stability.This retrospective review included 64 patients undergoing resections of a pheochromocytoma from 2003 to 2011. PB or NC was used preoperatively, with MgSO(4) use distributed equally in the population. Pre-, intra-, and postoperative hemodynamics and outcomes were compared.There was no difference in NC (n = 7) versus PB (n = 57) or +MgSO(4) (n = 33) versus -MgSO(4) (n = 31) groups for demographics with the exception of age. The NC group had smaller median tumor size and lesser plasma baseline levels of normetanephrine than the PB group, but subgroup analysis of all neoplasms3.0 cm revealed no differences. Pre-, intra- and postoperative hemodynamic stability and outcomes were similar for NC versus PB analyses as well as the +MgSO(4) versus -MgSO(4) groups.NC use may be an equivalent alternative to PB in preoperative preparation, especially for smaller pheochromocytomas. Intraoperative MgSO(4) use does not seem to have a substantive effect on hemodynamic stability.

Macrophage inflammation protein-3alpha (MIP-3alpha) is a chemokine expressed in inflamed tissue and capable of inducing migration of immature dendritic cells (DCs) or Langerhans cells. We postulated that conditioning vaccination sites with MIP-3alpha might enhance the efficacy of subsequently administered DC-based cancer vaccines. Our results demonstrate that subcutaneously injection of irradiated tumor cells expressing MIP-3alpha induces substantial cell infiltration to the injection site. Vaccination of irradiated tumor cells expressing MIP-3alpha followed by DCs pulsed with irradiated tumor cells can effectively suppress tumor growth in animals, which is significantly better than vaccination with irradiated MIP-3alpha-producing tumor cells or DCs pulsed with tumor cells alone. The protective effect was most evident when the MIP-3alpha-producing tumor cells and DC-based vaccines were injected at the same site. These results support the notion that this combination vaccination strategy might generate a more effective immune response to suppress the growth of tumor cells in animals.

INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is gaining acceptance for men with low risk prostate cancer (PCa) to prevent over-treatment related morbidity. Variability exists regarding the timing of the confirmatory biopsy (CBx) after diagnostic biopsy (DBx) in AS protocols. We analyze the Prostate Cancer Active Surveillance (PASS) cohort, determining timing and rates of PCa adverse reclassification (henceforth called reclassification) on CBx. METHODS: Men (N1⁄4422) with low risk PCA on AS were selected from the multicenter PASS cohort (1,067 screened). Criteria included enrollment within 1 year of DBx, receipt of CBx after enrollment, DBx with 1⁄47 or to >1⁄434% cores involved. The PASS protocol requires a CBx within the first 6-12 months of DBx. The time interval from DBx to CBx in tertiles was 0-8.8, 8.9-12.4 and > 12.5 months. For simplicity, rates of reclassification on CBx were calculated at 13 months post-DBx. Multivariable logistic regression determined association between reclassification, CBx timing, and other clinical and pathologic parameters. RESULTS: 90 men (21.3%) experienced reclassification on CBx. CBx was performed 11 months (median) after DBx (IQR 7.8-13.8). Rates of reclassification at 13 months were 23.5% (28/ 199 CBx), 19.5% (34/174 CBx), and 21.7% (28/129 CBx), respectively (p1⁄40.71). On multivariable analysis factors associated with reclassification were BMI and prostate volume. BMI (categorized as 35 kg/m (OR 6.1 95% CI 2.0, 18.7) compared to those with BMI < 30 kg/m. Moderate (30-60ml; OR 0.28 95% CI 0.14, 0.57) and large (60mlþ; OR 0.14 95% CI 0.05, 0.40) prostate volume were associated with decreased odds of reclassification compared to volume

BACKGROUND The authors conducted a pilot clinical trial to explore the vaccination of patients with late-stage lung carcinoma with dendritic cells (DCs) pulsed with necrotic tumor cells derived from malignant pleural effusion specimens, and to evaluate the antitumor immune response induced by this therapy. METHODS Autologous DCs were generated by culturing adherent mononuclear cells with interleukin-4 and granulocyte-macrophage–colony-stimulating factor for 7 days. Day-7 DCs were cocultured overnight with autologous necrotic tumor cells derived from pleural effusion specimens to allow internalization of tumor antigens. DCs were then treated with tumor necrosis factor-alpha for 16 hours. The antigen-loaded DCs were injected into each patient's inguinal lymph nodes under sonographic guidance. Eight patients with late-stage nonsmall cell lung carcinoma were treated in this manner. Patients were vaccinated once weekly for 4 weeks and then boosted twice biweekly. RESULTS The authors found that there was no Grade II/III toxicity and autoimmune response in all patients after intranodal injection of the DC vaccine. Minor to moderate increases in T-cell responses against tumor antigens were observed after DC vaccination in six of eight patients. Five patients had progressive disease. One patient had minor tumor response and two patients had stable disease. The two patients who had longer disease control also had better T-cell responses. CONCLUSIONS The results indicated that it was feasible to immunize patients with lung carcinoma intranodally with DCs pulsed with necrotic tumor cells enriched from pleural effusion specimens, and this approach may generate T-cell responses and provide clinical benefit in some patients. Cancer 2005. © 2005 American Cancer Society.

Purpose: We intranodally immunized metastatic colorectal carcinoma patients, who had failed standard chemotherapy, with dendritic cells (DCs) pulsed with HLA-A*0201- or HLA-A*2402-restricted carcinoembryonic antigen (CEA) peptides to evaluate the safety of this treatment and the immune response against CEA peptides before and after the treatment. Experimental Design: Six patients with the HLA-A*2402 genotype and 4 patients with the HLA-A*0201 genotype were enrolled. A single CEA peptide (YLSGANLNL) or two CEA peptides (QYSWFVNGTF and TYACFVSNL) were used for patients with the HLA-A*0201 or HLA-A*2402 genotype, respectively. Autologous DCs were generated by culturing adherent mononuclear cells with interleukin 4 and granulocyte macrophage colony-stimulating factor for 6 days. Maturation of DCs was then induced with tumor necrosis factor α for 40 h. Mature DCs were pulsed with appropriate CEA peptides for 2 h. After washing, 1 million peptide-pulsed DCs were injected into one inguinal lymph node under sonographic guidance. Each patient received four injections. Results: No grade II/III toxicity or autoimmunity was observed. An increase in the number of CEA-specific T cells after DC vaccination could be detected in 7 of 10 (70%) patients. Two (20%) patients had stable disease for at least 12 weeks. One of these 2 patients experienced a transient decrease in CEA levels during the treatment period and also had the most significant T-cell response against the immunizing CEA peptides. Conclusions: These results suggest that our vaccination procedure can generate or boost specific T-cell responses and may provide clinical benefit in certain cancer patients.

The present study examines how display model, English proficiency and cognitive preference affect English as a Foreign Language (EFL) learners’ listening comprehension of authentic videos and cognitive load degree. EFL learners were randomly assigned to one of two groups. The control group received single coding and the experimental group received dual coding. The results show that the display model affects EFL learners’ cognitive load and listening comprehension of CNN news. There is no interaction among English proficiency, cognitive preference and experimental conditions on the listening comprehension scores and cognitive load scale. Learners with a low aptitude for visual learning had poorer performance and a higher cognitive load than those with a high aptitude for visual learning. All learners, regardless of cognitive styles and level of English, benefited from dual coding. The dual-code display model thus seems to be effective in reducing EFL learners’ cognitive load.

To cope with environmental high osmolarity, the budding yeast Saccharomyces cerevisiae activates the mitogen-activated protein kinase (MAPK) Hog1, which controls an array of osmoadaptive responses. Two independent, but functionally redundant, osmosensing systems involving the transmembrane sensor histidine kinase Sln1 or the tetraspanning membrane protein Sho1 stimulate the Hog1 MAPK cascade. Furthermore, the Sho1 signaling branch itself also involves the two functionally redundant osmosensors Hkr1 and Msb2. However, any single osmosensor (Sln1, Hkr1, or Msb2) is sufficient for osmoadaptation. We found that the signaling mechanism by which Hkr1 or Msb2 stimulated the Hog1 cascade was specific to each osmosensor. Specifically, activation of Hog1 by Msb2 required the scaffold protein Bem1 and the actin cytoskeleton. Bem1 bound to the cytoplasmic domain of Msb2 and thus recruited the kinases Ste20 and Cla4 to the membrane, where either of them can activate the kinase Ste11. The cytoplasmic domain of Hkr1 also contributed to the activation of Ste11 by Ste20, but through a mechanism that involved neither Bem1 nor the actin cytoskeleton. Furthermore, we found a PXXP motif in Ste20 that specifically bound to the Sho1 SH3 (Src homology 3) domain. This interaction between Ste20 and Sho1 contributed to the activation of Hog1 by Hkr1, but not by Msb2. These differences between Hkr1 and Msb2 may enable differential regulation of these two proteins and provide a mechanism through Msb2 to connect regulation of the cytoskeleton with the response to osmotic stress.

Fine particulate matter (PM) air pollution has been associated with alterations in circulating endothelial progenitor cell (EPC) levels, which may be one mechanism whereby exposures promote cardiovascular diseases. However, the impact of coarse PM on EPCs is unknown.We aimed to determine the effect of acute exposure to coarse concentrated ambient particles (CAP) on circulating EPC levels.Thirty-two adults (25.9 ± 6.6 years) were exposed to coarse CAP (76.2 ± 51.5 μg m(-3)) in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Peripheral venous blood was collected 2 and 20 h post-exposures for circulating EPC (n = 21), white blood cell (n = 24) and vascular endothelial growth factor (VEGF) (n = 16-19) levels. The changes between exposures were compared by matched Wilcoxon signed-rank tests.Circulating EPC levels were elevated 2 [108.29 (6.24-249.71) EPC mL(-1); median (25th-75th percentiles), p = 0.052] and 20 h [106.86 (52.91-278.35) EPC mL(-1), p = 0.008] post-CAP exposure compared to the same time points following FA [38.47 (0.00-84.83) and 50.16 (0.00-104.79) EPC mL(-1)]. VEGF and white blood cell (WBC) levels did not differ between exposures.Brief inhalation of coarse PM from a rural location elicited an increase in EPCs that persisted for at least 20 h. The underlying mechanism responsible may reflect a systemic reaction to an acute "endothelial injury" and/or a circulating EPC response to sympathetic nervous system activation.