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Gastric cancer (GC) is one of the leading causes of cancer mortality in the world. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for GC treatment. Auranofin (AF), clinically used to treat rheumatic arthritis, but it exhibited preclinical efficacy in GC cells. By increasing intracellular reactive oxygen species (ROS) levels, AF induces a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in cultured GC cells. Blockage of ROS production reversed AF-induced ER stress and mitochondrial pathways activation as well as apoptosis. In addition, AF displays synergistic lethality with an ROS-generating agent piperlongumine, which is a natural product isolated from the long pepper Piper longum L. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer. More importantly, it reveals that increased ROS generation might be an effective strategy in treating human gastric cancer.

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No RNA is completely naked from birth to death. RNAs function with and are regulated by a range of proteins that bind to them. Therefore, the development of innovative methods for studying RNA–protein interactions is very important. Here, we developed a new tool, the CRISPR-based RNA-United Interacting System (CRUIS), which captures RNA–protein interactions in living cells by combining the power of CRISPR and PUP-IT, a novel proximity targeting system. In CRUIS, dCas13a is used as a tracker to target specific RNAs, while proximity enzyme PafA is fused to dCas13a to label the surrounding RNA-binding proteins, which are then identified by mass spectrometry. To identify the efficiency of CRUIS, we employed NORAD (Noncoding RNA activated by DNA damage) as a target, and the results show that a similar interactome profile of NORAD can be obtained as by using CLIP (crosslinking and immunoprecipitation)-based methods. Importantly, several novel NORAD RNA-binding proteins were also identified by CRUIS. The use of CRUIS facilitates the study of RNA–protein interactions in their natural environment, and provides new insights into RNA biology.

Background: Neonatal mouse cardiomyocytes undergo a metabolic switch from glycolysis to oxidative phosphorylation, which results in a significant increase in reactive oxygen species (ROS) production that induces DNA damage. These cellular changes contribute to cardiomyocyte cell cycle exit and loss of the capacity for cardiac regeneration. The mechanisms that regulate this metabolic switch and the increase in ROS production have been relatively unexplored. Current evidence suggests that elevated ROS production in ischemic tissues occurs due to accumulation of the mitochondrial metabolite succinate during ischemia via succinate dehydrogenase (SDH), and this succinate is rapidly oxidized at reperfusion. Interestingly, mutations in SDH in familial cancer syndromes have been demonstrated to promote a metabolic shift into glycolytic metabolism, suggesting a potential role for SDH in regulating cellular metabolism. Whether succinate and SDH regulate cardiomyocyte cell cycle activity and the cardiac metabolic state remains unclear. Methods: Here, we investigated the role of succinate and succinate dehydrogenase (SDH) inhibition in regulation of postnatal cardiomyocyte cell cycle activity and heart regeneration. Results: Our results demonstrate that injection of succinate in neonatal mice results in inhibition of cardiomyocyte proliferation and regeneration. Our evidence also shows that inhibition of SDH by malonate treatment after birth extends the window of cardiomyocyte proliferation and regeneration in juvenile mice. Remarkably, extending malonate treatment to the adult mouse heart following myocardial infarction injury results in a robust regenerative response within 4 weeks following injury via promoting adult cardiomyocyte proliferation and revascularization. Our metabolite analysis following SDH inhibition by malonate induces dynamic changes in adult cardiac metabolism. Conclusions: Inhibition of SDH by malonate promotes adult cardiomyocyte proliferation, revascularization, and heart regeneration via metabolic reprogramming. These findings support a potentially important new therapeutic approach for human heart failure.

In this paper, we present a novel framework to detect line segments in man-made environments. Specifically, we propose to describe junctions, line segments and relationships between them with a simple graph, which is more structured and informative than end-point representation used in existing line segment detection methods. In order to extract a line segment graph from an image, we further introduce the PPGNet, a convolutional neural network that directly infers a graph from an image. We evaluate our method on published benchmarks including York Urban and Wireframe datasets. The results demonstrate that our method achieves satisfactory performance and generalizes well on all the benchmarks. The source code of our work is available at https://github.com/svip-lab/PPGNet.

The industrialization of lithium–sulfur (Li–S) batteries is simultaneously impeded by the shuttle effect of lithium polysulfides and dendrites growth on lithium anode. To address both issues, a novel sulfiphilic and lithiophilic interlayer of Mo2N quantum dots decorated N‐doped graphene‐nanosheet (Mo2N@NG) are presented on polypropylene separator via a facile scalable method. Benefiting from the strong chemisorption ability, eminent electrocatalysis for LiPSs, and high chemical affinity with lithium‐ion (Li+), Mo2N@NG can efficiently catalyze the rapid transformation of LiPSs and induce uniform deposition of Li+. Theoretical calculation and in situ Raman synergistically elucidate the inhibition of shuttle effect and alleviation of dendrite growth. As a result, the assembled Li–S cell with Mo2N@NG/PP separator exhibits remarkable rate performance (860.2 mA h g–1 at 4 C), good cycling stability (0.039% capacity decay per cycle after 800 cycles at 2 C), a high areal capacity of 3.89 mA h cm–2 of Li–S pouch cell (4.5 mg cm–2 and 6 µL mg–1 at 0.2 C), and steady performance in protecting the lithium anode (at 5 mA cm–2 for 1500 h). This present strategy of quantum dots in a hybrid framework has great potential to be generalized to other transition metal‐based catalysts for advanced Li–S batteries.