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Background: The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood. Methods: Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT–PCR), western blotting, immunofluorescence (IF), and immunohistochemistry. Extensive in vitro and in vivo experiments were carried out to determine the role of ERO1α and its downstream target, member 11 of the solute carrier family 7 (SLC7A11), in mTORC1-mediated cell proliferation, angiogenesis, ferroptosis resistance, and tumor growth. The regulatory mechanism of ERO1α on SLC7A11 was investigated via RNA-sequencing, a cytokine array, an enzyme-linked immunosorbent assay, qRT–PCR, western blotting, IF, a luciferase reporter assay, and a chromatin immunoprecipitation assay. The combined therapeutic effect of ERO1α inhibition and the ferroptosis inducer imidazole ketone erastin (IKE) on mTORC1-activated cells was evaluated using cell line-derived xenografts, LSCC organoids, and LSCC patient-derived xenograft models. Results: ERO1α is a functional downstream target of mTORC1. Elevated ERO1α induced ferroptosis resistance and exerted pro-oncogenic roles in mTORC1-activated cells via upregulation of SLC7A11. Mechanically, ERO1α stimulated the transcription of SLC7A11 by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ERO1α inhibition combined with treatment using the ferroptosis inducer IKE exhibited synergistic antitumor effects on mTORC1-activated tumors. Conclusions: The ERO1α/IL-6/STAT3/SLC7A11 pathway is crucial for mTORC1-mediated ferroptosis resistance and tumor growth, and combining ERO1α inhibition with ferroptosis inducers is a novel and effective treatment for mTORC1-related tumors. [ABSTRACT FROM AUTHOR]

Background: As the most populous nation in the world, China has now becoming an emerging ageing society. Shanghai is the first city facing the challenge of ageing demographics. Against this background, a study that employs self-rated health (SRH) assessment system was designed to explore the health status of Shanghai elders, and learn their attitudes toward health issues; as well as to investigate the determinants of SRH among Shanghai elders. Understanding SRH is crucial for finding appropriate solutions that could effectively tackle the increasing eldercare demand.Methods: This study adopted a quantitative research strategy. Using a multistage stratified cluster sampling method, we conducted a questionnaire survey in August 2011 in Shanghai, which collected 2001 valid survey responses. SRH assessments were categorized by five levels: very good, fairly good, average, fairly poor, or poor. The respondents' functional status was evaluated using the Barthel index of activities for daily living. In the data analysis, we used chi-squared test to determine differences in socio-demographic characteristics among various groups. Along with statistics, several logistic regression models were designed to determine the associations between internal influence factors and SRH.Results: Younger age (χ2 = 27.5, p < 0.05), male sex (χ2 = 11.5, p < 0.1), and living in the suburbs (χ2 = 55.1, p < 0.05) were associated with better SRH scores. Higher SRH scores were also linked with health behaviour of the respondents; namely, do not smoke (χ2 = 18.0, p < 0.1), do not drink (χ2 = 18.6, p < 0.1), or engage in regular outdoor activities (χ2 = 69.3, p < 0.05). The respondents with better social support report higher SRH scores than those without. Respondents' ability to hear (χ2 = 38.7, p < 0.05), speak (χ2 = 16.1, p < 0.05) and see (χ2 = 78.3, p < 0.05) impacted their SRH scores as well. Meanwhile, chronic illness except asthma was a major influence factor in low SRH score. Applying multiple regression models, a series of determinants were analysed to establish the extent to which they contribute to SRH. The impact of these variables on SRH scores were 6.6% from socio-demographic and health risk behaviours, 2.4% from social support, 8.5% from mental health, 20% from physical conditions, and13% from chronic diseases.Conclusions: This is the first study that examines the determinants of SRH among Shanghai elders. Nearly 40% of our study's respondents reported their health status as "good". The main determinants of SRH among elders include living condition, health risk behaviour, social support, health status, and the economic status of the neighbourhood. [ABSTRACT FROM AUTHOR]