Nature最新文献

The nuclear pore complex (NPC) mediates nucleocytoplasmic exchange, catalysing a massive flux of protein and nucleic acid material in both directions¹. Distinct trafficking pathways for import and export would be an elegant solution to avoid unproductive collisions and opposing movements. However, the three-dimensional (3D) nanoscale spatiotemporal dynamics of macromolecules traversing the NPC remains challenging to visualize on the timescale of millisecond-scale transport events. Here we used 3D MINFLUX² to identify the nuclear pore scaffold and then to simultaneously monitor both nuclear import and nuclear export, thereby establishing that both transport processes occur in overlapping regions of the central pore. Whereas translocation-arrested import complexes bound at the pore periphery, tracks of translocating complexes within the central pore region revealed a preference for an approximately 40- to 50-nm diameter annulus with minimal circumferential movement, indicating activity-dependent confinement within the permeability barrier. Movement within the pore was approximately 1,000-fold slower than in solution and was interspersed with pauses, indicating a highly restricted environment with structural constraints and/or transient binding events during transport. These results demonstrate that high spatiotemporal precision with reduced photobleaching is a major advantage of MINFLUX tracking, and that the NPC permeability barrier is divided into annular rings with distinct functional properties.

The landscapes of somatic mutation in normal cells inform us about the processes of mutation and selection operative throughout life, providing insight into normal ageing and the earliest stages of cancer development¹. Here, by whole-genome sequencing of 238 microdissections² from 30 individuals, including 18 with gastric cancer, we elucidate the developmental trajectories of normal and malignant gastric epithelium. We find that gastric glands are units of monoclonal cell populations that accrue roughly 28 somatic single-nucleotide variants per year, predominantly attributable to endogenous mutational processes. In individuals with gastric cancer, metaplastic glands often show elevated mutation burdens due to acceleration of mutational processes linked to proliferation and oxidative damage. Unusually for normal cells, gastric epithelial cells often carry recurrent trisomies of specific chromosomes, which are highly enriched in a subset of individuals. Surveying 829 polyclonal gastric microbiopsies by targeted sequencing, we find somatic ‘driver’ mutations in a distinctive repertoire of known cancer genes, including ARID1A, ARID1B, ARID2, CTNNB1 and KDM6A. The prevalence of mutant clones increases with age to occupy roughly 8% of the gastric epithelial lining by age 60 years and is significantly increased by the presence of severe chronic inflammation. Our findings provide insights into intrinsic and extrinsic influences on somatic evolution in the gastric epithelium in healthy, precancerous and malignant states.

Many technological breakthroughs in electronics and photonics were made possible by downscaling—the process of making elementary devices smaller in size^1,2,3,4,5. The downsizing of light-emitting diodes (LEDs) based on III–V semiconductors led to micro-LEDs^{5,6,7,8,9,10,11,12}, an ‘ultimate technology’ for displays. However, micro-LEDs are costly to produce and they exhibit severe efficiency losses when the pixel sizes are reduced to about 10 μm or less, hindering their potential in commercial applications. Here we show the downscaling of an emerging class of LEDs based on perovskite semiconductors to below the conventional size limits. Micro- and nano-perovskite LEDs (micro-PeLEDs/nano-PeLEDs) with characteristic pixel lengths from hundreds of micrometres down to about 90 nm are demonstrated, through a localized contact fabrication scheme that prevents non-radiative losses at the pixel boundaries. For our near-infrared (NIR) and green micro-PeLEDs, average external quantum efficiencies (EQEs) are maintained at around 20% across a wide range of pixel lengths (650 to 3.5 μm), exhibiting minimum performance reduction on downsizing. Our nano-PeLEDs with characteristic pixel lengths down to about 90 nm represent the smallest LEDs reported, enabling a record-high pixel density of 127,000 pixels per inch (PPI) among all classes of LED arrays. Our demonstration showcases the strength of micro- and nano-PeLEDs as a next-generation light-source technology with unprecedented compactness and scalability.

Defence from environmental threats is provided by physical barriers that confer mechanical protection and prevent the entry of microorganisms¹. If microorganisms overcome those barriers, however, innate immune cells use toxic chemicals to kill the invading cells^2,3. Here we examine immune diversity across tissues and identify a population of neutrophils in the skin that expresses a broad repertoire of proteins and enzymes needed to build the extracellular matrix. In the naive skin, these matrix-producing neutrophils contribute to the composition and structure of the extracellular matrix, reinforce its mechanical properties and promote barrier function. After injury, these neutrophils build ‘rings’ of matrix around wounds, which shield against foreign molecules and bacteria. This structural program relies on TGFβ signalling; disabling the TGFβ receptor in neutrophils impaired ring formation around wounds and facilitated bacterial invasion. We infer that the innate immune system has evolved diverse strategies for defence, including one that physically shields the host from the outside world.