Forest parks are important for ecological conservation, recreation, and the health and well-being of the people who use them. However, forest parks located in urban areas often face the problem of ...crowding. To better understand perceived crowding in urban forest parks and to improve tourists’ recreation experiences and satisfaction, we constructed a conceptual model of the relationships between perceived crowding, emotion, and satisfaction with mechanisms of adjustment based on survey data from Dafu Mountain Forest Park in China. The results indicate that, in urban forest parks, perceived crowding significantly and negatively affects tourists’ satisfaction, but there is no significant difference in satisfaction between different activity types. Both positive and negative emotions have partially mediating effects on the relationship between perceived crowding and satisfaction. Crucially, our modeled mechanisms of adjustment play a moderating role in the effect of crowding on tourist satisfaction, and the choice of adjustment behaviors varies according to the activity type. This work enriches the research related to perceived crowding, mechanisms of adjustment, and satisfaction in tourist destinations and provides a theoretical basis for the future management of urban forest parks.
Leisure innovation theory holds that taking up new leisure activities by older people may facilitate healthy aging. To examine this theory in an urban Asian context, I conducted a case study of older ...adults in Guangzhou, China. I undertook in-depth interviews with 27 adults aged 50-80 years; I analyzed the data with open, axial, and selective coding using NVivo 8.0. I obtained the following findings. First, the participants practiced four main types of leisure activities: cultural and physical activities; digital leisure; artistic creation; and intellectual games. Second, those activities led to positive outcomes with respect to health, self-development, place identity, and social interaction. Finally, the main factors influencing leisure innovation comprised internal factors (values of life and leisure) and external factors (availability of time, money, institution, and space; institution and space were the most important).
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•A comprehensive Emodin-associated network was identified and visualized.•NHL-related pathways were screened out from enriched Emodin-associated pathways.•Genetic alterations of ...Emodin-associated genes in the NHL were excavated.•TP53 and PI3K/AKT pathway were involved in Emodin affecting DLBCL.•A novel approach to guide experiments based on given drug information was provided.
Non–Hodgkin’s Lymphoma (NHL) is a group of lymphoid malignancies with unsatisfactory treatment effect in some aggressive subtypes, including diffuse large B cell lymphoma (DLBCL). Emodin is an anthraquinone with potent anti-cancer activities. However, the molecular mechanism of Emodin repressing aggressive NHL remains to be revealed in detail. This study delineated the active mechanism of Emodin action in aggressive NHL by using bioinformatics analysis and in vitro assay. 4 Emodin’s primary direct protein targets (DPT) were identified and the DPTs-associated proteins/genes were predicted. Those Emodin-related proteins/genes were subject to enrich Emodin-associated pathways, from which 3 significantly NHL-related signal pathways were refined identified. Advanced integrated analysis exhibited TP53 and PI3K as the significant molecule and pathway by which Emodin may function in NHL. To verify those bioinformatics findings, effects of Emodin and E35, a novel derivative of emodin were investigated on DLBCL cell lines SU-DHL4. Emodin and E35 suppressed proliferation and induced apoptosis of SU-DHL4 cells in a time- and dose-dependent manner. Emodin and E35 declined TP53 protein expression and decreased phosphorylation of PI3K/AKT protein in a dose-dependent manner. All of above showed that combined bioinformatics analysis with experiments offered a novel approach for outlining the mechanisms of Emodin action in DLBCL with convenience and integrity.
Purpose
Most patients with acute lymphoblastic leukemia (ALL) are treated with chemotherapy as primary care. Although the treatment response is usually positive, resistance and relapse often occur ...via unknown mechanisms. The purpose of this study was to identify factors associated with chemotherapy resistance in ALL. Here, we present clinical and experimental evidence that overexpression of nucleolin (NCL), a multifunctional nucleolar protein, is linked to drug resistance in ALL.
Methods
NCL mRNA and protein levels were compared between cell lines and patient samples using qRT-PCR and immunoblotting. NCL mRNA levels were compared between patients of different disease stages from our clinic patients’ specimens and publicly available ALL patient datasets. Cells and patient-derived xenograft mouse experiments were performed to assess the effect of NCL inhibition on ALL chemotherapy effectiveness.
Results
Analysis of patient specimens, and publicly available RNA-sequencing datasets revealed a strong correlation between the abundance of NCL and disease relapse or poor survival in B-ALL. Altering NCL expression results in changes in drug sensitivity in ALL cell lines. High levels of NCL upregulated components of the ATP-binding cassette transporters via activation of the ERK pathway, resulting in a decrease in drug accumulation inside the cells. Targeting NCL with AS1411, an NCL-binding oligonucleotide aptamer, significantly increased the sensitivity of ALL cell lines and cells/patient-derived ALL xenograft mice to chemotherapeutic drugs and prolonged mouse survival.
Conclusion
Our results highlight NCL as a prognostic marker in B-ALL and a potential therapeutic target to combat chemotherapy resistance in ALL.
The present study was designed to investigate the expression of multidrug resistance (MDR)-related genes, verify the synergistic effects of baicalin and Adriamycin (ADM) and investigate the related ...mechanisms in ADM-resistant leukaemic HL-60/ADM cells.
We used a HL-60/ADM cell line. Cytotoxicity and flow cytometry assays were employed to verify the cytotoxic effects of baicalin. Real-time polymerase chain reaction and Western blotting assays were used to assess the expression of MDR-related genes and the changes in gene expression (both MDR-related and PI3K/Akt pathway-related) induced by administration of baicalin.
We found that only multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and Bcl-2 genes were expressed in both HL-60 and HL-60/ADM cells. HL-60/ADM cells exhibited significantly higher expression (p < 0.05). We also observed that low-dose baicalin (5 and 10 µmol/L) can induce growth inhibition and apoptotic effects on HL-60/ADM cells by increasing the intracellular accumulation of ADM. The synergistic effect of baicalin and ADM was verified. Concerning the potential mechanisms involved in this process, we showed that baicalin down-regulated the expression of several MDR-related and PI3K/Akt pathway-related genes.
We confirmed the increased expression of MRP1, LRP and Bcl-2 genes in HL-60/ADM cells compared to regular HL-60 cells, which are recommended for future investigation on MDR. The present study provided evidence of the synergistic effect of baicalin and ADM in HL-60/ADM cells. Therefore, baicalin may be considered as a potential therapeutic agent against resistant leukaemia. Suppression of the PI3K/Akt signalling pathway, followed by inhibition of the expression of MDR-related genes may be a common mechanism in combination treatments with ADM for the reduction of resistance to ADM.
Urban parks are of great significance improving the physical and mental health of residents. However, there is still a lack of systematic discussion of the relationship between visitor ...characteristics, physical activity (PA) levels, and urban park environments, especially within subtropical areas of Asia. We took 12 urban parks in Guangzhou, China as the research objects, comprehensively used BRAT and SOPARC to observe the microenvironment and visitors’ PA in the urban parks, and supplemented the research with interviews. The results of the study revealed that: (1) The urban parks in Guangzhou cannot fully encourage visitors to engage in high PA levels, and due to the temperature of subtropical areas most visitors chose medium and high PA levels in the morning. (2) Leisure preferences and environment features determined that females tended to engage in medium and high PA levels more than males. Minors preferred high PA levels, while other age groups preferred low PA levels. (3) All groups attached great importance to rest facilities and shade. Among them, the youth paied more attention to the quality of the landscape and the middle-aged were attracted by the scent. (4) Low PA levels were affected largely by the site elements and high PA levels were greatly affected by varying terrains and shade. (5) Areas that including recreation and sport facilities had the highest concentration of medium and high PA levels; however, were insufficient to meet the needs of multiple age groups. Finally, we made recommendations to improve the PA levels of visitors in subtropical areas and gave advice concerning more humanized park planning.
Urban parks, one of the most significant outdoor leisure areas, are particularly important for the physical and mental health of older adults. In order to investigate the benefits and constraints of ...leisure activities that older adults perceived in urban parks, as well as their negotiation mechanisms, this study was conducted using a qualitative method, interviewing 102 retired older adults aged 55 or older in Guangzhou, China, and using Rost CM 6.0 for word frequency analysis. The study findings indicated that due to the lack of age-friendly public leisure facilities in Guangzhou, Chinese older adults expressed multiple expectations regarding the benefits of urban parks, mainly in terms of physical, psychological, and social interaction, with physical benefits being their primary drivers. Leisure constraints can be intrapersonal, interpersonal, or structural. Older adults who visited parks and those who did not were affected by different levels of limitations, with the oldest people experiencing the most pronounced constraints. Older adults were able to access leisure opportunities through a variety of constraint negotiation strategies, including cognitive adaptability, spatiotemporal adaptation, interpersonal coordination, skill acquisition, and alternative leisure activities. The results of this study might assist related management departments in building more age-friendly parks based on the framework of the benefits and constraints of park recreation for older adults, in terms such as institutional design and planning to enhance the role of urban parks in healthy aging.
Glucocorticoids (GC) are the foundation of the chemotherapy regimen in acute lymphoblastic leukemia (ALL). However, resistance to GC is observed more frequently than resistance to other chemotherapy ...agents in patients with ALL relapse. Moreover, the mechanism underlying the development of GC resistance in ALL has not yet been fully uncovered. In this study, we used bioinformatic analysis methods to integrate the candidate genes and pathways participating in GC resistance in ALL and subsequently verified the bioinformatics findings with in vitro cell experiments. Ninety‐nine significant common differentially expressed genes (DEGs) associated with GC resistance were determined by integrating two gene profile datasets, including GC‐sensitive and ‐resistant samples. Using Kyoto Encyclopedia of Genes and Genomes (KEGG) and REACTOME pathways analysis, the signaling pathways in which DEGs were significantly enriched were clustered. The GC resistance‐related biologically functional interactions were visualized as DEG‐associated Protein–Protein Interaction (PPI) network complexes, with 98 nodes and 127 edges. MYC, a node which displayed the highest connectivity in all edges, was highlighted as the core gene in the PPI network. Increased C‐MYC expression was observed in adriamycin‐resistant BALL‐1/ADR cells, which we demonstrated was also resistant to dexamethasone. These results outlined a panorama in which the solitary and scattered experimental results were integrated and expanded. The potential promising target of the candidate pathways and genes involved in GC resistance of ALL was concomitantly revealed.
These results outlined a panorama in which the solitary and scattered experimental results were integrated and extended. The potential promising target of the candidate pathways and genes in GC resistant acute lymphoblastic leukemia was concomitantly revealed.
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