Spatiotemporal Changes of Antibiotic Resistance, Potential Pathogens, and Health Risk in Kindergarten Dust.

The microorganisms present in kindergartens are extremely important for children's health during their three-year preschool education. To assess the risk of outdoor dust in kindergartens, the antibiotic resistome and potential pathogens were investigated in dust samples collected from 59 kindergartens in Xiamen, southeast China in both the winter and summer. Both high-throughput quantitative PCR and metagenome analysis revealed a higher richness and abundance of antibiotic resistance genes (ARGs) in winter (P < 0.05). Besides, the bloom of ARGs and potential pathogens was evident in the urban kindergartens. The co-occurrence patterns among ARGs, mobile genetic elements (MGEs), and potential pathogens suggested some bacterial pathogens were potential hosts of ARGs and MGEs. We found a large number of high-risk ARGs in the dust; the richness and abundance of high-risk ARGs were higher in winter and urban kindergartens compared to in summer and peri-urban kindergartens, respectively. The results of the co-occurrence patterns and high-risk ARGs jointly reveal that urbanization will significantly increase the threat of urban dust to human beings and their risks will be higher in winter. This study unveils the close association between ARGs/mobile ARGs and potential pathogens and emphasizes that we should pay more attention to the health risks induced by their combination.

Dynamics of Microbial Community and Potential Microbial Pollutants in Shopping Malls.

Shopping malls offer various niches for microbial populations, potentially serving as sources and reservoirs for the spread of microorganisms of public health concern. However, knowledge about the microbiome and the distribution of human pathogens in malls is largely unknown. Here, we examine the microbial community dynamics and genotypes of potential pathogens from floor and escalator surfaces in shopping malls and adjacent road dusts and greenbelt soils. The distribution pattern of microbial communities is driven primarily by habitats and seasons. A significant enrichment of human-associated microbiota in the indoor environment indicates that human interactions with surfaces might be another strong driver for mall microbiomes. Neutral community models suggest that the microbial community assembly is strongly driven by stochastic processes. Distinct performances of microbial taxonomic signatures for environmental classifications indicate the consistent differences of microbial communities of different seasons/habitats and the strong anthropogenic effect on homogenizing microbial communities of shopping malls. Indoor environments harbored higher concentrations of human pathogens than outdoor samples, also carrying a high proportion of antimicrobial resistance-associated multidrug efflux genes and virulence genes. These findings enhanced the understanding of the microbiome in the built environment and the interactions between humans and the built environment, providing a basis for tracking biothreats and communicable diseases and developing sophisticated early warning systems. IMPORTANCE Shopping malls are distinct microbial environments which can facilitate a constant transmission of microorganisms of public health concern between humans and the built environment or between human and human. Despite extensive investigation of the natural environmental microbiome, no comprehensive profile of microbial ecology has been reported in malls. Characterizing microbial distribution, potential pathogens, and antimicrobial resistance will enhance our understanding of how these microbial communities are formed, maintained, and transferred and help establish a baseline for biosurveillance of potential public health threats in malls.

Clinical features and genetic variations of severe neonatal hyperbilirubinemia: Five case reports.

BACKGROUND: Neonatal hyperbilirubinemia is a common problem faced by pediatricians. The role of genetic factors in neonatal jaundice has been gradually recognized. This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing (NGS). CASE SUMMARY: Five neonates with severe hyperbilirubinemia were retrospectively studied. They exhibited bilirubin encephalopathy, hypothyroidism, ABO blood type incompatibility hemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency and premature birth, respectively. A customized 22-gene panel was designed, and NGS was carried out for these neonates. Eight variations (G6PD c.G1388A, HBA2 c.C369G, ABCC2 c.C3825G, UGT1A1 c.G211A, SPTB c.A1729G, EPB41 c.G520A, c.1213-4T>G and c.A1474G) were identified in these five neonates. Genetic mutations of these genes are associated with G6PD deficiency, thalassemia, Dubin-Johnson syndrome, Gilbert syndrome, hereditary spherocytosis, and hereditary elliptocytosis. One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A (p.E174K), but no elliptocyte was seen on his blood smear of 4 years old. CONCLUSION: Pathological factors of severe neonatal hyperbilirubinemia are complicated. Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia, and severe jaundice in neonates may be related to a cumulative effect of genetic variants.

Ammonium has stronger Cd detoxification ability than nitrate by reducing Cd influx and increasing Cd fixation in Solanum nigrum L.

Cadmium (Cd) is a harmful heavy metal that affects the growth and development of plants. Nitrogen (N) is an essential nutrient for plants, and appropriate N management can improve Cd tolerance. The aim of our study was to explore the effects of different forms of N on the molecular and physiological responses of the hyperaccumulator Solanum nigrum to Cd toxicity. Measurement of biomass, photosynthetic parameters, and Cd2+ fluxes using non-invasive micro-test technique, Cd fluorescent dying, biochemical methods and quantitative real-time PCR analysis were performed in our study. Our results showed that ammonium (NH4+) has stronger Cd detoxification ability than nitrate (NO3-), which are likely attributed to the following three reasons: (1) NH4+ decreased the influx and accumulation of Cd2+ by regulating the transcription of Cd transport-related genes; (2) the ameliorative effects of NH4+ were accompanied by the increased retention of Cd in the cell walls of roots; and (3) NH4+ up-regulated SnExp expression.

Natural killer cells promote the differentiation of follicular helper T cells instead of inducing apoptosis in myasthenia gravis.

Recent evidence has shown that natural killer (NK) cells have an immunoregulatory function in the pathogenesis of myasthenia gravis (MG). In this study, the phenotype and function of NK cell subsets in peripheral blood of new-onset MG (N-MG) and stable MG (S-MG) patients were explored. Circulating CD56dim and CD56bright NK cells were increased and decreased, respectively, in patients with N-MG and S-MG compared with healthy control (HC). Moreover, all circulating NK cell subsets from N-MG patients showed significantly lower expression of activating receptor NKG2D and production of Interferon (IFN) -γ than that from HC. The killing effects of NK cells on CD4+ T cells and Tfh cells were impaired in MG patients, whereas, they promoted the differentiation and activation of Tfh cells. These data indicated that the immune-regulation of NK cells on CD4+ T cells and Tfh cells in MG patients was abnormal, which may contribute to the immune-pathological mechanism of MG.

Analysis of key genes reveal lysine demethylase 5B promotes prostate cancer progression.

Prostate cancer (PCa) is one of the most common types of cancer in males globally. However, the molecular mechanisms underlying PCa progression remain largely unclear. In the present study, Gene Expression Omnibus (GEO) datasets and datasets from The Cancer Genome Atlas (TCGA) were used to analyze the expression of lysine demethylase 5B (KDM5B) in PCa. Proliferation, cell cycle and migration assays were used to detect the functional roles of KDM5B. It was found KDM5B was upregulated in PCa tissues by analyzing GEO and TCGA datasets. KDM5B knockdown significantly suppressed proliferation and cell cycle progression in PCa cells. In additional, KDM5B knockdown inhibited PCa cell migration. By analyzing a TCGA dataset, KDM5B was found to be upregulated in patients at N1 stage compared with N0 stage PCa, in patients at T3+T4 stages compared with T2 stage and in patients with Gleason score ≥8 compared with those with score ≤7. Kaplan-Meier analysis revealed that higher expression of KDM5B was associated with shorter biochemical recurrence-free survival and overall survival time in patients with PCa. These results suggest that expression of KDM5B may serve as a biomarker to predict the outcome of PCa.

Fate of Labile Organic Carbon in Paddy Soil Is Regulated by Microbial Ferric Iron Reduction.

Global paddy soil is the primary source of methane, a potent greenhouse gas. It is therefore highly important to understand the carbon cycling in paddy soil. Microbial reduction of iron, which is widely found in paddy soil, is likely coupled with the oxidation of dissolved organic matter (DOM) and suppresses methanogenesis. However, little is known about the biotransformation of small molecular DOM accumulated under flooded conditions and the effect of iron reduction on the biotransformation pathway. Here, we carried out anaerobic incubation experiments using field-collected samples amended with ferrihydrite and different short-chain fatty acids. Our results showed that less than 20% of short-chain fatty acids were mineralized and released to the atmosphere. Using Fourier transform ion cyclotron resonance mass spectrometry, we further found that a large number of recalcitrant molecules were produced during microbial consumption of these short-chain fatty acids. Moreover, the biotransformation efficiency of short-chain fatty acids decreased with the increasing length of carbon chains. Ferrihydrite addition promoted microbial assimilation of short-chain fatty acids as well as enhanced the activation and biotransformation of indigenous stable carbon in the soil replenished with formate. This study demonstrates the significance of ferrihydrite in the biotransformation of labile DOM and promotes a more comprehensive understanding of the coupling of iron reduction and carbon cycling in paddy soils.

Adaptive Learning Control for Nonlinear Systems With Randomly Varying Iteration Lengths.

This paper proposes adaptive iterative learning control (ILC) schemes for continuous-time parametric nonlinear systems with iteration lengths that randomly vary. As opposed to the existing ILC works that feature nonuniform trial lengths, this paper is applicable to nonlinear systems that do not satisfy the globally Lipschitz continuous condition. In addition, this paper introduces a novel composite energy function based on newly defined virtual tracking error information for proving the asymptotical convergence. Both an original update algorithm and a projection-based update algorithm for estimating the unknown parameters are proposed. Extensions to cases with unknown input gains, iteration-varying tracking references, nonparametric uncertainty, high-order nonlinear systems, and multi-input-multi-output systems are all elaborated upon. Illustrative simulations are provided to verify the theoretical results.

A New Differential Evolution Algorithm for Minimax Optimization in Robust Design.

Minimax optimization, which is actively involved in numerous robust design problems, aims at pursuing the solutions with best worst-case performances. Although considerable research has been devoted to the development of minimax optimization algorithms, there still exist several fundamental limitations for existing approaches, e.g., restriction on problem types, excessively high computational cost, and low optimization efficiency. To address these issues, a minimax differential evolution algorithm is proposed in this paper. First, a novel bottom-boosting scheme enables the algorithm to identify the promising solutions in a reliable yet efficient manner. After that, a partial-regeneration strategy together with a new mutation operator contribute to an in-depth exploration over solution space. Finally, a proper integration of these newly proposed mechanisms leads to an algorithmic structure that can appropriately handle various types of problems. Empirical comparison with seven famous methods demonstrates the statistical superiority of the proposed algorithm. Successful applications in two open problems of robust design further validate the effectiveness of the new approach.

A mathematical prognosis model for pancreatic cancer patients receiving immunotherapy.

Pancreatic cancer is one of the most deadly types of cancer since it typically spreads rapidly and can seldom be detected in its early stage. Pancreatic cancer therapy is thus a challenging task, and appropriate prognosis or assessment for pancreatic cancer therapy is of critical importance. In this work, based on available clinical data in Niu et al. (2013) we develop a mathematical prognosis model that can predict the overall survival of pancreatic cancer patients who receive immunotherapy. The mathematical model incorporates pancreatic cancer cells, pancreatic stellate cells, three major classes of immune effector cells CD8+ T cells, natural killer cells, helper T cells, and two major classes of cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ). The proposed model describes the dynamic interaction between tumor and immune cells. In order for the model to be able to generate appropriate prognostic results for disease progression, the distribution and stability properties of equilibria in the mathematical model are computed and analysed in absence of treatments. In addition, numerical simulations for disease progression with or without treatments are performed. It turns out that the median overall survival associated with CIK immunotherapy is prolonged from 7 to 13months compared with the survival without treatment, this is consistent with the clinical data observed in Niu et al. (2013). The validity of the proposed mathematical prognosis model is thus verified. Our study confirms that immunotherapy offers a better prognosis for pancreatic cancer patients. As a direct extension of this work, various new therapy methods that are under exploration and clinical trials could be assessed or evaluated using the newly developed mathematical prognosis model.

[Pollution Characteristics and Ecological Risk Assessment of Vanadium in Sediments of the Three Gorges Reservoir (Chongqing-Yichang Section)].

In order to investigate the pollution characteristics of vanadium in sediments of the Three Gorges Reservoir (TGR), 67 sediment samples were collected from the section between Chongqing to Yichang in TGR. The concentration and chemical speciation of vanadium were measured and the spatial distribution of vanadium was discussed. Current pollution level of vanadium in TGR sediments was assessed by index of geoaccumulation and Häkanson ecological risk index. The results showed that:1the range of vanadium concentrations in TGR was 89.4-175.2 mg·kg-1 and the average concentration was 123.7 mg·kg-1, which was slightly higher than the background value in sediments of Yangtze River. 2the spatial distribution of vanadium in TGR sediments showed that vanadium concentrations in the mainstream of TGR were higher than those in tributaries and the vanadium contents in the sediments in downstream were higher than those in upstream in term of the mainstream of TGR. 3highest vanadium concentration was found in the sediment in a developed county, indicating that this high level of vanadium concentration was attributed to anthropogenic input. 4chemical forms of vanadium in sediments were mainly in residual state (80%-89%, mass fraction), which had a significant positive correlation with total concentrations in sediments. 5vanadium contamination degree and potential environmental risk in TGR sediments were weak.

Isoflavone Attenuates the Caspase-1 and Caspase-3 Level in Cell Model of Parkinsonism.

The study has investigated the effect of isoflavone attenuates the caspase-1 and caspase-3 level in cell model of Parkinsonism. The subjects were PC12 cells. They were randomly divided into six groups: control, MPP(+) (250 µmol/L), isoflavone (10 µM), isoflavone (10 µM) + MPP(+) (250 µmol/L), Z-YVAD-CHO (10 nM) + MPP(+) group, and Z-DEVD-CHO (10 nM) + MPP(+) group. Cell viability was measured by MTT methods; the content of tyrosine hydroxylase was measured by immunocytochemistry method of avidinbiotin peroxidase complex; apoptosis ratio was measured by flow cytometry. The results showed that cell viability in the MPP(+) group was lower than in all other five groups. There was no difference in cell viability between isoflavone + MPP(+) and control group. Optical density of TH positive cells in isoflavone group was higher than in control, isoflavone + MPP(+), and MPP(+) only groups. The apoptosis ratio in the isoflavone + MPP(+) group and control group and the Z-YVAD-CHO + MPP(+) and Z-DEVD-CHO + MPP(+) group was similar, which was lower than in the MPP(+) group. The lowest apoptosis ratio was found in the isoflavone only group.

Using Three-Dimensional Fluorescence Spectrum Technology to Analyze the Effects of Natural Dissolved Organic Matter on the Pesticide Residues in the Soil.

The behavior of pesticide in soil is influenced by dissolved organic matter (DOM) through competition adsorption, adsorption, solubilization, accelerated degradation, and so on. Thus DOM and its components play an important role in the environmental risk in the soil ecosystem and groundwater environment. Currently, most studies focused on the short-term effect of high concentration of DOM on the pesticide residues. However, soil DOM is mainly at low level. Therefore, there is of some practical significance to probe into the environmental behavior of soil pesticides under natural level of DOM. Thus a site investigation was conducted in the farmland with long-term application history of pesticide. By using the three dimensional excitation-emission fluorescence matrix (3D-EEM) technology, together with the fluorescence regional integration (FRI) quantitative method, the long-term effects of pesticide residues under low concentration of natural DOM were analyzed. Results showed that: (1) The long-term effects of the natural DOM components on the environment behavior of most soil organochlorine pesticides were not significant except for a few pesticides such as y-HCH, p, p'-DDE, etc. (2) The influencing effects of DOM components on different type of pesticides were varied. Among which, the content of tyrosine component showed a significantly negative correlation (p < 0.05) with the concentration of y-HCH and p, p'-DDE. There were significant positive correlations (p < 0.05) between the byproducts of microbial degradation in DOM components and the concentration of heptachlor. There were also a significant positive correlation (p < 0.05) between the content of active humus component of humic acid in the DOM and the concentration of heptachlor epoxide. These results suggested that the distribution of different types of pesticides residue in the soil was influenced by different components at different levels of significance. (3) The humification degree of soil organic matter showed minor effect of DOM on the pesticide residues in the soil. In this study, 3D-EEM and FRI technology were firstly coupled in use for studying the influence of different components of DOM in soil on the environmental behavior of pesticides, which provides a new idea for the research on the mechanism of pesticides transportation and transformation in soil and groundwater environment.

A 3D undulatory locomotion system inspired by nematode C. elegans.

This paper provides an undulatory locomotion model inspired by C. elegans, whose nervous system and muscular structure are well studied. C. elegans is divided into 11 muscle segments according to its anatomical structure, and represented as a multi-joint rigid link model in this work. In each muscle segment, there are four pieces of muscles located in four quadrants. The muscles change their lengths according to the outputs of nervous system. In this work, the dynamic neural networks (DNN) are adopted to represent the nervous system. The DNN are divided into the head DNN and the body DNN. The head DNN produces the sinusoid waves to generate the forward and backward undulatory movements. The body DNN with 11 segments is responsible for passing the sinusoid wave and creating the phase lag. The 3D locomotion of this system are implemented by using the DNN to control the muscle lengths, and then using the muscle lengths to control the angles between two consecutive links on both horizontal and vertical planes. The test results show good performances of this model in both forward and backward locomotion in 3D, which could serve as a prototype of the micro-robot for clinical use.

Biological modeling of complex chemotaxis behaviors for C. elegans under speed regulation--a dynamic neural networks approach.

In this paper, the modeling of several complex chemotaxis behaviors of C. elegans is explored, which include food attraction, toxin avoidance, and locomotion speed regulation. We first model the chemotaxis behaviors of food attraction and toxin avoidance separately. Then, an integrated chemotaxis behavioral model is proposed, which performs the two chemotaxis behaviors simultaneously. The novelty and the uniqueness of the proposed chemotaxis behavioral models are characterized by several attributes. First, all the chemotaxis behavioral model sare on biological basis, namely, the proposed chemotaxis behavior models are constructed by extracting the neural wire diagram from sensory neurons to motor neurons, where sensory neurons are specific for chemotaxis behaviors. Second, the chemotaxis behavioral models are able to perform turning and speed regulation. Third, chemotaxis behaviors are characterized by a set of switching logic functions that decide the orientation and speed. All models are implemented using dynamic neural networks (DNN) and trained using the real time recurrent learning (RTRL) algorithm. By incorporating a speed regulation mechanism, C. elegans can stop spontaneously when approaching food source or leaving away from toxin. The testing results and the comparison with experiment results verify that the proposed chemotaxis behavioral models can well mimic the chemotaxis behaviors of C. elegans in different environments.

Effects of synaptic connectivity on liquid state machine performance.

The Liquid State Machine (LSM) is a biologically plausible computational neural network model for real-time computing on time-varying inputs, whose structure and function were inspired by the properties of neocortical columns in the central nervous system of mammals. The LSM uses spiking neurons connected by dynamic synapses to project inputs into a high dimensional feature space, allowing classification of inputs by linear separation, similar to the approach used in support vector machines (SVMs). The performance of a LSM neural network model on pattern recognition tasks mainly depends on its parameter settings. Two parameters are of particular interest: the distribution of synaptic strengths and synaptic connectivity. To design an efficient liquid filter that performs desired kernel functions, these parameters need to be optimized. We have studied performance as a function of these parameters for several models of synaptic connectivity. The results show that in order to achieve good performance, large synaptic weights are required to compensate for a small number of synapses in the liquid filter, and vice versa. In addition, a larger variance of the synaptic weights results in better performance for LSM benchmark problems. We also propose a genetic algorithm-based approach to evolve the liquid filter from a minimum structure with no connections, to an optimized kernel with a minimal number of synapses and high classification accuracy. This approach facilitates the design of an optimal LSM with reduced computational complexity. Results obtained using this genetic programming approach show that the synaptic weight distribution after evolution is similar in shape to that found in cortical circuitry.

Relations between plasma von Willebrand factor or endothelin-1 and restenosis following carotid artery stenting.

OBJECTIVE: This study was designed to investigate the relation between plasma von Willebrand factor (VWF) or endothelin-1 (ET-1) and post-carotid artery stenting (CAS) restenosis. MATERIALS AND METHODS: Plasma levels of VWF and ET-1 were measured in 61 patients (36 males, mean age 64.4 ± 6.8 years) before and after CAS. The mean follow-up time was 13.8 ± 1.7 months (range, 6-63). In-stent restenosis was defined as a >10% narrowing of the vascular lumen with or without ischemic symptoms following CAS. RESULTS: In-stent restenosis was identified in 14 (23%) patients, including 3 with >50% restenosis. In the restenosis group, mean VWF and ET-1 levels at 2 weeks, 1 and 6 months after CAS were higher than the baseline levels (p < 0.05 or p < 0.01). Mean levels of VWF and ET-1 in the restenosis group were higher than in the non-restenosis group within 6 months after CAS (p < 0.05 or p < 0.01). CONCLUSION: Persistent elevation in plasma VWF and ET-1 within the first 6 months of CAS was found in patients with in-stent restenosis.

Adaptive learning control for finite interval tracking based on constructive function approximation and wavelet.

Using a constructive function approximation network, an adaptive learning control (ALC) approach is proposed for finite interval tracking problems. The constructive function approximation network consists of a set of bases, and the number of bases can evolve when learning repeats. The nature of the basis allows the continuous adaptive learning of parameters when the network undergoes any structural changes, and consequently offers the flexibility in tuning the network structure. The expandability of the bases guarantees precision of the function approximation and avoids the trial-and-error procedure in structure selection for any fixed structure network. Two classes of unknown nonlinear functions, namely, either global L(2) or local L(2) with a known bounding function, are taken into consideration. Using the Lyapunov method, the existence of solution and the convergence property of the proposed ALC system are discussed in a rigorous manner. By virtue of the celebrated orthonormal and multiresolution properties, wavelet network is used as the universal function approximator, with the weights tuned by the proposed adaptive learning mechanism.

High prevalence of impaired fasting glucose in Chinese children and adolescents with prehypertension/hypertension.

AIM: To assess the prevalence of impaired fasting glucose among Chinese children and adolescents with prehypertension/hypertension (PHP/HP), overweight/obesity (OW/OB) or both in the general population. METHODS: In total, 3409 children and adolescents among the age group of 10-18 years were enrolled. These subjects were then divided into four groups: OW/OB, PHP/HP, OW/OB + PHP/HP and a control group. Fasting plasma glucose (FPG) and lipid levels were measured in children with a body mass index > or =85th percentile and/or blood pressure > or =90th percentile and in 100 subjects randomly selected from the control group. The oral glucose tolerance test was performed in all the subjects with fasting glucose > or =5.6 mmol/L. RESULTS: Eighty-one impaired fasting glucose subjects and one girl with type 2 diabetes were identified. The prevalence of impaired fasting glucose in PHP/HP (7.03%) was not significantly different from that in the OW/OB + PHP/HP group (8.59%), but was higher than that in the OW/OB group (3.31%). CONCLUSION: Although the American Diabetes Association does not recommend the FPG test for children and adolescents with PHP/HP, in this study, we found that children and adolescents with PHP/HP have a higher prevalence of impaired fasting glucose than those with OW/OB. Further validation of these findings is warranted and a type 2 diabetes screening protocol for Chinese children and adolescents needs to be established.