Photoreceptor apoptosis is recognized as one key pathogenesis of retinal degeneration, the counteraction of which represents a promising approach to safeguard visual function. Recently, mesenchymal stem cell transplantation (MSCT) has demonstrated immense potential to treat ocular disorders, in which extracellular vesicles (EVs), particularly exosomes, have emerged as effective ophthalmological therapeutics. However, whether and how MSCT protects photoreceptors against apoptotic injuries remains largely unknown. Here, we discovered that intravitreal MSCT counteracted photoreceptor apoptosis and alleviated retinal morphological and functional degeneration in a mouse model of photoreceptor loss induced by N-methyl-N-nitrosourea (MNU). Interestingly, effects of MSCT were inhibited after blockade of exosomal generation by GW4869 preconditioning. Furthermore, MSC-derived exosomal transplantation (EXOT) effectively suppressed MNU-provoked photoreceptor injury. Notably, therapeutic efficacy of MSCT and EXOT on MNU-induced retinal degeneration was long-lasting as photoreceptor preservance and retinal maintenance were detected even after 1–2 months post to injection for only once. More importantly, using a natural occurring retinal degeneration model caused by a nonsense mutation of Phosphodiesterase 6b gene (Pde6bmut), we confirmed that MSCT and EXOT prevented photoreceptor loss and protected long-term retinal function. In deciphering therapeutic mechanisms regarding potential exosome-mediated communications, we identified that miR-21 critically maintained photoreceptor viability against MNU injury by targeting programmed cell death 4 (Pdcd4) and was transferred from MSC-derived exosomes in vivo for functional regulation. Moreover, miR-21 deficiency aggravated MNU-driven retinal injury and was restrained by EXOT. Further experiments revealed that miR-21 mediated therapeutic effects of EXOT on MNU-induced photoreceptor apoptosis and retinal dysfunction. These findings uncovered the efficacy and mechanism of MSCT-based photoreceptor protection, indicating exosomal miR-21 as a therapeutic for retinal degeneration.

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Since the industrial revolution, it has been assumed that fossil-fuel combustions dominate increasing nitrogen oxide (NOx) emissions. However, it remains uncertain to the actual contribution of the non-fossil fuel NOx to total NOx emissions. Natural N isotopes of NO3− in precipitation (δ15Nw-NO3−) have been widely employed for tracing atmospheric NOx sources. Here, we compiled global δ15Nw-NO3− observations to evaluate the relative importance of fossil and non-fossil fuel NOx emissions. We found that regional differences in human activities directly influenced spatial-temporal patterns of δ15Nw-NO3− variations. Further, isotope mass-balance and bottom-up calculations suggest that the non-fossil fuel NOx accounts for 55 ± 7% of total NOx emissions, reaching up to 21.6 ± 16.6Mt yr−1 in East Asia, 7.4 ± 5.5Mt yr−1 in Europe, and 21.8 ± 18.5Mt yr−1 in North America, respectively. These results reveal the importance of non-fossil fuel NOx emissions and provide direct evidence for making strategies on mitigating atmospheric NOx pollution.

Exotic plant invasion has been changing the vegetation composition and function of terrestrial ecosystems. Nitrogen (N) and phosphorus (P) are often the limiting nutrients for terrestrial plants. However, under invasive pressure, in situ plant N and P usage mechanisms remain poorly understood but are pivotal for a better understanding of plant invasion and coexistence in invaded ecosystems. Nitrogen and P concentrations, natural 15N abundance (δ15N values) were investigated in leaves and soils under different invasive pressures (here expressed as the biomass percentages of invasive plants in each plot) for two invasive species (Chromolaena odorata and Ageratina adenophora) in Xishuangbanna in tropical China. Soil N and P concentrations revealed the relatively N‐rich but P‐poor status of our study site. Under invasion, soil inorganic N (dominated by ammonium) and available P did not increase significantly. The leaf N and P of invasive plants increased, while leaf N increased but P decreased for native species. Natural δ15N mass balance between leaves and soil inorganic N sources revealed that ammonium dominated N utilization in both natives and invaders. Invasive plants showed ammonium utilization with increasing leaf N levels, while native plants under no invasion showed nitrate utilization with increasing leaf N levels. Synthesis. Increased soil ammonium availability contributed to preferential ammonium utilization by invasive plants and elevated ammonium utilization in natives, but the P competition of natives decreased in invaded ecosystems. These novel insights into nutrient dynamics in invaded ecosystems enhance our understanding of plant invasion and coexistence mechanisms.

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