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Abstract Background Gastric cancer (GC) is a highly chemoresistant malignancy with a poor prognosis. Paclitaxel’s low response rate as second-line chemotherapy for advanced GC has prompted intensive research into its molecular basis and prospective targeted therapies to enhance its therapeutic efficacy. The objective of this study was to investigate the synergistic effects of NRF2 silencing in combination with paclitaxel treatment on GC cell viability, apoptosis, proliferation, autophagy, and migration. Methods \After the siRNA-mediated silencing of NRF2 in AGS cells, the transfection efficacy was evaluated by qRT-PCR. The MTT assay was then applied to assess cell viability, followed by flow cytometry analysis for apoptosis, proliferation, and autophagy in AGS cells treated with NRF2 siRNA, paclitaxel, or their combination. Thereafter, the migration of cells was measured using a wound-healing assay. Ultimately, the relative gene expression levels of apoptotic (Bax, Caspase-3, and Caspase-9), anti-apoptotic (Bcl-2), metastatic (MMP-2), and cell cycle (P53) genes were measured by qRT-PCR in all experiment groups to further assess the molecular basis for the combination therapy. Results NRF2 siRNA transfection significantly enhanced paclitaxel-induced apoptosis and sensitized AGS cells to paclitaxel via modulating the expression of apoptosis-related genes including Bcl-2, Bax, Caspase-3, and Caspase-9. Besides, NRF2 siRNA and paclitaxel synergistically induced cell cycle arrest at the G2 phase, promoted autophagy activation, and inhibited AGS cell migration via MMP-2 downregulation. Additionally, P53, a key regulator of cell growth, was significantly upregulated in the treated groups compared to the control group. Conclusions Our findings suggest that paclitaxel combined with siRNA-mediated silencing of NRF2 might represent a promising therapeutic strategy for GC, however further translational and clinical research are warranted.

Abstract Background Youth voice has been largely absent from deliberations regarding public health measures intended to prevent SARS-CoV-2 transmission, despite being one of the populations most impacted by school-based policies. To inform public health strategies and messages, we examined the level of student support of mask use in public spaces and school mask requirements, as well as factors associated with students’ perspectives. Methods We used cross-sectional survey data from 42,767 adolescents attending 133 Canadian secondary schools that participated in the COMPASS study during the 2020/2021 school year. Multinomial regression models assessed support for i) wearing a mask in indoor public spaces and ii) schools requiring students to wear masks, in association with COVID-19 knowledge, concerns, and perceived risk. Results Wearing masks in indoor public spaces was supported by 81.9% of students; 8.7% were unsupportive and 9.4% were neutral/undecided. School mask requirements were supported by 67.8%, with 23.1% neutral and 9.1% unsupportive. More females supported mask wearing in public spaces (83.9% vs. 79.1%) and school mask requirements (70.8% vs. 63.5%) than males. Students had increased odds of supporting mask use in public spaces and school mask requirements if they reported concerns about their own or their family’s health, had discussions regarding ways to prevent infection, perceived COVID-19 to be a risk to young people, and knew that signs are not always present in COVID-19 cases and that masks prevent SARS-CoV-2 transmission if someone coughs. Conclusions During the year following the beginning of the pandemic, most students supported the required use of masks in schools and wearing masks in indoor public spaces. Improving knowledge around the effectiveness of masks appears likely to have the largest impact on mask support in adolescent populations among the factors studied.

Purpose: The objective of this scoping review was to summarize systematically the available literature investigating the relationships between the coronavirus disease 2019 (COVID-19) pandemic and movement behaviors (physical activity, sedentary behavior, and sleep) of school-aged children (aged 5−11 years) and youth (aged 12−17 years) in the first year of the COVID-19 outbreak. Methods: Searches for published literature were conducted across 6 databases on 2 separate search dates (November 25, 2020, and January 27, 2021). Results were screened and extracted by 2 reviewers (DCP and KR) independently, using Covidence. Basic numeric analysis and content analysis were undertaken to present thematically the findings of included studies according to the associated impact on each movement behavior. Results: A total of 1486 records were extracted from database searches; of those, 150 met inclusion criteria and were included for analysis. Of 150 articles, 110 were empirical studies examining physical activity (n = 77), sedentary behavior/screen time (n = 58), and sleep (n = 55). Results consistently reported declines in physical-activity time, increases in screen time and total sedentary behavior, shifts to later bed and wake times, and increases in sleep duration. The reported impacts on movement behaviors were greater for youth than for children. Conclusion: The COVID-19 pandemic is related to changes in the quantity and nature of physical activity, sedentary behavior, and sleep among children and youth. There is an urgent need for policy makers, practitioners, and researchers to develop solutions for attenuating adverse changes in physical activity and screen time among children and youth.

Abstract Background It is important to engage stakeholders and end users in the development of guidelines for knowledge translation purposes. The aim of this study was to examine stakeholders’ (experts in pediatric and family medicine, physical activity knowledge translation, and research) and end users’ (parents and early childhood educators) perceptions of the Canadian 24-Hour Movement Guidelines for the Early Years (0–4 years). Methods Stakeholders (n = 10) engaged in telephone interviews and end users (n = 92) participated in focus groups (n = 14) to discuss perceived clarity and need for the guidelines, potential barriers to implementation, identification of credible messengers, and methods for dissemination of the guidelines. A thematic analysis was conducted. Results The proposed guidelines were very well received by both stakeholders and end users. A clear need for such guidelines was identified, and most believed the guidelines were achievable. Stakeholders and end users identified several potential barriers to uptake, including low awareness of current guidelines; ‘daily challenges’ such as allure of screen time, lack of time, and competing priorities; and challenges in the context of shifting social norms. A range of methods and messengers of dissemination were identified. Medical and child care settings were the most frequently cited places for dissemination, and physicians and early childhood educators were the most common suggestions for messengers. Conclusions There was consistent support for the Canadian 24-Hour Movement Guidelines for the Early Years (0–4 years) from both stakeholders and end users. Moving forward, it is important to dedicate appropriate support and funding toward dissemination efforts in order to reach end users, particularly parents and early childhood educators.