Reducing Fear Overgeneralization with Safety Learning: Attention Bias as a Moderator

Anxiety disorders are the most prevalent mental health condition and affect one out of nine individuals around the world. Fear generalization is a neurocognitive mechanism thought to maintain and exacerbate anxiety, and thus is an important target of therapeutic interventions. Yet, intervention research and practice place relatively little emphasis on its importance. Given that a significant proportion of individuals do not respond to extant treatments of anxiety disorders, a strengthened focus on fear generalization may inform the development and personalization of new treatment approaches. Recent notions have linked fear generalization to failures in distinguishing between signals that predict the occurrence of an aversive event (threat cues) and those predicting the non-occurrence of an aversive event (safety cues). As such, a careful investigation of learning safety cues (i.e., safety learning) may advance our understanding of anxiety and fear generalization. The goal of the current dissertation tested the hypothesis that successful safety learning will reduce fear generalization. A secondary goal was to test whether individual differences in attention bias moderate the impact of safety learning on fear generalization. Attention bias, defined as selective and exaggerated attention toward threatening information and stimuli, varies across individuals and has been theorized to interact with learning processes to influence the development and maintenance of anxiety. This study examined a sample including individuals aged 18 to 45 years old (M = 24.05, SD = 6.07) who reported at least low to moderate levels of anxiety symptoms. Participants were randomly assigned to one of the following four groups: fear learning, safety learning without enhanced cue saliency, or one of the two additional safety learning groups with enhanced cue saliency. During a 2-day study period, all participants completed a fear/safety learning task, a fear generalization task, and a dot-probe task, with their subjective risk ratings, behavioral responses, skin conductance response (SCR), and event-related potentials (ERP) recorded simultaneously. Fear generalization was measured with risk ratings, SCR, and ERP. Attention bias was assessed with ERP and trial-level bias scores (TLBS) calculated using reaction times. Analyses revealed no sufficient evidence to support the predicted effect of safety learning procedures on fear generalization. Yet, individual differences were documented. Among participants who went through the safety learning with enhanced cue saliency, those who had attention bias towards threat exhibited reduced physiological responses to generalized and safety cues, suggesting reduced fear generalization. In sum, this dissertation provided initial evidence for the interplay between cognitive and learning processes in anxiety. Findings also demonstrated the importance of studying the impact of safety learning on fear generalization in the context of individual differences in disrupted processing of threat

DC32, a Dihydroartemisinin Derivative, Ameliorates Collagen-Induced Arthritis Through an Nrf2-p62-Keap1 Feedback Loop

Artemisinins have been reported to have diverse functions, such as antimalaria, anticancer, anti-inflammation, and immunoregulation activities. DC32 [(9α,12α-dihydroartemisinyl) bis(2′-chlorocinnmate)], a dihydroartemisinin derivative possessing potent immunosuppressive properties, was synthesized in our previous study. Collagen-induced arthritis (CIA) in DBA/1 mice and inflammatory model in NIH-3T3 cells were established to evaluate the effect of DC32 on RA and discover the underlying mechanisms. The results showed that DC32 could markedly alleviate footpad inflammation, reduce cartilage degradation, activate the Nrf2/HO-1 signaling pathway, and increase the transcription of p62 in DBA/1 mice with CIA. Further mechanistic exploration with NIH-3T3 cells indicated that DC32 could increase the transcription, expression, and nuclear translocation of Nrf2. In addition, DC32 promoted degradation of Keap1 protein and upregulated HO-1 and p62 expression. Furthermore, the effect of DC32 on Keap1 degradation could be prevented by p62 knockdown using siRNA. Administration of DC32 could inhibit the activation of Akt/mTOR and ERK, and pretreatment of NIH-3T3 cells with the autophagy inhibitor 3-methyladenine (3-MA) attenuated the degradation of Keap1 induced by DC32. These results suggest that DC32 inhibits the degradation of Nrf2 by promoting p62-mediated selective autophagy and that p62 upregulation contributed to a positive feedback loop for persistent activation of Nrf2. In summary, our present study demonstrated that DC32 significantly suppressed rheumatoid arthritis (RA) via the Nrf2-p62-Keap1 feedback loop by increasing the mRNA and protein levels of Nrf2 and inducing p62 expression. These findings provide new mechanisms for artemisinins in RA treatment and a potential strategy for discovering antirheumatic drugs

YiQiFuMai Powder Injection Attenuates Coronary Artery Ligation-Induced Heart Failure Through Improving Mitochondrial Function via Regulating ROS Generation and CaMKII Signaling Pathways

The YiQiFuMai powder injection (YQFM), a traditional Chinese medicine (TCM) prescription re-developed based on Sheng-Mai-San, is widely applied for the treatment of cardiovascular diseases. However, its potential molecular mechanism remains obscure. The present study was designed to observe the effects of YQFM and underlying mechanisms on coronary artery ligation (CAL)-induced heart failure (HF) and cell hypoxia of 24 h oxygen-glucose deprivation (OGD) in neonatal rat ventricular myocytes (NRVMs). HF was induced by permanent CAL for 2 weeks in ICR mice. The results demonstrated that YQFM significantly attenuated CAL-induced HF via improving the cardiac function, cardiac systolic function, cardiac structure impairment, cardiac histological features and fibrosis. YQFM markedly attenuated mitochondrial dysfunction through improving mitochondrial morphology, increasing mitochondria membrane potential (Δψm), mitochondrial ROS generation and expression of Mitofusin-2 (Mfn2), meanwhile, decreasing phosphorylation of dynamin-related protein 1 (p-Drp1). Mechanistically, YQFM could significantly decrease the expression of isoforms of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit NADPH oxidase 2 (NOX2), p67phox and NADPH oxidase 4 (NOX4), ultimately reducing reactive oxygen species (ROS) generation. In addition, YQFM could down-regulate expression of calcium voltage-gated channel subunit α1C (CACNA1C) and phosphorylation of calmodulin dependent protein kinase II (p-CaMKII). These results suggest that YQFM ameliorates mitochondrial function in HF mice, partially through inhibiting ROS generation and CaMKII signaling pathways. Therefore, the present study provided scientific evidence for the underlying mechanism of YQFM

Food quality and motivation: A refined low-fat diet induces obesity and impairs performance on a progressive ratio schedule of instrumental lever pressing in rats

IntroductionPurified high-fat diet (HFD) feeding causes deleterious metabolic and cognitive effects when compared with unrefined low-fat diets in rodent models. These effects are often attributed to the diet's high content of fat, while less attention has been paid to other mechanisms associated with the diet's highly refined state. Although the effects of HFD feeding on cognition have been explored, little is known about the impact of refined vs. unrefined food on cognition. We tested the hypothesis that a refined low-fat diet (LFD) increases body weight and adversely affects cognition relative to an unrefined diet.Materials and methodsRats were allowed ad libitum access to unrefined rodent chow (CON, Lab Diets 5001) or a purified low-fat diet (REF, Research Diets D12450B) for 6 months, and body weight and performance on an instrumental lever pressing task were recorded.ResultsAfter six months on their respective diets, group REF gained significantly more weight than group CON. REF rats made significantly fewer lever presses and exhibited dramatically lower breaking points than CON rats for sucrose and water reinforcement, indicating a chronic reduction of motivation for instrumental performance. Switching the rats' diet for 9 days had no effect on these measures.ConclusionsDiet-induced obesity produces a substantial deficit in motivated behavior in rats, independent of dietary fat content. This holds implications for an association between obesity and motivation. Specifically, behavioral traits comorbid with obesity, such as depression and fatigue, may be effects of obesity rather than contributing causes. To the degree that refined foods contribute to obesity, as demonstrated in our study, they may play a significant contributing role to other behavioral and cognitive disorders

Pole-to-Ground Fault Analysis and Fast Protection Scheme for HVDC Based on Overhead Transmission Lines

Flexible direct current (DC) transmission network technology is an effective method for large capacity clean energy access to power grids, but the DC short-circuit fault detection for it is a difficult problem. In this paper, the pole-to-ground fault transient characteristics in a multi-terminal DC power grid, based on overhead transmission lines and DC circuit breakers, are analyzed firstly. Then, a fast protection scheme is proposed according to the fault transient characteristics. Only local information is utilized for fault detection and location in the proposed scheme. Moreover, the scheme is verified to have the advantages of fast action speed, high reliability and the ability to resist the transition resistance. A four terminal DC power grid model based on actual engineering parameters is established in PSCAD/EMTDC, and the validity of the protection scheme under different fault conditions is verified by simulation results

The Changsha Historic Urban Area: A Study on the Changing Accessibility of the Road Network

In this study, we used a complex network analysis to examine the accessibility features of changing road networks in historic urban areas. We aimed to discover the pattern of evolution after studying the accessibility of the road network in the Changsha historic urban area over four periods of time. The results were as follows: the layout of the urban road network shows repetitive cluster–parent–subsidiary development, which provides evidence of adaptive adjustment in urban road development; vulnerability has been kept low in the changing urban road network, while the spatial framework of the Changsha historic center is fixed; the evolving urban road network generally shows a deteriorating level of stability, which is largely affected by the shape of the network; the degree centrality (1877, 1.87%; 1917, 1.32%; 1987, 1.85%; 2021, 1.51%) of the urban road network shows a decreasing trend, meaning that the network is generally becoming more balanced in its evolution; and the accessibility of land plots currently used to preserve cultural relics and historic sites remains at a medium to low level, and improvements are needed for some plots. In analyzing the changing accessibility of urban roads in the historic center of Changsha city, two major problems for road renewal were identified: (1) unbalanced development of the urban space due to capital-based projects and (2) providing an appropriate increase in plot accessibility while putting equal emphasis on the protection of the spatial framework in the historic urban area. We conclude that a dynamic review of urban road network accessibility and its targeted optimization are of great significance for the protection and development of Changsha’s historic urban area

Cloud and Snow Identification Based on DeepLab V3+ and CRF Combined Model for GF-1 WFV Images

Cloud and snow identification in remote sensing images is critical for snow mapping and snow hydrology research. Aimed at the problem that the semantic segmentation model is prone to producing blurred boundaries, slicing traces and isolated small patches for cloud and snow identification in high-resolution remote sensing images, the feasibility of combining DeepLab v3+ and conditional random field (CRF) models for cloud and snow identification based on GF-1 WFV images is studied. For GF-1 WFV images, the model training and testing experiments under the conditions of different sample numbers, sample sizes and loss functions are compared. The results show that, firstly, when the number of samples is 10,000, the sample size is 256 × 256, and the loss function is the Focal function, the model accuracy is the optimal and the Mean Intersection over Union (MIoU) and the Mean Pixel Accuracy (MPA) reach 0.816 and 0.918, respectively. Secondly, after post-processing with the CRF model, the MIoU and the MPA are improved to 0.836 and 0.941, respectively, compared with those without post-processing. Moreover, the misclassifications such as blurred boundaries, slicing traces and isolated small patches are significantly reduced, which indicates that the combination of the DeepLab v3+ and CRF models has high accuracy and strong feasibility for cloud and snow identification in high-resolution remote sensing images. The conclusions can provide a reference for high-resolution snow mapping and hydrology applications using deep learning models

Research on the Revitalization Path of Ethnic Villages Based on the Inheritance of Spatial Cultural Genes—Taking Tujia Village of Feng Xiang Xi in Guizhou Province as a Case Study

The development of rural ethnic culture resources is conducive to protecting the cultural characteristics of traditional ethnic villages and achieving the great goal of the industrialized utilization of rural cultural heritage resources as well. Oriented by the goal of rural revitalization, this article targets the characteristics and problems of the development of the Tujia village of Feng Xiang Xi in Guizhou Province. Employing the methods of field investigation and cultural gene identification, this paper analyzes the cultural genes of the Tujia ethnic identity and summarizes the characteristics of its spatial representation. It is essential for us to summarize the current difficulties of rural protection and development and clarify the relationship between cultural revitalization, rural revitalization, and sustainable development, which then puts forward a new path for rural revitalization, especially by virtue of the inheritance of the spatial cultural genes of the Tujia village. Specifically, the “protection of the cultural genes of the Tujia ethnic identity” is determined as the principal policy for rural development, the rural spatial structure is reconstructed based on the study tour of the Tujia village, and the public cultural space is reconstructed based on the inheritance and utilization of the cultural genes of Tujia. In the meantime, attention should be paid to orderly construction, and priority should be given to the construction of transportation and service facilities. Finally, it is expected that the research can provide an implementation path for rural revitalization with distinctive ethnic cultures