Stability and Equilibrium Structures of Unknown Ternary Metal Oxides Explored by Machine-Learned Potentials.

Ternary metal oxides are crucial components in a wide range of applications and have been extensively cataloged in experimental materials databases. However, there still exist cation combinations with unknown stability and structures of their compounds in oxide forms. In this study, we employ extensive crystal structure prediction methods, accelerated by machine-learned potentials, to investigate these untapped chemical spaces. We examine 181 ternary metal oxide systems, encompassing most cations except for partially filled 3d or f shells, and determine their lowest-energy crystal structures with representative stoichiometry derived from prevalent oxidation states or recommender systems. Consequently, we discover 45 ternary oxide systems containing stable compounds against decomposition into binary or elemental phases, the majority of which incorporate noble metals. Comparisons with other theoretical databases highlight the strengths and limitations of informatics-based material searches. With a relatively modest computational resource requirement, we contend that heuristic-based structure searches, as demonstrated in this study, offer a promising approach for future materials discovery endeavors.

Solution-Processed Cu2S Nanostructures for Solar Hydrogen Production.

Cu2S is a promising solar energy conversion material due to its suitable optical properties, high elemental earth abundance, and nontoxicity. In addition to the challenge of multiple stable secondary phases, the short minority carrier diffusion length poses an obstacle to its practical application. This work addresses the issue by synthesizing nanostructured Cu2S thin films, which enables increased charge carrier collection. A simple solution-processing method involving the preparation of CuCl and CuCl2 molecular inks in a thiol-amine solvent mixture followed by spin coating and low-temperature annealing was used to obtain phase-pure nanostructured (nanoplate and nanoparticle) Cu2S thin films. The photocathode based on the nanoplate Cu2S (FTO/Au/Cu2S/CdS/TiO2/RuO x ) reveals enhanced charge carrier collection and improved photoelectrochemical water-splitting performance compared to the photocathode based on the non-nanostructured Cu2S thin film reported previously. A photocurrent density of 3.0 mA cm-2 at -0.2 versus a reversible hydrogen electrode (V RHE) with only 100 nm thickness of a nanoplate Cu2S layer and an onset potential of 0.43 V RHE were obtained. This work provides a simple, cost-effective, and high-throughput method to prepare phase-pure nanostructured Cu2S thin films for scalable solar hydrogen production.

SEPHS1: Its evolution, function and roles in development and diseases.

Selenophosphate synthetase (SEPHS) was originally discovered in prokaryotes as an enzyme that catalyzes selenophosphate synthesis using inorganic selenium and ATP as substrates. However, in contrast to prokaryotes, two paralogs, SEPHS1 and SEPHS2, occur in many eukaryotes. Prokaryotic SEPHS, also known as SelD, contains either cysteine (Cys) or selenocysteine (Sec) in the catalytic domain. In eukaryotes, only SEPHS2 carries out selenophosphate synthesis and contains Sec at the active site. However, SEPHS1 contains amino acids other than Sec or Cys at the catalytic position. Phylogenetic analysis of SEPHSs reveals that the ancestral SEPHS contains both selenophosphate synthesis and another unknown activity, and that SEPHS1 lost the selenophosphate synthesis activity. The three-dimensional structure of SEPHS1 suggests that its homodimer is unable to form selenophosphate, but retains ATPase activity to produce ADP and inorganic phosphate. The most prominent function of SEPHS1 is that it is implicated in the regulation of cellular redox homeostasis. Deficiency of SEPHS1 leads to the disturbance in the expression of genes involved in redox homeostasis. Different types of reactive oxygen species (ROS) are accumulated in response to SEPHS deficiency depending on cell or tissue types. The accumulation of ROS causes pleiotropic effects such as growth retardation, apoptosis, DNA damage, and embryonic lethality. SEPHS1 deficiency in mouse embryos affects retinoic signaling and other related signaling pathways depending on the embryonal stage until the embryo dies at E11.5. Dysregulated SEPHS1 is associated with the pathogenesis of various diseases including cancer, Crohn's disease, and osteoarthritis.

The Contribution of Nutrients of Concern to the Diets of 18-to-30-Year-Old Australians from Food Prepared Outside Home Differs by Food Outlet Types: The MYMeals Cross-Sectional Study.

Young adults are frequent consumers of food prepared outside the home (FOH). In a cross-sectional survey, the MYMeals study, we showed FOH provided one-third of meals and snacks for young Australian adults, yet it contributed higher proportions of energy and nutrients of concern, such as saturated fat and sodium. This study aimed to determine the detailed proportional contribution of nutrients of concern from the nine food outlet types captured in the MYMeals study. Young adults residing in New South Wales (NSW), Australia, (n = 1001) used a validated smartphone app to report all types and amounts of food and beverages consumed for three consecutive days, as well as their preparation location. The proportions of daily energy, macronutrients, sodium, total sugars, and saturated fat were calculated for each of the nine following outlet types: bakeries or patisseries, coffee chains, cold-drink chains, fast-food chains, ice creamery or frozen yoghurt outlets, independent cafes or restaurants, pubs (hotels) and clubs, service stations or convenience stores, and others not fitting the above categories. Of all FOH outlet types, independent cafes or restaurants contributed the most energy (17.5%), sodium (20.0%) and saturated fat (17.8%) to the total diet, followed by fast-food chains (12.0% energy, 15.8% sodium, and 12.0% saturated fat) and other outlets, with smaller proportions. For males, the proportion of energy and nutrients contributed by fast-food outlets was higher than for females (14.8% versus 9.8% energy). Menu labelling at independent cafes and restaurants is recommended, comprising, in addition to the energy labels already in use in fast-food restaurants, the labelling of nutrients of concern. The feasibility of this recommendation warrants further exploration.

Selenophosphate synthetase 1 deficiency exacerbates osteoarthritis by dysregulating redox homeostasis.

Aging and mechanical overload are prominent risk factors for osteoarthritis (OA), which lead to an imbalance in redox homeostasis. The resulting state of oxidative stress drives the pathological transition of chondrocytes during OA development. However, the specific molecular pathways involved in disrupting chondrocyte redox homeostasis remain unclear. Here, we show that selenophosphate synthetase 1 (SEPHS1) expression is downregulated in human and mouse OA cartilage. SEPHS1 downregulation impairs the cellular capacity to synthesize a class of selenoproteins with oxidoreductase functions in chondrocytes, thereby elevating the level of reactive oxygen species (ROS) and facilitating chondrocyte senescence. Cartilage-specific Sephs1 knockout in adult mice causes aging-associated OA, and augments post-traumatic OA, which is rescued by supplementation of N-acetylcysteine (NAC). Selenium-deficient feeding and Sephs1 knockout have synergistic effects in exacerbating OA pathogenesis in mice. Therefore, we propose that SEPHS1 is an essential regulator of selenium metabolism and redox homeostasis, and its dysregulation governs the progression of OA.

Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction.

The primary function of selenophosphate synthetase (SEPHS) is to catalyze the synthesis of selenophosphate that serves as a selenium donor during selenocysteine synthesis. In eukaryotes, there are two isoforms of SEPHS (SEPHS1 and SEPHS2). Between these two isoforms, only SEPHS2 is known to contain selenophosphate synthesis activity. To examine the function of SEPHS1 in endothelial cells, we introduced targeted null mutations to the gene for SEPHS1, Sephs1, in cultured mouse 2H11 endothelial cells. SEPHS1 deficiency in 2H11 cells resulted in the accumulation of superoxide and lipid peroxide, and reduction in nitric oxide. Superoxide accumulation in Sephs1-knockout 2H11 cells is due to the induction of xanthine oxidase and NADPH oxidase activity, and due to the decrease in superoxide dismutase 1 (SOD1) and 3 (SOD3). Superoxide accumulation in 2H11 cells also led to the inhibition of cell proliferation and angiogenic tube formation. Sephs1-knockout cells were arrested at G2/M phase and showed increased gamma H2AX foci. Angiogenic dysfunction in Sephs1-knockout cells is mediated by a reduction in nitric oxide and an increase in ROS. This study shows for the first time that superoxide was accumulated by SEPHS1 deficiency, leading to cell dysfunction through DNA damage and inhibition of cell proliferation.

Identification of Signaling Pathways for Early Embryonic Lethality and Developmental Retardation in Sephs1-/- Mice.

Selenophosphate synthetase 1 (SEPHS1) plays an essential role in cell growth and survival. However, the underlying molecular mechanisms remain unclear. In the present study, the pathways regulated by SEPHS1 during gastrulation were determined by bioinformatical analyses and experimental verification using systemic knockout mice targeting Sephs1. We found that the coagulation system and retinoic acid signaling were most highly affected by SEPHS1 deficiency throughout gastrulation. Gene expression patterns of altered embryo morphogenesis and inhibition of Wnt signaling were predicted with high probability at E6.5. These predictions were verified by structural abnormalities in the dermal layer of Sephs1-/- embryos. At E7.5, organogenesis and activation of prolactin signaling were predicted to be affected by Sephs1 knockout. Delay of head fold formation was observed in the Sephs1-/- embryos. At E8.5, gene expression associated with organ development and insulin-like growth hormone signaling that regulates organ growth during development was altered. Consistent with these observations, various morphological abnormalities of organs and axial rotation failure were observed. We also found that the gene sets related to redox homeostasis and apoptosis were gradually enriched in a time-dependent manner until E8.5. However, DNA damage and apoptosis markers were detected only when the Sephs1-/- embryos aged to E9.5. Our results suggest that SEPHS1 deficiency causes a gradual increase of oxidative stress which changes signaling pathways during gastrulation, and afterwards leads to apoptosis.

The Contribution of Foods Prepared Outside the Home to the Diets of 18- to 30-Year-Old Australians: The MYMeals Study.

Young adults are the highest consumers of food prepared outside home (FOH) and gain most weight among Australian adults. One strategy to address the obesogenic food environment is menu labelling legislation whereby outlets with >20 stores in one state and >50 Australia-wide must display energy content in kJ. The aim of this study was to assess the contribution of FOH to the energy and macronutrients, saturated fat, total sugars and sodium intakes of young Australians. One thousand and one 18 to 30-year-olds (57% female) residing in Australia's most populous state recorded all foods and beverages consumed and the location of preparation for three consecutive days using a purpose-designed smartphone application. Group means for the daily consumption of energy, percentage energy (%E) for protein, carbohydrate, total sugars, total and saturated fats, and sodium density (mg/1000 kJ) and proportions of nutrients from FOH from menu labelling and independent outlets were compared. Overall, participants consumed 42.4% of their energy intake from FOH with other nutrients ranging from 39.8% (sugars) to 47.3% (sodium). Independent outlets not required to label menus, contributed a greater percentage of energy (23.6%) than menu labelling outlets (18.7%, p < 0.001). Public health policy responses such as public education campaigns, extended menu labelling, more detailed nutrition information and reformulation targets are suggested to facilitate healthier choices.

Efficient Atomic-Resolution Uncertainty Estimation for Neural Network Potentials Using a Replica Ensemble.

Neural network potentials (NNPs) are gaining much attention as they enable fast molecular dynamics (MD) simulations for a wide range of systems while maintaining the accuracy of density functional theory calculations. Since NNP is constructed by machine learning on training data, its prediction uncertainty increases drastically as atomic environments deviate from training points. Therefore, it is essential to monitor the uncertainty level during MD simulations to judge the soundness of the results. In this work, we propose an uncertainty estimator based on the replica ensemble in which NNPs are trained over atomic energies of a reference NNP that drives MD simulations. The replica ensemble is trained quickly, and its standard deviation provides atomic-resolution uncertainties. We apply this method to a highly reactive silicidation process of Si(001) overlaid with Ni thin films and confirm that the replica ensemble can spatially and temporally trace simulation errors at atomic resolution, which in turn guides the augmentation of the training set. The refined NNP completes a 3.6 ns simulation without any noticeable problems. By suggesting an efficient and atomic-resolution uncertainty indicator, this work will contribute to achieving reliable MD simulations by NNPs.

Compression Stocking Length Effects on Oedema, Pain, and Satisfaction in Nursing Students: A Pilot Randomized Trial.

Professional practitioners who are required to stand for long periods of time frequently complain about vein-related symptoms. Compression stocking are effective for vein-related symptoms, but there is not enough evidence on the effect of the length of compression stockings for nursing students. To compare oedema, pain, and satisfaction according to different lengths of compression stockings worn by female nursing students. This study was conducted as a randomized clinical trial. The participants included 20 female nursing students in their first semester of clinical practice training. Compression stockings with 25-32 mmHg pressure were used in the study; the participants were divided into two groups based on the length of compression stocking: knee length and thigh length. Differences between groups regarding pain, oedema, and satisfaction were analysed using t-tests, paired t-tests, and Mann-Whitney U tests, when appropriate. There were no significant differences in pain, oedema, and satisfaction between the two groups. However, pain in right legs of the thigh-length stocking group significantly increased after clinical training shift compared with that before the shift (t = -2.377, p = 0.041). Both groups reported high satisfaction. There were no differences in pain, oedema, and satisfaction in both legs based on the length of compression stockings, but side effects appeared in participants wearing the thigh-length stockings; nevertheless, satisfaction was high in both groups. It may be important to suggest nursing students to wear knee-length compression stockings during clinical practice training.

A Tool to Measure Young Adults' Food Intake: Design and Development of an Australian Database of Foods for the Eat and Track Smartphone App.

BACKGROUND: Dietary assessment is reliant on the collection of accurate food and beverage consumption data. Technology has been harnessed to standardize recording and provide automatic nutritional analysis to reduce cost and researcher burden. OBJECTIVE: To better assess the diet of young adults, especially relating to the contribution of foods prepared outside the home, a database was needed to support a mobile phone data collection app. The app also required usability testing to assure ease of entry of foods and beverages. This paper describes the development of the Eat and Track app (EaT app) and the database underpinning it. METHODS: The Australian Food and Nutrient Database 2011-13, consisting of 5740 food items was modified. Four steps were undertaken: (1) foods not consumed by young adults were removed, (2) nutritionally similar foods were merged, (3) foods available from the 30 largest ready-to-eat food chains in Australia were added, and (4) long generic food names were shortened and simplified. This database was used to underpin the EaT app. Qualitative, iterative usability testing of the EaT app was conducted in three phases using the "Think Aloud" method. Responses were sorted and coded using content analysis. The System Usability Scale (SUS) was administered to measure the EaT app's perceived usability. RESULTS: In total, 1694 (29.51%) foods were removed from the Australian Food and Nutrient Database, including 608 (35.89%) ingredients, 81 (4.78%) foods already captured in the fast food chain information, 52 (3.07%) indigenous foods, 25 (1.48%) nutrients/dietary supplements, and 16 (0.94%) child-specific foods. The remaining 912 (53.84%) foods removed were not consumed by young adults in previous surveys or were "not defined" in the Australian Food and Nutrient Database. Another 220 (3.83%) nutritionally similar foods were combined. The final database consisted of 6274 foods. Fifteen participants completed usability testing. Issues identified by participants fell under six themes: keywords for searching, history list of entered foods, amounts and units, the keypad, food names, and search function. Suggestions for improvement were collected, incorporated, and tested in each iteration of the app. The SUS of the final version of the EaT app was rated 69. CONCLUSIONS: A food and beverage database has been developed to underpin the EaT app, enabling data collection on the eating-out habits of 18- to 30-year-old Australians. The development process has resulted in a database with commonly used food names, extensive coverage of foods from ready-to-eat chains, and commonly eaten portion sizes. Feedback from app usability testing led to enhanced keyword searching and the addition of functions to enhance usability such as adding brief instructional screens. There is potential for the features of the EaT app to facilitate the collection of more accurate dietary intake data. The database and the app will be valuable dietary assessment resources for researchers.

Selenophosphate synthetase 1 and its role in redox homeostasis, defense and proliferation.

Selenophosphate synthetase (SEPHS) synthesizes selenophosphate, the active selenium donor, using ATP and selenide as substrates. SEPHS was initially identified and isolated from bacteria and has been characterized in many eukaryotes and archaea. Two SEPHS paralogues, SEPHS1 and SEPHS2, occur in various eukaryotes, while prokaryotes and archaea have only one form of SEPHS. Between the two isoforms in eukaryotes, only SEPHS2 shows catalytic activity during selenophosphate synthesis. Although SEPHS1 does not contain any significant selenophosphate synthesis activity, it has been reported to play an essential role in regulating cellular physiology. Prokaryotic SEPHS contains a cysteine or selenocysteine (Sec) at the catalytic domain. However, in eukaryotes, SEPHS1 contains other amino acids such as Thr, Arg, Gly, or Leu at the catalytic domain, and SEPHS2 contains only a Sec. Sequence comparisons, crystal structure analyses, and ATP hydrolysis assays suggest that selenophosphate synthesis occurs in two steps. In the first step, ATP is hydrolyzed to produce ADP and gamma-phosphate. In the second step, ADP is further hydrolyzed and selenophosphate is produced using gamma-phosphate and selenide. Both SEPHS1 and SEPHS2 have ATP hydrolyzing activities, but Cys or Sec is required in the catalytic domain for the second step of reaction. The gene encoding SEPHS1 is divided by introns, and five different splice variants are produced by alternative splicing in humans. SEPHS1 mRNA is abundant in rapidly proliferating cells such as embryonic and cancer cells and its expression is induced by various stresses including oxidative stress and salinity stress. The disruption of the SEPHS1 gene in mice or Drosophila leads to the inhibition of cell proliferation, embryonic lethality, and morphological changes in the embryos. Targeted removal of SEPHS1 mRNA in insect, mouse, and human cells also leads to common phenotypic changes similar to those observed by in vivo gene knockout: the inhibition of cell growth/proliferation, the accumulation of hydrogen peroxide in mammals and an unidentified reactive oxygen species (ROS) in Drosophila, and the activation of a defense system. Hydrogen peroxide accumulation in SEPHS1-deficient cells is mainly caused by the down-regulation of genes involved in ROS scavenging, and leads to the inhibition of cell proliferation and survival. However, the mechanisms underlying SEPHS1 regulation of redox homeostasis are still not understood.

Examining the Frequency and Contribution of Foods Eaten Away From Home in the Diets of 18- to 30-Year-Old Australians Using Smartphone Dietary Assessment (MYMeals): Protocol for a Cross-Sectional Study.

BACKGROUND: Young Australians aged between 18 and 30 years have experienced the largest increase in the body mass index and spend the largest proportion of their food budget on fast food and eating out. Frequent consumption of foods purchased and eaten away from home has been linked to poorer diet quality and weight gain. There has been no Australian research regarding quantities, type, or the frequency of consumption of food prepared outside the home by young adults and its impact on their energy and nutrient intakes. OBJECTIVES: The objective of this study was to determine the relative contributions of different food outlets (eg, fast food chain, independent takeaway food store, coffee shop, etc) to the overall food and beverage intake of young adults; to assess the extent to which food and beverages consumed away from home contribute to young adults' total energy and deleterious nutrient intakes; and to study social and physical environmental interactions with consumption patterns of young adults. METHODS: A cross-sectional study of 1008 young adults will be conducted. Individuals are eligible to participate if they: (1) are aged between 18 and 30 years; (2) reside in New South Wales, Australia; (3) own or have access to a smartphone; (4) are English-literate; and (5) consume at least one meal, snack, or drink purchased outside the home per week. An even spread of gender, age groups (18 to 24 years and 25 to 30 years), metropolitan or regional geographical areas, and high and low socioeconomic status areas will be included. Participants will record all food and drink consumed over 3 consecutive days, together with location purchased and consumed in our customized smartphone app named Eat and Track (EaT). Participants will then complete an extensive demographics questionnaire. Mean intakes of energy, nutrients, and food groups will be calculated along with the relative contribution of foods purchased and eaten away from home. A subsample of 19.84% (200/1008) of the participants will complete three 24-hour recall interviews to compare with the data collected using EaT. Data mining techniques such as clustering, decision trees, neural networks, and support vector machines will be used to build predictive models and identify important patterns. RESULTS: Recruitment is underway, and results will be available in 2018. CONCLUSIONS: The contribution of foods prepared away from home, in terms of energy, nutrients, deleterious nutrients, and food groups to young people's diets will be determined, as will the impact on meeting national recommendations. Foods and consumption behaviors that should be targeted in future health promotion efforts for young adults will be identified.