Long-term non-phosphorus application increased paddy methane emission by promoting organic acid and methanogen abundance in Tai Lake region, China.

Rice paddy is a significant source of atmospheric methane (CH4), a major global warming source. CH4 emission from paddy fields is greatly influenced by phosphorus (P) management, especially the long-term non-P application on CH4 emission is largely unexplored. In the present study, long-term non-P application (NK) and P application (NPK) treatments of two paddy fields in Suzhou (from 1980) and Yixing (from 2009), Tai Lake region was done. The effect of P application on CH4 emissions and related microorganisms (i.e., methanogens and methanotrophs) from 2019 to 2020 was analyzed. Results revealed that long-term NK treatment didn't alter the seasonal trend of CH4 flux, but significantly promoted CH4 emissions at the tillering stage. The non-P application for >12 years caused the cumulative CH4 emissions of NK treatment in the whole rice season significantly increased by 41.9-221 % in two fields compared to NPK treatment in 2019 and 2020. NK treatment increased the abundance and diversity of methanogens, while reducing the abundance and diversity of methanotrophs. Community composition of soil pmoA gene differed in two experiment sites. Correlation analysis revealed that the CH4 emission was significant and positively related to soil mcrA gene and C/P while negatively related to soil pmoA gene and P. Structure equation model analysis show the low soil available P content was the dominant driving factor for the high CH4 emission under long-term non-P application through its direct impact on soil mcrA and pmoA genes. The increased soil organic acid content was another driver which was positively related to soil mcrA gene and negatively to soil pmoA gene. Our findings demonstrate the important role of soil P in regulating CH4 emissions from paddy fields in the Tai Lake region, China, and suitable P application is necessary for ensuring the yield while reducing CH4 emission.

Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells.

Vγ2Vδ2 T cell-based immunotherapy has benefited some patients in clinical trials, but the overall efficacy is low for solid tumor patients. In this study, a bispecific antibody against both PD-L1 and CD3 (PD-L1 x CD3), Y111, could efficiently bridge T cells and PD-L1 expressing tumor cells. The Y111 prompted fresh CD8+ T cell-mediated lysis of H358 cells, but spared this effect on the fresh Vδ2+ T cells enriched from the same donors, which suggested that Y111 could bypass the anti-tumor capacity of the fresh Vγ2Vδ2 T cells. As the adoptive transfer of the expanded Vγ2Vδ2 T cells was approved to be safe and well-tolerated in clinical trials, we hypothesized that the combination of the expanded Vγ2Vδ2 T cells with the Y111 would provide an alternative approach of immunotherapy. Y111 induced the activation of the expanded Vγ2Vδ2 T cells in a dose-dependent fashion in the presence of PD-L1 positive tumor cells. Moreover, Y111 increased the cytotoxicity of the expanded Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines with the releases of granzyme B, IFNγ, and TNFα in vitro. Meanwhile, the adoptive transferred Vγ2Vδ2 T cells together with the Y111 inhibited the growth of the established xenografts in NPG mice. Taken together, our data suggested a clinical potential for the adoptive transferring the Vγ2Vδ2 T cells with the Y111 to treat PD-L1 positive solid tumors.

CDC5L drives FAH expression to promote metabolic reprogramming in melanoma.

Metabolic reprogramming allows tumor cells to thrive in the typically hypoxic tumor microenvironment. Using immunodetection and clinical data analyses, we demonstrate here that fumarylacetoacetate hydrolase (FAH) is highly expressed in melanoma and correlates with poor survival. FAH knockdown inhibits proliferation and migration, while promoting apoptosis in melanoma cells, result in prolonged survival in tumor-bearing mice. Molecular analyses using real time RT-PCR, western blot, and 13C tracing showed that these changes are driven by strong stimulation of anaplerotic reactions through the TCA cycle and the pentose-phosphate pathway, resulting in increased fatty acid and nucleotide synthesis. Using bioinformatic, ChIP-PCR, and gene silencing analyses, we determined that cell division cycle 5-like protein (CDC5L) is an important transcription factor regulating FAH expression in melanoma cells. These findings reveal that FAH induces metabolic reprogramming in melanoma and so emerges as both a potentially useful independent prognostic indicator and an attractive therapeutic target.