资源环境科技发展态势分析平台

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer(1-3). However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer.

The recently discovered flat electronic bands and strongly correlated and superconducting phases in magic-angle twisted bilayer graphene (MATBG)(1,2) crucially depend on the interlayer twist angle, theta. Although control of the global theta with a precision of about 0.1 degrees has been demonstrated(1-7), little information is available on the distribution of the local twist angles. Here we use a nanoscale on-tip scanning superconducting quantum interference device (SQUID-on-tip)(8) to obtain tomographic images of the Landau levels in the quantum Hall state(9) and to map the local theta variations in hexagonal boron nitride (hBN)-encapsulated MATBG devices with relative precision better than 0.002 degrees and a spatial resolution of a few moire periods. We find a correlation between the degree of theta disorder and the quality of the MATBG transport characteristics and show that even state-of-the-art devices-which exhibit correlated states, Landau fans and superconductivity-display considerable local variation in theta of up to 0.1 degrees, exhibiting substantial gradients and networks of jumps, and may contain areas with no local MATBG behaviour. We observe that the correlated states in MATBG are particularly fragile with respect to the twist-angle disorder. We also show that the gradients of theta generate large gate-tunable in-plane electric fields, unscreened even in the metallic regions, which profoundly alter the quantum Hall state by forming edge channels in the bulk of the sample and may affect the phase diagram of the correlated and superconducting states. We thus establish the importance of theta disorder as an unconventional type of disorder enabling the use of twist-angle gradients for bandstructure engineering, for realization of correlated phenomena and for gate-tunable built-in planar electric fields for device applications.

SQUID-on-tip tomographic imaging of Landau levels in magic-angle graphene provides nanoscale maps of local twist-angle disorder and shows that its properties are fundamentally different from common types of disorder.

The X-ray crystal structure of the potassium channel TASK-1 reveals the presence of an X-gate, which traps small-molecule inhibitors in the intramembrane vestibule and explains their low washout rates from the channel.

Halide perovskite materials have promising performance characteristics for low-cost optoelectronic applications. Photovoltaic devices fabricated from perovskite absorbers have reached power conversion efficiencies above 25 per cent in single-junction devices and 28 per cent in tandem devices(1,2). This strong performance (albeit below the practical limits of about 30 per cent and 35 per cent, respectively(3)) is surprising in thin films processed from solution at low-temperature, a method that generally produces abundant crystalline defects(4). Although point defects often induce only shallow electronic states in the perovskite bandgap that do not affect performance(5), perovskite devices still have many states deep within the bandgap that trap charge carriers and cause them to recombine non-radiatively. These deep trap states thus induce local variations in photoluminescence and limit the device performance(6). The origin and distribution of these trap states are unknown, but they have been associated with light-induced halide segregation in mixed-halide perovskite compositions(7) and with local strain(8), both of which make devices less stable(9). Here we use photoemission electron microscopy to image the trap distribution in state-of-the-art halide perovskite films. Instead of a relatively uniform distribution within regions of poor photoluminescence efficiency, we observe discrete, nanoscale trap clusters. By correlating microscopy measurements with scanning electron analytical techniques, we find that these trap clusters appear at the interfaces between crystallographically and compositionally distinct entities. Finally, by generating time-resolved photoemission sequences of the photo-excited carrier trapping process(10,11), we reveal a hole-trapping character with the kinetics limited by diffusion of holes to the local trap clusters. Our approach shows that managing structure and composition on the nanoscale will be essential for optimal performance of halide perovskite devices.

The mammalian claustrum, owing to its widespread connectivity with other forebrain structures, has been hypothesized to mediate functions that range from decision-making to consciousness(1). Here we report that a homologue of the claustrum, identified by single-cell transcriptomics and viral tracing of connectivity, also exists in a reptile-the Australian bearded dragon Pogona vitticeps. In Pogona, the claustrum underlies the generation of sharp waves during slow-wave sleep. The sharp waves, together with superimposed high-frequency ripples(2), propagate to the entire neighbouring pallial dorsal ventricular ridge (DVR). Unilateral or bilateral lesions of the claustrum suppress the production of sharp-wave ripples during slow-wave sleep in a unilateral or bilateral manner, respectively, but do not affect the regular and rapidly alternating sleep rhythm that is characteristic of sleep in this species(3). The claustrum is thus not involved in the generation of the sleep rhythm itself. Tract tracing revealed that the reptilian claustrum projects widely to a variety of forebrain areas, including the cortex, and that it receives converging inputs from, among others, areas of the mid- and hindbrain that are known to be involved in wake-sleep control in mammals(4-6). Periodically modulating the concentration of serotonin in the claustrum, for example, caused a matching modulation of sharp-wave production there and in the neighbouring DVR. Using transcriptomic approaches, we also identified a claustrum in the turtle Trachemys scripta, a distant reptilian relative of lizards. The claustrum is therefore an ancient structure that was probably already present in the brain of the common vertebrate ancestor of reptiles and mammals. It may have an important role in the control of brain states owing to the ascending input it receives from the mid- and hindbrain, its widespread projections to the forebrain and its role in sharp-wave generation during slow-wave sleep.

A structure homologous to the mammalian claustrum exists in reptiles and has a role in generating sharp waves in the brain during slow-wave sleep.