Gaps and opportunities for the World Heritage Convention to contribute to global wilderness conservation.

Wilderness areas are ecologically intact landscapes predominantly free of human uses, especially industrial-scale activities that result in substantial biophysical disturbance. This definition does not exclude land and resource use by local communities who depend on such areas for subsistence and bio-cultural connections. Wilderness areas are important for biodiversity conservation and sustain key ecological processes and ecosystem services that underpin planetary life-support systems. Despite these widely recognized benefits and values of wilderness, they are insufficiently protected and are consequently being rapidly eroded. There are increasing calls for multilateral environmental agreements to make a greater and more systematic contribution to wilderness conservation before it is too late. We created a global map of remaining terrestrial wilderness following the established last-of-the-wild method, which identifies the 10% of areas with the lowest human pressure within each of Earth's 62 biogeographic realms and identifies the 10 largest contiguous areas and all contiguous areas >10,000 km2 . We used our map to assess wilderness coverage by the World Heritage Convention and to identify gaps in coverage. We then identified large nationally designated protected areas with good wilderness coverage within these gaps. One-quarter of natural and mixed (i.e., sites of both natural and cultural value) World Heritage Sites (WHS) contained wilderness (total of 545,307 km2 ), which is approximately 1.8% of the world's wilderness extent. Many WHS had excellent wilderness coverage, for example, the Okavango Delta in Botswana (11,914 km2 ) and the Central Suriname Nature Reserve (16,029 km2 ). However, 22 (35%) of the world's terrestrial biorealms had no wilderness representation within WHS. We identified 840 protected areas of >500 km2 that were predominantly wilderness (>50% of their area) and represented 18 of the 22 missing biorealms. These areas offer a starting point for assessing the potential for the designation of new WHSs that could help increase wilderness representation on the World Heritage list. We urge the World Heritage Convention to ensure that the ecological integrity and outstanding universal value of existing WHS with wilderness values are preserved.

Icariin inhibits osteoblast ferroptosis via Nrf2/HO-1 signaling and enhances healing of osteoporotic fractures.

The incidence of osteoporotic fractures is increasing every year because of population aging around the world. The reduced osteoblast activity in osteoporotic fracture has been associated with ferroptosis. A recent study showed that the antioxidant icariin (ICA) reduced iron deposition in the bone marrow of osteoporotic mice, although the underlying regulatory mechanisms were not explored. The objective of present study was to assess the therapeutic effects of ICA in a rat osteoporotic fracture model, with particular focus on its impact on ferroptosis. Primary rat osteoblasts were exposed to the ferroptosis inducer erastin, and then treated with ICA or the ferroptosis inhibitor ferrostatin-1 (Fer-1) as the positive control group. The levels of Nrf2 signaling factors and osteogenesis-related factors were examined by RT-PCR and western blotting. An osteoporotic fracture model was established in rats, and the effect of ICA on bone formation was evaluated by X-ray, Micro CT analysis, histological examination and Safranin O staining. Furthermore, the levels of GPX4, Bax, Nrf2 and Runx2 proteins at the fracture site were examined by immunohistochemistry. ICA significantly reduced ROS levels in the erastin-treated osteoblasts, and downregulated glutathione peroxidase 4 (GPX4) and cystine glutamate antiporter (SLC7A11). Moreover, ICA also upregulated Nrf2, NQO-1, HO-1, Runx2, ALP, OPG and OCN in these cells, which was reversed by inhibitors of the Nrf2 signaling pathway and Nrf2 silencing. X-ray and Micro CT analysis showed that ICA increased the trabecular bone and promoted callus formation in the osteoporotic fracture model, and also enhanced the transition from fibrous to osseous callus. Furthermore, ICA upregulated GPX4, Nrf2 and Runx2 at the fracture site, and significantly reduced the expression of the apoptotic genes of Bax. Taken together, our findings indicate that ICA promotes osteoporotic fracture healing by inhibiting osteoblast ferroptosis via activation of the antioxidant Nrf2/HO-1 signaling pathway.

Did Artificial Intelligence Invade Humans? The Study on the Mechanism of Patients' Willingness to Accept Artificial Intelligence Medical Care: From the Perspective of Intergroup Threat Theory.

Artificial intelligence (AI) has become one of the core driving forces for the future development of the medical industry, but patients are skeptical about the use of AI in medical care. Based on the intergroup threat theory (ITT), this study verified that patients would regard AI as an external group, triggering the perceived threat of the external group, which results in avoidance behaviors in the treatment (experiment 1: n = 446) and diagnosis (experiment 2: n = 330) scenarios. The results show that despite AI can provide expert-level accuracy in medical care, patients are still more likely to rely on human doctors and experience more negative emotions as AI is more involved in medical care (experiment 1). Furthermore, patients pay more attention to threats at the individual level related to themselves, such as realistic threats related to privacy issues and symbolic threats related to the neglect of personal characteristics. In contrast, realistic threats and symbolic threats at the group level had less effect on patients in the medical scenario (experiment 2).

Icariin Promotes the Osteogenesis of Bone Marrow Mesenchymal Stem Cells through Regulating Sclerostin and Activating the Wnt/ß-Catenin Signaling Pathway.

Osteoporosis (OP) is a metabolic disease characterized by decreased bone mass and increased risk of fragility fractures, which significantly reduces the quality of life. Stem cell-based therapies, especially using bone marrow mesenchymal stem cells (BMSCs), are a promising strategy for treating OP. Nevertheless, the survival and differentiation rates of the transplanted BMSCs are low, which limits their therapeutic efficiency. Icariin (ICA) is a traditional Chinese medicine formulation that is prescribed for tonifying the kidneys. It also promotes the proliferation and osteogenic differentiation of BMSCs, although the specific mechanism remains unclear. Based on our previous research, we hypothesized that ICA promotes bone formation via the sclerostin/Wnt/ß-catenin signaling pathway. We isolated rat BMSCs and transfected them with sclerostin gene (SOST) overexpressing or knockdown constructs and assessed osteogenic induction in the presence or absence of ICA. Sclerostin significantly inhibited BMSC proliferation and osteogenic differentiation, whereas the presence of ICA not only increased the number of viable BMSCs but also enhanced ALP activity and formation of calcium nodules during osteogenic induction. In addition, the osteogenic genes including Runx2, ß-catenin, and c-myc as well as antioxidant factors (Prdx1, Cata, and Nqo1) were downregulated by sclerostin and restored by ICA treatment. Mechanistically, ICA exerted these effects by activating the Wnt/ß-catenin pathway. In conclusion, ICA can promote the proliferation and osteogenic differentiation of BMSCs in situ and therefore may enhance the therapeutic efficiency of BMSC transplantation in OP.

Measuring the extent of overlaps in protected area designations.

Over the past decades, a number of national policies and international conventions have been implemented to promote the expansion of the world's protected area network, leading to a diversification of protected area strategies, types and designations. As a result, many areas are protected by more than one convention, legal instrument, or other effective means which may result in a lack of clarity around the governance and management regimes of particular locations. We assess the degree to which different designations overlap at global, regional and national levels to understand the extent of this phenomenon at different scales. We then compare the distribution and coverage of these multi-designated areas in the terrestrial and marine realms at the global level and among different regions, and we present the percentage of each county's protected area extent that is under more than one designation. Our findings show that almost a quarter of the world's protected area network is protected through more than one designation. In fact, we have documented up to eight overlapping designations. These overlaps in protected area designations occur in every region of the world, both in the terrestrial and marine realms, but are more common in the terrestrial realm and in some regions, notably Europe. In the terrestrial realm, the most common overlap is between one national and one international designation. In the marine realm, the most common overlap is between any two national designations. Multi-designations are therefore a widespread phenomenon but its implications are not well understood. This analysis identifies, for the first time, multi-designated areas across all designation types. This is a key step to understand how these areas are managed and governed to then move towards integrated and collaborative approaches that consider the different management and conservation objectives of each designation.