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Abstract Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan–Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024–1.692; P

Thermoelectric materials play a crucial role in converting heat into electricity, offering significant potential for applications in waste heat recovery and cooling. Herein, an innovative approach that combines an organic–inorganic hybrid superlattice structure with nanocrystal‐amorphous composite nanolayers is introduced. The nanocrystal‐amorphous composite enhances the Seebeck coefficient resulting in a notable twofold improvement in the power factor. The superlattice, alternating self‐assembled organic monolayers and inorganic nanolayers, effectively reduces lattice thermal conductivity by creating multiple interfaces that scatter phonons effectively. The integration of the nanocrystal‐amorphous composite nanolayers into the superlattice provides a dual advantage, simultaneously boosting the power factor and suppressing thermal conductivity. This synergistic effect leads to exceptional thermoelectric performance in the 4‐mercaptophenol/Sb2Te3 superlattice, with achieved figure of merit (ZT) values of 3.48 at 300 K and reaching a peak ZT value exceeding 4.0 at 400 K while surpassing 2.5 over the temperature range from 300 to 500 K. These results suggest that this innovative approach paves the way for the development of highly efficient thermoelectric materials, propelling efforts toward more energy‐efficient and environmentally friendly solutions.

AbstractHepatocellular carcinoma (HCC) is a leading cause of cancer-related death. FGFR4 has been implicated in HCC progression, making it a promising therapeutic target. We introduce an approach for identifying novel FGFR4 inhibitors by sequentially adding fragments to a common warhead unit. This strategy resulted in the discovery of a potent inhibitor, 4c, with an IC50 of 33 nM and high selectivity among members of the FGFR family. Although further optimisation is required, our approach demonstrated the potential for discovering potent FGFR4 inhibitors for HCC treatment, and provides a useful method for obtaining hit compounds from small fragments.

Placeness is believed to play a significant role in enhancing the well-being and place-use of individuals, contributing profoundly to how spaces are experienced and interacted with. Despite its perceived importance, there is ongoing debate and insufficient clarity about how exactly placeness influences people’s behavior. This study aims to bridge this gap by theorizing and investigating the pathways from placeness to people’s behavioral intentions, emphasizing the roles of personal place attachment and public place image as pivotal mediators in this relationship. To explore these dynamics, we conducted a survey in Japan, examining the complex interplay between placeness and behavioral intentions, given their rich cultural heritage and modern urban pressures. We employed the Partial Least Squares Structural Equation Modeling (PLS-SEM) approach for path analysis. The analysis suggests that placeness influences behavioral intention through personal place attachment. While placeness does affect public place image, this public image does not have an impact on behavioral intention. The results demonstrated that an individual’s activities, experiences, and cognition of a place are significant factors in creating the intention to engage in word-of-mouth, recommendation, and revisiting behaviors. Policymakers, urban planners, and designers need to understand how to foster people’s behavioral intentions when creating a place imbued with placeness.

Inhalation of ultrafine particles, aerosol contaminants, and cigarette smoke can induce respiratory diseases. As humans are constantly exposed to various exogenous substances, it is crucial to study their impacts on respiratory diseases and airway dysfunction. Recently, organ-on-a-chip technology has been applied in many research studies to understand disease mechanisms, drug screening, and drug testing. The combination of organ-on-a-chip technology and the air-liquid interface (ALI) culture method is emerging as a new platform for realistically mimicking the microenvironment and physiological motions of the human lungs. Breathing motion can be simulated through cyclic stretching, while blood flow can be replicated using channel flow within the chip. The ALI system is critical for mucociliary differentiation, pseudostratified morphology, and epithelial barrier function development. The combination of organ-on-a-chip technology and ALI systems allows the integration of cyclic stretch as a breathing motion and microfluidic channels as circulatory systems. The chip system can also integrate the lung epithelial cells, extracellular matrix, and microstructures, providing microenvironments such as fibroblast, collagen, and immune cells to the epithelial cells. This review discusses chip systems as effective tools for recapitulating human lung environments and how they are applied in biological studies against various pulmonary diseases such as infections or inflammation, fibrosis, and malignancy.

Energy consumption in buildings contributes to over a third of global energy consumption and 28% of greenhouse gas emissions. With urbanization and population growth, rising building energy demand can lead to environmental degradation. While significant renewable resources are used to generate electricity to mitigate environmental problems, demand-side management remains crucial for achieving net-zero emissions and enhancing energy efficiency. Accurate building load forecasting is pivotal in devising optimal demand response schemes to shift or reduce the demand on power grids. Recent studies have achieved progressive breakthroughs in building energy forecasting through machine learning algorithms. However, most studies focused on building-level energy forecasting rather than individual load forecasting, which cannot support controlled demand response programs. In this study, we propose a multi-task learning model incorporating Patch, Temporal Convolutional Network and Time-Series Transformer (PatchTCN-TST) based on the channel-independent strategy for floor-level multiple electricity loads and indoor environmental forecasting. The PatchTCN-TST model is implemented to predict future data ranging from one-step ahead to three-step ahead on a real-world office building in Bangkok, Thailand. The experiment results indicate that the prediction performance of our model outperforms the prevalent methods, including LSTM, GRU, TCN, Transformer, Informer and Autoformer. The PatchTCN-TST model demonstrates superior accuracy in three forecasting scenarios, significantly reducing MAE, MSE, RMSE, and aSMAPE by 34%, 23%, 12%, and 36.4%, respectively, compared to the best baseline model.

PURPOSE Physical activity confers benefits by mitigating the adverse physical and mental effects of coronavirus disease 2019 (COVID-19). Nevertheless, during a public health crisis, in which group-based physical activity is restricted, participation in such activities may be influenced not only by social distancing policies, but also by individual and environmental factors. As such, this study adopted a socio-ecological perspective to explore the impact of multidimensional factors on physical activity across diverse regions during the COVID-19 pandemic. METHODS Cross-sectional data from the 2021 Chinese General Social Survey (CGSS) were used. A total of 8148 respondents from 12 provinces and metropolitan cities were pooled. Two types of physical activity (walking and moderate-to-vigorous exercise) were included in the statistical tests. A three-step hierarchical regression analysis was used to analyze the incremental predictive power of factors related to intrapersonal, interpersonal and community resources for physical activity. RESULTS Findings highlighted the significance of intrapersonal (e.g., age, sex, socio-economic status, health status, and household registration area), interpersonal (e.g., neighborhood help and friendship), and community (e.g., exercise facility, fresh food accessibility, public facility, and residential safety) resources. These factors were significantly associated with Chinese adults’ participation in physical activity across various regions. CONCLUSIONS Findings of this study provide an initial validation of the socio-ecological approach to studying physical activity during the COVID-19 pandemic, suggesting that strategies aimed at promoting the benefits of exercise should include multiple factors that influence the likelihood of Chinese adults engaging in physical activity.

Background/Aims Cardiorespiratory fitness (CRF), as measured by maximal oxygen consumption (VO2max), is an important independent predictive factor of cardiovascular outcomes in patients with heart failure (HF). However, it is unclear whether conventional equations for estimating CRF are applicable to patients with HF with preserved ejection fraction (HFpEF). Methods This study included 521 patients with HFpEF (EF ≥ 50%) whose CRF was directly measured by cardiopulmonary exercise test using a treadmill. We developed a new equation (Kor-HFpEF) for half of the patients in the HFpEF cohort (group A, n = 253) and validated it for the remaining half (group B, n = 268). The accuracy of the Kor-HFpEF equation was compared to that of the other equations in the validation group. Results In the total HFpEF cohort, the directly measured VO2max was significantly overestimated by the FRIEND and ACSM equations (p < 0.001) and underestimated by the FRIEND-HF equation (p

Abstract With the progress of renewable energy generation and energy storage technologies, more and more renewable sources and devices are integrated into the power system. Due to the complexity of the power system, single and multiple power quality disturbances (PQDs) occur more frequently. Hence, real‐time detection of PQDs is the primary issue to mitigate the risk of distortions. This study presents the real‐time PQDs classification using fused convolutional neural networks (CNN) combined with long short‐term memory (fused CNN‐LSTM) architecture based on time and frequency domain features. The frequency‐domain features were obtained from time‐series data using fast Fourier transform. The original time‐domain and frequency‐domain features are extracted by respective CNN‐LSTM structures. The extracted time and frequency domain features are concatenated to classify the PQD through fully connected layers. Our proposed method was trained and tested using 16 types of synthetic noise PQDs data generated by mathematical models, in accordance with the standard IEEE‐1159. Moreover, to further verify the performance of our approach, a simulation distributed power system is carried out to detect various PQDs. We compared three advanced neural network approaches: Deep CNN, CNN‐LSTM, and multifusion CNN (MFCNN). The fused CNN‐LSTM model takes only 0.64 ms to classify each PQDs signal and achieves an accuracy of 98.95% and 98.89% in synthetic data and simulated power systems which indicates our proposed method outperformed compared methods.

Breaking the limitations of the urban perspective, there is an urgent need to study the influence of the village environment on the willingness of rural households to resettle. This paper explored the determinants and the mechanism of village environment factors on resettlement willingness using full-sample survey data (872,414 households) of 1382 administrative villages in Huai'an, a typical agricultural area in Eastern China. The result revealed that environmental factors generally have a greater impact on the spatial heterogeneity of resettlement willingness, in the order of natural environment, economic environment, social environment, and policy environment; among which geographic location, housing conditions, behavioral tendency of farmers and planning guidance are the key factors. In addition, the absolute location of the urban area in the geographic region has a significantly greater effect than that of the county, and the "following behavior" of the farmers affected their resettlement decision. Therefore, differentiated policies should be formulated according to the spatial distribution of the resettlement willingness, building a dual-core village and town system within the county.

This study examines the relationship between different types of new town development and their impact on commuting patterns. It provides an empirical analysis of how development in Technopole Newtown and Residential Newtown influences commuting time and distance. Technopole Newtown is characterized by a blend of technological institutional clusters and residential development, while Residential Newtown primarily emphasizes residential development. Seoul Metropolitan Area was chosen as the case study, with data sourced from the Household Travel Survey. This study reveals a surprising commuting paradox in Technopole Newtown, where the plan was to blend job opportunities with residential development. The findings indicate that commuters did not benefit. Instead, they endured longer commutes in both time and distance compared to those in Residential Newtown, which is typically characterized as a bedroom community. The integration of job opportunities for the development of new towns should be considered a crucial factor in creating urban sustainability in the future.

Reports have shown an increase in the use of disinfectants in wastewater treatment plants, prompted by the detection of residual viruses in sewage. However, the release of disinfection byproducts (DBPs) in final effluents has raised concerns about their potential adverse effects, such as endocrine disruption, on aquatic environments. Despite these concerns, few studies have examined the endocrine-disrupting effects of DBPs on fish, which may be vulnerable to DBPs. The aim of this case study was to investigate the endocrine-disrupting properties of four commonly formed DBPs: chloroiodomethane (CIM), dibromochloromethane (DBCM), bromodichloromethane (BDCM), and trichloroacetic acid (TCA) on the estrogen receptor-α in zebrafish (zERα). The results indicated that all four DBPs have high anti-estrogenic activity against zERα; with CIM, BDCM, DBCM, and TCA yielding 80.8%, 78.4%, 49.0%, and 64.1% anti-estrogenic effects on zERα, respectively. Moreover, all DBPs demonstrated negligible estrogenic effects on zERα. Our study sheds new light on the adverse effects of DBPs, particularly the endocrine-disrupting activity of CIM, which, as part of the dihalomethanes group, has received limited research attention in the past. This study shows the molecular interactions in terms of the endocrine disruption of DBP on zERα, warranting further studies to understand the overall impact of fish in affected aquatic ecosystems.

Subciliary incision is a common approach for facial fracture surgery; however, it has a higher incidence of lower lid ectropion, which can be particularly challenging for beginning surgeons to manage. This study reports the usage of lateral tarsoplasty combined with a full-thickness skin graft (FTSG) to correct severe ectropion following the subciliary approach for infra-orbital rim fractures. We retrospectively reviewed all facial fracture cases involving infra-orbital rim fractures through a subciliary approach treated in our department between March 2021 and May 2023. Electronic medical records and clinical digital photographs of patients who met the inclusion criteria were reviewed. After reviewing 196 cases that used the subciliary approach, we found 6 patients (3.06%; 4 males and 2 females; mean age, 68.5 ± 4.89 years) with postoperative severe ectropion managed using lateral tarsoplasty and FTSG. The mean ectropion development and correction times after facial fracture surgery were 0.78 ± 0.24 and 0.91 ± 0.37 months, respectively. At the 12-month follow-up, all patients showed favorable outcomes, and the position of their lower eyelids was well maintained without ectropion recurrence. Based on these successful outcomes, lateral tarsoplasty combined with FTSG is proposed to be an effective and straightforward method for managing lower eyelid ectropion caused by facial fracture surgery.

Background: It has been reported that significant endothelial dysfunction or clinically evident vasospasm can be associated with drug-eluting stents (DESs). However, the impact of DES associated coronary artery spasm (CAS) on long-term clinical outcomes has not been fully elucidated as compared with those of patients with vasospastic angina. Methods: A total of 2797 consecutive patients without significant coronary artery lesion (

Abstract Background Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid–polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD. Results Gb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old male B6;129-Gla tm1Kul /J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved. Conclusions PEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease. Graphical Abstract

The internet-of-Vehicle (IoV) can facilitate seamless connectivity between connected vehicles (CV), autonomous vehicles (AV), and other IoV entities. Intrusion Detection Systems (IDSs) for IoV networks can rely on machine learning (ML) to protect the in-vehicle network from cyber-attacks. Blockchain-based Federated Forests (BFFs) could be used to train ML models based on data from IoV entities while protecting the confidentiality of the data and reducing the risks of tampering with the data. However, ML models are still vulnerable to evasion, poisoning and exploratory attacks by adversarial examples. The BFF-IDS offers partial defence against poisoning but has no measure for evasion attacks, the most common attack/threat faced by ML models. Besides, the impact of adversarial examples transferability in CAN IDS has largely remained untested. This paper investigates the impact of various possible adversarial examples on the BFF-IDS. We also investigated the statistical adversarial detector’s effectiveness and resilience in detecting the attacks and subsequent countermeasures by augmenting the model with detected samples. Our investigation results established that BFF-IDS is very vulnerable to adversarial examples attacks. The statistical adversarial detector and the subsequent BFF-IDS augmentation (BFF-IDS(AUG)) provide an effective mechanism against the adversarial examples. Consequently, integrating the statistical adversarial detector and the subsequent BFF-IDS augmentation with the detected adversarial samples provides a sustainable security framework against adversarial examples and other unknown attacks.

This paper reports the geometrical characteristics and the growth of aggregate silica particles generated in a premixed flame using thermophoretic sampling, a light scattering technique, and aggregate dynamics modeling only for a premixed flat flame condition. The area equivalent size and the morphology of thermophoretically collected silica aggregate particles were analyzed through images taken from a transmission electron microscope. The particle stream in flames was visualized through a planar light scattering technique. Light scattering intensity at 90° using an Ar-ion laser (wavelength, 514 nm) was monitored for various flame conditions. The results of aggregate dynamics modeling under a one-dimensional assumption indicated that the silica particles grew as the height above the burner increased. Aggregate particles produced at various equivalence ratios showed different levels of OH-species. The OH-related species increased as the equivalence ratio decreased, which implies that a high equivalence ratio is recommended to produce pure silica particles. In this study, the purest silica aggregate particles were produced at the equivalence ratio of 11.4, among others. Our study helps to determine which flame condition is best in terms of the quality and/or quantity of silica aggregate particles generated by a coflow burner.

PURPOSE Rapid urbanization has witnessed a dramatic decrease in physical activity. The purpose of this research was to explore the vulnerable inactivity group influenced by urbanization in China. METHODS Cross-sectional data from the 2015 China Health and Nutrition Survey were utilized. A total of 7,319 households, including 20,914 individuals within 12 provinces, were pooled. Seven types of physical activity were included in statistical testing. Commu-nity-level urbanization was measured on an urbanicity scale consisting of 12 dimensions. Cross-level logistic regression analysis was conducted to estimate the direct and interactive effects of individual socioeconomic statuses and community-level urbanization on a leisure time physical activity (LTPA). After removing incomplete responses, 8,617 samples were selected for the statistical analyses. RESULTS Community-level urbanization was positively related to participation probability in the LTPA. With an increase of one standard deviation (SD) in the level of urbanization, the odds of participating in the LTPA increased by approximately six times in the most urbanized areas compared with the least urbanized areas. The effect of employment status on the probability of participation in the LTPA differed across the levels of urbanization in each community. For white-collar workers who resided in the most urbanized communities, the odds of participating in the LTPA decreased by approximately 46% compared to their peers in the least urbanized communities. CONCLUSIONS Community-level urbanization should be addressed when developing interventions and health policies to promote physical activity during leisure time, especially for individuals who are white-collar workers living in urbanized communities.

Abstract Background trans-cinnamic acid (t-CA) is a phenylpropanoid with a broad spectrum of biological activities including antioxidant and antibacterial activities, and it also has high potential in food and cosmetic applications. Although significant progress has been made in the production of t-CA using microorganisms, its relatively low product titers still need to be improved. In this study, we engineered Corynebacterium glutamicum as a whole-cell catalyst for the bioconversion of l-phenylalanine (l-Phe) into t-CA and developed a repeated bioconversion process. Results An expression module based on a phenylalanine ammonia lyase-encoding gene from Streptomyces maritimus (SmPAL), which mediates the conversion of l-Phe into t-CA, was constructed in C. glutamicum. Using the strong promoter PH36 and ribosome binding site (RBS) (in front of gene 10 of the T7 phage), and a high-copy number plasmid, SmPAL could be expressed to levels as high as 39.1% of the total proteins in C. glutamicum. Next, to improve t-CA production at an industrial scale, reaction conditions including temperature and pH were optimized; t-CA production reached up to 6.7 mM/h in a bioreactor under optimal conditions (50 °C and pH 8.5, using NaOH as base solution). Finally, a recycling system was developed by coupling membrane filtration with the bioreactor, and the engineered C. glutamicum successfully produced 13.7 mM of t-CA (24.3 g) from 18.2 mM of l-Phe (36 g) and thus with a yield of 75% (0.75 mol/mol) through repetitive supplementation. Conclusions We developed a highly efficient bioconversion process using C. glutamicum as a biocatalyst and a micromembrane-based cell recycling system. To the best of our knowledge, this is the first report on t-CA production in C. glutamicum, and this robust platform will contribute to the development of an industrially relevant platform for the production of t-CA using microorganisms.

The objective of this study was evaluation of pig behavior changes related to temperature, relative humidity, volatile organic compounds (VOCs), and illuminance. A total of 24 growing pigs ([Yorkshire × Landrace] × Duroc) were used in the experiment. A sensor was installed at a height of 0.5 m in the center of the pig house. In experiment 1, temperature was changed every four days to 18°C (T1), 22°C (T2), 26°C (T3), and then 30°C (T4). In experiment 2, relative humidity was adjusted to 45% (low humidity [LH]), 60% (middle humidity [MH]), and then 75% (high humidity [HH]) for four days. In experiment 3, after cleaning the pig house just before experiment, only minimal ventilation was provided. VOCs and pig behaviors were observed for 7 days without cleaning the pig house. In experiment 4, three light bulbs of 40 W (470 lumens / 45 lx; low illuminance [LI]), 75 W (1,055 lumens / 103 lx; middle illuminance [MI]), and 100 W (1,521 lumens / 146 lx; high illuminance [HI]) were used for four days each. Pig behavior analysis was performed for following criteria : Feed intake, Standing, Lying, Sitting, Drink water, Rooting, Posture transition (lying-standing), Posture transition (standing-lying), Wallowing, and Biting. In experiment 1, feed intake time was lower (p < 0.05) for the T3 than other treatment groups. Standing time was highest (p < 0.05) for the T1 and lowest (p < 0.05) for the T3. Lying time was shorter (p < 0.05) in T1 and T2 compared to T3 and T4. Drinking frequency was higher (p < 0.05) for the T4 than other treatment groups. In experiment 2, the frequency of rooting and wallowing increased (p < 0.05) with increasing humidity. LH showed the lowest (p < 0.05) rooting frequency and HH showed the highest (p < 0.05) rooting frequency. In experiment 3, VOCs concentration did not (p > 0.05) change pig behavior. In experiment 4, lying time was the longest (p < 0.05) at LI and shortest (p < 0.05) at HI. Therefore, pig behavior is heavily influenced by the environment, especially temperature and humidity. However, correlation between pig behavior to VOCs and illuminance seems to be needed more research.

Abstract Computer-assisted reporting (CAR) tools were suggested to improve radiology report quality by context-sensitively recommending key imaging biomarkers. However, studies evaluating machine learning (ML) algorithms on cross-lingual ontological (RadLex) mappings for developing embedded CAR algorithms are lacking. Therefore, we compared ML algorithms developed on human expert-annotated features against those developed on fully automated cross-lingual (German to English) RadLex mappings using 206 CT reports of suspected stroke. Target label was whether the Alberta Stroke Programme Early CT Score (ASPECTS) should have been provided (yes/no:154/52). We focused on probabilistic outputs of ML-algorithms including tree-based methods, elastic net, support vector machines (SVMs) and fastText (linear classifier), which were evaluated in the same 5 × fivefold nested cross-validation framework. This allowed for model stacking and classifier rankings. Performance was evaluated using calibration metrics (AUC, brier score, log loss) and -plots. Contextual ML-based assistance recommending ASPECTS was feasible. SVMs showed the highest accuracies both on human-extracted- (87%) and RadLex features (findings:82.5%; impressions:85.4%). FastText achieved the highest accuracy (89.3%) and AUC (92%) on impressions. Boosted trees fitted on findings had the best calibration profile. Our approach provides guidance for choosing ML classifiers for CAR tools in fully automated and language-agnostic fashion using bag-of-RadLex terms on limited expert-labelled training data.

In the context of China’s New Urbanization Strategy, it is of great practical significance to study rural–urban population migration from the perspective of house purchases by rural households. In this paper, the Huai’an Rural Survey Dataset (872,414 households) was used to study the heterogeneity of rural households’ house purchases in different classes of urban destinations, and its influencing factors were analyzed with GeoDetector. The results show that the urban house purchase destinations preferred by farmers were county towns, townships, foreign cities, and metropolitan areas, indicating that in situ urbanization has become the main path of urbanization for farmers in Huai’an. Among the environmental influencing factors, the rural environment had the greatest influence on house purchases locally (in the township and county town), and this influence decreased with the outward shift of house purchase destinations. The housing environment, the settlement environment, and the population and family environment were the main environmental impact elements. The natural environment and the policy environment had little influence on the house-purchasing behavior of farmers, and the location environment was critical in exotic locations (metropolitan areas and foreign cities). Therefore, this paper argues that a higher demand for housing is growing in China’s less developed rural areas, creating a situation in which the metropolitan area is the core and the county town is the main contributor. In terms of policy improvements, it is important to pay more attention to small cities such as counties and to offer housing concessions and welfare to “new citizens” from rural areas, as well as to significantly improve the housing, earnings, and public service environment for those who prefer to stay in the countryside.

Background: Disinfection byproducts (DBPs) cause endocrine disruption via estrogenic or anti-estrogenic effects on estrogen receptors. However, most studies have focused on human systems, with little experimental data being presented on aquatic biota. This study aimed to compare the effects of nine DBPs on zebrafish and human estrogen receptor alpha (zERα and hERα). Methods: In vitro enzyme response-based tests, including cytotoxicity and reporter gene assays, were performed. Additionally, statistical analysis and molecular docking studies were employed to compare ERα responses. Results: Iodoacetic acid (IAA), chloroacetonitrile (CAN), and bromoacetonitrile (BAN) showed robust estrogenic activity on hERα(maximal induction ratios of 108.7%, 50.3%, and 54.7%, respectively), while IAA strongly inhibited the estrogenic activity induced by 17β-estradiol (E2) in zERα (59.8% induction at the maximum concentration). Chloroacetamide (CAM) and bromoacetamide (BAM) also showed robust anti-estrogen effects in zERα (48.1% and 50.8% induction at the maximum concentration, respectively). These dissimilar endocrine disruption patterns were thoroughly assessed using Pearson correlation and distance-based analyses. Clear differences between the estrogenic responses of the two ERαs were observed, whereas no pattern of anti-estrogenic activities could be established. Some DBPs strongly induced estrogenic endocrine disruption as agonists of hERα, while others inhibited estrogenic activity as antagonists of zERα. Principal coordinate analysis (PCoA) showed similar correlation coefficients for estrogenic and anti-estrogenic responses. Reproducible results were obtained from computational analysis and the reporter gene assay. Conclusions: Overall, the effects of DBPs on both human and zebrafish highlight the importance of controlling their differences in responsiveness for estrogenic activities including the water quality monitoring and endocrine disruption, as DBPs have species-specific ligand-receptor interactions.

Abstract Background High-intensity statin therapy is typically used in patients with acute myocardial infarction (AMI) for secondary prevention. However, there have been consistent concerns regarding its association with diabetes mellitus. We investigated the effect of high-intensity atorvastatin and rosuvastatin on new-onset diabetes mellitus (NODM) and cardiovascular outcomes over a 3-year follow-up period. Methods Data from the Korea Acute Myocardial Infarction Registry were collected from November 2011 to October 2015, and 13,104 patients with AMI were enrolled from major cardiovascular centers. Among them, 2221 patients without diabetes who had been administered with high-intensity atorvastatin (40–80 mg) and rosuvastatin (20 mg) were investigated. The atorvastatin and rosuvastatin groups were evaluated for the incidence of NODM and major adverse cardiac events (MACE) including death, myocardial infarction, and revascularization cases in the following 3 years. Results Baseline characteristics were comparable between the two groups. Event-free survival rate of NODM was not significantly different between the atorvastatin and rosuvastatin groups (92.5% vs. 90.8%, respectively; Log-rank P-value = 0.550). The event-free survival rate of MACE was also not significantly different between atorvastatin and rosuvastatin groups (89.0% vs. 89.6%, respectively; Log rank P-value = 0.662). Multivariate Cox analysis revealed that statin type was not a prognostic factor in the development of NODM and MACE. Conclusions Administering high-intensity atorvastatin and rosuvastatin in patients with AMI produced comparable effects on NODM and clinical outcomes, suggesting their clinical equivalence in secondary prevention.

In-vehicle communication systems are usually managed by controller area networks (CAN). By broadcasting packets to their bus, the CAN facilitates the interaction between Electronic Control Units (ECU) that coordinate, monitor and control internal vehicle components. With no authentication mechanism for identifying the legitimacy and source of packets, CAN are vulnerable to cyber-attacks. An Intrusion Detection System (IDS) can detect attacks on CAN and machine learning can be used to create the models for the IDSs to detect non-linear attack patterns. However, car manufacturers and owners might want to keep the sensitive information required for training the models confidential. Therefore, we proposed a Blockchain-based Federated Forest Software-Defined Networking (SDN)-enabled IDS (BFF-IDS) to address the problem of data sharing the sensitive CAN data. To ensure scalability, we used InterPlanetary File System (IPFS) to host the models, and the blockchain is designed to store only a hash of the model and a pointer to its location. The SDN provides the dynamic routing of packets and model exchanges. We used Federated Learning (FL) to create a random forest model. Individuals provide partially trained models, allowing them to keep the underlying data confidential. Using Fourier transform, we decomposed the CAN IDs cycle from CAN bus traffic in the frequency domain for better generalization in multiclass detection of attacks. Multiple statistical and entropy features were extracted to handle the high complexity and non-linearity in CAN bus traffic. The proposed system allows manufacturers and car owners to contribute to the training of the models, as their sensitive data is protected. By storing hashes of the models on a blockchain, the risk of adversaries poisoning the models is reduced and a single point of failure is avoided. We evaluated the proposed system by conducting experiments on a testbed. We found that the proposed system has efficient use of memory and CPU resources and that the detection rate of closely related attacks was high. We recorded the highest model attack detection rate of about 0.981.

Mechanisms and consequences of the acclimation of soil respiration to warming are unclear. Here, the authors combine soil respiration, metagenomics, and functional gene results from a 7-year grassland warming experiment to a microbial-enzyme decomposition model, showing functional gene information to lower uncertainty and improve fit.

Abstract Shifts in dominance and species reordering can occur in response to global change. However, it is not clear how altered precipitation and disturbance regimes interact to affect species composition and dominance. We explored community‐level diversity and compositional similarity responses, both across and within years, to a manipulated precipitation gradient and annual clipping in a mixed‐grass prairie in Oklahoma, USA. We imposed seven precipitation treatments (five water exclusion levels [−20%, −40%, −60%, −80%, and −100%], water addition [+50%], and control [0% change in precipitation]) year‐round from 2016 to 2018 using fixed interception shelters. These treatments were crossed with annual clipping to mimic hay harvest. We found that community‐level responses were influenced by precipitation across time. For instance, plant evenness was enhanced by extreme drought treatments, while plant richness was marginally promoted under increased precipitation. Clipping promoted species gain resulting in greater richness within each experimental year. Across years, clipping effects further reduced the precipitation effects on community‐level responses (richness and evenness) at both extreme drought and added precipitation treatments. Synthesis: Our results highlight the importance of studying interactive drivers of change both within versus across time. For instance, clipping attenuated community‐level responses to a gradient in precipitation, suggesting that management could buffer community‐level responses to drought. However, precipitation effects were mild and likely to accentuate over time to produce further community change.

Oral cancer: Stopping the spread Resveratrol, a naturally occurring compound present in grape skins, peanuts, and blueberries, reduces the ability of oral squamous cell carcinoma (OSCC) cells to spread to other parts of the body. Over half a million new cases of OSCC are diagnosed each year, and spread beyond the mouth is the most common cause of death. Hoi Young Lee at Konyang University, Daejon, Republic of Korea, and co-workers investigated whether a protein called RCP, which increases the invasiveness of many but not all types of cancer, is implicated in aggressive spread of OSCC. They found that RCP does increase the invasiveness of OSCC. Resveratrol is known to suppress the spread of many cancers, and strongly curtailed the spread of OSCC by blocking RCP activity. These results shed light on OSCC invasiveness, and offer a potential new treatment.

Abstract Grassland ecosystems provide essential services to society. To maintain ecosystem functions and services of grasslands under changing environments, it is critical to understand how grasslands respond and feedback to climate change. Here, we present results from a long‐term (16 years) warming and clipping (to mimic hay harvesting or grazing) experiment conducted in a grassland ecosystem dominated by C4 grasses in the Great Plains, USA. We analyzed responses of net primary production (NPP), aboveground NPP (ANPP), and belowground NPP (BNPP) to the expanded ranges of climate conditions observed in the experiment. NPP, ANPP, and BNPP all responded to the climatic variables nonlinearly, with higher degrees of nonlinearity for BNPP than that for ANPP. BNPP peaked at the optimum air temperature of 17.5–18.5°C while ANPP peaked at the optimum air temperature of 18.5–20.0°C. The optimum air temperatures for both ANPP and BNPP were higher than mean annual temperature (16.3°C) at the site. The optimum precipitation for BNPP was intermediate levels (775–1250 mm) while ANPP was maximized in wetter conditions (1250–1605 mm) compared with BNPP. Clipping significantly reduced ANPP and shifted the optimum conditions for BNPP to warmer and wetter conditions. In summary, C4‐grass dominant ecosystems have the potential to increase NPP in future warmer and wetter conditions, and clipping may amplify this positive effect in this grassland ecosystem.

BackgroundDespite strong evidence of clinical benefit, cardiac rehabilitation (CR) programs are currently underutilized and smartphone-based CR strategies are thought to address this unmet need. However, data regarding the detailed process of development are scarce. ObjectiveThis study focused on the development of a smartphone-based, patient-specific, messaging app for patients who have undergone percutaneous coronary intervention (PCI). MethodsThe AnSim app was developed in collaboration with a multidisciplinary team that included cardiologists, psychiatrists, nurses, pharmacists, nutritionists, and rehabilitation doctors and therapists. First, a focus group interview was conducted, and the narratives of the patients were analyzed to identify their needs and preferences. Based on the results, health care experts and clinicians drafted messages into 5 categories: (1) general information regarding cardiovascular health and medications, (2) nutrition, (3) physical activity, (4) destressing, and (5) smoking cessation. In each category, 90 messages were developed according to 3 simplified steps of the transtheoretical model of behavioral change: (1) precontemplation, (2) contemplation and preparation, and (3) action and maintenance. After an internal review and feedback from potential users, a bank of 450 messages was developed. ResultsThe focus interview was conducted with 8 patients with PCI within 1 year, and 450 messages, including various forms of multimedia, were developed based on the transtheoretical model of behavioral change in each category. Positive feedback was obtained from the potential users (n=458). The mean Likert scale score was 3.95 (SD 0.39) and 3.91 (SD 0.39) for readability and usefulness, respectively, and several messages were refined based on the feedback. Finally, the patient-specific message delivery system was developed according to the baseline characteristics and stages of behavioral change in each participant. ConclusionsWe developed an app (AnSim), which includes a bank of 450 patient-specific messages, that provides various medical information and CR programs regarding coronary heart disease. The detailed process of multidisciplinary collaboration over the course of the study provides a scientific basis for various medical professionals planning smartphone-based clinical research.

Objective: Smoking is a modifiable cardiovascular risk factor closely related to arterial stiffness (AS). However, data are lacking regarding the chronic effects of smoking on AS, especially in ex-smoker (ES) who faces remnant cardiovascular risk when compared to never-smokers (NS). Methods: Among 1722 health screening participants, we retrospectively evaluated 652 healthy men with different smoking history [240 current smoker (CS) vs. 228 ES vs. 184 NS]. To assess AS, augmentation index (AIx), pulse pressure amplification (PPamp), and carotid-femoral pulse wave velocity (cfPWV) were measured and compared. Results: Baseline characteristics were similar except age and triglyceride level. AIx was lowest in NS, followed by ES, and was highest in CS. PPamp was highest in NS, lowest in CS, and ES was of intermediate level. The differences were more robust after adjustment for baseline covariates (AIx, p = 0.005; PPamp: p = 0.001). On the other hand, no significant intergroup difference was observed for cfPWV in our middle-aged population. With the regression analyses revealing an independent association between smoking duration and AS in ES, subgroup analysis demonstrated that long-term ES (smoking duration ≥20 years) had significantly higher AS than short-term ES (

Objectives Intracoronary injection of acetylcholine (Ach) has been shown to induce significant coronary artery spasm (CAS) in patients with vasospastic angina. Clinical significance and angiographic characteristics of patients with ischemic electrocardiogram (ECG) changes during the Ach provocation test are not clarified yet. Methods A total 4,418 consecutive patients underwent coronary angiography with Ach provocation tests from 2004 to 2012 were enrolled. Ischemic ECG changes were defined as transient ST-segment depression or elevation ( > 1 mm) and T inversion with/without chest pain. Finally, a total 2,293 patients (28.5% of total subjects) proven CAS were enrolled for this study. Results A total 119 patients (5.2%) showed ECG changes during Ach provocation tests. The baseline clinical and procedural characteristics are well balanced between the two groups. Ischemic ECG change group showed more frequent chest pain, higher incidence of baseline spasm, severe vasospasm, multi-vessel involvement, and more diffuse spasm ( > 30 mm) than those without ischemic ECG changes. At 5 years, the incidences of death, major adverse cardiac events (MACE) and major adverse cardiac and cerebral events (MACCE) were higher in the ischemic ECG change group despite of optimal medical therapy. Conclusions The patients with ischemic ECG changes during Ach provocation tests were associated with more frequent chest pain, baseline spasm, diffuse, severe and multi-vessel spasm than patients without ischemic ECG changes. At 5-years, the incidences of death, MACE and MACCE were higher in the ischemic ECG change group, suggesting more intensive medical therapy with close clinical follow up will be required.

Percutaneous transluminal angioplasty (PTA) is considered an effective treatment in patients with critical limb ischemia (CLI). However, the long-term durability of below-the-knee (BTK) PTA is known to be limited. This study sought to compare the 1-year clinical outcomes following stenting versus balloon angioplasty alone in BTK lesions. This study included 357 consecutive patients (400 limbs, 697 lesions) with BTK lesions who underwent PTA from September 2010 to December 2016. All enrolled patients were treated either by stenting (stent group; 111 limbs of 102 patients) or plain old balloon angioplasty (POBA group; 289 limbs of 255 patients). Stent group includes both primary and provisional stenting. Angiographic outcomes, procedural success, complications, and clinical outcomes were compared between the two groups up to 1 year. After propensity score matching (PSM) analysis, 56 pairs were generated, and the baseline and angiographic characteristics were balanced. The procedural success and complications were similar between the two groups; however, the incidence of procedure-related perforation was higher in the POBA group than in the stenting group [5(11.9%) vs.1 (0.9%), P = 0.009]. Six- to 9-month computed tomography or angiographic follow-up showed similar incidences of binary restenosis, primary patency, and secondary patency. In the 1-year clinical follow-up, there were similar incidences of individual hard endpoints, including mortality, myocardial infarction, limb salvage, and amputation rate, with the exception of target extremity revascularization (TER), which tended to be higher in the stenting group than in the POBA group [21 (20.8%) vs. 11 (10.9%), P = 0.054]. Although there was a trend toward a higher incidence of TER risk in the stenting group, stent implantation, particularly in bail-out stenting seemed to have acceptable 1-year safety and efficacy compared to POBA alone in patients undergoing BTK PTA.

Background Sleep fragmentation and sleep apnea are common in patients with atrial fibrillation (AF). We investigated the impact of radio‐frequency catheter ablation (RFCA) on sleep quality in patients with paroxysmal AF and the effect of a change in sleep quality on recurrence of AF. Methods and Results Of 445 patients who underwent RFCA for paroxysmal AF between October 2007 and January 2017, we analyzed 225 patients who had a 24‐hour Holter test within 6 months before RFCA. Sleep quality was assessed by cardiopulmonary coupling analysis using 24‐hour Holter data. We compared cardiopulmonary coupling parameters (high‐frequency coupling, low‐frequency coupling, very‐low‐frequency coupling) before and after RFCA. Six months after RFCA, the high‐frequency coupling (marker of stable sleep) and very‐low‐frequency coupling (rapid eye movement/wake marker) was significantly increased (29.84%–36.15%; P

Background: Endeavor®-zotarolimus-eluting stent (E-ZES) was the first ZES to be developed, and Resolute integrity®-ZES (I-ZES) has been developed more recently. Comparative studies on long-term usage of these two ZESs have been rare. Objectives: The aim of this study was to compare the efficacy and safety of E-ZES and I-ZES during a long-term follow-up of patients who underwent percutaneous coronary intervention (PCI). Methods: A total of 767 patients who underwent PCI with E-ZES or I-ZES were eligible for this study. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as the composite of all-cause death, non-fatal myocardial infarction (MI), and any repeat revascularization. The secondary endpoint was stent thrombosis (ST). Results: After propensity score-matched (PSM) analysis, two PSM groups (193 pairs, n = 386, C-statistic = 0.824) were generated. During the 3-year follow-up period, the cumulative inci­dence of MACEs (hazard ratio [HR], 0.837; 95% confidence interval [CI], 0.464–1.508; p = 0.553) and ST (HR, 0.398; 95% CI, 0.077–2.052; p = 0.271) was similar for the E-ZES and I-ZES groups. Additionally, the cumulative incidences of all-cause death, cardiac death, non-fatal MI, and any repeat revascularization were not significantly different between the two groups. Conclusions: Although I-ZES utilizes a more advanced stent platform, stent design, and polymer system than E-ZES, both the ZESs showed comparable efficacy and safety during the 3-year follow-up period in this single-center, all-comers registry. However, further large-scaled, randomized, well-controlled trials with long-term follow-up are needed to verify these results.

BackgroundBeta-blockers are often not the preferred treatment for patients with vasospastic angina. However, nebivolol, beta-blocker with nitric oxide-releasing effect, could theoretically improve coronary vasospasm. We compared nebivolol versus diltiazem in improving coronary vasospasm and quality of life in patients with hypertensive vasospastic angina during a 12-week follow-up.MethodsFifty-one hypertensive patients with documented coronary vasospasm were randomly allocated into 3 treatment groups: (1) Nebivolol Group (5mg for 2 weeks/10mg for 10 weeks); (2) Diltiazem Group (90mg for 2 weeks/180mg for 10 weeks); (3) Low-dose Combination Group (2.5mg + 45mg for 2 weeks/5mg + 90mg for 10 weeks). The primary endpoint was to compare the percent changes in coronary vasospasm at 12 weeks from baseline among the 3 groups. The secondary endpoints included changes in quality of life based on the Seattle Angina Questionnaire and changes in blood pressure at 12 weeks from baseline.ResultsSignificant improvements in coronary vasospasm were found in all groups; however, the improvement in percent changes in coronary artery spasm was greatest in the Diltiazem Group (50.4±8.8% vs. 67.8±12.8% vs. 46.8±12.3%, Nebivolol Group vs. Diltiazem Group p = 0.008; Nebivolol Group vs. Low-dose Combination Group p = 0.999; Diltiazem Group vs. Low-dose Combination Group p = 0.017). The overall Seattle Angina Questionnaire scores were significantly elevated at 12 weeks compared to the baseline in entire study population. There were no significant differences between the three groups in the overall Seattle Angina Questionnaire score changes and blood pressure changes.ConclusionsBoth nebivolol and diltiazem showed significant coronary vasospasm reduction effect, but the effect was greater for diltiazem.

To investigate whether specific time series patterns for blood pressure (BP), heart rate (HR), and sympathetic tone are associated with metabolic factors and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). A total of 989 patients who underwent simultaneous 24-hour ambulatory BP and Holter electrocardiogram monitoring were enrolled. The patients were categorized into sixteen groups according to their circadian patterns using the consensus clustering analysis method. Metabolic factors, including cholesterol profiles and apolipoprotein, were compared. The 10-year ASCVD risk was estimated based on the Framingham risk model. Overall, 16 significant associations were found between the clinical variables and cluster groups. Age was commonly associated with all clusters in systolic BP (SBP), diastolic BP (DBP), HR, and sympathetic tone. Metabolic indicators, including diabetes, body mass index, total cholesterol, high-density lipoprotein, and apolipoprotein, were associated with the four sympathetic tone clusters. In the crude analysis, the ASCVD risk increased incrementally from clusters 1 to 4 across SBP, DBP, HR, and sympathetic tone. After adjustment for multiple variables, however, only sympathetic tone clusters 3 and 4 showed a significantly high proportion of patients at high risk (≥7.5%) of 10-year ASCVD (odds ratio OR=5.90, 95% confidential interval CI=1.27–27.46, and P value = 0.024 and OR=15.28, 95% CI=3.59–65.11, and P value < 0.001, respectively). Time series patterns of BP, HR, and sympathetic tone can serve as an indicator of aging. Circadian variations in sympathetic tone can provide prognostic information about patient metabolic profiles and indicate future ASCVD risk.

Energy demand has grown explosively in recent years, leading to increased attention of energy efficiency (EE) research. Demand response (DR) programs were designed to help power management entities meet energy balance and change end-user electricity usage. Advanced real-time meters (RTM) collect a large amount of fine-granular electric consumption data, which contain valuable information. Understanding the energy consumption patterns for different end users can support demand side management (DSM). This study proposed clustering algorithms to segment consumers and obtain the representative load patterns based on diurnal load profiles. First, the proposed method uses discrete wavelet transform (DWT) to extract features from daily electricity consumption data. Second, the extracted features are reconstructed using a statistical method, combined with Pearson’s correlation coefficient and principal component analysis (PCA) for dimensionality reduction. Lastly, three clustering algorithms are employed to segment daily load curves and select the most appropriate algorithm. We experimented our method on the Manhattan dataset and the results indicated that clustering algorithms, combined with discrete wavelet transform, improve the clustering performance. Additionally, we discussed the clustering result and load pattern analysis of the dataset with respect to the electricity pattern.

Ovarian cancer: Natural compound suppresses cancer cell invasiveness Rab coupling protein (RCP)-induced tumor cell migration has been implicated in tumor pathophysiology and patient outcomes. Hoi Young Lee and colleagues at Konyang University in Daejeon, South Korea, have previously shown that RCP promotes ovarian cancer cell invasiveness by stabilizing cell adhesion receptors. In their latest study they find that RCP also increases the levels of two of its protein-binding partners and activates an important mediator of growth factor signaling, Focal Adhesion Kinase (FAK). Interestingly, treating ovarian cancer cells with curcumin, a natural compound extracted from the spice turmeric, not only blocked the effects of RCP on cell adhesion and FAK activation, it also potentiated the inhibitory effects of the chemotherapeutic agent doxorubicin on cell invasiveness. Further research will determine whether curcumin could be used to halt ovarian cancer progression.

Abstract Background Hypertension is a risk factor for coronary heart disease and stroke, and is one of the leading causes of death. Although over a billion people are affected worldwide, only half of them receive adequate treatment. Current guidelines on antihypertensive treatment recommend combination therapy for patients not responding to monotherapy, but as the number of pills increase, patient compliance tends to decrease. As a result, fixed-dose combination drugs with different antihypertensive agents have been developed and widely used in recent years. CCBs have been shown to be better at reducing central blood pressure and arterial stiffness than diuretics. Recent studies have reported that central blood pressure and arterial stiffness are associated with cardiovascular outcomes. This trial aims to compare the efficacy of combination of calcium channel blocker (CCB) or thiazide diuretic with an angiotensin receptor blocker (ARB). Methods This is a multicenter, double-blinded, active-controlled, phase 4, randomized trial, comparing the antihypertensive effects of losartan/amlodipine and losartan/hydrochlorothiazide in patients unresponsive to treatment with losartan. The primary endpoint is changes in mean sitting systolic blood pressure (msSBP) after 4 weeks of treatment. Secondary endpoints are changes in msSBP, mean 24-h ambulatory mobile blood pressure, mean 24-h ambulatory mobile central SBP, mean 24-h ambulatory carotid-femoral pulse wave velocity, ambulatory augmentation index, and microalbuminuria/proteinuria after 20 weeks of treatment. The sample size will be 119 patients for each group in order to confer enough power to test for non-inferiority regarding the primary outcome. Conclusion The investigators aim to prove that combination of a CCB with ARB shows non-inferiority in lowering blood pressure compared with a combination of thiazide diuretic and ARB. We also hope to distinguish the subset of patients that are more responsive to certain types of combination drugs. The results of this study should aid physicians in selecting appropriate combination regimens to treat hypertension in certain populations. Trial registration ClinicalTrials.gov NCT02294539. Registered 12 November 2014.

Background The purpose of this study was to assess the correlation between the 2-dimensional (2D) extent of orbital defects and the 3-dimensional (3D) volume of herniated orbital content in patients with an orbital wall fracture. Methods This retrospective study was based on the medical records and radiologic data of 60 patients from January 2014 to June 2016 for a unilateral isolated orbital wall fracture. They were classified into 2 groups depending on whether the fracture involved the inferior wall (group I, n=30) or the medial wall (group M, n=30). The 2D area of the orbital defect was calculated using the conventional formula. The 2D extent of the orbital defect and the 3D volume of herniated orbital content were measured with 3D image processing software. Statistical analysis was performed to evaluate the correlations between the 2D and 3D parameters. Results Varying degrees of positive correlation were found between the 2D extent of the orbital defects and the 3D herniated orbital volume in both groups (Pearson correlation coefficient, 0.568−0.788; R2=32.2%−62.1%). Conclusions Both the calculated and measured 2D extent of the orbital defects showed a positive correlation with the 3D herniated orbital volume in orbital wall fractures. However, a relatively large volume of herniation (>0.9 cm3) occurred not infrequently despite the presence of a small orbital defect (

Hypoxia is an important cause of acute kidney injury (AKI) in various conditions because kidneys are one of the most susceptible organs to hypoxia. In this study, we investigated whether nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase 4 (Nox4) plays a role in hypoxia induced AKI in a cellular and animal model. Expression of Nox4 in cultured human renal proximal tubular epithelial cells (HK-2) was significantly increased by hypoxic stimulation. TGF-β1 was endogenously secreted by hypoxic HK-2 cells. SB4315432 (a TGF-β1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells through the Smad-dependent cell signaling pathway. Silencing of Nox4 using Nox4 siRNA and pharmacologic inhibition with GKT137831 (a specific Nox1/4 inhibitor) reduced the production of ROS and attenuated the apoptotic pathway. In addition, knockdown of Nox4 increased cell survival in hypoxic HK-2 cells and pretreatment with GKT137831 reproduce these results. This study demonstrates that hypoxia induces HK-2 cell apoptosis through a signaling pathway involving TGF-β1 via Smad pathway induction of Nox4-dependent ROS generation. In an ischemia/reperfusion rat model, pretreatment of GKT137831 attenuated ischemia/reperfusion induced acute kidney injury as indicated by preserved kidney function, attenuated renal structural damage and reduced apoptotic cells. Therapies targeting Nox4 may be effective against hypoxia-induced AKI.

In statin therapy, the prognostic role of achieved low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) in cardiovascular outcomes has not been fully elucidated. A total of 4,803 percutaneous coronary intervention (PCI)-naïve patients who prescribed moderate intensity of statin therapy were followed up. Total and each component of major adverse cardiovascular events (MACE) according to LDL-C and hsCRP quartiles were compared. The incidence of 5-year total MACEs in the highest quartile group according to the followed-up hsCRP was higher than that in the lowest quartile (hazard ratio (HR) = 2.16, p

Lysophosphatidic acid (LPA), a bioactive lipid produced extracellularly by autotaxin (ATX), has been known to induce various pathophysiological events, including cancer cell invasion and metastasis. Discoidin domain receptor 2 (DDR2) expression is upregulated in ovarian cancer tissues, and is closely associated with poor clinical outcomes in ovarian cancer patients. In the present study, we determined a critical role and signaling cascade for the expression of DDR2 in LPA-induced ovarian cancer cell invasion. We also found ectopic expression of ATX or stimulation of ovarian cancer cells with LPA-induced DDR2 expression. However, the silencing of DDR2 expression significantly inhibited ATX- and LPA-induced ovarian cancer cell invasion. In addition, treatment of the cells with pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and mTOR abrogated LPA-induced DDR2 expression. Moreover, we observed that HIF-1α, located downstream of the mTOR, is implicated in LPA-induced DDR2 expression and ovarian cancer cell invasion. Finally, we provide evidence that LPA-induced HIF-1α expression mediates Twist1 expression to upregulate DDR2 expression. Collectively, the present study demonstrates that ATX, and thereby LPA, induces DDR2 expression through the activation of the PI3K/Akt/mTOR/HIF-1α/Twist1 signaling axes, aggravating ovarian cancer cell invasion.

We investigate the role of tellurite on a lithium-silicate glass 0.1 TeO2 − 0.9 (Li2O-2SiO2) (LSTO) system proposed for the use in solid electrolyte for lithium ion batteries. The measurements of electrical impedance are performed in the frequency 100 Hz–30 MHz and temperature from 50 to 150 °C. The electrical conductivity of LSTO glass increases compared with that of Li2O-2SiO2 (LSO) glass due to an increase in the number of Li+ ions. The ionic hopping and relaxation processes in disordered solids are generally explained using Cole–Cole, power law and modulus representations. The power law conductivity analysis, which is driven by the modified Rayleigh equation, presents the estimation of the number of ionic charge carriers explicitly. The estimation counts for direct contribution of about a 14% increase in direct current conductivity in the case of TeO2 doping. The relaxation process by modulus analysis confirms that the cations are trapped strongly in the potential wells. Both the direct current and alternating current activation energies (0.62–0.67 eV) for conduction in the LSO glass are the same as those in the LSTO glass.