O2, NO2 and NH3 coordination to Co-porphyrin studied with scanning tunneling microscopy on Au(111).

The coordination structure between small molecules and metalloporphyrins plays a crucial role in functional reactions such as bio-oxidation and catalytic activation. Their vertical, tilting, and dynamic structures have been actively studied with diffraction and resonance spectroscopy for the past four decades. Contrastingly, real-space visualization beyond simple protrusion and depression is relatively rare. In this paper, high-resolution scanning tunnelling microscopy (STM) images are presented of di-, tri-, and tetra-atomic small molecules (O2, NO2, and NH3, respectively) coordinated to Co-porphyrin on Au(111). A square ring structure was observed for O2, a rectangular ring structure for NO2, and a bright-center structure for NH3 at 80 K. The symmetries of experimental STM images were reproduced in density functional theory (DFT) calculations, considering the precession motion of the small molecules. Thus, this study shows that the structure of small molecules coordinated to metalloporphyrins can be visualized using high-resolution STM and DFT calculations.

A comparison of 4-year entecavir efficacy in nucleos(t)ide analog-naïve and -experienced adult Taiwanese chronic hepatitis B patients.

PURPOSE: To compare the efficacy of entecavir (ETV) monotherapy up to 4 years in nucleos(t)ide analog (NA)-experienced and -naïve subjects. METHODS: One hundred sixty NA-experienced and 282 naïve chronic hepatitis B patients who were treated with ETV were enrolled. Of the 160 NA-experienced patients, 49 had prior lamivudine (LAM)-resistant mutants, 18 had resistant mutants to LAM followed by adefovir (ADV) after switching to ADV sequential therapy (LAM/ADV resistance), and 9 had prior ADV-resistant mutants. NA-resistant mutants were detected by line probe assay. RESULTS: Four years of ETV therapy resulted in virological response (VR, HBV DNA < 300 copies/ml), HBeAg seroconversion, and ETV-resistant mutants development in 98.2, 45.2, and <1 % of naïve patients, respectively. LAM- and ADV-experienced patients who never developed LAM-resistant mutants had similar VR and ETV-resistant mutant rates to NA-naïve patients. In contrast, prior LAM-resistant mutants were significantly associated with higher ETV-resistant mutants development and reduced VR rates. Patients with prior LAM-resistant mutants but not at baseline had a lower rate of ETV-resistant mutants compared to those with baseline LAM-resistant mutants [hazard ratio (HR): 0.58, 95 % confidence interval (CI): 0.35-0.95] and those who had LAM/ADV resistance (HR:0.16, 95 % CI:1.0.03-0.76). Early add-on ADV achieved VR in eight of nine patients with ETV-resistant mutants when HBV DNA was <2 × 10(5) copies/ml. CONCLUSIONS: Entecavir was highly efficacious and low resistance in NA-naïve, LAM-, or ADV-experienced patients without LAM-resistant mutants. Patients with prior LAM-resistant mutants but not at baseline had lower ETV-resistant mutant rates compared to those with baseline LAM-resistant mutants or LAM/ADV resistance.

Treatment response and evolution of HBV resistance during lamivudine plus adefovir or entecavir therapy in patients with adefovir-resistant mutants.

BACKGROUND: Here, we investigated the treatment response and evolution of HBV resistance during lamivudine (LAM) plus adefovir (ADV) and entecavir (ETV) monotherapy in patients with ADV-resistant mutants. METHODS: Of the 53 patients with ADV-resistant mutants, 25 received combined LAM plus ADV therapy (LAM+ADV group) and 28 received ETV monotherapy (ETV group) for at least 12 months (median 24 months and range 12-67 months). RESULTS: During 24 months therapy, no significant difference was noted in HBV DNA reduction from baseline, HBV DNA<200 copies/ml, hepatitis B e antigen loss and ALT normalization between the two groups. In the LAM+ADV group, patients with single rtN236T resistant mutation had higher rates of undetectable HBV DNA than those with the double mutant rtA181T/V+rtN236T at months 3-18 of therapy. No virological breakthrough occurred except for one patient with rtN236T resistant mutation who experienced virological and biochemical breakthrough after the emergence of an additional rtA181T mutant under LAM+ADV therapy. Of the 28 patients receiving ETV monotherapy, ETV-resistant mutants developed in 8. The cumulative rates of ETV-resistant mutations and virological breakthrough at months 12, 24 and 36 were 3.6%, 25.7% and 46.8%, respectively. ADV-resistant mutations were rapidly replaced by LAM-resistant mutations (median 12 months) followed by ETV-resistant mutations. CONCLUSIONS: There was no significant difference in virological response between the LAM+ADV and ETV groups in patients with ADV-resistant mutants. LAM+ADV were less effective in patients with the double mutant rtA181T/V+rtN236T than the single rtN236T mutation. The incidence of ETV-resistant mutation was high in patients with LAM/ADV-resistant mutants treated with ETV monotherapy.

Characteristics of adefovir resistance in patients with or without lamivudine-resistant hepatitis B virus treated with adefovir: a 4-year experience.

BACKGROUND/AIM: We investigated the 4-year incidence and predictors of adefovir resistance in chronic hepatitis B patients with or without lamivudine (LAM)-resistance treated with adefovir dipivoxil with or without short-term LAM overlapping. METHODS: One hundred and two LAM-resistant patients and 79 without LAM resistance (36 naïve and 43 prior LAM exposure) treated with adefovir for >12 months were prospectively examined. RESULTS: Cumulative incidences of adefovir resistance at month 12, 24, 36 and 48 were 3.9, 21.1, 31.8 and 43% respectively in LAM-resistant patients. Cirrhosis was a significant risk factor for adefovir resistance. A similar rate of adefovir resistance was observed for LAM-resistant patients and those with prior LAM exposure without resistance. Regarding LAM-resistant patients, compared with those having hepatitis B virus (HBV) DNA levels <300 copies/ml, patients having HBV DNA levels >10(4) copies/ml at week 24 of therapy had a hazard ratio (HR) of 9.8 for adefovir resistance development, while those without LAM resistance having the same HBV DNA levels at week 48 had a similar HR (9.5). Multidrug-resistant (LAM+adefovir) variants were detected by direct sequencing in three of 35 LAM-resistant patients treated with a switch to adefovir. Two of them had resistant mutations to both drugs on the same viral genome as determined by molecular cloning and sequencing. CONCLUSION: The incidence of adefovir resistance was high in LAM-resistant patients treated with sequential adefovir. High HBV DNA levels at week 24 and 48 of therapy were the strongest predictors for adefovir resistance development in patients with and without LAM resistance respectively.

Conformational and adsorptive characteristics of albumin affect interfacial protein boundary lubrication: from experimental to molecular dynamics simulation approaches.

The lifetime of artificial joints is mainly determined by their biotribological properties. Synovial fluid which consists of various biological molecules acts as the lubricant. Among the compositions of synovial fluid, albumin is the most abundant protein. Under high load and low sliding speed articulation of artificial joint, it is believed the lubricants form protective layers on the sliding surfaces under the boundary lubrication mechanism. The protective molecular layer keeps two surfaces from direct collision and thus decreases the possibility of wear damage. However, the lubricating ability of the molecular layer may vary due to the conformational change of albumin in the process. In this study, we investigated the influence of albumin conformation on the adsorption behaviors on the articulating surfaces and discuss the relationship between adsorbed albumin and its tribological behaviors. We performed the friction tests to study the effects of albumin unfolding on the frictional behaviors. The novelty of this research is to further carry out molecular dynamics simulation, and protein adsorption experiments to investigate the mechanisms of the albumin-mediated boundary lubrication of arthroplastic materials. It was observed that the thermal processes induce the loss of secondary structure of albumin. The compactness of the unfolded structure leads to a higher adsorption rate onto the articulating material surface and results in the increase of friction coefficient.