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NF-κB signalling involves the scaffold protein NEMO, which can be bound by the oncoprotein vFLIP to promote cell survival and oncogenic transformation. Here the authors rationally engineer a tertiary protein mimic of NEMO to disrupt the vFLIP-NEMO interaction to induce cell death.

In this study, a porous membrane with a cellulose acetate (CA) matrix was fabricated using propylene glycol with a water pressure treatment without a metal salt as an additive. The water pressure treatment of the fabricated CA membrane with propylene glycol yielded nanopores. The nanopores were formed as the additives in the CA chains led to plasticization. The weakened chains of the parts where the plasticization occurred were broken by the water pressure, which generated the pores. Compared to the previous study with glycerin as an additive, the size of the hydration region was controlled by the number of hydrophilic functional groups. When water pressure was applied to the CA membrane containing propylene glycol as an additive, the hydration area was small, so it was effective to control the pore size and the number of nano pores than glycerin. In addition, the number of nanopores and pore size could be easily adjusted by the water pressure. The porosity of the membrane was increased owing to the trace amount of propylene glycol, confirmed by scanning electron microscopy (SEM) and porosimetry. The interaction between the CA and propylene glycol was verified by Fourier-transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). Consequently, it was the optimum composition to generate pores at the CA/propylene glycol 1:0.2 ratio, and porosity of 69.7% and average pore diameter of 300 nm was confirmed. Since it is a membrane with high porosity and nano sized pores, it is expected to be applied in various fields.

In this study, a cellulose acetate (CA) membrane with pores generated by a water pressure treatment was investigated for its ability to serve as a pretreatment filter device for the detection of 2-n-octyl-4-isothiazolin-3-one (OIT). Pores were generated by applying a water pressure of 8 bar to a membrane manufactured using a CA-based polymer solution. The CA used for the manufacturing was an environment-friendly, low-cost and highly energy-efficient material. Furthermore, since the fabricated porous CA polymeric film possessed many hydrophilic functional groups, it could strongly bind hydrophilic substances while avoiding interaction with hydrophobic substances. OIT, which comprises a hydrophobic bond that forms weak bonds over time, can break down more easily than hydrophilic impurities. The different extents of interaction occurring between either the toxic fungicide OIT or the hydrophilic impurities and the CA film were determined by Fourier-transform infrared (FT-IR) spectroscopy. The physicochemical changes in the resulting membrane, which occurred when the pores were generated, were investigated through scanning electron microscopy (SEM) and thermogravimetric analysis (TGA).

Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC50 values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 μM and 44.7 μM, while those of magnolol were 19.0 μM and 47.3 μM, respectively. Notably, the systemic exposure (AUC and Cmax) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC50 values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and Vss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents.

The sodium-dependent phosphate co-transporter 2b (NPT2b) plays an important role in maintaining phosphate homeostasis. In previous studies, we have shown that high dietary inorganic phosphate (Pi) consumption in mice stimulated lung tumorigenesis and increased NPT2b expression. NPT2b has also been found to be highly expressed in human lung cancer tissues. The association of high expression of NPT2b in the lung with poor prognosis in oncogenic lung diseases prompted us to test whether knockdown of NPT2b may regulate lung cancer growth. To address this issue, aerosols that contained small interfering RNA (siRNA) directed against NPT2b (siNPT2b) were delivered into the lungs of K-ras (LA1) mice, which constitute a murine model reflecting human lung cancer. Our results clearly showed that repeated aerosol delivery of siNPT2b successfully suppressed lung cancer growth and decreased cancer cell proliferation and angiogenesis, while facilitating apoptosis. These results strongly suggest that NPT2b plays a role lung tumorigenesis and represents a novel target for lung cancer therapy.

Aberrant Ras signaling is linked to a wide spectrum of hyperproliferative diseases, and components of the signaling pathway, including Ras, have been the subject of intense and ongoing drug discovery efforts. The cellular activity of Ras is modulated by its association with the guanine nucleotide exchange factor Son of sevenless (Sos), and the high-resolution crystal structure of the Ras-Sos complex provides a basis for the rational design of orthosteric Ras ligands. We constructed a synthetic Sos protein mimic that engages the wild-type and oncogenic forms of nucleotidebound Ras and modulates downstream kinase signaling. The Sos mimic was designed to capture the conformation of the Sos helix-loop-helix motif that makes critical contacts with Ras in its switch region. Chemoproteomic studies illustrate that the proteomimetic engages Ras and other cellular GTPases. The synthetic proteomimetic resists proteolytic degradation and enters cells through macropinocytosis. As such, it is selectively toxic to cancer cells with upregulated macropinocytosis, including those that feature oncogenic Ras mutations. [ABSTRACT FROM AUTHOR]

A PEMFC needs to be maintained at an appropriate temperature and humidity in a rapidly changing environment for automobile applications. In this study, a pseudo-multi-dimensional dynamic model for predicting the heat and mass transfer performance of a plate-and- frame membrane humidifier for PEMFC vehicles is developed. Based on the developed model, the variations in the temperature and relative humidity at the dry air outlet are investigated according to the air flow acceleration. Moreover, the dynamic response is analyzed as a function of the amplitude and period of the sinusoidal air flow rate at actual operating conditions. The effects of heat transfer on the dynamic response are more dominant than those of mass transfer. The settling time of the temperature and relative humidity at the dry air outlet decrease with the increase in air flow acceleration. In addition, the variations in the temperature and relative humidity at the dry air outlet increase with the increases in the amplitude and period of the sinusoidal air flow rate. [ABSTRACT FROM AUTHOR]

Air freshener could be one of the multiple sources that release volatile organic compounds (VOCs) into the indoor environment. The use of these products may be associated with an increase in the measured level of terpene, such as xylene and other volatile air freshener components, including aldehydes, and esters. Air freshener is usually used indoors, and thus some compounds emitted from air freshener may have potentially harmful health impacts, including sensory irritation, respiratory symptoms, and dysfunction of the lungs. The constituents of air fresheners can react with ozone to produce secondary pollutants such as formaldehyde, secondary organic aerosol (SOA), oxidative product, and ultrafine particles. These pollutants then adversely affect human health, in many ways such as damage to the central nervous system, alteration of hormone levels, etc. In particular, the ultrafine particles may induce severe adverse effects on diverse organs, including the pulmonary and cardiovascular systems. Although the indoor use of air freshener is increasing, deleterious effects do not manifest for many years, making it difficult to identify air freshener-associated symptoms. In addition, risk assessment recognizes the association between air fresheners and adverse health effects, but the distinct causal relationship remains unclear. In this review, the emitted components of air freshener, including benzene, phthalate, and limonene, were described. Moreover, we focused on the health effects of these chemicals and secondary pollutants formed by the reaction with ozone. In conclusion, scientific guidelines on emission and exposure as well as risk characterization of air freshener need to be established. [ABSTRACT FROM AUTHOR]

Atopic dermatitis, one of the most important skin diseases, is characterized by both skin barrier impairment and immunological abnormalities. Although several studies have demonstrated the significant relationship between atopic dermatitis and immunological abnormalities, the role ofhydroxyeicosatetraenoic acids (HETE) in atopic dermatitis remains unknown. To develop chiral methods for characterization of 12-HETE enantiomers in a l-chloro-2,4-dinitrochlorobenzene (DNCB)-induced atopic dennatitis mouse model and evaluate the effects of 12-HETE on atopic dermatitis, BALB/c mice were treated with either DNCB or acetone/olive oil (AOO) to induce atopic dermatitis, after which 12(R)- and 12(S)-HETEs in the plasma, skin, spleen, and lymph nodes were quantified by chiral liquid chromatography-tandem mass spectrometry. 12(R)- and 12(S)-HETEs in biological samples of DNCB-induced atopic dermatitis mice increased significantly compared with the AOO group, reflecting the involvement of 12(R)- and 12(S)-HETEs in atopic dermatitis. These findings indicate that 12(R)- and 12(S)-HETEs could be a useful guide for understanding the pathogenesis of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Steam explosions by the interaction of molten corium with water have been studied extensively because they may have the potential to impact the integrity of the containment. Since breakup and fragmentation processes during premixing are important mechanisms that influence steam explosion behavior, the particle she distribution characteristics on fuel-coolant interaction (FCI) have been investigated in the TROI (Test for Real cOrium Interaction with water) test facility. The data characteristics indicate that FCI characteristics depend upon the composition of the prototypic corium material, and the particle size of the debris is related to the intensity of the dynamic pressure produced by an explosion. The mass mean diameters of the debris produced by explosive compositions were less than that of the non-explosive compositions. A mass mean diameter of 2 mm was found to be a boundary size produced by a steam explosion of corium. The particle sizes of the molten corium involving a steam explosion were shown to be mainly 3 to 6 mm depending on the material and composition, but the size distribution shifted to smaller sizes if a steam explosion occurred. Small corium droplets of less than ~3 mm did not seem to contribute to a steam explosion owing to solidification at an early stage before the explosion, but large droplets contributed due to their liquid state. Zirconia, with the largest fusion heat, has almost always exploded, and the explosions have been energetic, while the eutectic composition (UO2/ZrO2 = 70/30 at weight percentage) frequently exploded. On the other hand, noneutectic compositions rarely exploded, even though the heat of the fusion was very similar to the eutectic composition that frequently exploded. The main reason why noneutectic corium compositions do not explode seemed to be that they undergo solidification by forming a "mushy zone" with a small freezing temperature range. To determine whether noneutectic corium melts cooled down through the mushy zone, particles of this composition were analyzed from the surface inward using a scanning electron microscope, an electron probe microanalyzer, and X-ray diffraction. However, all particles were found to have a homogeneous solid solution. The large particles showed the typical solidification shapes of a general molten material. The small particles generally had only a few small pores and small cracks. The morphologies of the large and small particles were found to be similar. [ABSTRACT FROM AUTHOR]

Inorganic phosphate (Pi) plays crucial roles in several biological processes and signaling pathways. Pi uptake is regulated by sodium-dependent phosphate (Na/Pi) transporters (NPTs). Moreover, Pi is used as a food additive in food items such as sausages, crackers, dairy products, and beverages. However, the high serum concentration of phosphate (> 5.5 mg/dL) can cause adverse renal effects, cardiovascular effects including vascular or valvular calcification, and stimulate bone resorption. In addition, Pi can also alter vital cellular signaling, related to cell growth and cap-dependent protein translation. Moreover, intake of dietary Pi, whether high (1.0%) or low (0.1%), affects organs in developing mice, and is related to tumorigenesis in mice. The recommended dietary allowance (RDA) of Pi is the daily dietary intake required to maintain levels above the lower limit of the range of normal serum Pi concentration (2.7 mg/dL) for most individuals (97-98%). Thus, adequate intake of Pi (RDA; 700 mg/day) and maintenance of normal Pi concentration (2.7-4.5 mg/dL) are important for health and prevention of diseases caused by inadequate Pi intake. [ABSTRACT FROM AUTHOR]

Background: Metastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed. Methodology/Principal Finding: Aerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model. Conclusion/Significance: Aerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors. [ABSTRACT FROM AUTHOR]

Water service pipes made of galvanized steel were assessed by direct diagnosis according to major water basins, age of pipe, and their diameters. The tubercle growth and the hydraulic cross sectional area reduction rates from examination with the visual assessment showed that there was little difference among main water basins. However, comparing the results showed that their rates depended on the age of pipe indicating that as ages increase, their rates tend to decrease. Also, in the case of over 40mm diameter, those rates tend to be higher than the case of less than 40mm diameter. From the results of physical properties analysis, even though most of the sampled pipes satisfied Korea Standards (KS) of tensile strength and chemical composition, 90% of the sampled galvanized steel pipes could not satisfy KS of elongation. It could be thought that elongation was seriously effected by pipe deterioration in the view of physical properties and chemical compositions. In addition, the results of scale composition analysis revealed that the component ratio of Fe was highest, whose percentage was from 54.3 ∼ 69.8%, and then that of Zn was 0.09 ∼ 6.34%. In comparing corrosion rates on three water basins, the maximum corrosion rates of Nakdong-River basin was 0.064 mm/year (mmpy), higher than those of other basins. Also, the diameters of the sampled galvanized steel pipes increased the corrosion rates. [ABSTRACT FROM AUTHOR]

The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown. In this study, we investigated hepatotoxicity and key regulation of mitophagy in ephedrine-treated LX-2 cells. Ephedrine triggered mitochondrial oxidative stress and depolarization. Mitochondrial swelling and autolysosome were observed in ephedrine-treated cells. Ephedrine also inhibited mitochondrial biogenesis, and the mitochondrial copy number was decreased. Parkin siRNA recovered the ephedrine-induced mitochondrial damage. Excessive mitophagy lead to cell death through imbalance of autophagic flux. Moreover, antioxidants and reducing Parkin level could serve as therapeutic targets for ephedrine-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

A visualization test of the fuel–coolant interaction in the Test for Real cOrium Interaction with water (TROI) test facility was carried out. To experimentally simulate the In-Vessel corium Retention (IVR)- External Reactor Vessel Cooling (ERVC) conditions, prototypic corium was released directly into the coolant water without a free fall in a gas phase before making contact with the coolant. Corium (34.39 kg) consisting of uranium oxide and zirconium oxide with a weight ratio of 8:2 was superheated, and 22.54 kg of the 34.39 kg corium was passed through water contained in a transparent interaction vessel. An image of the corium jet behavior in the coolant was taken by a high-speed camera every millisecond. Thermocouple junctions installed in the vertical direction of the coolant were cut sequentially by the falling corium jet. It was clearly observed that the visualization image of the corium jet taken during the fuel–coolant interaction corresponded with the temperature variations in the direction of the falling melt. The corium penetrated through the coolant, and the jet leading edge velocity was 2.0 m/s. Debris smaller than 1 mm was 15% of the total weight of the debris collected after a fuel–coolant interaction test, and the mass median diameter was 2.9 mm.

Inorganic phosphate (Pi) is required by all living organisms for the development of organs such as bone, muscle, brain, and lungs, regulating the expression of several critical genes as well as signal transduction. However, little is known about the effects of prolonged dietary Pi consumption on lung cancer progression. This study investigated the effects of a high-phosphate diet (HPD) in a mouse model of adenocarcinoma. K-rasLA1 mice were fed a normal diet (0.3% Pi) or an HPD (1% Pi) for 1, 2, or 4 months. Mice were then sacrificed and subjected to inductively coupled plasma mass/optical emission spectrometry and laser ablation inductively coupled plasma mass-spectrometry analyses, western blot analysis, histopathological, immunohistochemical, and immunocytochemical analyses to evaluate tumor formation and progression (including cell proliferation, angiogenesis, and apoptosis), changes in ion levels and metabolism, autophagy, epithelial-to-mesenchymal transition, and protein translation in the lungs. An HPD accelerated tumorigenesis, as evidenced by increased adenoma and adenocarcinoma rates as well as tumor size. However, after 4 months of the HPD, cell proliferation was arrested, and marked increases in liver and lung ion levels and in energy production via the tricarboxylic acid cycle in the liver were observed, which were accompanied by increased autophagy and decreased angiogenesis and apoptosis. These results indicate that an HPD initially promotes but later inhibits lung cancer progression because of metabolic adaptation leading to tumor cell quiescence. Moreover, the results suggest that carefully regulated Pi consumption are effective in lung cancer prevention.

[This corrects the article DOI: 10.1371/journal.pone.0077121.].