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- ItemSurface Plasmon Resonance Sensitivity Enhancement Based on Protonated Polyaniline Films Doped by Aluminum Nitrate(Basel : MDPI, 2022) Al-Bataineh, Qais M.; Shpacovitch, Victoria; Sadiq, Diyar; Telfah, Ahmad; Hergenröder, RolandComplex composite films based on polyaniline (PANI) doped hydrochloric acid (HCl) incorporated with aluminum nitrate (Al(NO3)3) on Au-layer were designed and synthesized as a surface plasmon resonance (SPR) sensing device. The physicochemical properties of (PANI-HCl)/Al(NO3)3 complex composite films were studied for various Al(NO3)3 concentrations (0, 2, 4, 8, 16, and 32 wt.%). The refractive index of the (PANI-HCl)/Al(NO3)3 complex composite films increased continuously as Al(NO3)3 concentrations increased. The electrical conductivity values increased from 5.10 µS/cm to 10.00 µS/cm as Al(NO3)3 concentration increased to 32 wt.%. The sensitivity of the SPR sensing device was investigated using a theoretical approach and experimental measurements. The theoretical system of SPR measurement confirmed that increasing Al(NO3)3 in (PANI-HCl)/Al(NO3)3 complex composite films enhanced the sensitivity from about 114.5 [Deg/RIU] for Au-layer to 159.0 [Deg/RIU] for Au-((PANI-HCl)/Al(NO3)3 (32 wt.%)). In addition, the signal-to-noise ratio for Au-layer was 3.95, which increased after coating by (PANI-HCl)/Al(NO3)3 (32 wt.%) complex composite layer to 8.82. Finally, we conclude that coating Au-layer by (PANI-HCl)/Al(NO3)3 complex composite films enhances the sensitivity of the SPR sensing device.
- ItemMetabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets(Basel : MDPI, 2022) Alwahsh, Mohammad; Knitsch, Robert; Marchan, Rosemarie; Lambert, Jörg; Hoerner, Christian; Zhang, Xiaonan; Schalke, Berthold; Lee, De-Hyung; Bulut, Elena; Graeter, Thomas; Ott, German; Kurz, Katrin S.; Preissler, Gerhard; Schölch, Sebastian; Farhat, Joviana; Yao, Zhihan; Sticht, Carsten; Ströbel, Philipp; Hergenröder, Roland; Marx, Alexander; Belharazem, DjedaThymomas and thymic carcinomas (TC) are malignant thymic epithelial tumors (TETs) with poor outcome, if non-resectable. Metabolic signatures of TETs have not yet been studied and may offer new therapeutic options. Metabolic profiles of snap-frozen thymomas (WHO types A, AB, B1, B2, B3, n = 12) and TCs (n = 3) were determined by high resolution magic angle spinning 1H nuclear magnetic resonance (HRMAS 1H-NMR) spectroscopy. Metabolite-based prediction of active KEGG metabolic pathways was achieved with MetPA. In relation to metabolite-based metabolic pathways, gene expression signatures of TETs (n = 115) were investigated in the public “The Cancer Genome Atlas” (TCGA) dataset using gene set enrichment analysis. Overall, thirty-seven metabolites were quantified in TETs, including acetylcholine that was not previously detected in other nonendocrine cancers. Metabolite-based cluster analysis distinguished clinically indolent (A, AB, B1) and aggressive TETs (B2, B3, TCs). Using MetPA, six KEGG metabolic pathways were predicted to be activated, including proline/arginine, glycolysis and glutathione pathways. The activated pathways as predicted by metabolite-profiling were generally enriched transcriptionally in the independent TCGA dataset. Shared high lactic acid and glutamine levels, together with associated gene expression signatures suggested a strong “Warburg effect”, glutaminolysis and redox homeostasis as potential vulnerabilities that need validation in a large, independent cohort of aggressive TETs. If confirmed, targeting metabolic pathways may eventually prove as adjunct therapeutic options in TETs, since the metabolic features identified here are known to confer resistance to cisplatin-based chemotherapy, kinase inhibitors and immune checkpoint blockers, i.e., currently used therapies for non-resectable TETs.
- ItemE/Z reversible photoisomerization of methyl orange doped polyacrylic acid-based polyelectrolyte brush films(Hoboken, NJ [u.a.] : Wiley InterScience, 2022) Al‐Bataineh, Qais M.; Telfah, Ahmad D.; Ahmad, Ahmad A.; Bani‐Salameh, Areen A.; Abu‐Zurayk, Rund; Hergenröder, RolandThe photoswitching behavior of the polyacrylic acid (PAA) doped by methyl orange (MO) brush film was investigated using spectral analysis of UV-Vis absorbance, Fourier Transformation Infrared spectroscopy, 2D electrical conductivity mapping and Atomic Force Microscopy. The kinetics and time evolution of the photoisomerization of the PAA-MO PEBs film from E-state to Z-state by UV-light irradiation, and reverse thermal relaxation to E-state was explored. The results confirm that the photoisomerization kinetics of the overall peak is the superposition of the photoisomerization kinetics of (Formula presented.) transition, low- and high-frequency of the (Formula presented.) transition bands. The E–Z transformation led to transforming the azobenzene from flat with no dipole moment to 3.0 D dipole moment. Hence, the electrical conductivity escalated accordingly. The transformation of E-state to Z-state led to the collapse of the formed brushes because of the angular rotational momentum consequent to E–Z isomerization.
- ItemOptical, electrical and chemical properties of PEO:I2 complex composite films(Heidelberg [u.a.] : Springer, 2022) Telfah, Ahmad; Al-Bataineh, Qais M.; Tolstik, Elen; Ahmad, Ahmad A.; Alsaad, Ahmad M.; Ababneh, Riad; Tavares, Carlos J.; Hergenröder, RolandSynthesized PEO:I2 complex composite films with different I2 concentrations were deposited onto fused silica substrates using a dip-coating method. Incorporation of PEO films with I2 increases the electrical conductivity of the composite, reaching a maximum of 46 mS/cm for 7 wt% I2. The optical and optoelectronic properties of the complex composite films were studied using the transmittance and reflectance spectra in the UV-Vis region. The transmittance of PEO decreases with increasing I2 content. From this study, the optical bandgap energy decreases from 4.42 to 3.28 eV as I2 content increases from 0 to 7 wt%. In addition, the refractive index for PEO films are in the range of 1.66 and 2.00.1H NMR spectra of pure PEO film shows two major peaks at 3.224 ppm and 1.038 ppm, with different widths assigned to the mobile polymer chains in the amorphous phase, whereas the broad component is assigned to the more rigid molecules in the crystalline phase, respectively. By adding I2 to the PEO, both peaks (amorphous and crystal) are shifted to lower NMR frequencies indicating that I2 is acting as a Lewis acid, and PEO is acting as Lewis base. Hence, molecular iodine reacts favorably with PEO molecules through a charge transfer mechanism, and the formation of triiodide (I3-), the iodite (IO2-) anion, I 2· · · PEO and I2+···PEO complexes. PEO:I2 complex composite films are expected to be suitable for optical, electrical, and optoelectronic applications.
- ItemGlycolytic flux control by drugging phosphoglycolate phosphatase([London] : Nature Publishing Group UK, 2022) Jeanclos, Elisabeth; Schlötzer, Jan; Hadamek, Kerstin; Yuan-Chen, Natalia; Alwahsh, Mohammad; Hollmann, Robert; Fratz, Stefanie; Yesilyurt-Gerhards, Dilan; Frankenbach, Tina; Engelmann, Daria; Keller, Angelika; Kaestner, Alexandra; Schmitz, Werner; Neuenschwander, Martin; Hergenröder, Roland; Sotriffer, Christoph; von Kries, Jens Peter; Schindelin, Hermann; Gohla, AntjeTargeting the intrinsic metabolism of immune or tumor cells is a therapeutic strategy in autoimmunity, chronic inflammation or cancer. Metabolite repair enzymes may represent an alternative target class for selective metabolic inhibition, but pharmacological tools to test this concept are needed. Here, we demonstrate that phosphoglycolate phosphatase (PGP), a prototypical metabolite repair enzyme in glycolysis, is a pharmacologically actionable target. Using a combination of small molecule screening, protein crystallography, molecular dynamics simulations and NMR metabolomics, we discover and analyze a compound (CP1) that inhibits PGP with high selectivity and submicromolar potency. CP1 locks the phosphatase in a catalytically inactive conformation, dampens glycolytic flux, and phenocopies effects of cellular PGP-deficiency. This study provides key insights into effective and precise PGP targeting, at the same time validating an allosteric approach to control glycolysis that could advance discoveries of innovative therapeutic candidates.