Highlights d Quantitative lipidomic and metabolomic profiling of COVID-19 plasma d Plasma metabolite panel distinguished COVID-19 from healthy controls (AUC = 0.975) d Differential correlation analyses uncovered metabolic dysregulation in COVID-19 d GM3-enriched exosomes are positively correlated with COVID-19 pathogenesis

Background Cisplatin (CDDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). A better understanding of the mechanisms of CDDP resistance can greatly improve therapeutic efficacy in patients with GC. Circular RNAs (circRNAs) are a class of noncoding RNAs whose functions are related to the pathogenesis of cancer, but, in CDDP resistance of GC remains unknown. Methods circAKT3 (hsa_circ_0000199, a circRNA originating from exons 8, 9, 10, and 11 of the AKT3 gene) was identified by RNA sequencing and verified by quantitative reverse transcription PCR. The role of circAKT3 in CDDP resistance in GC was assessed both in vitro and in vivo. Luciferase reporter assay, biotin-coupled RNA pull-down and fluorescence in situ hybridization (FISH) were conducted to evaluate the interaction between circAKT3 and miR-198. Functional experiments were measured by western blotting, a cytotoxicity assay, clonogenic assay and flow cytometry. Results The expression of circAKT3 was higher in CDDP-resistant GC tissues and cells than in CDDP-sensitive samples. The upregulation of circAKT3 in GC patients receiving CDDP therapy was significantly associated with aggressive characteristics and was an independent risk factor for disease-free survival (DFS). Our data indicated that circAKT3 promotes DNA damage repair and inhibits the apoptosis of GC cells in vivo and in vitro. Mechanistically, we verified that circAKT3 could promote PIK3R1 expression by sponging miR-198. Conclusions circAKT3 plays an important role in the resistance of GC to CDDP. Thus, our results highlight the potential of circAKT3 as a therapeutic target for GC patients receiving CDDP therapy. Electronic supplementary material The online version of this article (10.1186/s12943-019-0969-3) contains supplementary material, which is available to authorized users.

The goal of our paper is to semantically edit parts of an image matching a given text that describes desired attributes (e.g., texture, colour, and background), while preserving other contents that are irrelevant to the text. To achieve this, we propose a novel generative adversarial network (ManiGAN), which contains two key components: text-image affine combination module (ACM) and detail correction module (DCM). The ACM selects image regions relevant to the given text and then correlates the regions with corresponding semantic words for effective manipulation. Meanwhile, it encodes original image features to help reconstruct text-irrelevant contents. The DCM rectifies mismatched attributes and completes missing contents of the synthetic image. Finally, we suggest a new metric for evaluating image manipulation results, in terms of both the generation of new attributes and the reconstruction of text-irrelevant contents. Extensive experiments on the CUB and COCO datasets demonstrate the superior performance of the proposed method. Code is available at https://github.com/mrlibw/ManiGAN.

Materials that resist nonspecific protein adsorption are needed for many applications. However, few are able to achieve ultralow fouling in complex biological milieu. Zwitterionic polymers emerge as a class of highly effective ultralow fouling materials due to their superhydrophilicity, outperforming other hydrophilic materials such as poly(ethylene glycol). Unfortunately, there are only three major classes of zwitterionic materials based on poly(phosphorylcholine), poly(sulfobetaine), and poly(carboxybetaine) currently available. Inspired by trimethylamine N-oxide (TMAO), a zwitterionic osmolyte and the most effective protein stabilizer, we here report TMAO-derived zwitterionic polymers (PTMAO) as a new class of ultralow fouling biomaterials. The nonfouling properties of PTMAO were demonstrated under highly challenging conditions. The mechanism accounting for the extraordinary hydration of PTMAO was elucidated by molecular dynamics simulations. The discovery of PTMAO polymers demonstrates the power of molecular understanding in the design of new biomimetic materials and provides the biomaterials community with another class of nonfouling zwitterionic materials.

Summary The capsaicin receptor TRPV1 ion channel is a polymodal nociceptor that responds to heat with exquisite sensitivity through an unknown mechanism. Here we report the identification of a toxin, RhTx, from the venom of Chinese red-headed centipede that potently activates TRPV1 to produce excruciating pain. RhTx is a 27-amino acid small peptide that forms a compact polarized molecule with very rapid binding kinetics and high affinity for TRPV1. We show that RhTx targets the channel’s heat activation machinery to cause powerful activation at normal body temperature. The RhTx-TRPV1 interaction is mediated by the toxin’s highly charged C-terminus, which associates tightly to the charge-rich outer pore region of the channel where it can directly interact with the pore helix and turret. These findings demonstrate that RhTx binding to the outer pore can induce TRPV1 heat activation, therefore providing crucial new structural information on the heat activation machinery.

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Vanadium dioxide (VO2) is a promising material for developing energy-saving “smart windows,” owing to its infrared thermochromism induced by metal-insulator transition (MIT). However, its practical application is greatly limited by its relatively high critical temperature (~68°C), low luminous transmittance (<60%), and poor solar energy regulation ability (<15%). Here, we developed a reversible and nonvolatile electric field control of the MIT of a monoclinic VO2 film. With a solid electrolyte layer assisting gating treatment, we modulated the insertion/extraction of hydrogen into/from the VO2 lattice at room temperature, causing tristate phase transitions that enable control of light transmittance. The dramatic increase in visible/infrared transmittance due to the phase transition from the metallic (lightly H-doped) to the insulating (heavily H-doped) phase results in an increased solar energy regulation ability up to 26.5%, while maintaining 70.8% visible luminous transmittance. These results break all previous records and exceed the theoretical limit for traditional VO2 smart windows, making them ready for energy-saving utilization.

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