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Life satisfaction is closely related to emotional, behavioural, social, and environmental youth functioning. Starting from the hypothesis that positive youth development (PYD) qualities such as aspects of eudaimonic well-being lead to higher youth life satisfaction (the hedonic aspect of well-being), we explored predictions of Serbian youth life satisfaction based on the Five Cs on a sample of 215 Belgrade secondary school students (34.9% male students). The research results show that: the youth were mostly satisfied with their friends, their living environment, themselves, and their families, and least satisfied with their school; the Five Cs variables explain the highest percentage of variance in youth satisfaction with the family, and the lowest for satisfaction with the living environment; higher impacts on domain-specific life satisfaction were observed for connection (self-satisfaction, satisfaction with the family and school), confidence (satisfaction with the family and school), and caring (satisfaction with the living environment, school and friends), while competence only predicted self-safisfaction. Providing support for PYD promotion leads to greater satisfaction with different aspects of youth development ecology.

In recent decades, the positive youth development approach has gained momentum among researchers and practitioners who focus on youth potential and adolescent well-being. In this study, 1435 academic works on positive youth development (PYD) are collected from the Web of Science using CiteSpace, reviewed and analyzed. First, the number, subject distribution, country, and institution of published papers are presented, and the author collaboration network involved in PYD is analyzed using network analysis. The results show that authors and institutions in Western societies are the main contributors to PYD research and that interdisciplinary collaboration is gradually growing. Using document co-citation analysis, research hotspots in the field were investigated. Furthermore, the research frontiers and trendy topics in PYD from 2010 to 2019 were found by using burst detection, and research gaps were identified. The findings provide research directions for future PYD studies in the field of applied quality of life research.

Purpose: Coronavirus disease 2019 (COVID-19) poses a global health challenge with widespread transmission. Growing concerns about vaccine side effects, diminishing effcacy, and religious-based hesitancy highlight the need for alternative pharmacological approaches. Our study investigates the impact of the ethanol extract of Antrodia cinnamomea (AC), a native medicinal fungus from Taiwan, on COVID-19 in both in vitro and in vivo contexts. Methods: We measured the mRNA and protein levels of angiotensin-converting enzyme-2 (ACE2) in human lung cells using realtime reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Additionally, we determined the enzymatic activity of ACE2 using the fuorogenic peptide substrate Mca-YVADAPK(Dnp)-OH. To assess the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we used SARS-CoV-2 pseudovirus infections in human embryonic kidney 293T cells expressing ACE2 to measure infection rates. Furthermore, we evaluated the in vivo efficacy of AC in mitigating COVID-19 by conducting experiments on hamsters infected with the Delta variant of SARS-CoV-2. Results: AC effectively decreased ACE2 mRNA and protein levels, a critical host receptor for the SARS-CoV-2 spike protein, in human lung cells. It also prevented the spike protein from binding to human lung cells. Dehydrosulphurenic acid, an isolate from AC, directly inhibited ACE2 protease activity with an inhibitory constant of 1.53 [micro]M. In vitro experiments showed that both AC and dehydrosulphurenic acid significantly reduced the infection rate of SARS-CoV-2 pseudovirus. In hamsters infected with the Delta variant of SARS-CoV-2, oral administration of AC reduced body weight loss and improved lung injury. Notably, AC also inhibited IL-1[beta] expression in both macrophages and the lung tissues of SARS-CoV-2-infected hamsters. Conclusion: AC shows potential as a nutraceutical for reducing the risk of SARS-CoV-2 infection by disrupting the interaction between ACE2 and the SARS-CoV-2 spike protein, and for preventing COVID-19-associated lung inflammation. Keywords: coronavirus disease 2019, angiotensin-converting enzyme-2, severe acute respiratory syndrome coronavirus 2, Antrodia cinnamomea, the intracellular sensor NACHT, LRR, PYD domain-containing protein 3 infammasome, cytokine

MicroRNA-233-3p (miR-223-3p) is considered an important cancer-associated marker. The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome represents a novel potential target for the treatment of breast cancer. Therefore, it was hypothesized that miR-223-3p may affect tumor growth and immunosuppression in breast cancer by inhibiting the NLRP3 inflammasome. In the present study, an increased expression level of NLRP3 was detected in three breast cancer cell lines compared with normal mammary epithelial cells (HMEC). Suppressing the expression of NLRP3 in MCF-7 cell lines increased the apoptotic rate of breast cancer cells and reduced the proliferative capacity. NLRP3 was identified to be a direct target of miR-233-3p using a luciferase assay. In addition, miR-233-3p mimics inhibited the NLRP3-dependent processes in cancer cells by suppressing the NLRP3 expression level and the protein expression levels of its downstream factors, including PYD and CARD domain containing protein, interleukin-1β and interleukin-18. In vivo experiments demonstrated the suppressive effect of miR-233-3p in tumor growth and immunosuppression. Collectively these findings suggested that the inactivation of the NLRP3 inflammasome driven by miR-223-3p reduced the growth and immunosuppression of breast cancer in vitro and in vivo, and may represent a novel therapeutic strategy in treating breast cancer.

Background Extracellular adenosine triphosphate (ATP), a key danger-associated molecular pattern (DAMP) molecule, is released to the extracellular medium during inflammation by injured parenchymal cells, dying leukocytes, and activated platelets. ATP directly activates the plasma membrane channel P2X7 receptor (P2X7R), leading to an intracellular influx of K + , a key trigger inducing NLRP3 inflammasome activation. However, the mechanism underlying P2X7R-mediated activation of NLRP3 inflammasome is poorly understood, and additional molecular mediators have not been identified. Here, we demonstrate that Paxillin is the molecule connecting the P2X7 receptor and NLRP3 inflammasome through protein interactions. Results We show a distinct mechanism by which Paxillin promotes ATP-induced activation of the P2X7 receptor and NLRP3 inflammasome. Extracellular ATP induces Paxillin phosphorylation and then facilitates Paxillin-NLRP3 interaction. Interestingly, Paxillin enhances NLRP3 deubiquitination and activates NLRP3 inflammasome upon ATP treatment and K + efflux. Moreover, we demonstrated that USP13 is a key enzyme for Paxillin-mediated NLRP3 deubiquitination upon ATP treatment. Notably, extracellular ATP promotes Paxillin and NLRP3 migration from the cytosol to the plasma membrane and facilitates P2X7R-Paxillin interaction and PaxillinNLRP3 association, resulting in the formation of the P2X7R-Paxillin-NLRP3 complex. Functionally, Paxillin is essential for ATP-induced NLRP3 inflammasome activation in mouse BMDMs and BMDCs as well as in human PBMCs and THP-1-differentiated macrophages. Conclusions We have identified paxillin as a mediator of NLRP3 inflammasome activation. Paxillin plays key roles in ATP-induced activation of the P2X7 receptor and NLRP3 inflammasome by facilitating the formation of the P2X7R-Paxillin-NLRP3 complex.

The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function. In several inflammatory diseases, ASC specks can be found in the extracellular space and its presence correlates with poor prognosis. Here, we review the role of ASC in inflammation, and focus on the structural mechanisms that lead to ASC speck formation, the regulation of ASC function during inflammasome assembly, and the importance of ASC specks in disease.

Background The Positive Youth Development (PYD) framework posits that young people possess both inner and outer resources to thrive, and that, therefore, they can develop constructive behaviours, express their talents, and identify their strengths. The present study examines the relationship between the dimensions of the Positive Youth Development (PYD), the Developmental Assets (DA), and Purpose in Life (PIL) among Peruvian university students. In addition, the research informs on gender differences, and tests the predictive role of the 5Cs of the PYD and key Developmental Assets on Purpose in Life (as the criterion variable), in the studied population. Methods 1026 Peruvian university students were approached on a paper-based questionnaire by convenience sampling; 55.6% (570) were female, and 44.4% (456) were male. The questionnaires used in the research were the Positive Youth Development Short-Form (PYD-SF), the Developmental Assets Profile (DAP), and the abbreviated version of the Purpose in Life Scale for Emerging Adults (PILEA). The students ranged in age from 17 to 30 ( M  = 19.6, SD  = 2.1). Results All the tested PYD dimensions correlated positively at p  <.01, regardless of whether they belonged to the PYD or the DA framework. Male students scored significantly higher than females on competence, confidence, positive identity, and purpose in life. In contrast, female students scored higher than men on care and commitment to learning. Multiple regression analysis revealed that competence, confidence, support, commitment to learning, and positive identity significantly and directly predicted purpose in life, explaining 49.5% of it. Conclusions This study provides empirical evidence on the effect of PYD dimensions on Peruvian university students’ purpose in life. The 5Cs and key developmental assets had a significant and positive impact on purpose in life, potentially having long-lasting effects on the overall health of Peruvian students.

The silent information regulator 2 homolog 1-NACHT, LRR and PYD domains-containing protein 3 (SIRT1-NLRP3) pathway has a crucial role in regulation of the inflammatory response, and is closely related to the occurrence and development of several inflammation-related diseases. NLRP3 is activated to produce the NLRP3 inflammasome, which leads to activation of caspase-1 and cleavage of pro-interleukin (IL)-1β and pro-IL-18 to their active forms: IL-1β and IL-18, respectively. They are proinflammatory cytokines which then cause an inflammatory response.SIRT1 can inhibit this inflammatory response through nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B pathways. This review article focuses mainly on how the SIRT1-NLRP3 pathway influences the inflammatory response and its relationship with melatonin, traumatic brain injury, neuroinflammation, depression, atherosclerosis, and liver damage. BPNQFHKpbhyXXVwX1GGRJd Video Abstract

Acute lung injury (ALI) and the more severe acute respiratory distress syndrome are common and complex inflammatory lung diseases. MicroRNAs (miRs) have emerged as novel gene regulatory molecules, serving a crucial role in a variety of complex diseases, including ALI. In the present study, the anti-inflammatory action of miR-223 on inflammation in ALI was demonstrated and the possible mechanism was further examined. In lipopoly-saccharide-induced ALI, the expression of miR-223 was reduced compared with that in the control normal group. An in vitro model was used to analyze the effect of miR-223 downregulation on an ALI model, which increased inflammation, and induced the activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome and Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway via rho-related GTP-binding protein RhoB (RHOB). In addition, the overexpression of miR-223 reduced inflammation and suppressed the NLRP3 inflammasome and TLR4/NF-κB signaling pathway via RHOB in the in vitro model. Furthermore, TLR4 inhibitor or NLRP3 inhibitor reduced the pro-inflammatory effect of miR-223 downregulation in ALI. In conclusion, the results of the present study indicated that miR-223 functioned as a biological indicator by regulating inflammation in ALI, and may represent a novel potential therapeutic target and prognostic marker of ALI.

With the gradual decline in COVID-19 cases, there is a need to re-visit the mental health of adolescents and emerging adults in the post-pandemic period. Several observations can be highlighted from the scientific literature. First, while some studies suggest that mental health of young people has worsened in the post-pandemic period, there are inconsistent and conflicting findings. Second, there are more studies on psychological morbidity than on positive psychological attributes. Third, compared with the West, there are relatively fewer Chinese studies. Fourth, compared with adolescents, there are relatively fewer studies on emerging adults. Based on these observations of the existing literature, I have detailed several reflections on the mental health of young people, including enhancing positive psychological attributes in young people through positive youth development (PYD) programs, building up the individual resilience of young people, strengthening family resilience, adopting multidisciplinary, interdisciplinary and transdisciplinary approaches in understanding the mental health of young people, building more well-articulated theoretical models, charting future research directions, and developing intervention strategies in the post-pandemic period.