No abstract

The combined-immunotherapy of adoptive cell therapy (ACT) and cyclophosphamide (CTX) is one of the most efficient treatments for melanoma patients. However, no synergistic effects of CTX and ACT on the spatio-temporal dynamics of immunocytes in vivo have been described. Here, we visualized key cell events in immunotherapy-elicited immunoreactions in a multicolor-coded tumor microenvironment, and then established an optimal strategy of metronomic combined-immunotherapy to enhance anti-tumor efficacy. Intravital imaging data indicated that regulatory T cells formed an 'immunosuppressive ring' around a solid tumor. The CTX-ACT combined-treatment elicited synergistic immunoreactions in tumor areas, which included relieving the immune suppression, triggering the transient activation of endogenous tumor-infiltrating immunocytes, increasing the accumulation of adoptive cytotoxic T lymphocytes, and accelerating the infiltration of dendritic cells. These insights into the spatio-temporal dynamics of immunocytes are beneficial for optimizing immunotherapy and provide new approaches for elucidating the mechanisms underlying the involvement of immunocytes in cancer immunotherapy.DOI: http://dx.doi.org/10.7554/eLife.14756.001

Immune responses are based on the coordinated searching behaviors of immunocytes that are aimed at tracking down specific targets. The search efficiency of immunocytes significantly affects the speed of initiation and development of immune responses. Previous studies have shown that not only the intermittent walk but also the zigzag turning preference of immunocytes contributes to the search efficiency. However, among existing models describing immunocytes' search strategy, none has captured both features. Here we propose a zigzag generalized Lévy walk model to describe the search strategy of immunocytes more accurately and comprehensively by considering both the intermittent and the zigzag-turning walk features. Based on the analysis of the searching behaviors of typical immune cell types, dendritic cells and leukocytes, in their native physiological environment, we demonstrate that the model can describe the in vivo search strategy of immunocytes well. Furthermore, by analyzing the search efficiency, we find that this type of search strategy enables immunocytes to capture rare targets in approximately half the time than the previously proposed generalized Lévy walk. This study sheds new light on the fundamental mechanisms that drive the efficient initiation and development of immune responses and in turn may lead to the development of novel therapeutic approaches for diseases ranging from infection to cancer.

Layered metal hydroxides (LMHs) are promising catalysts for oxygen evolution reaction. However, the hydrogen evolution reaction (HER) activity of LMHs is unsatisfactory due to their poor conductivity and limited active sites. Herein, taking Ni(OH)2 as demonstration, a novel “one stone five birds” plasma activation strategy synergistic with Ru single atoms (Ru SAs) doping is developed to boost the HER activity of Ni(OH)2 by constructing heterostructured β‐Ni(OH)2/Ni‐Ru SAs nanosheet arrays (NSAs). Benefiting from the structural/compositional features and optimized electronic state, the as‐obtained β‐Ni(OH)2/Ni‐Ru SAs NSAs exhibit splendid HER activity with a low overpotential of 16 mV at 10 mA cm−2 and a small Tafel slope of 21 mV dec−1 in alkaline solution. Excellent HER performance in alkaline seawater and neutral solutions are also demonstrated by the β‐Ni(OH)2/Ni‐Ru SAs NSAs. The plasma activation and Ru SAs doping play important roles in enhancing water adsorption and accelerating the kinetics of water dissociation. Density functional theory (DFT) calculations reveal that the introduction of Ru SAs in the system facilitates the generation of surface OH vacancies for providing more active sites as well as decreases the antibonding state density of the generated mid‐gap state for enhancing H adsorption strength toward the optimal range.

No abstract

No abstract

G q -coupled receptors regulate numerous physiological processes by activating enzymes and inducing intracellular Ca 2+ signals.There is a strong need for an optogenetic tool that enables powerful experimental control over G q signaling. Here, we present chicken opsin 5 (cOpn5) as the long sought-after, single-component optogenetic tool that mediates ultra-sensitive optical control of intracellular G q signaling with high temporal and spatial resolution. Expressing cOpn5 in HEK 293T cells and primary mouse astrocytes enables blue light-triggered, G q -dependent Ca 2+ release from intracellular stores and protein kinase C activation.Strong Ca 2+ transients were evoked by brief light pulses of merely 10 ms duration and at 3 orders lower light intensity of that for common optogenetic tools. Photostimulation of cOpn5-expressing cells at the subcellular and single-cell levels generated fast intracellular Ca 2+ transition, thus demonstrating the high spatial precision of cOpn5 optogenetics. The cOpn5-mediated optogenetics could also be applied to activate neurons and control animal behavior in a circuit-dependent manner. cOpn5 optogenetics may find broad applications in studying the mechanisms and functional relevance of G q signaling in both non-excitable cells and excitable cells in all major organ systems.

The remote sensing 3D reconstruction of mountain areas has a wide range of applications in surveying, visualization, and game modeling. Different from indoor objects, outdoor mountain reconstruction faces additional challenges, including illumination changes, diversity of textures, and highly irregular surface geometry. Traditional neural network-based methods that lack discriminative features struggle to handle the above challenges, and thus tend to generate incomplete and inaccurate reconstructions. Truncated signed distance function (TSDF) is a commonly used parameterized representation of 3D structures, which is naturally convenient for neural network computation and computer storage. In this paper, we propose a novel deep learning method with TSDF-based representations for robust 3D reconstruction from images containing mountain terrains. The proposed method takes in a set of images captured around an outdoor mountain and produces high-quality TSDF representations of the mountain areas. To address the aforementioned challenges, such as lighting variations and texture diversity, we propose a view fusion strategy based on reweighted mechanisms (VRM) to better integrate multi-view 2D features of the same voxel. A feature enhancement (FE) module is designed for providing better discriminative geometry prior in the feature decoding process. We also propose a spatial–temporal aggregation (STA) module to reduce the ambiguity between temporal features and improve the accuracy of the reconstruction surfaces. A synthetic dataset for reconstructing images containing mountain terrains is built. Our method outperforms the previous state-of-the-art TSDF-based and depth-based reconstruction methods in terms of both 2D and 3D metrics. Furthermore, we collect real-world multi-view terrain images from Google Map. Qualitative results demonstrate the good generalization ability of the proposed method.