A series of perylene diimide cathode interlayer materials for green solvent processing in conventional organic photovoltaics.

Herein, we report on the design, synthesis, physical and chemical properties, and organic photovoltaic (OPV) device performance of four new cathode interlayer (CIL) materials based on bay N-annulated perylene diimides. Starting from the previously reported N-annulated perylene diimide (PDIN-H), the N-position was functionalized with a benzyl and pentafluorobenzyl group to make PDIN-B and PDIN-FB, respectively. Similarly, starting from the previously reported cyanated N-annulated perylene diimide (CN-PDIN-H), the N-position was functionalized with a benzyl and pentafluorobenzyl group to make CN-PDIN-B and CN-PDIN-FB, respectively. The materials exhibit solubility in the green solvent, ethyl acetate, and thus were processed into thin films using ethyl acetate as the solvent. The optoelectronic properties were assessed for both solution and film, and the electrochemical properties were probed in solution. To validate the potential as electron transporting layers, each film was used in conventional OPVs as the CIL with processing from ethyl acetate, while using a bulk heterojunction (BHJ) comprised of PM6:Y6. High power conversion efficiencies (PCEs) of 13% were achieved compared to control devices using the standard PFN-Br CIL.

How varying surface wettability of different PEDOT:PSS formulations and their mixtures affects perovskite crystallization and the efficiency of inverted perovskite solar cells.

The physico-chemical interaction, surface, and electrical properties of hole transport layers (HTLs) significantly affect the wettability and film crystallization of the deposited perovskite and the corresponding performance of inverted perovskite solar cells (PSCs). One of the most frequently used HTLs for inverted PSCs is poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS). Various commercial PEDOT:PSS formulations have already been tested as HTLs. Until now mixtures of these remained rather unexplored. In this study, three commercially available PEDOT:PSS formulations (PH, PH1000, and AI4083), as well as three mixtures (PH:PH1000, PH:AI4083, and PH:PH1000:AI4083; in a 1 : 1 and 1 : 1 : 1 ratios) were used as HTLs to investigate the crystallization of perovskite films and the performance of associated PSCs. Of the three formulations, PEDOT:PSS PH showed better perovskite crystallization, resulting in better solar cell performance followed by both PH:AI4083 and PH:PH1000:AI4083 layers. The pioneering work on mixing PEDOT:PSS resulted in new combinations of PEDOT:PSS, with new properties (work function, surface wettability, and roughness) which are very important parameters for perovskite crystallization and corresponding device efficiencies and stabilities. All PSCs that use the mixed PEDOT:PSS as HTLs revealed higher fill factor and open-circuit voltage values above 900 mV, which is not the same except for PEDOT:PSS PH. As a result, we believe that such a mixing strategy could aid in the creation of various PEDOT:PSS combinations with tuneable properties for certain applications.

Glycosphingolipids are mediators of cancer plasticity through independent signaling pathways.

The molecular repertoire promoting cancer cell plasticity is not fully elucidated. Here, we propose that glycosphingolipids (GSLs), specifically the globo and ganglio series, correlate and promote the transition between epithelial and mesenchymal cells. The epithelial character of ovarian cancer remains stable throughout disease progression, and spatial glycosphingolipidomics reveals elevated globosides in the tumor compartment compared with the ganglioside-rich stroma. CRISPR-Cas9 knockin mediated truncation of endogenous E-cadherin induces epithelial-to-mesenchymal transition (EMT) and decreases globosides. The transcriptomics analysis identifies the ganglioside-synthesizing enzyme ST8SIA1 to be consistently elevated in mesenchymal-like samples, predicting poor outcome. Subsequent deletion of ST8SIA1 induces epithelial cell features through mTORS2448 phosphorylation, whereas loss of globosides in ΔA4GALT cells, resulting in EMT, is accompanied by increased ERKY202/T204 and AKTS124. The GSL composition dynamics corroborate cancer cell plasticity, and further evidence suggests that mesenchymal cells are maintained through ganglioside-dependent, calcium-mediated mechanisms.

Exploring the signaling space of a GPCR using bivalent ligands with a rigid oligoproline backbone.

G protein-coupled receptors (GPCRs) are one of the most important drug-target classes in pharmaceutical industry. Their diversity in signaling, which can be modulated with drugs, permits the design of more effective and better-tolerated therapeutics. In this work, we have used rigid oligoproline backbones to generate bivalent ligands for the gastrin-releasing peptide receptor (GRPR) with a fixed distance between their recognition motifs. This allows the stabilization of GPCR dimers irrespective of their physiological occurrence and relevance, thus expanding the space for medicinal chemistry. Specifically, we observed that compounds presenting agonists or antagonists at 20- and 30-Å distance induce GRPR dimerization. Furthermore, we found that 1) compounds with two agonists at 20- and 30-Å distance that induce dimer formation show bias toward Gq efficacy, 2) dimers with 20- and 30-Å distance have different potencies toward ß-arrestin-1 and ß-arrestin-2, and 3) the divalent agonistic ligand with 10-Å distance specifically reduces Gq potency without affecting ß-arrestin recruitment, pointing toward an allosteric effect. In summary, we show that rigid oligoproline backbones represent a tool to develop ligands with biased GPCR signaling.

Transition of Mesenchymal and Epithelial Cancer Cells Depends on α1-4 Galactosyltransferase-Mediated Glycosphingolipids.

The reversible transitions of cancer cells between epithelial and mesenchymal states comprise cellular and molecular processes essential for local tumor growth and respective dissemination. We report here that globoside glycosphingolipid (GSL) glycosyltransferase-encoding genes are elevated in epithelial cells and correlate with characteristic EMT signatures predictive of disease outcome. Depletion of globosides through CRISPR-Cas9-mediated deletion of the key enzyme A4GALT induces EMT, enhances chemoresistance, and increased CD24low/CD44high cells. The cholera toxin-induced mesenchymal-to-epithelial transition occurred only in cells with functional A4GALT. Cells undergoing EMT lost E-cadherin expression through epigenetic silencing at the promoter region of CDH1 However, in ΔA4GALT cells, demethylation was able to rescue E-cadherin-mediated cell-cell adhesion only in the presence of exogenous A4GALT. Overall, our data suggest another class of biomolecules vital for epithelial cancer cells and for maintaining cell integrity and function.Significance: This study highlights the essential role of glycosphingolipids in the maintenance of epithelial cancer cell properties. Cancer Res; 78(11); 2952-65. ©2018 AACR.

Altered (neo-) lacto series glycolipid biosynthesis impairs α2-6 sialylation on N-glycoproteins in ovarian cancer cells.

The (neo-) lacto series glycosphingolipids (nsGSLs) comprise of glycan epitopes that are present as blood group antigens, act as primary receptors for human pathogens and are also increasingly associated with malignant diseases. Beta-1, 3-N-acetyl-glucosaminyl-transferase 5 (B3GNT5) is suggested as the key glycosyltransferase for the biosynthesis of nsGSLs. In this study, we investigated the impact of CRISPR-Cas9 -mediated gene disruption of B3GNT5 (∆B3GNT5) on the expression of glycosphingolipids and N-glycoproteins by utilizing immunostaining and glycomics-based PGC-UHPLC-ESI-QTOF-MS/MS profiling. ∆B3GNT5 cells lost nsGSL expression coinciding with reduction of α2-6 sialylation on N-glycoproteins. In contrast, disruption of B4GALNT1, a glycosyltransferase for ganglio series GSLs did not affect α2-6 sialylation on N-glycoproteins. We further profiled all known α2-6 sialyltransferase-encoding genes and showed that the loss of α2-6 sialylation is due to silencing of ST6GAL1 expression in ∆B3GNT5 cells. These results demonstrate that nsGSLs are part of a complex network affecting N-glycosylation in ovarian cancer cells.

Naturally occurring anti-glycan antibodies binding to Globo H-expressing cells identify ovarian cancer patients.

BACKGROUND: Glycosphingolipids are important compounds of the plasma membrane of mammalian cells and a number of them have been associated with malignant transformation and progression, reinforcing tumour aggressiveness and metastasis. Here we investigated the levels of naturally occurring anti-glycan antibodies to Globo H in blood plasma obtained from high-grade serous ovarian cancer patients (SOC) and women without gynaecological malignancies (control) using suspension glycan array technology employing chemically synthesized glycans as antibody targets. RESULTS: We found that anti-human Globo H IgG antibodies were able to significantly discriminate SOC from controls (P < 0.05). A combination with the clinically used tumour marker CA125 increased the diagnostic performance (AUC 0.8711). We next compared suspension array with standard flow cytometry in plasma samples and found that the level of anti-Globo H antibodies highly correlated (r = 0.992). The incubation of plasma-derived anti-glycan antibodies with chemically synthesized (presented on fluorescence microspheres) and native Globo H (expressed on Globo H-positive cell lines) revealed strong reactivity of naturally occurring human anti-Globo H antibodies towards its antigen expressed on ovarian cancer cells. CONCLUSIONS: Our data demonstrate that human plasma-derived antibodies to Globo H as well as the presence of the antigen might be considered as therapeutic option in ovarian cancer.

Glucosylceramide synthase inhibitors differentially affect expression of glycosphingolipids.

Glucosylceramide synthase (GCS) catalyzes the first committed step in the biosynthesis of glucosylceramide (GlcCer)-related glycosphingolipids (GSLs). Although inhibitors of GCS, PPMP and PDMP have been widely used to elucidate their biological function and relevance, our comprehensive literature review revealed that the available data are ambiguous. We therefore investigated whether and to what extent GCS inhibitors affect the expression of lactosylceramide (LacCer), neolacto (nLc4 and P1), ganglio (GM1 and GD3) and globo (Gb3 and SSEA3) series GSLs in a panel of human cancer cell lines using flow cytometry, a commonly applied method investigating cell-surface GSLs after GCS inhibition. Their cell-surface GSL expression considerably varied among cell lines and more importantly, sublethal concentrations (IC10) of both inhibitors preferentially and significantly reduced the expression of Gb3 in the cancer cell lines IGROV1, BG1, HT29 and T47D, whereas SSEA3 was only reduced in BG1. Unexpectedly, the neolacto and ganglio series was not affected. LacCer, the precursor of all GlcCer-related GSL, was significantly reduced only in BG1 cells treated with PPMP. Future research questions addressing particular GSLs require careful consideration; our results indicate that the extent to which there is a decrease in the expression of one or more particular GSLs is dependent on the cell line under investigation, the type of GCS inhibitor and exposure duration.

Identification of the Fungal Pathogen that Causes Strawberry Anthracnose in Bangladesh and Evaluation of In Vitro Fungicide Activity.

This study was conducted to identify the Colletotrichum species causing anthracnose disease of strawberry in Balgladesh and to evaluate in vitro activity of commercial fungicides it. Based on morphological and cultural characteristics, all 22 isolates were identified as Colletotrichum gloeosporioides. They developed white or glittery colonies with grey to dark grey reverse colony colors and they produced cylindrical conidia. The efficacy of five commercial fungicides, Bavistin DF, Dithane M-45, Sulcox 50 WP, Corzim 50 WP and Rovral 50 WP, were tested against the fungus. Bavistin inhibited radial growth completely and was followed in efficacy by Dithane M-45. In Bavistin DF treated media, the fungus did not produce conidia. The percent inhibition of radial growth of the fungus was increased with the increasing concentrations of fungicide.

Biological Screening of a Novel Nickel (II) Tyrosine Complex.

A newly synthesized Nickel (II) tyrosine complex was screened as potential antimicrobial agent against a number of medically important bacteria (Bacillus subtilis, Streptococcus ß-haemolytica, Escherichia coli, Shigella dysenterae) and fungi (Aspergillus fumigatus, Candida albicans, Aspergillus niger, Aspergillus flavus, Penicillium sp.) strains. were used for antifungal activity. The antimicrobial activity was evaluated using the Agar Disc method. Moreover, the minimum inhibitory concentration of the complexes was determined against the same pathogenic bacteria and the values were found between 4~64 µg ml (-1). Brine shrimp bioassay was carried out for cytotoxicity measurements of the complexes. The LC50 values were calculated after probit transformation of the resulting mortality data and found to be 6 µg ml (-1).

Effect of Fungicides and Plant Extracts on the Conidial Germination of Colletotrichum gloeosporioides Causing Mango Anthracnose.

In Northern Bangladesh, generally mango trees are planted as agroforest that gives higher Net Present Value (NPV) than traditional agriculture. Mango anthracnose caused by Colletotrichum gloeosporioides Penz. is seen as a very destructive and widely distributed disease, which results in poor market value. Five fungicides such as Cupravit, Bavistin, Dithane M-45, Thiovit and Redomil were tested against conidial germination of C. gloeosporioides. Dithane M-45 and Redomil were the most effective when the conidia were immersed for 10~20 minutes at 500~1000 ppm concentrations. Antifungal activities of 13 plant extracts were tested against conidial germination of C. gloeosporioides. Conidial germination of C. gloeosporioides was completely inhibited in Curcuma longa (leaf and rhizome), Tagetes erecta (leaf) and Zingiber officinales (rhizome) after 15 minutes of incubation respectively.