资源环境科技发展态势分析平台

Cellular senescence is characterized by stable cell-cycle arrest and a secretory program that modulates the tissue microenvironment(1,2). Physiologically, senescence serves as a tumour-suppressive mechanism that prevents the expansion of premalignant cells(3,4)and has a beneficial role in wound-healing responses(5,6). Pathologically, the aberrant accumulation of senescent cells generates an inflammatory milieu that leads to chronic tissue damage and contributes to diseases such as liver and lung fibrosis, atherosclerosis, diabetes and osteoarthritis(1,7). Accordingly, eliminating senescent cells from damaged tissues in mice ameliorates the symptoms of these pathologies and even promotes longevity(1,2,8-10). Here we test the therapeutic concept that chimeric antigen receptor (CAR) T cells that target senescent cells can be effective senolytic agents. We identify the urokinase-type plasminogen activator receptor (uPAR)(11)as a cell-surface protein that is broadly induced during senescence and show that uPAR-specific CAR T cells efficiently ablate senescent cells in vitro and in vivo. CAR T cells that target uPAR extend the survival of mice with lung adenocarcinoma that are treated with a senescence-inducing combination of drugs, and restore tissue homeostasis in mice in which liver fibrosis is induced chemically or by diet. These results establish the therapeutic potential of senolytic CAR T cells for senescence-associated diseases.

Chimeric antigen receptor (CAR) T cells targeting uPAR, a cell-surface protein that is upregulated on senescent cells, eliminate senescent cells in vitro and in vivo and reduce liver fibrosis in mice.

Room-temperature electrical switching of a topological antiferromagnetic state in polycrystalline Mn3Sn thin films is demonstrated using the same protocol as that used for conventional ferromagnetic metals.

Electrical manipulation of phenomena generated by nontrivial band topology is essential for the development of next-generation technology using topological protection. A Weyl semimetal is a three-dimensional gapless system that hosts Weyl fermions as low-energy quasiparticles(1-4). It has various exotic properties, such as a large anomalous Hall effect (AHE) and chiral anomaly, which are robust owing to the topologically protected Weyl nodes(1-16). To manipulate such phenomena, a magnetic version of Weyl semimetals would be useful for controlling the locations of Weyl nodes in the Brillouin zone. Moreover, electrical manipulation of antiferromagnetic Weyl metals would facilitate the use of antiferromagnetic spintronics to realize high-density devices with ultrafast operation(17,18). However, electrical control of a Weyl metal has not yet been reported. Here we demonstrate the electrical switching of a topological antiferromagnetic state and its detection by the AHE at room temperature in a polycrystalline thin film(19) of the antiferromagnetic Weyl metal Mn3Sn9,10,12,20, which exhibits zero-field AHE. Using bilayer devices composed of Mn3Sn and nonmagnetic metals, we find that an electrical current density of about 10(10) to 10(11) amperes per square metre induces magnetic switching in the nonmagnetic metals, with a large change in Hall voltage. In addition, the current polarity along the bias field and the sign of the spin Hall angle of the nonmagnetic metals-positive for Pt (ref. (21)), close to 0 for Cu and negative for W (ref. (22))-determines the sign of the Hall voltage. Notably, the electrical switching in the antiferromagnet is achieved with the same protocol as that used for ferromagnetic metals(23,24). Our results may lead to further scientific and technological advances in topological magnetism and antiferromagnetic spintronics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.