Exploration of novel 20S proteasome activators featuring anthraquinone structures and their application in hypoxic cardiomyocyte protection.

Under hypoxic conditions, the accumulation of misfolded proteins primarily relies on the autonomous activity of 20S proteasome for degradation. The buildup of toxic proteins in cardiomyocyte contribute to various cardiovascular diseases. Therefore, enhancing the 20S proteasome degradation capacity and restoring protein homeostasis in myocardial cells with small molecule activators represent a promising therapeutic strategy for the treatment of ischemic cardiomyopathy.

Architecture-driven quantitative nanoscopy maps cytoskeleton remodeling.

Cytoskeleton remodeling which generates force and orchestrates signaling and trafficking to govern cell migration remains poorly understood, partly due to a lack of an investigation tool with high system flexibility, spatiotemporal resolution, and computational sensitivity. Herein, we developed a multimodal superresolution imaging system-based architecture-driven quantitative (ADQ) framework in spatiotemporal-angular hyperspace to enable both identification of the optimal imaging mode with well-balanced fidelity and phototoxicity and accurate postcharacterization of microtubule remodeling. In the ADQ framework, a pixel/voxel-wise metric reflecting heterogeneous intertubule alignment was proposed with improved sensitivity over previous efforts and further incorporated with temporal features to map dynamic microtubule rearrangements.

Identification of key immune-related genes and potential therapeutic drugs in diabetic nephropathy based on machine learning algorithms.

Background: Diabetic nephropathy (DN) is a major contributor to chronic kidney disease. This study aims to identify immune biomarkers and potential therapeutic drugs in DN.

Methods: We analyzed two DN microarray datasets (GSE96804 and GSE30528) for differentially expressed genes (DEGs) using the Limma package, overlapping them with immune-related genes from ImmPort and InnateDB.

Untrained neural network enabling fast and universal structured-illumination microscopy.

Structured-illumination microscopy (SIM) offers a twofold resolution enhancement beyond the optical diffraction limit. At present, SIM requires several raw structured-illumination (SI) frames to reconstruct a super-resolution (SR) image, especially the time-consuming reconstruction of speckle SIM, which requires hundreds of SI frames. Considering this, we herein propose an untrained structured-illumination reconstruction neural network (USRNN) with known illumination patterns to reduce the amount of raw data that is required for speckle SIM reconstruction by 20 times and thus improve its temporal resolution.

A bio-inspired co-simulation crawling robot enabled by a carbon dot-doped dielectric elastomer.

Flexible actuation materials play a crucial role in biomimetic robots. Seeking methods to enhance actuation and functionality is one of the directions in which actuators strive to meet the high-performance and diverse requirements of environmental conditions. Herein, by utilizing the method of adsorbing N-doped carbon dots (NCDs) onto SiO to form clusters of functional particles, a NCDs@SiO/PDMS elastomer was prepared and its combined optical and electrical co-stimulation properties were effectively harnessed to develop a biomimetic crawling robot resembling (firefly).

High-throughput multiplexed fluorescence lifetime microscopy.

Fluorescence lifetime microscopy has been widely used in quantifying cellular interaction or histopathological identification of different stained tissues. A novel, to the best of our knowledge, approach for high-throughput multiplexed fluorescence lifetime imaging is presented. To establish a high-throughput fluorescence lifetime acquisition system, a uniformed illumination optical focus array was generated by a novel computer-generated hologram algorithm based on matrix triple product.

Three-dimensional multi-color optical nanoscopy at sub-10-nm resolution based on small-molecule organic probes.

Achieving nanometer-scale resolution remains challenging in expansion microscopy due to photon loss. To address this concern, here we develop a multi-color expansion stimulated emission depletion technique based on small-molecule probes to realize high labeling density and intensity. Our method substantially lowers the barrier to visualizing diverse intracellular proteins and their interactions in three dimensions.

Far-field super-resolution chemical microscopy.

Far-field chemical microscopy providing molecular electronic or vibrational fingerprint information opens a new window for the study of three-dimensional biological, material, and chemical systems. Chemical microscopy provides a nondestructive way of chemical identification without exterior labels. However, the diffraction limit of optics hindered it from discovering more details under the resolution limit.

High-speed spatially re-modulated structured illumination microscopy.

Structured illumination microscopy (SIM) allows non-invasive visualization of nanoscale subcellular structures. However, image acquisition and reconstruction become the bottleneck to further improve the imaging speed. Here, we propose a method to accelerate SIM imaging by combining the spatial re-modulation principle with Fourier domain filtering and using measured illumination patterns.

Role of VPS39, a key tethering protein for endolysosomal trafficking and mitochondria-lysosome crosstalk, in health and disease.

The coordinated interaction between mitochondria and lysosomes, mainly manifested by mitophagy, mitochondria-derived vesicles, and direct physical contact, is essential for maintaining cellular life activities. The VPS39 subunit of the homotypic fusion and protein sorting complex could play a key role in the regulation of organelle dynamics, such as endolysosomal trafficking and mitochondria-vacuole/lysosome crosstalk, thus contributing to a variety of physiological functions. The abnormalities of VPS39 and related subunits have been reported to be involved in the pathological process of some diseases.

Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation.

The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations exacerbate inflammation has not been explored. Here, using antibiotic treatment and fecal microbial transfers, we showed that sepsis susceptibility is driven by pregnancy-induced changes to gut microbiome in mice and humans.

Alternative deep learning method for fast spatial-frequency shift imaging microscopy.

Spatial-frequency shift (SFS) imaging microscopy can break the diffraction limit of fluorescently labeled and label-free samples by transferring the high spatial-frequency information into the passband of microscope. However, the resolution improvement is at the cost of decreasing temporal resolution since dozens of raw SFS images are needed to expand the frequency spectrum. Although some deep learning methods have been proposed to solve this problem, no neural network that is compatible to both labeled and label-free SFS imaging has been proposed.

Dual inhibition of CHK1/FLT3 enhances cytotoxicity and overcomes adaptive and acquired resistance in FLT3-ITD acute myeloid leukemia.

FLT3 inhibitors (FLT3i) are widely used for the treatment of acute myeloid leukemia (AML), but adaptive and acquired resistance remains a primary challenge. Inhibitors simultaneously blocking adaptive and acquired resistance are highly demanded. Here, we observed the potential of CHK1 inhibitors to synergistically improve the therapeutic effect of FLT3i in FLT3-mutated AML cells.

Enhanced axial resolution of lattice light sheet microscopy by fluorescence differential detection.

Lattice light-sheet microscopy (LLSM) is promising in long-term biological volumetric imaging due to its high spatiotemporal resolution and low phototoxicity. However, three-dimensional (3D) isotropic spatial resolution remains an unmet goal in LLSM because of its poorer axial resolution. Combing LLSM with fluorescence differential detection, namely LLSDM, has been proposed to improve the axial resolution of LLSM in simulation.

High-Refractive-Index Chip with Periodically Fine-Tuning Gratings for Tunable Virtual-Wavevector Spatial Frequency Shift Universal Super-Resolution Imaging.

Continued research in fields such as materials science and biomedicine requires the development of a super-resolution imaging technique with a large field of view (FOV) and deep subwavelength resolution that is compatible with both fluorescent and nonfluorescent samples. Existing on-chip super-resolution methods exclusively focus on either fluorescent or nonfluorescent imaging, and, as such, there is an urgent requirement for a more general technique that is capable of both modes of imaging. In this study, to realize labeled and label-free super-resolution imaging on a single scalable photonic chip, a universal super-resolution imaging method based on the tunable virtual-wavevector spatial frequency shift (TVSFS) principle is introduced.

Ratiometric photon reassignment based on fluorescence lifetime to improve resolution in pulse STED microscopy.

Depletion beams with long pulse durations (∼600) have recently been applied in stimulated emission depletion (STED) microscopy to reduce photobleaching and phototoxicity. Therefore, improving the resolution of pulse STED at lower depletion power for the super-resolution imaging of live biological specimens has attracted increasing interest. Herein, we present a simple method termed ratiometric photon reassignment based on the fluorescence lifetime, in which highly spatially resolved long-lifetime fluorophore components in the center are extracted, and short-lifetime fluorophore components in the periphery are discarded to improve resolution without increasing the depletion power.

A Labeling Strategy for Living Specimens in Long-Term/Super-Resolution Fluorescence Imaging.

Despite the urgent need to image living specimens for cutting-edge biological research, most existing fluorescent labeling methods suffer from either poor optical properties or complicated operations required to realize cell-permeability and specificity. In this study, we introduce a method to overcome these limits-taking advantage of the intrinsic affinity of bright and photostable fluorophores, no matter if they are supposed to be live-cell incompatible or not. Incubated with living cells and tissues in particular conditions (concentration and temperature), some Atto and BODIPY dyes show live-cell labeling capability for specific organelles without physical cell-penetration or chemical modifications.

Quantitative objective-based ring TIRFM system calibration through back focal plane imaging.

Being the established imaging tool for cell membrane-associated studies, total internal reflection fluorescence microscopy (TIRFM) still has some limitations. The most important one is the inhomogeneous evanescent excitation field mainly caused by the large-angle and fixed-azimuth illumination scheme, which can be eliminated by using ring-shaped illumination (ring TIRFM). However, it is challenging in assembling a ring TIRFM system with precise parameter control that works well.

Erratum: Author Correction: Simple and efficient delivery of cell-impermeable organic fluorescent probes into live cells for live-cell superresolution imaging.

[This corrects the article DOI: 10.1038/s41377-019-0188-0.].

Ultra-fast, universal super-resolution radial fluctuations (SRRF) algorithm for live-cell super-resolution microscopy.

For a long term, spatial resolution of fluorescence microscopy was strictly restricted by the diffraction limit. To solve this problem, various super-resolution technologies have been developed. Super-resolution radial fluctuations (SRRF), an emerging type of super-resolution microscopy, directly analyze raw images and generate super-resolution results without fluorophore localization, thereby showing more advantages in handling high-density data.

Sulfonic SiO nanocolloid doped perfluorosulfonic acid films with enhanced water uptake and inner channel for IPMC actuators.

This study provides a facile and effective strategy to fabricate sulfonic SiO nanocolloid (HSO-SiO) doped perfluorosulfonic acid (PFSA) films with enhanced water uptake and inner channel for high-performance and cost-effective ionic exchange polymer metal composite (IPMC) actuators. A commercial precursor of mercaptopropyl trimethoxysilane was hydrolyzed to form thiol functionalized SiO nanocolloids (SH-SiO, ∼25 nm in diameter), which were further oxidized into sulfonic SiO nanocolloids (HSO-SiO, ∼14 nm in diameter). Both SiO nanocolloids were used as additives to dope PFSA film for fabricating IPMC-used matrix films.

Simultaneous Two-Angle Axial Ratiometry for Fast Live and Long-Term Three-Dimensional Super-Resolution Fluorescence Imaging.

The application of optical microscopy in four-dimensional (spatial and temporal) super-resolution imaging poses challenges because of the requirement of a long acquisition time or high illumination intensity. In this paper, we introduce simultaneous two-angle axial ratiometry (STARII) for <20 nm axial super-resolution imaging and for fast and long-term imaging of live cells up to hundreds of frames per second. This method involves recording two raw images in two incident angle channels in the context of evanescent wave illumination and obtaining the corresponding intensity ratio.

Simple and efficient delivery of cell-impermeable organic fluorescent probes into live cells for live-cell superresolution imaging.

Numerous commercial organic fluorophores with excellent optical properties are precluded from live-cell superresolution imaging due to poor cell permeability. Here, we develop a simple but effective strategy that renders cells permeable to cell-impermeable, organic fluorescent probes by using a novel peptide vehicle, PV-1. By simple coincubation with PV-1, 22 different cell-impermeable, organic fluorescent probes were efficiently delivered into live cells and specifically labeled a variety of organelles.