Impact of near-surface wind speed variability on wind erosion in the eastern agro-pastoral transitional zone of Northern China, 1982-2016 [Póster]

Póster presentado en: EGU General Assembly 2019 celebrada del 7 al 12 de abril en Viena, Austria.The Wind erosion in arid and semi-arid areas is an important global environmental issue, and changes in wind speed trends over time play a key role in wind erosion dynamics. In a warming climate, scientists have recently observed a widespread decline in wind speed, termed "stilling". Here, we apply the Revised Wind Erosion Equation Model (RWEQ) to simulate the variability of wind erosion and quantify the impact of wind speed changes on soil degradation dynamics over the eastern agro-pastoral transitional zone of Northern China (EANC) from 1982 to 2016. Our results show that a significant (i.e., p<0.05) decrease (-0.007 m s-1 year-1) of near-surface wind speed was observed annually, with significant declining trends in spring (-0.010 m s-1 year-1 ）and autumn (-0.009 m s-1 year-1). At the same time, wind erosion simulations reveal a negative trend for the annual soil loss from wind erosion (SLWE,-6.20 t hectare-2 year-1 , p<0.05; affecting 99.8% of the study region), with significant declining trends in all seasons, particularly in spring (-3.49 t hectare-2 year-1) and autumn (-1.26 hectare-2 year-1). Further, we isolate the effects of wind variability on wind erosion (SLWED) from 1982 to 2016 by the model variable control method. This shows that wind speed variability strongly weakens wind erosion at-8.14 t hectare-2 year-1 (p<0.05) annually, with the strongest stilling recorded in spring leading to major decreases of wind erosion in spring (-4.77 t hectare-2 year-1 , p<0.05). Meanwhile, the weakest stilling in summer had the opposite influence on wind erosion (+0.40 t hectare-2 year-1 , p<0.10). To summarize, our findings have shown a significant impact of wind stilling on the decline of soil erosion rates in Northern China.This research is funded by the National Natural Science Foundation of China (Grant No. 41621061), and funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 703733 (STILLING project). This work has been also supported by the VR Project (2017-03780) funded by the Swedish Research Council

Nanocarrier-Mediated Chemo-Immunotherapy Arrested Cancer Progression and Induced Tumor Dormancy in Desmoplastic Melanoma

In desmoplastic melanoma, tumor cells and tumor-associated fibroblasts are the major dominators playing a critical role in the fibrosis morphology as well as the immunosuppressive tumor microenvironment (TME), compromising the efficacy of therapeutic options. To overcome this therapeutic hurdle, we developed an innovative chemo-immunostrategy based on targeted delivery of mitoxantrone (MIT) and celastrol (CEL), two potent medicines screened and selected with the best anticancer and antifibrosis potentials. Importantly, CEL worked in synergy with MIT to induce immunogenic tumor cell death. Here, we show that when effectively co-delivered to the tumor site at their optimal ratio by a TME-responsive nanocarrier, the 5:1 combination of MIT and CEL significantly triggered immunogenic tumor apoptosis and recovered tumor antigen recognition, thus eliciting overall antitumor immunity. Furthermore, the strong synergy benefitted the host in reduced drug exposure and side effects. Collectively, the nanocarrier-mediated chemo-immunotherapy successfully remodeled fibrotic and immunosuppressive TME, arrested cancer progression, and further inhibited tumor metastasis to major organs. The affected tumors remained dormant long after dosing stopped, resulting in a prolonged progression-free survival and sustained immune surveillance of the host bearing desmoplastic melanoma

Nanoparticle-Mediated Trapping of Wnt Family Member 5A in Tumor Microenvironments Enhances Immunotherapy for B‑Raf Proto-Oncogene Mutant Melanoma

Development of an effective treatment against advanced tumors remains a major challenge for cancer immunotherapy. Approximately 50% of human melanoma is driven by B-Raf proto-oncogene mutation (BRAF mutant). Tumors with such mutation are desmoplastic, highly immunosuppressive, and often resistant to immune checkpoint therapies. We have shown that immunotherapy mediated by low-dose doxorubicin-induced immunogenic cell death was only partially effective for this type of tumor and not effective in long-term inhibition of tumor progression. Wnt family member 5A (Wnt5a), a signaling protein highly produced by BRAF mutant melanoma cells, has been implicated in inducing dendritic cell tolerance and tumor fibrosis, thus hindering effective antigen presentation and T-cell infiltration. We hypothesized that Wnt5a is a key molecule controlling the immunosuppressive tumor microenvironment in metastatic melanoma. Accordingly, we have designed and generated a trimeric trap protein, containing the extracellular domain of Fizzled 7 receptor that binds Wnt5a with a <i>K</i>_d ∼ 278 nM. Plasmid DNA encoding for the Wnt5a trap was delivered to the tumor by using cationic lipid-protamine-DNA nanoparticles. Expression of Wnt5a trap in the tumor, although transient, was greater than that of any other major organs including liver, resulting in a significant reduction of the Wnt5a level in the tumor microenvironment without systematic toxicity. Significantly, combination of Wnt5a trapping and low-dose doxorubicin showed great tumor growth inhibition and host survival prolongation. Our findings indicated that efficient local Wnt5a trapping significantly remodeled the immunosuppressive tumor microenvironment to facilitate immunogenic cell-death-mediated immunotherapy