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1.
Immunity ; 52(5): 767-781.e6, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32277911

RESUMO

The enzyme cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA in infected and malignant cells and catalyzes the formation of 2'3'cGMP-AMP (cGAMP), which in turn triggers interferon (IFN) production via the STING pathway. Here, we examined the contribution of anion channels to cGAMP transfer and anti-viral defense. A candidate screen revealed that inhibition of volume-regulated anion channels (VRACs) increased propagation of the DNA virus HSV-1 but not the RNA virus VSV. Chemical blockade or genetic ablation of LRRC8A/SWELL1, a VRAC subunit, resulted in defective IFN responses to HSV-1. Biochemical and electrophysiological analyses revealed that LRRC8A/LRRC8E-containing VRACs transport cGAMP and cyclic dinucleotides across the plasma membrane. Enhancing VRAC activity by hypotonic cell swelling, cisplatin, GTPγS, or the cytokines TNF or interleukin-1 increased STING-dependent IFN response to extracellular but not intracellular cGAMP. Lrrc8e-/- mice exhibited impaired IFN responses and compromised immunity to HSV-1. Our findings suggest that cell-to-cell transmission of cGAMP via LRRC8/VRAC channels is central to effective anti-viral immunity.


Assuntos
Fibroblastos/imunologia , Interferons/imunologia , Proteínas de Membrana/imunologia , Nucleotídeos Cíclicos/imunologia , Canais de Ânion Dependentes de Voltagem/imunologia , Animais , Antivirais/imunologia , Antivirais/metabolismo , Efeito Espectador , Linhagem Celular , Células Cultivadas , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Células HeLa , Herpes Simples/imunologia , Herpes Simples/virologia , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/fisiologia , Humanos , Interferons/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/imunologia , Nucleotidiltransferases/metabolismo , Canais de Ânion Dependentes de Voltagem/metabolismo
2.
Small ; 20(24): e2308276, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38161263

RESUMO

Dielectric polymer composites exhibit great application prospects in advanced pulse power systems and electric systems. However, the decline of breakdown strength by loading of single high dielectric constant nanofiller hinders the sustained increase in energy density of the composites. Here, a sandwich-structured nanocomposite prepared with mica nanosheets as the second filler exhibits decoupled modulation of dielectric constant and breakdown strength. The traditional layered clay mineral mica is exfoliated into nanosheets and filled into polyvinylidene difluoride (PVDF), which shows a special depolarization effect in the polymer matrix. In Kelvin probe microscopy characterization and thermally stimulated depolarization current indicates that the mica nanosheets provided space charge traps for the polymer matrix and effectively suppressed the carrier motion. A sandwich structure composite material with mica nanosheets as the central layer has achieved a high energy density of 11.48 J cm-3, 2.4 times higher than the pure PVDF film. This is due to the fact that randomly oriented distribution of nanosheets in a polymer matrix provide better current blocking. This work provides an effective method to improve the energy density of dielectric polymer composites by synergistically introducing insulating nanosheets and high dielectric constant nanofillers.

3.
Chem Commun (Camb) ; 59(64): 9734-9737, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37477537

RESUMO

Herein, copper cysteamine (CC) was loaded with montmorillonite (MMT) to form a montmorillonite-copper cysteamine (MCC) composite that showed enhanced fluorescence properties. This enhancement was determined to have arisen from electron transfer, improved structural stability, and a nonradiative deactivation process.

4.
ACS Appl Mater Interfaces ; 15(2): 3141-3151, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36598369

RESUMO

Bio-derived nanomaterials are promising candidates for spinning high-performance sustainable textiles, but the inherent flammability of biomass-based fibers seriously limits their applications. There is still an urgent need to improve fiber flame retardancy while maintaining excellent mechanical performance. Here, inspired by the structural properties of layered nanoclay, we report a novel and efficient strategy to synthesize the strong, super tough, and flame-retardant nanocellulose/clay/sodium alginate (CRS) macrofibers via wet-spinning and directional drying. Benefiting from the precise modulation of arrangement and orientation of nanoclay in macrofibers, the new inorganic structure exhibits excellent mechanical and thermal functional properties. The anisotropic structure contributes to high toughness: the tensile strength was 373.3 MPa and the toughness was 26.92 MJ·m-3. Remarkably, rectorite nanosheets as a thermal and qualitative insulator significantly improve the flame retardancy of the CRS fibers with a heat release rate as low as 6.07 W/g, thermal conductivity of 90.5 mW/(m·K), and good temperature tolerance (ranging from -196 to 100 °C). This facile and high-efficiency strategy may have great scalability in manufacturing high-strength, super tough, and flame-retardant fibers for emerging biodegradable next-generation artificial fibers.

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