Novel xanthone antibacterials: Semi-synthesis, biological evaluation, and the action mechanisms.

α-Mangostin (α-MG) has demonstrated to display potent activities against Gram-positive bacterial. However, the contribution of phenolic hydroxyl groups of α-MG to the antibacterial activity remains obscure, severely hampering selection of structure modification to develop more potential α-MG-based anti-bacterial derivatives. Herein, twenty-one α-MG derivatives are designed, synthesized and evaluated for the antibacterial activities. The structure activity relationships (SARs) reveal that the contribution of the phenolic groups ranks as C3 > C6 > C1, and the phenolic hydroxyl group at C3 is essential to the antibacterial activity. Of note, compared to the parent compound α-MG, 10a with one acetyl at C1 exhibits the higher safety profiles due to its higher selectivity and no hemolysis, and the more potent antibacterial efficacy in an animal skin abscess model. Our evidences further present that, in comparison with α-MG, 10a has a stronger ability in depolarizing membrane potentials and leads to more leakage of bacterial proteins, consistent with the results observed by transmission electron microscopy (TEM). Transcriptomics analysis demonstrates those observations possibly relate to disturbed synthesis of proteins participating in the biological process of membrane permeability and integrity. Collectively, our findings provide a valuable insight for developing α-MG-based antibacterial agents with little hemolysis and new action mechanism via structural modifications at C1.

Vigilance and Automation Dependence in Operation of Multiple Unmanned Aerial Systems (UAS): A Simulation Study.

OBJECTIVE: This simulation study investigated factors influencing sustained performance and fatigue during operation of multiple Unmanned Aerial Systems (UAS). The study tested effects of time-on-task and automation reliability on accuracy in surveillance tasks and dependence on automation. It also investigated the role of trait and state individual difference factors. BACKGROUND: Warm's resource model of vigilance has been highly influential in human factors, but further tests of its applicability to complex, real-world tasks requiring sustained attention are necessary. Multi-UAS operation differs from standard vigilance paradigms in that the operator must switch attention between multiple subtasks, with support from automation. METHOD: 131 participants performed surveillance tasks requiring signal discrimination and symbol counting with a multi-UAS simulation configured to impose low cognitive demands, for 2 hr. Automation reliability was manipulated between-groups. Five Factor Model personality traits were measured prior to performance. Subjective states were assessed with the Dundee Stress State Questionnaire. RESULTS: Performance accuracy on the more demanding surveillance task showed a vigilance decrement, especially when automation reliability was low. Dependence on automation on this task declined over time. State but not trait factors predicted performance. High distress was associated with poorer performance in more demanding task conditions. CONCLUSIONS: Vigilance decrement may be an operational issue for multi-UAS surveillance missions. Warm's resource theory may require modification to incorporate changes in information processing and task strategy associated with multitasking in low-workload, fatiguing environments. APPLICATION: Interface design and operator evaluation for multi-UAS operations should address issues including motivation, stress, and sustaining attention to automation.

A novel three-dimensional-printed paranasal sinus-skull base anatomical model.

PURPOSE: A novel precision three-dimensional (3D)-printed paranasal sinus-skull base anatomical model was generated with a commercial grade desktop 3D printer. A specific page-turning pattern was employed in this model, to display the internal spatial structure of the paranasal sinus. METHODS: The CT image data of paranasal sinus were imported into the Mimics software to construct a 3D digital paranasal sinus-skull base model. Then, the model was sliced in the coronal position and loaded into the 3D printer to print each slice of the paranasal sinus-skull base model at a ratio of 1:1 in size. Based on CT image data, nine senior doctors assessed the simulation and accuracy of the anatomical structure features of the paranasal sinus-skull base, and the advantages and educational value of the 3D printing model using a seven-point Likert scale. RESULTS: A life-like 3D paranasal sinus-skull base structural model was successfully printed, with its internal spatial details clearly displayed. Nine senior doctors all thought that the profile of the printed anatomical structure was similar to that displayed by CT scan; however, the model provided more 3D spatial visual information. In addition, the model was considered to be of great value in the anatomy teaching and complicated surgery of the paranasal sinus-skull base, which had a material cost of only 3 dollars. CONCLUSIONS: The 3D printed paranasal sinus-skull base model has 3D visual functions, which provides a novel tool for anatomical studies on paranasal sinus, resident training, pre-surgical education and surgical planning.

Trust in the Danger Zone: Individual Differences in Confidence in Robot Threat Assessments.

Effective human-robot teaming (HRT) increasingly requires humans to work with intelligent, autonomous machines. However, novel features of intelligent autonomous systems such as social agency and incomprehensibility may influence the human's trust in the machine. The human operator's mental model for machine functioning is critical for trust. People may consider an intelligent machine partner as either an advanced tool or as a human-like teammate. This article reports a study that explored the role of individual differences in the mental model in a simulated environment. Multiple dispositional factors that may influence the dominant mental model were assessed. These included the Robot Threat Assessment (RoTA), which measures the person's propensity to apply tool and teammate models in security contexts. Participants (N = 118) were paired with an intelligent robot tasked with making threat assessments in an urban setting. A transparency manipulation was used to influence the dominant mental model. For half of the participants, threat assessment was described as physics-based (e.g., weapons sensed by sensors); the remainder received transparency information that described psychological cues (e.g., facial expression). We expected that the physics-based transparency messages would guide the participant toward treating the robot as an advanced machine (advanced tool mental model activation), while psychological messaging would encourage perceptions of the robot as acting like a human partner (teammate mental model). We also manipulated situational danger cues present in the simulated environment. Participants rated their trust in the robot's decision as well as threat and anxiety, for each of 24 urban scenes. They also completed the RoTA and additional individual-difference measures. Findings showed that trust assessments reflected the degree of congruence between the robot's decision and situational danger cues, consistent with participants acting as Bayesian decision makers. Several scales, including the RoTA, were more predictive of trust when the robot was making psychology-based decisions, implying that trust reflected individual differences in the mental model of the robot as a teammate. These findings suggest scope for designing training that uncovers and mitigates the individual's biases toward intelligent machines.

Overload and automation-dependence in a multi-UAS simulation: Task demand and individual difference factors.

Future unmanned aerial systems (UAS) operations will require control of multiple vehicles. Operators are vulnerable to cognitive overload, despite support from system automation. This study tested whether attentional resource theory predicts impacts of cognitive demands on performance measures, including automation-dependence and stress. It also investigated individual differences in response to demands. One-hundred and 1 university student participants performed a multi-UAS simulation mission incorporating 2 surveillance tasks. Cognitive demands and level of automation (LOA) of key tasks were manipulated between-subjects. Results were partially consistent with predictions. Higher task demands impaired performance and elevated distress and workload, as expected. Higher LOA produced greater dependence on automation, but failed to mitigate workload. It was expected that, as the automation was quite reliable, participants would attempt to conserve resources by depending more on automation under high demand. In fact, the opposite tendency was observed. Individuals high in conscientiousness were especially likely to override the automation under high demand, apparently taking charge personally. Neuroticism and distress were also associated with performance, but results did not fit a resource theory interpretation. Thus, understanding impacts of overload in the multi-UAS context requires understanding operator strategy as well as resource insufficiency. Findings have implications for system design, and operator selection and training. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Dangerous intersections? A review of studies of fatigue and distraction in the automated vehicle.

The impacts of fatigue on the vehicle driver may change with technological advancements including automation and the increasing prevalence of potentially distracting in-car systems. This article reviews the authors' simulation studies of how fatigue, automation, and distraction may intersect as threats to safety. Distinguishing between states of active and passive fatigue supports understanding of fatigue and the development of countermeasures. Active fatigue is a stress-like state driven by overload of cognitive capabilities. Passive fatigue is produced by underload and monotony, and is associated with loss of task engagement and alertness. Our studies show that automated driving reliably elicits subjective symptoms of passive fatigue and also loss of alertness that persists following manual takeover. Passive fatigue also impairs attention and automation use in operators of Remotely Piloted Vehicles (RPVs). Use of in-vehicle media has been proposed as a countermeasure to fatigue, but such media may also be distracting. Studies tested whether various forms of phone-based media interacted with automation-induced fatigue, but effects were complex and dependent on task configuration. Selection of fatigue countermeasures should be guided by an understanding of the form of fatigue confronting the operator. System design, regulation of level of automation, managing distraction, and selection of fatigue-resilient personnel are all possible interventions for passive fatigue, but careful evaluation of interventions is necessary prior to deployment.

Metabolic profiling reveals disorder of amino acid metabolism in four brain regions from a rat model of chronic unpredictable mild stress.

Chronic stress is closely linked to clinical depression, which could be assessed by a chronic unpredictable mild stress (CUMS) animal model. We present here a GC/MS-based metabolic profiling approach to investigate neurochemical changes in the cerebral cortex, hippocampus, thalamus, and remaining brain tissues. Multi-criteria assessment for multivariate statistics could identify differential metabolites between the CUMS-model rats versus the healthy controls. This study demonstrates that the significantly perturbed metabolites mainly involving amino acids play an indispensable role in regulating neural activity in the brain. Therefore, results obtained from such metabolic profiling strategy potentially provide a unique perspective on molecular mechanisms of chronic stress.

JNK Inhibition Inhibits Lateral Line Neuromast Hair Cell Development.

JNK signaling is known to play a role in regulating cell behaviors such as cell cycle progression, cell proliferation, and apoptosis, and recent studies have suggested important roles for JNK signaling in embryonic development. However, the precise function of JNK signaling in hair cell development remains poorly studied. In this study, we used the small molecule JNK inhibitor SP600125 to examine the effect of JNK signaling abrogation on the development of hair cells in the zebrafish lateral line neuromast. Our results showed that SP600125 reduced the numbers of both hair cells and supporting cells in neuromasts during larval development in a dose-dependent manner. Additionally, JNK inhibition strongly inhibited the proliferation of neuromast cells, which likely explains the decrease in the number of differentiated hair cells in inhibitor-treated larvae. Furthermore, western blot and in situ analysis showed that JNK inhibition induced cell cycle arrest through induction of p21 expression. We also showed that SP600125 induced cell death in developing neuromasts as measured by cleaved caspase-3 immunohistochemistry, and this was accompanied with an induction of p53 gene expression. Together these results indicate that JNK might be an important regulator in the development of hair cells in the lateral line in zebrafish by controlling both cell cycle progression and apoptosis.

Hair cell damage recruited Lgr5-expressing cells are hair cell progenitors in neonatal mouse utricle.

Damage-activated stem/progenitor cells play important roles in regenerating lost cells and in tissue repair. Previous studies reported that the mouse utricle has limited hair cell regeneration ability after hair cell ablation. However, the potential progenitor cell population regenerating new hair cells remains undiscovered. In this study, we first found that Lgr5, a Wnt target gene that is not usually expressed in the neonatal mouse utricle, can be activated by 24 h neomycin treatment in a sub-population of supporting cells in the striolar region of the neonatal mouse utricle. Lineage tracing demonstrated that these Lgr5-positive supporting cells could regenerate new hair cells in explant culture. We isolated the damage-activated Lgr5-positive cells with flow cytometry and found that these Lgr5-positive supporting cells could regenerate hair cells in vitro, and self-renew to form spheres, which maintained the capacity to differentiate into hair cells over seven generations of passages. Our results suggest that damage-activated Lgr5-positive supporting cells act as hair cell progenitors in the neonatal mouse utricle, which may help to uncover a potential route to regenerate hair cell in mammals.

An optimized procedure for metabonomic analysis of rat liver tissue using gas chromatography/time-of-flight mass spectrometry.

In this paper, we present a tissue metabonomic method with an optimized extraction procedure followed by instrumental analysis with gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) and spectral data analysis with multivariate statistics. Metabolite extractions were carried out using three solvents: chloroform, methanol, and water, with design of experiment (DOE) theory and multivariate statistical analysis. A two-step metabolite extraction procedure was optimized using a mixed solvent of chloroform-methanol-water (1:2:1, v/v/v) and then followed by methanol alone. This approach was subsequently validated using standard compounds and liver tissues. Calibration curves were obtained in the range of 0.50-125.0mug/mL for standards and 0.02-0.25g/mL acceptable for liver tissue samples. For most of the metabolites investigated, relative standard deviations (RSD) were below 10% within a day (reproducibility) and below 15% within a week (stability). Rat liver tissues of carbon tetrachloride-induced acute liver injury models (n=10) and healthy control rats (n=10) were analyzed which demonstrated the applicability of the developed procedure for the tissue metabonomic study.

[Selective neurotomy of anterior ethmoid nerve and squeezing operation of inferior turbinate for the treatment of perennial allergic rhinitis].

OBJECTIVE: To explore the treatment effect of selective neurotomy of anterior ethmoid nerve and squeezing operation of inferior turbinate in the treatment of perennial allergic rhinitis (PAR). METHOD: Seventy cases of perennial allergic rhinitis were selected and subjected to selective neurotomy of anterior ethmoid nerve and squeezing operation of inferior turbinate,and the treatment effect was observed by analysis of the the symptoms and signs score of all cases preoperatively and postoperatively. RESULT: The total effective rate were 90.0% at 1 year follow-up. CONCLUSION: Selective neurotomy of anterior ethmoid nerve and squeezing operation of inferior turbinate were effective for the patients with PAR. It is worthy to be popularized for its convent and rare complications.

Effect of hyperlipidemia on endothelial VCAM-1 expression and the protective role of fenofibrate.

The effect of hyperlipidemia and inflammation on endothelial functions was studied. The enrolled included control (basic chow), hyperlipidemia and fenofibrate-treated groups (high fat diet). The hyperlipidemia model was set up by four-week atherogenic diet, followed by a 16-week treatment in the fenofibrate-treated group (fenofibrate 40 mg/kg every day) and without treatment in the hyperlipidemia group, respectively. In the 20th week, serum lipid level and NO levels were measured, and the expression of vascular cell adhesion molecule-1 (VCAM-1) and cell adhesiveness in aortic endothelia observed by computer-aided system. Compared with the control group, hyperlipidemia rats showed lower levels of NO and increases in leukocyte accumulation on the endothelial surface, also stronger and more extensive endothelial expression of VCAM-1. In fenofibrate-treated group, the expression of VCAM-1 and leukocyte accumulation on the endothelial surface was decreased, while serum levels of NO were increased as compared with hyperlipidemia group. Hyperlipidemia can inhibit the NO activity and promote the damage of VACA-1 to aortic endothelia. Fenofibrate can effectively prevent the pathogenesis of atherosclerosis by restoring NO levels and down-regulating the VCAM-1 expression.

[Impact of fenofibrate on NO and endothelial VCAM-1 expression in hyperlipidemic rats].

OBJECTIVE: To investigate the mechanism of hyperlipidemia- and imflammation-induced functional impairment of the endothelium. METHODS: The experiment was conducted using 3 groups of rats fed for 20 weeks with standard chow (control group), high-fat diet and high-fat diet with daily fenofibrate treatment (10 mg/kg, starting since the fifth week), respectively. After 4 and 20 weeks of feeding, respectively, serum lipid level and NO concentration were measured in the rats, and the epithelial vascular cell adhesion molecule-1 (VCAM-1) expression and cell adhesiveness to the aortic endothelium were observed. RESULTS: Compared with the control group, the rats with hyperlipidemia induced by long-term high-fat diet feeding showed lower NO concentration and increased leukocyte accumulation on the endothelial surface, exhibiting also stronger and more extensive endothelial expression of VCAM-1. In contrast, the hyperlipidemic rats with fenofibrate treatment shoed significantly decreased VCAM-1 expression and leukocyte adhesion with recovery of the NO level. CONCLUSION: NO deficiency and activation of inflammation are involved in vascular impairment in rats with high-fat diet-induced hyperlipidemia, and fenofibrate can effectively prevent atherosclerosis by restoring NO concentration and down-regulating VCAM-1 expression in these rats.

[Security assortment and guarding method after tracheotomy].

OBJECTIVE: To discuss the assortment method of security and to find out measures in order to avoid the asphyxia death owing to obstruction and collapse of canal after tracheotomy. METHOD: During the period from June 1998 to September 2003, 346 patients were operated the tracheotomy for different reasons. Then they were assorted according to the causes if there was an obstruction in superior airway, the patients' mental health, age and the capacity of saving themselves. We divided them into three kinds, which were security, dangerousness (temporalily or permanently) and relative dangerousness. The corresponding methods of operation therapy and nursing care had been proposed. RESULT: One hundred and sixty cases were the secure kind; 17 cases the dangerous kind (12 cases permanently, 5 cases temporalily), 169 cases the relatively dangerous kind. After adopting corresponding method of operation and nursing cars, the asphyxia death due to obstruction or collapse of canal didnt happen. CONCLUSION: The security assortment has significance after tracheotomy for reducing the asphyxia death rate.