The value of a risk model combining specific risk factors for predicting postoperative severe morbidity in biliary tract cancer.

Purpose: Several surgical risk models are widely utilized in general surgery to predict postoperative morbidity. However, no studies have been undertaken to examine the predictive efficacy of these models in biliary tract cancer patients, and other perioperative variables can also influence morbidity. As a result, the study's goal was to examine these models alone, as well as risk models combined with disease-specific factors, in predicting severe complications.

Maintenance of dimer conformation by the dengue virus core protein α4-α4' helix pair is critical for nucleocapsid formation and virus production.

The virion of dengue virus (DENV) is composed of a viral envelope covering a nucleocapsid formed by a complex of viral genomic RNA and core protein (CP). DENV CP forms a dimer via the internal α2 and α4 helices of each monomer. Pairing of α2-α2' creates a continuous hydrophobic surface, while the α4-α4' helix pair joins the homodimer via side-chain interactions of the inner-edge residues.

A novel dengue virus inhibitor, BP13944, discovered by high-throughput screening with dengue virus replicon cells selects for resistance in the viral NS2B/NS3 protease.

Dengue virus (DENV) causes disease globally, resulting in an estimated 25 to 100 million new infections per year. No effective DENV vaccine is available, and the current treatment is only supportive. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease.

RNA binding property and RNA chaperone activity of dengue virus core protein and other viral RNA-interacting proteins.

In this study we showed that the dengue virus (DENV) core protein forms a dimer with an α-helix-rich structure, binds RNA and facilitates the strand annealing process. To assess the RNA chaperone activity of this core protein and other dengue viral RNA-interacting proteins, such as NS3 helicase and NS5 proteins, we engineered cis- and trans-cleavage hammerhead ribozyme constructs carrying DENV genomic RNA elements. Our results indicate that DENV core protein facilitates typical hammerhead structure formation by acting as an RNA chaperone and DENV NS5 has a weak RNA chaperone activity, while DENV NS3 helicase failed to refold RNA with a complex secondary structure.

HCV NS3 protein helicase domain assists RNA structure conversion.

NS3H, the helicase domain of HCV NS3, possesses RNA-stimulated ATPase and ATP hydrolysis-dependent dsRNA unwinding activities. Here, the ability of NS3H to facilitate RNA structural rearrangement is studied using relatively long RNA strands as the model substrates. NS3H promotes intermolecular annealing, resolves three-stranded RNA duplexes, and assists dsRNA and ssRNA inter-conversions to establish a steady state among RNA structures.

Analysis of the nucleoside triphosphatase, RNA triphosphatase, and unwinding activities of the helicase domain of dengue virus NS3 protein.

The helicase domain of dengue virus NS3 protein (DENV NS3H) contains RNA-stimulated nucleoside triphosphatase (NTPase), ATPase/helicase, and RNA 5'-triphosphatase (RTPase) activities that are essential for viral RNA replication and capping. Here, we show that DENV NS3H unwinds 3'-tailed duplex with an RNA but not a DNA loading strand, and the helicase activity is poorly processive. The substrate of the divalent cation-dependent RTPase activity is not restricted to viral RNA 5'-terminus, a protruding 5'-terminus made the RNA 5'-triphosphate readily accessible to DENV NS3H.

Characterization and application of the selective strand annealing activity of the N terminal domain of hepatitis delta antigen.

We used synthetic DNA oligos to investigate the nucleic acid chaperone properties of the N terminal domain of hepatitis delta antigen (NdAg). We found that NdAg possessed a bona fide chaperone activity. NdAg could distinguish subtle differences in the thermal stability of the base pairing region, and enabled DNA oligos to form a more stable duplex among competing sequences through facilitating strand annealing selectively, stimulating duplex conversion selectively, and stabilizing the more stable duplex.

Nucleic acid binding properties of the nucleic acid chaperone domain of hepatitis delta antigen.

The N terminal region of hepatitis delta antigen (HDAg), referred to here as NdAg, has a nucleic acid chaperone activity that modulates the ribozyme activity of hepatitis delta virus (HDV) RNA and stimulates hammerhead ribozyme catalysis. We characterized the nucleic acid binding properties of NdAg, identified the structural and sequence domains important for nucleic acid binding, and studied the correlation between the nucleic acid binding ability and the nucleic acid chaperone activity. NdAg does not recognize the catalytic core of HDV ribozyme specifically.

Selective strand annealing and selective strand exchange promoted by the N-terminal domain of hepatitis delta antigen.

We have previously shown that the N-terminal domain of hepatitis delta virus (NdAg) has an RNA chaperone activity in vitro (Huang, Z. S., and Wu, H.