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Abstract Conventional superconducting flux qubits require the application of a precisely tuned magnetic field to set the operation point at half a flux quantum through the qubit loop, which complicates the on-chip integration of this type of device. It has been proposed that by inducing a π-phase shift in the superconducting order parameter using a precisely controlled nanoscale-thickness superconductor/ferromagnet/superconductor Josephson junction, commonly referred to as π-junction, it is possible to realize a flux qubit operating at zero magnetic flux. Here, we report the realization of a zero-flux-biased flux qubit based on three NbN/AlN/NbN Josephson junctions and a NbN/PdNi/NbN ferromagnetic π-junction. The qubit lifetime is in the microsecond range, which we argue is limited by quasiparticle excitations in the metallic ferromagnet layer. Our results pave the way for developing quantum coherent devices, including qubits and sensors, that utilize the interplay between ferromagnetism and superconductivity.

Phthalates and bisphenols (BPs) are well-known endocrine disrupting chemicals (EDCs) that are widely used in diverse consumer and personal care products. Despite their vulnerability, children are frequently exposed to phthalates and BPs in their surrounding environments. Although pre-school children spend most of their time in kindergarten, no comprehensive assessment of children’ exposure to EDCs has been conducted according to the type of kindergarten. In this study, the urinary concentrations of phthalate metabolites and BPs were determined in Korean children attending conventional and eco-friendly kindergartens. The exposure levels and contaminant profiles were investigated according to kindergarten type and their association with oxidative stress was assessed. Di-(2-ethylhexyl) phthalate (DEHP) metabolites, such as mono-(2-ethyl-5-carboxypentyl) phthalate (median: 47.1 ng/mL) and mono-[(2-carboxymethyl)hexyl] phthalate (8.45 ng/mL) had the highest levels, indicating that they were the primary contaminants to which the children were exposed. Urinary concentrations of phthalate metabolites and bisphenol A (BPA) were higher in children from conventional kindergarten than an eco-friendly kindergarten. Conversely, bisphenol S (BPS) concentrations were significantly higher in children from the eco-friendly kindergarten than in those from conventional kindergartens, implying that eco-friendly plastic products might contain BPS as a replacement for BPA. The estimated daily intakes of BPA for all children exceeded the new tolerable daily intake proposed by the European Food Safety Authority. Malondialdehyde levels were significantly associated with the urinary concentrations of certain phthalate metabolites, indicating potential adverse health outcomes from phthalate exposure in children. The study highlights the need for targeted interventions to reduce EDC exposure in children, especially in settings where alternative chemicals may still pose health risks.

Terahertz (THz) emission from electrically biased graphene is studied under high magnetic fields. A quantum well (QW)-based charge-sensitive infrared phototransistor (CSIP) is used to detect weak THz emission from a graphene Hall bar. THz emission is clearly observed at around 5 T when the Hall voltage exceeds the corresponding Landau-level (LL) energy spacing between the zero-energy (N = 0) and first excited (N = +1 or N = −1) LLs, suggesting that the emission occurs primarily at the carrier entry and exit corners of the current contacts in the Hall bar. We also investigate the emission spectra through measurements of the QW spectrum of the CSIP. The emission spectra are well explained by the N = +1 → 0 (or N = −1 → 0) inter-LL radiative transition in monolayer graphene. The linewidth of the emission spectra is estimated to be on the order of 10 meV, even though no explicit LL splitting is observed in the magnetotransport at 5 T.

Summary: Purpose: Although the importance of health promotion for nurses is increasing, there is a lack of meta-analyses targeting nurses in the world. This study aimed to identify the effect sizes between the health-promoting behaviors and related variables of nurses working in Korea. Methods: Systematic review and meta-analysis were conducted according to the PRISMA and MOOSE guidelines. The literature included in this meta-analysis was published between 1994 and 2022 in core databases such as KMbase, KISS, KoreaMed, ScienceON, DBpia, NAL, RISS, CINAHL, CENTRAL, WoS, PubMed, and hand searched. In this study, the PICO-SD framework was applied with Participants being nurses actively working in various healthcare settings across Korea, and for a more comprehensive search, intervention and comparisons were not set. The outcomes measured were nurses' health-promoting behaviors, assessed using structured tools. The study design included observational studies. The Comprehensive Meta-Analysis and the R software program were used for meta-analysis. Results: In total, 50 articles were selected for the systematic review and meta-analysis. The total effect size of the 50 articles was moderate (correlation effect size [ESr] = 0.30). The individual variables presented in the 50 articles were classified into nine sub-categories according to Pender's Health Promotion Model (HPM). Among them, situational influences demonstrated the largest effect size (ESr = 0.44, number of studies [k] = 2), followed by perceived self-efficacy (ESr = 0.39, k = 10) and activity-related affect (ESr = 0.32, k = 12). Conclusions: To achieve the optimal health status of nurses through health promotion intervention programs, these effective variables – situational influences, perceived self-efficacy, and activity-related affect – should be considered when developing the intervention program for nurses. Registration: CRD42022299907.

Abstract Background It is not unusual to see some parts of tissues are excluded in the field of view of CT simulation images. A typical mitigation is to avoid beams entering the missing body parts at the cost of sub-optimal planning. Methods This study is to solve the problem by developing 3 methods, (1) deep learning (DL) mechanism for missing tissue generation, (2) using patient body outline (PBO) based on surface imaging, and (3) hybrid method combining DL and PBO. The DL model was built upon a Globally and Locally Consistent Image Completion to learn features by Convolutional Neural Networks-based inpainting, based on Generative Adversarial Network. The database used comprised 10,005 CT training slices of 322 lung cancer patients and 166 CT evaluation test slices of 15 patients. CT images were from the publicly available database of the Cancer Imaging Archive. Since existing data were used PBOs were acquired from the CT images. For evaluation, Structural Similarity Index Metric (SSIM), Root Mean Square Error (RMSE) and Peak signal-to-noise ratio (PSNR) were evaluated. For dosimetric validation, dynamic conformal arc plans were made with the ground truth images and images generated by the proposed method. Gamma analysis was conducted at relatively strict criteria of 1%/1 mm (dose difference/distance to agreement) and 2%/2 mm under three dose thresholds of 1%, 10% and 50% of the maximum dose in the plans made on the ground truth image sets. Results The average SSIM in generation part only was 0.06 at epoch 100 but reached 0.86 at epoch 1500. Accordingly, the average SSIM in the whole image also improved from 0.86 to 0.97. At epoch 1500, the average values of RMSE and PSNR in the whole image were 7.4 and 30.9, respectively. Gamma analysis showed excellent agreement with the hybrid method (equal to or higher than 96.6% of the mean of pass rates for all scenarios). Conclusions It was first demonstrated that missing tissues in simulation imaging could be generated with high similarity, and dosimetric limitation could be overcome. The benefit of this study can be significantly enlarged when MR-only simulation is considered.

Abstract Background Access to healthcare services is important, especially for patients with chronic diseases. We evaluated the effect of the COVID-19 pandemic on outpatient visits and medication for patients with hypertension and diabetes in South Korea. Methods Nationwide claims data were extracted for patients with hypertension and diabetes from January 2019 to July 2020. We used an interrupted time series (ITS) analysis to evaluate the pandemic’s impact on outpatient care using the number of outpatient visits and days of medication supplied per visit. We identified the change in the continuity of care in medication, a consequence of the change in outpatient care, using the Medication Possession Ratio (MPR). Results The number of outpatient visits for diabetes significantly declined in February 2020, when community transmission began. However, when high-intensity social distancing was relaxed in April 2020, outpatient visits for hypertension and diabetes rebounded significantly. Moreover, when the outpatient visits declined, the number of days of medication supplied per visit increased. Consequently, the average MPRs significantly increased compared to 2019, increasing the ratio of patients with appropriate medication supply (MPR ≥ 0.8). Conclusions Outpatient visits decreased immediately when COVID-19 spread to local communities. However, the number of days of medication supplied per visit increased to compensate for the longer intervals between visits. Rather, the change in the continuity of care in medication improved; thus, the temporary decrease in outpatient visits might have had a limited negative impact on health outcomes.

Abstract Background Aggregated amyloid-β (Aβ) is considered a pathogenic initiator of Alzheimer’s disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal of amyloid burden from AD patient brains by antibodies has shown therapeutic potential, the development of small molecule drugs inducing chemical dissociation and clearance of Aβ is compelling as a therapeutic strategy. In this study, we synthesized and screened aryloxypropanolamine derivatives and identified 1-(3-(2,4-di-tert-pentylphenoxy)-2-hydroxypropyl)pyrrolidin-1-ium chloride, YIAD002, as a strong dissociator of Aβ aggregates. Methods The dissociative activity of aryloxypropanolamine derivatives against Aβ aggregates were evaluated through in vitro assays. Immunohistochemical staining, immunoblot assays, and the Morris water maze were used to assess the anti-Alzheimer potential in YIAD002-treated 5XFAD and transgenic APP/PS1 mice. Target-ligand interaction mechanism was characterized via a combination of peptide mapping, fluorescence dissociation assays, and constrained docking simulations. Results Among 11 aryloxypropanolamine derivatives, YIAD002 exerted strongest dissociative activity against β-sheet-rich Aβ aggregates. Upon oral administration, YIAD002 substantially reduced amyloid burden and accordingly, improved cognitive performance in the Morris water maze and attenuated major pathological hallmarks of AD including tauopathy, neuroinflammation, and synaptic protein loss. Mechanism studies suggest that YIAD002 interferes with intermolecular β-sheet fibrillation by directly interacting with KLVFFA and IGLMVG domains of Aβ. In addition, YIAD002 was found to possess dissociative activity against aggregates of pyroglutamate-modified Aβ and tau. Conclusions Collectively, our results evince the potential of chemical-driven dissociation of Aβ aggregates by aryloxypropanolamines as a therapeutic modality of the amyloid clearance approach.

To develop the risk prediction technology for mixture toxicity, a reliable and extensive dataset of experimental results is required. However, most published literature only provides data on combinations containing two or three substances, resulting in a limited dataset for predicting the toxicity of complex mixtures. Complex mixtures may have different mode of actions (MoAs) due to their varied composition, posing difficulty in the prediction using conventional toxicity prediction models, such as the concentration addition (CA) and independent action (IA) models. The aim of this study was to generate an experimental dataset comprising complex mixtures. To identify the target complex mixtures, we referred to the findings of the HBM4EU project. We identified three groups of seven to ten components that were commonly detected together in human bodies, namely environmental phenols, perfluorinated compounds, and heavy metal compounds, assuming these chemicals to have different MoAs. In addition, a separate mixture was added consisting of seven organophosphate flame retardants (OPFRs), which may have similar chemical structures. All target substances were tested for cytotoxicity using HepG2 cell lines, and subsequently 50 different complex mixtures were randomly generated with equitoxic mixtures of EC10 levels. To determine the interaction effect, we calculated the model deviation ratio (MDR) by comparing the observed EC10 with the predicted EC10 from the CA model, then categorized three types of interactions: antagonism, additivity, and synergism. Dose–response curves and EC values were calculated for all complex mixtures. Out of 50 mixtures, none demonstrated synergism, while six mixtures exhibited an antagonistic effect. The remaining mixtures exhibited additivity with MDRs ranging from 0.50 to 1.34. Our experimental data have been formatted to and constructed for the database. They will be utilized for further research aimed at developing the combined CA/IA approaches to support mixture risk assessment.

Long coherence times are a key property of superconducting qubits, but in conventional Al-based Josephson junctions they are limited by microscopic two-level systems. Here, NbN-based qubits on Si promise to overcome this limitation, showing an energy relaxation time T1 = 16.3 μs and a spin-echo dephasing time T2 = 21.5 μs.

We investigate the dynamics of a qubit-oscillator system under the influence of a linear sweep of system parameters. We consider two main cases. In the first case, we consider sweeping the parameters between the regime of a weakly correlated ground state and the regime of a strongly correlated ground state, a situation that can be viewed as a finite-duration quench between two phases of matter: the normal phase and the superradiant phase. Excitations are created as a result of this quench. We investigate the dependence of the excitation probabilities on the various parameters. We find a qualitative asymmetry in the dynamics between the cases of a normal-to-superradiant and superradiant-to-normal quench. The second case of parameter sweeps that we investigate is the problem of a Landau–Zener sweep in the qubit bias term for a qubit coupled to a harmonic oscillator. We analyze a theoretical formula based on the assumption that the dynamics can be decomposed into a sequence of independent Landau–Zener transitions. In addition to establishing the conditions of validity for the theoretical formula, we find that under suitable conditions, deterministic and robust multi-photon state preparation is possible in this system.

Chronic kidney disease (CKD) is a global health threat of growing concern. Recently, exposure to endocrine disrupting compounds (EDCs) such as phthalates and bisphenol A has been suggested as a risk factor for CKD. However, most epidemiological studies have focused on a limited number of urinary chemicals. This study aimed to identify chemical determinants of the urinary albumin-to-creatinine ratio (ACR), which is a kidney function marker, among multiple major EDCs including phthalate metabolites, bisphenols, and benzophenones in a Korean female population (20–45 years old, n = 441). First, the creatinine-adjusted urinary concentration of each urinary chemical was associated with ACR in a linear regression model (single-pollutant model). Then, compounds with a significant association with ACR in the single-pollutant model were added in a multi-pollutant model and evaluated for their association with ACR. Moreover, to prevent potential reverse causality due to impaired kidney function, quartile analyses were performed for the subjects with healthy renal function (ACR

Phthalates and bisphenol A (BPA) have been suspected as risk factors for obesity and diabetes mellitus (DM) among humans. However, associations between phthalates and environmental phenols are often inconsistent across different populations. In this study, we recruited the adult population (n = 3782) of the Korean National Environmental Health Survey (KoNEHS) 2015–2017 (Cycle 3) and assessed the associations between urinary biomarkers of phthalate, BPA, and paraben exposure with obesity and DM. A potential collider issue with the use of urinary creatinine (Cr) or specific gravity (SG) exists when adjusting urinary dilution; therefore, a covariate-adjusted standardization (CAS) was employed for adjustment, and the results were compared. In the present population, the direction of the association often varied depending on the choices made to adjust urinary dilution. When using CAS, the direction of association resembled those of previously reported experimental observations. With Cr or SG adjustment, ORs for obesity decreased in the highest quartiles of monocarboxyoctyl phthalate (MCOP) [OR (95% CI) = Cr: 0.71 (0.54, 0.93); SG: 0.68 (0.52, 0.90)], monocarboxy-isononyl phthalate (MCNP) [OR (95% CI) = Cr: 0.67 (0.52, 0.87); SG: 0.68 (0.52, 0.89)], and mono(3-carboxylpropyl) phthalate (MCPP) in the urine [OR (95% CI) = Cr: 0.60 (0.47, 0.76); SG: 0.61 (0.48, 0.77)]; however, with CAS, these negative associations disappeared. Instead, mono-benzyl phthalate (MBzP) [OR (95% CI) = 1.31 (1.03, 1.66)], BPA [OR (95% CI) = 1.62 (1.27, 2.06)], or ethyl paraben (EtP) [OR (95% CI) = 1.51 (1.19, 1.91)] concentrations in the highest quartile showed positive associations with a higher risk of obesity. On the other hand, for DM, an overall decrease in ORs was observed for phthalate metabolites and BPA following SG adjustment and disappeared with CAS adjustment. In addition, the highest quartiles of BPA, methyl paraben (MeP), and ethyl paraben (EtP) showed a significantly higher risk of DM than those in the lowest quartiles following CAS [OR (95% CI) = BPA: 1.65 (1.06, 2.59); MeP: 1.68 (1.08, 2.60); and EtP: 2.74 (1.77, 4.24), respectively]. The present observations outline the importance of using an appropriate adjustment method for urinary dilution in association studies on obesity and DM. In addition, several phthalates, BPA, and parabens were identified as potential chemical risk factors for these outcomes. Further studies are warranted in other populations to confirm these observations.

Increasing number of consumer chemicals have been associated with chronic kidney disease (CKD) in human populations. However, many studies that investigated estimated glomerular filtration rate (eGRF) as an outcome reported inconsistent associations. In the present study, we employed a subset (n = 1292) of a nationally representative adult population participating in Korean National Environmental Health Survey (KoNEHS) 2015–2017, and assessed associations of major phthalates, bisphenol A (BPA), and parabens with both eGRF and albuminuria. In order to address a potential collider issue, a covariate-adjusted standardization method was applied, in addition to the conventional creatinine-correction, for adjusting urine dilution. Regardless of adjustment method, urinary DEHP metabolites showed significant positive associations with albumin to creatinine ratio (ACR). In addition, urinary metabolites of other heavy molecular weight phthalates such as MCOP and MCNP showed significant positive associations with ACR in the female population, but only following the covariate-adjusted standardization. For eGFR, conventional creatinine-correction resulted in positive associations with most of measured phthalate metabolites. However, with the covariate-adjusted standardization, most of positive associations with eGFR disappeared, and instead, significant negative associations were observed for MnBP, BPA, and EtP. Secondary analysis following stratification by CKD status, as well as principal component analysis (PCA), generally supported the observed associations. The present observations highlight the importance of urine dilution adjustment method for association studies on eGFR, and suggest potential effects of several consumer chemicals on adverse kidney function among humans.

Exposure to consumer chemicals such as phthalates and phenolic compounds has been associated with thyroid hormone disruption in humans. However, information related to factors that may influence such associations, e.g., transport and activation of the hormones, and autoimmunity status, is limited. In the present study, we employed a subpopulation of adults (n = 1,254) who participated in the Korean National Environmental Health Survey (KoNEHS) 2015–2017, and associated urinary concentrations of major phthalate metabolites, bisphenol A (BPA), and parabens, with thyroid hormone-related measures, including free and total T3 and T4, TSH, thyroxine-binding globulin (TBG), calculated peripheral deiodinase (DIO) activity, and thyroid autoantibodies of thyroperoxidase (TPO) and thyroglobulin (Tg). Phthalate metabolites were negatively associated with total T4 and free T3, and positively associated with total T3. These observations could be explained by TBG levels and calculated peripheral DIO activity that were positively associated with phthalates exposure. In contrast, BPA was positively associated with total T4 and negatively associated with total T3, without any changes in TBG concentration. Serum TPO and Tg antibodies were not associated with urinary phthalate metabolites and BPA. However, thyroid autoantibody status appeared to modulate the association of some phthalates with thyroid hormones. For parabens, little to negligible association was observed. The results of our observation show potential underlying mechanisms of phthalates-induced thyroid hormone disruption, and suggests the importance of consideration of thyroid autoimmunity status in association studies for thyroid disrupting chemicals.

Background: Antihyperglycemic effects of Panax ginseng berry have never been explored in humans. The aims of this study were to assess the efficacy and safety of a 12-wk treatment with ginseng berry extract in participants with a fasting glucose level between 100 mg/dL and 140 mg/dL. Methods: This study was a 12-wk, randomized, double-blind, placebo-controlled clinical trial. A total of 72 participants were randomly allocated to two groups of either ginseng berry extract or placebo, and 63 participants completed the study. The parameters related to glucose metabolism were assessed. Results: Although the present study failed to show significant antihyperglycemic effects of ginseng berry extract on the parameters related to blood glucose and lipid metabolism in the total study population, it demonstrated that ginseng berry extract could significantly decrease serum concentration of fasting glucose by 3.7% (p = 0.035), postprandial glucose at 60 min during 75 g oral glucose tolerance test by 10.7% (p = 0.006), and the area under the curve for glucose by 7.7% (p = 0.024) in those with fasting glucose level of 110 mg/dL or higher, while the placebo group did not exhibit a statistically significant decrease. Safety profiles were not different between the two groups. Conclusion: The present study suggests that ginseng berry extract has the potential to improve glucose metabolism in human, especially in those with fasting glucose level of 110 mg/dL or higher. For a more meaningful benefit, further research in people with higher blood glucose levels is required.

This study investigated the effect and the underlying mechanism of ginseng berry (GB) in a mouse model of type 2 diabetes, supplied with 0.05% or 0.1% dietary GB for 12 weeks. GB significantly improved hyperglycemia and insulin resistance, as demonstrated by the blood glucose and insulin levels, HOMA-IR, and GTT. Moreover, the expression of gluconeogenic genes such as PEPCK and G6Pase and the hepatic metabolites involved in the pathway of gluconeogenesis, such as glucose-6-phosphate and dihydroxyacetone phosphate, were significantly reduced by GB. Hepatic steatosis was also significantly ameliorated; TG content and expression of lipogenic enzymes and transcriptional factors such as FAS, ACC, and SREBP1 were reduced by GB. Simultaneously, AMPK phosphorylation was increased both in fatty liver and in lipid-accumulated HepG2 cells by GB. In conclusion, GB improved hyperglycemia by downregulating hepatic glucose production and hepatic steatosis, and AMPK appeared to be an important regulator of these effects.

Background: The ginseng berry has various bioactivities, including antidiabetic, anticancer, antiinflammatory, and antioxidative properties. Moreover, we have revealed that the active antiaging component of the ginseng berry, syringaresinol, has the ability to stimulate longevity via gene activation. Despite the many known beneficial effects of ginseng, its effects on skin aging are poorly understood. In this study, we investigated the effects of ginseng and the ginseng berry on one of the skin aging processes, melanogenesis, and age-related pigment lipofuscin accumulation, to elucidate the mechanism of action with respect to antiaging. Methods: The human melanoma MNT1 cell line was treated with ginseng root extract, ginseng berry extract, or syringaresinol. Then, the cells were analyzed using a melanin assay, and the tyrosinase activity was estimated. The Caenorhabditis elegans wild type N2 strain was used for the life span assay to analyze the antiaging effects of the samples. A lipofuscin fluorescence assay was performed during 10 passages with the syringaresinol treatment. Results: A 7-d treatment with ginseng berry extract reduced melanin accumulation and tyrosinase activity more than ginseng root extract. These results may be due to the active compound of the ginseng berry, syringaresinol. The antimelanogenic activity was strongly coordinated with the activation of the longevity gene foxo3a. Moreover, the ginseng berry extract had more potent antiaging effects, caused a life span extension, and reduced lipofuscin accumulation. Conclusion: Taken together, our results suggest that these antimelanogenic effects and antiaging effects of ginseng berry mediate the activation of antioxidation–FoxO3a signaling.

Uterine leiomyomas are estrogen-dependent benign tumors with unknown etiologies. Phthalates are endocrine-disrupting chemicals and ubiquitous in the environment; thus, it has been suggested that they play a role in the development of uterine leiomyoma. We aimed to investigate whether the pathogenesis of uterine leiomyoma is related to methylation changes in promoter regions of estrogen receptor α (ESR1) and progesterone receptor (PGR) genes in response to phthalates and alternative plasticizers exposure. Urinary concentrations of 20 phthalate metabolites and seven metabolites of di-2-ethylhexyl terephthalate (DEHTP) and di (isononyl) cyclohexane-1,2-dicarboxylate (DINCH) were measured by UHPLC-MS/MS in thirty leiomyoma patients, who provided both paired leiomyoma and myometrium tissues. Methylation levels of ESR1 and PGR were analyzed by pyrosequencing assay. A total of 12 phthalate metabolites and 5 alternative metabolites (3 DEHTP and 2 DINCH) were detected >70% among study participants. The methylation of ESR1 and PGR were significantly lower in leiomyoma tissues compared to those in myometrium (18.10 ± 4.41 vs. 28.72 ± 4.95; 2.32 ± 0.81 vs. 3.27 ± 0.56, respectively). ESR1 methylation in leiomyoma was negatively associated with mono-2-carboxylmethyl-hexyl phthalate (2cx-MMHP) and mono-3-carbocyl-propyl phthalate (MCPP) after adjusting for confounding factors. However, 1-mono-2-ethyl-5-oxohexyl-benzene-1,4-dicarboxylate (5OXO-MEHTP), one of the alternatives, showed positive association with ESR1 methylation in leiomyoma. PGR methylation in leiomyoma was significantly associated with mono butyl phthalate (MnBP), but negatively associated with cyclohexane-1,2-dicarboxylate-mono-7-hydroxy-4-methyl-heptyl ester (cx-MINCH). Our results suggest that phthalates exposure may contribute to leiomyoma pathogenesis via ESR1 and PGR methylation changes.

Decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6-tribromo-phenoxy) ethane (BTBPE) are novel brominated flame retardants (NBFRs) and have been detected in variety of environment and biota. Although sex endocrine-disrupting potential has been suggested in experimental studies, their adverse effects on sex steroid hormones and underlying mechanisms are largely unclear. The purpose of the present study is to investigate the sex hormone-disrupting effects of two NBFRs using in vivo and in vitro models together. For this, male zebrafish (Danio rerio) along with human adrenocortical carcinoma (H295R) and breast carcinoma (MVLN) cell lines were employed. In male zebrafish, 14-day exposure to DBDPE significantly increased 17β-estradiol (E2) concentrations. Disruption of sex hormone regulation was also suggested after exposure to BTBPE, i.e., the increasing trend of E2 levels, E2/11-ketotestosterone (11-KT) ratio, and estrogen receptor-alpha (erα) and erβ gene expression levels. In H295R cells, an E2/T ratio showed an increasing trend by DBDPE exposure, but transcriptions of major genes in steroidogenesis pathway were not affected. Taken together, our observation implies that two NBFRs could cause the sex hormone disruption potential in male zebrafish and H295R cells but probably not through alteration of steroidogenesis pathway.

Global regulations of biocides have been continuously enhanced for protecting human health and the environment from potentially harmful biocidal products. Such regulations consider the combined toxicity caused by mixture components in a biocidal product of which approval and authorization are to be enhanced. Although the combined exposure scenarios of components in mixtures are firstly needed to conduct the mixture risk assessment, systematic combined exposure scenarios are still lacking. In this study, combined inhalation exposure scenarios of biocides in household chemical and biocidal products marketed in South Korea were investigated based on the European Union (EU) and Korean chemical product databases and various data sources integration. The information of 1058 biocidal products and 675 household chemical products that are likely to cause inhalation exposure with two or more biocides was collected, and mixture combination patterns were investigated. Binary mixtures occupied 72% in biocidal products. The most frequently appearing binary mixture was phthalthrin and d-phenothrin. Based on the frequency of use, we suggested a priority list of biocide mixture combinations which need to be firstly evaluated for identifying their combined toxicity for the mixture risk assessment. This study highlights that the derived combined inhalation exposure scenarios can support and facilitate further studies on priority settings for mixture risk assessment and management of potentially inhalable biocides.

Personal care products and cosmetics have been identified as major sources of paraben exposure among humans. However, the contribution of dietary factors has not been well understood. We recruited temple stay participants (n = 25) who followed a strict Buddhist vegetarian diet during a five-day period, and assessed the influence of this lifestyle change, employing their urine samples collected before and after the temple stay. Before the temple stay, methylparaben (MeP) was detected at the highest levels, followed by ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and benzophenones (BPs) in the urine samples. Following the temple stay, the urinary EtP concentrations remarkably increased from 14.0 to 105 μg/L, and were around two orders of magnitude higher than those reported from other countries. Dietary factors associated with the temple diet may partly explain the increase, because EtP is allowed in Korea for seasoning and condiments, which are frequently added in vegetarian diets. Following the temple stay, however, MeP, PrP, and BPs did not show significant decreasing trends. In contrast, BuP levels decreased significantly, especially in male urine samples, that is, from 3.60 to 1.03 μ/L, suggesting a reduced use of certain personal care products during the temple stay. Our observations outline the potential importance of dietary factors on EtP exposure, and might help explain its high exposure levels among Korean population.

Bilingualism is a worldwide phenomenon and provides an opportunity to understand how the brain represents language processing. Although many studies have investigated the neural mechanism of bilingualism, it still remain unclear how brain systems are involved in the second language processing. Here, we examined the neural dynamics of bilinguals with medium proficiency during auditory word processing. Korean–English (K–E) bilinguals were recruited for the study (L1: Korean and L2: English). They performed a word comprehension task on phonological and semantic aspects by hearing words. We compared their task performance, task-induced regional activity, and functional connectivity (FC) between L1 and L2 processing. Brain activation analyses revealed that L2 evoked more widespread and stronger activation in brain regions involved in auditory word processing and the increased regional activity in L2 was prominent during phonological processing. Moreover, L2 evoked up-regulation during semantic processing was associated with L2 proficiency. FC analyses demonstrated that the intra-network connectivity showed stronger in the language network (LN), dorsal attention network (DAN), and default mode network (DMN) in L2 than L1. For the L2 phonological processing, the increased FC within the DAN was positively correlated with individuals’ L2 proficiency. Also, L2 semantic processing induced the enhanced internetwork connectivity between the LN and DMN. Our findings suggest that L2 processing in K–E bilinguals induces dynamic changes in the brain at a regional and network-level and FC analysis can disentangle the different networks involvement in L2 auditory word processing according to two key features: phonology and semantics.

This study aims to provide convergent understanding of the neural basis of auditory word processing efficiency using a multimodal imaging. We investigated the structural and functional correlates of word processing efficiency in healthy individuals. We acquired two structural imaging (T1-weighted imaging and diffusion tensor imaging) and functional magnetic resonance imaging (fMRI) during auditory word processing (phonological and semantic tasks). Our results showed that better phonological performance was predicted by the greater thalamus activity. In contrary, better semantic performance was associated with the less activation in the left posterior middle temporal gyrus (pMTG), supporting the neural efficiency hypothesis that better task performance requires less brain activation. Furthermore, our network analysis revealed the semantic network including the left anterior temporal lobe (ATL), dorsolateral prefrontal cortex (DLPFC) and pMTG was correlated with the semantic efficiency. Especially, this network acted as a neural efficient manner during auditory word processing. Structurally, DLPFC and cingulum contributed to the word processing efficiency. Also, the parietal cortex showed a significate association with the word processing efficiency. Our results demonstrated that two features of word processing efficiency, phonology and semantics, can be supported in different brain regions and, importantly, the way serving it in each region was different according to the feature of word processing. Our findings suggest that word processing efficiency can be achieved by in collaboration of multiple brain regions involved in language and general cognitive function structurally and functionally.

Persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) are of global concern because of their widespread contamination and adverse health effects. Potential endocrine disruption, especially of thyroid status by PCBs has been repeatedly suggested in both experimental and epidemiological studies. However the associations with PBDEs or OCPs have been arguable especially in human populations. We investigated the associations between major groups of POPs and thyroid hormone balances among pregnant women. One hundred five pregnant women at delivery were recruited from four cities of Korea in 2011 and were investigated. Blood samples were collected within a day before delivery. Serum was then analyzed for 19 PCBs, 19 PBDEs, and 19 OCPs, along with five thyroid hormones (free and total T3 and T4, and TSH). Several PCBs such as PCB28, 52, and 118 showed negative associations with T3 or T4. BDE47 and total PBDEs showed significant associations with T3 or T4. For OCPs, dichlorodiphenyltrichloroethanes (DDTs) and hexachlorobenzene (HCB) were generally associated with reduction of T3 or T4. The thyroid hormone levels of all subjects were within the reference range, however exposure to several target POPs were clearly related with potential for disrupting thyroid hormone balance among pregnant women, at the current level of exposure. Although subtle, the changes in thyroid hormones should be seen with caution because even minor changes within pregnant women may have significant consequences especially on sensitive population like fetus. Keywords: Polychlorinated biphenyls, Polybrominated diphenyl ethers, Organochlorine pesticides, Pregnant women, Thyroid hormones

Caveolin is the principal protein of caveolae and has been implicated in the pathogenesis of cerebral ischemia. To investigate whether changed expression of caveolins has a pivotal role in focal cerebral ischemia, we induced middle cerebral artery occlusion (MCAo)-reperfusion and examined expression of caveolins, inflammatory activation markers, and mediators of autophagic cell death. We also treated MCAo rats with forced exercise to determine its effects on neurological outcome. Particularly, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used to compare the effects of hypertension on focal cerebral ischemia. All MCAo groups showed neurological deficiencies, motor dysfunction, and disruption of balancing ability; however, these pathological changes were more severe in SHR than WKY rats. Expression of caveolins was decreased in MCAo brain tissue, whereas the levels of iNOS and glial fibrillary acidic protein (GFAP) increased. Additionally, LC3-II and beclin-1 levels were elevated in the MCAo groups. Forced exercise attenuated both molecular and behavioral changes in MCAo animals, but SHR rats showed delayed functional recovery and residual molecular changes when compared to WKY rats. These results suggest that forced exercise may be beneficial for promoting functional recovery following cerebral ischemia through caveolin-dependent mechanisms or interactions between caveolins and these signaling molecules in ischemic brain regions.

Background: This study aimed to investigate the antidepressant-like effect of lactate and elucidate its mechanisms in ovariectomized rats with repeated stress. Methods: Two experiments were conducted on female rats in which all groups, except normal, were ovariectomized and underwent immobilization for 14 days. Lactate was administered orally (100, 250, and 500 mg/kg) for 14 consecutive days, and the rats’ cutaneous body temperature was measured during the same period. Depression-like behavior in rats was assessed by the tail suspension test (TST) and forced swimming test (FST). Furthermore, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were conducted to evaluate the changes that occurred in the neurotransmitter levels and activity. Results: The lactate 100 and 250 groups had reduced time spent immobile in TST and FST and decreased peripheral body temperature. In ELISA tests, the lactate 250 group expressed elevated levels of serotonin and dopamine in many brain areas. Tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and protein kinase C (PKC) immunoreactive cells showed increased density and cell counts in lactate administered groups. Conclusion: Results indicated that lactate has an antidepressant effect that is achieved by activation of PKC and upregulation of TH and TPH expression, which eventually leads to enhanced serotonin and dopamine levels in the menopausal rat’s brain.

Current knowledge on adverse endocrine disruption effects of persistent organic pollutants (POPs) among newborn infants is limited and often controversial. To investigate the associations between prenatal exposure to major POPs and thyroid hormone levels among newborn infants, both cord serum or maternal serum concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) were compared with five thyroid hormones in cord serum of newborn infants as well as TSH in bloodspot collected at 2 day after birth (n=104). Since cord serum thyroid hormones could be affected by those of mothers, thyroid hormone concentrations of the matching mothers at delivery were adjusted. In cord serum, BDE-47, -99, and Σchlordane (CHD) showed significant positive associations with cord or bloodspot TSH. At the same time, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorbenzene (HCB) showed negative associations with total T3 and total T4 in cord serum, respectively. Maternal exposure to β-hexachlorhexane (β-HCH), ΣCHD, ΣDDT, or p,p'-DDE were also associated with neonatal thyroid hormones. Although the sample size is small and the thyroid hormone levels of the subjects were within the reference range, our observation supports thyroid disrupting potential of several POPs among newborn infants, at the levels occurring in the general population. Considering the importance of thyroid hormones during gestation and early life stages, health implication of thyroid hormone effects by low level POPs exposure deserves further follow up investigations.

We have previously used the ATAD5-luciferase high-throughput screening assay to identify genotoxic compounds with potential chemotherapeutic capabilities. The successful identification of known genotoxic agents, including the histone deacetylase inhibitor (HDACi) trichostatin A (TSA), confirmed the specificity of the screen since TSA has been widely studied for its ability to cause apoptosis in cancer cells. Because many cancers have acquired mutations in DNA damage checkpoints or repair pathways, we hypothesized that these cancers may be susceptible to treatments that target compensatory pathways. Here, we used a panel of isogenic chicken DT40 B lymphocyte mutant and human cell lines to investigate the ability of TSA to define selective pathways that promote HDACi toxicity.HDACi induced a DNA damage response and reduced viability in all repair deficient DT40 mutants although ATM-nulls were least affected. The most dramatic sensitivity was observed in mutants lacking the homology dependent repair (HDR) factor BLM or the non-homologous end-joining (NHEJ) and HDR factors, KU/RAD54, suggesting an involvement of either HDR or NHEJ in HDACi-induced cell death. To extend these findings, we measured the frequencies of HDR and NHEJ after HDACi treatment and monitored viability in human cell lines comparably deficient in HDR or NHEJ. Although no difference in HDR frequency was observed between HDACi treated and untreated cells, HDR-defective human cell lines were clearly more sensitive than wild type. Unexpectedly, cells treated with HDACis showed a significantly elevated NHEJ frequency.HDACi targeting drugs induced significant increases in NHEJ activity in human cell lines but did not alter HDR frequency. Moreover, HDR is required for cellular resistance to HDACi therapy; therefore, NHEJ does not appear to be a critical axis for HDACi resistance. Rather, HDACi compounds induced DNA damage, most likely double strand breaks (DSBs), and HDR proficiency is correlated with cell survival.