As the global population ages, the burden of cancer is increasing. We aimed to assess the impact of population ageing on cancer-related disability-adjusted life years (DALYs). We used the decomposition method to estimate the impact of ageing, population growth, and epidemiological change on cancer-related DALYs from 1990 to 2019, stratified by 204 countries/territories and by their sociodemographic index (SDI). This approach separates the net effect of population ageing from population growth and change in age-specific DALY rates. Cancer-related DALYs among individuals aged ≥65 years increased by 95.14% between 1990 (52.25 million) and 2019 (101.96 million). Population growth was the main contributor to cancer-related DALYs (92.38 million, attributed proportion: 60.91%), followed by population ageing (41.38 million, 27.28%). Cancer-related DALYs attributed to population ageing followed a bell-shaped pattern when stratified by SDI, meaning they peaked in middle-SDI countries. Cancer-related DALYs attributed to ageing increased in 171 and decreased in 33 countries/territories. The top three cancer types with the highest increase in the absolute number of cancer-related DALYs associated with ageing were tracheal, bronchus, and lung (8.72 million); stomach (5.06 million); and colorectal (4.28 million) cancers, while the attributed proportion of DALYs was the highest in prostate (44.75%), pancreatic (40.93%), and non-melanoma skin (38.03%) cancers. Population ageing contributed to global cancer-related DALYs, revealing a bell-shaped pattern when stratified by socioeconomic development, affecting middle-SDI countries the most. To respond to the growing ageing population and reduce cancer-related DALYs, it is necessary to allocate health care resources and prioritize interventions for older adults.

Despite recent advances in the mechanism of oxidized DNA activating NLRP3, the molecular mechanism and consequence of oxidized DNA associating with NLRP3 remains unknown. Cytosolic NLRP3 binds oxidized DNA which has been released from the mitochondria, which subsequently triggers inflammasome activation. Human glycosylase (hOGG1) repairs oxidized DNA damage which inhibits inflammasome activation. The fold of NLRP3 pyrin domain contains amino acids and a protein fold similar to hOGG1. Amino acids that enable hOGG1 to bind and cleave oxidized DNA are conserved in NLRP3. We found NLRP3 could bind and cleave oxidized guanine within mitochondrial DNA. The binding of oxidized DNA to NLRP3 was prevented by small molecule drugs which also inhibit hOGG1. These same drugs also inhibited inflammasome activation. Elucidating this mechanism will enable the design of drug memetics that treat inflammasome pathologies, illustrated herein by NLRP3 pyrin domain inhibitors which suppressed interleukin-1β (IL-1β) production in macrophages.

Concatemeric viral DNA is packaged into bacteriophage P22 procapsids via a headful packaging mechanism mediated by a molecular machine consisting of small (gp3) and large (gp2) terminase subunits. Although a negative stain reconstruction exists for the terminase holoenzyme, it is not clear how this complex binds the dodecameric portal protein located at a 5-fold mismatch vertex. Herein, we describe new assemblies for the holoenzyme. Both native mass spectrometry and transmission electron microscopy reveal that the P22 terminase complex adopts three main assemblies, which include a nonameric S-terminase bound to two L-terminase 1(gp3)₉:2(gp2), two nonameric S-terminase bound to five L-terminase 2(gp3)₉:5(gp2), and three nonameric S-terminase bound to seven L-terminase 3(gp3)₉:7(gp2). Native agarose gel electrophoresis shows that the terminase complex interacts with procapsids with mild crosslinking. These results herein illustrate the P22 terminase complex can adopt a variety of conformations and assembly states.