Systemic loss of CD36 aggravates NAFLD-related HCC through MEK1/2-ERK1/2 signaling pathway.

BACKGROUND & AIMS: CD36, a membrane protein widely present in various tissues, is crucial role in regulating energy metabolism. The rise of HCC as a notable outcome of NAFLD is becoming more apparent. Patients with hereditary CD36 deficiency are at increased risk of NAFLD. However, the impact of CD36 deficiency on NAFLD-HCC remains unclear. METHODS: Global CD36 knockout mice (CD36KO) and wild type mice (WT) were induced to establish NAFLD-HCC model by N-nitrosodiethylamine (DEN) plus high fat diet (HFD). Transcriptomics was employed to examine genes that were expressed differentially. RESULTS: Compared to WT mice, CD36KO mice showed more severe HFD-induced liver issues and increased tumor malignancy. The MEK1/2-ERK1/2 pathway activation was detected in the liver tissues of CD36KO mice using RNA sequencing and Western blot analysis. CONCLUSION: Systemic loss of CD36 leaded to the advancement of NAFLD to HCC by causing lipid disorders and metabolic inflammation, a process that involves the activation of MAPK signaling pathway. We found that CD36 contributes significantly to the maintenance of metabolic homeostasis in NAFLD-HCC.

CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis.

Liver metastasis is highly aggressive and treatment-refractory, partly due to macrophage-mediated immune suppression. Understanding the mechanisms leading to functional reprogramming of macrophages in the tumor microenvironment (TME) will benefit cancer immunotherapy. Herein, we find that the scavenger receptor CD36 is upregulated in metastasis-associated macrophages (MAMs) and deletion of CD36 in MAMs attenuates liver metastasis in mice. MAMs contain more lipid droplets and have the unique capability in engulfing tumor cell-derived long-chain fatty acids, which are carried by extracellular vesicles. The lipid-enriched vesicles are preferentially partitioned into macrophages via CD36, that fuel macrophages and trigger their tumor-promoting activities. In patients with liver metastases, high expression of CD36 correlates with protumoral M2-type MAMs infiltration, creating a highly immunosuppressive TME. Collectively, our findings uncover a mechanism by which tumor cells metabolically interact with macrophages in TME, and suggest a therapeutic potential of targeting CD36 as immunotherapy for liver metastasis.

[Preparation and evaluation of hydrophilic interaction/reversed-phase mixed-mode chromatographic packing based on polylsilsesquioxane microspheres].

Hydrophilic interaction (HILIC)/reversed-phase (RPLC) mixed-mode chromatography is widely used in separating both hydrophobic and hydrophilic compounds, but its pH range is limited which is harmful to the separation of alkaline drugs. Monodispersed and porous cysteine-modified vinyl functionalized polymethylsilsesquioxane (C-V-PMSQ) microspheres were prepared by thiol-ene click chemistry. Elemental analysis revealed that cysteine was successfully bonded to the surface of microspheres. C-V-PMSQ microspheres had excellent monodispersity, favorable chemical stability and simple preparation process. The chromatographic behavior of C-V-PMSQ stationary phase was investigated by employing several nucleosides and nucleic acids under HILIC mode and RPLC mode. Retention factors versus volume percentage of aqueous solution exhibited a U-curve, which can be evaluated as an indication for HILIC/RPLC mixed-mode behavior of the stationary phase. This new stationary phase presented stronger retention behavior when employing alkylbenzenes as evaluation system. In addition, a series of hydrophilic and hydrophobic compounds were separated at the same time using this new stationary phase. Furthermore, baseline separation for the major three active components of Chinese herbal medicine Radix Sophorae flavescentis was achieved under HILIC and RPLC modes with highly alkaline mobile phase. The excellent chemical stability and base deactivated nature make the organosilicas ideal stationary phases for the separation of basic compounds. What's more, it even can achieve two-dimensional liquid chromatography separation on an HPLC column.

Molecular Spectrum Capture by Tuning the Chemical Potential of Graphene.

Due to its adjustable electronic properties and effective excitation of surface plasmons in the infrared and terahertz frequency range, research on graphene has attracted a great deal of attention. Here, we demonstrate that plasmon modes in graphene-coated dielectric nanowire (GNW) waveguides can be excited by a monolayer graphene ribbon. What is more the transverse resonant frequency spectrum of the GNW can be flexibly tuned by adjusting the chemical potential of graphene, and amplitude of the resonance peak varies linearly with the imaginary part of the analyte permittivity. As a consequence, the GNW works as a probe for capturing the molecular spectrum. Broadband sensing of toluene, ethanol and sulfurous anhydride thin layers is demonstrated by calculating the changes in spectral intensity of the propagating mode and the results show that the intensity spectra correspond exactly to the infrared spectra of these molecules. This may open an effective avenue to design sensors for detecting nanometric-size molecules in the terahertz and infrared regimes.