Effect of Ions and Sequence Variants on the Antagonist Binding Properties of the Histamine H1 Receptor

The histamine H₁ receptor (H₁R) is a G protein-coupled receptor (GPCR) and represents a main target in the treatment of allergic reactions as well as inflammatory reactions and depressions. Although the overall effect of antagonists on H₁ function has been extensively investigated, rather little is known about the potential modulatory effect of ions or sequence variants on antagonist binding. We investigated the dynamics of a phosphate ion present in the crystal structure and of a sodium ion, for which we determined the position in the allosteric pocket by metadynamics simulations. Both types of ions exhibit significant dynamics within their binding site; however, some key contacts remain stable over the simulation time, which might be exploited to develop more potent drugs targeting these sites. The dynamics of the ions is almost unaffected by the presence or absence of doxepin, as also reflected in their small effect (less than 1 kcal·mol⁻¹) on doxepin binding affinity. We also examined the effect of four H₁R sequence variants observed in the human population on doxepin binding. These variants cause a reduction in doxepin affinity of up to 2.5 kcal·mol⁻¹, indicating that personalized medical treatments that take into account individual mutation patterns could increase precision in the dosage of GPCR-targeting drugs.     

Effects of pretreatments on colour alterations of litchi during drying and storage

The objective of this research was to study the effect of osmotic pretreatment with combined anti-browning agents (acid, glycerol and/or trehalose) on the colour characteristics of dried litchi after drying and during 5 months of storage compared to samples without pretreatment. The pretreated samples showed good inhibition of polyphenol oxidase activity when compared with the control, while the total phenolic contents in the dried products were not reduced. The results demonstrated that water activity, lightness difference, chroma, degree of browning (DB), and 5-hydroxymethylfurfural values of all pretreated samples increased, while hue angle decreased with storage time. Samples pretreated with glycerol showed the best potential for browning retardation, followed by glycerol combined with trehalose, and trehalose, respectively. In addition, the colour parameters were used to calculate the luminescence values, representing the data in grey scale, which were correlated with a non-enzymatic browning index. The results showed grey value could be adequately used to represent the DB of dried litchi with r ² value of 0.92.     

Hydrogen microscopy – Distribution of hydrogen in buckled niobium hydrogen thin films

Hydrogen absorption in thin metal films clamped to rigid substrates results in mechanical stress that changes the hydrogen's chemical potential by Δμ_H(σ) = −1.124σ kJ/mol_H for σ measured in [GPa]. In this paper we show that local stress relaxation by the detachment of niobium hydrogen thin films from the substrate affects the chemical potential on the local scale: using coincident proton–proton scattering at a proton microprobe, the hydrogen concentration is determined with μm resolution, revealing that hydrogen is not homogenously distributed in the film. The local hydrogen solubility of the film changes with its local stress state, mapping the buckled film fraction. In niobium hydrogen thin films loaded up to nominal concentrations in the two-phase coexistence region, the clamped film fraction remains in the solid solution phase, while the buckles represent the hydride phase. These results are compared to a simple model taking the stress impact on the chemical potential into account.     

Glycosidase inhibitory phenolic compounds from the seed of Psoralea corylifolia

The seeds of Psoralea corylifolia were extracted into five different polar solvents: chloroform, 50% ethanol in water, ethanol, methanol and water. All extracts were evaluated for glycosidase inhibitory activity. The chloroform extract (CE) showed the lowest IC₅₀ values against α-glucosidase (82.9 μg/ml) and α-mannosidase (132 μg/ml). Chromatography of CE yielded nine phenolic compounds which were identified as isovabachalcone (1), 4′-O-methylbavachalcone (2), isobavachromene (3), corylifolin (4), bavachinin (5), psoralidin (6), neobavaisoflavone (7), corylifol A (8), and bakuchiol (9). All isolated compounds, apart from compound 5, possessed α-glucosidase inhibitory activities. Among them, compounds 6–8 exhibited potent inhibition with IC₅₀s of 13.7, 27.7 and 11.3 μM, respectively. Furthermore, compounds 2 and 6 showed α-mannosidase inhibitory activity. Mechanistic analysis of their inhibition modes against α-glucosidase showed that compounds (6 and 7) were noncompetitive, whereas compound 8 was mixed. Furthermore, the most active glycosidase inhibitors (2, 6–8) were proven to be present in the native seed in high quantities by an HPLC chromatogram.     

Peptide Bioconjugates of Electron‐Poor Metallocenes: Synthesis,Characterization, and Anti‐Proliferative Activity

We report the synthesis of metallocene compounds Cp₂M with two different electron‐withdrawing substituents on both cyclopentadienyl rings (hexafluoroacetone (HFA) and chlorobenzoyl ( 1 – 5 ); HFA and COOH ( 6 and 7 ), M=Fe or Ru). The COOH‐containing derivatives were used to synthesize peptide bioconjugates with enkephalin ( 8 and 9 ) and neurotensin ( 10 and 11 ) as well as fluorescein‐labeled neurotensin ( 12 ). All the molecules were fully characterized, including X‐ray structures for 6 and 7 . The physicochemical properties (lipophilicity and electrochemistry) and cytotoxicity on MCF‐7, HT‐29, and PT‐45 cancer cells were evaluated for selected compounds. Electrochemical investigation by cyclic voltammetry revealed that all bis‐substituted metallocenes are up to 300 mV harder to oxidize compared to the monosubstituted 2‐ferrocenylhexafluoropropan‐2‐ol (FcHFA: Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =214 mV; disubstituted derivatives: up to Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =512 mV; both vs. FcH^0/+). For the bis‐substituted compounds, log P determinations by RP‐HPLC showed increased lipophilicity in comparison to the monosubstituted FcHFA and RcHFA. Cellular uptake was investigated by fluorescence microcopy, and this revealed endosomal entrapment for 12 .     

Produktschonende Betriebs‐ und Designparameter von Wärmeübertragern für temperaturempfindliche Prozessströme

To allow the calculation of product degradation rates as extension to the currently used thermotechnical design calculations for heat exchangers, a volume‐related, reaction‐kinetic approach was developed. Therefore, a model system was selected and the product protection design parameters were determined for a lab‐scale heat exchanger with the help of simulations. The validation was demonstrated in an experiment. Additionally, the product‐protecting operating parameters for the heat exchanger were calculated with a technically relevant set of compounds.     

Li-intercalation behaviour of vanadium oxide thin film prepared by thermal oxidation of vanadium metal

In order to produce thin films of crystalline V₂O₅, vanadium metal was thermally oxidised at 500 °C under oxygen pressures between 250 and 1000 mbar for 1-5 min. The oxide films were characterised by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), X-ray diffraction (XRD) and Rutherford backscattering spectrometry (RBS). The lithium intercalation performance of the oxide films was investigated by cyclic voltammetry (CV), chronopotentiometry and electrochemical impedance spectroscopy (EIS). It was shown that the composition, the crystallinity and the related lithium intercalation properties of the thin oxide films were critically dependent on the oxidation conditions. The formation of crystalline V₂O₅ films was stimulated by higher oxygen pressure and longer oxidation time. Exposure for 5 min at 750 mbar O₂ at 500 °C resulted in a surface oxide film composed of V₂O_5, and consisting of crystallites up to 200 nm in lateral size. The thickness of the layer was about 100 nm. This V₂O₅ oxide film was found to have good cycling performance in a potential window between 3.8 and 2.8 V, with a stable capacity of 117 ± 10 mAh/g at an applied current density of 3.4 μA/cm². The diffusion coefficients corresponding to the two plateaus at 3.4 and 3.2 V were determined from the impedance measurements to (5.2 and 3.0) × 10⁻¹³ cm² s⁻¹, respectively. Beneath the V₂O₅ layer, lower oxides (mainly VO₂) were found close to the metal. At lower oxygen pressure and shorter exposure times, the oxide films were less crystalline and the amount of V⁴⁺ increased in the surface oxide film, as revealed by XPS. At intermediate oxygen pressures and exposure times a mixture of crystalline V₂O₅ and V₆O₁₃ was found in the oxide film.     

康复花园

20世纪50年代后,美国日渐泛滥程式化的医疗建筑设计,产生了很多负面影响,一种以病人为本的全新设计理念,在户外辅助治疗的"康复花园"于90年代开始出现.介绍了康复花园的15种设计原则,这些原则有源于经验的,也有基于常识的,是目前所知的最好的康复花园的设计原则,能带来积极的康复效果.现在西方国家的设计师们运用康复花园的经验和理念,在医疗诊断的基础上针对特殊病人对花园的要求设计花园.还有专门为成人和儿童生理复原、精神治疗、老年痴呆、烧伤、艾滋和癌症患者建造的花园等,有很多领域有待深八研究.     

The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.     

新型COCOON手动变形机

介绍了COCOON手动变形机的特点.COCOON采用ATT和导丝盘等新部件,变形加工效率提高,通过节能注重对自然资源的节约.COCOON变形机达到了新的水平,它能使DTY加工商和下游加工商都受益.