Genotoxicity evaluation of silica nanoparticles in murine: a systematic review and meta-analysis.

Silica nanoparticles (SiNPs) have been widely used in nanotechnology, and more attention has been paid to their safety evaluation. However, there are still inconsistent conclusions about the genotoxicity of SiNPs. A systematic review was conducted to explore whether SiNPs have genotoxicity followed by a meta-analysis of in vivo and in vitro murine genotoxicity tests. A total of 26 eligible studies were identified in this meta-analysis through a detailed process of inclusion and exclusion, which included 9 in vivo studies, 15 in vitro studies, and 2 in both. The results of in vitro studies showed that SiNPs exposure significantly increased the indicators of the comet assay, such as tail DNA content (T DNA%), tail length (TL), and olive tail moment (OTM). Indicators of mutagenicity had not been affected in vitro studies, such as mutation frequency (MF) and micronucleus (MN) frequency. There was a significant increase in MN frequency, but there was no influence on T DNA% in vivo. Results of subgroup analysis indicated that size and treatment time of SiNPs were the associated factors in vitro genotoxicity. The size of SiNPs, <21 nm, induced more DNA damage than larger sized SiNPs. It could induce MN formation when the treatment time of SiNPs was <12 h, and even more DNA damage when the exposure time over 12 h. SiNPs can induce genotoxicity both in vivo and in vitro. Comet assay may be more sensitive to detect in vitro genotoxicity, and MN frequency may be more suitable to detect in vivo genotoxicity.

Attention allocation in pilots based on climbing and circling mission behavior.

OBJECTIVE: Exploration of changes in eye movement at different flight conditions can enrich scholarly understanding of situation awareness (SA) and inform new scanning behavior training techniques for efficient and effective pilot education. BACKGROUND: The SA requirements for pilots vary from mission to mission. Eye tracking is often used to analyze various attention allocation and SA acquisition processes at work in different missions. METHODS: Pilot eye movements were measured during a climbing task and circling task using a cockpit-based simulator. RESULTS: Results of situation awareness rating technique (SART) tests show that there are significant differences between attention processes during climbing versus circling flight tasks. Fixation frequency during climbing is lower than in the circling task. Additionally, saccade frequency and average fixation time in the climbing task are markedly higher than those in the circling task. Wilcoxon test results show that the pilot has a higher fixation count and fixation time during the circling phase in out-view (OV) areas of interest (AOI) than during the climbing phase. Notably, the attention probability is higher in climbing task than in circling task when the current area of fixation (AOF) is in the head-up display (HUD) AOI and the next fixation area is in the instrumentation panel left (IPL); when the current AOF is in the out-view right (OVR) and the next AOF is HUD, the attention probability is higher in climbing task than in circling task; when the current fixation is in the IPL and the next fixation probability is to the out-view left (OVL), the attention probability is higher in task climbing task than in circling task. In terms of the Markov stationary distribution, the Wilcoxon test shows that, when IPL AOI is the area of the maximum probability of fixation in both tasks, the attention probability of HUD AOI and instrumentation panel right (IPR) is higher in climbing task than in circling task. CONCLUSION: Circling tasks require efficient eye movement patterns accompanied by strict attention distribution, which yields high SA level and flight performance when performed properly. APPLICATION: This paper summarizes the attention characteristics at different flight phases and various requirements of different tasks according to pilot eye movement tracking results. Similar activities, as routine training, can enhance the efficiency of a novice pilot's attention distribution.

The Influence of Emotion Induced by Accidents and Incidents on Pilots' Situation Awareness.

(1) Background: This study examines the differences in emotions induced by accidents and incidents as emotional stimuli and the effects on pilot situation awareness (SA) after induction. (2) Method: Forty-five jet pilots were randomly divided into three groups after which their emotions were induced using the pictures of accident, incident, and neutral stimulus, respectively. (3) Results: The conditions of accidents and incidents both induced changes in the pilots' happiness and sadness and the changes in the emotion were regulated by the emotional intelligence of pilots in the high SA group. The emotion induction, which caused a direct change in pilot's happiness and fear, resulted in conditions that indirectly affected level 1 of SA in pilots. (4) Conclusions: The research elucidates the difference between accident and incident in inducing pilot emotions, and reminds us that SA level exerts the regulating effects on the same emotional induction conditions.

Lycopene Alleviates Titanium Dioxide Nanoparticle-Induced Testicular Toxicity by Inhibiting Oxidative Stress and Apoptosis in Mice.

PURPOSE: The research was carried out to investigate the possible ameliorative effect of lycopene on TiO2 NPs-induced male reproductive toxicity and explore the possible mechanism. METHODS: Ninety-six healthy male Institute of Cancer Research (ICR) mice were equally divided into eight groups (control group, 50 mg/kg TiO2 NPs group, 5 mg/kg LYC group, 20 mg/kg LYC group, 40 mg/kg LYC group, 50 mg/kg TiO2 NPs + 5 mg/kg LYC group, 50 mg/kg TiO2 NPs + 20 mg/kg LYC group, 50 mg/kg TiO2 NPs + 40 mg/kg LYC group), and the mice were treated by intragastric administration every day for 30 days in this research. Sperm parameters, testicular histopathology, oxidant and antioxidant enzymes, and cell apoptosis-related protein expression in the testicular tissue were analyzed. RESULTS: The results showed that TiO2 NPs exposure significantly decreased sperm count and motility, and TiO2 NPs also increased sperm malformation in the epididymis; these characteristics were improved when co-administration with LYC. Testicular histopathological lesions like disorder of germ cells arrange, detachment, atrophy, and vacuolization were observed after TiO2 NPs exposure, and these abnormalities were effectively ameliorated by co-administration with LYC. Oxidative stress was induced by TiO2 NPs exposure as evidenced by increased the level of MDA and decreased the activity of SOD as well as the level of anti-O2-, and these alterations were effectively prevented by co-administration with LYC. LYC also alleviated TiO2 NPs-induced germ cell apoptosis by inhibiting mitochondrial apoptotic pathway, as shown by the upregulation of Bcl-2, the downregulation of Bax, Cleaved Caspase 3, and Cleaved Caspase 9. CONCLUSION: LYC could ameliorate TiO2 NPs-induced testicular damage via inhibiting oxidative stress and apoptosis, which could be used to alleviate the testicular toxicity associated with TiO2 NPs intake.

Exploring the pharmacological action mechanism of Ligusticum Chuanxiong-Piper Longum couplet medicines on the treatment of migraine based on network pharmacology.

Objective: To study the mechanisms of the Ligusticum chuanxiong Hort.-Piper longum L. herbal pair (LPHP) in the treatment of migraine using network pharmacology. Methods: The active constituents of LPHP and their targets were searched for and screened using the Chinese Medicine System Pharmacology Database. Genes related to migraine were searched on GeneCards, Online Mendelian Inheritance in Man and other databases. Cytoscape was used to construct and combine active component-target and disease-target networks. The core target was screened by network topology analysis, and the Metascape database was used for gene ontology analysis of key targets and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to explore the molecular mechanisms in the treatment of migraine. Results: A total of 28 active constituents of LPHP were obtained through database screening and literature review, and 60 cross-linking targets were obtained. The target sites were analysed using a protein-protein interaction network to obtain six target proteins with a greater degree of relevance. These were identified as the main targets for the treatment of hypertension, and these key targets were found to be associated with 20 signalling pathways, including neuroactive ligand-receptor interaction, the calcium signalling pathway, the cGMP-PKG signalling pathway, pathways in cancer and the cyclic adenosine 3',5'-cyclic monophosphate (cAMP) signalling pathway. Conclusion: This study reveals the molecular mechanism of LPHP in the treatment of migraine from the perspective of network pharmacology and provides a basis for further research and molecular mechanism research.

Nanosized Titanium Dioxide Induced Apoptosis and Abnormal Expression of Blood-Testis Barrier Junction Proteins Through JNK Signaling Pathway in TM4 Cells.

Nanosized titanium dioxide (nano-TiO2) has been widely used in consumer products. It can cross the blood-testis barrier (BTB), and it has adverse effects on the male reproductive system. However, the specific mechanism has not been fully elucidated. The purpose of this study was to understand the role of the JNK signaling pathway in the apoptosis and abnormal expression of BTB junction proteins induced by nano-TiO2 in TM4 cells. After different concentration of nano-TiO2 treatments, the cell viability, apoptosis, mitochondrial membrane potential (Δψm), BTB junction proteins (Claudin-11, ZO-1, ß-catenin), apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3), and phosphorylated (p)-JNK protein were examined. The results showed that cell viability, apoptosis rates, Δψm, and apoptosis-related protein levels changed in a concentration-dependent manner. Cell viability decreased significantly from 100 µg/mL nano-TiO2 group. Apoptosis rates increased significantly from 150 µg/mL nano-TiO2 group, and Δψm decreased significantly from 150 µg/mL nano-TiO2 group. The protein levels of Bax, cleaved caspase-9, and cleaved caspase-3 increased significantly from 150 µg/mL nano-TiO2 group, and the protein level of Bcl-2 decreased significantly from 100 µg/mL nano-TiO2 group. The protein level of p-JNK increased significantly from 100 µg/mL nano-TiO2 group. Abnormal expression of ZO-1 and ß-catenin started from 150 µg/mL nano-TiO2 group, and abnormal expression of Claudin-11 started from 100 µg/mL nano-TiO2 group. Cells were treated with JNK inhibitor SP100625 to determine whether the changes of the above indicators in the concentration of 150 µg/mL nano-TiO2 group can be reversed. We found that SP100625 at 20 µM significantly reversed these effects. These results highlighted that nano-TiO2 could activate the JNK signaling pathway to induce mitochondria-mediated apoptosis and abnormal expression of BTB junction proteins in TM4 cells.

The Role of Work Engagement in the Association between Psychological Capital and Safety Citizenship Behavior in Coal Miners: A Mediation Analysis.

With the development of science and technology and the increasing importance attached by to these domains by the state and government departments in recent years, China's coal production and safety supervision level continue to increase. However, the prevalence of frequent coal mine safety accidents has not been effectively curbed. The main purpose of this study was to explore the mediating role of work engagement in the relationship between psychological capital and safety citizenship behavior among Chinese coal miners. Data for 317 coal miners were collected from five coal and energy enterprises. The Psychological Capital Questionnaire (PCQ), the Job Engagement Scale (JES), and the Safety Citizenship Behavior Scale (SCBS) were used to evaluate the coal miners' psychological capital, work engagement, and safety citizenship behavior. The causal steps approach and bootstrap Method were used in this study to assess the proposed mediation models. A correlation analysis indicated that psychological capital, work engagement, and safety citizenship behavior were significantly correlated with each other. Furthermore, the mediation analysis showed that work engagement mediated the relationship between psychological capital and safety citizenship behavior. Psychological capital does not only have a direct impact on coal miners' safety citizenship behavior, but it also has an indirect impact on coal miners' safety citizenship behavior via work engagement. Therefore, effectively enhancing an individual's psychological capital and work engagement may be a basic factor determining coal miners' safety citizenship behavior, which further promotes safety production within the enterprise.

The influence of pilot's attention allocation on instrument reading during take-off: The mediating effect of attention span.

The aim of this study was to examine the relationship among attention span, instrument reading, and eye movement mode. Sixteen pilots participated in procedural tests for attention span and instrument reading ability while completing simulated flight take-offs. Different instrument types corresponded to different reaction times - as response time increased, presentation time decreased. It can also be seen from the attention distribution of the instrument area in take-off that different instruments receive different attention resources. Breadth and attention span not only have a direct impact on the ability to read the table but also have a mediating effect on eye movement pattern during flight. The study found a direct relationship between attention span and instrument reading and also verified the impact of the two on attention allocation during take-off. The results suggest that integration training for attention ability with instrument reading may enable more efficient pilot performance.

Effect of Nano-Titanium Dioxide on Blood-Testis Barrier and MAPK Signaling Pathway in Male Mice.

Some studies have found that nano-sized titanium dioxide (nano-TiO2) has adverse effects on the male reproductive system. Blood-testis barrier (BTB), as one of the tightest blood-tissue restriction, is crucial to the male reproductive system. However, the potential effects on BTB and signaling pathway changes in testis tissue induced by nano-TiO2 remain poorly understood. Therefore, in this study, 60 Institute of Cancer Research mice were divided randomly into four groups (per group = 15). The mice of four groups were intragastrically administered with 0, 10, 50, and 100 mg/kg BW nano-TiO2 respectively for 30 days to analyze the changes of BTB structure, BTB-related proteins, and MAPK signal pathways. Besides, testosterone level, estradiol level, and sperm parameter (sperm count, sperm motility, and sperm malformation rate) changes were also studied in this research. The results indicated that nano-TiO2 could induce the BTB structural damage and accompanied by the BTB main protein (ZO-1, Claudin-11, and F-actin) elevation of irritability. Nano-TiO2 could also activate the MAPK signaling pathways (p38, JNK, and ERK) of mice testis tissue. The testosterone and estradiol levels in serum reduced. Besides when the mice were administered with nano-TiO2, we also found the sperm motility rate decreased, and sperm malformation increased. The above changes may be associated with BTB damage and the activation of MAPK signaling pathways, thereby causing male reproductive dysfunction.

Genotoxicity Evaluation of Titanium Dioxide Nanoparticles In Vitro: a Systematic Review of the Literature and Meta-analysis.

With the wide use of titanium dioxide nanoparticles (TiO2-NPs), the genotoxicity of TiO2-NPs, which is a factor for safety assessment, has attracted people's attention. However, their genotoxic effects in vitro remain controversial due to inconsistent reports. Therefore, a systematic review was conducted followed by a meta-analysis to reveal whether TiO2-NPs cause genotoxicity in vitro. A total of 59 studies were identified in this review through exhaustive database retrieval and exclusion. Meta-analysis results were presented based on different evaluation methods. The results showed that TiO2-NP exposure considerably increased the percentage of DNA in tail and olive tail moment in comet assay. Gene mutation assay revealed that TiO2-NPs could also induce gene mutation. However, TiO2-NP exposure had no effect on micronucleus (MN) formation in the MN assay. Subgroup analysis showed that normal cells were more vulnerable to toxicity induced by TiO2-NPs. Moreover, mixed form and small particles of TiO2-NPs increased the percentage of DNA in tail. In addition, short-term exposure could detect more DNA damage. The size, coating, duration, and concentration of TiO2-NPs influenced MN formation. This study presented that TiO2-NP exposure could cause genotoxicity in vitro. The physicochemical properties of TiO2-NPs and experimental protocols influence the genotoxic effects in vitro. Comet and gene mutation assays may be more sensitive to the detection of TiO2-NP genotoxic effects.

Attention and Entropy in Simulated Flight with Varying Cognitive Loads.

INTRODUCTION: This study is conducted to observe the effects of cognitive load on the visual search and attention allocation strategies of pilots. Research on pilots' visual search strategies can provide valuable information regarding attention distribution and transformation, as well as useful situation awareness (SA) predictions.METHODS: A total of 18 pilots performed flight tasks in a two-condition (high and low cognitive load) within-subject experiment to compare their flight performance and eye movement indicators. Eye movements were tracked during the flight mission by a portable eye-tracking device.RESULTS: Compared to the low cognitive load task, in the high cognitive load task, the subjects exhibited shorter average fixation times (M = 420.38, SD = 60.56), higher fixation frequencies (M = 2.27, SD = 0.30), and lower saccade frequencies (M = 2.7, SD = 0.31). Their flight performance was better during the low cognitive load task, as evidenced by the lower entropy (M = 0.11, SD = 0.03) of their eye movements. Analysis of fixation time percentages and fixation counts showed that the distribution of attention to each area of interest was adjusted dynamically over the course of the given task.DISCUSSION: Significant differences were observed in both fixation order and fixation frequency across the instrument array. When the cognitive load is high, the subjects used more efficient eye movement patterns and search strategies accompanying a higher level of SA.Lu T, Lou Z, Shao F, Li Y, You X. Attention and entropy in simulated flight with varying cognitive loads. Aerosp Med Hum Perform. 2020; 91(6):489-495.

A systematic review protocol of Tuina for children with acute bronchitis: A protocol for systematic review.

BACKGROUND: Acute bronchitis (AB) is a common cause of childhood morbidity. Tuina, a kind of Chinese massage, is frequently used for the treatment of AB in children by traditional Chinese medicine doctors. However, there is no relevant systematic review show its effectiveness and safety. The study aims to evaluate the effectiveness and safety of Tuina for children with AB. METHODS: The following electronic databases will be searched from the respective dates of database inception to January 1st, 2020: The Cochrane Library, Web of Science, the World Health Organization International Clinical Trials Registry Platform, Springer, EMBASE, MEDLINE, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Wanfang database, the Chinese Scientific Journal Database, and other sources. All published randomized controlled trials and blinded researches that are relevant to the subject of interest only will be contained. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis and/or descriptive analysis will be performed based on the included data conditions. RESULTS: High-quality synthesis and/or descriptive analysis of current evidence will be provided from the bronchitis severity score, symptom, and quality-of-life questionnaires, the questionnaire of clinical symptoms of cough and sputum, Patient Satisfaction Scale and adverse reactions. CONCLUSION: This study will provide the evidence of whether Tuina is an effective and safe intervention for children with AB. PROSPERO REGISTRATION NUMBER: CRD42019140667.

Tuina for children with myopia: A protocol for a systematic review.

BACKGROUND: The study aims to evaluate the effectiveness and safety of Tuina for children with myopia. METHODS: The following electronic databases will be searched from establishment to July 2019: Cochrane Library, MEDLINE, EMBASE, Web of Science, Springer, World Health Organization International Clinical Trials Registry Platform (ICTRP), China National Knowledge Infrastructure (CNKI), Wan-fang database, Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Databases (CBM), and other databases. All published randomized controlled trials (RCTs) about this topic will be included. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis, and/or descriptive analysis will be performed based on the included data conditions. RESULTS: High-quality synthesis and/or descriptive analysis of current evidence will be provided from improvement of distant vision, improvement of myopic diopter, and side effects. CONCLUSION: This study will provide the evidence of whether Tuina is an effective and safe intervention for children with myopia. PROSPERO REGISTRATION NUMBER: CRD42019142283.

Arabidopsis Duodecuple Mutant of PYL ABA Receptors Reveals PYL Repression of ABA-Independent SnRK2 Activity.

Abscisic acid (ABA) is an important phytohormone controlling responses to abiotic stresses and is sensed by proteins from the PYR/PYL/RCAR family. To explore the genetic contribution of PYLs toward ABA-dependent and ABA-independent processes, we generated and characterized high-order Arabidopsis mutants with mutations in the PYL family. We obtained a pyl quattuordecuple mutant and found that it was severely impaired in growth and failed to produce seeds. Thus, we carried out a detailed characterization of a pyl duodecuple mutant, pyr1pyl1/2/3/4/5/7/8/9/10/11/12. The duodecuple mutant was extremely insensitive to ABA effects on seed germination, seedling growth, stomatal closure, leaf senescence, and gene expression. The activation of SnRK2 protein kinases by ABA was blocked in the duodecuple mutant, but, unexpectedly, osmotic stress activation of SnRK2s was enhanced. Our results demonstrate an important role of basal ABA signaling in growth, senescence, and abscission and reveal that PYLs antagonize ABA-independent activation of SnRK2s by osmotic stress.