Pronounced T cell exhaustion characterizes immunosuppressive tumors, with the tumor microenvironment (TME) employing multiple mechanisms to elicit this suppression. Traditional immunotherapies, such as immune checkpoint blockade, often fail due to their focus primarily on T cells. To overcome this, we utilized a proinflammatory cytokine, interleukin (IL)-12, that re-wires the immunosuppressive TME by inducing T cell effector function while also repolarizing immunosuppressive myeloid cells.
View Article and Find Full Text PDFThe COVID-19 stay-at-home orders issued in the United States caused significant reductions in traffic and economic activities. To understand the pandemic's perturbations on US emissions and impacts on urban air quality, we developed near-real-time bottom-up emission inventories based on publicly available energy and economic datasets, simulated the emission changes in a chemical transport model, and evaluated air quality impacts against various observations. The COVID-19 pandemic affected US emissions across broad-based energy and economic sectors and the impacts persisted to 2021.
View Article and Find Full Text PDFUnlabelled: The immunosuppressive milieu in pancreatic cancer (PC) is a significant hurdle to treatments, resulting in survival statistics that have barely changed in 5 decades. Here we present a combination treatment consisting of stereotactic body radiation therapy (SBRT) and IL-12 mRNA lipid nanoparticles delivered directly to pancreatic murine tumors. This treatment was effective against primary and metastatic models, achieving cures in both settings.
View Article and Find Full Text PDFWe tested whether Shoshone pupfish and Amargosa River pupfish respond behaviourally to conspecific chemical alarm cues released when epidermal tissue is damaged by a predator. We found that both subspecies reduced activity and vertical position in the water column in response to alarm cues. We then tested if pupfish can use alarm cue to acquire recognition of a novel predator.
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