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Abstract Background Given the global shifts in environmental conditions and dietary habits, understanding the potential impact of dietary factors and body mass index (BMI) on respiratory diseases, including asthma, is paramount. Investigating these relationships can contribute to the formulation of more effective prevention strategies. The Planetary Health Diet Index (PHDI), a dietary scoring system that balances human health with environmental sustainability, underscores the importance of increasing the consumption of plant-based foods while reducing the intake of red meat, sugar, and highly processed foods. The objective of this study was to assess the association between PHDI and the prevalence of asthma and the mediation effect of BMI in a US general population. Methods This study utilized data from 32,388 participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018. Multivariate logistic regression and weighted quantile sum (WQS) regressions were employed to investigate the association between PHDI, individual nutrients, and asthma. Restricted cubic spline (RCS) analysis explored the linear or non-linear relationship between PHDI and asthma. Interaction analyses were conducted on subgroups to validate the findings. Mediation analysis was performed to examine the effect of BMI on the relationship between PHDI and asthma. Results There was a significant negative association between PHDI and asthma. After adjusting for covariates, for every 10-point increase in PHDI, there was a 4% decrease in the prevalence of asthma (P = 0.025). Moreover, as PHDI increased, there was a trend towards lower asthma prevalence (P for trend

BackgroundWhile prior research has established a correlation between dietary choline intake and bone density in the elderly, the relationship in adolescents remains ambiguous. This study seeks to examine the association between dietary choline intake and bone density in American adolescents.MethodsData from the National Health and Nutrition Examination Survey (NHANES) for 2005 to 2018 were used in this study, encompassing participants aged 12–19 years. The relationship between dietary choline intake and bone density was assessed using multivariate linear regression models and restricted cubic spline (RCS) models. Subgroup analyses were also performed to investigate differences across various subgroups.Results3,800 participants with an average age of 15 years were included in this study. After adjusting for relevant confounding factors, a positive correlation was observed between dietary choline intake and total bone density in adolescents (95% CI: 0.03–0.17, p = 0.010). Gender-specific analysis indicated a significant positive correlation between dietary choline intake and total bone density in males (95% CI: 0.07–0.23, p

BackgroundThe relationship between CDAI and suicidal ideation is unclear. This study investigates the relationship between CDAI and suicidal ideation and examines the association between CDAI and all-cause mortality (ACM) or cardiovascular disease mortality (CVM) among participants with and without suicidal ideation.MethodsData from seven NHANES cycles (2005–2018) were analyzed using cross-sectional and prospective cohort studies. Weighted multivariable logistic regression models, restricted cubic spline (RCS) plots, and subgroup analyses explored the association between CDAI and suicidal ideation. Kaplan–Meier (KM) curves, weighted multivariable Cox proportional hazards models, and RCS assessed the relationship between CDAI and CVM or ACM.ResultsAmong 30,976 participants aged over 20, 1,154 (3.72%) had suicidal ideation. Higher CDAI levels (Quartile 4) were associated with a 28% reduction in suicidal ideation compared to lower levels (Quartile 1). Over an average follow-up of 89 months, 3,267 participants (7.6%) died, including 808 (1.8%) from cardiovascular causes. Higher CDAI levels were linked to a 30, 68, and 28% reduction in ACM in the total population, those with suicidal ideation, and those without, respectively. CVM was reduced by 40% in the total population and by 41% in those without suicidal ideation.ConclusionCDAI is negatively associated with suicidal ideation and correlated with reduced ACM and CVM among participants with and without suicidal ideation.

Abstract Background Epidemiologic studies have suggested that elevated concentrations of particulate matter (PM) are strongly associated with an increased risk of developing cardiovascular diseases, including arrhythmia. However, the cellular and molecular mechanisms by which PM exposure causes arrhythmia and the component that is mainly responsible for this adverse effect remains to be established. In this study, the arrhythmogenicity of mobilized organic matter from two different types of PM collected during summer (SPM) and winter (WPM) seasons in the Seoul metropolitan area was evaluated. In addition, differential effects between polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs (oxy-PAHs) on the induction of electrophysiological instability were examined. Results We extracted the bioavailable organic contents of ambient PM, measuring 10 μm or less in diameter, collected from the Seoul metropolitan area using a high-volume air sampler. Significant alterations in all factors tested for association with electrophysiological instability, such as intracellular Ca2+ levels, reactive oxygen species (ROS) generation, and mRNA levels of the Ca2+-regulating proteins, sarcoplasmic reticulum Ca2+ATPase (SERCA2a), Ca2+/calmodulin-dependent protein kinase II (CaMK II), and ryanodine receptor 2 (RyR2) were observed in cardiomyocytes treated with PM. Moreover, the alterations were higher in WPM-treated cardiomyocytes than in SPM-treated cardiomyocytes. Three-fold more oxy-PAH concentrations were observed in WPM than SPM. As expected, electrophysiological instability was induced higher in oxy-PAHs (9,10-anthraquinone, AQ or 7,12-benz(a) anthraquinone, BAQ)-treated cardiomyocytes than in PAHs (anthracene, ANT or benz(a) anthracene, BaA)-treated cardiomyocytes; oxy-PAHs infusion of cells mediated by aryl hydrocarbon receptor (AhR) was faster than PAHs infusion. In addition, ROS formation and expression of calcium-related genes were markedly more altered in cells treated with oxy-PAHs compared to those treated with PAHs. Conclusions The concentrations of oxy-PAHs in PM were found to be higher in winter than in summer, which might lead to greater electrophysiological instability through the ROS generation and disruption of calcium regulation.

Translanguaging theory highlights the dynamic use of multiple languages and communication modes by multilingual people in their daily experiences. Museums are informal family learning spaces where multilingual families use languages and other semiotic resources to create learning opportunities for their children. Using a microethnographic approach to discourse analysis and multimodal interaction analysis, I examined how a multilingual family uses translanguaging practices to organize their family learning in museums and the role of pointing gestures as part of their translanguaging repertoires in multilingual family learning. The analysis of two literacy events highlights that a child and his mother translanguaged with various semiotic resources to organize museum performances, joint attention, and telling, and that pointing gestures played a role in constructing a translanguaging space as they organized the two performances. Pointing involved the family in reading signage texts and allowed the mother to translate them for the child. Viewing translation as part of the translanguaging repertoire, this study recognizes the importance of the role of pointing gestures in constructing family learning at museums, enriching children's schooling and literacy learning in classrooms. I argue that recognizing pointing as a critical component of translanguaging allows educators to develop strategies that leverage families' unique repertoires to support multilingual students' language and literacy learning.

Sanger sequencing, also known as dideoxy sequencing, is a widely used method for DNA sequencing, particularly for cloned plasmids and clinical samples. This technique requires a combination of essential biochemistry skills, such as a chain-termination reaction, gel electrophoresis, and fluorescence detection. Unfortunately, there is a lack of activities that replicate the Sanger sequencing process for students to learn and practice these skills. To address this issue, a manipulative-based Sanger sequencing activity was developed that incorporates colorful pop beads to demonstrate a chain-termination reaction, separation of products, and fluorescence detection. The beads represent deoxynucleotides and dideoxynucleotides, allowing for a visual representation of DNA fragment generation. This kinesthetic learning activity offers a high visual impact for students, aiding in their understanding of the Sanger sequencing process, and can also be used to illustrate polymerase chain reaction (PCR)-based techniques.

Background/Aims: Anoctamin1 (Ca2+-activated Cl- channel, ANO1) is a specific marker of the interstitial cells of Cajal (ICC) in the gastrointestinal tract, and are candidate proteins that can function as pacemaker channels. Recently, novel selective ANO1 inhibitors were discovered and used to study Ca2+-activated Cl- channels. Therefore, to investigate whether ANO1 channels function as pacemaker channels, selective ANO1 inhibitors were tested with respect to the pacemaker potentials in ICC. Methods: Whole-cell patch-clamp recording, RT-PCR, and intracellular Ca2+ ([Ca2+]i) imaging were performed in cultured ICC obtained from mice. Results: Though CaCCinh-A01 (5 µM), T16Ainh-A01 (5 µM), and MONNA (5 µM) (selective ANO1 inhibitors) blocked the generation of pacemaker potentials in colonic ICC, they did not do so in small intestinal ICC. Though nifulmic acid (10 µM) and DIDS (10 µM) (classical Ca2+-activated Cl- channel inhibitors) also had no effect in small intestinal ICC, they suppressed the generation of pacemaker potentials in colonic ICC. In addition, knockdown of ANO1 reduced the pacemaker potential frequency in colonic ICC alone. Though ANO1 inhibitors suppressed [Ca2+]i oscillations in colonic ICC, they did not do so in small intestinal ICC. T-type Ca2+ channels were expressed in the both the small intestinal and colonic ICC, but mibefradil (5 µM) and NiCl2 (30 µM) (T-type Ca2+ channel inhibitors) inhibited the generation of pacemaker potentials in colonic ICC alone. Conclusion: These results indicate that though ANO1 and T-type Ca2+ channels participate in generating pacemaker potentials in colonic ICC, they do not do so in small intestinal ICC. Therefore, the mechanisms underlying pacemaking in ICC might be different in the small intestine and the colon.

Background: Chronic treatment with the dietary flavonoid quercetin is known to lower blood pressure and restore endothelial dysfunction in animal models of hypertension. This study investigated the direct effects of quercetin on vascular response in chronic 2-kidney, 1-clip (2K1C) renal hypertensive rats. The effects of antioxidant vitamin ascorbic acid on the vasoreactivity were also examined. Methods: 2K1C renal hypertension was induced by clipping the left renal artery; age-matched rats that received sham treatment served as controls. Thoracic aortae were mounted in tissue baths for the measurement of isometric tension. Results: Relaxant responses to acetylcholine were significantly attenuated in 2K1C rats in comparison with sham rats. Quercetin or ascorbic acid augmented acetylcholine-induced relaxation in 2K1C rats, whereas no significant differences were noted in sham rats. The relaxation response to sodium nitroprusside was comparable between 2K1C and sham rats, and sodium nitroprusside–induced relaxation was not altered by quercetin or ascorbic acid in either group. The contractile response to phenylephrine was significantly enhanced in 2K1C rats compared with sham rats. Phenylephrine-induced contraction was inhibited by pretreatment with quercetin or ascorbic acid in 2K1C rats, whereas neither chemical affected responses in sham rats. Nw-nitro-L-arginine methyl ester markedly augmented the contractile response to phenylephrine in sham rats, whereas no significant differences were observed in 2K1C rats. Quercetin or ascorbic acid did not affect phenylephrine-induced contraction in the presence of Nw-nitro-L-arginine methyl ester in either 2K1C or sham rats. Conclusion: Acute exposure to quercetin appears to improve endothelium-dependent relaxation and inhibit the contractile response, similar to the effect of ascorbic acid in 2K1C hypertension. These results partially explain the vascular beneficial effects of quercetin in renal hypertension.

Background: The plant-derived estrogen biochanin A is known to cause vasodilation, but its mechanism of action in hypertension remains unclear. This study was undertaken to investigate the effects and mechanisms of biochanin A on the thoracic aorta in two-kidney, one clip (2K1C) renovascular hypertensive rats. Methods: Hypertension was induced by clipping the left renal artery, and control age-matched rats were sham treated. Thoracic aortae were mounted in tissue baths to measure isometric tension. Results: Biochanin A caused concentration-dependent relaxation in aortic rings from 2K1C hypertensive and sham-treated rats, which was greater in 2K1C rats than in sham rats. Biochanin A-induced relaxation was significantly attenuated by removing the endothelium in aortic rings from 2K1C rats, but not in sham rats. Nω-Nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, did not affect the biochanin A-induced relaxation in aortic rings from 2K1C and sham rats. By contrast, treatment with glibenclamide, a selective inhibitor of adenosine triphosphate-sensitive K+ channels, or tetraethylammonium, an inhibitor of Ca2+-activated K+ channels, significantly reduced biochanin A-induced relaxation in aortic rings from both groups. However, 4-aminopyridine, a selective inhibitor of voltage-dependent K+ channels, inhibited the relaxation induced by biochanin A in 2K1C rats, whereas no significant differences were observed in sham rats. Conclusion: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K+ channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K+ channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.

Background/Aims: Ginseng regulates gastrointestinal (GI) motor activity but the underlying components and molecular mechanisms are unknown. We investigated the effect of gintonin, a novel ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, on the pacemaker activity of the interstitial cells of Cajal (ICC) in murine small intestine and GI motility. Materials and Methods: Enzymatic digestion was used to dissociate ICC from mouse small intestines. The whole-cell patch-clamp configuration was used to record pacemaker potentials and currents from cultured ICC in the absence or presence of gintonin. In vivo effects of gintonin on gastrointestinal (GI) motility were investigated by measuring the intestinal transit rate (ITR) of Evans blue in normal and streptozotocin (STZ)-induced diabetic mice. Results: We investigated the effects of gintonin on pacemaker potentials and currents in cultured ICC from mouse small intestine. Gintonin caused membrane depolarization in current clamp mode but this action was blocked by Ki16425, an LPA1/3 receptor antagonist, and by the addition of GDPβS, a GTP-binding protein inhibitor, into the ICC. To study the gintonin signaling pathway, we examined the effects of U-73122, an active PLC inhibitor, and chelerythrine and calphostin, which inhibit PKC. All inhibitors blocked gintonin actions on pacemaker potentials, but not completely. Gintonin-mediated depolarization was lower in Ca2+-free than in Ca2+-containing external solutions and was blocked by thapsigargin. We found that, in ICC, gintonin also activated Ca2+-activated Cl- channels (TMEM16A, ANO1), but not TRPM7 channels. In vivo, gintonin (10-100 mg/kg, p.o.) not only significantly increased the ITR in normal mice but also ameliorated STZ-induced diabetic GI motility retardation in a dose-dependent manner. Conclusions: Gintonin-mediated membrane depolarization of pacemaker activity and ANO1 activation are coupled to the stimulation of GI contractility through LPA1/3 receptor signaling pathways in cultured murine ICC. Gintonin might be a ingredient responsible for ginseng-mediated GI tract modulations, and could be a novel candidate for development as a prokinetic agent that may prevent or alleviate GI motility dysfunctions in human patients.

Background: Endothelial dysfunction is linked to exaggerated production of superoxide anions. This study was conducted to examine the effects of oxidative stress on endothelial modulation of contractions in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. Methods: The 2K1C hypertension was induced by clipping the left renal artery; age-matched rats receiving sham treatment served as controls. Thoracic aortae were isolated and mounted in tissue baths for measurement of isometric tension. Results: Norepinephrine-induced contraction was augmented by the removal of the endothelium, which was more pronounced in sham rats than in 2K1C rats. Nω-nitro-L-arginine methyl ester, an inhibitor of nitric oxide production, had a similar augmenting effect. Vitamin C inhibited the contraction in aortic rings with intact endothelium from 2K1C rats but not from sham rats. The contraction was also suppressed by treatment with diphenyleneiodonium or apocynin, inhibitors of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase, in the aortae with intact endothelium from 2K1C rats but not in those from sham rats. Superoxide anions generated by xanthine oxidase/hypoxanthine enhanced the contraction in the aortae with intact endothelium from sham rats, but had no effect in 2K1C rats. Enhanced contractile responses to norepinephrine by xanthine oxidase/hypoxanthine in sham rats were reversed by vitamin C. Conclusion: These results suggest that the effect on endothelial modulation of endothelium-derived nitric oxide is impaired in 2K1C hypertension. The impairment is, at least in part, related to increased production of superoxide anions by NADH/NADPH oxidase.

The electrical switching behavior of the GeTe phase-changing material grown by atomic layer deposition is characterized for the phase change random access memory (PCRAM) application. Planar-type PCRAM devices are fabricated with a TiN or W bottom electrode (BE). The crystallization behavior is characterized by applying an electrical pulse train and analyzed by applying the Johnson−Mehl−Avrami kinetics model. The device with TiN BE shows a high Avrami coefficient (>4), meaning that continuous and multiple nucleations occur during crystallization (set switching). Meanwhile, the device with W BE shows a smaller Avrami coefficient (~3), representing retarded nucleation during the crystallization. In addition, larger voltage and power are necessary for crystallization in case of the device with W BE. It is believed that the thermal conductivity of the BE material affects the temperature distribution in the device, resulting in different crystallization kinetics and set switching behavior.

This study predicted the performance of an inlet guide vane to be installed later by applying an absolute flow angle (ß) at the axial pump inlet. The pump’s performance was predicted based on changes in inlet ß, and the influence of variations in inlet ß on the low-flow area was analyzed. For turbulence flow analyses, the Reynolds-averaged Navier–Stokes equations were discretized based on the finite volume method. The internal flow was analyzed in detail through transient analysis. Furthermore, the impact of changes in the absolute flow angle at the inlet on the rotating stall occurring inside the pump in the low-flow-rate region was analyzed. The analysis of the internal flow field confirmed that the absolute flow angle at the inlet affects the stability of the internal flow. Results showed that energy reduction and efficient operation scenarios can be established compared with the existing valve control method by changing inlet ß. Through fast Fourier-transform analysis, it was confirmed that when the inlet angle (θ) is changed in the low-flow-rate region, a more stable operation is possible compared with the existing one.

Abstract The effectiveness of dual‐doping as a method of improving the conductivity of sulfide solid electrolytes (SEs) is not in doubt; however, the atomic‐level mechanisms underpinning these enhancements remain elusive. In this study, we investigate the atomic mechanisms associated with the high ionic conductivity of the Li7P3S11 (LPS) SE and its response to Ag/Cl dual dopants. Synthesis and electrochemical characterizations show that the 0.2 M AgCl‐doped LPS (Li6.8P3Ag0.1S10.9Cl0.1) exhibited an over 80% improvement in ionic conductivity compared with the undoped LPS. The atomic‐level structures responsible for the enhanced conductivity were generated by a set of experiment and simulation techniques: synchrotron X‐ray diffractometry, Rietveld refinement, density functional theory, and artificial neural network‐based molecular dynamics simulations. This thorough characterization highlights the role of dual dopants in altering the structure and ionic conductivity. We found that the PS4 and P2S7 structural motifs of LPS undergo transformation into various PSx substructures. These changes in the substructures, in conjunction with the paddle‐wheel effect, enable rapid Li migration. The dopant atoms serve to enhance the flexibility of PS4–P2S7 polyhedral frameworks, consequently enhancing the ionic conductivity. Our study elucidates a clear structure–conductivity relationship for the dual‐doped LPS, providing a fundamental guideline for the development of sulfide SEs with superior conductivity.

Abstract EGFR mutations are a major prognostic factor in lung adenocarcinoma. However, current detection methods require sufficient samples and are costly. Deep learning is promising for mutation prediction in histopathological image analysis but has limitations in that it does not sufficiently reflect tumor heterogeneity and lacks interpretability. In this study, we developed a deep learning model to predict the presence of EGFR mutations by analyzing histopathological patterns in whole slide images (WSIs). We also introduced the EGFR mutation prevalence (EMP) score, which quantifies EGFR prevalence in WSIs based on patch‐level predictions, and evaluated its interpretability and utility. Our model estimates the probability of EGFR prevalence in each patch by partitioning the WSI based on multiple‐instance learning and predicts the presence of EGFR mutations at the slide level. We utilized a patch‐masking scheduler training strategy to enable the model to learn various histopathological patterns of EGFR. This study included 868 WSI samples from lung adenocarcinoma patients collected from three medical institutions: Hallym University Medical Center, Inha University Hospital, and Chungnam National University Hospital. For the test dataset, 197 WSIs were collected from Ajou University Medical Center to evaluate the presence of EGFR mutations. Our model demonstrated prediction performance with an area under the receiver operating characteristic curve of 0.7680 (0.7607–0.7720) and an area under the precision‐recall curve of 0.8391 (0.8326–0.8430). The EMP score showed Spearman correlation coefficients of 0.4705 (p = 0.0087) for p.L858R and 0.5918 (p = 0.0037) for exon 19 deletions in 64 samples subjected to next‐generation sequencing analysis. Additionally, high EMP scores were associated with papillary and acinar patterns (p = 0.0038 and p = 0.0255, respectively), whereas low EMP scores were associated with solid patterns (p = 0.0001). These results validate the reliability of our model and suggest that it can provide crucial information for rapid screening and treatment plans.

Background: Ferulic acid (FA) is a naturally occurring nutritional compound. Although it has been shown to have antihypertensive effects, its effects on vascular function have not been intensively established. The aim of this study was to assess the vasoreactivity of FA in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. Methods: Hypertension was induced in 2K1C rats by clipping the left renal artery and age-matched rats that received a sham treatment served as a control. Thoracic aortas were mounted in tissue baths to measure isometric tension. The effects of FA on vasodilatory responses were evaluated based on contractile responses induced by phenylephrine in the aortic rings obtained from both 2K1C and sham rats. Basal nitric oxide (NO) bioavailability in the aorta was determined by the contractile response induced by NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME). Results: FA induced concentration-dependent relaxation responses which were greater in 2K1C hypertensive rats than in sham-clipped control rats. This relaxation induced by FA was partially blocked by the removal of endothelium or by pretreating with l-NAME. l-NAME-induced contractile responses were augmented by FA in 2K1C rats, while no significant differences were noted in sham rats. FA improved acetylcholine-induced endothelium-dependent vasodilation in 2K1C rats, but not in sham rats. The simultaneous addition of hydroxyhydroquinone significantly inhibited the increase in acetylcholine-induced vasodilation by FA. Conclusion: These results suggest that FA restores endothelial function by altering the bioavailability of NO in 2K1C hypertensive rats. The results explain, in part, the mechanism underlying the vascular effects of FA in chronic renal hypertension.

The aim of the study is to formulate an injectable nanocrystalline suspension (NS) of dutasteride (DTS), a hydrophobic 5α-reductase inhibitor used to treat benign prostatic hyperplasia and scalp hair loss, for parenteral long-acting delivery. A DTS-loaded NS (DTS-NS, 40 mg/mL DTS) was prepared using a lab-scale bead-milling technique. The optimized DTS-NS prepared using Tween 80 (0.5% w/v) as a nano-suspending agent, was characterized as follows: rod/rectangular shape; particle size of 324 nm; zeta potential of −11 mV; and decreased drug crystallinity compared with intact drug powder. The DTS-NS exhibited a markedly protracted drug concentration-time profile following intramuscular injection, reaching a maximum concentration after 8.40 days, with an elimination half-life of 9.94 days in rats. Histopathological observations revealed a granulomatous inflammatory response at the injection site 7 days after intramuscular administration, which significantly subsided by day 14 and showed minimal inflammation by day 28. These findings suggest that the nanosuspension system is a promising approach for the sustained release parenteral DTS delivery, with a protracted pharmacokinetic profile and tolerable local inflammation.