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- Hyun, Gyu Hwan, et al.
(författare)
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Multivalent Carbohydrate Nanocomposites for Tumor Microenvironment Remodeling to Enhance Antitumor Immunity
- 2023
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 17:12, s. 11567-11582
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Tidskriftsartikel (refereegranskat)abstract
- Current cancer immunotherapeutic strategies mainly focus on remodeling the tumor microenvironment (TME) to make it favorable for antitumor immunity. Increasing attention has been paid to developing innovative immunomodulatory adjuvants that can restore weakened antitumor immunity by conferring immunogenicity to inflamed tumor tissues. Here, a galactan-enriched nanocomposite (Gal-NC) is developed from native carbohydrate structures through an optimized enzymatic transformation for effective, stable, and biosafe innate immunomodulation. Gal-NC is characterized as a carbohydrate nanoadjuvant with a macrophage-targeting feature. It is composed of repeating galactan glycopatterns derived from heteropolysaccharide structures of plant origin. The galactan repeats of Gal-NC function as multivalent pattern-recognition sites for Toll-like receptor 4 (TLR4). Functionally, Gal-NC-mediated TLR activation induces the repolarization of tumor-associated macrophages (TAMs) toward immunostimulatory/tumoricidal M1-like phenotypes. Gal-NC increases the intratumoral population of cytotoxic T cells, the main effector cells of antitumor immunity, via re-educated TAMs. These TME alterations synergistically enhance the T-cell-mediated antitumor response induced by αPD-1 administration, suggesting that Gal-NC has potential value as an adjuvant for immune checkpoint blockade combination therapies. Thus, the Gal-NC model established herein suggests a glycoengineering strategy to design a carbohydrate-based nanocomposite for advanced cancer immunotherapies.
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| 2. |
- Lin, Xiaojing, et al.
(författare)
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Metal-enriched Neutral Gas Reservoir around a Strongly Lensed Low-mass Galaxy at z = 4 Identified by JWST/NIRISS and VLT/MUSE
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 944:2
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Tidskriftsartikel (refereegranskat)abstract
- Direct observations of low-mass, low-metallicity galaxies at z ≳ 4 provide an indispensable opportunity for detailed inspection of the ionization radiation, gas flow, and metal enrichment in sources similar to those that reionized the universe. Combining the James Webb Space Telescope (JWST), Very Large Telescope/MUSE, and Atacama Large Millimeter/submillimeter Array, we present detailed observations of a strongly lensed, low-mass (≈107.6 M ⊙) galaxy at z = 3.98 (also see Vanzella et al.). We identify strong narrow nebular emission, including C iv λ λ1548, 1550, He ii λ1640, O iii] λ λ1661, 1666, [Ne iii] λ3868, [O ii] λ3727, and the Balmer series of hydrogen from this galaxy, indicating a metal-poor H ii region (≲0.12 Z ⊙) powered by massive stars. Further, we detect a metal-enriched damped Lyα system (DLA) associated with the galaxy with the H i column density of N H I ≈ 1021.8 cm−2. The metallicity of the associated DLA may reach the supersolar metallicity (≳Z ⊙). Moreover, thanks to JWST and gravitational lensing, we present the resolved UV slope (β) map at the spatial resolution of ≈100 pc at z = 4, with steep UV slopes reaching β ≈ −2.5 around three star-forming clumps. Combining with low-redshift analogs, our observations suggest that low-mass, low-metallicity galaxies, which dominate reionization, could be surrounded by a high covering fraction of the metal-enriched, neutral-gaseous clouds. This implies that the metal enrichment of low-mass galaxies is highly efficient, and further supports that in low-mass galaxies, only a small fraction of ionizing radiation can escape through the interstellar or circumgalactic channels with low-column-density neutral gas.
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