Extensive metabolism of flavonoids relevant to their potential efficacy on Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder, the incidence of which is climbing with ever-growing aged population, but no cure is hitherto available. The epidemiological studies unveiled that chronic intake of flavonoids was negatively associated with AD risk. Flavonoids, a family of natural polyphenols widely distributed in human daily diets, were readily conjugated by phase II drug metabolizing enzymes after absorption in vivo, and glucuronidation could occur in 1 min following intravenous administration. Recently, as many as 191 metabolites were obtained after intragastric administration of a single flavonoid, indicating that other bioactive metabolites, besides conjugates, might be formed and account for the contradiction between efficacy of flavonoids in human or animal models and low systematic exposure of flavonoid glycosides or aglycones. In this review, metabolism of complete 68 flavonoid monomers potential for AD treatment, grouped in flavonoid O-glycosides, flavonoid aglycones, flavonoid C-glycosides, flavonoid dimers, flavonolignans and prenylated flavonoids according to their common structural elements, respectively, has been systematically retrospected, summarized and discussed, including their unequivocally identified metabolites, metabolic interconversions, metabolic locations, metabolic sites (regio- or stereo-selectivity), primarily involved metabolic enzymes or intestinal bacteria, and interspecies correlations or differences in metabolism, and their bioactive metabolites and the underlying mechanism to reverse AD pathology were also reviewed, providing whole perspective about advances on extensive metabolism of diverse potent flavonoids in vivo and in vitro up to date and aiming at elucidation of mechanism of actions of flavonoids on AD or other central nervous system (CNS) disorders.

Synthesis of fully porous silica microspheres with high specific surface area for fast HPLC separation of intact proteins and digests of ovalbumin.

Fully porous silica microspheres (FPSM) with high specific surface area and hierarchical pore as matrix for HPLC were prepared. First, the porous silica nanospheres with controllable particle size and pore diameter were successfully synthesized using a dual-templating approach, the pore size of nanospheres can be increased to 18.4 nm by changing the molar ratios of octyltrimethylammonium bromide (TOMAB) and cetyltrimethyl ammonium bromide (CTAB), which is suitable for separation and analysis of biomolecules without pore enlargement. Then, the micron FPSM with hierarchical pore were synthesized by polymerization-induced colloid aggregation (PICA) using the porous nanospheres as a silicon source, which has a large mesoporous structure (35.2 nm) and high specific surface area (560 m2 g-1). Subsequently, the FPSM modified with octadecyltrichlorosilane were studied as stationary phase for separation of cytochrome C, lysozyme, ribonuclease A, and ovalbumin, bovine serum albumin, and the baseline separation of five proteins was achieved within 1 min. The prepared column was also applied to the fast separation of digests of ovalbumin, and more chromatographic peaks were obtained compared to a commercial column under the same gradient elution conditions. In addition, the static-binding capacity of the functionalized FPSM for bovine serum albumin (BSA) was measured to be 276 mg g-1, which was nearly twice the static adsorption given in literature. Therefore, these FPSM with high specific surface area and hierarchical pore structure are expected to have great potential for the separation of complex biological samples using HPLC. Graphical abstract A synthetic strategy was provided towards FPSM with hierarchical pores and high specific surface area using porous nanospheres as silicon source. The outstanding performance of the FPSM is that it has a high specific surface area while maintaining a large mesoporous size, which overcomes the disadvantage of sacrificing the specific surface area when increasing the pore size of porous silica microspheres prepared by using the traditional PICA method.

One-pot synthesis of SiO2@SiO2 core-shell microspheres with controllable mesopore size as a new stationary phase for fast HPLC separation of alkyl benzenes and ß-agonists.

Monodisperse SiO2@SiO2 core-shell silica microspheres (CSSM) with enlarged mesopores perpendicular to the particles surface were prepared using a dual-templating approach. With cetyltrimethyl ammonium bromide as the template and octyltrimethyl ammonium bromide as an auxiliary chemical, the pore size can be enlarged from 2.6 to 10.6 nm. The average shell thickness can be increased from 31 nm to 97 nm by adjusting the concentrations of the surfactants under continuous addition of tetraethyl orthosilicate. After coating twice, the resulting CSSM has a uniform mesoporous shell of about 198 nm thickness and a narrow pore size distribution. The CSSM were then modified with octadecyltrichlorosilane to give a material referred to as CS-C18. It was evaluated by separating the mixture of methylbenzene (toluene), ethylbenzene, n-propylbenzene, n-butylbenzene, n-amylbenzene and hexylbenzene. The baseline separation of the six alkyl benzenes is achieved within 2 min. Compared to a commercial column of type BEH-C18, CS-C18 shows a faster and better separation even at lower back pressure. It was also applied to the fast separation of benzo[a]pyrene, salbutamol, ractopamine and clenbuterolin residues in pork samples. The high column efficiency and better reproducibility suggest that the CSSM can be used as a matrix for fast separation and analysis of several kinds of small analytes. Graphical abstract A dual-templating approach was utilized to produce the core shell microsphere with controllable mesopore channels by using hexadecyltrimethylammonium bromide (CTAB) as the template and trioctylmethylammonium bromide (TOMAB) as an auxiliary chemical to enlarge the size of CTAB micelles.

Preparation of a weak anion exchange/hydrophobic interaction dual-function mixed-mode chromatography stationary phase for protein separation using click chemistry.

In this study, 3-diethylamino-1-propyne was covalently bonded to the azide-silica by a click reaction to obtain a novel dual-function mixed-mode chromatography stationary phase for protein separation with a ligand containing tertiary amine and two ethyl groups capable of electrostatic and hydrophobic interaction functionalities, which can display hydrophobic interaction chromatography character in a high-salt-concentration mobile phase and weak anion exchange character in a low-salt-concentration mobile phase employed for protein separation. As a result, it can be employed to separate proteins with weak anion exchange and hydrophobic interaction modes, respectively. The resolution and selectivity of the stationary phase were evaluated in both hydrophobic interaction and ion exchange modes with standard proteins, respectively, which can be comparable to that of conventional weak anion exchange and hydrophobic interaction chromatography columns. Therefore, the synthesized weak anion exchange/hydrophobic interaction dual-function mixed-mode chromatography column can be used to replace two corresponding conventional weak anion exchange and hydrophobic interaction chromatography columns to separate proteins. Based on this mixed-mode chromatography stationary phase, a new off-line two-dimensional liquid chromatography technology using only a single dual-function mixed-mode chromatography column was developed. Nine kinds of tested proteins can be separated completely using the developed method within 2.0 h.

Identification of ginkgolic acid (15:1) metabolites in rats following oral administration by high-performance liquid chromatography coupled to tandem mass spectrometry.

1. In this article, metabolites of ginkgolic acid (GA) (15:1) in rats plasma, bile, urine and faeces after oral administration have been investigated for the first time by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) with the aid of on-line hydrogen/deuterium (H/D) exchange technique and ß-glucuronidase hydrolysis experiments. 2. After oral administration of GA (15:1, M0) to rats at a dose of 10 mg/kg, it was found that metabolites M1-M5 together with parent compound (M0) existed in rat plasma; parent compound (M0) and metabolites M2-M5 were observed in rat bile, and parent compound (M0) with metabolites M1 and M2 were discovered in rat faeces, and there was no parent compound and metabolite detectable in rat urine. 3. Two oxidative metabolites of GA (15:1, M0) were identified as 2-hydroxy-6-(pentadec-8-enyl-10-hydroxy) benzoic acid (M1) and 2-hydroxy-6-(pentadec-8-enyl-11-hydroxy-13-carbonyl) benzoic acid (M2), respectively. Metabolites M3, M4 and M5 were identified as the mono-glucuronic acid conjugates of parent compound (M0), M1 and M2, respectively. 4. The results indicated that M1 and M2 with parent compound (M0) were mainly eliminated in faeces and three glucuronide metabolites (M3, M4 and M5) excreted in bile as the predominant forms after oral administration of GA (15:1) to rats.

Analyte-triggered cascade signal amplification strategy for highly sensitive detection of iodate in table salt with dual-readout signals.

A novel and highly sensitive upconversion fluorescence and colorimetric dual readout iodate (IO3-) nanosensor system was constructed by using both the outstanding optical performance of NaYF4:Yb, Tm upconversion nanoparticles (UCNPs) and the analyte-triggered cascade signal amplification (CSA) technique. The construction of the sensing system consisted of three processes. First, IO3- oxidized o-phenylenediamine (OPD) to diaminophenazine (OPDox), while IO3- was reduced to I2. Second, the generated I2 can further oxidize OPD to OPDox. This mechanism has been verified by 1H NMR spectra titration analysis and HRMS measurement, which effectively improves the selectivity and sensitivity of the measurement of IO3-. Third, the generated OPDox can effectively quench the fluorescence of UCNPs via the inner filter effect (IFE), realize analyte-triggered CSA, and allow quantitative determination of IO3-. Under the optimized conditions, the fluorescence quenching efficiency showed a good linear relationship to IO3- concentration in the range of 0.06-100 µM, and the detection limit reached 0.026 µM (3RSD/slope). Moreover, this method was applied to detect IO3- in table salt samples, yielding satisfactory determination results with excellent recoveries (95.5-105%) and high precision (RSD <5.5%). These results suggest that the dual-readout sensing strategy with well-defined response mechanisms has promising application prospects in physiological and pathological studies.

Two-dimensional lateral anatase-rutile TiO2 phase junctions with oxygen vacancies for robust photoelectrochemical water splitting.

Exploiting the photoelectrode materials with broad solar light response, high-efficient separation of photogenerated charges and abundant active sites is extremely vital yet enormously challenging. Herein, an innovative two-dimensional (2D) lateral anatase-rutile TiO2 phase junctions with controllable oxygen vacancies perpendicularly aligned on Ti mesh is presented. Our experimental observations and theoretical calculations corroborate explicitly that the 2D lateral phase junctions together with three-dimensional arrays not only exhibit the high-efficient photogenerated charges separation guaranteed by the build-in electric field at the side-to-side interface, but also furnish enriching active sites. Moreover, the interfacial oxygen vacancies generate new defect energy levels and serve as electron donors, hence extending visible light response and further accelerating the separation and transfer of photogenerated charges. Profiting from these merits, the optimized photoelectrode yield a pronounced photocurrent density of 1.2 mA/cm2 at 1.23 V vs. RHE with Faradic efficiency of 100%, which is approximately 2.4 times larger than that of pristine 2D TiO2 nanosheets. Furthermore, the incident photon to current conversion efficiency (IPCE) of the optimized photoelectrode is also boosted within both ultraviolet and visible light regions. This research is envisioned deliver the new insight in developing the novel 2D lateral phase junctions for PEC applications.

The intrinsic enzyme mimetic activity of platinum oxide for biosensing of glucose.

Given the enzymatic properties and the oxidized surface of Pt nanomaterials, we demonstrated the intrinsic oxidase-like and peroxidase-like activities of platinum oxide (PtO2). The surface clean PtO2 nanoparticles with high water dispersibility were synthesized by a simple and green method. X-ray diffraction (XRD) and X-ray photoelectron spectra (XPS) results demonstrated that the prepared PtO2 nanoparticles mainly consisted of Pt (Ⅳ) state without Pt(0) chemical state. The enzymatic activity of PtO2 nanoparticles was verified by catalytic oxidation of several chromogenic substrates. Catalytic mechanism analysis suggested that PtO2 nanopartiles acted as peroxidase and oxidase enzyme mimics by promoting the generation of the reactive oxygen species (ROS). By combining glucose oxidase, a colorimetric assay for glucose detection was developed with the limit of detection of 10.8 µM. The successful application of the proposed detection assay in human serum samples demonstrated the promising practical application in clinical diagnosis, pharmacy and food.

pH-dependent selective separation of acidic and basic proteins using quaternary ammoniation functionalized cysteine-zwitterionic stationary phase with RPLC/IEC mixed-mode chromatography.

In this paper, a cysteine-functionalized zwitterionic stationary phase (Cys-silica) was prepared based on the "thiol-ene" click chemistry between cysteine and vinyl-functionalized silica, and was further modified with bromoethane, 1-bromooctane and 1-bromooctadecane, respectively, to obtain a series of quaternary ammoniation-functionalized stationary phases (Cys-silica-Cn, n = 2, 8 and 18). These zwitterionic stationary phases were regarded as reversed-phase/ion-exchange (RP/IEC) mixed-mode chromatography (MMC) stationary phases for protein separation. The retention behaviors of proteins on these zwitterionic stationary phases were carefully investigated. The results indicated that the retentions of acidic and basic proteins on these zwitterinonic stationary phases were significantly influenced by the acetonitrile and salt concentrations, pH of mobile phase as well as the hydrophobicity of the ligand. The separation selectivity of proteins on these zwitterionic stationary phases strongly depended on the pH value of mobile phase. The baseline separation of 6 kinds of basic proteins can be achieved at pH 8.0 using Cys-silica-C2 or Cys-silica-C8 column, and 5 kinds of acidic proteins can also be separated completely at pH 4.0 with Cys-silica-C2 column. Moreover, owing to the quaternary ammoniation-functionalization on Cys-silica by using appropriately hydrophobic bromoalkanes, the selectivity and separation efficiency of proteins can be enhanced greatly. As a result, the acidic and basic proteins can be separated completely step by step from the complex sample by adjusting pH of mobile phase using a single Cys-silica-C2 column, which illustrates that the cysteine-functionalized zwitterionic stationary phase has a great potential for protein separation.

Preparation of Core-Shell Silica Microspheres with Controllable Shell Thickness for Fast High Performance Liquid Chromatography Separation of Alkyl Benzenes and Intact Proteins.

As it is difficult to prevent secondary nucleation and agglomeration during the preparation of core-shell silica microspheres, these issues have been successfully resolved in this study using template-dissolution-induced redeposition. The non-porous particles are transformed into core-shell silica microspheres (CSSMs) in the presence of cetyltrimethylammonium bromide and octyltrimethylammonium bromide under basic conditions. The shell thickness and pore sizes of the CSSMs are controlled by adjusting the etching time and molar ratio of the template, respectively. The CSSMs are modified using octadecyltrimethylammonium chloride to separate the mixture of alkyl benzenes, and a high column separation efficiency is achieved within two minutes. The CSSMs are used for the separation and analysis of proteins and the digests of bovine serum albumin. The chromatographic column packed with core-shell particles affords a significantly higher separation efficiency than the commercial column. Therefore, as a chromatographic stationary phase, these core-shell particles can potentially be used for the fast separation of proteins, small solutes, and complex samples.

Facile synthesis of carbon dots from wheat straw for colorimetric and fluorescent detection of fluoride and cellular imaging.

Colorimetric and fluorescent detection of F- have attracted enormous interest owing to their simplicity, low-cost and high selectivity. However, traditional colorimetric and fluorescent sensors mainly based on the insoluble and toxic organic molecules, which is not favorable for sensing F- in water media and living cells. In this work, we designed fluorescent carbon dots (CDs) with excellent water solubility and good biocompatibility as a colorimetric and fluorescent dual-model probe for the detection of F-. The CDs were prepared by a green, one-step hydrothermal strategy from wheat straw without any additives and surface passivation. The obtained CDs exhibited a bright blue fluorescence, special response to F- and low cytotoxicity. More interestingly, a significant color change from light yellow to red can be observed by the naked eye upon addition of F- ions to the CDs solution probably due to the formation of hydrogen bonding between CDs and F-. Besides, the fluorescence of CDs also can be selectively quenched by F- with the detection limit of about 49 µM. Additionally, the CDs are also applied to intracellular imaging and sensing of F- in living cells. This strategy may provide a new method for the detection of F- in water media and biological systems.

Metabolites of protoberberine alkaloids in human urine following oral administration of Coptidis Rhizoma decoction.

Coptidis Rhizoma has been used as a traditional Chinese herbal medicine to treat typhoid, pharyngolaryngitis, diabetes mellitus, gastroenteritis and secretory diarrhea for more than a thousand years in China. However, there is little information on the IN VIVO chemical constituents of Coptidis Rhizoma following oral administration. In this paper, the alkaloid constituents in urine were studied in humans following oral administration of Coptidis Rhizoma decoction. Using macroporous adsorption resin chromatography, open ODS column chromatography, and preparative high-performance liquid chromatography, twelve protoberberine alkaloid constituents were isolated. Their structures were elucidated by chemical evidence, enzymatic deconjugation and analyses of mass, (1)H-NMR and NOESY spectra. The identified alkaloid constituents include berberine ( P1), groenlandicine 3-O- ß-D-glucuronide (M1), dehydrocheilanthifoline 2-O-ß-D-glucuronide (M2), thalifendine 10-O-ß-D-glucuronide (M3), jatrorrhizine 3-O-ß-D-glucuronide (M4), columbamine 2-O-ß-D-glucuronide (M5), berberrubine 9-O-ß-D-glucuronide (M6), jatrorrhizine 3-O-sulfate (M7), demethyleneberberine 2-O-sulfate (M8), dehydrocorydalmine 10-O-sulfate (M9), 3,10-demethylpalmatine 10-O-sulfate (M10) and 2,3,10-trihydroxyberberine 2-O-sulfate ( M11). No other parent protoberberine alkaloids from Coptidis Rhizoma except for a trace of berberine were found in the urine. These findings suggested that the protoberberine alkaloids, which were absorbed in vivo following oral administration of Coptidis Rhizoma decoction, were mainly conjugated with glucuronic acid or sulfuric acid to form phase II metabolites directly or after biotransformation to phase I metabolites, and finally excreted in urine.

[Research progress on core-shell silica stationary phases for high performance liquid chromatography].

Fast and efficient separation by using high performance liquid chromatography (HPLC) is challenging for a wide range of samples. In recent years, core-shell silica microspheres have been widely investigated and used for highly efficient and fast separation under reasonably low pressure for small solutes, biopolymers, and complex samples. In this paper, the mechanism for fast separation and preparation methods of core-shell silica microspheres are introduced, along with their application for HPLC-based separation of small molecules, peptides, and biological macromolecules in HPLC. The developing trends of using core-shell microspheres in HPLC are also presented.

Synthesis and optimization of SiO2@SiO2 core-shell microspheres by an improved polymerization-induced colloid aggregation method for fast separation of small solutes and proteins.

Recently, superficially porous particles (SPPs) have been intensively studied and employed for highly efficient and fast separations. In this paper, the SiO2@SiO2 SPPs were synthesized by an improved polymerization-induced colloid aggregation (PICA) method using urea-formaldehyde polymer as the template. The agglomeration of silica core during modification with ureidopropyltrimethoxysilane (UPS) can not only be avoided by reflux in neutral ethanol solution, but also the secondary nucleation of the colloidal silica sol can be inhibited via optimizing the reaction conditions including pH, temperature, colloidal silica sol concentration and the reaction time. The shell thickness and pore size of SPPs can be controlled successfully by adjusting the weight ratio of silica core/colloidal silica sol and the particle size of colloidal silica sol, respectively. The SPP-C18 columns packed using octadecyltrichlorosilane (ODS) modified SPPs with different pore sizes were employed to separate small solutes and proteins. The baseline separations of 6 kinds of alkyl benzenes and 5 kinds of aromatic alcohol homologues were achieved within 4 min by the SPP-C18 column with 8 nm pore size. Compared with the commercial BEH-C18 column, more than 50,000/m of the plate number of propylbenzene was obtained, and the former provided higher column efficiency to separate small solutes than the latter. Meanwhile, 6 kinds of proteins were also separated completely within 2 min using the SPP-C18 column with 40 nm pore size. In addition, the SPP-C18 capillary column was applied to separate and identify the BSA/HeLa/mouse liver digests with capillary LC-MSMS, respectively. The results indicate that more proteins and peptides can be identified using SPP-C18 capillary column compared with commercial silica-C18 capillary column. The result demonstrates that the prepared SPP-C18 column provides higher column efficiency and the SPPs synthesized with the improved PICA method shows a great potential application for the fast separation of small solutes and proteins.

A novel reversed-phase and weak anion-exchange mixed-mode stationary phase based on horizontal polar-copolymerized approach for separation of small organic molecules and inorganic anions.

A novel silica-based reversed-phase/weak anion-exchange mixed-mode chromatography (MMC) stationary phase referred to as OTAS was synthesized based on the horizontal polar-copolymerized approach using trichlorooctadecylsilane (ODS) and (3-glycidyloxypropyl)trimethoxysilane (GPS) as ligands, and then followed by the reaction of epoxy group with diethylamine to introduce the tertiary ammonium functional group. The new stationary phase was characterized by instrumental analysis, and evaluated by separating the mixture of alkylbenzene homologues in reversed-phase mode and acidic organic compounds in ion-exchange chromatography mode, respectively. The results indicate that not only the baseline separation of 11 kinds of neutral and acidic organic compounds can be achieved successfully, but also 5 kinds of inorganic anions can be separated completely. The chromatographic property of OTAS column can be controlled by adjusting the molar ratio of ODS to GPS. Moreover, the OTAS column was used successfully to analyze the inorganic anions in the actual water samples. The good separation and selectivity of OTAS column suggests that the new MMC stationary phase can be used for the analysis of complex samples containing of neutral and acidic organic compounds or inorganic anions.

Branched polyethyleneimine-assisted boronic acid-functionalized silica nanoparticles for the selective enrichment of trace glycoproteins.

Boronate affinity materials have attracted more and more attention in extraction, separation and enrichment of glycoproteins due to the important roles that glycoproteins take on in recent years. However, conventional boronate affinity materials suffer from low binding affinity mainly because of the use of single boronic acids. This makes the extraction of glycoproteins of trace concentration become rather difficult or impossible. Here we present a novel boronate avidity material, polyethyleneimine (PEI)-assisted boronic acid-functionalized silica nanoparticles (SNPs). Branched PEI was applied as a scaffold to amplify the number of boronic acid moieties. While 3-carboxybenzoboroxole, exhibiting high affinity and excellent water solubility toward glycoproteins, was used as an affinity ligand. Due to the PEI-assisted synergistic multivalent binding, the boronate avidity SNPs exhibited strong binding strength toward glycoproteins with dissociation constants of 10-7 M, which was the highest among reported boronic acid-functionalized materials that can be applied for glycoproteomic analysis. Such a high avidity enabled the selective extraction of trace glycoproteins as low as 0.4 pg/mL. This feature greatly favored the selective enrichment of trace glycoproteins from real samples. Meanwhile, the boronate avidity SNPs was tolerant of the interference of abundant sugars. In addition, the PEI-assisted boronate avidity SNPs exhibited high binding capacity and low binding pH. The feasibility for practical applications was demonstrated with the selective enrichment of trace glycoproteins in human saliva.

A method for analyzing electrical impedance spectroscopy data from breast cancer patients.

Research on freshly-excised malignant breast tissues and surrounding normal tissues in an in vitro impedance cell has shown that breast tumors have different conductivity and permittivity from normal or non-malignant tissues. This contrast may provide a basis for breast cancer detection using electrical impedance imaging. This paper describes a procedure for collecting electrical impedance spectroscopy data simultaneously and in register with tomosynthesis data from patients. We describe the methods used to analyze the data in order to determine if the electrodes are making contact with the breast of the patient. Canonical voltage patterns are applied and used to synthesize the data that would have resulted from constant voltage patterns applied to each of two parallel mammography plates. A type of Cole-Cole plot is generated and displayed from each of the currents measured on each of the electrodes for each of the frequencies (5, 10, 30, 100 and 300 kHz) of applied voltages. We illustrate the potential usefulness of these displays in distinguishing breast cancer from benign lesions with the Cole-Cole plots for two patients--one having cancer and one having a benign lesion--by comparing these graphs with electrical impedance spectra previously found by Jossinet and Schmitt in tissue samples taken from a variety of patients.

A compensated radiolucent electrode array for combined EIT and mammography.

Electrical impedance tomography (EIT), a non-invasive technique used to image the electrical conductivity and permittivity within a body from measurements taken on the body's surface, could be used as an indicator for breast cancer. Because of the low spatial resolution of EIT, combining it with other modalities may enhance its utility. X-ray mammography, the standard screening technique for breast cancer, is the first choice for that other modality. Here, we describe a radiolucent electrode array that can be attached to the compression plates of a mammography unit enabling EIT and mammography data to be taken simultaneously and in register. The radiolucent electrode array is made by depositing thin layers of metal on a plastic substrate. The structure of the array is presented along with data showing its x-ray absorbance and electrical properties. The data show that the electrode array has satisfactory radiolucency and sufficiently low resistance.

Effects of breviscapine on amyloid beta 1-42 induced Alzheimer's disease mice: A HPLC-QTOF-MS based plasma metabonomics study.

Herba Erigerontis has long been used to cure apoplexy hemiplegia and precordial pain in China. In addition, the bioactivities of its total flavonoids-breviscapine included inhibiting amyloid beta (Aß) fibril formation, antioxidation and metal chelating, which are beneficial to treat Alzheimer's disease (AD). Hence, A HPLC-QTOF-MS based plasma metabonomics approach was applied to investigate the neuroprotective effects of breviscapine on intracerebroventricular injection of aggregated Aß 1-42 induced AD mice for the first time in the study. Ten potential biomarkers were screened out by multivariate statistical analysis, eight of which were further identified as indoleacrylic acid, C16 sphinganine, LPE (22:6), sulfolithocholic acid, LPC (16:0), PA (22:1/0:0), taurodeoxycholic acid, and PC (0:0/18:0). According to their metabolic pathways, it was supposed that breviscapine ameliorated the learning and memory deficits of AD mice predominantly by regulating phospholipids metabolism, elevating serotonin level and lowering cholesterols content in vivo.

Preparation and characterization of monodisperse large-porous silica microspheres as the matrix for protein separation.

High performance liquid chromatography (HPLC) is a kind of efficient separation technology and has been used widely in many fields. Micro-sized porous silica microspheres as the most popular matrix have been used for fast separation and analysis in HPLC. In this paper, the monodisperse large-porous silica microspheres with controllable size and structure were successfully synthesized with polymer microspheres as the templates and characterized. First, the poly(glycidyl methacrylate-co-ethyleneglycol dimethacrylate) microspheres (PGMA-EDMA) were functionalized with tetraethylenepentamine (TEPA) to generate amino groups which act as a catalyst in hydrolysis of tetraethyl orthosilicate (TEOS) to form Si-containing low molecular weight species. Then the low molecular weight species diffused into the functionalized PGMA-EDMA microspheres by induction force of the amino groups to form polymer/silica hybrid microspheres. Finally, the organic polymer templates were removed by calcination, and the large-porous silica microspheres were obtained. The compositions, morphology, size distribution, specific surface area and pore size distribution of the porous silica microspheres were characterized by infrared analyzer, scanning-electron microscopy, dynamic laser scattering, the mercury intrusion method and thermal gravimetric analysis, respectively. The results show that the agglomeration of the hybrid microspheres can be overcome when the templates were functionalized with TEPA as amination reagent, and the yield of 95.7% of the monodisperse large-porous silica microspheres can be achieved with high concentration of polymer templates. The resulting large-porous silica microspheres were modified with octadecyltrichlorosilane (ODS) and the chromatographic evaluation was performed by separating the proteins and the digest of BSA. The baseline separation of seven kinds of protein standards was achieved, and the column delivered a better performance when separating BSA digests comparing with the commercial one currently available. The high column efficiency and good reproducibility present that the large-porous silica microspheres obtained can be used as a matrix for peptide and protein separation.