First charge-transfer complexes between tetrathiafulvalene and 1,2,5-chalcogenadiazole derivatives: Design,synthesis, crystal structures,electronic and electrical properties

The first charge-transfer complexes of tetrathiafulvalene (1) with 1,2,5-chalcogenadiazole derivatives, i.e. with [1,2,5]thiadiazolo[3,4-c][1,2,5]thiadiazole (2) and 3,4-dicyano-1,2,5-telluradiazole (3), were designed, prepared in the form of air and thermally stable single crystals and structurally defined by X-ray diffraction as 1·2 and 1·3₂, respectively. Starting compound 2 (effective electron acceptor with potentially broad application in the field) was synthesized by a new efficient one-pot method from 3,4-diamino-1,2,5-oxadiazole and disulfur dichloride. The electronic structure of complexes 1·2 and 1·3₂ and thermodynamics of their formation were studied by means of DFT and QTAIM calculations and UV–Vis spectroscopy. The electrical properties of single crystals of the complexes were investigated revealing semiconductor properties with an activation energy of 0.34 eV for 1·2 and 0.40 eV for 1·3₂. Polycrystalline films of the complexes displayed photoconductive effects with increased conductivity under white-light illumination.     

Relationships of Gut Microbiota Composition,Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients

Emerging evidence has suggested that dysbiosis of the gut microbiota may influence the drug efficacy of colorectal cancer (CRC) patients during cancer treatment by modulating drug metabolism and the host immune response. Moreover, gut microbiota can produce metabolites that may influence tumor proliferation and therapy responsiveness. In this study we have investigated the potential contribution of the gut microbiota and microbial-derived metabolites such as short chain fatty acids and polyamines to neoadjuvant radiochemotherapy (RCT) outcome in CRC patients. First, we established a profile for healthy gut microbiota by comparing the microbial diversity and composition between CRC patients and healthy controls. Second, our metagenomic analysis revealed that the gut microbiota composition of CRC patients was relatively stable over treatment time with neoadjuvant RCT. Nevertheless, treated patients who achieved clinical benefits from RTC (responders, R) had significantly higher microbial diversity and richness compared to non-responder patients (NR). Importantly, the fecal microbiota of the R was enriched in butyrate-producing bacteria and had significantly higher levels of acetic, butyric, isobutyric, and hexanoic acids than NR. In addition, NR patients exhibited higher serum levels of spermine and acetyl polyamines (oncometabolites related to CRC) as well as zonulin (gut permeability marker), and their gut microbiota was abundant in pro-inflammatory species. Finally, we identified a baseline consortium of five bacterial species that could potentially predict CRC treatment outcome. Overall, our results suggest that the gut microbiota may have an important role in the response to cancer therapies in CRC patients.     

Effect of Berberine Isolated from Barberry Species by Centrifugal Partition Chromatography on Memory and the Expression of Parvalbumin in the Mouse Hippocampus Proper

Neurodegenerative diseases associated with memory disturbances are important health issues occurring due to a prolonged life span. This article presents the results of a study targeting the emergence of a drug candidate with antiamnesic properties. The effect of berberine (BBR), an isoquinoline alkaloid isolated from the overground parts of Berberis sibirica Pall., on memory and expression of parvalbumin in the mouse hippocampus proper were determined. High-purity BBR was isolated by centrifugal partition chromatography from a methanolic extract from B. sibirica by using a methyl-tert-butyl ether and water (1:1 v/v) solvent system with 10 mmol/L of triethylamine and hydrochloric acid. In an in vivo study, we assessed the influence of the chronic administration of BBR on different stages of memory-related responses in mice. Our results indicated that the chronic administration of BBR in a higher dose (5 mg/kg) improves long-term memory acquisition in mice, as determined in the passive avoidance test. The hippocampal CA1–CA3 fields showed an increased number of parvalbumin-immunoreactive neurons (PV-IR) and nerve fibers as compared to the control. No significant changes in the dentate gyrus were observed between the groups. The HPLC-ESI-QTOF-MS/MS analysis of the biological material revealed the content of BBR as 363.4 ± 15.0 ng (4.11% of RSD) per brain, 15.06 ± 0.89 ng (5.91% of RSD) per hippocampus, and 54.45 ± 1.40 (4.05% of RSD) ng in 100 µL plasma. The study showed that BBR could be a factor influencing the expression of PV in hippocampal neurons. We speculate that BBR may modulate the level of Ca²⁺ in neurons and thus potentially act as a neuroprotective factor against neuronal damages.     

The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential

Background: Clinical management of ischemic events and prevention of vascular disease is based on antiplatelet drugs. Given the relevance of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) as a candidate target in thrombosis, the main goal of the present study was to identify novel antiplatelet agents within the existing inhibitors blocking PI3K isoforms. Methods: We performed a biological evaluation of the pharmacological activity of PI3K inhibitors in platelets. The effect of the inhibitors was evaluated in intracellular calcium release and platelet functional assays, the latter including aggregation, adhesion, and viability assays. The in vivo drug antithrombotic potential was assessed in mice undergoing chemically induced arterial occlusion, and the associated hemorrhagic risk evaluated by measuring the tail bleeding time. Results: We show that PI3K Class IA inhibitors potently block calcium mobilization in human platelets. The PI3K p110δ inhibitor Idelalisib inhibits platelet aggregation mediated by ITAM receptors GPVI and CLEC-2, preferentially by the former. Moreover, Idelalisib also inhibits platelet adhesion and aggregation under shear and adhesion to collagen. Interestingly, an antithrombotic effect was observed in mice treated with Idelalisib, with mild bleeding effects at high doses of the drug. Conclusion: Idelalisib may have antiplatelet effects with minor bleeding effects, which provides a rationale to evaluate its antithrombotic efficacy in humans.     

Novel Coumarin-Thiadiazole Hybrids and Their Cu(II) and Zn(II) Complexes as Potential Antimicrobial Agents and Acetylcholinesterase Inhibitors

A series of coumarin-thiadiazole hybrids and their corresponding Cu(II) and Zn(II) complexes were synthesized and characterized with the use of spectroscopic techniques. The results obtained indicate that all the coumarin-thiadiazole hybrids act as bidentate chelators of Cu(II) and Zn(II) ions. The complexes isolated differ in their ligand:metal ratio depending on the central metal. In most cases, the Zn(II) complexes are characteristic of a 1:1 ligand:metal ratio, while in the Cu(II) complexes the ligand:metal ratio is 2:1. All compounds were tested as potential antibacterial agents against Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacterial strains demonstrating activities notably lower than commercially available antibiotics. The more promising results were obtained from the assessment of antineurodegenerative potency as all compounds showed moderate acetylcholinesterase (AChE) inhibition activity     

Poly(ether-imide) and poly(ether-imide)-polydimethyl-siloxane containing isopropylidene groups

Summary A poly(ether-imide) was prepared by thermal imidization of poly(amic-acid) intermediate resulting from the solution polycondensation reaction of a bis(ether-anhydride), namely 2,2′-bis-[(3,4-dicarboxyphenoxy)phenyl]-1,4-phenylene-diisopropylidene dianhydride, with an aromatic diamine containing two isopropylidene groups, namely 4,4′-(1,4-phenylenediisopropylidene)bisaniline. A poly(ether-imide)-polydimethylsiloxane copolymer was prepared by polycondensation reaction of the same bis(ether-anhydride) with an equimolar quantity of the aromatic diamine having isopropylidene groups and a bis(aminopropyl)polydimethylsiloxane oligomer of controlled molecular weight. A solution imidization procedure was used to convert quantitatively the poly(amic-acid) intermediates to the corresponding polyimides. The polymers were easily soluble in polar organic solvents and showed good thermal stability with decomposition temperature being above 400 °C. Electrical insulating properties of poly(ether-imide)-polydimethylsiloxane copolymer film were evaluated on the basis of dielectric constant and dielectric loss and their variation with frequency and temperature.     

Heparin Modulates the Mitogenic Activity of Fibroblast Growth Factor by Inducing Dimerization of its Receptor. A 3D View by Using NMR

In vitro mitogenesis assays have shown that sulfated glycosaminoglycans (GAGs; heparin and heparan sulfate) cause an enhancement of the mitogenic activity of fibroblast growth factors (FGFs). Herein, we report that the simultaneous presence of FGF and the GAG is not an essential requisite for this event to take place. Indeed, preincubation with heparin (just before FGF addition) of cells lacking heparan sulfate produced an enhancing effect equivalent to that observed when the GAG and the protein are simultaneously added. A first structural characterization of this effect by analytical ultracentrifugation of a soluble preparation of the heparin‐binding domain of fibroblast growth factor receptor 2 (FGFR2) and a low molecular weight (3 kDa) heparin showed that the GAG induces dimerization of FGFR2. To derive a high resolution structural picture of this molecular recognition process, the interactions of a soluble heparin‐binding domain of FGFR2 with two different homogeneous, synthetic, and mitogenically active sulfated GAGs were analyzed by NMR spectroscopy. These studies, assisted by docking protocols and molecular dynamics simulations, have demonstrated that the interactions of these GAGs with the soluble heparin‐binding domain of FGFR induces formation of an FGFR dimer; its architecture is equivalent to that in one of the two distinct crystallographic structures of FGFR in complex with both heparin and FGF1. This preformation of the FGFR dimer (with similar topology to that of the signaling complex) should favor incorporation of the FGF component to form the final assemblage of the signaling complex, without major entropy penalty. This cascade of events is probably at the heart of the observed activating effect of heparin in FGF‐driven mitogenesis.     

Performance evaluation of the UVAPS: influence of physiological age of airborne bacteria and bacterial stress

This study evaluated the effect of bacterial physiology, such as physiological age and stress, on the performance of the ultraviolet aerodynamic particle sizer (UV-APS, model 3312, TSI Inc., St. Paul, MN). Intensity of the fluorescent signals was measured for three bacteria having various sensitivities to environmental stresses, Bacillus subtilus (spores and vegetative cells), Pseudomonas fluorescens, and Micrococcus luteus. The performance of the UVAPS was found to depend on the type of airborne bacteria. In addition, the fluorescence signals for stationary-phase bacteria were generally stronger than for their log-phase counterparts. These results indicated that bacterial injury due to environmental stresses has a strong influence on the measured fluorescence signals. This hypothesis was confirmed by obtaining a linear relationship between the percentage of fluorescent particles and the proportion of injured bacteria in the total population of cultivable bacteria in samples simultaneously collected with the AGI-30 impingers. This indicates that the amount of fluorophors (specifically NADH) within injured bacteria is below the UVAPS sensitivity level. The practical implications of these findings are discussed in the paper. The reported results contribute to broadening our understanding of the method and may assist in developing sampling strategies for the application of the UVAPS to various bioaerosol studies.     

Crystallization and polymorphic behaviors of cocoa butter alternatives: A review

Although cocoa butter (CB) has remarkable physical properties, its high price, growing difficulties, and increased consumption have been the main incentive to explore alternatives to replace or improve it. The potential of fats systems obtained from tropical butters, mixtures of them with vegetable oils, or marine fats as cocoa butter equivalent (CBE), extender (CBEx), substitute (CBS), replacer (CBR), or improver (CBI) have been deeply investigated and their physical chemical properties have been compared to those of CB. The TAGs composition of fats systems is a key factor that determines fats crystallization and polymorphic behaviors, and the suitability for an application. Fats with high concentrations of the TAGs StOSt, StOA, or StOB and low concentrations of POP compared to CB show some incompatibility with CB as analyzed by iso-solid diagrams and a more complex polymorphic behavior. The presence of low melting TAGs such as POO, StOO, and AOO also leads to significant differences in physical behavior compared to CB. In those fats systems, co-crystallization and polymorphic transitions of co-existing solid solutions were reported. A few of the studied fat systems may behave as CBE. However, most of them have potential as CBS, CBR, CBEx or CBI in confectionery products. Studies reported the relevance of fractionation and interesterification processes to modify TAGs composition and the need of finding the right processing conditions and additives to extend fats applications.     

Dy(III) sorption from water solutions by mesoporous silicas functionalized with phosphonic acid groups

The sorption properties towards dysprosium(III) ions of three samples of mesoporous silicas functionalized with phosphonic groups????Si(CH₂)₂P(O)(OH)₂ were studied. It was found that for the sample synthesized by spray-drying using OTAB as a template both sorption and desorption rate of Dy³⁺ ions is high, due to the defined porosity of the sorbent. Sorption of Dy³⁺ ions by bridged silsesquioxane xerogels with disordered structure is significantly hindered by diffusion processes, due to the chaotic packing of globules. Using a model for the chemical reactions, the composition of dysprosium(III) complexes with surface phosphonic groups were determined, and their formation constants were calculated. It was shown that xerogels with higher surface concentration of ligand groups (L), can form complexes DyL₃ and DyL₄ ^?. Meanwhile, the sample synthesized by spray-drying method forms only DyL₂ ⁺ and DyL₃ complexes. For this sample, complexes DyL₃ are more stable than for xerogels. So, mesoporous silica derived by spray-drying method, with defined spatial porosity and relatively low surface concentration complexation groups, is characterized by the best sorption properties towards dysprosium(III) (adsorption and desorption kinetics, the value of the static sorption capacity).