Histone lactylation inhibits RARγ expression in macrophages to promote colorectal tumorigenesis through activation of TRAF6-IL-6-STAT3 signaling.

Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype and how to manipulate them for therapeutic purposes remain to be explored. Here, we show that in the TME, RARγ is downregulated in macrophages, and its expression correlates with poor prognosis in patients with colorectal cancer (CRC). In macrophages, RARγ interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), which prevents TRAF6 oligomerization and autoubiquitination, leading to inhibition of nuclear factor κB signaling. However, tumor-derived lactate fuels H3K18 lactylation to prohibit RARγ gene transcription in macrophages, consequently enhancing interleukin-6 (IL-6) levels in the TME and endowing macrophages with tumor-promoting functions via activation of signal transducer and activator of transcription 3 (STAT3) signaling in CRC cells. We identified that nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding to RARγ to inhibit TRAF6-IL-6-STAT3 signaling. This study unravels lactate-driven macrophage function remodeling by inhibition of RARγ expression and highlights NDGA as a candidate compound for treating CRC.

Comparative study on the interaction between flavonoids with different core structures and hyaluronidase.

Hyaluronidase (HAase) is an important enzyme involved in a promoting inflammation pathway. Flavonoids are a group of major polyphenols including flavonols (such as myricetin and rutin), dihydroflavones (such as naringin and hesperidin), and isoflavones (such as genistein and puerarin), which have been proved to possess anti-inflammatory effects. In this study, the binding of the six flavonoids to HAase was investigated by steady state and time-resolved fluorescence, circular dichroism (CD) spectroscopy and molecular docking methods. Fluorescence data reveal that the fluorescence quenching mechanism of HAase by flavonoids is all static quenching procedure regardless of their core structure. The binding affinity is strongest for rutin and ranks in the order rutin > hesperidin > myricetin > puerarin > genistein > naringin. The thermodynamic analysis implies that hydrophobic interaction, electrostatic force and hydrogen bonding are the main interaction forces. Synchronous fluorescence spectroscopy and CD spectroscopy indicate that flavonoids have the same core structure and have similar effects on the microenvironment around Trp and Tyr residues and the secondary structure of HAase. The results of molecular docking show that the binding of flavonoids with the catalytic amino acid residues of HAase may lead to the decrease of enzyme activity.

Magnetic zeolite imidazole framework material-8 as an effective and recyclable adsorbent for removal of ceftazidime from aqueous solution.

Zeolitic imidazolate framework-8 (ZIF-8) was synthesized by solvothermal method and the adsorption pore size was adjusted by changing the amount of template agent. The ZIF-8@SiO2@Fe3O4 derived from self-assembly of ZIF-8 and SiO2@Fe3O4 were then synthesized and used for ceftazidime (CAZ) removal. ZIF-8 was a regular dodecahedral particle with uniform particle size. The pore diameter was 6.47 nm and the specific surface area was 1182.5 m²·g-1 in ZIF-8@SiO2@Fe3O4. The adsorption of CAZ on ZIF-8@SiO2@Fe3O4 as a function of adsorption temperature, contact time, ionic strength solution pH, and humic acid concentration were investigated. The error of equilibrium adsorption capacity between model fitting and actual experiments is only 1.19%. Kinetics for CAZ removal on ZIF-8@SiO2@Fe3O4 was found to follow pseudo-second-order kinetics. Langmuir, Freundlich and Sips isotherm fitted the adsorption data well and gave similar correlation coefficients, suggesting a single layer adsorption of CAZ on ZIF-8@SiO2@Fe3O4. The ZIF-8@SiO2@Fe3O4 showed no apparent loss in CAZ adsorption after five cycles. These features indicate that the ZIF-8@SiO2@Fe3O4 may be a promising adsorbent for CAZ removal from aqueous solution.