Functionalization of silica (II) - oxidation of cyclohexanes in the presence of functionalized silica complexed by iron and copper

Silica gel was modified with (N,N-dimethyl-3- aminopropyl)trimethoxysilane and the functionalized silica catalysts thus prepared complexed with iron and copper to produce FS-1{Fe},FS-1{Cu}. 11.2% of methylcyclohexane was oxidized in the presence of oxygen with FS-1(Fe) at 60°C. 2-Hydroxymethylcyclohexane was obtained in 59% yield. The structural differences between FS-1 (Fe)and FS-1 {Cu} are discussed.     

Thermal stability of UNEX/HCCD-PEG diluent FS-13

Phenyl trifluoromethyl sulfone (FS-13) is an inert diluent used in HCCD/PEG process for isolation and recovery of cesium and strontium from highly radioactive raffinate waste. There is no experimental data available in open literature describing pressurization due to the thermal decomposition of FS-13 at elevated temperatures. Experiments were conducted for determination of flash point and heating of FS-13 under pressurized closed-vent conditions in an adiabatic calorimeter. During adiabatic experiments, negligible pressurization was observed.     

Haptoglobin subtyping with anti-haptoglobin alpha chain antibodies

Specific antibodies against the human haptoglobin (HP) alpha chain were raised and used for immunoblotting after isoelectric focusing to determine Hp alpha subtypes in a reproducible and simplified manner. By eliminating the staining of the HP beta chain, HP alpha subtypes were visualized more precisely and simply than by previously reported methods. Subtypes of a total of 1211 sera, obtained from two different populations in Japan, were examined by the new method. Four HP alpha subtypes (HP 1S-1S,2FS-1S, 2FS-2FS and 2FS-2SS) and five subtypes combined with a new variant (HP 2FS-1V1, 2V1-1S, 2FS-2V1, 2FS-2V2 and 2FS-2V3) were observed. HP 1V1 belonged to HP alpha 1, and HP 2V1, 2V2 and 2V3 belonged to HP alpha 2, and their alleles were designated HP A*1V1, HP A*2V1, HP A*2V2 and HP A*2V3, respectively. The allele frequencies were calculated to be as follows: HP A*1S, 0.2597; HP A*1V1, 0.0004; HP A*2FS, 0.7333; HP A*2SS, 0.0008; HP A*2V1, 0.0045; HP A*2V2, 0.0008; and HP A*2V3, 0.0004. The allele frequency of HP A*2SS, which is common in the European population, is less frequent than HP A*2V1 in the Japanese population.     

Physicomechanical and Tribological Properties of Polymer Composites Filled with Lubricant-Containing Microcapsules

Polymer composite materials based on Fenilon S-2 (FS-2) heat-resistant aromatic polyamide and filled with microcapsules containing a lubricating material were developed and used for tribological purposes. FS-2 acts both as a matrix and as a material of microcapsule shells. The choice of oils suitable for preparing the composite is limited and is determined by the capability of oils to preserve lubricating properties at high temperatures of FS-2 forming, up to 320°С. The tribotechnical and physicomechanical tests of the developed composites containing microcapsules demonstrated significant improvement of the tribological characteristics of the materials relative to the initial polymer. The polymer composites filled with microcapsules form an oriented lubricating film on the friction surfaces; this film is retained under high loads for a long time.     

PVT properties of UNEX/HCCD-PEG diluent phenyl trifluoromethyl sulfone (FS-13) and experimental measurement of vapour pressure in 283.15–363.15?K range

Phenyl trifluoromethyl sulfone (FS-13) is a polar diluent, proposed in literature as an alternate to nitrobenzene, in UNEX/HCCD-PEG processes for better physical properties. Its PVT properties and accurate expression for estimation of its vapour pressure are not available in the literature. Recently PVT properties of FS-13 were estimated by authors and its vapour pressure was experimentally measured at temperatures ranging from 263.15 to 363.15 K. In this paper, results of these studies are presented.     

基于磺酸酯的荧光探针用于活细胞内过氧化氢的成像检测

基于过氧化氢（H2O2）特异性催化水解磺酸酯,设计合成了新型绿色荧光探针：荧光素二磺酸酯（FS—1）和二氯荧光素二磺酸酯（FS-2）两种螺环内酯型化合物,用于活细胞内过氧化氢的检测．探针结构由元素分析、IR、^1H NMR及^13C NMR表征．实验表明：探针FS-1和FS-2在模拟生物体系中检测过氧化氢具有良好的选择性和灵敏度,且线性范围较宽．细胞成像显示：探针FS-1和FS-2用于PMA刺激或外加不同浓度H2O2孵育的小鼠腹膜巨噬细胞均呈现明亮的绿色荧光,且能对细胞内H2O2微摩尔级浓度变化产生响应,证明两探针均具有良好的膜渗透性、高的选择性及良好的灵敏度．该方法的建立对研究生物体内H2O2的产生,H2O2导致的各种疾病机制及H2O2介导的信号转导途径具有重要的理论及实际意义．     

Development and validation of a stability-indicating RP-HPLC method for determination of atomoxetine hydrochloride in tablets

This paper describes the development of a stability-indicating RP-HPLC method for the determination of atomoxetine hydrochloride (ATX) in the presence of its degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of acid, base, oxidation, wet heat, dry heat, and photodegradation. In stability tests, the drug was susceptible to acid, base, oxidation, and dry and wet heat degradation. It was found to be stable under the photolytic conditions tested. The drug was successfully separated from the degradation products formed under stress conditions on a Phenomenex C18 column (250 x 4.6 mm id, 5 microm particle size) by using acetonitrile-methanol-0.032 M ammonium acetate (55 + 05 + 40, v/v/v) as the mobile phase at 1.0 mL/min and 40 degrees C. Photodiode array detection at 275 nm was used for quantitation after RP-HPLC over the concentration range of 0.5-5 microg/mL with a mean recovery of 100.8 +/- 0.4% for ATX. Statistical analysis demonstrated that the method is repeatable, specific, and accurate for the estimation of ATX. Because the method effectively separates the drug from its degradation products, it can be used as a stability-indicating method.     

PHOTOREACTIVATION OF ULTRAVIOLET RADIATION-INDUCED RELEASE OF ARACHIDONIC ACID FROM MARSUPIAL CELLS

Exposure of an established marsupial cell line, PtK2 (Potorous tridactylus), to ultraviolet radiation (UVR) from an FS-40 sunlamp (280-400 nm) resulted in a fluence-dependent release of radiolabeled arachidonic acid (AA) from cell membranes. Post-UVR, but not pre-UVR, exposure to photoreactivating light reversed UVR-induced pyrimidine dimers in DNA and suppressed the UVR-induced release of AA. These data indicate that DNA damage contributes to the release of AA from membrane phospholipids.     

Synthesis and Biological Activities of Simplified Analogs of the Natural PKC Ligands,Bryostatin‐1 and Aplysiatoxin

Protein kinase C (PKC) isozymes play central roles in signal transduction on the cell surface and could serve as promising therapeutic targets of intractable diseases like cancer, Alzheimer's disease, and acquired immunodeficiency syndrome (AIDS). Although natural PKC ligands like phorbol esters, ingenol esters, and teleocidins have the potential to become therapeutic leads, most of them are potent tumor promoters in mouse skin. By contrast, bryostatin‐1 (bryo‐1) isolated from marine bryozoan is a potent PKC activator with little tumor‐promoting activity. Numerous investigations have suggested bryo‐1 to be a promising therapeutic candidate for the above intractable diseases. However, there is a supply problem of bryo‐1 both from natural sources and by organic synthesis. Recent approaches on the synthesis of bryo‐1 have focused on its simplification, without decreasing the ability to activate PKC isozymes, to develop new medicinal leads. Another approach is to use the skeleton of natural PKC ligands to develop bryo‐1 surrogates. We have recently identified 10‐methyl‐aplog‐1 ( 26 ), a simplified analog of tumor‐promoting aplysiatoxin (ATX), as a possible therapeutic lead for cancer. This review summarizes recent investigations on the simplification of natural PKC ligands, bryo‐1 and ATX, to develop potential medicinal leads.     

Sulfonate-based fluorescent probes for imaging hydrogen peroxide in living cells

Based on the mechanism of H₂O₂-mediated hydrolysis of sulfonates, two fluorescein disulfonates compounds (FS-1 and FS-2) were designed and synthesized as the highly selective and sensitive fluorescent probes for imaging H₂O₂ in living cells. The probes were detected with elemental analysis, IR, ¹H NMR and ¹³C NMR. Upon reaction with H₂O₂, the probes exhibit strong fluorescence responses and high selectivity for H₂O₂ over other reactive oxygen species and some biological compounds. Furthermore, the sulfonate-based probes, as novel fluorescent reagents, are cell-permeable and can detect micromolar changes in H₂O₂ concentrations in living cells by using confocal microscopy. Supported by the National Basic Research Program of China (Grant No. 2007CB936000), the National Natural Science Funds for Distinguished Young Scholar (Grant No. 20725518), Major Program of the National Natural Science Foundation of China (Grant No. 90713019), the National Natural Science Foundation of China (Grant No. 20875057), the Natural Science Foundation of Shandong Province, China (Grant No. Y2007B02), and the Science and Technology Development Programs of Shandong Province, China (Grant No. 2008GG30003012)     

USE OF REGRESSION ANALYSIS TO ESTIMATE UV SPECTRAL IRRADIANCE FROM BROAD BAND RADIOMETER READINGS UNDER FS-40 FLUORESCENT SUNLAMPS FILTERED WITH CELLULOSE ACETATE

Abstract— Weighted and unweighted UV spectral irradiances were measured under a 2-lamp fluorescent fixture containing Westinghouse FS-40 fluorescent sunlamps filtered with (6 h aged) 0.127 mm (0.005 in.) cellulose acetate by use of newly developed broadband UV radiometers and an automated UV spectro-radiometer. Measurements were taken at 10-cm intervals between 20 and 110 cm from the lamps. Correlations were determined between sets of data measured with the broadband radiometers and the UV spectroradiometer.
By use of linear regression analyses on the weighted and unweighted spectral data, regression equations were developed for predicting UV-B irradiance (unweighted mWm-²), biologically effective UV (BUV) (weighted mWm) in the 280–320 nm (UV-B) region, UV-B sun equivalents, and incident flux density in the UV-B region in photons m-²× 10²¹ integrated over a 6-h exposure. Examination of the correlation coefficients ( r values) indicated that agreement was excellent between measured and predicted values for all comparisons (r values from 0.9972 to 0.9998).
Use of regression equations should permit accurate. rapid estimation of both weighted and unweighted UV irradiances at any location in an experimental set-up and provide a useful means for intra- and inter-laboratory comparisons of spectral measurements, made in the interagency BACER program under FS-40 fluorescent sunlamps filtered with 0.127 mm cellulose acetate (aged for 6h).     

In vitro cytotoxicity evaluation of thiourea derivatives bearing Salix sp. constituent against HK-1 cell lines

Abstract

In searching for drugs from natural product scaffolds has gained interest among researchers. In this study, a series of twelve halogenated thiourea (ATX 1-12) via chemical modification of aspirin (a natural product derivative) and evaluated for cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines, HK-1 via MTS-based colorimetric assay. The cytotoxicity studies demonstrated that halogens at meta position of ATX showed promising activity against HK-1 cells (IC₅₀ value ≤15?µM) in comparison to cisplatin, a positive cytotoxic drug (IC₅₀ value =8.9?±?1.9?µM). ATX 11, bearing iodine at meta position, showed robust cytotoxicity against HK-1 cells with an IC₅₀ value of 4.7?±?0.7?µM. Molecular docking interactions between ATX 11 and cyclooxygenase-2 demonstrated a robust binding affinity value of ?8.1?kcal/mol as compared to aspirin’s binding affinity value of ?6.4?kcal/mol. The findings represent a promising lead molecule from natural product with excellent cytotoxic activity against NPC cell lines.     

Substituting Both the N-Terminal and “Cord” Regions of a Xylanase from <Emphasis Type="Italic">Aspergillus oryzae</Emphasis> to Improve Its Temperature Characteristics

To improve the temperature characteristics of AoXyn11A, a mesophilic glycoside hydrolase family (GHF) 11 xylanase from Aspergillus oryzae CICC40186, its N-terminal and “cord” regions were selected to be substituted by means of the computer-aided analysis and calculation. In brief, one mutant, named ATX11A⁴¹, possessing the lowest root-mean-square deviation (RMSD) value was designed based on the molecular dynamics (MD) simulation by substituting the N-terminal 41 amino acids of AoXyn11A with the corresponding 42 ones of pXYL11, a thermophilic GHF11 xylanase from Thermobifida fusca. On the basis of the primary structure alignment of pXYL11 with ATX11A⁴¹ (or AoXyn11A), another mutant, named ATX11A^41/cord, was designed by substituting the cord region (⁹³GTYNPGSGG¹⁰¹) of ATX11A⁴¹ with the corresponding one (⁹³GTYRPTG⁹⁹) of pXYL11. Both mutant-encoding genes, ATx11A⁴¹ and ATx11A^41/cord, were constructed as designed theoretically by a megaprimer PCR technique and were expressed in Pichia pastoris GS115. The specific activities of recombinant (re) AoXyn11A, ATX11A⁴¹, and ATX11A^41/cord were 2916.7, 2667.6, and 2457.0 U/mg, respectively. The analysis of temperature characteristics displayed that the temperature optimum (T_opt) of reATX11A⁴¹ or reATX11A^41/cord was 65 °C, which was 15 °C higher than that of reAoXyn11A. The thermal inactivation half-life (t_1/2) values of reATX11A⁴¹ and reATX11A^41/cord at 60 °C were 55 and 83 min, respectively, whereas that of reAoXyn11A was only 18 min at 50 °C. The melting temperature (T_m) values of reAoXyn11A, reATX11A⁴¹, and reATX11A^41/cord were 54.2, 66.7, and 71.9 °C, respectively. In conclusion, the above findings indicated that the substitution of both the N-terminal and cord regions of a mesophilic AoXyn11A greatly contributed to its improved temperature characteristics.     

Preparative Isolation and Purification of Altertoxin I from an Alternaria sp. by HSCCC

Altertoxin I (ATX I) is one of the common mycotoxins produced by genus Alternaria which is a common food pathogen of fruits and grains. To prepare enough quantity of pure ATX I for further research of mutagenicity and toxicology tests, a novel method using preparative high-speed counter-current chromatography (HSCCC) was developed. The ethyl acetate crude extracts of the acetone washes obtained after fermentation of Alternaria sp. was separated using a two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (2:5:5:6, v/v). Collected fractions were analyzed by LC and identified by EI–MS and NMR analysis. The technique can isolate mg levels of the target compound per run.     

Preparative Isolation and Purification of Altertoxin I from an Alternaria sp. by HSCCC

Altertoxin I (ATX I) is one of the common mycotoxins produced by genus Alternaria which is a common food pathogen of fruits and grains. To prepare enough quantity of pure ATX I for further research of mutagenicity and toxicology tests, a novel method using preparative high-speed counter-current chromatography (HSCCC) was developed. The ethyl acetate crude extracts of the acetone washes obtained after fermentation of Alternaria sp. was separated using a two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (2:5:5:6, v/v). Collected fractions were analyzed by LC and identified by EI–MS and NMR analysis. The technique can isolate mg levels of the target compound per run.

     

Designing Dual Inhibitors of Autotaxin-LPAR GPCR Axis

The ATX-LPA-LPAR1 signaling pathway plays a universal role in stimulating diverse cellular responses, including cell proliferation, migration, survival, and invasion in almost every cell type. The ATX-LPAR1 axis is linked to several metabolic and inflammatory diseases including cancer, fibrosis, and rheumatoid arthritis. Numerous selective ATX or LPAR1 inhibitors have been developed and so far, their clinical efficacy has only been evaluated in idiopathic pulmonary fibrosis. None of the ATX and LPAR1 inhibitors have advanced to clinical trials for cancer and rheumatoid arthritis. Nonetheless, several research groups, including ours, have shown considerable benefit of simultaneous ATX and LPAR1 inhibition through combination therapy. Recent research suggests that dual-targeting therapies are superior to combination therapies that use two selective inhibitors. However, limited reports are available on ATX-LPAR1 dual inhibitors, potentially due to co-expression of multiple different LPARs with close structural similarities at the same target. In this review, we discuss rational design and future directions of dual ATX-LPAR1 inhibitors.     

Synthesis, pharmacology, and cell biology of sn-2-aminooxy analogues of lysophosphatidic acid

An efficient enantioselective synthesis of sn-2-aminooxy (AO) analogues of lysophosphatidic acid (LPA) that possess palmitoyl and oleoyl acyl chains is presented. Both sn-2-AO LPA analogues are agonists for the LPA1, LPA2, and LPA4 G-protein-coupled receptors, but antagonists for the LPA3 receptor and inhibitors of autotaxin (ATX). Moreover, both analogues stimulate migration of intestinal epithelial cells in a scratch wound assay.     

LACK OF INHIBITION OF ULTRAVIOLET RADIATION-INDUCED ORNITHINE DECARBOXYLASE ACTIVITY BY RETINOIC ACID

Abstract— Normally present at low levels, ornithine decarboxylase (ODC) activity is induced to higher levels in animal skin by such disparate agents as tumor promoter 12–0-tetradecanoylphorbol-13-acetate (TPA), UV radiation, and hair plucking. Retinoids are known to inhibit induction by TPA. Repeated applications of retinoic acid (RA) in acetone have also been reported to inhibit UV-induced ODC in hairless mice. As a preliminary study, it was of interest to know whether RA in a cream vehicle would have the same effect. Groups of Skh-hairless-1 albino mice were irradiated once with Westinghouse FS-20 lamps (0.045 Joules/cm^/). Immediately post-irradiation, RA was applied to the dorsum in different concentrations (0.001%, 0.002%, 0.02%), vehicles (cream and acetone) and on various time schedules (1–5 times). Sacrifice was by cervical dislocation 24 h later. Epidermis was obtained by mild heat separation and two epidermal sheets were pooled for each extract. In all experiments, the 70-fold increase in UV-induced ODC activity was further increased by retinoic acid by a factor ∼ 1.6. Since ODC levels are usually elevated in proliferating systems, the results are in concordance with the fact that both UV radiation and RA induce epidermal hyperplasia.     

Photoreactivity of UV-b damage in bacteriophage phi X174 DNA

Abstract— The fraction of biological damage in isolated single-strand and double-strand forms of bac-teriophage DNA resulting from pyrimidine dimers following exposure to germicidal UV (254 nm) and UV-B (280-320. nm) radiation has been compared. Radiation from a Westinghouse FS-40 sunlamp filtered through a cellulose acetate sheet was used as the UV-B radiation source. Biological damage from pyrimidine dimers was determined by measuring the survival of the viral DNA with and without photoreactivation, an enzymatic process specific for repair of pyrimidine dimers. The same fraction of biological damage in the single strand and double–strand forms of φX174 DNA is repairable by photo-reactivation following exposures to germicidal UV and UV-B radiation.     

LAMP/FILTER SYSTEMS FOR SIMULATION OF SOLAR UV IRRADIANCE UNDER REDUCED ATMOSPHERIC OZONE*

Abstract— Lamp/filter systems for simulation of solar ultraviolet irradiance corresponding to various degrees of stratospheric ozone decrease are described for use in field and growth-chamber biological experiments. In growth-chamber applications, a constant ultraviolet enhancement simulation can be achieved with a 6000 W xenon arc with glass filters. For field applications, Westinghouse FS-40 ‘sun lamps’ filtered with plastic films provide an ultraviolet supplement for use when solar altitudes exceed 40°.