Engaging patients in the decarbonisation of primary care: findings from a cross-sectional survey in England.

Premature ovarian failure (POF) is a non-physiological disease, as a type of ovarian dysfunction, which seriously affects women’s physical and mental health and is associated with serious consequences such as autoimmune diseases, cardiovascular diseases, psychological disorders and infertility [, ]. Globally, this condition affects 1%-5% of women under 40 years old, manifesting through sex hormone imbalance and accelerated follicular atresia []. The ovarian granulosa cells (GCs) are the main functioning cells that secrete estrogen, and maintain hormonal balance in the ovarian niche, in order to promote oocyte maturation autocrine and paracrine mechanisms []. Apoptosis of the GCs in the follicles leads to follicular atrophy and atresia, ultimately leading to POF []. Mechanistically, excessive reactive oxygen species (ROS) accumulation coupled with compromised antioxidant defense mechanisms induces oxidative stress-mediated apoptosis in ovarian tissue, thereby accelerating POF progression []. While hormone replacement therapy (HRT) remains the clinical mainstay, its long-term application carries substantial risks including thromboembolic complications and endocrine disruption []. Therefore, finding therapeutic strategies targeting the regulation of GCs apoptosis and redox homeostasis restoration may represent a promising approach to extend ovarian function longevity and mitigate POF-associated pathological manifestations. Gut microbiota acts as a regulator in a bidirectional relationship with many key organs of the host, and in regulating host health processes is beneficial, including metabolic and nutritional homeostasis, immune system maturation, and stimulation [, ]. Emerging evidence suggests ovarian senescence triggers gut microbiota dysbiosis, while fecal microbiota transplantation (FMT) from young donors to aged murine models demonstrates remarkable ovarian rejuvenation effects, including attenuated granulosa cells apoptosis and follicular atresia []. Despite these advances, the role of microbial communities in POF remains underexplored. The development of diseases in distal organs is influenced by the gut microbiota, which establishes an ‘gut-x axis’ through bacterial translocation, metabolic changes and systemic humoral factors []. The gut microbiota significantly influences intestinal barrier function, and impairment of the intestinal barrier can lead to bacterial translocation, thereby exacerbating the pathophysiology of inflammatory and metabolic disorders. Notably, small-molecule metabolites from the gut microbiota are essential in maintaining the integrity of the intestinal barrier []. Therefore, targeting metabolites regulated by gut microbiota and treating POF by restoring intestinal barrier function may be a new strategy. Among various dietary additives, N-carbamylglutamate (NCG) has emerged as a particularly promising candidate, garnering growing attention in recent biomedical research []. Dietary NCG supplementation enhances animal growth performance, intestinal integrity, and antioxidant status through stimulating lymphocyte proliferation and modulating cytokine synthesis [, , ]. Furthermore, NCG administration regulates amino acid and lipid metabolism in rat models []. However, the regulatory effect and potential mechanism of NCG on the disorder of gut microbiota in POF, especially its metabolic function, have not been explored. Therefore, the present study systematically investigated the mitigating effect of NCG on POF using the cyclophosphamide (Cy)-induced POF mice model. Cy is recognized as a drug that leads to the depletion of ovarian reserve and thus POF [].