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Environmentally persistent free radicals (EPFRs) can pose exposure risks by inducing the generation of reactive oxygen species. As a new class of pollutants, EPFRs have been frequently detected in atmospheric particulate matters. In this study, the seasonal variations and sources of EPFRs in a severe cold region in Northeastern China were comprehensively investigated, especially for the high pollution events. The geomean concentration of EPFRs in the total suspended particle was 6.58 × 1013 spins/m3 and the mean level in winter was one order of magnitude higher than summer and autumn. The correlation network analysis showed that EPFRs had significantly positive correlation with carbon component, K+ and PAHs, indicating that EPFRs were primarily emitted from combustion and pyrolysis process. The source appointment by the Positive Matrix Factorization (PMF) model indicated that the dominant sources in the heating season were coal combustion (48.4%), vehicle emission (23.1%) and biomass burning (19.4%), while the top three sources in the non-heating season were others (41.4%), coal combustion (23.7%) and vehicle emissions (21.2%). It was found that the high EPFRs in cold season can be ascribed to the extensive use of fossil fuel for heating demand; while the high EPFRs occurred in early spring were caused by the large-scale opening combustion of biomass. In summary, this study provided important basic information for better understanding the pollution characteristics of EPFRs, which suggested that the implementation of energy transformation and straw utilization was benefit for the control of EPFRs in severe cold region. [Display omitted] • EPFRs in winter was one order of magnitude higher than other seasons. • EPFRs showed significantly positive correlation with carbon components and PAHs. • EPFRs in heating season were mainly from coal combustion. • High EPFRs in spring was directly influenced by large-scale opening biomass burning. • Energy transformation and straw utilization was benefit for EPFRs control. [ABSTRACT FROM AUTHOR]

Phthalates have become a matter of public health concern due to their extensive use worldwide and negative health effects. The evaluation of potential sources of phthalate exposure is crucial to design prevention strategies, especially for vulnerable populations. This study included 528 mother-child pairs in the Taiwan Mother Infant Cohort Study who were followed up at ages 3–6 years between 2016 and 2020. Each mother was interviewed by using a structured questionnaire containing questions on demographic characteristics and household environment factors, such as the use of plastic food packaging, residential visible mold, insecticide sprays, and electric mosquito repellents. Eleven phthalate metabolites were analyzed in urine samples simultaneously collected from the mother-child pairs. The phthalate metabolite urinary concentrations were higher among the children than among their mothers, except those of mono-ethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Multiple linear regression analyses showed that urine samples collected during the summer showed higher concentrations of phthalate metabolites than those collected during the winter. Family income levels had negative associations with the concentrations of MnBP and metabolites of di-2-ethylhexyl phthalate (DEHP) in children. The use of plastic food packaging was positively associated with mono-n-butyl phthalate (MnBP) and metabolites of DEHP in mothers. Residential visible mold or mold stains were significantly associated with higher MnBP and DEHP metabolite concentrations in children. The use of insecticide sprays was positively associated with MnBP concentrations in children. Significant associations between household environmental factors and phthalate exposure were mostly found in children, potentially indicating different exposure pathways between mothers and their children. Findings from this study provide additional information for the design of prevention strategies to protect the health of children and women. [Display omitted] • Phthalate levels in children were higher than those in their mothers, except MEP and MEHP levels. • Residential visible mold was positively associated with MnBP and DEHP levels in children. • Insecticide spray use was positively associated with MnBP levels in children. • Plastic food packaging was associated with higher MnBP and metabolites of DEHP in mothers. [ABSTRACT FROM AUTHOR]

Hypoxia is an important microenvironmental factor that induces Endometriosis (EMs), but its mechanism remains unclear. Our study aims to investigate the mechanisms of miR-150-5p on hypoxia-induced EMs. Ovarian endometriosis cyst wall stromal cell lines CRL-7566 cells were treated with hypoxia. Cell migration ability was measured by Transwell assay. qRT-PCR was performed to detect miR-150-5p and PDCD4 expression. The autophagy-related proteins (LC3-I, LC3-II, Beclin-1, and p62), epithelial-mesenchymal transition (EMT) related proteins (E-cadherin, N -cadherin, and Vimentin) and NF-κB signaling pathway related proteins p65 expression were measured by western blot. Dual-luciferase reporter gene assay verified the binding relationship between miR-150-5p and PDCD4. After hypoxia treatment, the miR-150-5p expression was up-regulated in CRL-7566 cells, while the expression of PDCD4 was down-regulated. In CRL-7566 cells, autophagy, migration and EMT were increased after hypoxia treatment. The autophagy inhibitor 3-MA inhibited hypoxia-induced the autophagy, migration and EMT of CRL-7566 cells. Hypoxia-induced autophagy and EMT of CRL-7566 cells were inhibited after knocking down miR-150-5p. Then miR-150-5p negatively regulated PDCD4 expression. PDCD4 knockdown reversed the inhibitory effect of miR-150-5p silencing on hypoxia-induced autophagy and EMT of CRL-7566 cells. Inhibiting the NF-κB signaling pathway weakened the effect of PDCD4 knockdown on hypoxia-induced autophagy and EMT of CRL-7566 cells. MiR-150-5p silencing inhibited hypoxia-induced autophagy and EMT of endometriotic cells by regulating the PDCD4/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O 2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100 μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8 Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine > methamphetamine > hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation and, possibly, normal blood flow in the brainstem. [ABSTRACT FROM AUTHOR]

This study ascertained whether self-efficacy and collective efficacy in the cognitive theory of stress model explains people's self-reported proenvironmental behavior more effectively separately or in combination. A questionnaire study was conducted among 707 Taiwanese respondents. The results of structural equation modeling analysis corroborated previous findings that the cognitive theory of stress model can be applied to environmental problems to effectively explain people's self-reported proenvironmental behavior. Moreover, compared with self-efficacy, collective efficacy is a stronger predictor of people's problem-focused coping and self-reported proenvironmental behavior for respondents in this collectivist cultures; failing to include collective efficacy in the cognitive theory of stress model can reduce the power of the model to explain such behavior. The research results regarding the external validation and internal validation of the cognitive theory of stress model were elaborated in this study to more effectively understand people's self-reported proenvironmental behavior. [ABSTRACT FROM AUTHOR]

Abstract: The partial quadratic eigenvalue assignment problem (PQEAP) is to compute a pair of feedback matrices such that a small number of unwanted eigenvalues in a structure are reassigned to suitable locations while keeping the remaining large number of eigenvalues and the associated eigenvectors unchanged. The problem arises in active vibration control of structures. For real-life applications, it is not enough just to compute the feedback matrices. They should be computed in such a way that both closed-loop eigenvalue sensitivity and feedback norms are as small as possible. Also, for practical effectiveness, the time-delay between the measurement of the state and implementation of the feedback controller should be considered while solving the PQEAP. These problems are usually solved using only system matrices and do not necessarily take advantage of the receptances which are available by measurements. In this paper, we propose hybrid methods, combining the system matrices and measured receptances, for solutions of the multi-input PQEAP and the minimum-norm PQEAP, both for systems with and without time-delay. These hybrid methods are more efficient than the standard methods which only use the system matrices and not the receptances. These hybrid methods also offer several other computational advantages over the standard methods. Our results generalize the recent work by Ram et al. [Partial pole placement with time delay in structures using the receptance and the system matrices, Linear Algebra and its Applications 434 (2011) 1689–1696]. The results of numerical experiments demonstrate the effectiveness of the proposed methods. [Copyright &y& Elsevier]

Abstract: Functional foods marketed as promoting health or reducing the risk of disease open a promising avenue for consumers to pursue a healthier life. Despite the stable growth in functional foods in Taiwan, at present little is known about whether or not consumers with varying degrees of health consciousness and different healthy lifestyles will have dissimilar attitudes toward functional foods and will vary in their willingness to use them. Regression analysis of this empirical study verifies that consumers’ attitudes toward functional foods do have an impact on their willingness to use such foods. Moreover, moderated regression analysis (MRA) reveals that the joint moderator of health consciousness and healthy lifestyle indeed exerts an impact on consumers’ willingness to consume functional foods. Finally, one-way ANOVA tests show that there are some differences between the consumers of the “Healthy Life Attentive” group and those of the “Healthy Life Inattentive” one both in attitudes toward and in willingness to consume functional foods. The empirical results and findings from this study would be valuable for the marketers in the functional food industry to formulate marketing communication strategies and facilitate this industry''s development. [Copyright &y& Elsevier]

Abstract: Complement activation is involved in the pathogenesis of age-related macular degeneration. How complement is activated in the retina is not known. Previously we have shown that complement factor H (CFH) is constitutively expressed by retinal pigment epithelial (RPE) cells and the production of CFH is negatively regulated by inflammatory cytokines and oxidative insults. Here we investigated the production and regulation of complement factor B (CFB) in RPE cells. Immunohistochemistry showed that CFB is expressed at low levels on the apical portion of the RPE cells in normal physiological conditions. With age, CFB expression increases and extends to the basal part of RPE cells. Confocal microscopy and real-time PCR of RPE cultures indicated that the production of CFB by RPE cells is positively regulated by TNF-α, IFN-γ and long-term (30days) photoreceptor outer segments treatments. Increased CFB expression in RPE cells in vivo is accompanied by the accumulation of complement C3 and C3a deposition at the Bruch''s membrane and the basal layer of RPE cells. Our results suggest that RPE cells play important roles in regulating complement activation in the retina. Increased complement activation in the aged retina may be important for retinal homeostasis in the context of accumulating photoreceptor waste products. [Copyright &y& Elsevier]

• A time-frequency hybrid GFM is proposed to model the periodic slab dynamics. • A GFM-based vehicle-track dynamic interaction model is established. • Truncation errors are studied to determine the truncated parameters. • The effectiveness of the proposed model is validated by comparing with FEM. Periodic slab tracks, as a type of non-ballasted track, are widely used in the high-speed railway and urban subway. Efficient and accurate dynamics modelling of the periodic slab track is a crucial issue for solving the vehicle-track dynamic interaction. In this paper, a time-frequency hybrid Green's function method (GFM) is first developed to model the dynamics of the periodic slab track, in light of the properties of the periodicity, symmetry and attenuation of the Green's functions. By combining with the classical vehicle-rail dynamics model, the simulation of the vehicle-track dynamic interaction is then performed. To improve the computational efficiency, the step-moving window strategy is introduced to characterize the vehicle moving on the infinite length track. The floating slab track, a representation of the periodic slab track, is adopted to reflect the time-spatial distribution of the Green's functions. The truncation errors caused by the presented GFM are analysed by calculating dynamic responses induced by a metro vehicle moving on the floating slab track to determine the truncation parameters. The proposed GFM-based vehicle-track dynamic interaction model is finally validated by comparing with the finite element method (FEM) and the basic dynamic characteristics of the periodic slab track are further investigated. Numerical studies show that the computational accuracy of the GFM-based model is nearly the same with the FEM-based model, but the efficiency can be greatly improved. Moreover, it is concluded that the longitudinal uneven stiffness of the periodic slab track shows a significant influence on the slab displacement and stress, while has a slight influence on the fastener force and slab acceleration. [ABSTRACT FROM AUTHOR]

Abstract: Complement activation is thought to be involved in the pathogenesis of age-related macular degeneration (AMD), in part because certain gene polymorphisms in complement factor H (CFH), an important regulator of the alternative complement activation pathway, are high risk factors for AMD. How CFH is regulated locally at the retina/choroid interface and how this contributes to AMD development remain unknown. In the present study, we have confirmed that CFH was detectable by immunohistochemistry in the choroid, and at low levels in the RPE cell and interphotoreceptor matrix, but appeared to be concentrated in dense patches in Bruch''s membrane. In vitro, cultured human and mouse RPE cells expressed high levels of CFH as evidenced by immunohistochemistry and western blot. Using a stabilized mouse RPE cell line, we confirmed that RPE cells constitutively synthesise CFH. Synthesis of CFH was not affected by a short-term (2h) photoreceptor outer segment (POS) treatment. However, long-term (24–48h) treatment of RPE cells with oxidised POS (ox-POS) but not normal POS (n-POS) markedly down-regulated CFH mRNA expression. Phagocytosis of both ox-POS and n-POS appeared to reduce intracellular CFH protein expression in RPE cultures. Synthesis of CFH by cultured RPE cells was also reduced at the mRNA level by the proinflammatory cytokines TNF-α and IL-6. Other cytokines tested including IFN-γ, IL-1α and IL-4 showed no effect on either CFH protein or mRNA levels. Our results support the view that RPE cells synthesise and express CFH and are probably a major local source of this protein at the retina/choroid interface, secreting CFH into the interphotoreceptor matrix as well as Bruch''s membrane. Prolonged phagocytosis of POS, particularly if modified by oxidative processes as occurs in inflammation, appears to markedly impair synthesis and secretion of CFH, with potential loss of important regulatory functions in counteracting the pro-inflammatory effects of activated complement. [Copyright &y& Elsevier]

Abstract: Human hepatoma up-regulated protein (HURP), a cell-cycle regulator, is found consistently overexpressed in human hepatocellular carcinoma. At present, the function of HURP in cell-cycle regulation and carcinogenesis remains unclear. In database mining, we have identified a mars gene in Drosophila, which encodes a protein with a high similarity to HURP in its guanylate kinase-associated protein (GKAP) motif. Overexpression but not down-regulation of mars in eye discs resulted in a higher mitotic index along with a high frequency of mitotic defects, including misalignment of chromosomes and mispositioned centrosomes, at the second mitotic wave (SMW). The consequence of mitotic defects impairs cell-cycle progression, and causes cell death posterior to the furrow. Immunocytochemical studies also have indicated that the expression of Mars is cell cycle regulated, and that its subcellular localization is dynamically changed during cell-cycle progression. Furthermore, we also demonstrated that the first 198 amino acids at the N-terminus of Mars are responsible for the degradation of Mars in non-mitotic cells. Together, we report the use Drosophila eye as a model system to characterize the function of the mars gene in cell-cycle regulation. [Copyright &y& Elsevier]

We explored the dysfunction of tachykinins on monocrotaline (MCT)-induced pulmonary hypertension by using double-stranded preprotachykinin (ds PPT) RNA and neurokinin receptor (NK) antagonists. Here, we showed the possibility to attenuate the PPT gene expression by ds RNA, RNA interference (RNAi), in fully developed tissue of rats. We designed four groups (control, MCT, RNAi + MCT, and solvent + MCT) of experiments in series 1 and seven groups (control, MCT, MCT + CP-96345-3.4, MCT + CP-96345-10, MCT + CP-96344-10, MCT + SR-48968, and MCT + SR-48965) of experiments in series 2. Rats in the control groups received saline injection. MCT-treated rats received a single MCT injection (60 mg/kg sc). One day prior to MCT, bilateral nodose ganglia were microinjected with ds PPT RNA in rats of the RNAi + MCT group or with solvent in the solvent + MCT group. Beginning from 1 day post-MCT, MCT-treated rats received a daily injection of the NK1 receptor antagonist, CP-96345 (3.4 or 10 mg/kg ip) or its inactive enantiomer CP-96344 (10 mg/kg ip). The NK2 receptor antagonist SR-48968 (3 mg/kg ip) or its inactive enantiomer SR-48965 (3 mg/kg ip) was injected to MCT-treated rats every other day starting 1 day post-MCT. Functional study was carried out 2 weeks (series 1) or 3 weeks (series 2) after MCT. MCT induced right ventricular hypertrophy, as well as increases in pulmonary arterial pressure, PPT mRNA (nodose ganglia and lung tissue), and lung tissue substance P level. All of the above MCT-induced alterations were attenuated by either RNAi or NK receptor antagonists. We conclude that tachykinins play an important role in MCT-induced pulmonary hypertension. [Copyright &y& Elsevier]

A two-parametric model for a channel in a two-dimensional electron gas (2DEG) is proposed which allows for the explicit analytical solution for the problem of quantum electron transport through the constriction. Conductance step smearing appears naturally and a simple criterion for the step occurrence in terms of channel parameters is given. [Copyright &y& Elsevier]

Plastic pollution has become a global threat to the marine environment. Many studies have indicated that marine creatures are at risk of plastic ingestion, but relevant studies are still lacking in Taiwan. In this study, we quantified plastic debris ingestion by marine fish in the coastal waters of the Hengchun Peninsula, including the Kenting National park, located in southern Taiwan. We also investigated possible biotic and abiotic factors associated with the quantity of ingested plastic by fish. In the 117 fish samples we examined, 94.87% of them had ingested plastic debris, and all of the observed debris was microplastics (<5 mm). The average number of ingested microplastics was 5.6 ± 5.1 pieces per fish (ranged 0–32 pieces per fish). The major type and color of microplastics were fiber (96%) and blue (43%), respectively. The quantity of ingested microplastics was not significantly different between the reef and pelagic fish. However, reef fish from the more populated west and south coast ingested more microplastics than that from the east coast, suggesting that microplastic ingestion by fish is related to human activity. Regarding biotic factors, the size, trophic level, and taxonomic family of the fish were not significantly associated with the number of ingested microplastics. Our results, the first investigation of microplastic ingestion in marine fish of Taiwan, show a high prevalence of microplastic ingestion but no biomagnification of microplastics in the fish. More research is much needed to better characterize the biological and ecological impacts of plastic debris on fish. • This is the first study to report plastic ingestion by fish in Taiwan. • Prevalence of plastic ingestion was about 95%, and all of the debris was microplastics. • Fibers represented 96% of microplastics found in the analyzed fish. • Number of ingested microplastics is related to coastal human activity. • No biomagnification of microplastics was observed. [ABSTRACT FROM AUTHOR]

Vascular dysfunction plays a critical role in the pathogenesis of sepsis. We elucidated the mechanisms underlying the amelioration of lipopolysaccharide (LPS)-induced vascular inflammation by oroxylin A (OroA) post-treatment in rats. The animals were intraperitoneally injected with LPS (10 mg/kg) to induce systemic inflammation and intravenously (iv) administered OroA (15 mg/kg) 6 h after the LPS treatment. The assessments included biochemical changes in peripheral blood, vascular reactivity which was evaluated by blood-vessel myography, morphological/histological assessment of inflammation, toll-like receptor (TLR)-4-mediated interleukin-1-receptor-associated-kinase (IRAK)-4 activation, changes in adhesion molecule expression, and endothelial junctional stability in the aorta. LPS significantly enhanced the proinflammatory cytokine release, increased vascular cell adhesion molecule (VCAM)-1 expression, disrupted endothelial tight junction, reduced vascular endothelial barrier stability, and increased macrophage infiltration and accumulation in the aorta. All observed pathological changes and vascular inflammation were significantly reversed by the OroA post-treatment. Importantly, OroA suppressed the increased adhesion molecule expression and the endothelial barrier disruption by inhibiting LPS-activated IRAK-4-targeted inhibitory nuclear factor kappa B kinase (IKK) α/β complex phosphorylation, without directly affecting the interaction between LPS and TLR-4. Moreover, the iNOS activity induced by the LPS challenge was inhibited by the OroA pretreatment of the isolated aortic rings. These results suggest that OroA regulates the vascular tone by inhibiting vascular hyporeactivity caused by NO overproduction and reverses the endothelial barrier dysfunction and inflammation by inhibiting the IRAK-4-mediated IKKα/β phosphorylation. Overall, these findings suggest OroA administration as a potentially useful therapeutic approach for clinical interventions in septic shock. • Oroxylin A posttreatment reverses lipopolysaccharide-induced vascular inflammation. • Oroxylin A inhibits the upregulated expression of the adhesion molecules, VCAM-1. • Oroxylin A preserves an endothelial function by inhibiting the IRAK-4 activation. • Oroxylin A improves the vascular hyporeactivity to the vasoconstrictor challenge. [ABSTRACT FROM AUTHOR]

The life style and child raising environment in Asia are quite different compared with Western countries. Besides, the children's environmental threats and difficulties in conducting studies could be different. To address children's environmental health in Asia area, the Birth Cohort Consortium of Asia (BiCCA) was co-established in 2011. We reviewed the mercury, polychlorinated biphenyls, perfluoroalkyl substances, phthalates, and environmental tobacco smoke in pervious based on birth cohort studies in Asia. The aim of this study was to summarize the traditional environmental pollution and the target subjects were also based on the birth cohort in Asia area. Environmental pollutants included air pollutants, pesticides focusing on organochlorine pesticides, diakylphosphates, and pyrethroid, and heavy metals including lead, arsenic, cadmium, manganese, vanadium, and thallium. Fetal growth and pregnancy outcomes, childhood growth and obesity, neurodevelopment and behavioral problems, and allergic disease and immune function were classified to elucidate the children's health effects. In total, 106 studies were selected in this study. The evidences showed air pollution or pesticides may affect growth during infancy or childhood, and associated with neurodevelopmental or behavioral problems. Prenatal exposure to lead or manganese was associated with neurodevelopmental or behavioral problems, while exposure to arsenic or cadmium may influence fetal growth. In addition to the harmonization and international collaboration of birth cohorts in Asia; however, understand the whole picture of exposure scenario and consider more discipline in the research are necessary. • Air pollution, pesticides, and heavy metals were associated with adverse effects on Asia children. • Air pollution and pesticides showed more evidence on children's growth during infancy or childhood and neurodevelopment. • Lead and manganese reported the impact on children's neurodevelopment; arsenic or cadmium showed may influence fetal growth. [ABSTRACT FROM AUTHOR]

• This review presents the step-by-step protocols for EV separation methods from brain tissue. • This review describes EV separation methods from human cerebrospinal fluids. • This review compares the quality control measures of separation protocols by biophysical and proteomic characterizations. Extracellular vesicle (EV) is a unified terminology of membrane-enclosed vesicular species ubiquitously secreted by almost every cell type and present in all body fluids. They carry a cargo of lipids, metabolites, nucleic acids and proteins for their clearance from cells as well as for cell-to-cell communications. The exact composition of EVs and their specific functions are not well understood due to the underdevelopment of the separation protocols, especially those from the central nervous system including animal and human brain tissues as well as cerebrospinal fluids, and the low yield of proteins in the separated EVs. To understand their exact molecular composition and their functional roles, development of the reliable protocols for EV separation is necessary. Here we report the methods for EV separation from human and mouse unfixed frozen brain tissues by a sucrose step gradient ultracentrifugation method, and from human cerebrospinal fluids by an affinity capture method. The separated EVs were assessed for morphological, biophysical and proteomic properties of separated EVs by nanoparticle tracking analysis, transmission electron microscopy, and labeled and label-free mass spectrometry for protein profiling with step-by-step protocols for each assessment. [ABSTRACT FROM AUTHOR]

The degree of withering significantly affected the formation of tea quality. This study analyzed the effects of light withering (LW), moderate withering (MW) and heavy withering (HW) on tea quality jointly by transcriptome and metabolomics. It was found that LW was more beneficial in increasing gene expression of the ko00500, ko00511, ko00940, ko00944, ko00941, ko00740 and ko02010 pathways in tea leaves, thereby increasing the content of quinones, phenolic acids, lignans and coumarins, and flavonoids; MW was more beneficial in increasing gene expression of ko00500, ko00511, ko00130, ko00380 and ko00520 pathways, thereby increasing the content of terpenoids, organic acids and lipids. The aroma intensity was highest in moderately withering tea leaves and bitterness intensity was highest in lightly withering tea leaves, while the intensity of mellowness, fresh and brisk taste was significantly higher in MW and LW than in HW. This study provides an important basis for guiding the processing of Wuyi rock tea with different flavors. • The degree of withering can significantly change the taste of tea. • Light withering mainly enhanced gene expression of 7 metabolic pathways. • Light withering mainly increased the content of 4 categories metabolites. • Aroma intensity was strongest in tea leaves with moderate withering. • Bitterness intensity was strongest in tea leaves with light withering. [ABSTRACT FROM AUTHOR]

In response to the increased demand for high-resolution video, the new generation of video standards, High Efficiency Video Coding (HEVC) and its scalable extension (SHVC) have been finalized. The compression of HEVC/SHVC is efficiently improved and supports ultra-high resolution (UHD). Therefore, the coding complexity of HEVC/SHVC is much higher than those of previous standards. The framework of SHVC is based on HEVC and is divided into several types of scalable video. SHVC can be decoded into various video resolutions, frame rates and qualities, and only needs to be encoded once, but with higher complexity than HEVC. Thus, how to reduce the coding complexity of SHVC is the purpose of this paper. Our proposed algorithm accelerates the enhancement layer (EL) prediction by utilizing encoded Coding Unit (CU) sizes, prediction modes, motion vectors and Rate-Distortion Costs (RD-Costs) of the base layer (BL) and encoded CU sizes of the enhancement layer for quality scalability of SHVC. Experimental results show that the proposed algorithm can save lots of time while maintaining good video quality, and the performance is better than those of previous works. [ABSTRACT FROM AUTHOR]

The lesser grain borer, Rhyzopertha dominica, which is a primary pest of stored products, breaks up whole grains and makes them susceptible to secondary infestation by other pests. Insecticide application is the main control measure against this borer. A resistant strain of R. dominica against the insecticide, spinosad, was selected in the laboratory. The full-length cDNA of the target site of spinosad, nicotinic acetylcholine receptor subunit α6, from R. dominica ( Rdα6 ) was cloned and analyzed using reverse transcription PCR and rapid amplification of cDNA ends. The complete 2133-bp cDNA contains the open reading frame of 1497 bp encoding a 498-amino-acid protein. There are four predicted transmembrane (TM) regions, and six extracellular ligand-binding sites at the N-terminus, upstream from the first TM in Rdα6 . Three mutations have been found in the resistant strain compared with the susceptible one: (1) a 181-bp fragment truncated at the N-terminus, resulting in the appearance of a premature stop codon, (2) one missing bp at the position 997, causing a frame-shift mutation, and (3) an 87-bp fragment truncated in the TM2 region. In addition, real-time quantitative PCR was applied to detect the transcriptional expression of Rdα6 in both the susceptible and resistant strains. The results indicated that the expression of Rdα6 was significantly lower in then resistant strain than in susceptible one. In conclusion, mutation of Rdα6 may cause R. dominica resistant to spinosad due to target site insensitivity. [ABSTRACT FROM AUTHOR]

Iron overload-induced cardiovascular toxicity is one of the most common causes of morbidity and mortality in beta-thalassemia major patients. We have previously shown that iron overload-induced systemic arterial changes characterized by endothelial dysfunction are associated with increased endothelial microparticle (EMP) release. In this study, we further demonstrate how EMP release is associated with iron-induced mitochondrial injury and apoptosis of endothelial cells. Iron increased the production of reactive oxygen species (ROS) and calcium influx into mitochondria [Ca 2 + ] m . Iron also disturbed mitochondrial respiration function and eventually led to loss of mitochondrial membrane potential (ΔΨ m ). A significant increase in apoptotic cells and EMPs were found under iron treatment. EMPs contained tissue factor (TF), which has potential clinical impact on thromboembolic phenomenon. Then, we investigated the salvaging effect of deferiprone (L1) on endothelial cell damage and EMP release. We found that L1 could inhibit iron-induced ROS generation, and decrease mitochondrial damage with the resultant effect of less endothelial cell apoptosis and EMP release. L1 could protect endothelial cells from iron-induced toxic effects and minimize EMP release, which could be potentially helpful in a subgroup of thalassemia patients who have increased thromboembolic complications. [ABSTRACT FROM AUTHOR]

Intracellular lipid droplet (LD) generation is the primary site of energy storage, which is necessary for physiological homeostasis but is related to pathological metabolic disorders. Lipid metabolism is critical for maintaining innate and adaptive immunity; however, it is mainly undefined in peripheral immune cells. Flow cytometry-based immune profiling in healthy peripheral blood cells showed significant original generation of LDs in dendritic cells (DCs, CD3−CD19−CD56−CD11+), monocytes (CD3−CD19−CD56−CD14+), natural killer cells (NK, CD3−CD19−CD56+), and B cells (CD3−CD19+). CD36, a common scavenger receptor of lipids, was also highly expressed in LD-accumulated DCs and monocytes. Following short-term treatment with oxidized LDL (oxLDL) in an experimental ex vivo model, CD14+ monocytes showed an effective increase in LD generation, but there were no alterations in the immune cell populations. Furthermore, oxLDL-treated CD14+ monocytes displayed CD36 expression. However, oxLDL-primed CD14+ monocytes showed a blockade in the uptake of extra oxLDL, even while expressing increased CD36, indicating a defect in lipid clearance. Exogenous treatment with oxLDL caused monocyte type 1 polarization accompanied by increased LD accumulation and CD36 expression. This study describes a method to monitor LD generation and CD36 expression in peripheral immune cells and identified an immunomodulatory effect of oxLDL on monocytes by tilting them towards type 1 polarization. [Display omitted] • Flow cytometryoic analysis measures the intracellular lipid droplet (LD) generation in dendritic cells, monocytes, natural killer cells, and B cells. • CD36 is expressed in LD-accumulated immune cell populations. • Treatment of oxidized LDL (oxLDL) causes LD generation and CD36 expression in CD14+ monocytes. • OxLDL-primed CD14+ monocytes show a blockade in the uptake of extra oxLDL and type 1 polarization. [ABSTRACT FROM AUTHOR]

Ilexgenin A is a natural triterpenoid with beneficial effects on lipid disorders. This study aimed to investigate the effects of ilexgenin A on endothelial homeostasis and its mechanisms. Palmitate (PA) stimulation induced endoplasmic reticulum stress (ER stress) and subsequent thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome activation in endothelial cells, leading to endothelial dysfunction. Ilexgenin A enhanced LKB1-dependent AMPK activity and improved ER stress by suppression of ROS-associated TXNIP induction. However, these effects were blocked by knockdown of AMPKα, indicating AMPK is essential for its action in suppression of ER stress. Meanwhile, ilexgenin A inhibited NLRP3 inflammasome activation by down-regulation of NLRP3 and cleaved caspase-1 induction, and thereby reduced IL-1β secretion. It also inhibited inflammation and apoptosis exposed to PA insult. Consistent with these results in endothelial cells, ilexgenin A attenuated ER stress and restored the loss of eNOS activity in vascular endothelium, and thereby improved endothelium-dependent vasodilation in rat aorta. A further analysis in high-fat fed mice showed that oral administration of ilexgenin A blocked ER stress/NLRP3 activation with reduced ROS generation and increased NO production in vascular endothelium, well confirming the beneficial effect of ilexgenin A on endothelial homeostasis in vivo. Taken together, these results show ER stress-associated TXNIP/NLRP3 inflammasome activation was responsible for endothelial dysfunction and ilexgenin A ameliorated endothelial dysfunction by suppressing ER-stress and TXNIP/NLRP3 inflammasome activation with a regulation of AMPK. This finding suggests that the application of ilexgenin A is useful in the management of cardiovascular diseases in obesity. [ABSTRACT FROM AUTHOR]

The ubiquitin-proteasome system (UPS) plays a key role in maintaining cellular protein homeostasis and participates in modulating various cellular functions. Target of rapamycin (TOR), a highly conserved Ser/Thr kinase found across species from yeasts to humans, forms two multi-protein complexes, TORC1 and TORC2, to orchestrate cellular processes crucial for optimal growth, survival, and stress responses. While UPS-mediated regulation of mammalian TOR complexes has been documented, the ubiquitination of yeast TOR complexes remains largely unexplored. Here we report a functional interplay between the UPS and TORC2 in Saccharomyces cerevisiae. Using avo3-2 ts, a temperature-sensitive mutant of the essential TORC2 component Avo3 exhibiting TORC2 defects at restrictive temperatures, we obtained evidence for UPS-dependent protein degradation and downregulation of the TORC2 component Avo2. Our results established the involvement of the E3 ubiquitin ligase Ubr1 and its catalytic activity in mediating Avo2 degradation in cells with defective Avo3. Coimmunoprecipitation revealed the interaction between Avo2 and Ubr1, indicating Avo2 as a potential substrate of Ubr1. Furthermore, depleting Ubr1 rescued the growth of avo3-2 ts cells at restrictive temperatures, suggesting an essential role of Avo2 in sustaining cell viability under heat stress and/or TORC2 dysfunction. This study uncovers a role of UPS in yeast TORC2 regulation, highlighting the impact of protein degradation control on cellular signaling. • Yeast cells with defective Avo3, a TORC2 essential component, display accelerated degradation of Avo2 protein. • Avo2 is ubiquitinated and the extent of ubiquitination is increased in cells with defective Avo3. • Avo2 physically associates with the E3 ubiquitin ligase Ubr1 and the association is upregulated in cells with defective Avo3. • Depleting Ubr1 ameliorates the growth defect in cells with Avo3 dysfunction. [ABSTRACT FROM AUTHOR]

Synaptic plasticity is crucial as it dynamically molds the strength and connectivity of neural circuits, influencing learning, memory, and the development of neurological disorders. Metformin, a widely prescribed anti-diabetic medication, has been shown to readily cross the blood-brain barrier (BBB) and the placenta. However, its prolonged impact on neuronal morphology and functions remains underexplored. In this study, we investigated the influence of metformin on dendrite development and synaptic plasticity in embryonic brains and primary rat cortical neurons. Our findings reveal a negative modulation of dendrite development by metformin, as evidenced by altered dendritic arborization, impaired dendritic spine morphology and disruptions in synaptic plasticity, suggesting a potential link between metformin exposure and aberrations in neuronal connectivity. In addition, we extend our insights to the impact of maternal metformin exposure on embryonic brains, revealing a significant inhibition of dendrite development in E18.5 rat brains. In conclusion, this study adds to the expanding knowledge base on the non-metabolic effects of metformin, emphasizing the significance of assessing its potential influence on both neuronal structure and function. There is an urgent need for further investigations into the enduring impact of prolonged metformin administration on the structural and functional aspects of neurons. [Display omitted] • Metformin impairs dendrite development in the developing cortex and cortical neurons likely by targeting Map2. • Metformin alters dendritic spine morphology in primary cortical neurons. • Metformin reduces dendritic arborization and synaptic plasticity in primary cortical neurons. [ABSTRACT FROM AUTHOR]

• An optical fiber weak magnetic sensing system based on Michelson interferometer is proposed. • A new improved phase-generated carrier demodulation algorithm. • Suitable for optical fiber interference weak signal demodulation. • The sensing unit support frame was fabricated using 3D printing. The detection of weak magnetic fields is integral to applications in geophysical monitoring, biomagnetism, and remote sensing. This paper presents a new sensing unit structure and signal demodulation algorithm for optical fiber weak magnetic sensing system. The system uses a strip-ring sensing unit structure that combines magnetostrictive effects with optical fibers through 3D printing technology. This integration facilitates the conversion of magnetostrictive displacement into optical phase. An improved Phase Generated Carrier (PGC) algorithm is employed to demodulate the phase information, enhancing the signal to noise ratio (SNR) by 4.33 dB compared to the traditional PGC algorithm, and achieving a phase resolution of 29.51 µrad/Hz1/2 at 500 Hz. Experimental results demonstrate that the suggested sensing system can detect a minimum magnetic field of 140 nT, with an AC magnetic field phase resolution of 15.78 nT/Hz1/2 at 500 Hz. The demodulation sensitivity reaches 1.87 × 10−6 rad/nT under a magnetic field of 140–1400 nT. The capability of the proposed system demonstrated great potential as an efficient approach for detecting weak magnetic signals in many practical applications. [ABSTRACT FROM AUTHOR]

Abstract: Alexander disease is a primary genetic disorder of astrocyte caused by dominant mutations in the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). While most of the disease-causing mutations described to date have been found in the conserved α-helical rod domain, some mutations are found in the C-terminal non-α-helical tail domain. Here, we compare five different mutations (N386I, S393I, S398F, S398Y and D417M14X) located in the C-terminal domain of GFAP on filament assembly properties in vitro and in transiently transfected cultured cells. All the mutations disrupted in vitro filament assembly. The mutations also affected the solubility and promoted filament aggregation of GFAP in transiently transfected MCF7, SW13 and U343MG cells. This correlated with the activation of the p38 stress-activated protein kinase and an increased association with the small heat shock protein (sHSP) chaperone, αB-crystallin. Of the mutants studied, D417M14X GFAP caused the most significant effects both upon filament assembly in vitro and in transiently transfected cells. This mutant also caused extensive filament aggregation coinciding with the sequestration of αB-crystallin and HSP27 as well as inhibition of the proteosome and activation of p38 kinase. Associated with these changes were an activation of caspase 3 and a significant decrease in astrocyte viability. We conclude that some mutations in the C-terminus of GFAP correlate with caspase 3 cleavage and the loss of cell viability, suggesting that these could be contributory factors in the development of Alexander disease. [Copyright &y& Elsevier]

Abstract: Experimental autoimmune uveoretinitis (EAU), a widely used animal model of human posterior/pan-uveitis, is extremely valuable in allowing understanding of the pathogenesis of uveitis as well as in developing new treatments. Depending on the animal strain and immunization protocol used, the clinical course of EAU can be acute, severe and involving the anterior and posterior part of the eye, or chronic, mild and involving only the posterior part of the eye. Clinical signs of EAU can be examined by bio-microscopy. Using appropriate criteria EAU can be quantitatively evaluated clinically in living animals. However, correlation of research within different laboratories is difficult since clinical grading systems are subjective and susceptible to considerable variability. In this study, we have developed a recordable, image-based clinical grading system for the chronic models of EAU. Fundus images were taken from EAU mice using an endoscopic imaging system. Fundus changes were classified as (1) inflammatory changes (including optic disc inflammation, vasculitis and retinal tissue inflammation) and (2) retinal structural damage. Each element was scored separately based on the severity of the lesions, and the average score of the three inflammatory elements was used as the overall EAU clinical inflammation grade of the eye. The validity and reproducibility of the grading system was tested using a set of images scored independently in a masked manner by 5 individuals. The grading system proved robust, easy to use and reliable. We offer this image-based EAU clinical grading system as a useful quantitative evaluation method for clinical grading of the severity of inflammation in the chronic EAU model, in which the inflammation can be mild and mainly involves posterior part of the eye. [Copyright &y& Elsevier]

Abstract: Four novel mrkD alleles namely mrkD V1, mrkD V2, mrkD V3, and mrkD V4 were identified in seventeen Klebsiella pneumoniae meningitis strains using PCR-RFLP and sequence determination. Comparative analysis revealed a most variable region containing an RGD motif in the receptor domain of MrkDV3. In order to determine if the sequence confers the K. pneumoniae mrkD V3 the highest level of the fimbrial activity, a type 3 fimbriae display system was constructed in Escherichia coli. The E. coli JM109[pmrkABCDV3F] displaying meshwork-like fimbriae also had the most fimbrial activity, supporting a possible role of the varied sequences. In a dose-dependent manner, the GRGDSP hexapeptide appeared to inhibit the adhesion of the E. coli JM109[pmrkABCDV3F] to HCT-8, an ileocecal epithelial cell line. In addition, the adhesion activity was reduced by the addition of anti-α5β1 integrin monoclonal antibody, indicating that the RGD containing region in MrkDV3 is responsible for the binding of type 3 fimbriae to integrin. [Copyright &y& Elsevier]

Abstract: Human lactoferrin (hLF) is a member of the transferrin family and is found in most body fluids of human. Recent study showed that hLF played some roles in the regulation of cell growth. However, the biological function of hLF in the central nervous system and neuronal cells is still unclear. The MTT was used to assay cell viability, ELISA tests were used to assay caspase activities, and TUNEL staining was used to test the cytotoxicity of hLF to the cells. Our result showed that 700μg/ml hLF significantly reduced the cell viability and increased the caspase 3 and 8 activities in PC12 neuronal cells. TUNEL staining further showed that 700μg/ml hLF was cytotoxic to the PC12 through apoptosis-mediated pathway. In addition, 700μg/ml hLF significantly decreased the protein expressions of phosphorylated extracellular-signal-regulated kinase 1/2 (ERK1/2) and Bcl-2 in PC12 cells, whereas 50μg/ml hLF significantly increased the phosphorylation of ERK1/2 which could be specifically inhibited by PD98059. Furthermore, 50μg/ml hLF could not only up-regulate the Bcl-2 expression but also protect PC12 cells from FasL-induced apoptosis. In conclusion, hLF plays a crucial role in the regulation of apoptosis and anti-apoptosis in PC12 neuronal cells via ERK1/2 phosphorylation pathway. [Copyright &y& Elsevier]

[Display omitted] Electrospinning is an effective technique to fabricate one-dimensional materials. In this study, cobalt-embedded carbon nanofibers (Co@CNFs) are obtained via carbonization of electrospun cobalt Prussian blue analogue (Co-Co PBA) under nitrogen atmosphere. The Co@CNFs have metallic cobalt surrounded by graphitic carbon shells and possess high specific surface area, rich porosity, high graphitic degree, and rational nitrogen doping. The structure merits endow them with excellent electrocatalytic performances for oxygen reduction reaction (ORR): an onset potential of 0.867 V vs. RHE and 0.784 V vs. RHE at j = − 3 mA cm−2 with a four-electron transfer process. Through a further mild oxidation process, we obtain Co 3 O 4 nanoparticles-embedded nitrogen-doped carbon (Co 3 O 4 @CNFs) with spindle-like morphology. When working as the anode materials for lithium-ion batteries (LIBs), Co 3 O 4 @CNFs show high specific capacity, good stability, and excellent rate capability. The Co 3 O 4 @CNFs anode delivers a discharge specific capacity of 1404 mA h g−1 after 100 cycles at a current density of 100 mA g−1 and about 500 mA h g−1 after 500 cycles at 2000 mA g−1. The diffusion- and capacitive-controlled processes both contribute to the charge storage of the Co 3 O 4 @CNFs electrode. This study provides a new strategy to fabricate the excellent electrocatalysts for ORR and anode materials for LIBs via facile electrospinning. [ABSTRACT FROM AUTHOR]

We showed previously that lipopolysaccharide (LPS) induces noncholinergic airway hyperreactivity to capsaicin via an upregulation of tachykinin synthesis. This study was designed to test whether double-stranded preprotachykinin (ds PPT) RNA, RNA interference (RNAi), prevents the LPS-induced alterations. First, cultured primary nodose ganglial cells of newborn Brown–Norway rats were divided into four groups: control; LPS; LPS+RNAi; and LPS+RNAi+liposome. Second, young Brown–Norway rats for the in vivo study were divided into three groups (control; LPS; and LPS+RNAi), and ds PPT RNA was microinjected bilaterally into the nodose ganglia in the LPS+RNAi group. Then, ganglial cells were collected from the culture whereas the nodose ganglia and lungs were sampled from the animals, and PPT mRNA and substance P (SP) levels were analyzed. Also, airway reactivity to capsaicin was performed in vivo. LPS induced significant increases in PPT mRNA and SP levels in vitro and in vivo and an increase in airway reactivity to capsaicin in vivo. However, ds PPT RNA, but not scrambled RNA, prevented all LPS-induced alterations. The effect of ds PPT RNA was not enhanced by liposome in vitro. Therefore, we demonstrated that the local application of RNAi prevents effectively the activation of the noncholinergic system modulating the lungs/airways. [Copyright &y& Elsevier]

The human lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor (TNF) receptor superfamily, is essential for not only the development and organization of secondary lymphoid tissues, but also for chemokine release. Even though LTβR was shown to recruit TNF-receptor-associated factor (TRAF) 2, 3, and 5, and to induce cell apoptosis or NF-κB activation, however, the downstream signaling leading to chemokine expression is not illustrated yet. In this study, we find that overexpression of LTβR in HEK293 cells increases IL-8 promoter activity and leads to IL-8 release. LTβR-induced IL-8 gene expression requires NF-κB (−80 to −71) and AP-1 (−126 to −12) binding sites located in IL-8 promoter, and NF-κB is more crucial than AP-1 for IL-8 gene expression. Reporter assay with dominant-negative mutants of TRAFs reveals that TRAF2, 3, and 5, as well as the downstream signal molecules NIK, IKKα, and IKKβ, are involved in IL-8 gene expression. LTβR-mediated IL-8 response was inhibited by the dominant-negative mutants of ASK1, MKK4, MKK7, and JNK, but not by those of MEKK1, TAK1, MEK, ERK, and p38 MAPK. This suggests that IL-8 induction by LTβR is via TRAFs-elicited signaling pathways, including NIK/IKK-dependent NF-κB activation and ASK/MKK/JNK-dependent AP-1 activation. [Copyright &y& Elsevier]

Per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA), are common persistent environmental organic pollutants. Animal studies have indicated that PFAS influence inflammatory responses and lung development. However, whether prenatal or childhood PFAS exposure affects children's lung function remains unclear. This study aimed to investigate both in utero exposure and childhood exposure to PFAS and the relationships between them and lung function development in childhood. In total, 165 children were recruited from the Taiwan Birth Panel Study (TBPS). Cord blood plasma and children's serum were collected when they were eight years old. PFAS levels were analysed by ultra-high-performance liquid chromatography/tandem mass spectrometry. When these children reached eight years of age, we administered detailed questionnaires and lung function examinations. The mean concentrations of PFOA, PFOS, PFNA and PFUA in cord blood among the 165 study children were 2.4, 6.4, 6.0, and 15.4 ng/mL, respectively. The mean concentrations in serum from eight-year-olds were 2.7, 5.9, 0.6, and 0.3 ng/mL, respectively. At eight years of age, the mean FEV1 (forced expiratory volume per sec), FVC (forced vital capacity), PEF (peak expiratory flow) and FEV1/FVC values were 1679 mL, 1835 mL, 3846 mL/s and 92.0%, respectively. PFOA, PFOS, PFNA and PFUA levels in cord blood were inversely associated with FEV1, FVC and PEF values. The PFOS concentration in cord blood was the most consistently correlated with decreasing lung function before and after adjusting for confounding factors. The PFOS concentration was also significantly inversely correlated with lung function in subgroups with lower birth weight and allergic rhinitis. Our cohort study revealed that the concentrations of PFOA, PFOS, PFNA and PFUA were higher in cord blood than in serum from eight-year-olds. Some trends were also noted between intrauterine PFOS exposure and children's decreasing FEV1, FVC and PEF, especially in subgroups with lower birth weight and allergic rhinitis. Therefore, intrauterine PFAS exposure, especially PFOS, may play a vital role in lung development. • The concentrations of PFOA, PFOS, PFNA and PFUA were higher in cord blood than in serum from eight-year-olds. • Intrauterine PFAS exposure, especially PFOS, may play a vital role in lung development. [ABSTRACT FROM AUTHOR]

Sexual dysfunction has been reported in women following treatment for gynecological cancer. However, the actual sexual activities adopted by these women are not well understood. The aims of this study were to (1) explore a relatively new concept, diversity of sexual activities (DSA), and (2) identify factors associated with DSA in women with gynecological cancer. This cross-sectional study included 136 Taiwanese long-term partnered women with gynecologic cancer treated in a large medical center. DSA was measured with the Diversity of Sexual Activities Scale, which assesses the number of sexual activities adopted in the past 6 months. Covariates included sexual knowledge and sexual attitudes, perceived changes in relationships of intimacy since treatment, and demographic and clinical factors. The mean age of participants was 51.2 years (SD = 8.66); cancer diagnoses were cervical (50.7%), endometrial (31.6%), and ovarian (17.6%). The mean number of sexual activities was 2.88 (SD = 2.63); 29.4% of participants had no physical contact with their partners after treatment. The participants reported a significantly decreased overall satisfaction toward adopted sexual activities after cancer treatment. Lower DSA was associated with older age and receiving a combination of chemotherapy and radiotherapy. Cancer treatment has a significant impact on sexual activity in women with gynecological cancer. Around 30% of participants reported not having any physical contact with their partners since receiving cancer treatment. Sexual rehabilitation counseling that emphasizes alternative forms of sexual expression is suggested. • Diversity of sexual activities (DSA) was explored in partnered women following gynecological cancer treatment. • Nearly 30% of women had no physical contact with their partner after the treatment of gynecological cancer. • Receiving chemotherapy plus radiotherapy and older age was negatively associated with sexual diversity. [ABSTRACT FROM AUTHOR]

• A reflective fiber loop mirror is firstly used in flow rate sensing. • The proposed sensor exists an infinite temperature-sensitivity point, which can be adjusted. • The fiber thermal anemometer has high sensitivity and long-distance sensing capability. A highly-sensitive fiber thermal anemometer was proposed and numerically designed based on reflective fiber loop mirror (RFLM). One ethanol-infiltrated birefringent photonic crystal fiber (BPCF) was imbedded in the RFLM as the sensing head, whose output interference spectrum was sensitive to surrounding temperature. Laser was used to heat the BPCF to a fixed temperature, but the temperature changed with the variation of surrounding flow rate. Therefore, the flow rate could be measured by monitoring the wavelength shift of the output spectrum. Through numerical analyses on the characteristics of the RFLM, the relationship between the flow rate and the temperature of the BPCF was numerical studied and then the structure parameters of the BPCF were optimized. Finally, numerical results showed that the maximum detectable flow rate could be enlarged to 20.8 m/s with the detection limit of 0.3 m/s, when the laser power was 100 mW. In addition, the defined quality parameter Q demonstrated that the sensitivity was improved to about 20 times. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of 21 tricyclic and tetracyclic sulfamates as STS inhibitors. • Design novel nonsteroidal tetracyclic coumarin skeleton for STS inhibition. • Para substitutions at the phenyl ring of tricyclic analogs gave the best STS inhibition. • 9e and 10c had k inact / K I of 28.6 and 19.1 nM−1min−1 on human STS, respectively. • Cytotoxicity of 9e (IC 50 of 0.65 µM) and 10c (IC 50 of 4.7 µM) on T-47D cells. Inhibition of steroid sulfatase (STS) decreases estrogen production and thus, suppresses tumor proliferation. Inspired by irosustat, the first STS inhibitor in clinical trials, we explored twenty-one tricyclic and tetra-heterocyclic coumarin–based derivatives. Their STS enzyme kinetic parameters, docking models, and cytotoxicity toward breast cancer and normal cells were evaluated. Tricyclic derivative 9e and tetracyclic derivative 10c were the most promising irreversible inhibitors developed in this study, with K I of 0.05 and 0.4 nM, and k inact / K I ratios of 28.6 and 19.1 nM−1min−1 on human placenta STS, respectively. [ABSTRACT FROM AUTHOR]

Abstract Objectives The host immune response could be an imperative factor in the pathogenesis of neurosyphilis, but the role of T lymphocyte subsets remains unclear. In the present study, we assessed the CD4+ T and CD8+ T cell subsets in the peripheral blood of patients with HIV-negative symptomatic neurosyphilis and then explored the clinical application value of neurosyphilis. Methods In total, 24 patients with HIV-negative symptomatic neurosyphilis and 22 patients with syphilis/non-neurosyphilis were included in this study and cerebrospinal fluid (CSF) and blood samples were obtained. Th1, Th2, Th17, Th9, CD8+IFN-γ+, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells were identified by flow cytometry. Results The levels of CD8+IFN-γ+ were significantly increased in the peripheral blood of neurosyphilis patients compared to that in syphilis/non-neurosyphilis patients, but it was opposite to Th2, Th9, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells. Dendritic cells (DCs) of neurosyphilis matured by T. pallidum induced the development of a combination of IFN-γ-producing Th1 cells. The number of CD8+IL-17 + cells was significantly correlated with the CSF RPR and CSF TPPA levels. ROC curve analysis revealed that the number of CD8+IFN-γ+ cells could be a potential biomarker for neurosyphilis from non-neurosyphilis/syphilis. Conclusions High expression of CD8+IFN-γ+ cells and low expression of CD8+IL-17 + cells in patients with symptomatic neurosyphilis, which explains the pathogenesis of symptomatic neurosyphilis, meanwhile CD8+IFN-γ+ cells may be a better indicator in classifying symptomatic neurosyphilis from non-neurosyphilis/syphilis among patients without HIV infection. Highlights • The host immune response could be an imperative factor in the pathogenesis of neurosyphilis. • A comparative analysis of the CD4+ and CD8+ T cell subsets in the peripheral blood of HIV-negative symptomatic neurosyphilis patients. • The levels of CD8+IFN-γ+ were significantly increased in the peripheral blood of neurosyphilis patients compared to that in syphilis/non-neurosyphilis patients. • CD8+IFN-γ+ cells may be a better indicator in differentiating neurosyphilis from non-neurosyphilis/syphilis patients. [ABSTRACT FROM AUTHOR]

Retinal ischemia remains a common sight threatening end-point in blinding diseases such as diabetic retinopathy and retinopathy of prematurity. Endothelial colony forming cells (ECFCs) represent a subpopulation of endothelial progenitors with therapeutic utility for promoting reparative angiogenesis in the ischaemic retina. The current study has investigated the potential of enhancing this cell therapy approach by the dampening of the pro-inflammatory milieu typical of ischemic retina. Based on recent findings that ARA290 (cibinetide), a peptide based on the Helix-B domain of erythropoietin (EPO), is anti-inflammatory and tissue-protective, the effect of this peptide on ECFC-mediated vascular regeneration was studied in the ischemic retina. The effects of ARA290 on pro-survival signaling and function were assessed in ECFC cultures in vitro. Efficacy of ECFC transplantation therapy to promote retinal vascular repair in the presence and absence of ARA290 was studied in the oxygen induced retinopathy (OIR) model of retinal ischemia. The inflammatory cytokine profile and microglial activation were studied as readouts of inflammation. ARA290 activated pro-survival signaling and enhanced cell viability in response to H 2 O 2 -mediated oxidative stress in ECFCs in vitro. Preconditioning of ECFCs with EPO or ARA290 prior to delivery to the ischemic retina did not enhance vasoreparative function. ARA290 delivered systemically to OIR mice reduced pro-inflammatory expression of IL-1β and TNF-α in the mouse retina. Following intravitreal transplantation, ECFCs incorporated into the damaged retinal vasculature and significantly reduced avascular area. The vasoreparative function of ECFCs was enhanced in the presence of ARA290 but not EPO. Regulation of the pro-inflammatory milieu of the ischemic retina can be enhanced by ARA290 and may be a useful adjunct to ECFC-based cell therapy for ischemic retinopathies. • Endothelial colony-forming cells (ECFCs) express innate repair receptor (IRR) subunits. • ARA290 activates pro-survival pathways in ECFCs and is not angiogenic in vitro. • Pre-priming ECFCs with ARA290 does not improve their reparative capacity in ischemic retina. • Systemic ARA290 treatment improves vasoreparative potential of ECFCs and dampens inflammation in ischemic retina. • ARA290 may be a useful pharmacological adjunct to improve ECFC cell therapy. [ABSTRACT FROM AUTHOR]

Abstract Nonylphenol (NP) and/or bisphenol A (BPA) may have reproductive effects. Although the mechanisms of action remain unclear, steroid hormones biosynthesis, hypothalamus pituitary adrenal axis activity, oxidative stress, and crosstalk interaction of NP and BPA mixture and its pathways may play a contributory role. This cross-sectional study examined whether the interactive effects of NP/BPA and oxidative stress biomarkers played a role in reproductive indices (penis length and anogenital distance (AGD)) in 244 mother-fetus pairs. Four biomarkers of oxidative stress, (8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO 2 Gua), 8-iso-prostaglandin F 2α (8-isoPF 2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) were simultaneously analyzed using the high-performance liquid chromatography-electrospray ionization tandem mass spectrometry method. No significant associations were found between reproductive indices and NP/BPA or oxidative stress biomarkers. Maternal exposure to a mixture of NP and BPA may enhance 8-OHdG. Interactive effects were found in the high 8-isoPF 2α group, and prenatal NP exposure was inversely associated with penis length (β = −3.68 mm; p = 0.01). Similar results were noted among boys who were born to mothers in the high 8-isoPF 2α group, in which BPA was inversely associated with penis length (β = −4.43 mm; p = 0.005). Our findings suggest important implications for prenatal exposure to oxidative stress, as evidenced by the 8-isoPF2α level. Thus, NP and BPA may interact to shape fetal reproductive tract development, particularly in boys. The interactive effects of NP/BPA, oxidative stress, and reproductive indices should be considered. Highlights • Maternal NP exposure may induce 8-OHdG and 8-NO 2 Gua. • Prenatal BPA may induce 8-isoPF 2α. • Concurrent exposure to NP and BPA may enhance 8-OHdG. • In the high 8-isoPF 2α group, NP/BPA is inversely related with the fetal penis length. • The interactions of NP/BPA, oxidative stress and penis length should be considered. [ABSTRACT FROM AUTHOR]

Objective We investigated the effect of topotecan on injury and inflammation in a model of ventilator-induced lung injury (VILI). Methods Acute lung injury (ALI) was induced in mice by high-tidal volume ventilation, and the mice were then treated with topotecan or PBS. Lung tissue and bronchoalveolar lavage fluid were collected to assess pulmonary vascular leaks, inflammation, and cell apoptosis. Results Compared to PBS treatment, topotecan significantly decreased the ALI score, myeloperoxidase (MPO) content, total protein concentration, and presence of inflammatory cells and inflammatory cytokines in bronchoalveolar lavage fluid. Topotecan also reduced caspase-3 activation and type Ⅱ alveolar epithelial cell apoptosis. Moreover, topotecan inhibited NF-κB expression and activation in the VILI model. Conclusion Topotecan alleviates acute lung injury in the model of VILI through the inhibition of the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Background In patients with end-stage heart failure, the primary etiology often originates in the left ventricle, and eventually the contractile function of the right ventricle (RV) also becomes compromised. RV tissue-level deficits in contractile force and/or kinetics need quantification to understand involvement in ischemic and non-ischemic failing human myocardium. Methods and results The human population suffering from heart failure is diverse, requiring many subjects to be studied in order to perform an adequately powered statistical analysis. From 2009-present we assessed live tissue-level contractile force and kinetics in isolated myocardial RV trabeculae from 44 non-failing and 41 failing human hearts. At 1 Hz stimulation rate (in vivo resting state) the developed active force was not different in non-failing compared to failing ischemic nor non-ischemic failing trabeculae. In sharp contrast, the kinetics of relaxation were significantly impacted by disease, with 50% relaxation time being significantly shorter in non-failing vs. non-ischemic failing, while the latter was still significantly shorter than ischemic failing. Gender did not significantly impact kinetics. Length-dependent activation was not impacted. Although baseline force was not impacted, contractile reserve was critically blunted. The force-frequency relation was positive in non-failing myocardium, but negative in both ischemic and non-ischemic myocardium, while the β-adrenergic response to isoproterenol was depressed in both pathologies. Conclusions Force development at resting heart rate is not impacted by cardiac pathology, but kinetics are impaired and the magnitude of the impairment depends on the underlying etiology. Focusing on restoration of myocardial kinetics will likely have greater therapeutic potential than targeting force of contraction. [ABSTRACT FROM AUTHOR]

Highlights • Novel unit prediction method for efficient HEVC-to-SHVC transcoding is proposed. • Two proposed techniques are early termination and adaptive confidence interval. • We are among the first to propose a fast HEVC-to-SHVC transcoding framework. • Proposed method reduces encoding time of SHVC by 74.14% almost without quality loss. To support good video quality of experiences in heterogeneous environments, transcoding an existed HEVC (high efficiency video coding) video bitstream to a SHVC (scalability extension of HEVC) bitstream with quality scalability is highly required. A straightforward way is to first fully decode the input HEVC bitstream and then fully re-encode it with the SHVC encoder, which requires a tremendous computational complexity. To solve the problem, in this paper, a coding unit complexity (CUC)-based prediction method for predictions of CU (coding unit) depth and PU (prediction unit) mode for efficient HEVC-to-SHVC transcoding with quality scalability is proposed to significantly reduce the transcoding complexity. The proposed method contains two prediction techniques, including (i) early termination and (ii) adaptive confidence interval, and predicts the CU depth and PU mode relying on the decoded information from the input HEVC bitstream. Experimental results have shown that the proposed method significantly outperforms the traditional HEVC-to-SHVC method by 74.14% on average in reductions of encoding time for SHVC enhancement layer. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. Methods This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene ( DRD4 ) were identified. Results Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69 nmol/g cre. vs. 186.84 nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95 µg/g cre. vs. 16.55 µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24–0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13–1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12–65.04). Conclusion This study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected. [ABSTRACT FROM AUTHOR]

Introduction Phthalate exposure may reduce intellectual development in young children. In 2011, numerous Taiwanese children had been reported to have consumed phthalate-tainted products. We investigated the effects of phthalate exposure on the intellectual development of these children after the 2011 Taiwan di-2-ethylhexyl phthalate (DEHP) episode. Methods We recruited 204 children, aged 3–12 y, from 3 hospitals in Taiwan between 2012 and 2013. First-morning urine samples were collected for analyzing 5 phthalate metabolites. We applied a Bayesian model to estimate the past DEHP exposure ( est DEHP ADD ) of each participant before the 2011 DEHP episode. Demographic information, consumption of phthalate-tainted products, and maternal education, of each participant were obtained using a questionnaire. We used the Wechsler intelligence evaluation tools for assessing the children's and maternal intelligence quotient. Results and discussion The median levels of mono-2-ethylhexyl phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono- n -butyl phthalate, and mono- iso -butyl phthalate in the children were 9.97, 45.8, 32.2, 46.2, and 24.3 μg/g creatinine, respectively. Using the aforementioned urinary phthalate metabolites, we found that the children's verbal comprehension index (N =98) was significantly negatively associated with urinary log 10 MEOHP (β, −11.92; SE, 5.33; 95%CI, −22.52~ −1.33; P =0.028) and log 10 ΣDBP metabolites (β, −10.95; SE, 4.93; 95%CI, −20.74~ −1.16; P =0.029) after adjustment for age, gender, maternal IQ and education, passive smoking, est DEHP ADD , active and passive smoking during pregnancy. Through a tolerable daily intake-based approach, we only found a significant negative association between past estimate DEHP ADD and VIQ ≥3-<6 in preschool children whereas no correlation was observed between current DEHP exposure and IQ ≥3-<6 score with/ without estimate DEHP ADD adjustment. It revealed that the effect of past high-DEHP exposure on verbal-related neurodevelopment of younger child are more sensitive. Conclusion Our results are consistent with the hypothesis that exposure to DEHP and DnBP affects intellectual development in preschool and school-aged children, particularly their language learning or expression ability. [ABSTRACT FROM AUTHOR]

Background Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. Materials and methods In vitro fibrosis model was established by treatment with transforming growth factor-β1 (TGF-β1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis and fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). Results Under renal fibrosis conditions, TGF-β1 (5 ng/ml) increased ROS. Simultaneously, TGF-β1-induced extracellular fibronectin by ELISA assay. In addition, TGF-β1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2 μg/ml) expression vector dramatically reverse TGF-β1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2 μg/ml) significantly increased the expression of fibronectin of both intercellular and extracellular origins in NRK-49F cells. Discussion These finding suggest that NRF-1 plays a pivotal role on renal cellular fibrosis. Moreover, NRF-1 might act as a novel renal fibrosis antagonist by down-regulating fibrosis signaling in renal fibroblast cells. [ABSTRACT FROM AUTHOR]

Thymic stromal lymphopoietin (TSLP) has previously been linked to allergic inflammatory diseases, and tissue fibrosis and organ dysfunction may also arise from such inflammation. It remains unclear, however, whether TSLP plays any role in the occurrence of renal fibrosis, so this study investigated that possibility. An in vitro fibrosis model was established by treating normal rat kidney fibroblast (NRK-49F) cells with transforming growth factor-β1 (TGF-β1), after which the levels of various fibrogenic markers (e.g., fibronectin) and downstream fibrogenic signal proteins (e.g., smad 7) were investigated. Also, TSLP shRNA was used to silence the effects of TSLP, while an ELISA was conducted to evaluate the fibronectin secretions. The level of fibronectin in the NRK-49F cells was dose- and time-dependently increased by the administration of exogenous TSLP (P<0.05). TSLP also significantly increased the level of fibrosis signaling, in addition to inducing a marked decrease in the down-regulation of Smad7. Interestingly, the application of TSLP shRNA caused a stark reversal of the TGF-β1-induced cellular fibrosis while simultaneously leading to the suppression of fibronectin and fibrogenic signal proteins. Taken together, these observations provide insights into how extracellular matrices develop and could thus lead to potential therapeutic interventions for the suppression of renal fibrosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of 32 tricyclic sulfamates as STS irreversible inhibitors. • SAR studies revealed that adjacent halogen-bearing phenyl gave the best inhibition. • 19 m , 19v , and 19w , had K I of 0.02 to 0.11 nM against STS. • Cellular potency is significant correlated with covalent kinetics (k inact/ K I). Steroid sulfatase inhibitors block the local production of estrogenic steroids and are attractive agents for the treatment of estrogen-dependent cancers. Inspiration of coumarin-based inhibitors, we synthesized thirty-two 5-oxa-1,2,3,4-tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl sulfamates , focusing on the substitution derivatives on the adjacent phenyl ring and evaluated their abilities to block STS from human placenta and MCF-7 cells. SAR analysis revealed that the incorporation of chlorine at either meta and/or para position of the adjacent phenyl ring of the tricyclic skeleton enhanced STS inhibition. Di-substitutions at the adjacent phenyl ring were superior to mono and tri-substitutions. Further kinetic analysis of these compounds revealed that chloride-bearing compounds, such as 19 m , 19v , and 19w , had K I of 0.02 to 0.11 nM and k inact / K I ratios of 8.8–17.5 nM-1min-1, a parameter indicated for the efficiency of irreversible inhibition. We also used the docking model to illustrate the difference in STS inhibitory potency of compounds. Finally, the safety and anti-cancer activity of selected compounds 19 m , 19v , and 19w were also studied, showing the results of low cytotoxicity on NHDF cell line and being more potent than irosustat on ZR-75–1 cell, which was a hormone-dependent cancer cell line with high STS expression. [ABSTRACT FROM AUTHOR]

Environmental exposures to mixtures of toxic chemicals have potential interaction effects that may lead to hazard index values exceeding one. However, current regulation levels, such as tolerable daily intake (TDI), are mostly based on experimental studies conducted with a single chemical compound. In this study, we assessed the relationships between melamine and di-(2-ethylhexyl) phthalate (DEHP) exposure and their coexposure with the early renal injury markers N-acetyl -D-glucosaminidase (NAG), albumin/creatinine ratio (ACR), and microalbuminuria in 1236 pregnant women. Various generalized linear models with interaction terms and Bayesian kernel machine regression models were used for the (co-)exposure response associations. We derived the benchmark dose (BMD) and the corresponding one-sided 95% confidence bound BMDL based on the estimated (covariate-adjusted) average daily intake of melamine and DEHP metabolites measured in spot urine of the women collected during the third trimester. Given a benchmark response of 0.1, the BMDL level of melamine (DEHP) exposure on NAG (ACR, microalbuminuria) was 2.67 (11.20, 4.45) μg / kg _ bw / day , and it decreased to as low as 1.46 (3.83, 2.73) μg / kg _ bw / day when considering coexposure to DEHP (melamine) up to the 90th percentile. Both the exposure threshold levels of melamine and DEHP for early renal injuries in pregnant women were several-fold to one order lower than the current recommended TDIs by the WHO and the US FDA and EPA and were even lower considering coexposure. Because of concurrent exposures in real-world environments, more stringent regulation levels are recommended in susceptible populations, such as pregnant women, due to potential synergistic mixture effects. • Exposure threshold of melamine for NAG in pregnant women was 2.67 μg / kg _ bw / day. • Exposure threshold of DEHP for ACR (microalbuminuria) was 11.20 (4.45) μg / kg _ bw / day. • BMDLs decreased with coexposure to DEHP and melamine due to a synergistic effect. • Both the threshold levels were one order lower than the WHO regulation levels. • Mixture risk assessment based on early renal injury markers in pregnant women. [ABSTRACT FROM AUTHOR]

On May 23, 2011, a major scandal involving the illegal use of phthalates as clouding agents in food products was reported. Specifically, di(2-ethylhexyl) phthalate (DEHP) was purposefully added to foods as a substitute emulsifier. The purpose of this study was to examine the effects of DEHP exposure on the growth characteristics of the child victims of this scandal. Eighty-eight victims, originating from northern, central, and southern Taiwan and ranging in age from 6.0 to 10.5 years, were invited to participate in this study during clinic visits. The participants underwent follow-up health examinations from August 2012 to February 2013. We collected information on each participant's history of exposure to tainted food products using a questionnaire, and we analyzed their urinary concentrations of DEHP metabolites using high-performance liquid chromatography/tandem mass spectrometry. These data were then used to estimate their daily DEHP intake (DI All ) during the scandal. We also measured physical development parameters (height, weight, and bone age) and hormone levels (thyroid, sex and growth hormones) to evaluate their overall growth characteristics. The average (SD) duration of DEHP intake from tainted nutrition supplements was 1.39 (1.01) years. The median DI All values were 19.93 and 20.69 μg/kg bw/day for boys and girls, respectively. Among the enrolled children, the DI All values of 46.9% of boys and 51.3% of girls exceeded the reference dose (RfD) of 20 μg/kg bw/day established by the US Environmental Protection Agency. Our results demonstrate that DI All is negatively associated with the height percentile, weight percentile, bone age/chronological age, and insulin-like growth factor 1 (IGF-1) levels but not with IGF binding protein 3 (IGF-BP3) level, IGF-1/IGF-BP3, sex hormones, or thyroid hormone levels. The DEHP DI All value exceeded the RfD at high rates among children of both genders. Our results suggest that high levels of DEHP exposure due to the consumption of tainted food products are negatively associated with body weight, height, bone age, and IGF-1 levels in children. The likelihood of delayed puberty among the affected children is therefore a reasonable concern, and further follow-up is required. [ABSTRACT FROM AUTHOR]