Tumor‐associated macrophages (TAMs) are recognized as antitumor suppressors, but how TAMs behave in the hypoxic environment of hepatocellular carcinoma (HCC) remains unclear. Here, we demonstrated that hypoxia inducible factor 1α induced increased expression of triggering receptor expressed on myeloid cells‐1 (TREM‐1) in TAMs, resulting in immunosuppression. Specifically, TREM‐1‐positive (TREM‐1+) TAMs abundant at advanced stages of HCC progression indirectly impaired the cytotoxic functions of CD8+ T cells and induced CD8+ T‐cells apoptosis. Biological and functional assays showed that TREM‐1+ TAMs had higher expression of programmed cell death ligand 1 (PD‐L1) under hypoxic environment. However, TREM‐1+ TAMs could abrogate spontaneous and PD‐L1‐blockade‐mediated antitumor effects in vivo, suggesting that TREM‐1+ TAM‐induced immunosuppression was dependent on a pathway separate from PD‐L1/programmed cell death 1 axis. Moreover, TREM‐1+ TAM‐associated regulatory T cells (Tregs) were crucial for HCC resistance to anti‐PD‐L1 therapy. Mechanistically, TREM‐1+ TAMs elevated chemokine (C‐C motif) ligand 20 expression through the extracellular signal‐regulated kinase/NF‐κβ pathway in response to hypoxia and tumor metabolites leading to CCR6+Foxp3+ Treg accumulation. Blocking the TREM‐1 pathway could significantly inhibit tumor progression, reduce CCR6+Foxp3+ Treg recruitment, and improve the therapeutic efficacy of PD‐L1 blockade. Thus, these data demonstrated that CCR6+Foxp3+ Treg recruitment was crucial for TREM‐1+ TAM‐mediated anti‐PD‐L1 resistance and immunosuppression in hypoxic tumor environment. Conclusion: This study highlighted that the hypoxic environment initiated the onset of tumor immunosuppression through TREM‐1+ TAMs attracting CCR6+Foxp3+ Tregs, and TREM‐1+ TAMs endowed HCC with anti‐PD‐L1 therapy resistance.
A new doped system with pure phosphorescent emission is constructed using four 1-(4-(diphenylamino)phenyl)-2-phenylethan-1-one derivatives containing halogen atoms as the guests and benzophenone as the host. That is, the doped system...
Liquid–liquid Phase Separation (LLPS) of proteins and nucleic acids has emerged as a new paradigm in the study of cellular activities. It drives the formation of liquid-like condensates containing biomolecules in the absence of membrane structures in living cells. In addition, typical membrane-less condensates such as nuclear speckles, stress granules and cell signaling clusters play important roles in various cellular activities, including regulation of transcription, cellular stress response and signal transduction. Previous studies highlighted the biophysical and biochemical principles underlying the formation of these liquid condensates. The studies also showed how these principles determine the molecular properties, LLPS behavior, and composition of liquid condensates. While the basic rules driving LLPS are continuously being uncovered, their function in cellular activities is still unclear, especially within a pathological context. Therefore, the present review summarizes the recent progress made on the existing roles of LLPS in cancer, including cancer-related signaling pathways, transcription regulation and maintenance of genome stability. Additionally, the review briefly introduces the basic rules of LLPS, and cellular signaling that potentially plays a role in cancer, including pathways relevant to immune responses and autophagy.
A kind of glucose‐derived carbon‐rich silicon oxycarbide (glucose‐SiOC) nanocomposite with excellent electromagnetic wave absorbing performance is obtained via solvothermal method, and then pyrolyzed at high temperature (1300°C and 1400°C) under argon atmosphere. The structural evolutions and the electromagnetic wave absorbing capabilities of the nanocomposites have been systematically investigated. The resultant 3 mol/L glucose‐SiOC ceramic exhibits a heterostructure, in which nanosized glucose‐derived carbon and SiC particles decorate on amorphous SiOC network. Benefitting from the nanosized carbon, SiC particles and the heterostructure attributes, the 3 mol/L glucose‐SiOC ceramic displays a strong electromagnetic wave‐absorbing property. The minimum reflection coefficient of the 3 mol/L glucose‐SiOC ceramic pyrolyzed at 1400°C reaches −27.6 dB at 13.8 GHz. The widest effective absorption bandwidth attains 3.5 GHz in Kμ‐band. This work opens up a novel and simple route to fabricate polymer‐derived ceramics with excellent electromagnetic wave‐absorbing performance.
Nitrogen-doped titanium dioxide (N-dopedTiO2) photocatalyst was synthesized from nanotube titanic acid (denoted as NTA; molecular formulaH2Ti2O5·H2O) precursorviaa hydrothermal route in ammonia solution. As-synthesized N-dopedTiO2catalysts were characterized by means of X-ray diffraction, transmission electron microscopy, diffuse reflectance spectrometry, X-ray photoelectron spectroscopy, electron spin resonance spectrometry and Fourier transform infrared spectrometry. It was found that nanotube ammonium titanate (NAT) was produced as an intermediate during the preparation of N-dopedTiO2from NTA, as evidenced by the N1sX-ray photoelectron spectroscopic peak ofNH4 +at 401.7 eV. The catalyst showed much higher activities to the degradation of methylene blue and p-chlorophenol under visible light irradiation than Degussa P25. This could be attributed to the enhanced absorption of N-dopedTiO2in visible light region associated with the formation of single-electron-trapped oxygen vacancies and the inhibition of recombination of photo-generated electron-hole pair by doped nitrogen.
Nowadays, metal oxide-based electromagnetic wave absorbing materials have aroused widely attentions in the application of telecommunication and electronics due to their selectable mechanical and outstanding dielectric properties. Herein, the binary ZnO/NiCo2O4 nanoparticles were successfully synthesized via hydrothermal reaction and the electromagnetic wave absorption properties of the composites were investigated in detail. As a result, benefiting from the dielectric loss, the as-obtained ZnO/NiCo2O4-7 samples possessed a minimum reflection loss value of −33.49 dB at 18.0 GHz with the thickness of 4.99 mm. This work indicates that ZnO/NiCo2O4 composites have the promising candidate applications in electromagnetic wave absorption materials in the future.
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