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N-doped NiFe(B) (oxy)hydroxide can promote the catalytic activity for an alkaline oxygen evolution reaction (OER) significantly, but fabrication is difficult. Herein, we introduced a B-induction route to the N-NiFe(B) (oxy)hydroxide monolithic electrode under a relatively low temperature. We observed an excellent catalytic performance benefiting from an optimal electronic structure, enlarged surface area and improved hydrophilicity. Moreover, this mild protocol could be extended to fabricate an S-doped NiFe-based catalyst. This research could aid large-scale manufacture. [ABSTRACT FROM AUTHOR]

Abstract The Bayesian Lasso is constructed in the linear regression framework and applies the Gibbs sampling to estimate the regression parameters. This paper develops a new sparse learning model, named the Bayesian Lasso Sparse (BLS) model, that takes the hierarchical model formulation of the Bayesian Lasso. The main difference from the original Bayesian Lasso lies in the estimation procedure; the BLS uses a learning algorithm based on the type-II maximum likelihood procedure. Opposed to the Bayesian Lasso, the BLS provides sparse estimates of the regression parameters. The BLS is also derived for nonlinear supervised learning problems by introducing kernel functions. We compare the BLS model to the well known Relevance Vector Machine, the Fast Laplace, the Bayesian Lasso, and the Lasso, on both simulated and real data. The numerical results show that the BLS is sparse and precise, especially when dealing with noisy and irregular dataset. [ABSTRACT FROM AUTHOR]

The kinetic Alfvén solitons in a plasma with regularized kappa distributed electron are studied under the small‐amplitude assumption; the analytical solution of the kinetic Alfvén soliton is obtained using the reductive perturbation method. The numerical calculation reveals that the width and amplitude of the soliton decrease with the increase of the cut‐off parameter α$$ \alpha $$ for fixed spectral index κ$$ \kappa $$. However, the width and amplitude of the soliton increase for small spectral index and decrease for a larger spectral index in the case of the fixed cut‐off parameter. The properties of the soliton can explain the observed electrostatic structure observed in the Earth's inner magnetosphere. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess the long-term effects of the transition in iodine status on the incidence of thyroid disorders over 20 years of follow-up. Methods: The original prospective cohort study, started in 1999 (n = 3761), classified three regions in north China based on iodine status (insufficient iodine, more than adequate iodine, and excessive iodine, respectively) for 5 years. Subsequently, participants were followed for up to another 15 years to assess the long-term effects of shifts to adequate iodine on the incidence of thyroid disorders. Panshan transitioned from insufficient to adequate iodine, and Huanghua transitioned from excessive to more than adequate iodine. Both regions were compared with Zhangwu, in which iodine status changed from more than adequate to adequate iodine (from 214 to 167.2 μg/L). A cluster sampling method was used to select participants in the three regions. Participants completed questionnaires and underwent thyroid ultrasonography. Urinary iodine concentrations (UICs), serum thyroid hormone concentration, and thyroid antibodies were measured. Results: When the iodine status changed from insufficient to adequate (with the median UIC increasing from 88 to 141.9 μg/L), the incidence density of subclinical hyperthyroidism, positive thyroperoxidase antibody, positive thyroglobulin antibody (TgAb), and goiter decreased significantly (p < 0.05 for all). Additionally, the cumulative incidence of subclinical hypothyroidism was significantly lower compared with the region where the iodine status changed from being more than adequate to adequate (1.9% vs. 6.0%, p < 0.001). When the iodine status changed from excessive to more than adequate (median UIC from 634 to 266.7 μg/L), a significant decrease in the incidence density of subclinical hyperthyroidism, positive thyroid antibodies, positive TgAb, and goiter (p < 0.05 for all) were also found. However, an increase in thyroid nodule incidence density (17.26 vs. 28.25 per 1000 person-years, p < 0.001) was seen. Conclusions: The incidence of thyroid disorders (except for thyroid nodules) stabilized or decreased among adults in the three communities from year 5 to year 15 of follow-up. Appropriate iodine fortification is safe and effective over the long term. Restoring urinary iodine to appropriate levels reduces population risk for thyroid disorders. [ABSTRACT FROM AUTHOR]

The transverse strength of unidirectional carbon fiber reinforced polymer (UD-CFRP) composites is a high dimensional and nonlinear function of microstructure due to the wide scatter in mechanical properties and complex failure mechanisms, which is a challenging task to develop a general microstructure dependent strength criterion (MDSC) in theory or computation. Volume fraction and distribution of fibers are among the crucial influencing factors. A computational micromechanics and machine learning (ML) combined method is employed to uncover the transverse mechanical response of UD-CFRP composites. High-throughput finite element analyses (FEA) are performed to obtain the transverse behaviors of composites with varying fiber distribution and volume fraction under different loading states. They showed that fiber distribution has different effects on strengths in different failure modes, while the failure modes are closely related to loading states and fiber volume fractions. An ML model is then trained to characterize the relations between composite microstructure and composite strength. Then, the transverse strengths of 1000 new microstructures are predicted, which shows good agreement with FEA results, so that the MDSC of UD-CFRP is constructed by fully accounting for the influence of fiber distribution. Reliability of the method is verified by considering composites with various fiber volume fractions. [Display omitted] • High-throughput finite element analyses are performed to uncover the transverse mechanical response of UD-CFRP composites. • The transverse behaviors of composites with various fiber distribution and fiber volume fraction are presented. • The complex relations between microstructure of composites and transverse strengths are represented. • The microstructure dependent transverse strength criterion is constructed by considering the effect of fiber distribution. [ABSTRACT FROM AUTHOR]

• Unique dataset from Norway's largest dairy company. • Analysis based on domain knowledge and machine learning models. • Identification of important dairy herd features in forecasting milk deliveries. • Machine Learning models performs well in forecasting milk deliveries. • Discussion of models' property for short- and long-term forecasts. Accurate forecasts of milk deliveries to dairy are crucial to secure a stable milk supply to customers, the effective use of raw milk, and the reduction of logistics costs and greenhouse gas emissions. The primary aim of this study was to improve the prediction of the total milk supply from Norwegian dairy farmers to dairies, and to do so by utilizing a traditional time series model, as well as several modern statistical models and machine learning algorithms. The secondary aim was to explore the usefulness of dairy herd features as explanatory variables to forecast the target variable milk delivery to dairy. Several statistical learning models and machine learning algorithms were applied for forecasting, in addition to a traditional time series model and qualitative domain knowledge. Historical data of monthly milk deliveries were collected from Norwegian dairy companies, together with detailed dairy farm herd records. The herd records contain features or explanatory variables, such as the number of cows and inseminations that can influence the response variable – the monthly milk deliveries. Our results show that some of the models applied can predict monthly milk deliveries to dairies with a mean absolute prediction error of 1–2% up to 24-months ahead. While a generalized linear model performed the best up to 3-months ahead, the machine learning models performed the best up to one year ahead. Two years ahead a traditional seasonal autoregressive model performed the best. Because some of the models select the most important features to predict milk delivery, our analytical results also provide valuable information about which features are the most important to predict future milk delivery. [ABSTRACT FROM AUTHOR]

Allowable load is one of the core parameters for the design and service of composite structures (CSs). However, due to the large design parameters, cumbersome design procedure and complicated simulation model of CSs, considerable amounts of experiments and simulations are needed to determine the allowable load of CSs, which is costly and inefficient, hindering the wide application of CSs in industry. In this work, we present a general deep transfer learning approach to construct the allowable load space (ALS) of notched laminates by considering various design parameters such as geometries, materials, stacking angles, ply numbers, laminate types and load types. Initially, an ensemble deep neural network (Ensemble) is trained, which can predict the allowable loads of notched laminate with known design parameters well. Here the Ensemble guided by ensemble learning is trained to reduce the errors generated by manually setting. Then, the pre-trained Ensemble is transferred to new design parameters by fine-tuning it with scarce new samples. Finally, the ALS of notch laminates is constructed by integrating the pre-trained and fine-tuned models, covering both known and diverse new design parameters. Our approach can easily be extended to other CSs. [Display omitted] [ABSTRACT FROM AUTHOR]

Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48‐variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation‐selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4‐dihydro‐2‐quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L−1 day−1). Other oxidase activities, such as C−C bond desaturation, aromatization, and C−C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy‐functionalized derivatives of these building block molecules for synthesis and drug discovery. [ABSTRACT FROM AUTHOR]

Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48‐variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation‐selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4‐dihydro‐2‐quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L−1 day−1). Other oxidase activities, such as C−C bond desaturation, aromatization, and C−C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy‐functionalized derivatives of these building block molecules for synthesis and drug discovery. [ABSTRACT FROM AUTHOR]

Background: Although increasing data suggest that hyperthyroidism is associated with adverse pregnancy outcomes, there are only a few reports with different conclusions on whether the mild transient reduction in thyrotropin (TSH) with or without free thyroxine (FT4) elevation during the early stage of pregnancy also causes adverse pregnancy outcomes. Subjects and Methods: We analyzed data from 3,783 women in this study from August 2011 to December 2013. Participants completed a questionnaire survey. Samples of blood were obtained in the 4th–8th week of pregnancy and their TSH, FT4, thyroid peroxidase antibody, and thyroglobulin antibody were measured. We divided the participants into overt hyperthyroidism group (OHG), subclinical hyperthyroidism group (SHG), and control group based on their blood results and followed up on their pregnancy outcomes. Results: (1) The serum level of FT4 in the SHG was much higher than the control group (p < 0.05). No difference was found in the TSH between the OHG and SHG. The positive rate of autoimmune thyroid antibodies in the OHG (25.6%) was significantly higher than that in the SHG (14.2%) and control group (13.9%) (p < 0.05), whereas there was no difference between the SHG and control group. (2) The SHG had a lower incidence of miscarriage (1.7% vs. 7.2%; OR = 0.218, p = 0.016) than the control group, and the OHG had a higher incidence of placenta previa (3.3% vs. 0.8%; OR = 4.366, p = 0.039) than the control group. (3). We used a binary logistic regression to take other factors into consideration and found that subclinical hyperthyroidism was associated with a lower risk of abortion (OR = 0.206; 95% CI = 0.050–0.840; p = 0.028) but higher risk of preeclampsia (OR = 5.143; 95% CI = 1.463–18.076; p = 0.011) and placental abruption (OR = 4.676; 95% CI = 1.017–21.509; p = 0.048), and overt hyperthyroidism may increase the incidence of placenta previa (OR = 4.193; 95% CI = 1.222–14.382; p = 0.023). Conclusions: Subclinical hyperthyroidism during weeks 4–8 of pregnancy may be associated with the decreased incidence of abortion but might be a risk factor for preeclampsia and placental abruption. Meanwhile, pregnancy with overt hyperthyroidism may be an independent risk factor for placenta previa. [ABSTRACT FROM AUTHOR]

To realize the sensitive and rapid sensing of humidity, 2D as-prepared TiO 2 nanosheets (hereafter shorted as TiO 2 nanosheets) with characteristics of surface oxygen vacancy defects and large surface area were designed and synthesized. The TiO 2 nanosheets-based sensor exhibit superior humidity sensing performance with an ultrahigh sensitivity evidenced by the dramatic impedance variation of more than four orders of magnitude from relative humidity (RH) 11% to 95%, fast response (3 s) and recovery (50 s) process, as well as a small hysteresis (∼4.6%). Additionally, a systematic study of the sensing performances of sensors fabricated from TiO 2 nanosheets and two counterparts calcined in N 2 and O 2 with decreased specific surface area and controlled surface defects, namely TiO 2 -400 (N 2 ) and TiO 2 -400 (O 2 ), has been conducted. The results show that at low RH level of 33% and 54%, TiO 2 -400 (N 2 ) with highest surface oxygen vacancy defects concentration exhibits the highest response of 6.26 and 34, respectively, while at high RH range of 85% to 95%, the TiO 2 nanosheets with largest specific surface area shows the highest response which is almost 10 times higher than that of the calcined counterparts. Combining the complex impedance analysis, the overall ultrahigh humidity sensing performance of TiO 2 nanosheets-based sensor is attributed to the dissociating promotion by the abundant surface defect and enhanced electrolytic conduction by the large specific surface area. [ABSTRACT FROM AUTHOR]

The MADS-box gene SVP ( SHORT VEGETATIVE PHASE ) mediates the integration of signals involved in the control of flowering time and flower development by interacting with MADS-box proteins. Although SVP -like genes have been isolated from a wide range of plant species, their orthologs are not well-characterized in Prunus mume (mei), an important ornamental and fruit plant in the East Asia. To determine the role of SVP -like genes in mei flowering, two MADS-box genes with homology to Arabidopsis SVP , PmSVP1 and PmSVP2 , have been identified and analyzed in mei and functionally characterized in Arabidopsis . Phylogenetic analyses revealed that PmSVP1 and PmSVP2 fall into different sub-groups within the SVP -like gene group, which suggests distinct functions. Furthermore, expression was generally found in vegetative tissues, and decreased during flower bud differentiation development suggesting a role for these genes in the transition from the vegetative to reproductive phase. Overexpression of PmSVP1 and PmSVP2 in Arabidopsis led to a range of floral phenotype changes including additional trichomes, leaf-like sepals and increased rosette branches, whereas only PmSVP1 expression delayed flowering through down-regulation of FLOWERINGLOCUST ( FT ) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 ( SOC1 ). These results suggested that SVP -like genes in mei might have distinct roles during development of flowering. Our findings will help elucidate the molecular mechanisms important for the transition from vegetative to reproductive development in mei. [ABSTRACT FROM AUTHOR]

• A method coupling FEA and machine learning is derived. • The predicted data by ANN and RF model are well consistent with the curves of exact values. • Accuracy of predicted result by ANN model is higher than that by RF model. In order to predict mechanical properties of composite laminate, a method coupling finite element analysis (FEA) and machine learning is established to analyze three examples of composite laminates, such as failure factor of Puck theory under random stress state, failure factor and critical buckling eigenvalues of open-hole laminate. By writing Abaqus script, parametric FEA models of composite laminates are built and large samples are generated. Artificial neural network (ANN) model and random forest (RF) model are set up to learn these virtual samples to predict their corresponding mechanical properties for these examples. By analyzing predicted results and FEA values of these mechanical parameters, predicted data are well consistent with the curves of FEA values and the calculated root-mean-square errors are much smaller, which proves this FEA and machine learning coupled method is effective. Even if these errors predicted by ANN model are smaller than RF model, and the learning processes of RF model take less time, these methods with ANN model and RF model are all appropriate to predict mechanical properties of composite laminates. [ABSTRACT FROM AUTHOR]

This paper investigates how classical measurement error and additive outliers (AO) influence tests for structural change based onF-statistics. We derive theoretically the impact of general additive disturbances in the regressors on the asymptotic distribution of these tests for structural change. The small sample properties in the case of classical measurement error and AO are investigated via Monte Carlo simulations, revealing that sizes are biased upwards and that powers are reduced. Two-wavelet-based denoising methods are used to reduce these distortions. We show that these two methods can significantly improve the performance of structural break tests. [ABSTRACT FROM AUTHOR]

The hidden Markov model (HMM) has been widely used in regime classification and turning point detection for econometric series after the decisive paper by Hamilton (Econometrica 57(2):357-384, ). The present paper will show that when using HMM to detect the turning point in cyclical series, the accuracy of the detection will be influenced when the data are exposed to high volatilities or combine multiple types of cycles that have different frequency bands. Moreover, outliers will be frequently misidentified as turning points. The present paper shows that these issues can be resolved by wavelet multi-resolution analysis based methods. By providing both frequency and time resolutions, the wavelet power spectrum can identify the process dynamics at various resolution levels. We apply a Monte Carlo experiment to show that the detection accuracy of HMMs is highly improved when combined with the wavelet approach. Further simulations demonstrate the excellent accuracy of this improved HMM method relative to another two change point detection algorithms. Two empirical examples illustrate how the wavelet method can be applied to improve turning point detection in practice. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel cross-linked polymer system consisting of PVA as a core polymer, carbomer as a thickening and suspending agent is developed to prepare hydrogel-forming microneedles (HFMNs). • Two kinds of HFMNs were fabricated, characterised and compared using PVA as the primary material by heating (chemical cross-linking, CCMNs) and freeze-thaw cycles (physical cross-linking, PCMNs). • PCMNs were fabricated using PVA/carbomer via hydrogen bonds. CCMNs were fabricated by cross-linking PVA/carbomer with safe and non-tocix tartaric acid as a cross-linking reagent via covalent bonds. • The fabrication of CCMNs is more efficient and easier than PCMNs. • CCMNs possess more desirable properties for the efficient delivery of glabridin using 15% PVA and 1% carbomer as the building blocks of the hydrogel network compared to PCMNs. Poly(vinyl alcohol) (PVA) and carbomer were used as the hydrogel system to fabricate glabridin-loaded hydrogel-forming microneedles (HFMNs) by chemical cross-linking (CCMNs) and physical cross-linking (PCMNs). The properties and drug permeation effects of glabridin-loaded HFMNs with different methods were compared. They both owned excellent shapes, mechanical and insertion properties. PCMNs showed collapsed shapes during swelling due to the low cross-linking rate and high porosity, which probably results in resealing of skin pores during transdermal drug delivery. However, CCMNs could rapidly swell within 2 h with slightly bending. The infrared spectra indicate that CCMNs and PCMNs might form the hydrogel network by generating hydrogen and covalent bonds, respectively. The in vitro release studies showed that cumulative permeation amount within 24 h (1654 μg/cm2) of CCMNs significantly higher than that (372 μg/cm2) achieved by PCMNs and that (118 μg/cm2) achieved by glabridin-loaded gel. The skin barrier recovery test suggests the desirable security of both microneedles (MNs), notwithstanding the presence of mild erythema in the mouse skin applied CCMNs. These results indicate that CCMNs were more desirable for glabridin delivery using PVA and carbomer as a skeleton of the hydrogel network. [ABSTRACT FROM AUTHOR]

Background: This 8-year follow-up study is aimed at determining the relapse and development of Graves' disease (GD) and the potential risk factors that could be associated with the development of thyroid dysfunction and autoantibodies in Chinese pedigrees. Methods: Fifty-four Chinese Han GD pedigrees (322 members) were recruited in 2000. Forty-five pedigrees (263 members) were followed up. Their clinical and laboratory characteristics and fasting urinary iodine were measured with the same method at the two time points. Results: We found that the mean age for onset of GD in offspring was much younger than that of their parents ( p=0.013). At baseline, the prevalence of hyperthyroidism, hypothyroidism, and subclinical hypothyroidism in first-degree relatives were 5.5%, 1.6%, and 1.1%, respectively. Individuals with thyroid dysfunction were positive for thyroid autoantibodies. The prevalence of positive thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), or TSH receptor antibody (TRAb) in the first-degree relatives with euthyroidism in these pedigrees was 18.6%, 17.4%, or 56.9%, respectively. At follow-up, individuals with positive TPOAb were at risk of developing thyroid dysfunction, whereas patients with positive TRAb had increased risk for relapse even after drug treatment. The percentage of nonsmokers with positive TPOAb and TgAb was significantly higher than that of smokers ( p<0.05), but the levels of serum TRAb were significantly higher in smokers at follow-up than baseline ( p<0.01). Conclusions: Genetic factors are crucial for the development of autoimmune thyroid disease (AITD), thyroid dysfunction, and the outcomes of Graves' patients following treatment with medicines. Although smoking was negatively associated with the presence of thyroid antibodies (TPOAb/TgAb), smoking may induce or aggravate GD. [ABSTRACT FROM AUTHOR]

In this paper, we use simulated data to investigate the power of different causality tests in a two-dimensional vector autoregressive (VAR) model. The data are presented in a nonlinear environment that is modelled using a logistic smooth transition autoregressive function. We use both linear and nonlinear causality tests to investigate the unidirection causality relationship and compare the power of these tests. The linear test is the commonly used Granger causality F test. The nonlinear test is a non-parametric test based on Baek and Brock [A general test for non-linear Granger causality: Bivariate model. Tech. Rep., Iowa State University and University of Wisconsin, Madison, WI, 1992] and Hiemstra and Jones [Testing for linear and non-linear Granger causality in the stock price–volume relation, J. Finance 49(5) (1994), pp. 1639–1664]. When implementing the nonlinear test, we use separately the original data, the linear VAR filtered residuals, and the wavelet decomposed series based on wavelet multiresolution analysis. The VAR filtered residuals and the wavelet decomposition series are used to extract the nonlinear structure of the original data. The simulation results show that the non-parametric test based on the wavelet decomposition series (which is a model-free approach) has the highest power to explore the causality relationship in nonlinear models. [ABSTRACT FROM AUTHOR]

In this article, we use the wavelet technique to improve the over-rejection problem of the traditional Dickey-Fuller tests for unit root when the data is associated with volatility like the GARCH(1, 1) effect. The logic of this technique is based on the idea that the wavelet spectrum decomposition can separate out information of different frequencies in the data series. We prove that the asymptotic distribution of the test in the wavelet environment is still the same as the traditional Dickey-Fuller type of tests. The finite sample property is improved when the data suffers from GARCH error. The investigation of the size property and the finite sample distribution of the test is carried out by Monte Carlo experiment. An empirical example with data on the net immigration to Sweden during the period 1950-2000 is used to illustrate the performance of the wavelet improved test under GARCH errors. The results reveal that using the traditional Dickey-Fuller type of tests, the unit root hypothesis is rejected while our wavelet improved test do not reject as it is more robust to GARCH errors in finite samples. [ABSTRACT FROM AUTHOR]

In this article, we propose a nonlinear Dickey-Fuller F test for unit root against first-order Logistic Smooth Transition Autoregressive (LSTAR) (1) model with time as the transition variable. The nonlinear Dickey-Fuller F test statistic is established under the null hypothesis of random walk without drift and the alternative model is a nonlinear LSTAR (1) model. The asymptotic distribution of the test is analytically derived while the small sample distributions are investigated by Monte Carlo experiment. The size and power properties of the test were investigated using Monte Carlo experiment. The results showed that there is a serious size distortion for the test when GARCH errors appear in the Data Generating Process (DGP), which led to an over-rejection of the unit root null hypothesis. To solve this problem, we use the Wavelet technique to count off the GARCH distortion and improve the size property of the test under GARCH error. We also discuss the asymptotic distributions of the test statistics in GARCH and wavelet environments. [ABSTRACT FROM AUTHOR]

The development of high-energy-density electrostatic capacitors is critical to addressing the growing electricity need. Currently, the widely studied dielectric materials are polymer nanocomposites incorporated with high-dielectric-constant nanoparticles. However, the introduction of high-dielectric-constant nanoparticles can cause local electric field distortion and high leakage current, which limits the improvement in energy density. In this work, on the basis of conventional polymer nanocomposites containing high-dielectric-constant nanoparticles, oriented boron nitride nanosheets (BNNSs) are introduced as an extra filler phase. By changing the volume ratios of barium titanate (BT) and BNNSs, the dielectric property of polymer nanocomposites is adjusted, and thus the capacitive energy storage performance is optimized. Experimental results prove that the oriented BNNSs can suppress the propagation of charge carriers and decrease the conduction loss. Using poly(vinylidene fluoride-co-hexafluoropropylene) (P(VDF-HFP)) as the polymer matrix, the P(VDF-HFP)/BNNS/BT nanocomposite has a higher discharged energy density compared with the conventional nanocomposite with the freely dispersed BT nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Paroxysmal Supraventricular Tachycardia (PSVT) resulting from any cause can at times lead to diagnostic difficulty mainly when due to AVNRT and AVRT. In this study we used a non-invasive approach using esophageal ECG (ECGe) and ECG derived from the various right parasternal chest leads (RPCL) to correctly diagnose the type of PSVT as well the accessory pathways involved in AVRT. Methods and results: We studied a total of 161 patients (89 male) all having a history of palpitation. All the patients underwent routine 12 lead ECG, ECGe, RPCL and electrophysiologic study. With use of ECGe and RPCL, 71 (44.1%) were diagnosed as having AVNRT and 90 (55.9%) having AVRT with various accessory pathways compared to only 49 (30.4%) and 22 (13.7%) respectively with routine 12 lead ECG. With combined ECGe and RPCL, 80 (49.7%) showed accessory pathway in the left free wall, 4 (2.5%) showed in the right free wall, 6 (3.7%) septal accessory pathway, 60 (37.3%) in the anterior wall and 30 (18.6%) in the posterior wall. In comparison, EPS could show accessory pathways in the left free wall in 81 (50.3%), in the right free wall in 5 (3.1%), in the septum in 4 (2.5%), in the anterior wall in 53 (32.9%) and in the posterior wall in 37 (23.0%) out of the 161 patients. Conclusions: ECGe+RPCL can be used as a reliable noninvasive diagnostic tool to identify the nature of tachycardia and the pathways involved in the reentrant ring of PSVT especially in those with multiple atrioventricular accessory pathways or a combination of atrioventricular accessory pathways and dual atrioventricular nodal pathway. [Copyright &y& Elsevier]

[Display omitted] • Perchlorate turn-on sensing by supramolecular self-assembly of platinum(II) complex. • Hydrogel matrix was introduced to terminate the diffusion of generated 1D aggregates. • Direct, ultrasensitive and rapid detection of perchlorate particulate was realized. • Limit of detection with 1.12 ng by naked eye and 0.11 fg by common optical microscope was achieved. Onsite ultrasensitive identification of the airborne or deposited perchlorate particulates is crucial for homeland security, forensic analysis, and environment monitoring. However, few of the currently developed luminescent sensor focus on the direct and ultratrace detection of its solid particulates as the low level of analyte and the difficulty in exhaustive collection of the trace sample. Here, a general design strategy for the direct, ultrasensitive, and specific luminescent turn-on sensing of perchlorate particulates is proposed by triggering supramolecular self-assembly of cationic platinum(II) complex in a hydrogel matrix, in which the self-assembly of platinum(II) complex endows the luminescence turn-on response and the hydrogel matrix creates excellent confinement effect for terminating the diffusion of generated luminescent 1D aggregates. The proposed hydrogel-based sensor is capable to detect the airborne perchlorate particulate of 1.12 ng by naked eye and 0.11 fg by common optical microscope. Further practical sensing performances for real firecracker and buried perchlorate in soil demonstrates the excellent environmental adaptability, and the latent fingerprint visualization shows great potential for clue tracking. This study provides an inspirable strategy for designing ultrasensitive luminescent sensor for trace solid sample. [ABSTRACT FROM AUTHOR]

The rapid growth of the global population has resulted in a considerable increase in the demand for food crops. However, traditional crop breeding methods will not be able to satisfy the worldwide demand for food in the future. New gene-editing technologies, the most widely used of which is CRISPR/Cas9, may enable the rapid improvement of crop traits. Specifically, CRISPR/Cas9 genome-editing technology involves the use of a guide RNA and a Cas9 protein that can cleave the genome at specific loci. Due to its simplicity and efficiency, the CRISPR/Cas9 system has rapidly become the most widely used tool for editing animal and plant genomes. It is ideal for modifying the traits of many plants, including food crops, and for creating new germplasm materials. In this review, the development of the CRISPR/Cas9 system, the underlying mechanism, and examples of its use for editing genes in important crops are discussed. Furthermore, certain limitations of the CRISPR/Cas9 system and potential solutions are described. This article will provide researchers with important information regarding the use of CRISPR/Cas9 gene-editing technology for crop improvement, plant breeding, and gene functional analyses. [ABSTRACT FROM AUTHOR]

Ferroelectric polymers have been widely explored for film capacitor applications due to their high energy storage densities that are almost an order of magnitude greater than those of the commercial capacitor dielectrics. However, the existing ferroelectric polymers are designed exclusively for room-temperature operation, and suffer from poor capacitive performance at elevated temperature, which falls short of the need in the emerging harsh-environment applications. In this paper, we report multilayered ferroelectric polymer composites exhibiting simultaneous high energy density and high discharge efficiency at elevated temperature. The multilayered composites consist of two copolymers of polyvinylidene fluoride (PVDF) with similar chemical structures but distinct dielectric properties, where one contributes to high electrical polarization and the other offers high thermal stability and suppresses charge injection. More importantly, we demonstrate that the critical issue of charge conduction at elevated temperature in ferroelectric polymers is well tackled by the established highly miscible interlayer interfaces in the multilayered structure set up between the two electrically dissimilar phases. At 70 °C, the maximum discharged energy density above 80% discharge efficiency of the multilayered composites reaches 15.5 J/cm3, far outperforming all the existing ferroelectric polymers. This work sheds light on the design of high-energy-density ferroelectric polymers for high temperature capacitive energy storage. Image 1 [ABSTRACT FROM AUTHOR]

Aggregation‐induced emission (AIE) shows promising performance in chemical sensing relying on the change of the emission behavior of the probe molecule monomers to the aggregated product. However, whether the response contrast could be further boosted by utilizing the emission property of the aggregated probe and the aggregated product remains a big challenge. Here, an exciting AIE probe regulation strategy was proposed by coherently modulating the aggregation behavior and the intramolecular charge transfer (ICT) property of the probes and thus an aggregated‐to‐aggregated colorimetric‐fluorescent dual‐mode detection was achieved. The blue emissive film obtained with the optimal AIE probe has been proven to be effective to recognize the vapor of nerve agent analog DCP in air by emitting a sharp green fluorescence. In addition, a porous polymer‐based wet sensing chip loaded with the probe enables the immediate response to DCP vapor with a limit of detection (LOD) of 1.7 ppb, and it was further integrated into a wearable watch device for long‐term monitoring of DCP vapor up to two weeks. We expect the present probe design strategy would greatly deepen the AIE‐based science and provide new insights for long‐term monitoring sensors toward trace hazardous substances. [ABSTRACT FROM AUTHOR]

Aggregation‐induced emission (AIE) shows promising performance in chemical sensing relying on the change of the emission behavior of the probe molecule monomers to the aggregated product. However, whether the response contrast could be further boosted by utilizing the emission property of the aggregated probe and the aggregated product remains a big challenge. Here, an exciting AIE probe regulation strategy was proposed by coherently modulating the aggregation behavior and the intramolecular charge transfer (ICT) property of the probes and thus an aggregated‐to‐aggregated colorimetric‐fluorescent dual‐mode detection was achieved. The blue emissive film obtained with the optimal AIE probe has been proven to be effective to recognize the vapor of nerve agent analog DCP in air by emitting a sharp green fluorescence. In addition, a porous polymer‐based wet sensing chip loaded with the probe enables the immediate response to DCP vapor with a limit of detection (LOD) of 1.7 ppb, and it was further integrated into a wearable watch device for long‐term monitoring of DCP vapor up to two weeks. We expect the present probe design strategy would greatly deepen the AIE‐based science and provide new insights for long‐term monitoring sensors toward trace hazardous substances. [ABSTRACT FROM AUTHOR]

A number of studies have shown that aldosterone serves an important role in promoting renal interstitial fibrosis, although the specific mechanism remains to be elucidated. A previous study revealed that the fibrotic effect of aldosterone was associated with the expression of allograft inflammatory factor 1 (AIF-1) in RAW264.7 macrophage cells, in a time- and concentration-dependent manner. However, the exact mechanism through which aldosterone promotes renal interstitial fibrosis remains unknown. In the present study, the effects of aldosterone on renal inflammatory cell infiltration, collagen deposition and the expression levels of AIF-1, phosphatidylinositol 3-kinase (PI3K), AKT serine/threonine kinase (AKT), mammalian target of rapamycin (mTOR), the oxidative stress factor NADPH oxidase 2 (NOX2) and nuclear transcription factor erythroid-related factor 2 (Nrf2) were assessed in normal rats, rats treated with aldosterone, rats treated with aldosterone and spironolactone and those treated with spironolactone only (used as the control). The effect of aldosterone on these factors was also investigated in the renal interstitium of unilateral ureteral obstruction (UUO) rats. Additionally, the AIF-1 gene was overexpressed and knocked down in macrophage RAW264.7 cells, and the effects of aldosterone on PI3K, AKT, mTOR, NOX2 and Nrf2 were subsequently investigated. The results showed that aldosterone promoted inflammatory cell infiltration, collagen deposition and the expression of AIF-1, PI3K, AKT, mTOR and NOX2, but inhibited the expression of Nrf2. In the UUO rats, aldosterone also promoted renal interstitial inflammatory cell infiltration, collagen deposition and the expression of AIF-1, NOX2, PI3K, AKT and mTOR, whereas the expression of Nrf2 was downregulated by aldosterone compared with that in the UUO-only group; the influence of aldosterone was counteracted by spironolactone in the normal and UUO rats. In vitro, aldosterone upregulated the expression levels of AKT, mTOR, NOX2 and Nrf2 in RAW264.7 cells compared with those in untreated cells. Suppressing the expression of AIF-1 inhibited the effects of aldosterone, whereas the overexpression of AIF-1 enhanced these effects in RAW264.7 cells. These findings indicated that aldosterone promoted renal interstitial fibrosis by upregulating the expression of AIF-1 and that the specific mechanism may involve AKT/mTOR and oxidative stress signaling. [ABSTRACT FROM AUTHOR]

Objective: Gestational transient thyrotoxicosis (GTT) and Graves' disease (GD) are the most common causes of hyperthyroidism during pregnancy. However, few studies have compared pregnancy outcomes of patients who had GTT with those who had GD in the first trimester of pregnancy. Methods: We conducted a prospective multicenter cohort study in China. Participants received questionnaires, physical examinations, and underwent measurements of thyrotropin (TSH), free thyroxine (fT4), thyroid peroxidase antibody (TPOAb), TSH receptor antibody (TRAb), and urinary iodine in the first trimester. The patients diagnosed with either GTT or GD and normal thyroid function (NTF) group were followed until delivery. The thyroid function and pregnancy outcomes were reported. Results: A total of 125 pregnant women with thyrotoxicosis and 246 age-matched pregnant women with NTF were included. (1) The thyroid function of the GTT group returned to normal range in the third trimester, but was consistently abnormal in the GD group. (2) The incidence of gestational diabetes mellitus (GDM) in the GTT group (11.5%, 9/78) was significantly higher than that in NTF group (4.9%, 12/246) (p = 0.037). The incidence of premature delivery in the GD untreated (30.8%, 8/26, p = 0.002) and treated groups (28.6%, 6/21, p = 0.008) was both, respectively, higher than that in the NTF group (7.7%, 19/246). Miscarriage (15.4%, 4/26 vs. 3.7%, 9/246, p = 0.026) and gestational hypertension (19.2%, 5/26 vs. 3.3%, 8/246, p = 0.004) were more prevalent in the GD untreated group than in the NTF group. (3) The presence of positive TRAb and positive TPOAb in the first trimester were independent risk factors for miscarriage (odds ratio [OR] = 5.23, confidence interval [CI] = 1.11–24.78, p = 0.037) and low birth weight infants (OR = 7.76, CI = 1.23–48.86, p = 0.029), respectively. Conclusion: In conclusion, pregnancy outcomes appear variable, according to the etiology of first trimester thyrotoxicosis. GTT appears to be associated with GDM. GD appears to be associated with an increased risk of premature delivery, gestational hypertension, and miscarriage. The diagnosis of GTT and GD patients during early pregnancy and appropriate treatment of GD patients may be associated with improved pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Plants facing the seasonal variations always need a growth restraining mechanism when temperatures turn down. C-repeat binding factor (CBF) genes work essentially in the cold perception. Despite lots of researches on CBFs, the multiple crosstalk is still interesting on their interaction with hormones and dormancy-associated MADS (DAM) genes in the growth and dormancy control. Therefore, this study highlights roles of PmCBFs in cold-induced dormancy from different orgens. And a sense-response relationship between PmCBFs and PmDAMs is exhibited in this process, jointly regulated by six PmCBFs and PmDAM4–6. Meantime, GA3 and ABA showed negative and positive correlation with PmCBFs expression levels, respectively. We also find a high correlation between IAA and PmDAM1–3. Finally, we display the interaction mode of PmCBFs and PmDAMs, especially PmCBF1-PmDAM1. These results can disclose another view of molecular mechanism in plant growth between cold-response pathway and dormancy regulation together with genes and hormones. [ABSTRACT FROM AUTHOR]

In order to sensitively detect trace nitro-explosive vapors, the sensing properties of ZnO nanoparticles (NPs) are boosted by tailoring the doping level of indium (In). With the introduction of In, the shape of the ZnO NPs changes from sphere with grain size of 55.2 ± 9.6 nm to irregular NPs with a reduced size. The sensing performances of sensors towards room-temperature saturated nitro-explosive vapors generally increase firstly and then decrease, peaking at an atomic ratio of 1.29% (corresponding to 5% In in the precursor). The 5% In-doped ZnO nanoparticle-based sensor exhibited remarkably enhanced responses towards trace nitro-explosive vapors, including TNT of 9 ppb, DNT of 411 ppb, PNT of 647 ppb, PA of 0.97 ppb and RDX of 4.9 ppt at room temperature. For instance, compared with ZnO, the responses to nitro-explosive vapors were increased from 22.2, 8.5, 2.9, 4.9 and 9.8% to 54.7, 52.9, 57.2, 58.3 and 47.4%, respectively. Furthermore, much shorter response time (<6.3 s vs. 20–40 s) and recovery time (<14 s vs. 20–40 s) were achieved, which is of vital importance for on-site explosive detection. Combining the surface oxygen defects investigation, it is found that the remarkably increased oxygen vacancies are responsible for the sensing performance improvement. [ABSTRACT FROM AUTHOR]

The ZnO/rGO core/shell micro-Schottky junction was successfully prepared via a one-step facile hydrothermal method. It is found that the resulting gas sensor exhibited excellent capability to detect trace vapor of nitro-explosives, typically, the responses towards 9 ppb 2,4,6-trinitrotoluene (TNT) and 4.9 ppt hexogen (RDX) reach to 56.8% and 80%, respectively, and all the response times are less than 5 s. Most importantly, superior anti-interfering property is shown even towards interfering gases of ppm level. Furthermore, it is demonstrated that with the wrapping of rGO, the response values of the pure ZnO-based sensor for TNT and RDX detection were boosted by 5.5 and 3.4 times. The enhanced sensing performance is attributed to the micro-Schottky junction built at the interface of ZnO and rGO. The present work demonstrates that the ZnO/rGO core/shell micro-Schottky junction is an excellent candidate material for explosives detection. [ABSTRACT FROM AUTHOR]

Objective: The use of antithyroid drugs (ATDs) carries potential risk for teratogenic effects. For women with well-controlled hyperthyroidism on a low dose of ATDs, drug withdrawal upon pregnancy is recommended by international medical guidelines. Therefore, it is necessary to determine the characteristics of patients suitable for ATD withdrawal, subsequent changes in thyroid function after ATD discontinuation, and its impact on pregnancy and offspring outcomes. Methods: This prospective study recruited 63 pregnant women with well-controlled Graves' hyperthyroidism who had stopped ATDs during early pregnancy. Patients were followed up until the end of pregnancy and data on pregnancy outcomes were collected. Results: Overall, 20 patients (31.7%) had rebound of hyperthyroidism. Patients with either subnormal thyrotropin (TSH) levels (TSH <0.35 mIU/L, odds ratio [OR] = 5.12, confidence interval [CI = 1.29–20.34], p = 0.03) or positive thyrotropin receptor antibody (TRAb) (TRAb >1.75 IU/L, OR = 3.79, [CI = 1.17–12.30], p = 0.02) at the time of ATDs withdrawal presented a higher risk of rebound than those with either normal TSH levels or negative TRAb. Patients with both subnormal TSH and positive TRAb at the time of ATD withdrawal were more likely to experience rebound (83.3%, 5/6) than those with both normal TSH and negative TRAb (13%, 3/23, OR = 33.33, [CI = 2.83–392.60], p = 0.003). The prevalence of adverse pregnancy outcomes was significantly higher in patients who experienced rebound compared with those who did not (55.0% vs. 9.3%, OR = 11.92, [CI = 3.08–46.18], p = 0.0002). Conclusions: Subnormal TSH levels and TRAb positivity at the time of ATD withdrawal in early pregnancy may be associated with rebound of Graves' hyperthyroidism. Rebound of hyperthyroidism during pregnancy may increase the risk of adverse pregnancy outcomes. Larger prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Recent clinical studies have demonstrated the suppressive effect of selenium (Se) treatment on serum thyroid-specific antibody titers in patients with autoimmune thyroiditis (AIT), but the mechanism underlying this process is not clear. The aim of the present study was to investigate the effects of selenium on the incidence and severity of AIT, titers of thyroid autoantibodies, and selenoprotein expression in thyroid in a spontaneous autoimmune thyroiditis (SAT) model. Methods: NOD.H-2h4 mice at four weeks of age were randomly divided into control, iodine supplement (SAT), and selenium supplement groups (SAT+Se). Mice were given 0.005% sodium iodide water for eight weeks to induce SAT and then 0.3 mg/L sodium selenite in drinking water for 8 weeks and 16 weeks. The severity of lymphocytic infiltration in the thyroid, serum thyroglobulin antibody (TgAb) titers, serum selenium concentration, expression of glutathione peroxidase-1 (GPx1), thioredoxin reductase-1 (Txnrd1), and peroxiredoxin 5 were measured. Results: Serum selenium concentration significantly increased after selenium supplementation. Serum TgAb levels were significantly lower in the selenium group compared with the SAT group ( p<0.05). The prevalence of thyroiditis and the degree of infiltration of lymphocytes decreased gradually over time in the group provided with selenium supplementation. The expression of GPx1 and Txnrd1 by Western blotting were found to be significantly higher in the SAT+Se group than in other groups ( p<0.05). Conclusions: These results indicate that selenium treatment can increase the function of antioxidation by upregulating the expression of selenoproteins in the thyroid and have an inhibitory effect on TgAb titers, which may have an impact on AIT. [ABSTRACT FROM AUTHOR]

Determining the allowable compression load (ACL) of notched composite laminates (NCL) requires consideration of buckling, intra- and inter-laminar damage, which is a costly and repetitive task due to the high dimensional and nonlinear relation of ACL to the numerous design variables. In this work, a high-throughput finite element analysis (FEA) and machine learning (ML) combined approach is proposed to predict ACL of laminates. First, the high-throughput FEA model of NCL covering all of the design variables is generated, and the corresponding critical compression loads in terms of buckling, intra- and inter-laminar damage are obtained. Then, ML models are trained, with inputs being the design variables of NCL and outputs being the critical compression loads. ACL and initial failure mode are determined by the minimum compression load of the three failure modes. Moreover, transfer learning is introduced to laminates with new design variables of new ply number, notch shape and laminate type. By fine-tuning the pre-trained ML model using scarce new data, the fine-tuned models are suitable for new laminates. Consequently, ACL and initial failure mode of notched laminates with various design variables are predicted. [ABSTRACT FROM AUTHOR]

Failure assessment is one of the fundamental tasks for optimization of composite pressure vessels (CPVs). However, the extensive design space of composites usually leads to costly and repetitive work of failure assessment that hinders the design and optimization of CPVs. In this work, a combined FEM simulation and machine learning approach is used to predict the failure factors R of CPVs for further optimization. CPVs with various design parameters are automatically generated and analyzed in ABAQUS to obtain failure factors under various external loadings. Then, an assembled deep neural network (DNN) namely Multi-DNN is trained to map relations between design parameters and R of CPVs. Further, transfer learning (TL) is introduced to improve the extensibility of our approach by fine-tuning the pre-trained Multi-DNN using scarce data of new design space. Such a TL-Multi-DNN model can precisely predict R of CPVs with new design parameters. Additionally, combining the trained models and genetic algorithm, the optimization of CPVs is carried out with high efficiency and low computational cost. As a result, R of CPV with various given and new design parameters can be estimated directly by the trained models and the optimal layer sequence of CPV can be obtained efficiently. [ABSTRACT FROM AUTHOR]

This study investigates the intricate interplay of hydraulic coupling, creep damage, and permeability evolution mechanisms in phyllite, focusing on their relevance to tunnel engineering design and long-term stability in soft rock formations. To achieve this, conventional triaxial tests were conducted on saturated phyllite specimens under creep-seepage acoustic emission conditions. The results were systematically analyzed to unveil the inherent characteristics of creep deformation, seepage rate evolution, and damage progression in phyllite when subjected to stress–seepage coupling. Furthermore, a permeability model for representative volume element (RVE) was developed based on meso-mechanics principles, considering the distinctive attributes of low-permeability non-Darcy’s flow in rock. Consequently, a novel relationship between effective damage and permeability was established. We determined that seepage pressure induces three key effects on the creep damage mechanism of phyllite samples: (1) It adds to the existing stress through the superposition of osmotic pressure and axial load, (2) it induces tensile expansion stress because of pore water pressure, and (3) it softens the fracture surfaces to some extent. More importantly, this study validates the relationship between effective damage and permeability through the fitting of creep and damage parameters, which were obtained from the test results, and it reveals a square relationship between subsequent damage and permeability under stress conditions. The findings of this study provide a robust theoretical foundation for comprehending the evolution of damage and permeability characteristics during the creep process of rock under seepage conditions. We obtained essential insights and quantitative analyses for comprehending the damage mechanisms in rock creep under hydraulic coupling, which has significant implications for tunnel engineering and long-term rock stability assessments in soft rock environments. [ABSTRACT FROM AUTHOR]

published July 14, 2009; doi: 10.1 152/ajpendo.00205.2009.-Ghrelin is a stomach-derived peptide that has growth hormone-stimulating and orexigenic activities. Although there have been several reports of ghrelinoma cases, only a few cases have elevated circulating ghrelin levels, hampering the investigation of pathophysiological features of ghrelinoma and chronic effects of ghrelin excess. Furthermore, standard transgenic technique has resulted in desacyl ghrelin production only because of the limited tissue expression of ghrelin O-acyltransferase, which mediates acylation of ghrelin. Accordingly, we attempted to create ghrelin promoter SV4O T-antigen transgenic (OPTag Tg) mice, in which ghrelin-producing cells continued to proliferate and finally developed into ghrelinoma. Adult OP-Tag Tg mice showed elevated plasma ghrelin levels with preserved physiological regulation. Adult OP-Tag Tg mice with increased plasma ghrelin levels exhibited elevated IOF-I levels despite poor nutrition. Although basal growth hormone levels were not changed, those after growth hormone-releasing hormone injection tended to be higher. These results indicate that chronic elevation of ghrelin activates OH-IOF-I axis. In addition, OP-Tag Tg mice demonstrated glucose intolerance. Insulin secretion by glucose tolerance tests was significantly attenuated in OP-Tag Tg, whereas insulin sensitivity determined by insulin tolerance tests was preserved, indicating that chronic elevation of ghrelin suppresses insulin secretion and leads to glucose intorelance. Thus, we successfully generated a Tg model of ghrelinoma, which is a good tool to investigate chronic effects of ghrelin excess. Moreover, their characteristic features could be a hint on ghrelinoma. [ABSTRACT FROM AUTHOR]

Background: Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by increased bone fragility and a series of extraskeletal manifestations. Approximately 90 % of OI cases are caused by type I collagen variants encoded by the collagen type I alpha 1 (COL1A1) or type I alpha 2 (COL1A2) gene. Lumbar Scheuermann's disease is an atypical type of Scheuermann's disease accompanied by Schmorl's nodes and irregular endplates but without pronounced kyphosis. Although the etiology of Scheuermann's disease is unclear, genetic and environmental factors are likely.Case Presentation: Here, we report a 32-year-old male patient who experienced multiple brittle fractures. Gene sequencing revealed a heterozygous mutation, c.4048G > A (p.G1350S), in the COL1A2 gene, and the patient was diagnosed with OI. Magnetic resonance imaging of his thoracolumbar spine revealed multiple Schmorl's nodes.Conclusions: This is the first reported case of OI coexisting with the spinal presentation of Scheuermann's disease. It is speculated that the COL1A2 gene mutation might be an underlying novel genetic cause of Scheuermann's disease. In conclusion, this case demonstrates the relationship between Scheuermann's disease and OI for the first time and enriches the genotype-phenotype spectrum of OI. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are a class of critical epigenetic regulators involved in several autoimmune diseases. Our previous study reported an miR-326-induced increase in T helper (Th) 17 cells in a mouse model of Hashimoto's thyroiditis (HT), but the pathogenic effect of miR-326 in HT patients has not been verified. The goal of the present study was to explore the pathogenic role of miR-326 and its underlying molecular mechanism in HT patients. Methods: A total of 58 HT patients and 55 normal controls were enrolled in this study. We examined whether Th17 cells and miR-326 were aberrantly altered in the peripheral blood mononuclear cells (PBMCs) of HT patients with flow cytometry and real-time polymerase chain reaction. Levels of membrane interleukin (IL)-23R (mIL-23R) were determined by flow cytometry and Western blot to explore the critical role of mIL-23R in the development of Th17 cells. Isolated CD3+ T cells were used to further investigate the ectodomain shedding of mIL-23R by a disintegrin and metalloprotease (ADAM17). Furthermore, miR-326 inhibitor and mimics were transfected into PBMCs derived from HT patients and healthy controls to verify the regulation of ADAM17 by miR-326. Results: We observed elevated miR-326 levels in the PBMCs of HT patients compared with those in the PBMCs of healthy controls. Consistent with IL-23-induced STAT3 overactivation, substantially more HT patient-derived PBMCs differentiated into Th17 cells under polarization culture conditions, which may, at least in part, have resulted from enhanced mIL-23R levels. Furthermore, ADAM17, an ectodomain sheddase of mIL-23R, was targeted and negatively regulated by miR-326. Inhibiting ADAM17 might attenuate the ectodomain shedding of mIL-23R. Conclusions: Our findings suggest that the effect of miR-326 on the IL-23/IL-23R/Th17 cell axis in HT patients might be partially due to the targeting of ADAM17. [ABSTRACT FROM AUTHOR]

To understand the underlying fundamental mechanism affecting the optical sensitivity of a paper‐based substrate, a layered polyvinyl alcohol (PVA) network paper is proposed considering the physical geometry and chemical composition required to enhance the sensitivity. It is verified both theoretically and experimentally that the dimension confinement effect introduced by the Steiner network, layered and pore structures, as well as massive hydroxyl groups, play an essential role in enhancing the concentration signal on the surface. Trace chlorate droplets and particles are considered representative examples to prove the excellent structural design‐induced performance of the PVA network paper. A practical mass detection from potassium chlorate solution and particles could be as low as 9.9 pg and 0.34 fg, respectively, and the corresponding naked‐eye observation limit could reach 0.69 ng and 1.6 pg, respectively, assuming the distinguishable size for human eyes is 100 µm. Further, the detection time could be far less than 2 s, which is remarkably superior than the detection performance of the parallel filter paper counterpart. The dimension confinement effect demonstrated here is expected to be of great importance for advancing the development of paper‐based trace detection. [ABSTRACT FROM AUTHOR]

Abstract: Bi3.15Nd0.85Ti3O12 (BNT) ferroelectric thin films were grown on Pt/Ti/SiO2/Si substrates by a sol–gel method. The samples were exposed to different dosage of ionizing radiation. Distortions in the crystalline structure, changes in the surface roughness and decrease in the remnant polarization were observed after radiation. For films subjected to 100Mrad radiation, decrease in the leakage current up to four orders of magnitude was also observed, which can be explained by the increased grain boundary barrier height. Our results suggest that ionizing radiation could be an effective tool in modifying the properties of ferroelectric thin film for use in non-volatile memory devices. [Copyright &y& Elsevier]

Background: There is growing evidence that sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite synthesized intracellularly by two closely related sphingosine kinases (SphKs), SphK1 and SphK2, is involved in inflammation. However, the role of SphKs/S1P/S1P receptors (S1PRs) in autoimmune thyroiditis (AIT) has not been studied to date. Methods: This study examined whether SphK1/S1P/S1PR1 signaling is aberrantly altered in thyroid tissues and serum of both AIT patients and a spontaneously autoimmune thyroiditis (SAT) mouse model. Murine CD4+T cells were employed to further investigate the downstream signaling of SphK1/S1P/S1PR1. Furthermore, a total of 102 NOD.H-2h4 mice, randomly divided into different groups, were used to investigate the therapeutic effect of S1PR1 blockade and its potential mechanism. Results: We found that components of the SphK1/S1P/S1PR1 pathway were abnormally expressed in patients with Hashimoto thyroiditis and in a SAT mouse model. In addition, S1P could activate signal transducer and activator of transcription 3 (STAT3) through S1PR1 and its downstream signaling pathways in CD4+T cells of NOD.H-2h4 mice. Furthermore, an in vivo study demonstrated that blocking S1PR1 by FTY720 administration could reduce the incidence and severity of thyroiditis and goiter in SAT mice in a time-dependent manner. The proportions of STAT3-related and inflammation-related cell subtypes, such as T helper 1, T helper 17, and follicular T helper cells, were elevated in the SAT group when compared to the control group, and these cell subtypes decreased after FTY720 administration. Furthermore, the downstream inflammatory cytokines of STAT3 were also downregulated after FTY720 administration. Conclusion: The present study shows that blocking Sphk1/S1P/S1PR1 signaling can ameliorate the severity of AIT, providing evidence of a promising therapeutic target for AIT. [ABSTRACT FROM AUTHOR]

Objective. The purpose of the present study was to investigate serum trace elements in Graves’ disease (GD) patients with or without orbitopathy in Northeast China. Methods. Patients with newly diagnosed Graves’ disease (HyGD) (n=66), GD patients with euthyroid status or subclinical thyroidism after treatment (EUGD) (n=55), GO patients with euthyroid status or subclinical thyroidism after treatment (GO) (n=57), and normal controls (NC) (n=66) were enrolled in this study. Serum trace elements were measured with ICP-MS. Results. Serum selenium (Se) levels in EUGD group (median: 7.53 µg/dL), HyGD group (median: 6.76 µg/dL), and GO group (median: 7.40 µg/dL) were significantly lower than those in NC group (median: 9.20 µg/dL, all P<0.01). Serum copper (Cu) levels in GO group (median: 95.93 µg/dL) were significantly lower than those in the NC group (median: 113.59 µg/dL, P=0.015). After being adjusted for multivariables, thyroid-specific antibodies grade was associated with low Se levels. Hyperthyroidism and thyroid-specific antibodies grade were associated with high Cu levels. In addition, orbitopathy was associated with low Cu levels. Conclusions. Thyroid autoimmunity was associated with low Se levels. Hyperthyroidism and thyroid autoimmunity may be associated with relatively high serum Cu levels. Alternatively, ophthalmopathy may be related to low serum Cu levels. [ABSTRACT FROM AUTHOR]

Th17 and regulatory lymphocyte subsets such as Tregs and Bregs have been reported to play important roles in autoimmune diseases. The aim of this work was to perform quantitative studies of circulating Th17, Tregs, and Bregs in patients with new-onset Graves’ disease (GD). Twenty GD patients and 20 healthy controls were involved in this study. Blood samples were taken for flow cytometry detection of CD4+IL-17+ Th17, CD4+Foxp3+ Tregs, and CD19+CD1dhiCD5+ Bregs and meanwhile, for real-time PCR measurement of gene expressions of RORγt, IL-17 and IL-10. The proportions of Tregs and Bregs as well as the Foxp3 gene expression but not IL-10 were significantly decreased in GD group compared with the healthy controls. The frequency of Th17 together with the gene expressions of RORγt and IL-17 were significantly increased in the GD group. Furthermore, the Th17/Treg ratio was also significantly higher in GD group. A significant positive correlation between Th17 and TSAb (r=0.656, p<0.001) but significant negative correlations between Treg/Breg and TSAb (r=-0.339, p=0.032; r=-0.759, p<0.001) were identified among the participants. This study indicated that increased Th17 and impaired Treg responses, along with a decreased number of CD19+CD1dhiCD5+ Breg cells, were involved in GD pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The migration of cardiac fibroblasts to the infarct region plays a major role in the repair process after myocardial necrosis or damage. However, few studies investigated whether early hypoxia in cardiomyocytes induces the migration of cardiac fibroblasts. The purpose of this study was to assess the role of metabolites of early hypoxic cardiomyocytes in the induction of cardiac fibroblast migration. Methods: Neonatal rat heart tissue was digested with a mixture of trypsin and collagenase at an appropriate ratio. Cardiomyocytes and cardiac fibroblasts were cultured via differential adhesion. The cardiomyocyte cultures were subjected to hypoxia for 2, 4, 6, 8, 10, and 12 h. The supernatants of the cardiomyocyte cultures were collected to determine the differences in cardiac fibroblast migration induced by hypoxic cardiomyocyte metabolites at various time points using a Transwell apparatus. Meanwhile, ELISA was performed to measure TNF-α, IL-1β and TGF-β expression levels in the cardiomyocyte metabolites at various time points. Results: The metabolites of hypoxic cardiomyocytes significantly induced the migration of cardiac fibroblasts. The induction of cardiac fibroblast migration was significantly enhanced by cardiomyocyte metabolites in comparison to the control after 2, 4, and 6 h of hypoxia, and the effect was most significant after 2 h. The expression levels of TNF-α, IL-1β, IL-6, and TGF-β were substantially increased in the metabolites of cardiomyocytes, and neutralization with anti-TNF-α and anti-IL-1β antibodies markedly reduced the induction of cardiac fibroblast migration by the metabolites of hypoxic cardiomyocytes. Conclusion: The metabolites of early hypoxic cardiomyocytes can induce the migration of cardiac fibroblasts, and TNF-α and IL-1β may act as the initial chemotactic inducers. [ABSTRACT FROM AUTHOR]

Persistent infection with human papillomavirus (HPV), particularly type 16, is causally associated with cervical cancer and its precursors. The role of miRNAs in HPV16 persistence currently remains unclear. Preliminary analysis of miRNA profile demonstrated that HPV16 infection caused a striking downregulation of miR-34a. Through bioinformatics analysis and dual-luciferase assay with site-directed mutagenesis strategy, NLRC5, a negative regulator of NF-κB signaling, was identified to be a novel interactor of miR-34a. Transfection of miR-34a mimic strikingly downregulated NLRC5 in the HPV16-positive cervical cells, which might result in the nuclear accumulation of NF-κB p65. However, transfection of miR-34a inhibitor exhibited an opposite effect. The antagonistic expressions of NLRC5 and miR-34a were also observed in keratinocytes harboring HPV16 genome as well as in human cervical samples with persistent infection of HPV16. Our data uncover a previously unknown connection among HPV16 persistence, miR-34a and its interactor NLRC5. [ABSTRACT FROM AUTHOR]

In order to sensitively, selectively, and rapidly detect the constituents relevant to improvised explosive devices (IEDs), the sensing properties of ZnS nanocrystals (NCs) are regulated by tailoring the doping level of Mn2+. The responses of the sensors fabricated by ZnS NCs with different Mn-doping levels (Mn:ZnS) toward the constituents, such as sulphur powder and black powder, generally increases first and then decreases with the increase of the concentration of doped Mn2+, and reaches the climate with an atomic ratio of 2.23% at room temperature. The sensory array based on eight sensors of Mn:ZnS NCs can realize the detection of two typical military explosives and six constituents relevant to IEDs within 7 s and can recover in 19 s. Furthermore, the fingerprinting of the constituents is achieved by pattern recognizing the inherent kinetics and thermodynamics of interaction between the sensory array and the constituents. Thus, a simple chemiresistive sensing strategy based on semiconductor NCs which can rapidly, supersensitively, and discriminatively detect the constituents relevant to IEDs is explored for the first time. [ABSTRACT FROM AUTHOR]