Activity

When comparing those with an increase in lifestyle score of ≥2 with those who improved less or declined in achievement the HR was 0.74 (0.54-1.00) and 1.02 (0.84-1.24) for men and women respectively. These findings support the inclusion of lifestyle recommendations in cancer prevention guidelines. They further suggest that interventions to change health behaviours in middle-age may reduce risk of the most common preventable cancers in men, but this association was not observed in women. Strategies to encourage healthy lifestyles earlier in the life course may be more effective.In the absence of a vaccine, governments have focused on behaviour change (e.g. social distancing and enhanced hygiene procedures) to tackle the COVID-19 pandemic. Existing research on the predictors of compliance with pandemic measures has often produced discrepant results. One explanation for this may be that the determinants of compliance are context specific. Understanding whether this is the case is important for designing public health messaging and for evaluating the generalisability of existing research. We used data from the UCL COVID-19 Social Study; a large weekly panel of UK adults from first five months of lockdown in the UK (n = 22,625). We tested whether the extent to which demographic, socio-economic position, personality traits, social and pro-social motivations, and the living environment predict compliance changed across the pandemic using multilevel regression modelling. Low compliance was strongly related to younger age and also to risk attitudes, empathic concern, and high income, among other factors. The size of some of these associations was larger in later months when less stringent lockdown and household mixing measures were in place. The results showed that compliance was lower and fell faster across some groups, suggesting the importance that public health communications adopt a plurality of messages to maximize broad adherence.Breast cancer diagnosis and treatment can lead to longer term cognitive and emotional vulnerability, making the ability to efficiently adapt to setbacks critical. Whilst cancer-related cognitive impairments (CRCI) are often reported amongst breast cancer survivors, investigation into the capacity to efficiently process errors is limited. The present study investigated the neurocognitive correlates of cognitive-control related performance monitoring, an important function influencing behavioural adjustment to mistakes. 62 participants (30 Breast Cancer Survivors, 32 Non-Cancer) completed a modified flanker task designed to challenge response inhibition as we measured neurocognitive indices of performance monitoring (ERN, the error-related negativity; CRN, the correct-response negativity; Pe, the error positivity). Findings indicated a blunted CRN and larger ∆ERN in the breast cancer survivors compared to the non-cancer group, in the absence of performance effects. This was followed by a larger Pe in the breast cancer survivors’ group, indicating an exaggerated performance monitoring response. For women affected by breast cancer, findings suggest an early disrupted neural response to monitoring cognitive performance, followed by the requirement for more effortful processing in the conscious response to errors, indicating deficits in neurocognitive efficiency. These findings have important implications for developing cognitive rehabilitation programmes for breast cancer survivors affected by cognitive dysfunction to assist in the monitoring and adjustment of performance required to meet established goals in the face of adversity.Melanoma is the most lethal skin cancer caused by the malignant transformation of epidermal melanocytes. Recent progress in targeted therapy and immunotherapy has significantly improved the treatment outcome, but the survival of patients with advanced melanoma remains suboptimal. Ferroptosis, a cell death modality triggered by iron-dependent lipid peroxidation, reportedly participates in cancer pathogenesis and can mediate the effect of anti-PD-1 immunotherapy in melanoma. However, the detailed regulatory mechanism of ferroptosis remains far from being understood. In this study, we report that CAMKK2 defines the ferroptosis sensitivity of melanoma cells by regulating the AMPK‒NRF2 pathway. We first found that CAMKK2 was prominently activated in ferroptosis. Then we proved that CAMKK2 negatively regulated ferroptosis through the activation of NRF2 and the suppression of lipid peroxidation. Subsequent mechanistic studies revealed that AMPK connected CAMKK2 upregulation to NRF2-dependent antioxidative machinery in ferroptosis. In addition, the suppression of CAMKK2 increased the efficacy of ferroptosis inducer and anti-PD-1 immunotherapy in the preclinical xenograft tumor model by inhibiting the AMPK‒NRF2 pathway and promoting ferroptosis. Taken together, CAMKK2 plays a protective role in ferroptosis by activating the AMPK‒NRF2 pathway. Targeting CAMKK2 could be a potential approach to increase the efficacy of ferroptosis inducers and immunotherapy for melanoma treatment.Keloids are a benign dermal fibrotic disorder with features similar to malignant tumors. keloids remain a therapeutic challenge and lack medical therapies, which is partially due to the incomplete understanding of the pathogenesis mechanism. We performed single-cell RNA-seq of 28,064 cells from keloid skin tissue and adjacent relatively normal tissue. Unbiased clustering revealed substantial cellular heterogeneity of keloid tissue, which included 21 clusters assigned to 11 cell lineages. Lenvatinib solubility dmso We observed significant expansion of fibroblast and vascular endothelial cell subpopulations in keloids, reflecting their strong association with keloid pathogenesis. Comparative analyses were performed to identify the dysregulated pathways, regulators and ligand-receptor interactions in keloid fibroblasts and vascular endothelial cells. Our results highlight the roles of transforming growth factor beta and Eph-ephrin signaling pathways in both the aberrant fibrogenesis and angiogenesis of keloids. Critical regulators probably involved in the fibrogenesis of keloid fibroblasts, such as TWIST1, FOXO3 and SMAD3, were identified. TWIST1 inhibitor harmine could significantly suppress the fibrogenesis of keloid fibroblasts. In addition, tumor-related pathways were activated in keloid fibroblasts and vascular endothelial cells, which may be responsible for the malignant features of keloids. Our study put insights into the pathogenesis of keloids and provides potential targets for medical therapies.