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Herein, we employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatments on female mice. Controlling the addition of precursor HAuCl 4 allows for the fabrication of different atomic ratios of Au x Cu y . X-ray absorption near edge spectra indicates that Au and Cu are the predominant oxidation states of zero valence. This suggests that the charges of Au and Cu remain unchanged after galvanic replacement. Specifically, Au 0.02 Cu 0.98 composition reveals the enhanced •OH generation following O 2  → H 2 O 2  → •OH. The degradable Au 0.02 Cu 0.98 released Cu + and Cu 2+ resulting in oxygen reduction and Fenton-like reactions. Simulation studies indicate that Au single atoms boot zero-valent copper to reveal the catalytic capability of Au 0.02 Cu 0.98 for O 2  → H 2 O 2  → •OH as well. Instead of using endogenous H 2 O 2 , H 2 O 2 can be sourced from the O 2 in the air through the use of nanocubes. Notably, the Au 0.02 Cu 0.98 structure is degradable and renal-clearable. Single-atom catalysts emerge as nanocatalytic medicine in chemodynamic therapy but suffer from inefficient kinetics for the production of reactive oxygen species because of the cell’s antioxidative mechanisms. Here, the authors employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatment.

A bstract We study real-time correlators for N = 4 super Yang Mill fields coupled to a pair of entangled quarks using holography, in the setup that energy quanta sent from one quark perturb the quantum state of the fields and affect the other quark. We make the connection with the ER=EPR conjecture by considering the situation when two quarks are uniformly accelerating opposite to each other. The dynamics of quarks, in the gravity dual, is described by the string worldsheet theory, which in this case has the induced metric describing a two-sided AdS black hole, or a wormhole. Energy quanta sent by one of the quarks produce the shock wave on the worldsheet. We find the effect of shock wave on the boundary field correlators and we discuss the consequence for the ER=EPR conjecture.

This paper quantifies employer market power in US manufacturing and how it has changed over time. Using administrative data, we estimate plant-level markdowns—the ratio between a plant’s marginal revenue product of labor and its wage. We find most manufacturing plants operate in a monopsonistic environment, with an average markdown of 1.53, implying a worker earning only 65 cents on the marginal dollar generated. To investigate long-term trends for the entire sector, we propose a novel, theoretically grounded measure for the aggregate markdown. We find that it decreased between the late 1970s and the early 2000s, but has been sharply increasing since.

B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, the density of peptide/MHCII (pMHCII) complexes on GC B cells is the primary determinant of selection. Here we show in chimeric mice populated by B cells differing only in their capacity to express MHCII (MHCII +/+ and MHCII +/− ) that GC selection is insensitive to halving pMHCII density. Alone, both B cell types generate identical humoral responses; in competition, MHCII +/+ B cells are preferentially recruited to early GCs but this advantage does not persist once GCs are established. During GC responses, competing MHCII +/+ and MHCII +/− GC B cells comparably accumulate mutations and have indistinguishable rates of affinity maturation. We conclude that B-cell selection by pMHCII density is stringent in the establishment of GCs, but relaxed during GC responses. It has been thought that germinal center (GC) B cells with the highest density of peptide-MHCII molecules receive the most T cell help. Here the authors use heterozygous MHCII inactivation to instead show that after recruitment into the GCs, BCR affinity increases over time independent of the MHC density.

The purpose of this mixed-methods study was to investigate the influential factors of student satisfaction with online digital audio-visual flipped classroom learning. A total of 103 students enrolling in the two-credit compulsory code course participated in this flipped classroom research. Descriptive data analysis and grey relational analysis demonstrated that student respondents were most satisfied with repeated practice (1st), followed immediately by peer learning (2nd), and active learning (3rd). In terms of qualitative data, three themes emerged from the focus group analysis, including: improving independent learning, enhancing peer learning, and increasing teacher–student interaction. The flipped classroom model provided opportunities for students to strengthen their self-directed learning capabilities, improved students’ learning motivation, and to be a team player among third-year nursing students. The results were consistent with the actual circumstance. The results integrated descriptive data, the mathematic model, and interviews to validate the accuracy and rationality of the data. According to this study, an online digital audio-visual flipped classroom could improve student independent learning and enhance peer communication. The results provide an accurate assessment tool suitable for Taiwanese nursing students’ flipped classroom model learning experience.

This study introduces a novel approach to cancer treatment using covalent organic frameworks (COFs) with dual atomic metal sites, employing a galvanic reaction to integrate both gold (Au) and iridium (Ir) onto COF (COF/Aux/Ir1‐x). The integration of these metals enables a synergistic catalytic cycle that enhances glucose oxidation and the generation of reactive oxygen species (ROS) and reactive halogen species (RHS). Au catalyzes glucose oxidation, producing gluconic acid and hydrogen peroxide (H₂O₂), while Ir decomposes H₂O₂ into superoxide anion (O₂⁻) and, in the presence of chloride ions (Cl⁻), generates hypochlorous acid (HOCl). The dual metal atomic sites facilitate a feedback cycle where H₂O₂ is efficiently converted back to oxygen (O₂), amplifying ROS and RHS generation within cancer cells. By fine‐tuning the Au: Ir ratio through the galvanic reaction, optimal catalytic performance is achieved, creating a highly effective tumor treatment strategy. This work represents the first application of dual metal atomic sites on COFs for cancer therapy, demonstrating significant potential for catalysis‐based biomedical applications. The synergistic interactions between Au and Ir enhance catalytic efficiency, offering a new approach to exploiting endogenous cancer cell metabolites for targeted and efficient cancer treatment. A galvanic replacement is used to control dual atomic metals (Au and Ir) on a covalent organic framework (COF) nanoparticle and then coated with hyaluronic acid (HA). Under a specific bimetallic ratio (COF/Aux/Ir1‐x), the optimization can be achieved for the conversion of intracellular nutrients into reactive species (HOCl and O2• ─) and effectively inhibits the growth of liver cancer.

Charcoal-burning suicide has recently been spreading to many Asian countries. There have also been several cases involving this new method of suicide in Western countries. Restricting access to suicide means is one of the few suicide-prevention measures that have been supported by empirical evidence. The current study aims to assess the effectiveness of a community intervention program that restricts access to charcoal to prevent suicide in Taiwan. A quasi-experimental design is used to compare method-specific (charcoal-burning suicide, non-charcoal-burning suicide) and overall suicide rates in New Taipei City (the intervention site, with a population of 3.9 million) with two other cities (Taipei City and Kaohsiung City, the control sites, each with 2.7 million residents) before (Jan 1st 2009- April 30th 2012) and after (May 1st 2012-Dec. 31st 2013) the initiation of a charcoal-restriction program on May 1st 2012. The program mandates the removal of barbecue charcoal from open shelves to locked storage in major retail stores in New Taipei City. No such restriction measure was implemented in the two control sites. Generalized linear regression models incorporating secular trends were used to compare the changes in method-specific and overall suicide rates before and after the initiation of the restriction measure. A simulation approach was used to estimate the number of lives saved by the intervention. Compared with the pre-intervention period, the estimated rate reduction of charcoal-burning suicide in New Taipei City was 37% (95% CI: 17%, 50%) after the intervention. Taking secular trends into account, the reduction was 30% (95% CI: 14%, 44%). No compensatory rise in non-charcoal-burning suicide was observed in New Taipei City. No significant reduction in charcoal-burning suicide was observed in the other two control sites. The simulation approach estimated that 91 (95%CI [55, 128]) lives in New Taipei City were saved during the 20 months of the intervention. Our results demonstrate that the charcoal-restriction program reduced method-specific and overall suicides. This study provides strong empirical evidence that restricting the accessibility of common lethal methods of suicide can effectively reduce suicide rates.

PurposeThe purpose of this study is to explore the impact of mobile learning platforms on users' study efficiency and develop cognitive indicators to evaluate users' study efficiency on mobile learning platforms.Design/methodology/approachLayout style was the only independent factor that was investigated. A between-group experimental design was employed. Eye movement data were recorded during the experiment, following which participants were asked to complete an after-scenario questionnaire. This study evaluated the usability of the proposed new design using both subjective and objective data. The computer system usability questionnaire V3 (CSUQ) was used to measure subjective data. For the eye-tracking measure, gaze entropy, the proportion of fixation count and duration of each AOI were calculated. Gaze entropy reflects the complexity of information organization. Fixation counts and AOI duration represent the difficulty of information processing and attention distribution, respectively during the task.FindingsThe results indicated that interface layout presents significant effects on user's learning efficiency, usability and cognitive load. Sequential layout improved efficiency and satisfaction among participants and reduced information complexity. The results provided useful insights for designers whose goal is to improve user's learning efficiency under mobile learning scheme.Originality/valueThis study investigated the effects of interface layout on usability, user performance and cognitive load using subjective ratings and eye-tracking technology. Gaze entropy was used to measure the complexity of information organized by the interface design. Fixation count and duration proportion were used to identify the difficulty of information processing and distinguish users' distribution of cognitive resources. The results indicated that a vertical layout panel design was more efficient than a horizontal layout panel design. The design implications of the eye tracking indicators and research results were then summarized. This study is expected to encourage designers to optimize their design proposals using eye tracking testing.

Glucocorticoids serve important regulatory functions for many physiological processes and are critical mediators of the stress response. The stress response is a set of bodily processes aimed at counteracting a state of threatened homeostasis. Proper stress response is critical for the survival of an animal, however prolonged or abnormal stress response can be detrimental and is implicated in a number of human diseases such as depression and metabolic diseases. To dissect the underlying mechanism of this complex and important response, the zebrafish, Danio rerio offer important advantages such as ease of genetic manipulations and high-throughput behavioral analyses. However, there is a paucity of suitable methods to measure stress level in larval zebrafish. Therefore, an efficient low-cost method to monitor stress hormone levels will greatly facilitate stress research in zebrafish larvae. In this study, we optimized sample collection as well as cortisol extraction methods and developed a home-made ELISA protocol for measuring whole-body cortisol level in zebrafish larvae. Further, using our customized protocols, we characterized the response of larval zebrafish to a variety of stressors. This assay, developed for efficient cortisol quantification, will be useful for systematic and large-scale stress analyses in larval zebrafish.

Summary One of the goals of biofortification is to generate iron‐enriched crops to combat growth and developmental defects especially iron (Fe) deficiency anaemia. Fe‐fortification of food is challenging because soluble Fe is unstable and insoluble Fe is nonbioavailable. Genetic engineering is an alternative approach for Fe‐biofortification, but so far strategies to increase Fe content have only encompassed a few genes with limited success. In this study, we demonstrate that the ethyl methanesulfonate (EMS) mutant, iron deficiency tolerant1 (idt1), can accumulate 4–7 times higher amounts of Fe than the wild type in roots, shoots and seeds, and exhibits the metal tolerance and iron accumulation (Metina) phenotype in Arabidopsis. Fe‐regulated protein stability and nuclear localisation of the upstream transcriptional regulator bHLH34 were uncovered. The C to T transition mutation resulting in substitution of alanine to valine at amino acid position 320 of bHLH34 (designated as IDT1A320V) in a conserved motif among mono‐ and dicots was found to be responsible for a dominant phenotype that possesses constitutive activation of the Fe regulatory pathway. Overexpression of IDT1A320V in Arabidopsis and tobacco led to the Metina phenotype; a phenotype that has escalated specificity towards optimising Fe homeostasis and may be useful in Fe‐biofortification. Knowledge of the high tolerance and accumulation of heavy metals of this mutant can aid the development of tools for phytoremediation of contaminants.