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Background Pneumonia has been widely recognized as the leading cause of death in children worldwide, but its etiology still remains unclear. Objective We examined the association between maternal exposure to ambient air temperature during pregnancy and lifetime pneumonia in the offspring. Methods We conducted a cohort study of 2598 preschool children aged 3–6 years in Changsha, China. The lifetime prevalence of pneumonia was assessed using questionnaire. We backwards estimated each child's exposure to air temperature during prenatal and postnatal periods. Multiple regression model was used to examine the association between childhood pneumonia and exposure to air temperature in terms of odd ratios (OR) and 95% confidence interval (CI). Results Prevalence of childhood pneumonia in Changsha was high up to 38.6%. We found that childhood pneumonia was significantly associated with prenatal exposure to air temperature, with adjusted OR (95% CI) = 1.77 (1.23–2.54) for an interquartile range (IQR) increase in temperature, particularly during the second trimester with adjusted OR (95% CI) = 2.26 (1.32–3.89). Boys are more susceptible to the risk of pneumonia due to air temperature than girls. We further observed that maternal exposure to extreme heat days during pregnancy increased the risk of pneumonia in the offspring. Conclusions Maternal exposure to air temperature during pregnancy, particularly the second trimester, was associated with pneumonia in the children, providing the evidence for fetal origins of pneumonia. [ABSTRACT FROM AUTHOR]

The enzyme 4-oxalocrotonate tautomerase (4-OT) promiscuously catalyzes the Michael-type addition of acetaldehyde to β-nitrostyrene derivatives to yield chiral γ-nitroaldehydes, which are important precursors for pharmaceutically active γ-aminobutyric acids. In this study, we investigated the effect of different substituents at the aromatic ring of the Michael acceptor on the catalytic efficiency and stereoselectivity of the 4-OT-catalyzed acetaldehyde addition reactions. Highly enantioenriched ( R)- and ( S)-γ-nitroaldehydes and 4-substituted chroman-2-ol could be obtained in good to excellent yields by applying different substituents at appropriate positions of the aromatic substrate. Stereochemical control of these enzymatic Michael-type additions by 'substrate engineering' allowed the enantioselective synthesis of valuable γ-aminobutyric acid precursors. In addition, the results suggest a novel enzymatic synthesis route towards precursors for chromans and derivatives, which are valuable scaffolds for preparing biologically active natural products. [ABSTRACT FROM AUTHOR]

Numerous enzymes have been found to catalyze additional and completely different types of reactions relative to the natural activity they evolved for. This phenomenon, called catalytic promiscuity, has proven to be a fruitful guide for the development of novel biocatalysts for organic synthesis purposes. As such, enzymes have been identified with promiscuous catalytic activity for, one or more, eminent types of carbon–carbon bond-forming reactions like aldol couplings, Michael(-type) additions, Mannich reactions, Henry reactions, and Knoevenagel condensations. This review focuses on enzymes that promiscuously catalyze these reaction types and exhibit high enantioselectivities (in case chiral products are obtained). [ABSTRACT FROM AUTHOR]

Call me Michaelase: The enzyme 4‐oxalocrotonate tautomerase (4‐OT) promiscuously catalyzes the Michael‐type addition of acetaldehyde to a collection of aromatic and aliphatic nitroolefins with high stereoselectivity producing precursors of γ‐aminobutyric acid (GABA) analogues (see scheme). [ABSTRACT FROM AUTHOR]

Abstract: Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, has been reported to have the ability of influencing the invasion of human cancer cells. In the present study, using the human colon carcinoma cell line LOVO, we demonstrated that propofol stimulation significantly decreased the expression of MMP-2 and -9 and subsequently decreased the invasive activity of the cancer cells. Because MAPK signaling is one of the key regulators of MMP expression, we further evaluated MAPK signaling after stimulation with propofol. It was found that propofol stimulation inhibited the phosphorylation of MAPKs, including ERK1/2, JNK, and p38. Deactivation of ERK1/2 phosphorylation was sustained for up to 12h, while deactivation of phosphorylation of JNK and p38 returned to the endogenous level by 30min. It was noteworthy that the ras/raf/MEK/ERK pathway inhibitor PD98059 attenuated the down-regulation of propofol-induced MMP-9 expression of LOVO cells. We also demonstrated that the propofol-induced decrease in invasive ability via ERK1/2 down-regulation was mediated mainly through the GABA-A receptor. These results indicate that propofol stimulation inhibits cancer cell invasion and that the effect is partly due to ERK1/2-dependent down-regulation of MMPs. [ABSTRACT FROM AUTHOR]

To address the problems of low accuracy in fault diagnosis of oil-immersed transformers, poor state perception ability and real-time collaboration during diagnosis feedback, a fault diagnosis method for transformers based on the integration of digital twins is proposed. Firstly, fault sample balance is achieved through Iterative Nearest Neighbor Oversampling (INNOS), Secondly, nine-dimensional ratio features are extracted, and the correlation between dissolved gases in oil and fault types is established. Then, sparse principal component analysis (SPCA) is used for feature fusion and dimensionality reduction. Finally, the Aquila Optimizer (AO) is introduced to optimize the parameters of the Kernel Extreme Learning Machine (KELM), establishing the optimal AO-KELM diagnosis model. The final fault diagnosis accuracy reaches 98.1013%. Combining transformer digital twin models, real-time interaction mapping between physical entities and virtual space is achieved, enabling online diagnosis of transformer faults. Experimental results show that the method proposed in this paper has high diagnostic accuracy and strong stability, providing reference for the intelligent operation and maintenance of transformers. [ABSTRACT FROM AUTHOR]

• Calculation method of dynamic radiant heat transfer load based on harmonic reaction method is introduced. • The proposed method has certain accuracy and reliability through the validation of experiments. • The radiant heat transfer is calculated considering the direct radiation and reflection radiation. • Characteristics analysis of outdoor climatic conditions, building types and stratified heights is performed. The stratified air conditioning systems are widely used in large space buildings. Stratified air conditioning load (SACL) is the basis for determining the cooling capacity of air conditioning system, and it is also the key to assess its energy savings of stratified cooling. Calculation of the radiant heat transfer load (RHTL) is the difficult point to determine the SACL. In recent years, there have been many researches on the calculation of SACL. Most of them are steady-state calculation processes, and there are few studies on dynamic calculation processes. Therefore, the RHTL is taken as the research object, a novel calculation method is proposed according to the harmonic reaction method (HRM) and verified by the experiments. Experimental radiant heat transfer load can be received through convection and radiation separating method. The experimental and theoretical values of RHTL were compared and it was found that the theoretical values were in good agreement with experimental values. Therefore, the proposed method can be used to predict the unsteady RHTL accurately. Based on the verified calculation method, the effects of outdoor climatic conditions, building types and stratified heights on RHTL of an actual large space building are analyzed, which will contribute to the design and optimization of stratified air conditioning system for large space buildings. [ABSTRACT FROM AUTHOR]

Abstract Although ambient particulate matter or particles have been found to be associated with morbidity and mortality all over the world, specific health effects of particles from different sources need further elucidation. The objective of this work is to predict the deposition of particles from different sources in the human lung. The whole lung, consisting of 24 generations of branches from trachea to alveoli, was approximated using a one-dimensional lumped "trumpet" model with a variable cross-sectional area. The aerosol dynamics equation was numerically solved using a finite difference method to investigate the transport and deposition of particles in the lung model. Particles from various sources were assumed to be different in both size and density. We found that in general, coarse particles (> 2.5 µm) were mainly deposited in the tracheobronchial (TB) region by impaction, and fine particles (< 2.5 µm) were mainly deposited in the pulmonary (P) region by sedimentation and diffusion. However, the coarse particles with low density can be deposited in P region by sedimentation. As a comparison, our results found that soil particles, which are coarse with low density, were deposited in the deep lung more than traffic particles, which are fine with high density. Modeling of particle deposition in the human lung indicated that coarse particles generated by crustal sources may have adverse health effects as strong as those resulting from fine particles generated from combustion sources. Graphical abstract fx1 Highlights • We examined particle deposition in the human lung using a one-dimensional "trumpet" model. • Particles from various sources differ in both size and density. • Coarse particles with low density can be deposited deep in the lungs as fine particles with high density. • The health effects of soil dust may be strong as those caused by traffic particles. • Health effects of coarse particles cannot be ignored. [ABSTRACT FROM AUTHOR]

Background Pneumonia is a common early-childhood respiratory infection that leads to long-term health impacts, but its risk factors remain unclear. Objective To examine the association between early life exposure to both outdoor and indoor air pollution and childhood pneumonia. Methods We conducted a retrospective cohort study of 2598 children aged 3–6 years in Changsha, China (2011-2012). Children's life-time prevalence of pneumonia and exposure to indoor air pollution related to home renovation were surveyed by a questionnaire answered by the parents. Children's exposure to outdoor air pollution, including nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), and particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ), was estimated using the measured concentrations at monitoring stations. Association between childhood pneumonia and exposure to indoor and outdoor air pollution during both prenatal and postnatal periods were examined by using logistic regression model in terms of odds ratio (OR) and 95% confidence interval (CI). Results Life-time prevalence of pneumonia in preschool children in Changsha is high, up to 38.6%.We found that childhood pneumonia was associated with postnatal exposure to outdoor particulate air pollutant PM 10 , adjusted OR (95% CI) = 1.26 (1.00–1.57) for per 6 μg/m 3 increase in the concentration. Pneumonia was also associated with postnatal exposure to indoor renovation, adjusted OR (95% CI) = 1.30 (1.02–1.64) for new furniture and 1.30 (1.00–1.69) for redecoration. Combined exposure to outdoor high PM 10 and indoor renovation significantly increased the pneumonia risk. Sensitivity analysis indicated that the association was heterogeneous in different subgroups, but stronger in male and younger children. Conclusion High prevalence of childhood pneumonia in China may be associated with postnatal exposure to ambient particulate air pollution and house renovation. [ABSTRACT FROM AUTHOR]

The article presents chemical equations for article "Biocatalytic Michael-Type Additions of Acetaldehyde to Nitroolefins with the Proline- Based Enzyme 4-Oxalocrotonate Tautomerase Yielding Enantioenriched γ-Nitroaldehydes" by Y. Miao and others, in "Chemistry: A European Journal" in 2013.

Background: Evidence suggests that altered DNA methylation plays a causative role in the occurrence, progression and prognosis of gastric cancer (GC). Thus, methylated-differentially expressed genes (MDEGs) could potentially serve as biomarkers and therapeutic targets in GC. Methods: Four genomics profiling datasets were used to identify MDEGs. Gene Ontology enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis were used to explore the biological roles of MDEGs in GC. Univariate Cox and LASSO analysis were used to identify survival-related MDEGs and to construct a MDEGs-based signature. The prognostic performance was evaluated in two independent cohorts. Results: We identified a total of 255 MDEGs, including 192 hypermethylation-low expression and 63 Hypomethylation-high expression genes. The univariate Cox regression analysis showed that 83 MDEGs were associated with overall survival. Further we constructed an eight-MDEGs signature that was independent predictive of prognosis in the training cohort. By applying the eight-MDEGs signature, patients in the training cohort could be categorized into high-risk or low-risk subgroup with significantly different overall survival (HR = 2.62, 95% CI 1.71–4.02, P < 0.0001). The prognostic value of the eight-MDEGs signature was confirmed in another independent GEO cohort (HR = 1.35, 95% CI 1.03–1.78, P = 0.0302) and TCGA-GC cohort (HR = 1.85, 95% CI 1.16–2.94, P = 0.0084). Multivariate cox regression analysis proved the eight-MDEGs signature was an independent prognostic factor for GC. Conclusion: We have thus established an innovative eight-MDEGs signature that is predictive of overall survival and could be a potentially useful guide for personalized treatment of GC patients. [ABSTRACT FROM AUTHOR]

Abstract Although health benefits of physical activity are well known, the risk of physical activity in polluted air is unclear. Our objective is to investigate health effects resulting from physical activity in polluted air by looking at particle deposition in human tracheobronchial (TB) airways. Airflow and particle deposition in TB airways were investigated using a computational fluid dynamics (CFD) method. We chose three regional airways: upper (G3–G5), central (G9–G11) and lower (G14–G16). Physical activity was described by breathing rate at the mouth, for three levels of activity: sedentary (15 l/min), moderate (30 l/min) and intense (60 l/min). We found that particle deposition was strongly affected by physical activity. Particles are deposited in greater number in the lower airways (G14–G16) during sedentary activity, more in the upper airways (G3–G5) during intense activity, and uniformly in the airways during moderate activity. The difference in the deposition pattern was due to the reason that physical activity increased the airflow which increased inertial impaction. Our modeling of particle deposition in the human respiratory airways shows that there are different health effects for different activity levels: sedentary activity leads to chronic health effects, intense activity results in acute effects, and moderate activity minimizes the adverse health effects of physical activity in polluted air. Graphical abstract Unlabelled Image Highlights • Physical activity is generally good for health but increases exposure to air pollution. • We examined particle deposition in human airways for different levels of physical activity. • Inactivity increases particle deposition in lower airways resulting in chronic health effects. • Intense activity increases particle deposition in upper airways resulting in acute health effects. • We found health benefits of moderate activity when exposed to air pollution. [ABSTRACT FROM AUTHOR]

Background Thermal comfort in traditionally uniform environment is apparent and can be improved by increasing energy expenses. To save energy, non-uniform environment implemented by personalized conditioning system attracts considerable attention, but human response in such environment is unclear. Objectives To investigate regional- and whole-body thermal sensation and comfort in a cool environment with personalized heating. Methods In total 36 subjects (17 males and 19 females) including children, adults and the elderly, were involved in our experiment. Each subject was first asked to sit on a seat in an 18 °C chamber (uniform environment) for 40 min and then sit on a heating seat in a 16 °C chamber (non-uniform environment) for another 40 min after 10 min break. Subjects' regional- and whole-body thermal sensation and comfort were surveyed by questionnaire and their skin temperatures were measured by wireless sensors. We statistically analyzed subjects' thermal sensation and comfort and their skin temperatures in different age and gender groups and compared them between the uniform and non-uniform environments. Results Overall thermal sensation and comfort votes were respectively neutral and just comfortable in 16 °C chamber with personalized heating, which were significantly higher than those in 18 °C chamber without heating (p < 0.01). The effect of personalized heating on improving thermal sensation and comfort was consistent in subjects of different age and gender. However, adults and the females were more sensitive to the effect of personalized heating and felt cooler and less comfort than children/elderly and the males respectively. Variations of the regional thermal sensation/comfort across human body were consistent with those of skin temperature. Conclusions Personalized heating significantly improved human thermal sensation and comfort in non-uniform cooler environment, probably due to the fact that it increased skin temperature. However, the link between thermal sensation/comfort and variations of skin temperature is rather complex and warrant further investigation. [ABSTRACT FROM AUTHOR]

Apocynin is a widely used antioxidant in both basic and clinical research. The current study aimed to investigate the protective effect of apocynin in an established alcoholic steatohepatitis rat model. Healthy SD rats were gastrically fed with ethanol (4.0 g/kg) for 8 weeks to induce alcoholic steatohepatitis. After 8 weeks, rats were fed with ethanol for another 2 weeks with or without a daily intraperitoneal injection of 25 mg/kg apocynin. After sacrificing, serum and liver samples were subjected to hepatic injury measurements. After 8-week ethanol induction, rats exhibited typical alcoholic steatohepatitis features including reduced body weight, hepatic histological changes, elevated serum alanine transaminase (ALT) level, increased levels of oxidative stress and inflammatory markers, NADPH oxidases, and renin-angiotensin system (RAS) marker. Co-treatment of apocynin alleviated the hepatic injury and biochemical parameters induced by alcoholic steatohepatitis. In conclusion, addition of apocynin significantly attenuates hepatic oxidative stress and inflammation induced by alcoholic steatohepatitis. This effect is partly through the inhibition of the RAS system. [ABSTRACT FROM AUTHOR]

The physiologically based pharmacokinetic (PBPK) model is a useful tool to predict the pharmacokinetics of various types of nanoparticles (NPs). The endocytosis mechanism plays a key role in pharmacokinetics of NPs. However, the effect of endocytosis mechanism both in the blood and tissue are seldom considered in PBPK model. To investigate the biodistribution of intravenously injected pegylated AuNPs in mice and human using PBPK model considering the endocytosis mechanism both in the blood and tissue. Taking polyethylene glycol-coated gold nanoparticles (AuNPs) as an example, we developed a PBPK model to explore biodistribution of different size AuNPs. In the model, we considered the role of endocytosis mechanism both in the blood and tissue. In addition, the size-dependent permeability coefficient, excretion rate constant, phagocytic capacity, uptake rate, and release rate were derived from literatures. The mice PBPK model was extrapolated to the human by changing physiology parameters and the number of phagocytic cell (PCs). AuNPs were primarily distributed in the blood, liver, and spleen regardless of particle size, and almost all captured by the PCs in the liver and spleen, while few was captured in the blood. There are more organ distribution and longer circulation for smaller NPs. The 24-h accumulation of AuNPs decreased with increasing size in the most organ, while the accumulation of AuNPs showed an inverted U-shaped curve in the liver and slight U-shaped curve in the blood. The human results of model-predicted displayed a similar tendency with those in mice. Size, partition coefficients, and body weight were the key factors influencing the organ distribution of AuNPs. The size played an important role on the distribution and accumulation of AuNPs in various tissues. Our PBPK model was well predicted the NPs distribution in mice and human. A better understanding of these mechanisms could provide effective guides for nanomedine delivery. • Endocytosis was considered both in the blood and tissue. • The size-dependent phagocytic capacity, uptake rate, and release rate were derived. • The number concentration of AuNPs was adopted in the model. • Accumulation of AuNPs decreased with increasing size in the most organ. [ABSTRACT FROM AUTHOR]