Search

Structural variants of α-galactosylceramide (α-GalCer) that stimulate invariant natural killer T (iNKT) cells constitute an emerging class of immunomodulatory agents in development for numerous biological applications. Variations in lipid chain length and/or fatty acids in these glycoceramides selectively trigger specific pro-inflammatory responses. Studies that would link a specific function to a structurally distinct α-GalCer rely heavily on the availability of homogeneous and pure materials. To address this need, we report herein a general route to the diversification of the ceramide portion of α-GalCer glycolipids. Our convergent synthesis commences from common building blocks and relies on the Julia-Kocienski olefination as a key step. A cleavable fluorous tag is introduced at the non-reducing end of the sugar that facilitates quick purification of products by standard fluorous solid-phase extraction. The strategy enabled the rapid generation of a focused library of 61 α-GalCer analogs by efficiently assembling various lipids and fatty acids. Furthermore, when compared against parent α-GalCer in murine cells, many of these glycolipid variants were found to have iNKT cell stimulating activity similar to or greater than KRN7000. ELISA assaying indicated that glycolipids carrying short fatty N-acyl chains (1fc and 1ga), an unsubstituted (1fh and 1fi) or CF3-substituted phenyl ring at the lipid tail, and a flexible, shorter fatty acyl chain with an aromatic ring (1ge, 1gf, and 1gg) strongly affected the activation of iNKT cells by the glycolipid-loaded antigen-presenting molecule, CD1d. This indicates that the method may benefit the design of structural modifications to potent iNKT cell-binding glycolipids.

Background: MiR-484, implicated in various carcinomas, holds promise as a prognostic marker, yet its relevance to cervical cancer (CC) remains unclear. Our prior study demonstrated the Polyalthia longifolia downregulation of miR-484, inhibiting HeLa cells. This study investigates miR-484's potential as a biomarker and therapeutic target in CC through integrated bioinformatics and an in vitro analysis. Methods: MiR-484 levels were analyzed across cancers, including CC, from The Cancer Genome Atlas. The limma R package identified differentially expressed genes (DEGs) between high- and low-miR-484 CC cohorts. We assessed biological functions, tumor microenvironment (TME), immunotherapy, stemness, hypoxia, RNA methylation, and chemosensitivity differences. Prognostic genes relevant to miR-484 were identified through Cox regression and Kaplan–Meier analyses, and a prognostic model was captured via multivariate Cox regression. Single-cell RNA sequencing determined cell populations related to prognostic genes. qRT-PCR validated key genes, and the miR-484 effect on CC proliferation was assessed via an MTT assay. Results: MiR-484 was upregulated in most tumors, including CC, with DEGs enriched in skin development, PI3K signaling, and immune processes. High miR-484 expression correlated with specific immune cell infiltration, hypoxia, and drug sensitivity. Prognostic genes identified were predominantly epidermal and stratified patients with CC into risk groups, with the low-risk group showing enhanced survival and immunotherapeutic responses. qRT-PCR confirmed FGFR3 upregulation in CC cells, and an miR-484 mimic reversed the P. longifolia inhibitory effect on HeLa proliferation. Conclusion: MiR-484 plays a crucial role in the CC progression and prognosis, suggesting its potential as a biomarker for targeted therapy. [ABSTRACT FROM AUTHOR]

In this paper, the CoZrTaB thin films are fabricated using sputtering on different substrates and characterized comprehensively. The CoZrTaB thin films have been fabricated in the single-layer and multi-layer structures with SiO2 as the insulator layer, of which the vibrating sample magnetometer results suggest that the saturation field and the coercivity change of the multi-layer structure can be minimized while the lamination structure can suppress the eddy current at high working frequency. Compared with the continuously sputtered 400 nm CoZrTaB thin film, the multi-layer thin film shows a hysteresis loop with a single domain and small coercivity. The surface roughness of each CoZrTaB thin film and two kinds of polyimide substrates is extracted by the atomic force microscope instrument. Besides, material characterization such as X-ray powder diffraction and Rutherford backscattering spectrometry have been conducted to acquire the information of phase and element ratio of the CoZrTaB thin film. Also, the different process conditions that could affect the magnetic properties are investigated and verified. A comparison is made with the previously reported results, sustaining the improvement of the CoZrTaB thin film on different substrates.

We investigate the rich phase behavior of strongly confined semi-flexible (SFC) polymer–nanoparticle (NP) systems using the graphics processing unit accelerated Langevin dynamics simulation. Hard nanoparticles (HNP) that repel each other and ideal nanoparticles (INP) that do not interact with the same species are used as model additives to a strongly confined semiflexible polymer fluid. Both types of NPs exclude the monomer beads in the same way, but they have qualitatively different effects on the SFC isotropic–nematic (I–N) transition. For the total volume fraction ϕtot < 0.16, adding a low volume fraction of HNPs (ϕp) disrupts the long range nematic order of the polymers, whereas adding HNPs in a moderately packed system (0.16 < ϕtot < 0.32) facilitates polymer alignment due to the restricted polymer orientational degree of freedom. For dense packing (ϕtot > 0.32), polymers and NPs separate into layers along the slit height and the NPs form crystalline microdomains. In contrast, INP additives always promote inter-polymer alignment for low to moderate monomer volume fractions (ϕm). Furthermore, we found that INPs form a droplet-like fluid domain in dense nematic polymer systems. [ABSTRACT FROM AUTHOR]