Cervical extracellular matrix hydrogel optimizes tumor heterogeneity of cervical squamous cell carcinoma organoids.

Cervical cancer, primarily squamous cell carcinoma, is the most prevalent gynecologic malignancy. Organoids can mimic tumor development in vitro, but current Matrigel inaccurately replicates the tissue-specific microenvironment. This limitation compromises the accurate representation of tumor heterogeneity. We collected para-cancerous cervical tissues from patients diagnosed with cervical squamous cell carcinoma (CSCC) and prepared uterine cervix extracellular matrix (UCEM) hydrogels. Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase-AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor κB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.

Symmetry-Broken Ru Nanoparticles with Parasitic Ru-Co Dual-Single Atoms Overcome the Volmer Step of Alkaline Hydrogen Oxidation.

Efficient dual-single-atom catalysts are crucial for enhancing atomic efficiency and promoting the commercialization of fuel cells, but addressing the sluggish kinetics of hydrogen oxidation reaction (HOR) in alkaline media and the facile dual-single-atom site generation remains formidable challenges. Here, we break the local symmetry of ultra-small ruthenium (Ru) nanoparticles by embedding cobalt (Co) single atoms, which results in the release of Ru single atoms from Ru nanoparticles on reduced graphene oxide (Co1 Ru1,n /rGO). In situ operando spectroscopy and theoretical calculations reveal that the oxygen-affine Co atom disrupts the symmetry of ultra-small Ru nanoparticles, resulting in parasitic Ru and Co dual-single-atom within Ru nanoparticles. The interaction between Ru single atoms and nanoparticles forms effective active centers. The parasitism of Co atoms modulates the adsorption of OH intermediates on Ru active sites, accelerating HOR kinetics through faster formation of *H2 O. As anticipated, Co1 Ru1,n /rGO exhibits ultrahigh mass activity (7.68 A mgRu -1 ) at 50 mV and exchange current density (0.68 mA cm-2 ), which are 6 and 7 times higher than those of Ru/rGO, respectively. Notably, it also displays exceptional durability surpassing that of commercial Pt catalysts. This investigation provides valuable insights into hybrid multi-single-atom and metal nanoparticle catalysis.

Caffeic acid phenethyl ester suppresses the induction of eotaxin in human lung fibroblast cells.

BACKGROUND: Eotaxin, a CC chemokine, plays an important role in inflammation of airway allergic diseases. The authors investigated the activities of caffeic acid phenethyl ester (CAPE), the active component of propolis, in regulating eotaxin production in human lung fibroblast. MATERIAL AND METHODS: The authors used human lung fibroblasts, CCD-11Lu cells, stimulated with interleukin-13 (IL-13) and tumor necrosis factor-alpha (TNF-alpha), to induce eotaxin secretion. The cells were treated with CAPE of different concentrations and pretreatment duration to check its inhibition in eotaxin production. Enzyme-linked immunosorbent assay (ELISA) was used to measure eotaxin secretion; electrophoretic mobility shift assay (EMSA) to check nuclear factor kappa B (NF-kappaB)-promoter binding; and Western blot to quantitate the cyplasmic inhibitor of NF-kappaB (IkappaB) and nuclear NF-kappaB p65. RESULTS: CAPE inhibited the production of eotaxin in CCD-11Lu cells stimulated by IL-13 and TNF-alpha combination in a dose- and time-dependent manner. The authors also demonstrated CAPE to be able to inhibit NF-kappaB activation in CCD-11Lu cells. CONCLUSION: The authors suggest that CAPE is a promising agent in controlling eosinophils influx in human airway.