Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities.

Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide  additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage.

Phosphorylation of ribosomal protein S6 kinase 1 at Thr421/Ser424 and dephosphorylation at Thr389 regulates SP600125-induced polyploidization of megakaryocytic cell lines.

Megakaryocytes (MKs) are one of the few cell types that become polyploid; however, the mechanisms by which these cells are designated to become polyploid are not fully understood. In this investigation, we successfully established two relatively synchronous polyploid cell models by inducing Dami and CMK cells with SP600125. We found that SP600125 induced the polyploidization of Dami and CMK cells, concomitant with the phosphorylation of ribosomal protein S6 kinase 1 (S6K1) at Thr421/Ser424 and dephosphorylation at Thr389.

Study of the residues involved in the binding of β1 to β3 subunits in the sodium channel.

The voltage-gated sodium channel (VGSC) is a complex, which is composed of one pore-forming α subunit and at least one β subunit. Up to now, five β subunits are known: β1/β1A, β1B, β2, β3, and β4, encoded by four genes (SCN1B∼SCN4B). It is critical to have a deep understanding of the interaction between β1 and β3 subunits, two subunits which frequently appear in many diseases concurrently.

Site-directed mutagenesis of BmK AGP-SYPU1: the role of two conserved Tyr (Tyr5 and Tyr42) in analgesic activity.

In this study, the role of two conversed tyrosines (Tyr5 and Tyr42) from the scorpion toxin BmK AGP-SYPU1 was investigated with an effective Escherichia coli expression system. Site-directed mutagenesis was used to individually substitute Tyr5 and Tyr42 with hydrophobic or hydrophilic amino acids, and the extent to which these scorpion toxin BmK AGP-SYPU1 tyrosines contribute to analgesic activity was evaluated. The results of the mouse-twisting test showed that Tyr5 and Tyr42 are associated with the analgesic activity of the toxin because the analgesic activities of Y5F and Y42F were significantly increased compared with the rBmK AGP-SYPU1; however, the Y5W had decreased activity.

The role of glycine residues at the C-terminal peptide segment in antinociceptive activity: a molecular dynamics simulation.

Elucidating structural determinants in the functional regions of toxins can provide useful knowledge for designing novel analgesic peptides. Glycine residues at the C-terminal region of the neurotoxin BmK AGP-SYPU2 from the scorpion Buthus martensii Karsch (BmK) have been shown to be crucial to its analgesic activity. However, there has been no research on the structure-function relationship between the C-terminal segment of this toxin and its analgesic activity.

DFT investigation on the reaction mechanism catalyzed by α-phosphomannomutase1 in protonated/deprotonated states.

Congenital disorder of glycosylation type 1a (CDG-1a) which is a congenital disease, is caused by mutations in α-Phosphomannomutase1. The reaction mechanism of the α-phosphomannomutase1 enzyme has been investigated by means of density functional theory using the hybrid functional B3LYP. The α-phosphomannomutase1 catalyzes the interconversion of the α-D-mannose 1-phosphate to D-mannose 6-phosphate via a mannose-1,6-(bis) phosphate intermediate.

Analysis of a three-dimensional structure of human acidic mammalian chitinase obtained by homology modeling and ligand binding studies.

The three-dimensional (3D) model of the human acidic mammalian chitinase (hAMCase) was constructed based on the crystal structure of the human chitotriosidase (EC 3.2.1.

Homology modeling and molecular dynamics study on N-acetylneuraminate lyase.

With homology modeling techniques, molecular mechanics and molecular dynamics methods, a 3D structure model of N-acetylneuraminate lyase from human (hNAL, EC 4.1.3.