Pyroelectric effect mediated infrared photoresponse in Bi2Te3/Pb(Mg1/3Nb2/3)O3-PbTiO3 optothermal ferroelectric field-effect transistors.

The responses of material properties to multi-field stimulation are often exploited to construct new types of multi-functional devices. Here, we demonstrate electrical, optical and thermal modulation of the electronic properties of optothermal ferroelectric field-effect transistors (FeFETs) which are fabricated by growing Bi2Te3 films on (111)-oriented 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO 3 (PMN-PT) ferroelectric single-crystal substrates. Using the electric field to switch the polarization direction of PMN-PT, the carrier density and resistance of Bi2Te3 films are in situ, reversibly, and nonvolatilely modulated via the ferroelectric field effect. Moreover, through infrared light illumination on the bottom of PMN-PT substrates, the resistance of Bi2Te3 films in two polarization states could be further modulated, which is ascribed to the decreased polarization intensity at higher temperature due to the pyroelectric effect. Taking advantage of these two effects, the Bi2Te3/PMN-PT optothermal FeFETs exhibit multiple responses to optical and electric field stimulation at room temperature. Our work provides a strategy to design optoelectronic devices with both photodetector and memory functionalities.

Cu4 Cluster Doped Monolayer MoS2 for CO Oxidation.

The catalytic oxidation of CO molecule on a thermodynamically stable Cu4 cluster doped MoS2 monolayer is investigated by density functional theory (DFT) where the reaction proceeds in a new formation order of COOOCO* (O2* + 2CO* → COOOCO*), OCO* (COOOCO* → CO2 + OCO*), and CO2 (OCO* → CO2) desorption with the corresponding reaction barrier values of 0.220 eV, 0.370 eV and 0.119 eV, respectively. Therein, the rate-determining step is the second one. This low barrier indicates high activity of this system where CO oxidation could be realized at room temperature (even lower). As a result, the Cu4 doped MoS2 could be a candidate for CO oxidation with lower cost and higher activity without poisoning and corrosion problems.

Intracellular effects of the Hepatitis C virus nucleoside polymerase inhibitor RO5855 (Mericitabine Parent) and Ribavirin in combination.

Mericitabine (RG7128) is the prodrug of a highly selective cytidine nucleoside analog inhibitor (RO5855) of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. This study evaluated the effects of combining RO5855 and ribavirin on HCV replication in the HCV subgenomic replicon by using two drug-drug interaction models. The effects of RO5855 and ribavirin on the intracellular metabolism of each compound, on interferon-stimulated gene (ISG) expression, and on the viability of hepatocyte-derived cells were also investigated. RO5855 and ribavirin had additive inhibitory activities against HCV subgenomic replicon replication in drug-drug interaction analyses. RO5855 did not affect the uptake or phosphorylation of ribavirin in primary human hepatocytes, human peripheral blood mononuclear cells, or genotype 1b (G1b) replicon cells. Similarly, ribavirin did not affect the concentrations of intracellular species derived from RO5855 in primary human hepatocytes or the formation of the triphosphorylated metabolites of RO5855. Ribavirin at concentrations of >40 µM significantly reduced the viability of primary hepatocytes but not of Huh7, the G1b replicon, or interferon-cured Huh7 cells. RO5855 alone or with ribavirin did not significantly alter the viability of Huh7 or G1b replicon cells, and it did not significantly affect the viability of primary hepatocytes when it was administered alone. The viability of primary hepatocytes was reduced when they were incubated with RO5855 and ribavirin, similar to the effects of ribavirin alone. RO5855 alone or with ribavirin had no effect on ISG mRNA levels in any of the cells tested. In conclusion, RO5855 did not show any unfavorable interactions with ribavirin in human hepatocytes or an HCV subgenomic replicon system.

Characterization of hepatitis C virus (HCV) quasispecies dynamics upon short-term dual therapy with the HCV NS5B nucleoside polymerase inhibitor mericitabine and the NS3/4 protease inhibitor danoprevir.

In the INFORM-1 study, 73 patients with chronic hepatitis C virus infection received mericitabine plus danoprevir for up to 13 days. Seventy-two patients experienced a continuous decline in HCV RNA levels during treatment, and of these patients, 14 had viral loads that remained >1,000 IU/ml by day 13 and 1 met the definition for viral breakthrough. In-depth NS5B and NS3/4A population and clonal sequencing studies and mericitabine and danoprevir drug susceptibility testing were performed to assess the variability and quasispecies dynamics before and upon monotherapy or dual therapy. Sequence analysis of the viral quasispecies indicated that the mericitabine resistance mutation S282T was not present at baseline, nor was it selected (even at a low level) during treatment. Protease inhibitor resistance mutations, either as predominant or as minority species, were detected in 18 patients at baseline. No enrichment of minority protease inhibitor-resistant variants present at baseline was observed during treatment; viral population samples were fully susceptible to mericitabine and/or danoprevir, despite the presence within their quasispecies of minority variants confirmed to have reduced susceptibility to danoprevir or other protease inhibitors. It was also observed that certain NS3 amino acid substitutions affected protease inhibitor drug susceptibility in a compound-specific manner and varied with the genetic context. In summary, the slower kinetics of viral load decline observed in some patients was not due to the selection of danoprevir or mericitabine resistance during treatment. Over 2 weeks' therapy, mericitabine suppressed the selection of danoprevir resistance, results that could differ upon longer treatment periods.

In vitro resistance development for RO-0335, a novel diphenylether nonnucleoside reverse transcriptase inhibitor.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important components of current combination therapies for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. However, their low genetic barriers against resistance development, cross-resistance and serious side effects can compromise the benefits of the first generation compounds in this class (efavirenz and nevirapine). To study potential pathways leading to resistance against the novel diphenylether NNRTI, RO-0335, sequential passage experiments at low multiplicity of infection (MOI) were performed to solicit a stepwise selection of resistance mutations. Two pathways to loss of susceptibility to RO-0335 were observed, containing patterns of amino acid changes at either V106I/A plus F227C (with additional contributions from A98G, V108I, E138K, M230L and P236L) or V106I/Y188L (with a potential contribution from L100I, E138K and Y181C). Characterization of the observed mutations by site-directed mutagenesis in the isogenic HXB2D background demonstrated that a minimum of two or more mutations were required for significant loss of susceptibility, with the exception of Y188L, which requires a two-nucleotide change. Patterns containing F227C or quadruple mutations selected by RO-0335 showed a low relative fitness value when compared to wild-type HXB2D.

[Treatment of ABO blood type incompatibility caused early abortion with traditional Chinese medicine].

This results of 30 cases with the history of abortion due to ABO blood type incompatibility treated with traditional Chinese medicine (TCM) were reported. The titer of serum IgG anti A/B antibody were determined in these patients. Antibody titer < or = 1:128 before pregnancy or < or = 1:64 after pregnancy were treated with TCM till delivery. 25 cases gave birth at full term, 5 cases were before term. Abortion, stillbirth or hemolytic newborn death were not found. The lower the maternal serum IgG anti A/B titer, the lower the incidence of hemolytic jaundice; while the earlier the treatment after pregnancy, the lower the occurrence of hemolytic jaundice also.

[Surgical treatment of cancer of the base of the tongue and epiglottis].

This paper reports the surgical treatment of 10 cases of cancer of the base of the tongue and the epiglottis resected by a translaryngeal approach. In addition, a brief description of the technique is introduced. All patients had squamous cell cancer which was obviously advanced to stage IV and the tumor mass had extended to the whole root of the tongue, the vallecula and the epiglottis. After operation, all patients learned to swallow effectively and no persistent aspiration occurred. The speech articulation was satisfactory. Postoperative follow-up of all the patients, the shortest being 13 months, revealed no local or cervical lymphatic recurrence, but two patients died of lung metastasis, one after 18 months and the other after 48 months. The translaryngeal approach maintains the integrity of the mandibular and occlusal joints, avoids deformity to the face and the anterior oral cavity and prevents scarring in those tissues affording maximal mobility of the tongue.