Effect of Multidonor and Insertion Position of a Chromophore on the Photovoltaic Properties of Phenoxazine Dyes.

Research and development of new organic semiconductor materials can never be terminated because any structural fine-tuning may result in an important impact on its application performance, although the effect may be negative in many cases. Herein, we designed and synthesized a series of phenoxazine-based dyes, YH1, YH2, YH3, and YH4, whose absorption spectrum, electrochemical cyclic voltammetry, theoretical calculation, dye-sensitized solar cell photovoltaic characteristics, and electrochemical AC impedance are used to analyze the photophysical, electrochemical, and photovoltaic performance of the materials, aiming to study the effect of multidonor and adjustment of the chromophore insertion position on their photovoltaic performance. When donor triphenylamine is added at the end of YH1 and YH3, the absorption spectrum and photovoltaic performance of dyes YH2 and YH4 improved a little. The improvement is much greater when the chromophore (ethylenedioxy)thiophene in YH1 and YH2 is adjusted and inserted on the other side of phenoxazine and the energy conversion efficiencies (photon-to-current conversion efficiency) of the resulting dyes YH3 and YH4 reach 8.02 and 8.97%, respectively, which are 23 and 25% higher than those of YH1 and YH2, respectively. Although the improvement may be because of factors such as the dihedral angle, the result will undoubtedly provide some reference for the future study of the relationship between the structure and performance of organic dyes.

Inherent lipid metabolic dysfunction in glycogen storage disease IIIa.

We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C > T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients' cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.

N-glycosylation mutations within hepatitis B virus surface major hydrophilic region contribute mostly to immune escape.

BACKGROUND & AIMS: HBV immune escape represents a challenge to prevention, diagnosis, and treatment of hepatitis B. Here, we analyzed the molecular and clinical characteristics of HBV immune escape mutants in a Chinese cohort of chronically infected patients. METHODS: Two hundred sixteen patients with HBsAg and anti-HBs were studied, with one hundred eighty-two HBV carriers without anti-HBs as a control group. Recombinant HBsAg bearing the most frequent N-glycosylation mutations were expressed in CHO and HuH7 cells. After confirming N-glycosylation at the most frequent sites (129 and 131), together with inserted mutations, functional analysis were performed to study antigenicity and secretion capacity. RESULTS: One hundred twenty-three patients had the wild-type HBs gene sequence, 93 patients (43%) had mutants in the major hydrophilic region (MHR), and 47 of the 93 patients had additional N-glycosylation mutations, which were transmitted horizontally to at least 2 patients, one of whom was efficiently vaccinated. The frequency of N-glycosylation mutation in the case group was much higher than that of the control group (47/216 vs. 1/182). Compared with wild-type HBsAg, HBsAg mutants reacted weakly with anti-HBs using a chemiluminescent microparticle enzyme immunoassay. Native gel analysis of secreted virion in supernatants of transfected HuH7 cells indicated that mutants had better virion enveloping and secretion capacity than wild-type HBV. CONCLUSIONS: Our results suggest that specific HBsAg MHR N-glycosylation mutations are implicated in HBV immune escape in a high endemic area.

Asymmetric synthesis and cytotoxicity of (-)-saframycin A analogues.

(-)-Saframycin A and its nineteen analogues were prepared from L-tyrosine in 24 steps, and their structures were confirmed through NMR and HRMS. The cytotoxicities of these compounds were tested against HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-803, Hela, HELF and KB cell lines. The IC(50) values of the cytotoxicity of most compounds were at the level of nM. Compound 7d with 2-furan amide side chain showed the most potent cytotoxicity of all these compounds with an average IC(50) value of 6.06 nM.

Asymmetric total synthesis of (-)-saframycin A from L-tyrosine.

The asymmetric total synthesis of (-)-saframycin A, a natural antitumor product of the tetrahydroisoquinoline antitumor antibiotics family, has been accomplished by employing L-tyrosine as the starting chiral building block in 24 steps for the longest linear sequence in an overall yield of 9.7%. The key steps in the synthesis involve stereoselective intermolecular and intramolecular Pictet-Spengler reactions, which induced the correct stereochemistry at C-1 and C-11, respectively. The selective protection-deprotection protocol of an amino group in the two-step transformation from intermediate 10 to 12 and a hydroxyl group in the first two steps resulted in both high selectivity and efficiency of the synthetic route.

Association of genetic variation in IL28B with hepatitis C treatment-induced viral clearance in the Chinese Han population.

BACKGROUND: Genome-wide association studies have recently shown that the rs12979860 polymorphism in IL28B is associated with the response to chronic hepatitis C treatment. The aim of this study was to investigate whether rs12979860 could be used as a predictive marker for end-of-treatment response (ETR) or sustained virological response (SVR) in the Chinese Han population. METHODS: The rs12979860 genotype was detected in 259 individuals infected with HCV by DNA sequencing. Among them, 120 patients were administered complete pegylated interferon-α and ribavirin combination therapy and 92 patients were followed for 24 weeks after the cessation of treatment and were divided into different groups according to outcomes of treatment. RESULTS: The rs12979860 genotype CC was the primary genotype (87.64%, 227/259) and genotype TT was found in only one individual within this cohort. The patients with the rs12979860 genotype CC had higher rates of ETR (P=0.0044) and SVR (P=0.0046) than the patients with N-CC (CT or TT). In multivariate analyses, the rs12979860 genotype CC was associated with a substantial difference in rates of achieving ETR (odds ratio [OR] 8.983, 95% confidence interval [CI] 2.173-37.145; P=0.0024) and SVR (OR 24.298, 95% CI 2.27-259.90; P=0.0083). CONCLUSIONS: This study demonstrated for the first time that the rs12979860 variation in IL28B could be a predictor of ETR and SVR in Chinese Han patients infected with HCV. The high frequency of the rs12979860 genotype CC might explain why the SVR rate is higher than that of the average global population.

Synthesis and cytotoxicity of (-)-renieramycin G analogs.

(-)-Renieramycin G and fifteen C-22 analogs were prepared employing l-tyrosine as the chiral starting material. These analogs, along with (-)-renieramycin G itself, were evaluated in vitro for cytotoxicity against HCT-8, BEL-7402, A2780, MCF-7, A549, BGC-823, Ketr3, KB, Hela cells. The IC(50) values of most of these analogs were at the level of µM. Among these analogs, 2-thiophenecarboxylate ester derivative 17 exhibited potent cytotoxic activity against KB cell line with the IC(50) of 20 nM. From this study, it could be concluded that the C-22 side chain played an important role in the cytotoxic potency and specificity of this class of (-)-renieramycin G derivatives.