Planar digital image sensors facilitate broad applications in a wide range of areas^1–5, and the number of pixels has scaled up rapidly in recent years^2,6. However, the practical performance of imaging systems is fundamentally limited by spatially nonuniform optical aberrations originating from imperfect lenses or environmental disturbances^7,8. Here we propose an integrated scanning light-field imaging sensor, termed a meta-imaging sensor, to achieve high-speed aberration-corrected three-dimensional photography for universal applications without additional hardware modifications. Instead of directly detecting a two-dimensional intensity projection, the meta-imaging sensor captures extra-fine four-dimensional light-field distributions through a vibrating coded microlens array, enabling flexible and precise synthesis of complex-field-modulated images in post-processing. Using the sensor, we achieve high-performance photography up to a gigapixel with a single spherical lens without a data prior, leading to orders-of-magnitude reductions in system capacity and costs for optical imaging. Even in the presence of dynamic atmosphere turbulence, the meta-imaging sensor enables multisite aberration correction across 1,000 arcseconds on an 80-centimetre ground-based telescope without reducing the acquisition speed, paving the way for high-resolution synoptic sky surveys. Moreover, high-density accurate depth maps can be retrieved simultaneously, facilitating diverse applications from autonomous driving to industrial inspections.

Acetaminophen (APAP) is the most common cause of drug-induced liver injury (DILI); however, treatment options are limited. Mas is a G protein-coupled receptor whose role in APAP-induced hepatotoxicity has not yet been examined. Intrahepatic Mas expression was determined in both human and mouse DILI models. Mas1^-/-, Alb^creMas1^f/f, Ppara^-/-, Mas1^-/-Ppara^-/- and wild-type mice were challenged with APAP for the in vivo analyses of Mas-AKT-FOXO1 axis-dependent lipophagy and fatty acid oxidation (FAO), using pharmacological compounds and genetic tools. Liver samples were collected for RNA-sequencing, proteomics, metabolomics, lipidomics, and metabolic flux analysis. Live-imaging of liver and histological, biochemical, and molecular studies were performed to evaluate APAP-induced hepatotoxicity in mice. Primary hepatocytes and hepatic cell lines were exposed to APAP for in vitro analysis. Intrahepatic Mas expression was significantly upregulated in human and mouse DILI models. Mice with systemic, liver-specific, or hepatocyte-specific Mas1 deficiency were vulnerable to APAP-induced hepatotoxicity. They exhibited substantially impaired lipophagy and downstream FAO, which was accompanied by the activation of AKT and suppression of FOXO1. In addition, the prophylactic activation of Mas conferred strong protection against APAP challenge in mice, with remarkably enhanced lipophagy and FAO dependent on the AKT-FOXO1 axis. Moreover, the protective effects of AVE0991 were substantially diminished by the inhibition of either lipophagy or FAO. The activation of Mas on hepatocytes enhanced AKT-FOXO1-dependent lipophagy and downstream FAO, protecting mice from APAP-induced hepatotoxicity and indicating that hepatocyte-specific Mas might be a novel therapeutic target for DILI. Mas signalling arises as a novel therapeutic target for patients with APAP-induced liver injury. The Mas-AKT/FOXO1-fatty acid degradation pathway could be critical for the development of treatment strategies for APAP overdose. When Mas signalling is targeted, the extent of liver injury should be considered at the time of administration. These findings obtained from APAP-challenged mice still need to be confirmed in a clinical context.

High-speed three-dimensional (3D) intravital imaging in animals is useful for studying transient subcellular interactions and functions in health and disease. Light-field microscopy (LFM) provides a computational solution for snapshot 3D imaging with low phototoxicity but is restricted by low resolution and reconstruction artifacts induced by optical aberrations, motion and noise. Here, we propose virtual-scanning LFM (VsLFM), a physics-based deep learning framework to increase the resolution of LFM up to the diffraction limit within a snapshot. By constructing a 40 GB high-resolution scanning LFM dataset across different species, we exploit physical priors between phase-correlated angular views to address the frequency aliasing problem. This enables us to bypass hardware scanning and associated motion artifacts. Here, we show that VsLFM achieves ultrafast 3D imaging of diverse processes such as the beating heart in embryonic zebrafish, voltage activity in Drosophila brains and neutrophil migration in the mouse liver at up to 500 volumes per second.

Holistic understanding of physio-pathological processes requires noninvasive 3D imaging in deep tissue across multiple spatial and temporal scales to link diverse transient subcellular behaviors with long-term physiogenesis. Despite broad applications of two-photon microscopy (TPM), there remains an inevitable tradeoff among spatiotemporal resolution, imaging volumes, and durations due to the point-scanning scheme, accumulated phototoxicity, and optical aberrations. Here, we harnessed the concept of synthetic aperture radar in TPM to achieve aberration-corrected 3D imaging of subcellular dynamics at a millisecond scale for over 100,000 large volumes in deep tissue, with three orders of magnitude reduction in photobleaching. With its advantages, we identified direct intercellular communications through migrasome generation following traumatic brain injury, visualized the formation process of germinal center in the mouse lymph node, and characterized heterogeneous cellular states in the mouse visual cortex, opening up a horizon for intravital imaging to understand the organizations and functions of biological systems at a holistic level.

Light field microscopy, featuring with snapshot large-scale three-dimensional (3D) fluorescence imaging, has aroused great interests in various biological applications, especially for high-speed 3D calcium imaging. Traditional 3D deconvolution algorithms based on the beam propagation model facilitate high-resolution 3D reconstructions. However, such a high-precision model is not robust enough for the experimental data with different system errors such as optical aberrations and background fluorescence, which bring great periodic artifacts and reduce the image contrast. In order to solve this problem, here we propose a phase-space deconvolution method for light field microscopy, which fully exploits the smoothness prior in the phase-space domain. By modeling the imaging process in the phase-space domain, we convert the spatially-nonuniform point spread function (PSF) into a spatially-uniform one with a much smaller size. Experiments on various biological samples and resolution charts are demonstrated to verify the contrast enhancement with much fewer artifacts and 10-times less computational cost by our method without any hardware modifications required.