Quantum entanglement and interference at 3 µm.

Given the important advantages of the mid-infrared optical range (2.5 to 25 µm) for biomedical sensing, optical communications, and molecular spectroscopy, extending quantum information technology to this region is highly attractive. However, the development of mid-infrared quantum information technology is still in its infancy. Here, we report on the generation of a time-energy entangled photon pair in the mid-infrared wavelength band. By using frequency upconversion detection technology, we observe the two-photon Hong-Ou-Mandel interference and demonstrate the time-energy entanglement between twin photons at 3082 nm via the Franson-type interferometer, verifying the indistinguishability and nonlocality of the photons. This work is very promising for future applications of optical quantum technology in the mid-infrared band, which will bring more opportunities in the fields of quantum communication, precision sensing, and imaging.

Oxasmaragdyrins as New and Efficient Hole-Transporting Materials for High-Performance Perovskite Solar Cells.

The high performance of the perovskite solar cells (PSCs) cannot be achieved without a layer of efficient hole-transporting materials (HTMs) to retard the charge recombination and transport the photogenerated hole to the counterelectrode. Herein, we report the use of boryl oxasmaragdyrins (SM01, SM09, and SM13), a family of aromatic core-modified expanded porphyrins, as efficient hole-transporting materials (HTMs) for perovskite solar cells (PSCs). These oxasmaragdyrins demonstrated complementary absorption spectra in the low-energy region, good redox reversibility, good thermal stability, suitable energy levels with CH3NH3PbI3 perovskite, and high hole mobility. A remarkable power conversion efficiency of 16.5% (Voc = 1.09 V, Jsc = 20.9 mA cm-2, fill factor (FF) = 72%) is achieved using SM09 on the optimized PSCs device employing a planar structure, which is close to that of the state-of-the-art hole-transporting materials (HTMs), spiro-OMeTAD of 18.2% (Voc = 1.07 V, Jsc = 22.9 mA cm-2, FF = 74%). In contrast, a poor photovoltaic performance of PSCs using SM01 is observed due to the interactions of terminal carboxylic acid functional group with CH3NH3PbI3.

Growth inhibitory effect of KYKZL-1 on Hep G2 cells via inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest.

KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the inhibitory activity test on Hep G2 growth. We found that KYKZL-1 inhibited the growth of Hep G2 cells via inducing apoptosis. Further studies showed that KYKZL-1 activated caspase-3 through cytochrome c release from mitochondria and down regulation of Bcl-2/Bax ratio and reduced the high level of COX-2 and 5-LOX. As shown in its anti-inflammatory effect, KYKZL-1 also exhibited inhibitory effect on the PGE2 and LTB4 production in Hep G2 cells. Accordingly, exogenous addition of PGE2 or LTB4 reversed the decreases in cell viability. In addition, KYKZL-1 caused cell cycle arrest at the S-G2 checkpoint via the activation of p21(CIP1) protein and down-regulation of cyclin A expression. These data indicate that the growth inhibitory effect of KYKZL-1 is associated with inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest. Combined with our previous findings, KYKZL-1 exhibiting COX/5-LOX inhibition may be a promising potential agent not only for inflammation control but also for cancer prevention/therapy with an enhanced gastric safety profile.

Inhibition of hepatitis C replicon RNA synthesis by beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine: a specific inhibitor of hepatitis C virus replication.

beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) is a cytidine analogue with potent and selective anti-hepatitis C virus (HCV) activity in the subgenomic HCV replicon assay, 90% effective concentration (EC90)=4.6 +/- 2.0 microM. The spectrum of activity and cytotoxicity profile of PSI-6130 was evaluated against a diverse panel of viruses and cell types, and against two additional HCV-1b replicons. The S282T mutation, which confers resistance to 2'-C-methyl adenosine and other 2'-methylated nucleosides, showed only a 6.5-fold increase in EC90. When assayed for activity against bovine diarrhoea virus (BVDV), which is typically used as a surrogate assay to identify compounds active against HCV, PSI-6130 showed no anti-BVDV activity. Weak antiviral activity was noted against other flaviviruses, including West Nile virus, Dengue type 2, and yellow fever virus. These results indicate that PSI-6130 is a specific inhibitor of HCV. PSI-6130 showed little or no cytotoxicity against various cell types, including human peripheral blood mononuclear and human bone marrow progenitor cells. No mitochondrial toxicity was observed with PSI-6130. The reduced activity against the RdRp S282T mutant suggests that PSI-6130 is an inhibitor of replicon RNA synthesis. Finally, the no-effect dose for mice treated intraperitoneally with PSI-6130 for six consecutive days was > or =100 mg/kg per day.

Characterization of hepatitis B virus inhibition by novel 2'-fluoro-2',3'-unsaturated beta-D- and L-nucleosides.

The clinical emergence of lamivudine and adefovir resistance mutations on prolonged therapy further necessitates the development of additional drugs for the treatment of hepatitis B virus (HBV) infections. We have evaluated a number of novel 2'-fluoro-2',3'-unsaturated D- and L-nucleosides for their anti-HBV activity in the HepG2-2.2.15 cell system. The most potent nucleosides were beta-L-2'-fluoro-2',3'-dideoxy-2',3'-didehydrocy-tidine (L-2'-Fd4C) and beta-L-2'-fluoro-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (L-2'-Fd4FC) with median effective concentrations (EC50) of 0.002 microM and 0.004 microM, respectively. The D-enantiomers of the 2'-fluoro-substituted cytidine analogues in this series showed activity, with the 5-fluorocytidine (D-2'-Fd4FC) being the most potent (EC50 = 0.05 microM). The active compounds were not cytotoxic to a number of cell lines or to bone marrow progenitor cells. Furthermore, mitochondrial DNA synthesis and function were not affected by these nucleosides. L-2'-Fd4C did not affect viral transcription, implying that it does not inhibit cellular RNA polymerase II. Studies with the HBV polymerase in core particles revealed that the 5'-triphosphates of L-2'-Fd4C and D-2'-Fd4FC produced a dose-dependent inhibition of the incorporation of 32P-dCTP into the HBV DNA, indicating that the mechanism of action of these compounds is through specific inhibition of viral DNA synthesis. This class of nucleosides, which exhibit potent antiviral activity and a favourable safety profile, have potential for the treatment of HBV infections and warrant further development.

Mechanism of anti-human immunodeficiency virus activity of beta-D-6-cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine.

To better understand the importance of the oxygen in the ribose ring of planar unsaturated nucleoside analogs that target human immunodeficiency virus (HIV), a 6-cyclopropyl-substituted prodrug of 2',3'-didehydro-2',3'-dideoxyguanosine (cyclo-d4G) was synthesized, and its cellular metabolism, antiviral activity, and pharmacokinetic behavior were studied. Cyclo-d4G had selective anti-HIV activity in primary blood mononuclear cells (PBMCs), effectively inhibiting the LAI strain of HIV-1 by 50% at 1.1 +/- 0.1 microM while showing 50% inhibition of cell viability at 84.5 microM. The antiviral activity in PBMCs was not markedly affected by mutations of methionine to valine at position 184 or by thymidine-associated mutations in the viral reverse transcriptase. Mutations of leucine 74 to valine and of lysine 65 to arginine had mild to moderate resistance (as high as fivefold). Studies to delineate the mechanism of cellular metabolism and activation of cyclo-d4G showed reduced potency in inhibiting viral replication in the presence of the adenosine/adenylate deaminase inhibitor 2'-deoxycoformycin, implying that the antiviral activity is due to its metabolism to the 2'-dGTP analog d4GTP. Intracellular formation of sugar catabolites illustrates the chemical and potentially enzymatic instability of the glycosidic linkage in d4G. Further studies suggest that cyclo-d4G has a novel intracellular phosphorylation pathway. Cyclo-d4G had a lower potential to cause mitochondrial toxicity than 2',3'-dideoxycytidine and 2',3'-didehydro-3'-deoxythymidine in neuronal cells. Also, cyclo-d4G had advantageous synergism with many currently used anti-HIV drugs. Poor oral bioavailability observed in rhesus monkeys may be due to the labile glycosidic bond, and special formulation may be necessary for oral delivery.