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Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide. Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that binds to programmed cell death-1 (PD-1), which is expressed in activated T cells and other immune cells and has been employed in cancer therapy, including HCC. Recently, PD-L1 overexpression has been documented in treatment-resistant cancer cells. Sorafenib is a multikinase inhibitor and the only FDA-approved treatment for advanced HCC. However, several patients exhibit resistance to sorafenib during treatment. This study aimed to assess the effect of glucose deprivation on PD-L1 expression in HCC cells. We used PD-L1-overexpressing HepG2 cells and IFN-γ-treated SK-Hep1 cells to explore the impact of glycolysis on PD-L1 expression. To validate the correlation between PD-L1 expression and glycolysis, we analyzed data from The Cancer Genome Atlas (TCGA) and used immunostaining for HCC tissue analysis. Furthermore, to modulate PD-L1 expression, we treated HepG2, SK-Hep1, and sorafenib-resistant SK-Hep1R cells with rapamycin. Here, we found that glucose deprivation reduced PD-L1 expression in HCC cells. Additionally, TCGA data and immunostaining analyses confirmed a positive correlation between the expression of hexokinase II (HK2), which plays a key role in glucose metabolism, and PD-L1. Notably, rapamycin treatment  decreased the expression of PD-L1 and HK2 in both high PD-L1-expressing HCC cells and sorafenib-resistant cells. Our results suggest that the modulation of PD-L1 expression by glucose deprivation may represent a strategy to overcome PD-L1 upregulation in patients with sorafenib-resistant HCC.

In this work, we investigated the effect of hole transporting poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) interfacing with Mn-doped CdS/ZnS quantum dots (QDs) deposited on an indium tin oxide (ITO) substrate on the photoemission of upconverted hot electrons under weak continuous wave photoexcitation in a vacuum. Among the various factors that can influence the photoemission of the upconverted hot electrons, we studied the role of PEDOT:PSS in facilitating the hole transfer from QDs and altering the energy of photoemitted hot electrons. Compared to hot electrons emitted from QDs deposited directly on the ITO substrate, the addition of the PEDOT:PSS layer between the QD and ITO layers increased the energy of the photoemitted hot electrons. The increased energy of the photoemitted hot electrons is attributed in part to the reduced steady-state positive charge on the QDs under continuous photoexcitation, which reduces the energy required to eject the electron from the conduction band. [ABSTRACT FROM AUTHOR]

To apply semiconductor nanostructures as a solid matrix for laser desorption/ionization-mass spectrometry, the nanostructures should exhibit ionization activity through photocatalytic reactions and desorption enhancement through photothermal conversion. Herein, TiO2 aerogels were synthesized using titanium-(IV) butoxide as a precursor, and a controlled porous structure was obtained by adjusting the ethanol content and annealing temperatures. The photocatalytic activity of the TiO2 aerogel was estimated using pseudo-first-order kinetics on methylene blue degradation reactions. To achieve further desorption/ionization properties, a combi-matrix was produced using the TiO2 aerogel and a conventional organic matrix, α-cyano-4-hydroxynnamic acid (CHCA). The enhanced ionization efficiency of the TiO2 aerogel combi-matrix was demonstrated along with an improved signal-to-noise ratio from other solid matrix combi-matrix systems. Meanwhile, the distribution of CHCA crystals in TiO2 aerogel with various annealing conditions was investigated by differential scanning calorimetry with the Gibbs–Thomson equation. The radius of CHCA crystals was minimized at 550 °C but increased steeply at heat treatment temperatures higher than 600 °C, implying a collapse in the pore structure of the TiO2 aerogel. Furthermore, the activation energy for melting the CHCA nanocrystals was calculated using the Arrhenius equation. These results showed that CHCA nanocrystals in a combi-matrix with the TiO2 aerogel after annealing at 550 °C could be most effectively melted with lower activation energy via the pore structure and the binary phased TiO2 aerogel. Finally, the combi-matrix based on TiO2 aerogel was applied for the analysis of the sera from sepsis patients (n = 40), systemic inflammatory response syndrome (SIRS) patients (n = 20), and healthy controls (n = 20), finding that the combi-matrix based on TiO2 aerogel could be effectively used for the diagnosis of sepsis using lysophosphatidylcholine (LPC-16) as a biomarker. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (NP) participates in viral genome packaging and abundantly produced when infected. In this work, SPR biosensor for the detection of SARS-CoV-2 in viral fluid using Fv-antibodies with the binding affinity to nucleocapsid protein (NP) of SARS-CoV-2. The FV-antibodies with a specific binding activity to the SARS-CoV-2 NP were screened using the FV-antibody library, which was expressed on the outer membrane of E. coli. FV-antibodies comprised three complementarity-determining regions (CDRs) and four frame regions (FRs) of the heavy chain at the binding pocket of IgG. The FV-antibody library was prepared by performing site-directed mutagenesis and by using the autodisplay technology; FV-antibodies with specific binding activities to the nucleocapsid protein (NP) of SARS-CoV-2 were screened using NP-immobilized magnetic beads. First, E. coli isolates with the target FV-antibody were screened, and the binding affinity (KD) was estimated for the screened E. coli clones using FACS analysis. Then, the outer membrane (OM) of the screened E. coli clones with autodisplayed Fv-antibodies was obtained and layered on an SPR biosensor, and the binding curves of four different coronavirus (CoV) culture fluids, SARS-CoV-2, SARS-CoV, MERS-CoV, and CoV strain 229E, were compared. Finally, the FV-antibodies of the screened E. coli clones were synthesized as peptides (11 amino acid residues), and the binding constants (KD) to NP as well as the binding curves of the CoV strains in culture fluids were estimated. Using docking simulation, binding sites and interaction types between NP and each synthetic peptide were investigated. [ABSTRACT FROM AUTHOR]