Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Within-class multimodal classification

Multimedia Tools and Applications - In many real-world classification problems there exist multiple subclasses (or clusters) within a class; in other words, the underlying data distribution is...     

Photoactive Earth‐Abundant Iron Pyrite Catalysts for Electrocatalytic Nitrogen Reduction Reaction

The generation of ammonia, hydrogen production, and nitrogen purification are considered as energy intensive processes accompanied with large amounts of CO₂ emission. An electrochemical method assisted by photoenergy is widely utilized for the chemical energy conversion. In this work, earth‐abundant iron pyrite (FeS₂) nanocrystals grown on carbon fiber paper (FeS₂/CFP) are found to be an electrochemical and photoactive catalyst for nitrogen reduction reaction under ambient temperature and pressure. The electrochemical results reveal that FeS₂/CFP achieves a high Faradaic efficiency (FE) of ≈14.14% and NH₃ yield rate of ≈0.096 µg min^?1 at ?0.6 V versus RHE electrode in 0.25 m LiClO₄. During the electrochemical catalytic reaction, the crystal structure of FeS₂/CFP remains in the cubic pyrite phase, as analyzed by in situ X‐ray diffraction measurements. With near‐infrared laser irradiation (808 nm), the NH₃ yield rate of the FeS₂/CFP catalyst can be slightly improved to 0.1 µg min^?1 with high FE of 14.57%. Furthermore, density functional theory calculations demonstrate that the N₂ molecule has strong chemical adsorption energy on the iron atom of FeS₂. Overall, iron pyrite‐based materials have proven to be a potential electrocatalyst with photoactive behavior for ammonia production in practical applications.     

Chewing gum consumption in the United States among children,adolescents and adults

Data regarding chewing gum consumption habits and attitudes were collected for 963 children and adolescents (aged 6–14) and 3150 adolescents and adults (aged 13 years+) in the United States (U.S.) using a dedicated online food frequency questionnaire. A total of 79.6% of children/adolescents reported using chewing gum in the last 3 months, whereas 61.8% of adolescents/adults chewed gum in the previous 6 months. The mean and 90th percentile of consumption among children/adolescents aged 6–14 were 1.95 and 4.71 g day^?1, equivalent to 0.75 and 1.78 pieces per day, respectively. Stratification by gender and age brackets revealed that the consumption of chewing gum was more heavily reported in boys compared to girls. Among adolescents/adults aged 13 years and older, the mean and 90th percentile of consumption of chewing gum was estimated to be 2.98 and 7.67 g day^?1, or 1.05 and 3.00 pieces per day, respectively. Stratification by gender and by age brackets in this cohort did not reveal any marked patterns although it was noted that there was a decrease in the percent consuming with age (from 87.0 to 34.5%). The most commonly reported chew frequency among all ages was ‘two or three times a week’ (23.7 to 26.8%). The average and high-level estimates reported herein provide up-to-date estimates of chewing gum consumption in the U.S. Comparisons of the calculated intake values with those reported from the National Health and Nutrition Examination Survey dataset suggests that national nutrition surveys may result in an under-reporting of the percent consumers, but similar estimates for the daily intakes in g day^?1.     

Automatic brain tissue segmentation in MR images using hybrid atlas forest based on confidence-weighted probability matrix

The segmentation of specific tissues in an MR brain image for quantitative analysis can assist the disease diagnosis and medical research. Therefore, a robust and accurate method for automatic segmentation is necessary. Atlas-based-method is a common and effective method of automatic segmentation where an atlas refers to a pair of image consist of an intensity image and its corresponding label image. Apart from the general multi-atlas-based methods, which propagate labels through the single atlas then fuse them, we proposed a hybrid atlas forest based on confidence-weighted probability matrix to consider the atlases set as a whole and treat each voxel differently. In the framework, we first register the atlas to the image space of target and calculate the confidence of voxels in the registered atlas. Then, a confidence-weighted probability matrix is generated and it augments to the intensity image of the atlas or target for providing spatial information of the target tissue. Third, a hybrid atlas forest is trained to gather the features and correlation information among the atlases in the dataset. Finally, the segmentation of the target tissues is predicted by the trained hybrid atlas forest. The segment performance and the components efficiency of the proposed method are evaluated on the two public datasets. Based on the experiment results and quantitative comparisons, our method can gather spatial information and correlation among the atlases to obtain an accurate segmentation.     

Structure and crystallization behavior of complex mold flux glasses in the system CaO-Na2O-Li2O-CaF2-B2O3-SiO2: A multi-nuclear NMR spectroscopic study

The structure of mold flux glasses in the system CaO-(Na,Li)₂O-SiO₂-CaF₂ with unusually high modifier contents, stabilized by the addition of ∼4 mol% B₂O₃, is studied using ⁷Li, ²³Na, ¹⁹F, ¹¹B, and ²⁹Si magic-angle-spinning (MAS), and ⁷Li{¹⁹F} and ²³Na{¹⁹F} rotational echo double-resonance (REDOR) nuclear magnetic resonance (NMR) spectroscopy. When taken together, the spectroscopic results indicate that the structure of these glasses consists primarily of dimeric [Si₂O₇]⁻⁶ units that are linked to the (Ca,Na,Li)-O coordination polyhedra, and are interspersed with chains of corner-shared BO₃ units. The F atoms in the structure are exclusively bonded to Ca atoms, forming Ca(O,F)_n coordination polyhedra. This structural scenario is shown to be consistent with the crystallization of cuspidine (3CaO·2SiO₂·CaF₂) from the parent melts on slow supercooling. The progressive addition of Li to a Na-containing base composition results in a corresponding increase in the undercooling required for the nucleation of cuspidine in the melt, which is attributed to the frustrated local structure caused by the mixing of alkali ions.     

Particulate matter emitted from ultrasonic humidifiers—Chemical composition and implication to indoor air

Household humidification is widely practiced to combat dry indoor air. While the benefits of household humidification are widely perceived, its implications to the indoor air have not been critically appraised. In particular, ultrasonic humidifiers are known to generate fine particulate matter (PM). In this study, we first conducted laboratory experiments to investigate the size, quantity, and chemical composition of PM generated by an ultrasonic humidifier. The mass of PM generated showed a correlation with the total alkalinity of charge water, suggesting that CaCO₃ is likely making a major contribution to PM. Ion chromatography analysis revealed a large amount of SO₄²⁻ in PM, representing a previously unrecognized indoor source. Preliminary results of organic compounds being present in humidifier PM are also presented. A whole-house experiment was further conducted at an actual residential house, with five low-cost sensors (AirBeam) monitoring PM in real time. Operation of a single ultrasonic humidifier resulted in PM_2.5 concentrations up to hundreds of μg m⁻³, and its influence extended across the entire household. The transport and loss of PM_2.5 depended on the rate of air circulation and ventilation. This study emphasizes the need to further investigate the impact of humidifier operation, both on human health and on the indoor atmospheric chemistry, for example, partitioning of acidic and basic compounds.     

Physical,mechanical and thermal properties of cross laminated timber made with coconut wood

European Journal of Wood and Wood Products - The fundamental material properties of coconut wood cross-laminated timber (CLT) were experimentally evaluated with a focus on the effect of the...     

Three-dimensional finite element analysis of geosynthetic-reinforced soil walls with turning corners

The paper presents in-depth three-dimensional finite element analyses investigating geosynthetic-reinforced soil walls with turning corners. Validation of the 3D numerical procedure was first performed via comparisons between the simulated and reported results of a benchmark physical modeling built at the Royal Military College of Canada. GRS walls with corners of 90°, 105°, 120°, 135°, 150°, and 180° were simulated adopting the National Concrete Masonry Association guidelines. The behaviors of the GRS walls with corners, including the lateral facing displacement, maximum reinforcement load, factor of safety, potential failure surface, vertical separation of facing blocks, and types of corners were carefully evaluated. Our comprehensive results show (i) minimum lateral displacement occurs at the corner; (ii) lower strength of reinforcements are required at the corner; (iii) higher corner angles lead to lower stability; (iv) potential failure surface forms earlier at the end walls; (v) deeper potential failure surfaces are found at the corners; (vi) larger numbers of vertical separations are found at walls with smaller corner angles. The paper highlighted the salient influence of the corners on the behaviors of GRS walls and indicated that a 3D analysis could reflect the required reinforcement length and the irregular formation of the potential failure surfaces.