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Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects
The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.
Coastal wetland resilience through local, regional and global conservation
Coastal wetlands, including tidal marshes, mangrove forests and tidal flats, support the livelihoods of millions of people. Understanding the resilience of coastal wetlands to the increasing number and intensity of anthropogenic threats (such as habitat conversion, pollution, fishing and climate change) can inform what conservation actions will be effective. In this Review, we synthesize anthropogenic threats to coastal wetlands and their resilience through the lens of scale. Over decades and centuries, anthropogenic threats have unfolded across local, regional and global scales, reducing both the extent and quality of coastal wetlands. The resilience of existing coastal wetlands is driven by their quality, which is modulated by both physical conditions (such as sediment supply) and ecological conditions (such as species interactions operating from local through to global scales). Protection and restoration efforts, however, are often localized and focus on the extent of coastal wetlands. The future of coastal wetlands will depend on an improved understanding of their resilience, and on society’s actions to enhance both their extent and quality across different scales.
Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus
Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus (T2DM), which is characterized by suppressed osteoblast function and disrupted bone microarchitecture. In this study, we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM. Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM. Mechanistically, SIRT3 suppression results in hyperacetylation of FOXO3, hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria. Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3, thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM. Collectively, our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control, crucial for maintaining bone homeostasis in T2DM. These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.
Worldwide rooftop photovoltaic electricity generation may mitigate global warming
Rooftop photovoltaic (RPV) is often understood as a niche contribution to climate change mitigation. However, the global potential of RPVs to mitigate global warming is unknown. Here we map the global rooftop area at 1-km resolution, quantifying 286,393 km2 of rooftops worldwide through geospatial data mining and artificial intelligence techniques. Using nine advanced Earth system models from the coupled model intercomparison project phase 6, we reveal that RPVs could substantially contribute to reducing global temperatures by 0.05–0.13 °C before 2050. Region-specific analysis underscores the variability in RPV potential and the necessity of tailored approaches to optimize RPV deployment, considering local solar resources, existing infrastructure and grid carbon intensity. Our findings reveal that leveraging RPV systems offers a viable and impactful strategy for reducing carbon footprints and combating climate change globally, while advocating targeted interventions to enhance the benefits of RPVs, particularly in areas with high solar radiation or rapid urbanization.
Predicting the need for diabetic macular oedema treatment from photographic screening in the Singapore Integrated Diabetic Retinopathy Programme (SiDRP)
To identify diabetic maculopathy features from photographic screening that are predictive of treatment on referral to a tertiary care centre.
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