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Abstract Chronic high-altitude hypoxia (CHH) induces irreversible abnormalities in various organisms. Emerging evidence indicates that CHH markedly suppresses bone mass and bone strength. Targeting senescent cells and the consequent senescence-associated secretory phenotype (SASP) with senolytics is a recently developed novel therapy for multiple age-related diseases. The combination of dasatinib and quercetin (DQ) has been proven to selectively target senescent cells and attenuate SASP in multiple tissues. In this study, experimental mice were subjected to an environment simulating 5,000 m above sea level for 8 weeks to induce CHH conditions. Our results indicated that DQ supplementation was well-tolerated with negligible toxicity. In vivo, DQ prevented reductions in BMD and BMC and improved bone microarchitecture against CHH-induced changes. Biomechanical testing demonstrated that DQ significantly improved the mechanical properties of femoral bones in CHH-exposed mice. Furthermore, DQ mitigated senescence in LepR + BMSCs and decreased the population of senescent cells, as evidenced by reduced senescence markers and SA-β-Gal staining. An analysis of serum and bone marrow aspirates showed that DQ treatment preserved angiogenic and osteogenic coupling in the bone marrow microenvironment by maintaining type H vessels and angiogenic growth factors. The results suggest that DQ has significant anti-senescence effects on BMSCs and a positive impact on the bone marrow microenvironment, supporting its clinical investigation as a therapeutic agent for CHH-related osteoporosis.

Land use changes are thought to deeply impact the changes of terrestrial carbon sink, however, how the changes of land use pattern affect the carbon sink remains unclear. To investigate the response of Net Ecosystem Productivity (NEP) to the pattern of land use dynamics in China, a landscape pattern approach (with the 30 km moving window) was used to analyze the pattern dynamics with continuous Land Use and Land Cover Change (LUCC) data from 1981 to 2019 and the nonlinear trends of the NEP and the patterns of land use were explored from 1981 to 2019 using Ensemble empirical modal decomposition (EEMD) methods, and their interannual relationship was further explored using Pearson correlation. The results are as follows: (1) For NEP, nearly half of the regions did not experience significant changes. 90 %) have experienced significant changes in land use patterns, the fragmentation and shape complexity, diversity and evenness of land use types has increased, while the connection decreased, meanwhile, most of these changes are not monotonical, but experiencing trend shifts; (3) In most of the total area (>80 %), land use patterns showed insignificant relationship with NEP, especially in Qinghai-Tibetan Plateau. However, in Greater Khingan Range, Loess Plateau and southern Hilly area, it showed significant relationship with NEP. Our studies highlight the importance of nonlinear analysis for fully understanding the spatial–temporal changes of NEP and land use patterns, and deepened the understanding the impacts of land use changes on NEP.