Historical variability of cotton yield and response to climate and agronomic management in Xinjiang, China.

Cotton is the primary fibre crop in the world with high economic value, and its yield can be affected by climate and agronomic management. Xinjiang, the largest cotton-producing province in China, contributes to approximately 90 % of the national and over 20 % of global production. Earlier studies focused on cotton yield variability and/or drivers on the site scale, for only one to several counties or cities within Xinjiang, in several years before 2000, or provincial production for a short period. It remains poorly understood how and why cotton yields change in Xinjiang. This study analyzes the spatiotemporal variability of cotton yields at the provincial and county (73 counties) levels from 1989 to 2017 using yield statistics, and identifies the dominant climate and agronomic management factors as well as their optimal ranges, historical states, and interaction effects using the geographical detector method (Geodetector). The results show that the Xinjiang cotton yield has increased markedly over the past decades, with the long-term trend outweighing the interannual variability. High yields are mostly found in southern and northwestern Xinjiang. Yield has increased significantly in over 95.6 % of cotton-planting areas, primarily in the west. Nitrogen fertilization is the leading driver of cotton yield changes, mainly impacting long-term trends. The combination of nitrogen fertilization and agricultural mechanization enhances the explanatory power in a bivariate way and is the strongest in the interaction effect between factors. Temperature variability has the greatest influence on detrended yield variability, and the explanatory power is enhanced and the highest when combined with precipitation. In addition, historical states of these factors are generally lower than their optimal ranges, indicating potential for cotton yield enhancement through improved agronomic management practices and in the context of global warming. This study could enhance understanding of cotton Xinjiang yield variability and drivers, and provides scientific guidance for local cotton cultivation.

In Situ Synthesis of an Immune-Checkpoint Blocker from Engineered Bacteria Elicits a Potent Antitumor Response.

Immune-checkpoint blockade (ICB) reinvigorates T cells from exhaustion and potentiates T-cell responses to tumors. However, most patients do not respond to ICB therapy, and only a limited response can be achieved in a "cold" tumor with few infiltrated lymphocytes. Synthetic biology can be used to engineer bacteria as controllable bioreactors to synthesize biotherapeutics in situ. We engineered attenuated Salmonella VNP20009 with synthetic gene circuits to produce PD-1 and Tim-3 scFv to block immunosuppressive receptors on exhausted T cells to reinvigorate their antitumor response. Secreted PD-1 and Tim-3 scFv bound PD-1+ Tim-3+ T cells through their targeting receptors in vitro and potentiated the T-cell secretion of IFN-γ. Engineered bacteria colonized the hypoxic core of the tumor and synthesized PD-1 and Tim-3 scFv in situ, reviving CD4+ T cells and CD8+ T cells to execute an antitumor response. The bacteria also triggered a strong innate immune response, which stimulated the expansion of IFN-γ+ CD4+ T cells within the tumors to induce direct and indirect antitumor immunity.

Bioengineered Artificial Extracellular Vesicles Presenting PD-L1 and Gal-9 Ameliorate New-Onset Type 1 Diabetes.

An important factor in the development of type 1 diabetes (T1D) is the deficiency of inhibitory immune checkpoint ligands, specifically programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9), in ß-cells. Therefore, modulation of pancreas-infiltrated T lymphocytes by exogenous PD-L1 or Gal-9 is an ideal approach for treating new-onset T1D. We genetically engineered macrophage cells to generate artificial extracellular vesicles (aEVs) overexpressing PD-L1 and Gal-9, which could restrict islet autoreactive T lymphocytes and protect ß-cells from destruction. Intriguingly, overexpression of Gal-9 stimulated macrophage polarization to the M2 phenotype with immunosuppressive attributes. Alternatively, both PD-L1- and Gal-9-presenting aEVs (PD-L1-Gal-9 aEVs) favorably adhered to T cells via the interaction of programmed cell death protein 1/PD-L1 or T-cell immunoglobulin mucin 3/Gal-9. Moreover, PD-L1-Gal-9 aEVs prominently promoted effector T-cell apoptosis and splenic regulatory T (Treg) cell formation in vitro. Notably, PD-L1-Gal-9 aEVs efficaciously reversed new-onset hyperglycemia in NOD mice, prevented T1D progression, and decreased the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas, which together contributed to the preservation of residual ß-cell survival and mitigation of hyperglycemia.