Global S&T Development Trend Analysis Platform of Resources and Environment
Quantum mechanics governs the microscopic world, where low mass and momentum reveal a natural wave-particle duality. Magnifying quantum behaviour to macroscopic scales is a major strength of the technique of cooling and trapping atomic gases, in which low momentum is engineered through extremely low temperatures. Advances in this field have achieved such precise control over atomic systems that gravity, often negligible when considering individual atoms, has emerged as a substantial obstacle. In particular, although weaker trapping fields would allow access to lower temperatures(1,2), gravity empties atom traps that are too weak. Additionally, inertial sensors based on cold atoms could reach better sensitivities if the free-fall time of the atoms after release from the trap could be made longer(3). Planetary orbit, specifically the condition of perpetual free-fall, offers to lift cold-atom studies beyond such terrestrial limitations. Here we report production of rubidium Bose-Einstein condensates (BECs) in an Earth-orbiting research laboratory, the Cold Atom Lab. We observe subnanokelvin BECs in weak trapping potentials with free-expansion times extending beyond one second, providing an initial demonstration of the advantages offered by a microgravity environment for cold-atom experiments and verifying the successful operation of this facility. With routine BEC production, continuing operations will support long-term investigations of trap topologies unique to microgravity(4,5), atom-laser sources(6), few-body physics(7,8)and pathfinding techniques for atom-wave interferometry(9-12).
Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy(1-3). However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB4, mutations that cause loss of MHC-I are rarely found(5) despite the frequent downregulation of MHC-I expression(6-8). Here we show that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced expression of MHC-I at the cell surface and instead demonstrate predominant localization within autophagosomes and lysosomes. Notably, inhibition of autophagy restores surface levels of MHC-I and leads to improved antigen presentation, enhanced anti-tumour T cell responses and reduced tumour growth in syngeneic host mice. Accordingly, the anti-tumour effects of autophagy inhibition are reversed by depleting CD8(+) T cells or reducing surface expression of MHC-I. Inhibition of autophagy, either genetically or pharmacologically with chloroquine, synergizes with dual ICB therapy (anti-PD1 and anti-CTLA4 antibodies), and leads to an enhanced anti-tumour immune response. Our findings demonstrate a role for enhanced autophagy or lysosome function in immune evasion by selective targeting of MHC-I molecules for degradation, and provide a rationale for the combination of autophagy inhibition and dual ICB therapy as a therapeutic strategy against PDAC.
Inhibition of the autophagy-lysosome system upregulates surface expression of MHC class I proteins and enhances antigen presentation, and evokes a potent anti-tumour immune response that is mediated by CD8(+) T cells.
Ultrahot giant exoplanets receive thousands of times Earth'
Absorption lines of iron in the dayside atmosphere of an ultrahot giant exoplanet disappear after travelling across the nightside, showing that the iron has condensed during its travel.
