Enhanced Oxidative Stress Is Responsible for TRPV4-Induced Neurotoxicity

Transient receptor potential vanilloid 4 (TRPV4) has been reported to be responsible for neuronal injury in pathological conditions. Excessive oxidative stress can lead to neuronal damage, and activation of TRPV4 increases the production of reactive oxygen species and nitric oxide (NO) in many types of cells. The present study explored whether TRPV4-induced neuronal injury is mediated through enhancing oxidative stress. We found that intracerebroventricular injection of the TRPV4 agonist GSK1016790A increased the content of methane dicarboxylic aldehyde (MDA) and NO in the hippocampus, which was blocked by administration of the TRPV4 specific antagonist HC-067047. The activities of catalase (CAT) and glutathione peroxidase (GSH-Px) were decreased by GSK1016790A, whereas the activity of superoxide dismutase remained unchanged. Moreover, the protein level and activity of neuronal nitric oxide synthase (nNOS) were increased by GSK1016790A, and the GSK1016790A-induced increase in NO content was blocked by an nNOS specific antagonist ARL-17477. The GSK1016790A-induced modulations of CAT, GSH-Px and nNOS activities and the protein level of nNOS were significantly inhibited by HC-067047. Finally, GSK1016790A-induced neuronal death and apoptosis in the hippocampal CA1 area were markedly attenuated by administration of a reactive oxygen species scavenger Trolox or ARL-17477. We conclude that activation of TRPV4 enhances oxidative stress by inhibiting CAT and GSH-Px and increasing nNOS, which is responsible, at least in part, for TRPV4-induced neurotoxicity

Association of Allergic Symptoms in the First 2 Years of Life With Sleep Outcomes Among Chinese Toddlers

Background: Previous studies have linked allergic symptoms to sleep in children, but the associations might be different when considering different types of allergic symptoms or sleep outcomes. Moreover, the combined effects of multiple allergic symptoms remain unclear in early life. This study aimed to investigate the associations between multiple allergic symptoms and sleep outcomes in early life. Methods: We included 673 toddlers aged 2 years from a birth cohort in Guangzhou, China. We identified allergic symptoms (skin, eyes and nose, gastrointestinal tract, mouth and lips, and wheeze) within 2 years via standard questionnaires. Sleep outcomes including sleep duration and quality over the past month were assessed based on the Chinese version of the Brief Infant Sleep Questionnaire. Associations between allergic symptoms and sleep outcomes were examined using multivariable linear regression and logistic regression. Results: Compared to children without allergic symptoms, children with allergic nasal and ocular symptoms had higher odds of frequent nighttime awakenings (OR = 1.41; 95% CI: 1.03, 1.93) and irregular sleep (OR = 1.45, 95% CI: 1.05, 2.00); children with allergic gastrointestinal symptoms slept 0.28 h less during nighttime (95% CI: -0.48, -0.07) and 0.25 h less per day (95% CI: -0.43, -0.08), and had 59% higher odds of irregular sleep (95% CI: 1.24, 2.04). We also found significant association of multiple allergic symptoms with shortened nighttime sleep duration and increased irregular sleep. Whereas, allergic skin, mouth and lips, and wheeze symptoms were not significantly associated with sleep outcomes. Conclusion: Allergic symptoms within 2 years of age were adversely associated with sleep outcomes, which highlight the importance of early screening of allergic symptoms in toddlers in order to improve their sleep outcomes

Influence of photochemical loss of volatile organic compounds on understanding ozone formation mechanism

Volatile organic compounds (VOCs) tend to be consumed by atmospheric oxidants, resulting in substantial photochemical loss during transport. An observation-based model was used to evaluate the influence of photochemical loss of VOCs on the sensitivity regime and mechanisms of ozone formation. Our results showed that a VOC-limited regime based on observed VOC concentrations shifted to a transition regime with a photochemical initial concentration of VOCs (PIC-VOCs) in the morning. The net ozone formation rate was underestimated by 3 ppbh(-1) (similar to 36 ppb d(-1)) based on the measured VOCs when compared with the PIC-VOCs. The relative contribution of the RO2 path to ozone production based on the PIC-VOCs accordingly increased by 13.4 %; in particular, the contribution of alkene-derived RO(2 )increased by approximately 10.2 %. In addition, the OH-HO2 radical cycle was obviously accelerated by highly reactive alkenes after accounting for photochemical loss of VOCs. The contribution of local photochemistry might be underestimated for both local and regional ozone pollution if consumed VOCs are not accounted for, and policymaking on ozone pollution prevention should focus on VOCs with a high reactivity.Peer reviewe

Water quality grade identification for lakes in middle reaches of Yangtze River using landsat-8 data with deep neural networks (DNN) model

Water quality grade is an intuitive element for people to understand the condition of water quality. However, in situ water quality grade measurements are often labor intensive, which makes measurement over large areas very costly and laborious. In recent years, numerous studies have demonstrated the effectiveness of remote sensing techniques in monitoring water quality. In order to automatically extract the water quality information, machine learning technologies have been widely applied in remote sensing data interoperation. In this study, Landsat-8 data and deep neural networks (DNN) were employed to identify the water quality grades of lakes in two cities, Wuhan and Huangshi, in the middle reach of the Yangtze River, central China. Additionally, linear support vector machine (L-SVM), random forest (RF), decision tree (DT), and multi-layer perceptron (MLP) were selected as comparative methods. The experimental results showed that DNN achieved the most promising performance compared to the other approaches. For the lakes in Wuhan, DNN gave water quality results with overall accuracy (OA) of 93.37% and Kappa of 0.9028. For the lakes in Huangshi, OA and kappa given by DNN were 96.39% and 0.951, respectively. The results show that the use of remote sensing images for water quality grade monitoring is effective. In the future, our method can be used for water quality monitoring of lakes in large areas at a low cost

A New Type of Quartz Smog Chamber : Design and Characterization

Publisher Copyright: ©Since the 1960s, many indoor and outdoor smog chambers have been developed worldwide. However, most of them are made of Teflon films, which have relatively high background contaminations due to the wall effect. We developed the world's first medium-size quartz chamber (10 m(3)), which is jointed with 32 pieces of 5 mm thick polished quartz glasses and a stainless-steel frame. Characterizations show that this chamber exhibits excellent performance in terms of relative humidity (RH) (2-80%) and temperature (15-30 +/- 1 degrees C) control, mixing efficiency of the reactants (6-8 min), light transmittance (>90% above 290 nm), and wall loss of pollutants. The wall loss rates of the gas-phase pollutants are on the order of 10(-4) min(-1) at 298 K under dry conditions. It is 0.08 h(-1) for 100-500 nm particles, significantly lower than those of Teflon chambers. The photolysis rate of NO2 (J(NO2)) is automatically adjustable to simulate the diurnal variation of solar irradiation from 0 to 0.40 min(-1). The inner surface of the chamber can be repeatedly washed with deionized water, resulting in low background contaminations. Both experiments (toluene-NOx and alpha-pinene-ozone systems) and box model demonstrate that this new quartz chamber can provide high-quality data for investigating SOA and O-3 formation in the atmosphere.Peer reviewe

Serum Starvation Induced Cell Cycle Synchronization Facilitates Human Somatic Cells Reprogramming

Human induced pluripotent stem cells (iPSCs) provide a valuable model for regenerative medicine and human disease research. To date, however, the reprogramming efficiency of human adult cells is still low. Recent studies have revealed that cell cycle is a key parameter driving epigenetic reprogramming to pluripotency. As is well known, retroviruses such as the Moloney murine leukemia virus (MoMLV) require cell division to integrate into the host genome and replicate, whereas the target primary cells for reprogramming are a mixture of several cell types with different cell cycle rhythms. Whether cell cycle synchronization has potential effect on retrovirus induced reprogramming has not been detailed. In this study, utilizing transient serum starvation induced synchronization, we demonstrated that starvation generated a reversible cell cycle arrest and synchronously progressed through G2/M phase after release, substantially improving retroviral infection efficiency. Interestingly, synchronized human dermal fibroblasts (HDF) and adipose stem cells (ASC) exhibited more homogenous epithelial morphology than normal FBS control after infection, and the expression of epithelial markers such as E-cadherin and Epcam were strongly activated. Futhermore, synchronization treatment ultimately improved Nanog positive clones, achieved a 15–20 fold increase. These results suggested that cell cycle synchronization promotes the mesenchymal to epithelial transition (MET) and facilitates retrovirus mediated reprogramming. Our study, utilization of serum starvation rather than additional chemicals, provide a new insight into cell cycle regulation and induced reprogramming of human cells

Cell Membrane Is Impaired, Accompanied by Enhanced Type III Secretion System Expression in Yersinia pestis Deficient in RovA Regulator

BACKGROUND: In the enteropathogenic Yersinia species, RovA regulates the expression of invasin, which is important for enteropathogenic pathogenesis but is inactivated in Yersinia pestis. Investigation of the RovA regulon in Y. pestis at 26 °C has revealed that RovA is a global regulator that contributes to virulence in part by the direct regulation of psaEFABC. However, the regulatory roles of RovA in Y. pestis at 37 °C, which allows most virulence factors in mammalian hosts to be expressed, are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: The transcriptional profile of an in-frame rovA mutant of Y. pestis biovar Microtus strain 201 was analyzed under type III secretion system (T3SS) induction conditions using microarray techniques, and it was revealed that many cell-envelope and transport/binding proteins were differentially expressed in the ΔrovA mutant. Most noticeably, many of the T3SS genes, including operons encoding the translocon, needle and Yop (Yersinia outer protein) effectors, were significantly up-regulated. Analysis of Yop proteins confirmed that YopE and YopJ were also expressed in greater amounts in the mutant. However, electrophoresis mobility shift assay results demonstrated that the His-RovA protein could not bind to the promoter sequences of the T3SS genes, suggesting that an indirect regulatory mechanism is involved. Transmission electron microscopy analysis indicated that there are small loose electron dense particle-like structures that surround the outer membrane of the mutant cells. The bacterial membrane permeability to CFSE (carboxyfluorescein diacetate succinimidyl ester) was significantly decreased in the ΔrovA mutant compared to the wild-type strain. Taken together, these results revealed the improper construction and dysfunction of the membrane in the ΔrovA mutant. CONCLUSIONS/SIGNIFICANCE: We demonstrated that the RovA regulator plays critical roles in the construction and functioning of the bacterial membrane, which sheds considerable light on the regulatory functions of RovA in antibiotic resistance and environmental adaptation. The expression of T3SS was upregulated in the ΔrovA mutant through an indirect regulatory mechanism, which is possibly related to the altered membrane construction in the mutant