3-Ethyl-1H-1,2,4-triazole-5(4H)-thione

The mol­ecule of the title compound, C4H7N3S, exists as the thione tautomer in the solid state. The asymmetric unit consits of one mol­ecule in which all atoms are located on a crystallographic mirror plane. In the crystal, adjacent mol­ecules are linked by N—H⋯N and N—H⋯S hydrogen bonds into chains running along the a axis. π–π stacking inter­actions between the triazole rings [centroid–centroid distance = 3.740 (1) Å and inter­planar distance = 3.376 Å] may further stabilize the structure

3D-XY critical fluctuations of the thermal expansivity in detwinned YBa2Cu3O7-d single crystals near optimal doping

The strong coupling of superconductivity to the orthorhombic distortion in YBa2Cu3O7-d makes possible an analysis of the superconducting fluctuations without the necessity of subtracting any background. The present high-resolution capacitance dilatometry data unambiguously demonstrate the existence of critical, instead of Gaussian, fluctuations over a wide temperature region (+/- 10 K) around Tc. The values of the amplitude ratio A+/A-=0.9-1.1 and the leading scaling exponent |alpha|<0.018, determined via a least-squares fit of the data, are consistent with the 3D-XY universality class. Small deviations from pure 3D-XY behavior are discussed.Comment: 11 pages including three figure

Intracellular Metabolism and In Vitro Activity of Tenofovir against Hepatitis B Virus

Tenofovir is an acyclic nucleotide analog with activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Tenofovir disoproxil fumarate (tenofovir DF), a bis-alkoxyester prodrug of tenofovir, is approved for the treatment of HIV and is currently being developed to treat chronic hepatitis B. In this report, we further characterize the in vitro activity of tenofovir against HBV as well as its metabolism in hepatic cells. We show that tenofovir is efficiently phosphorylated to tenofovir diphosphate (TFV-DP) in both HepG2 cells and primary human hepatocytes. TFV-DP has a long intracellular half-life (95 h) and is a potent and competitive inhibitor of HBV polymerase (K(i) = 0.18 μM). Tenofovir has a 50% effective concentration of 1.1 μM against HBV in cell-based assays, and potency is improved >50-fold by the addition of bis-isoproxil progroups. Tenofovir has previously demonstrated full activity against lamivudine-resistant HBV in vitro and clinically. Here we show that the major adefovir resistance mutation, rtN236T, confers three- to fourfold-reduced susceptibility to tenofovir in cell culture; the clinical significance of this susceptibility shift has not yet been determined. The rtA194T HBV polymerase mutation recently identified in tenofovir DF-treated HIV/HBV-coinfected patients did not confer in vitro resistance to tenofovir as a single mutation or in a lamivudine-resistant viral background. Overall, the antiviral and metabolic profile of tenofovir supports its development for the treatment of chronic hepatitis B

In Vitro Drug Susceptibility Analysis of Hepatitis B Virus Clinical Quasispecies Populations▿

Analysis of the replication and drug resistance of patient serum hepatitis B virus (HBV) populations can contribute to the therapeutic management of chronic hepatitis B. We developed a procedure for cloning serum HBV quasispecies populations and for phenotypic analysis of the cloned populations for in vitro drug susceptibility. Equivalent sequences were compared to the respective serum HBV DNAs of the cloned quasispecies by population sequencing. Analysis of individual clones revealed that each population contained a diversity of HBV quasispecies. Furthermore, secreted HBV in the supernatant following transfection of the quasispecies populations remained mostly unchanged from the respective input populations. HBV obtained from patients who had developed resistance to adefovir or lamivudine, as demonstrated by development of the rtA181V or rtL180M/M204V mutations in HBV polymerase, respectively, were tested. Phenotypic analysis demonstrated that a population containing the HBV rtA181V mutation showed a 2.9-fold increase in the 50% effective concentration (EC50) for adefovir compared to the wild-type baseline isolate, while the lamivudine-resistant HBV quasispecies population showed a >1,000-fold increase in the lamivudine EC50. In summary, a strategy of cloning full genome HBV quasispecies populations from patient sera was developed, which could provide a useful tool in clinical HBV drug resistance phenotyping and studies of the evolution of clinical viral species

Rare Earth Ion Doped Luminescent Materials: A Review of Up/Down Conversion Luminescent Mechanism, Synthesis, and Anti-Counterfeiting Application

With the rapid development of modern technology and information systems, optical anti-counterfeiting and encryption have recently attracted considerable attention. The demand for optical materials is also constantly increasing, with new requirements proposed for performance and application fields. Currently, rare earth ion doped materials possess a unique electronic layer structure, underfilled 4f5d electronic configuration, rich electronic energy level, and long-life excited state, which can produce a variety of radiation absorption and emission. The distinctive properties of rare earth are beneficial for using in diverse optical output anti-counterfeiting. Design is essential for rare earth ion doped materials with multiple responsiveness and multi-channel optical information anti-counterfeiting in the field of information security. Therefore, this mini review summarizes the luminescent mechanisms, preparation methods, performance characteristics and anti-counterfeiting application of rare earth doped materials. In addition, we discuss some critical challenges in this field, and potential solutions that have been or are being developed to overcome these challenges

Antiviral Effects of Lamivudine, Emtricitabine, Adefovir Dipivoxil, and Tenofovir Disoproxil Fumarate Administered Orally Alone and in Combination to Woodchucks with Chronic Woodchuck Hepatitis Virus Infection ▿

Adefovir dipivoxil (ADV) and tenofovir disoproxil fumarate (TDF) are nucleotide analogs that inhibit the replication of wild-type hepatitis B virus (HBV) and lamivudine (3TC)-resistant virus in HBV-infected patients, including those who are coinfected with human immunodeficiency virus. The combination of ADV or TDF with other nucleoside analogs is a proposed strategy for managing antiviral drug resistance during the treatment of chronic HBV infection. The antiviral effect of oral ADV or TDF, alone or in combination with 3TC or emtricitabine (FTC), against chronic woodchuck hepatitis virus (WHV) infection was evaluated in a placebo-controlled study in the woodchuck, an established and predictive model for antiviral therapy. Once-daily treatment for 48 weeks with ADV plus 3TC or TDF plus FTC significantly reduced serum WHV viremia levels from the pretreatment level by 6.2 log10 and 6.1 log10 genome equivalents/ml serum, respectively, followed by TDF plus 3TC (5.6 log10 genome equivalents/ml), ADV alone (4.8 log10 genome equivalents/ml), ADV plus FTC (one survivor) (4.4 log10 genome equivalents/ml), TDF alone (2.9 log10 genome equivalents/ml), 3TC alone (2.7 log10 genome equivalents/ml), and FTC alone (2.0 log10 genome equivalents/ml). Individual woodchucks across all treatment groups also demonstrated pronounced declines in serum WHV surface antigen, characteristically accompanied by declines in hepatic WHV replication and the hepatic expression of WHV antigens. Most woodchucks had prompt recrudescence of WHV replication after drug withdrawal, but individual woodchucks across treatment groups had sustained effects. No signs of toxicity were observed for any of the drugs or drug combinations administered. In conclusion, the oral administration of 3TC, FTC, ADV, and TDF alone and in combination was safe and effective in the woodchuck model of HBV infection