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Critiquing arguments is important for K-12 science students to learn but not emphasized by the predominant claim-evidence-reasoning (CER) argumentation model. Drawing on the work of Yu and Zenker (2020), and Dove and Nussbaum (2018), we developed a tool for supplementing CER with critical questions (CQs) from philosophy that cover most, if not all, the logical dimensions of argument critique. Six middle school science teachers designed lessons involving argumentation, including the use of CQs. We assessed the effects on student self-efficacy for engaging in argument critique, teacher self-efficacy for using argument pedagogy, and teachers' perceptions of the value of CQs. Qualitative data included teacher interviews, lesson transcripts, and student work samples. Quantitative data included surveys of student self-efficacy administered at the beginning and end of the school year. There was evidence suggesting an increase over time in students' confidence for engaging in argument critique and teachers' confidence with argument pedagogy. However, only four of the six teachers were confident and skilled enough to include CQs in their lessons. Those who did use CQs tended to perceive them as providing a helpful structure for critique, prompts for deeper thinking, and a tool for fostering critical classroom norms. Discussion of CQs may have benefitted students' writing by promoting peer critique and encouragement to elaborate. Overall, CQs afford students with a framework for judging argument strength. Scientific argumentation involving CQs provides a more contemporary philosophical basis for scientific argumentation than CER or the Toulmin model as it emphasizes the critical and dialogic nature of science.

Moiré superlattices formed by twisting trilayers of graphene are a useful model for studying correlated electron behaviour and offer several advantages over their formative bilayer analogues, including a more diverse collection of correlated phases and more robust superconductivity. Spontaneous structural relaxation alters the behaviour of moiré superlattices considerably and has been suggested to play an important role in the relative stability of superconductivity in trilayers. Here we use an interferometric four-dimensional scanning transmission electron microscopy approach to directly probe the local graphene layer alignment over a wide range of trilayer graphene structures. Our results inform a thorough understanding of how reconstruction modulates the local lattice symmetries crucial for establishing correlated phases in twisted graphene trilayers, evincing a relaxed structure that is markedly different from that proposed previously.

BACKGROUND: Quantifying the dose and distribution of tobacco smoke in the respiratory system is critical for understanding its toxicity, addiction potential, and health impacts. Epidemiologic studies indicate that the incidence of lung tumors varies across different lung regions, suggesting there may be a heterogeneous deposition of smoke particles leading to greater health risks in specific regions. Despite this, few studies have examined the lobar spatial distribution of inhaled particles from tobacco smoke. This gap in knowledge, coupled with the growing popularity of little cigars among youth, underscores the need for additional research with little cigars. RESULTS: In our study, we analyzed the lobar deposition in rat lungs of smoke particles from combusted regular and mentholated Swisher Sweets little cigars. Twelve-week-old male and female Sprague-Dawley rats were exposed to smoke particles at a concentration of 84 ± 5 mg/m3 for 2 h, after which individual lung lobes were examined. We utilized Inductively Coupled Plasma Mass Spectrometry to quantify lobar chromium concentrations, serving as a smoke particle tracer. Our findings demonstrated an overall higher particle deposition from regular little cigars than from the mentholated ones. Higher particle deposition fraction was observed in the left and caudal lobes than other lobes. We also observed sex-based differences in the normalized deposition fractions among lobes. Animal study results were compared with the multi-path particle dosimetry (MPPD) model predictions, which showed that the model overestimated particle deposition in certain lung regions. CONCLUSIONS: Our findings revealed that the particle deposition varied between different little cigar products. The results demonstrated a heterogenous deposition pattern, with higher particle deposition observed in the left and caudal lobes, especially with the mentholated little cigars. Additionally, we identified disparities between our measurements and the MPPD model. This discrepancy highlights the need to enhance the accuracy of models before extrapolating animal study results to human lung deposition. Overall, our study provides valuable insights for estimating the dose of little cigars during smoking for toxicity research.

Introduction There is considerable variation in the approach to infants presenting to the emergency department (ED) with fever. The authors primary aim was to develop a robust set of algorithms using community ED data to inform modifications of broader clinical guidance. Methods The authors report the development of California Febrile Infant Risk Stratification Tool (CA FIRST) using key components of the Roseville Protocol (ROS) and American Academy of Pediatrics (AAP) Clinical Practice Guideline (CPG). Expanded guidance was derived using a retrospective analysis of a cohort of 3527 febrile infants aged 7-90 days presenting to any Kaiser Permanente Northern California ED between 2010 and 2019 who underwent a core febrile infant evaluation. Results Melding ROS and AAP CPG algorithms in infants 7-60 days old, CA FIRST Algorithms had comparable performance characteristics to ROS and AAP CPG. CA FIRST enhancements included guidance on febrile infants 61-90 days old, high-risk infants, infants with bronchiolitis, and infants who received immunizations within the prior 48 hours. This retrospective analysis revealed that of 235 febrile infants 22-90 days old with respiratory syncytial virus and 221 who had fever in the 48 hours following vaccination, there were no cases of invasive bacterial infection. Discussion CA FIRST is a set of 13 algorithms providing a thoughtful and flexible approach to the febrile infant while minimizing unnecessary interventions. Conclusions CA FIRST Algorithms empower clinicians to manage most febrile infants. Algorithms are being modified as new data become available, imparting useful and ever-current educational information within a learning health care system.

Graphene-based nanomaterials (GBNs) are widely used due to their chemical and physical properties for multiple commercial and environmental applications. From an occupational health perspective, there is concern regarding the effects of inhalation on the respiratory system, and many studies have been conducted to study inhalation impacts on lung. Similar to the respiratory system, the eyes may also be exposed to GBNs and thus impacted. In this study, immortalized human corneal epithelial (hTCEpi) cells and rabbit corneal fibroblasts (RCFs) were used to investigate the toxicity of eight types of GBN: graphene oxide (GO; 400 nm), GO (1 μm), partially reduced graphene oxide (PRGO; 400 nm), reduced graphene oxide (RGO; 400 nm), RGO (2 μm), graphene (110 nm), graphene (140 nm), and graphene (1 μm). We next examined the effects of these GBNs on hTCEpi cell migration. We also determined whether the expression of α-smooth muscle actin (αSMA), a myofibroblast marker, is altered by the GBNs using RCFs. We found that RGO (400 nm) and RGO (2 μm) were highly toxic to hTCEPi cells and RCFs meanwhile, PRGO (400 nm) was toxic only to hTCEpi cells. In addition, PRGO (400 nm), RGO (400 nm), and RGO (2 μm) inhibited hTCEpi cell migration and significantly increased αSMA mRNA expression. Further study in vivo is required to determine if RGO nanomaterials delay corneal epithelial healing and induce scar formation.

Abstract Tribolium castaneum and Rhyzopertha dominica are cosmopolitan, destructive postharvest pests. Although research has investigated how high densities of T. castaneum affect attraction to the aggregation pheromone by conspecifics, research into the behavioral response of both species to food cues after high density exposure has been lacking despite its importance to foraging ecology. Our goal was to manipulate and observe the effects of crowding on the behavioral response of both species to common food and pheromonal stimuli and to determine how the headspace emission patterns from grain differed under increasing densities. Densities of colonies for both species was altered (10–500 adults) on a fixed quantity of food (10 g of flour or whole wheat), then the behavioral response to common food and pheromonal cues was evaluated in a wind tunnel and release-recapture experiment, while volatiles were examined through gas chromatography coupled with mass spectrometry. Importantly, at least for T. castaneum, crowded conditions attenuate attraction to food-based stimuli, but not pheromonal stimuli. Crowding seemed to have no effect on R. dominica attraction to food and pheromonal stimuli in the wind tunnel, but exposure to high density cues did elicit 2.1–3.8-fold higher captures in traps. The relative composition and abundance of headspace volatiles emitted varied significantly with different densities of beetles and was also species-specific. Overall, our results have implications for expanding our understanding of the foraging ecology of two economically important pests.

Asthma is a common chronic respiratory disease exacerbated by multiple environmental factors. Acute ozone exposure has previously been implicated in airway inflammation, airway hyperreactivity, and other characteristics of asthma, which may be attributable to altered sphingolipid metabolism. This study tested the hypothesis that acute ozone exposure alters sphingolipid metabolism within the lung, which contributes to exacerbations in characteristics of asthma in allergen-sensitized mice. Adult male and female BALB/c mice were sensitized intranasally to house dust mite (HDM) allergen on days 1, 3, and 5 and challenged on days 12-14. Mice were exposed to ozone following each HDM challenge for 6 h/day. Bronchoalveolar lavage, lung lobes, and microdissected lung airways were collected for metabolomics analysis (N = 8/sex/group). Another subset of mice underwent methacholine challenge using a forced oscillation technique to measure airway resistance (N = 6/sex/group). Combined HDM and ozone exposure in male mice synergistically increased airway hyperreactivity that was not observed in females and was accompanied by increased airway inflammation and eosinophilia relative to control mice. Importantly, glycosphingolipids were significantly increased following combined HDM and ozone exposure relative to controls in both male and female airways, which was also associated with both airway resistance and eosinophilia. However, 15 glycosphingolipid species were increased in females compared with only 6 in males, which was concomitant with significant associations between glycosphingolipids and airway resistance that ranged from R2 = 0.33-0.51 for females and R2 = 0.20-0.34 in male mice. These observed sex differences demonstrate that glycosphingolipids potentially serve to mitigate exacerbations in characteristics of allergic asthma.

Most transgenic mouse models are generated through random integration of the transgene. The location of the transgene provides valuable information for assessing potential effects of the transgenesis on the host and for designing genotyping protocols that can amplify across the integration site, but it is challenging to identify. Here, we report the successful utility of optical genome mapping technology to identify the transgene insertion site in a CYP2A13/2B6/2F1-transgenic mouse model, which produces three human cytochrome P450 (P450) enzymes (CYP2A13, CYP2B6, and CYP2F1) that are encoded by neighboring genes on human chromosome 19. These enzymes metabolize many drugs, respiratory toxicants, and chemical carcinogens. Initial efforts to identify candidate insertion sites by whole genome sequencing was unsuccessful, apparently because the transgene is located in a region of the mouse genome that contains highly repetitive sequences. Subsequent utility of the optical genome mapping approach, which compares genome-wide marker distribution between the transgenic mouse genome and a reference mouse (GRCm38) or human (GRCh38) genome, localized the insertion site to mouse chromosome 14, between two marker positions at 4451324 base pair and 4485032 base pair. A transgene-mouse genome junction sequence was further identified through long-polymerase chain reaction amplification and DNA sequencing at GRCm38 Chr.14:4484726. The transgene insertion (∼2.4 megabase pair) contained 5-7 copies of the human transgenes, which replaced a 26.9-33.4 kilobase pair mouse genomic region, including exons 1-4 of Gm3182, a predicted and highly redundant gene. Finally, the sequencing results enabled the design of a new genotyping protocol that can distinguish between hemizygous and homozygous CYP2A13/2B6/2F1-transgenic mice. SIGNIFICANCE STATEMENT: This study characterizes the genomic structure of, and provides a new genotyping method for, a transgenic mouse model that expresses three human P450 enzymes, CYP2A13, CYP2B6, and CYP2F1, that are important in xenobiotic metabolism and toxicity. The demonstrated success in applying the optical genome mapping technology for identification of transgene insertion sites should encourage others to do the same for other transgenic models generated through random integration, including most of the currently available human P450 transgenic mouse models.

Lattice reconstruction and corresponding strain accumulation plays a key role in defining the electronic structure of two-dimensional moiré superlattices, including those of transition metal dichalcogenides (TMDs). Imaging of TMD moirés has so far provided a qualitative understanding of this relaxation process in terms of interlayer stacking energy, while models of the underlying deformation mechanisms have relied on simulations. Here, we use interferometric four-dimensional scanning transmission electron microscopy to quantitatively map the mechanical deformations through which reconstruction occurs in small-angle twisted bilayer MoS2 and WSe2/MoS2 heterobilayers. We provide direct evidence that local rotations govern relaxation for twisted homobilayers, while local dilations are prominent in heterobilayers possessing a sufficiently large lattice mismatch. Encapsulation of the moiré layers in hBN further localizes and enhances these in-plane reconstruction pathways by suppressing out-of-plane corrugation. We also find that extrinsic uniaxial heterostrain, which introduces a lattice constant difference in twisted homobilayers, leads to accumulation and redistribution of reconstruction strain, demonstrating another route to modify the moiré potential.

Cohesin rings interact with DNA and modulate the expression of thousands of genes. NIPBL loads cohesin onto chromosomes, and WAPL takes it off. Haploinsufficiency for NIPBL causes a developmental disorder, Cornelia de Lange syndrome (CdLS), that is modeled by Nipbl+/- mice. Mutations in WAPL have not been shown to cause disease or gene expression changes in mammals. Here, we show dysregulation of >1000 genes in WaplΔ/+ embryonic mouse brain. The patterns of dysregulation are highly similar in Wapl and Nipbl heterozygotes, suggesting that Wapl mutations may also cause human disease. Since WAPL and NIPBL have opposite effects on cohesin's association with DNA, we asked whether decreasing Wapl dosage could correct phenotypes seen in Nipbl+/- mice. Gene expression and embryonic growth are partially corrected, but perinatal lethality is not. Our data are consistent with the view that cohesin dynamics play a key role in regulating gene expression.

Moiré superlattices introduce a new degree of freedom, interlayer twist, for tuning the (opto)electronic behavior of materials, through spatially modulated interlayer coupling that produces localized electronic states. We highlight recent explorations into the chemistry of moiré materials and discuss future opportunities for twistronics as a versatile platform for the manipulation of interfacial reactivity.

Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO2 NPs), are used in a wide variety of medical and consumer applications. Inhaled AgNPs have been found to translocate to the olfactory bulb (OB) after inhalation and intranasal instillation. However, the biological effects of Ag-SiO2 NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO2 NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO2 NPs at a concentration of 1 mg/ml for 6 hours. On day 0, 1, 7, and 21 post-exposure, rats were necropsied and OB were harvested. Immunohistochemistry on OB tissues were performed with anti-ionized calcium-binding adapter molecule 1 and heme oxygenase-1 as markers of microglial activation and oxidative stress, respectively. Aerosol characterization indicated Ag-SiO2 NPs were sufficiently aerosolized with moderate agglomeration and high-efficiency deposition in the nasal cavity and olfactory epithelium. Findings suggested that acute inhalation of Ag-SiO2 NPs elicited transient and differential microglial activation in the OB without significant microglial recruitment or oxidative stress. The delayed and differential pattern of microglial activation in the OB implied that inhaled Ag-SiO2 may have translocated to the central nervous system via intra-neuronal pathways.

ObjectiveDescribe emergency department (ED) management and patient outcomes for febrile infants 29-60 days of age who received a lumbar puncture (LP), with focus on timing of antibiotics and type of physician performing LP.MethodsRetrospective observational study of 35 California EDs from January 1, 2010 through December 31, 2019. Primary analysis was among patients with successful LP and primary outcome was hospital length of stay (LOS). Logistic regression analysis included variables associated with LOS of at least 2 days. Secondary outcomes were bacterial meningitis, hospital admission, length of antibiotics, and readmission.ResultsAmong 2569 febrile infants (median age 39 days), 667 underwent successful LP and 633 received intravenous antibiotics. Most infants (n = 559, 88.3%) had their LP before intravenous antibiotic administration. Pediatricians performed 54% of LPs and emergency physicians 34%. Sixteen infants (0.6% of 2569) were diagnosed with bacterial meningitis, and none died. Five hundred and fifty-eight (88%) infants receiving an LP were hospitalized. Among patients receiving an LP and antibiotics (n = 633), 6.5% were readmitted within 30 days. Patients receiving antibiotics before LP had a longer length of antibiotics (+ 7.9 hours, 95% confidence interval [CI] 3.8-13.4). Primary analysis found no association between timing of antibiotics and LOS (odds ratio [OR] 0.67, 95% CI 0.34-1.30), but shorter LOS when emergency physicians performed the LP (OR 0.66, 95% CI 0.45-0.97).ConclusionsFebrile infants in the ED had no deaths and few cases of bacterial meningitis. In community EDs, where a pediatrician is often not available, successful LP by emergency physician was associated with reduced inpatient LOS.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Two-dimensional (2D) engineered nanomaterials are widely used in consumer and industrial goods due to their unique chemical and physical characteristics. Engineered nanomaterials are incredibly small and capable of being aerosolized during manufacturing, with the potential for biological interaction at first-contact sites such as the eye and lung. The unique properties of 2D nanomaterials that make them of interest to many industries may also cause toxicity towards epithelial cells. Using murine and human respiratory epithelial cell culture models, we tested the cytotoxicity of eight 2D engineered nanomaterials: graphene (110 nm), graphene oxide (2 um), graphene oxide (400 nm), reduced graphene oxide (2 um), reduced graphene oxide (400 nm), partially reduced graphene oxide (400 nm), molybdenum disulfide (400 nm), and hexagonal boron nitride (150 nm). Non-graphene nanomaterials were also tested in human corneal epithelial cells for ocular epithelial cytotoxicity. Hexagonal boron nitride was found to be cytotoxic in mouse tracheal, human alveolar, and human corneal epithelial cells. Hexagonal boron nitride was also tested for inhibition of wound healing in alveolar epithelial cells; no inhibition was seen at sub-cytotoxic doses. Nanomaterials should be considered with care before use, due to specific regional cytotoxicity that also varies by cell type. Supported by U01ES027288 and T32HL007013 and T32ES007059.

Tailoring electron transfer dynamics across solid-liquid interfaces is fundamental to the interconversion of electrical and chemical energy. Stacking atomically thin layers with a small azimuthal misorientation to produce moiré superlattices enables the controlled engineering of electronic band structures and the formation of extremely flat electronic bands. Here, we report a strong twist-angle dependence of heterogeneous charge transfer kinetics at twisted bilayer graphene electrodes with the greatest enhancement observed near the 'magic angle' (~1.1°). This effect is driven by the angle-dependent tuning of moiré-derived flat bands that modulate electron transfer processes with the solution-phase redox couple. Combined experimental and computational analysis reveals that the variation in electrochemical activity with moiré angle is controlled by a structural relaxation of the moiré superlattice at twist angles of

Abstract Background Quantifying the dose and distribution of tobacco smoke in the respiratory system is critical for understanding its toxicity, addiction potential, and health impacts. Epidemiologic studies indicate that the incidence of lung tumors varies across different lung regions, suggesting there may be a heterogeneous deposition of smoke particles leading to greater health risks in specific regions. Despite this, few studies have examined the lobar spatial distribution of inhaled particles from tobacco smoke. This gap in knowledge, coupled with the growing popularity of little cigars among youth, underscores the need for additional research with little cigars. Results In our study, we analyzed the lobar deposition in rat lungs of smoke particles from combusted regular and mentholated Swisher Sweets little cigars. Twelve-week-old male and female Sprague-Dawley rats were exposed to smoke particles at a concentration of 84 ± 5 mg/m3 for 2 h, after which individual lung lobes were examined. We utilized Inductively Coupled Plasma Mass Spectrometry to quantify lobar chromium concentrations, serving as a smoke particle tracer. Our findings demonstrated an overall higher particle deposition from regular little cigars than from the mentholated ones. Higher particle deposition fraction was observed in the left and caudal lobes than other lobes. We also observed sex-based differences in the normalized deposition fractions among lobes. Animal study results were compared with the multi-path particle dosimetry (MPPD) model predictions, which showed that the model overestimated particle deposition in certain lung regions. Conclusions Our findings revealed that the particle deposition varied between different little cigar products. The results demonstrated a heterogenous deposition pattern, with higher particle deposition observed in the left and caudal lobes, especially with the mentholated little cigars. Additionally, we identified disparities between our measurements and the MPPD model. This discrepancy highlights the need to enhance the accuracy of models before extrapolating animal study results to human lung deposition. Overall, our study provides valuable insights for estimating the dose of little cigars during smoking for toxicity research.

Paraquat (PQ) is an agrochemical known to cause pulmonary fibrosis. PQ-induced collagen deposition in the lung is thought to require enzymatic formation of PQ radicals, but the specific enzymes responsible for this bioactivation event in vivo have not been identified. We tested the hypothesis that lung P450 oxidoreductase (POR or CPR) is important in PQ-induced lung fibrosis in mice. A lung-Cpr-null mouse model was utilized, which undergoes doxycycline-induced, Cre recombinase-mediated deletion of the Por gene specifically in airway Club cells and alveolar type 2 cells in the lung. The lungs of lung-Cpr-null mice and their wild-type littermates were collected on day 15 after a single intraperitoneal injection of saline (control) or PQ (20 mg/kg). Lung tissue sections were stained with picrosirius red for detection of collagen fibrils. Fibrotic lung areas were found to be significantly smaller (1.6-fold for males and 1.4-fold for females) in PQ-treated lung-Cpr-null mice than in sex- and treatment-matched wild-type mice. The levels of collagen in lung tissue homogenate were also lower (1.4-2.3-fold; p < 0.05) in PQ-treated lung-Cpr-null mice compared to PQ-treated wild-type mice. In contrast, plasma PQ toxicokinetic profiles were not different between sex-matched wild-type and lung-Cpr-null mice. Taken together, these results indicate that lung POR plays an important role in PQ-induced pulmonary fibrosis.

The ocular surface, comprised of the transparent cornea, conjunctiva, and protective tear film, forms a protective barrier defending deeper structures of the eye from particulate matter and mechanical trauma. This barrier is routinely exposed to a multitude of naturally occurring and engineered nanomaterials (ENM). Metallic ENMs are particularly ubiquitous in commercial products with a high risk of ocular exposure, such as cosmetics and sunscreens. Additionally, there are several therapeutic uses for metallic ENMs owing to their attractive magnetic, antimicrobial, and functionalization properties. The increasing commercial and therapeutic applications of metallic ENMs come with a high risk of ocular exposure with poorly understood consequences to the health of the eye. While the toxicity of metallic ENMs exposure has been rigorously studied in other tissues and organs, further studies are necessary to understand the potential for adverse effects and inform product usage for individuals whose ocular health may be compromised by injury, disease, or surgical intervention. This review provides an update of current literature on the ocular toxicity of metallic ENMs in vitro and in vivo, as well as the risks and benefits of therapeutic applications of metallic ENMs in ophthalmology.

Lipids have not traditionally been considered likely candidates for catalyzing reactions in biological systems. However, there is significant evidence that aggregates of amphiphilic compounds are capable of catalyzing reactions in synthetic organic chemistry. Here, we demonstrate the potential for the hydrophobic region of a lipid bilayer to provide an environment suitable for catalysis by means of a lipid aggregate capable of speeding up a chemical reaction. By bringing organic molecules into the nonpolar or hydrophobic region of a lipid bilayer, reactions can be catalyzed by individual or collections of small, nonpolar, or amphiphilic molecules. We demonstrate this concept by the ester hydrolysis of calcein-AM to produce a fluorescent product, which is a widely used assay for esterase activity in cells. The reaction was first carried out in a two-phase octanol–water system, with the organic phase containing the cationic amphiphiles cetyltrimethylammonium bromide (CTAB) or octadecylamine. The octanol phase was then replaced with phospholipid vesicles in water, where the reaction was also found to be carried out. The reaction was monitored using quantitative fluorescence, which revealed catalytic turnover numbers on a scale of 10−7 to 10−8 s−1 for each system, which is much slower than enzymatic catalysis. The reaction product was characterized by 1H-NMR measurements, which were consistent with ester hydrolysis. The implications of thinking about lipids and lipid aggregates as catalytic entities are discussed in the context of biochemistry, pharmacology, and synthetic biology.

Naphthalene is a ubiquitous environmental contaminant produced by combustion of fossil fuels and is a primary constituent of both mainstream and side stream tobacco smoke. Naphthalene elicits region-specific toxicity in airway club cells through cytochrome P450 (P450)-mediated bioactivation, resulting in depletion of glutathione and subsequent cytotoxicity. Although effects of naphthalene in mice have been extensively studied, few experiments have characterized global metabolomic changes in the lung. In individual lung regions, we found metabolomic changes in microdissected mouse lung conducting airways and parenchyma obtained from animals sacrificed at 3 timepoints following naphthalene treatment. Data on 577 unique identified metabolites were acquired by accurate mass spectrometry-based assays focusing on lipidomics and nontargeted metabolomics of hydrophilic compounds. Statistical analyses revealed distinct metabolite profiles between the 2 lung regions. Additionally, the number and magnitude of statistically significant exposure-induced changes in metabolite abundance were different between airways and parenchyma for unsaturated lysophosphatidylcholines, dipeptides, purines, pyrimidines, and amino acids. Importantly, temporal changes were found to be highly distinct for male and female mice with males exhibiting predominant treatment-specific changes only at 2 h postexposure. In females, metabolomic changes persisted until 6 h postnaphthalene treatment, which may explain the previously characterized higher susceptibility of female mice to naphthalene toxicity. In both males and females, treatment-specific changes corresponding to lung remodeling, oxidative stress response, and DNA damage were observed. Overall, this study provides insights into potential mechanisms contributing to naphthalene toxicity and presents a novel approach for lung metabolomic analysis that distinguishes responses of major lung regions.

PurposeCorneal keratocyte-fibroblast-myofibroblast (KFM) transformation plays a critical role in corneal stromal wound healing. However, the impact of engineered nanomaterials (ENMs), found in an increasing number of commercial products, on this process is poorly studied. This study investigates the effects of metal oxide ENMs on KFM transformation in vitro and in vivo.MethodsCell viability of rabbit corneal fibroblasts (RCFs) was tested following treatment with 11 metal oxide ENMs at concentrations of 0.5 to 250 µg/ml for 24 hours. Messenger RNA (mRNA) and protein expression of αSMA, a marker of myofibroblast transformation, were measured using RCFs after exposure to 11 metal oxide ENMs at a concentration that did not affect cell viability, in media containing either 0 or 10 ng/ml of TGF-β1. Additionally, the effect of topical Fe2O3 nanoparticles (NPs) (50 ng/ml) on corneal stromal wound healing following phototherapeutic keratectomy (PTK) was determined.ResultsV2O5, Fe2O3, CuO, and ZnO ENMs were found to significantly reduce cell viability as compared to vehicle control and the other seven metal oxide ENMs tested. V2O5 nanoflakes significantly reduced mRNA and protein αSMA concentrations in the presence of TGF-β1. Fe2O3 NPs significantly increased αSMA mRNA expression in the presence of TGF-β1 but did not alter αSMA protein expression. Topically applied Fe2O3 NPs in an in vivo rabbit corneal stromal wound healing model did not delay healing.ConclusionsFe2O3 NPs promote corneal myofibroblast induction in vitro but do not impair corneal stromal wound healing in vivo.Translational relevanceThese experimental results can apply to human nanomedical research.

Background This article provides an update of the Reflective Practice Questionnaire (RPQ). The original RPQ consisted of 40-items with 10-sub-scales. In this article, the RPQ is streamlined into a 10-item single reflective practice construct, and a 30-item extended version that includes additional sub-scales of confidence, uncertainty/stress, and work satisfaction. Methods A total of 501 university students filled out an online questionnaire that contained the original Reflective Practice Questionnaire, and two general measures of reflection: The Self-Reflection and Insight Scale, and the Rumination-Reflection Questionnaire. Results Based on factor analysis, the RPQ was streamlined into a brief 10-item version, and an extended 30-item version. Small positive correlations were found between the RPQ reflective practice measure and the two measures of general reflection, providing discriminant validity evidence for the RPQ. The RPQ was found to be sensitive to differences among industries, whereas the general measures of reflection were not. Average reflective practice scores were higher for health and education industries compared to retail and food/accommodation industries.

High throughput screening of small molecules and natural products is costly, requiring significant amounts of time, reagents, and operating space. Although microarrays have proven effective in the miniaturization of screening for certain biochemical assays, such as nucleic acid hybridization or antibody binding, they are not widely used for drug discovery in cell culture due to the need for cells to internalize lipophilic drug candidates. Lipid droplet microarrays are a promising solution to this problem as they are capable of delivering lipophilic drugs to cells at dosages comparable to solution delivery. However, the scalablility of the array fabrication, assay validation, and screening steps has limited the utility of this approach. Here we take several new steps to scale up the process for lipid droplet array fabrication, assay validation in cell culture, and drug screening. A nanointaglio printing process has been adapted for use with a printing press. The arrays are stabilized for immersion into aqueous solution using a vapor coating process. In addition to delivery of lipophilic compounds, we found that we are also able to encapsulate and deliver a water-soluble compound in this way. The arrays can be functionalized by extracellular matrix proteins such as collagen prior to cell culture as the mechanism for uptake is based on direct contact with the lipid delivery vehicles rather than diffusion of the drug out of the microarray spots. We demonstrate this method for delivery to 3 different cell types and the screening of 92 natural product extracts on a microarray covering an area of less than 0.1 cm2. The arrays are suitable for miniaturized screening, for instance in high biosafety level facilities where space is limited and for applications where cell numbers are limited, such as in functional precision medicine.

Van der Waals heteroepitaxy allows deterministic control over lattice mismatch or azimuthal orientation between atomic layers to produce long-wavelength superlattices. The resulting electronic phases depend critically on the superlattice periodicity and localized structural deformations that introduce disorder and strain. In this study we used Bragg interferometry to capture atomic displacement fields in twisted bilayer graphene with twist angles

Abstract Lattice reconstruction and corresponding strain accumulation plays a key role in defining the electronic structure of two-dimensional moiré superlattices, including those of transition metal dichalcogenides (TMDs). Imaging of TMD moirés has so far provided a qualitative understanding of this relaxation process in terms of interlayer stacking energy, while models of the underlying deformation mechanisms have relied on simulations. Here, we use interferometric four-dimensional scanning transmission electron microscopy to quantitatively map the mechanical deformations through which reconstruction occurs in small-angle twisted bilayer MoS2 and WSe2/MoS2 heterobilayers. We provide direct evidence that local rotations govern relaxation for twisted homobilayers, while local dilations are prominent in heterobilayers possessing a sufficiently large lattice mismatch. Encapsulation of the moiré layers in hBN further localizes and enhances these in-plane reconstruction pathways by suppressing out-of-plane corrugation. We also find that extrinsic uniaxial heterostrain, which introduces a lattice constant difference in twisted homobilayers, leads to accumulation and redistribution of reconstruction strain, demonstrating another route to modify the moiré potential.

PurposePreviously we assessed healthcare professional students’ feelings about team-based learning, implicit bias, and service to the community using an in-house paper survey. In this study, we determined whether this survey is a reliable and valid measure of prospective medical students’ attitudes toward required service-learning in an Immunology course. To our knowledge, no published questionnaire has been shown to be dependable and useful for measuring such attitudes using only eight survey items.MethodsFifty-eight prospective medical students in Colorado (CO) and 15 in Utah (UT) completed the same Immunology course using remote technology. In addition to the usual course content, students were required to write critical reflections on required team service-learning. On the last day of class, they completed the survey of attitudes toward service-learning (SASL).ResultsData analyses found Cronbach’s alpha values of 0.84 and 0.85 for the surveys of UT and CO students, respectively. Factor analysis of CO student data revealed only one Eigenvalue greater than one (3.95) justifying retention of a single factor termed “attitudes toward required service-learning.” In addition, CO students’ attitudes toward community service were highly positive, while UT students’ attitudes were nearer neutral (p