Comprehensive characterization of Epimedium-Rhizoma drynariae herb pair in rat plasma, urine, and feces metabolic profiles by UHPLC-Q-Orbitrap HRMS combined with diagnostic extraction strategy and multicomponent pharmacokinetic study by UHPLC-MS/MS.

Epimedium-Rhizoma drynariae (EP-RD) was a well-known herb commonly used to treat bone diseases in traditional Chinese medicine. Nevertheless, there was incomplete pharmacokinetic behavior, metabolic conversion and chemical characterization of EP-RD in vivo. Therefore, this study aimed to establish metabolic profiles combined with multicomponent pharmacokinetics to reveal the in vivo behavior of EP-RD. Firstly, the diagnostic product ions (DPIs) and neutral losses (NLs) filtering strategy combined with UHPLC-Q-Orbitrap HRMS for the in vitro chemical composition of EP-RD and metabolic profiles of plasma, urine, and feces after oral administration of EP-RD to rats were proposed to comprehensively characterize the 47 chemical compounds and the 97 exogenous in vivo (35 prototypes and 62 metabolites), and possible biotransformation pathways of EP-RD were proposed, which included phase I reactions such as hydrolysis, hydrogenation, dehydrogenation, hydroxylation, dehydroxylation, isomerization, and demethylation and phase II reactions such as glucuronidation, acetylation, methylation, and sulfation. Moreover, a UHPLC-MS/MS quantitative approach was established for the pharmacokinetic analysis of seven active components: magnoflorine, epimedin A, epimedin B, epimedin C, icariin, baohuoside II, and icariin II. Results indicated that the established method was reliably used for the quantitative study of plasma active ingredients after oral administration of EP-RD in rats. Compared to oral EP alone, the increase in area under curves and maximum plasma drug concentration (P < 0.05). This study increased the understanding of the material basis and biotransformation profiles of EP-RD in vivo, which was of great significance in exploring the pharmacological effects of EP-RD.

Inexpensive NaX (X = I, Br, Cl) as a halogen donor in the practical Ag/Cu-mediated decarboxylative halogenation of aryl carboxylic acids under aerobic conditions.

Versatile and practical Ag/Cu-mediated decarboxylative halogenation between readily available aryl carboxylic acids and abundant NaX (X = I, Br, Cl) has been achieved under aerobic conditions in moderate to good yields. The halodecarboxylation is shown to be an effective strategy for S-containing heteroaromatic carboxylic acid and benzoic acids with nitro, chloro and methoxyl substituents at the ortho position. A gram-scale reaction and a three-step procedure to synthesize iniparib have been performed to evaluate the practicality of this protocol. A preliminary mechanistic investigation indicates that Cu plays a vital role and a radical pathway is involved in the transformation.

Decarboxylative Halogenation and Cyanation of Electron-Deficient Aryl Carboxylic Acids via Cu Mediator as Well as Electron-Rich Ones through Pd Catalyst under Aerobic Conditions.

Simple strategies for decarboxylative functionalizations of electron-deficient benzoic acids via using Cu(I) as promoter and electron-rich ones by employing Pd(II) as catalyst under aerobic conditions have been established, which lead to smooth synthesis of aryl halides (-I, Br, and Cl) through the decarboxylative functionalization of benzoic acids with readily available halogen sources CuX (X = I, Br, Cl), and easy preparation of benzonitriles from decarboxylative cyanation of aryl carboxylic acids with nontoxic and low-cost K4Fe(CN)6 under an oxygen atmosphere for the first time.

One-dimensional Europium-coordination polymer as luminescent sensor for highly selective and sensitive detection of 2,4,6-trinitrophenol.

Three isostructural lanthanide coordination polymers (LnCPs), [Ln(L)6(DMF)]n {HL = 2-(2-formylphenoxy) acetic acid, Ln = Sm (1); Eu (2); Tb (3)} have been synthesized by solvothermal reaction and characterized. Single crystal analyses revealed that the architectures of these LnCPs own one dimensional chain which can be further packed into two-dimensional architectures by hydrogen bonds. Moreover, these LnCPs can offer strategically placed uncoordinated formyl groups, which may act as hydrogen-bond acceptor in the sensing of nitro explosives. Luminescence measurements reveal that LnCPs 2 and 3 exhibit strong luminescence in solid states. LnCP 2 shows quick, highly selective and sensitive detection of 2,4,6-trinitrophenol (TNP) with the high quenching constant (2.6 × 104 M-1) and low detection limit (3.39 µM), which indicates that LnCP 2 is more efficient than most of Eu-based coordination polymers for the sensing of TNP. Furthermore, LnCP 2 represents the first example of one-dimensional Eu-based sensors with formyl group as hydrogen-bonding site in the detection of TNP.

Methyl 2-hydr-oxy-3-nitro-benzoate.

The title compound, C(8)H(7)NO(5), assumes an approximately planar mol-ecular structure with an intra-molecular O-H⋯O hydrogen bond between the hydr-oxy and carboxyl-ate groups. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

Facile preparation of magnetic composites based on carbon nanotubes: Utilization for removal of environmental pollutants.

The preparation of multifunctional composites that combine magnetic nanoparticles and supported nanomaterials has attracted great attention for various applications. In this work, a facile method was developed for the preparation of carbon nanotube (CNT)-based magnetic composites through a one-pot oxidation method using K2FeO4 as the oxidant, which was subsequently used as the reagent to generate the Fe3O4 nanoparticles and fabricate the magnetic CNT composites. This strategy could be performed at room temperature, so it is very mild and straightforward. The properties and structure of the as-fabricated CNT-Fe3O4 composites were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and vibrating sample magnetometry. The results suggested that this approach not only generated Fe3O4 magnetic nanoparticles on the surface of the CNTs but also produced a series of functional groups. In addition, the dried CNT-Fe3O4 composites were highly dispersible in water or organic solutions, and they also had a magnetic response that could satisfy the demand for magnetic separation. Finally, we adsorbed copper ions (Cu2+) and methylene blue (MB) using the CNT-Fe3O4 composites as adsorbents. The results indicated that the obtained composites could adsorb both Cu2+ and MB effectively. Taken together, we report a novel strategy for the fabrication of magnetic carbon nanotube composites through a facile oxidation and subsequent deposition procedure. These magnetic composites show great potential for the removal of environmental pollutants.

Fabrication and biological imaging of hydrazine hydrate cross-linked AIE-active fluorescent polymeric nanoparticles.

Amphiphilic copolymers play a paramount role in the fabrication of fluorescent polymeric nanoparticles (FPNs) through the self-assembly procedure. In this work, novel hydrazine hydrate cross-linked amphiphilic poly(PEG­co­FHMA) copolymers were constructed via reversible addition-fragmentation chain transfer (RAFT) polymerization, containing an aggregation-induced emission (AIE) active hydrophobic moiety and a hydrophilic poly(ethylene glycol) (PEG) group. Different characterization techniques have been employed to confirm their successful synthesis. Due to their amphiphilic property, the resulting poly(PEG­co­FHMA) copolymers can self-assemble into FPNs in aqueous solution and form poly(PEG­co­FHMA) FPNs with size ranging from 100 to 200 nm. The investigation of photophysical properties demonstrated poly(PEG­co­FHMA) FPNs possess strong fluorescence, large Stokes shift, excellent AIE characteristic, low critical micelle concentration and remarkable photostability. Biological assay results suggested that these cross-linked AIE-active FPNs are of low toxicity and excellent cell dyeing performances. All of these features make them promising candidates for biomedical applications. As compared with typical AIE-active FPNs based on the synthetic AIE-active compounds, the novel cross-linked AIE-active FPNs based on the Schiff base is rather simple, good designable and universal. More importantly, this strategy could also be adopted for preparation of a large number of AIE-active FPNs because of the well designability of copolymers and salicylaldehyde derivatives. Thus this work will provide a novel route for preparation of multifunctional AIE-active FPNs in a rather facile manner.

[The mathematical models and research prospect of neural system dynamics].

With the development of the brain research, a new cross subject-neural system dynamics has come into being. It is based on the brain's mathematical models. In this paper, we introduce a series of neuron mathematical models which are representative and widely useful. Then we discuss them in details and in expectation of the development in these models. At last, connecting them with the complex network research, we propose some valuable research directions.

A facile strategy for fabrication of aggregation-induced emission (AIE) active fluorescent polymeric nanoparticles (FPNs) via post modification of synthetic polymers and their cell imaging.

Aggregation-induced emission (AIE) active fluorescent polymeric nanoparticles (FPNs) have recently emerged as the promising nanoprobes for biological imaging for their intensive fluorescence, good photostability, desirable biocompatibility and well designability of structure and optical properties. Herein, we proposed a novel strategy for fabrication of AIE-active FPNs through the post modification of synthetic copolymers to form Schiff base. The size, morphology, optical properties and biocompatibility as well as cell uptake behavior were evaluated in detailed. To fabricate these AIE-active FPNs, poly(PEG-co-VA) copolymers were first obtained via addition-fragmentation chain transfer polymerization using poly(ethylene glycol) methyl ether methacrylate (PEGMA) and 3-vinylaniline (VA) as the monomers. Then the AIE-active SA-poly(PEG-co-VA) FPNs were formed through the reaction between salicylaldehyde (SA) and VA. Results demonstrated that SA-poly(PEG-co-VA) FPNs possess bright fluorescence, superior photo-bleaching resistance, excellent biocompatibility and efficient cell uptake behavior. To the best of our knowledge, this is the first report for fabrication AIE-active FPNs through post modification of synthetic copolymers. The facile fabrication procedure and the remarkable features suggested that these AIE-active FPNs promising candidates for biomedical applications.

Carbohydrate restriction alters lipoprotein metabolism by modifying VLDL, LDL, and HDL subfraction distribution and size in overweight men.

To determine the effects of carbohydrate restriction (CR) with and without soluble fiber on lipoprotein metabolism, 29 men participated in a 12-wk weight loss intervention. Subjects were matched by age and BMI and randomly assigned to consume 3 g/d of either a soluble fiber supplement (n=14) or placebo (n=15) with a macronutrient energy distribution of approximately 10% carbohydrate, approximately 65% fat, and approximately 25% protein. Because the groups did not differ in any of the variables measured, all data were pooled and comparisons were made between baseline and 12 wk. After 12 wk, subjects had a mean weight loss of 7.5 kg (P<0.001), and abdominal fat was reduced by 20% (P<0.001). Plasma LDL cholesterol and triglycerides (TG) were significantly reduced by 8.9 and 38.6%, respectively. Similarly, apolipoproteins C-I (-13.8%), C-III (-21.2%) and E (-12.5%) were significantly lower after the intervention. In contrast plasma HDL-cholesterol concentrations were increased by 12% (P<0.05). Changes in plasma TG were positively correlated with reductions in large (r=0.615, P<0.01) and medium VLDL particles (r=0.432, P<0.05) and negatively correlated with LDL diameter (r=-0.489, P<0.01). Changes in trunk fat were positively correlated with medium VLDL (r=0.474, P<0.0) and small LDL (r=0.405, P<0.05) and negatively correlated with large HDL (r=-0.556, P<0.01). We conclude that weight loss induced by CR favorably alters the secretion and processing of plasma lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreased risk for atherosclerosis and coronary heart disease.

Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress.

To evaluate the effects of grape polyphenols on plasma lipids, inflammatory cytokines, and oxidative stress, 24 pre- and 20 postmenopausal women were randomly assigned to consume 36 g of a lyophilized grape powder (LGP) or a placebo for 4 wk. The LGP consisted of 92% carbohydrate and was rich in flavans, anthocyanins, quercetin, myricetin, kaempferol, and resveratrol. After a 3-wk washout period, subjects were assigned to the alternate treatment for an additional 4 wk. The placebo consisted of an equal ratio of fructose and dextrose and was similar in appearance and energy content (554 kJ) to LGP. Plasma triglyceride concentrations were reduced by 15 and 6% in pre- and postmenopausal women, respectively (P < 0.01) after LGP supplementation. In addition, plasma LDL cholesterol and apolipoproteins B and E were lower due to LGP treatment (P < 0.05). Further, cholesterol ester transfer protein activity was decreased by approximately 15% with intake of LGP (P < 0.05). In contrast to these beneficial effects on plasma lipids, LDL oxidation was not modified by LGP treatment. However, whole-body oxidative stress as measured by urinary F(2)-isoprostanes was significantly reduced after LGP supplementation. LGP also decreased the levels of plasma tumor necrosis factor-alpha, which plays a major role in the inflammation process. Through alterations in lipoprotein metabolism, oxidative stress, and inflammatory markers, LGP intake beneficially affected key risk factors for coronary heart disease in both pre- and postmenopausal women.

Fatty acids increase presenilin-1 levels and [gamma]-secretase activity in PSwt-1 cells.

Presenilin-1 (PS1) is an important determinant of the gamma-secretase activity necessary for the generation of beta-amyloid (Abeta), likely the central pathogenic molecule in Alzheimer's disease. Most presenilin is rapidly degraded, and determinants of the level of the active cleaved form are unknown. We examined the influence of fatty acids on PS1 levels and gamma-secretase activity using stably transfected CHO cells that express human PS1 and the human amyloid precursor protein. Cells cultured with 0.4 mM oleic acid (OA), with 0.1 mM linoleic acid, or with a triglyceride emulsion expressed increased PS1 and Abeta. This effect was independent of any secondary increase in cellular cholesterol. Cells cultured in 0.4 mM OA also exhibited significantly increased gamma-secretase activity. PS1 mRNA levels were unchanged, and pulse-chase experiments indicated that OA slowed presenilin holoprotein degradation. Nontransfected human neuroblastoma cells also showed increased presenilin when cultured in 0.4 mM OA. Lipids may be important biological determinants of PS1 level and gamma-secretase activity.