The cytotoxicity of fatty acid/α‐lactalbumin complexes depends on the amount and type of fatty acid

Complexes of the milk protein, α‐lactalbumin, and the fatty acid, oleic acid, have previously been shown to be cytotoxic. Complexes of α‐lactalbumin and five different fatty acids (vaccenic, linoleic, palmitoleic, stearic, and elaidic acid) were prepared and compared to those formed with oleic acid. All complexes were cytotoxic to human promyelocytic leukemia‐derived (HL‐60) cells but to different degrees depending on the fatty acid. The amount of fatty acid per α‐lactalbumin molecule was found to correlate with the cytotoxicity; the higher the number of fatty acids per protein, the more cytotoxic the complex. Importantly, all the tested fatty acids were also found to be cytotoxic on their own in a concentration dependent manner. The cytotoxic effect of complexes between α‐lactalbumin and linoleic acid, vaccenic acid, or oleic acid was further investigated using flow cytometry and found to induce cell death resembling apoptosis on Jurkat cells. Practical applications: Cytotoxic complexes of α‐lactalbumin and several different fatty acids could be produced. The cytotoxicity of all the variants is similar to that previously determined for α‐lactalbumin/oleic acid complexes.     

Extraction Behavior of Americium and Curium on Selected Extraction Chromatography Resins from Pure Acidic Matrices

Due to the similar chemical properties between the neighboring trivalent actinide elements americium and curium, their extraction behavior is often perceived as indistinguishable. In this work, the characterization of seven extraction chromatography resins (TEVA, TRU, DGA(N), Actinide, Ln, Ln2, and Ln3) for these trivalent actinides from acidic matrices (HNO₃, HCl, and HBr) has provided some evidence to the contrary. In most cases, Am(III) and Cm(III) exhibit identical extraction properties. However, separation is possible with TRU and DGA(N) resins as demonstrated in this study. The extraction shows a strong dependency on the specific anion in solution that follows the order NO₃^?>Br^?>Cl^?.     

Voltage polarity dependent current paths through polycrystalline ZnO varistors

Due to the scatter of properties of individual grain boundaries, a scatter of the behavior of low-voltage varistor components and asymmetric current–voltage characteristics with respect to the electrical field direction is observed. Using complementary methods (thermography, scanning surface probe microscopy, electron back-scattered diffraction), we investigated the grain boundary behavior of Praseodymium type varistors. Measurements on the relevant grain boundaries revealed a newly observed effect: dependent on the field direction, the main current flows via different spatial paths.     

New inhibitors of the Tat-TAR RNA interaction found with a "fuzzy" pharmacophore model

TAR RNA is a potential target for AIDS therapy. Ligand-based virtual screening was performed to retrieve novel scaffolds for RNA-binding molecules capable of inhibiting the Tat-TAR interaction, which is essential for HIV replication. We used a "fuzzy" pharmacophore approach (SQUID) and an alignment-free pharmacophore method (CATS3D) to carry out virtual screening of a vendor database of small molecules and to perform "scaffold-hopping". A small subset of 19 candidate molecules were experimentally tested for TAR RNA binding in a fluorescence resonance energy transfer (FRET) assay. Both methods retrieved molecules that exhibited activities comparable to those of the reference molecules acetylpromazine and chlorpromazine, with the best molecule showing ten times better binding behavior (IC50 = 46 microM). The hits had molecular scaffolds different from those of the reference molecules.     

Aqueous heterophase polymerization of styrene—a study by means of multi-angle laser light scattering

An online multi-angle laser light scattering study of ab initio surfactant-free styrene emulsion polymerization reveals unexpected results regarding the development of the dispersity during the whole reaction starting from mixing styrene and water at reaction temperature. The experimentally observed change in the dispersity, which is an indirect measure of the average characteristic size of the colloidal objects, allows the identification of three characteristic intervals. During interval A the equilibration of styrene in water is characterized by the formation of styrene domains, which increase in number and size until an equilibrium state is reached. This means that there is virtually no homogeneous/molecular styrene in water solution but rather nanodroplets of about 200 nm in diameter (assuming spherical shape) are formed. During interval B, after initiation of the polymerization and particle formation, the dispersity increases again as the average size decreases and the number of scattering objects increases. The polymer particles suck up the monomer from the monomer nanodroplets, which leads to the disappearance of the nanodroplets and to a decrease in the average size. During interval C the average size increases again due to the predominantly growth of the polystyrene particles.     

Impact of Spatially Heterogeneous Trop-2 Expression on Prognosis in Oral Squamous Cell Carcinoma

Oral cancer often presents with aggressive behavior and a high risk of recurrence and metastasis. For oral squamous cell carcinoma (OSCC), which is the most frequent histological subtype, therapy strategies include surgery, radiation therapy, chemotherapy, immune checkpoint inhibitors, and EGFR inhibitors. Recently, a Trop-2 antibody-drug conjugate (ADC) has been approved in the United States of America for the treatment of advanced triple-negative breast cancer. However, this ADC has also been tested in other solid tumors including head & neck squamous cell carcinoma. The prognostic impact of Trop-2 has already been reported for several cancers. We studied the prognostic influence of Trop-2 protein expression on OSCC patients’ survival. The cohort comprised n = 229 OSCC patients with available archived tumor tissue and corresponding non-neoplastic oral mucosa tissue. Using immunohistochemistry, we investigated Trop-2 expression in both the central and peripheral regions of each tumor and in corresponding non-neoplastic oral mucosa. In patients suffering from OSCC with combined high central and low peripheral Trop-2 expression, five-year overall survival (OS) was 41.2%, whereas 55.6% of OSCC patients who presented lower central and/or higher peripheral tumoral Trop-2 expression were alive after five years (p = 0.075). In multivariate Cox regression, the expression pattern of high central tumoral and lower peripheral Trop-2 expression was significantly correlated with impaired OS (HR = 1.802, 95%-CI: 1.134–2.864; p = 0.013) and recurrence-free survival (RFS) (HR = 1.633, 95%-CI: 1.042–2.560; p = 0.033), respectively, when adjusting for co-variables. Hence, Trop-2 may serve as an independent prognostic biomarker in OSCC. In subsequent studies, the pathophysiological meaning of downregulated Trop-2 expression in the OSCC periphery has to be analyzed.     

A ¹⁸F-labeled fluorobutyl-substituted spirocyclic piperidine derivative as a selective radioligand for PET Imaging of sigma₁ receptors

In this study, we synthesized and evaluated a new spirocyclic piperidine derivative 3 , containing a 4‐fluorobutyl side chain, as a PET radioligand for neuroimaging of σ₁ receptors. In vitro, compound 3 displayed high affinity for σ₁ receptors (K_i=1.2 nM ) as well as high selectivity. [¹⁸F] 3 radiosynthesis was performed from the corresponding tosylate precursor, with high radiochemical yield (45–51 %), purity (>98 %), and specific activity (>201 GBq μmol^?1). Metabolic stability of [¹⁸F] 3 in the brain of CD‐1 mice was verified, and no penetration of peripheral radiometabolites into the cerebral tissue was observed. Results of ex vivo autoradiography revealed that the distribution of [¹⁸F] 3 in the brain corresponded to regions with high σ₁ receptor density. The highest region‐specific total‐to‐nonspecific ratio was determined in the facial nucleus (4.00). Biodistribution studies indicated rapid and high levels in brain uptake of [¹⁸F] 3 (2.2 % ID per gram at 5 min p.i.). Pre‐administration of haloperidol significantly inhibited [¹⁸F] 3 uptake into the brain and σ₁ receptor‐expressing organs, further confirming in vivo target specificity.     

Combined TPS, XPS, EXAFS, and NO-TPD study of the sulfiding of Mo/Al2O3

The sulfiding of Mo/Al₂O₃ in H₂S/Ar versus in H₂S/H₂ has been studied by temperature-programmed sulfiding (TPS), X-ray photon electron spectroscopy (XPS), extended X-ray absorption fine structure (EXAFS), and temperature-programmed desorption of NO (NO-TPD). All the applied techniques agree on the sulfur content in the sulfided catalysts and the findings are in accord with a model for the H₂S production reaction. The nucleation and growth of well-ordered MoS₂ clusters are probed by XPS during sulfiding with and without the presence of hydrogen. The resulting dispersion of the MoS₂ phase is evaluated on the basis of XPS, EXAFS, and NO-TPD, and is found to be highest when the sulfiding occurs in the presence of hydrogen.     

Comparative performance of carbon nanotube and nanoclay on thermal properties and flammability behavior of amorphous polyamide/SEBS blend

Multiwall carbon nanotubes (CNT) or montmorillonite clay (MMT-30B) were added to a poly(hexamethylene isophthalamide-co-terephthalamine) (an amorphous polyamide - aPA) and styrene-ethylene/butylene-styrene graphitized with maleic anhydride (SEBS) blend, in different concentrations, in order to investigate the morphology, thermal properties and flammability behavior. Different nanoparticle localizations in the phase blend were observed through transmission electronic microscopy. CNT nanoparticles are localized in SEBS phase, and MMT-30B nanoparticles in aPA phase. No significant changes were observed on transition temperatures and thermal stability with both nanoparticle additions. However, a slight increase on storage modulus for clay nanocomposites and a slight reduction for carbon nanotube nanocomposites were observed, due to their different phase localizations. Regarding flammability, CNT nanocomposites showed better performance as a flame retardant when compared to samples with MMT-30B. Although the MMT-30B nanocomposites could not be classified according to the UL-94 criteria, no dripped flaming particles were observed, due to the a char barrier formation on the polymer surface. The CNT nanocomposites were classified according to the UL-94 criteria as V-2. The CNT's selective localization on the SEBS phase decreases its heat-release rate, but no interconnected network structure was formed in the matrix to suppress the dripping flaming particles.     

Lignin from Annual Plants as Raw Material Source for Flavors and Basic Chemicals

The enzymatic conversion of lignins, possibly in combination with electrochemical oxidation, makes aromatics such as syringol, guaiacol, vanillin and catechol available in the qualities required by the fragrance industry. The lignins were obtained by soda digestion from wheat straw and Miscanthus, characterized and then converted with laccases. The overall yield amounted up to 9 wt % with a product spectrum confined to four substances. Catechol was the major product, with a fraction of ≈75 %. It can easily be isolated by extraction with acetone.