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A highly active [N^N−] iridium complex [Cp*Ir(pba)Cl] (3, Cp* = pentamethylcyclopentadiene, pba = 4-(picolinamido)benzoic acid) has been obtained with an anionic ligand, which exhibited the most robust performance for cofactor NADH regeneration in physiological conditions with HCOONa as the hydrogen source. The structure of complex 3 was revealed by X-ray single-crystal structure analysis. The turnover frequency (TOF) of complex 3 in the regeneration of NADH is 7825 h−1, which is about 22.7 times and 178 times higher than that of the C−^N type complex 2 (345 h−1) and N^N complex 1 (44 h−1) at 37 °C, respectively. The high activity of complex 3 seems to be critically affected by the negatively charged N− of the amide chelating ligand, which could promote the reaction rate of Ir–Cl conversion to Ir–H2O. Furthermore, complex 3 shows good biocompatibility for various biomolecules except SH-compounds (such as reduced glutathione (GSH)). When combined with NADH-dependent enzymes (KRED-101), the complex 3-based NADH-regeneration catalytic system shows stable chemoenzymatical coordinate catalytic activity for reducing acetophenone to the corresponding alcohol with high enantioselectivity.

Analysis of nicotinamide adenine dinucleotide (NAD+/NADH)-modified electrodes is important for in vitro monitoring of key biological processes. In this work, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to analyze NAD+/NADH-modified gold electrodes. Interestingly, no obvious characteristic peaks of nicotinamide fragment could be observed in the mass spectra of NAD+/NADH in their neutral sodium pyrophosphate form. However, after acidification, the characteristic peaks for both NAD+ and NADH were detected. This was due to the suppression effect of inner pyrophosphoric salts in both neutral molecules. Besides, it was proved that the suppression by inner salt was intramolecular. No obvious suppression was found between neighboring molecules. These results demonstrated the suppression effect of inner salts in ToF-SIMS analysis, providing useful evidence for the study of ToF-SIMS ionization mechanism of organic molecule-modified electrodes. Graphical Abstract ᅟ.

Impairment of mitochondrial biogenesis has been associated with vascular pathophysiology. The G-protein-coupled receptor (TGR5) is an important mediator of bile acid signaling and glucose metabolism. However, the effects of TGR5 on mitochondrial biogenesis in endothelial cells remain elusive. In this study, we found that activation of TGR5 using its specific agonist taurolithocholic acid (TLCA) promoted the expression of PGC-1α, a master regulator of mitochondrial biogenesis in human aortic endothelial cells (HAECs). Additionally, activation of TGR5 increased the expression of PGC-1α target genes, such as NRF1 and TFAM. Indeed, we found that TLCA treatment promoted mitochondrial biogenesis by increasing mitochondrial mass, mitochondrial-to-nuclear DNA (mtDNA/nDNA), COX-Ⅰ expression, and cytochrome c oxidase activity in HAECs. Notably, our results displayed that activation of TGR5 resulted in a functional gain in mitochondria by increasing the rate of respiration and ATP production. Mechanistically, we found that TLCA treatment activated the transcriptional factor CREB by inducing the phosphorylation of CREB at Ser133. Using the PKA/CREB inhibitor H89 abolished the effects of TLCA on PGC-1α, NRF1 and TFAM expression as well as the increase in mtDNA/nDNA and ATP production. These findings suggest that activation of TGR5 promoted mitochondrial biogenesis in endothelial cells, which is mediated by the CREB/PGC-1α signaling pathway.

Collision at a single molecule level was achieved based on the nanoimpact of an individual pyrroloquinoline quinone (PQQ) modified multiwalled carbon nanotube (MWCNT) at the carbon fiber ultramicroelectrode (C UME). Electrocatalytic amplification of the current responses was observed when the PQQ-modified MWCNT collided with C UME in the presence of hydrazine (N2H4) in a Tris-HCl buffer solution, which was also supported by the conventional cyclic voltammetry and chronoamperometry techniques. The enhanced catalytic oxidation of N2H4 was due to the “addition-elimination” redox cycling mechanism of PQQ/PQQH2, where the oxidation of N2H4 occurred together with the reduction of PQQ under an external bias, and the formed PQQH2 intermediate would be reoxidized back to PQQ simultaneously. The average collision current, duration, and charge for PQQ-modified MWCNT at 1.0 V vs Ag/AgCl were 105 pA, 0.45 ms, and 49 fC, respectively. As a result, the turnover frequency of electrocatalytic oxidation of N2H4 by PQQ was ...

Mulberroside A (MA) is an oxyresveratrol diglycoside that has many biological activities and pharmacological functions. To improve MA levels in the bark of isolated mulberry branches (Ramulus mori), a huge amount of agro-waste. We took isolated mulberry branches of a huge amount of agro-waste as experimental material and chose equivalent sections of branches for physiochemical treatments with three types of ultraviolet light (UVA, UVB and UVC) and salicylic acid. HPLC analysis showed that the most effective treatment on MA content was UVB irradiation in the wavelength range of 290–320 nm. The experimental results showed that the three types of UV irradiation stimulate the mulberry branch cortex to induce the biosynthesis and secretion of MA. When the isolated branches were soaked in different concentration of salicylic acid for different time, the MA concentration had increased significantly. The stimulatory effect of salicylic acid and UVA on MA synthesis in cortex cells of the isolated branches decreased with branch age; it was greatest in those harvested in June and lowest in those harvested in September. These results indicated that salicylic acid, like UV irradiation, can stimulate mulberry cortex cells and induce the biosynthesis and secretion of MA.

Pd nanoparticles supported on electrochemically reduced graphene oxide (ER-GO) were prepared by an effective electrochemical strategy. Electroactive 1,10-phenanthroline-5,6-dione (phen-dione) was anchorded on the surface of ER-GO by one step potential cycling of GO modified glassy carbon electrode (GCE) in 1,10-phenanthroline (phen) solution from −1 to 1 V (phen-dione/ER-GO/GCE), and Pd2+ was then absorbed on the phen-dione/ER-GO/GCE through coordination interaction followed by electro-reduction to form Pd/phen-dione/ER-GO/GCE. The prepared electrode exhibited excellent electrocatalytic activity towards the oxidation of hydrazine as well as the reduction of hydrogen peroxide (H2O2), which was used to achieve highly sensitive electrochemical sensing of hydrazine and H2O2. In addition, applicability of Pd/phen-dione/ER-GO/GCE for electrochemical detection of hydrazine in real sample was also successfully demonstrated.

Rabbits are widely used for the study of atherosclerosis; however, the lack of a unified and quantitative analysis of atheroma limits data interpretation and comparisons between laboratories. In this study, we applied a simple quantitative method, referred to as the oil red O (ORO) dye-eluting method, for analysis of atherosclerotic plaques in freshly isolated aortas. It employs ORO staining of the plaques followed by elution of the dye that is subjected to quantitative measurement. Atherosclerosis was induced in rabbits by feeding a 1% (w/w) high cholesterol diet for 4 or 12 weeks. Thoracic aortas were isolated and sufficiently stained by ORO. These dyes were easily and completely extracted by 100% ethanol and quantified by spectrophotometric measurement at 510 nm. A series of cross-sectional slices at 100-µm intervals were counterstained by elastic van Gieson. It was found that there was a highly positive correlation between the dye concentration and the amount of plaque tissue, determined as volume of plaques (regression coefficient r2: 0.8792, p

Inspired by the addition-elimination catalytic mechanism of natural pyrroloquinoline quinone (PQQ) containing proteins, PQQ-modified hybrid nanomaterials have been increasingly developed recently as biomimetic heterogeneous electrocatalysts. However, up until now, no existing electrochemical approach was able to assess the intrinsic catalytic activity of PQQ sites, impeding the design of efficient PQQ-based electrocatalysts. Herein, in this work, we introduced a new method to calculate the turnover frequency (TOF) of any individual PQQ functional group for electrocatalytic oxidation of tris(2-carboxyethyl)phosphine (TCEP), through the study of single PQQ-decorated carbon nanotube (CNT) collisions at a carbon fiber ultramicroelectrode by chronoamperometry. The core advantage of this approach is being able to resolve the number of PQQ catalytic sites grafted on each individual CNT, so that the charge of any CNT collision event can be accurately translated into the intrinsic activity of the respective PQQ functional groups. The resulting collision-induced current responses clearly showed that the functionalization of CNTs with PQQ could indeed enhance its catalytic performance by 3 times, reaching a TOF value of 133 s

A novel nanosensor was explored for the highly selective detection of intracellular carbon monoxide (CO) by surface enhanced Raman spectroscopy (SERS) on the basis of palladacycle carbonylation. By assembling new synthesized palladacycles (PC) on the surface of gold nanoparticles (AuNPs), SERS nanosensors (AuNP/PC) were prepared with good SERS activity and reactivity with CO. When the AuNP/PC nanosensors were incubated with a CO-containing system, carbonylation of the PC assembled on AuNPs was initiated, and the corresponding SERS spectra of AuNP/PC changed significantly, which allowed the carbonylation reaction to be directly observed in situ. Upon SERS observation of CO-dependent carbonylation, this SERS nanosensor was used for the detection of CO under physiological conditions. Moreover, benefiting from the specificity of the reaction coupled with the fingerprinting feature of SERS, the developed nanosensor demonstrated high selectivity over other biologically relevant species. In vivo studies further indicated that CO in normal human liver cells and HeLa cells at concentrations as low as 0.5 μM were successfully detected with the proposed SERS strategy, demonstrating its great promise for the analytical requirements in studies of physiopathological events involved with CO.

CMS-1, mainly composed of imperatorin as its active compound, is a partially purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has the potential to be further developed as a new treatment for hypertension. Thus, we studied its toxicity in both Sprague-Dawley rats and beagle dogs. Rats (0-900mg/kg/day) and dogs (0-450mg/kg/day) received CMS-1 orally for 30 consecutive days, followed by a 15-day recovery period. The major target organs of CMS-1 toxicity are the GI (inappetence), liver (hepatocellular necrosis, enzyme elevation), thymus (atrophy), cardiovascular (hypotension), changes in ECG T and P waveforms, elevation of nitrous oxide levels and hematological (RBC parameters disturbances) systems. Most treatment-induced adverse effects were reversible or showed a progressive recovery upon discontinuation of the treatment. The No Observed Adverse Effect Level (NOAEL) was 100mg/kg/day for rats and 50mg/kg/day for dogs. This non-clinical study suggests that clinical monitoring of CMS-1 in patients should focus on the gastrointestinal system, blood tests for liver functions, electrolytes, and blood homeostasis, cardiovascular functions, and immune functions.

The 2-arylidene-3-oxobutanenitrile derivatives 2 were prepared by the Knoevenagel condensation between aldehydes and 3-oxobutanenitrile 1, which was obtained by acid hydrolysis of β-aminocrotononitrile. 3-Acetyl-2-amino-4H-chromen-5(6H)-one derivatives 3 were synthesized by reaction of 2-arylidene-3-oxobutanenitrile 2 and 5-substituted-1,3-cyclohexanedione in ethylene glycol. The 11-methyl-3,8-disubstituted-12-aryl-3,4,7,8,9,12-hexahydro-1H-chromeno[2,3-b]quinoline-1,10(2H)-dione derivatives 4 were obtained by Friedlander reaction of compounds 3 with 5-substituted-1,3-cyclohexanedione, using p-toluenesulfonic acid monohydrate as catalyst. The structures of all novel compounds were characterized by elemental analysis, IR, MS, and 1H NMR spectra. The crystal and molecular structure of compound 4f has been determined by single crystal XRD analysis.

In this paper, the de-silicated fly ash (DSFA) was sintered with soda and calcium oxide. Detailed analysis and characterization was carried out by using thermal gravimetric analysis (TGA) and X-ray diffraction (XRD). Two dominant reactions take place in the sintering process. The kinetics was studied by using Jander mode, and the sintering activation energies were determined based on the weight loss of CO2.

The root of Angelica dahurica (Radix Angelicae Dahuricae, RAD), which contains coumarins and volatile oil as its main classes of active components, is often given in conjunction with Pueraria root (Radix Puerariae, RP), which contains the phytoestrogen puerarin. The two herbs are considered to be compatible ‘herb-pairs’ in traditional Chinese medicine. The present investigation investigates the absorption of puerarin from RP and the effect of the total coumarins and volatile oil from RAD on its absorption. The everted gut sac and single-pass intestinal perfusion methods were used, respectively. The results showed that the absorption of puerarin in the jejunum was significantly increased in the presence of the coumarins and/or volatile oil. The absorption rate constant (Ka) of puerarin increased gradually until the concentration reached 160 µg · mL−1, after which its absorption became saturated and the apparent permeability (Papp) values significantly decreased. The results showed that the intestinal absorption mechanisms of puerarin involved active transportation processes and that puerarin is likely to be a substrate of P-gp because verapamil significantly affected its Papp and Ka. The absorption of puerarin significantly increased (p

Before oxygen bleaching and hydrogen peroxide bleaching, wheat straw pulp was bleached using xylanase. The effect of enzymatic stage on pulp properties and bleachability has been studied and compared with reference (control) pulps, processed without enzyme addition. Experimental results showed that, the optimal concentration of wheat straw pulp was 10%, the optimal treatment time and dose of enzyme was 60 min and 1.25AXU/g respectively. Oxygen pressure decreased from 0.6MPa to 0.5MPa when conditions of hydrogen peroxide bleachingremained unchanged and wheat straw pulp achieved the same whiteness. Hydrogen peroxide consumption decreased from 2% to 1.8% when oxygen bleaching has the same conditions and achieved the same white degree.

Electrocatalysis of molecules is a hot research topic in biological and energy-related chemistry. Here, we develop a new system to study the electrocatalytic efficiency of a single catechol molecule for NADH oxidation by single functionalized nanoparticle collision at ultramicroelectrodes (UMEs). The proposed system is composed of gold nanoparticles (AuNPs) functionalized with catechol molecules and a carbon-fiber ultramicroelectrode. In the absence of NADH, when a functionalized AuNP collides with an UME at a suitable voltage, a small current spike is generated due to the oxidation of catechol molecules modified on the surface of AuNP. In the presence of NADH, the current spike is significantly amplified by the combined effects of the oxidation and electrocatalysis for NADH of catechol molecules. By analyzing the variations of the average peak charges and durations without or with NADH, we calculate that around five thousands NADH molecules could be catalyzed per second by a single catechol molecule, suggesting the successful establishment of this novel catalytic system. Thus, the proposed strategy could be used as a promising platform for research of other molecular electrocatalytic systems.

Ethnopharmacological relevance Angelicae Dahurica ( Hoffm. ) Benth.& Hook.f.ex Franch.&Sav combined with Pueraria labota ( Willd. ) Ohwi has been widely used as herb-pairs in traditional Chinese medicine (TCM) for utilization of antipyretic analgesic and anti-inflammatory drugs, and modern pharmacological studies have shown that application compatibility of the two drugs has the effects of cardiovascular disease treatment. The previous study has proved that Radix Angelicae Dahuricae extract could enhance the intestinal absorption of puerarin in Pueraria. But the underlying compatibility mechanism of the two herbs remains unknown. In this study we tried to further evaluate the improvement of Radix Angelicae Dahuricae extract on the puerarin using the Caco-2 cell model and explore the transport properties of puerarin through the above research to discuss the possible effect mechanism of Radix Angelicae Dahuricae extract on the transport of puerarin and the underlying compatibility mechanism of the two herbs. Aim of study The aim of this work was to study the transport properties of puerarin in Radix Pueraria across Caco-2 cell membrane and to explore how the Radix Angelicae Dahuricae extract affected the transport of puerarin using the well-characterized, human-based intestinal Caco-2 cell model as a platform. Materials and methods The bidirectional transport, and the effects of time, drug concentration, pH, P-gp inhibitors (Verapamil, Cyclosporin A), MRP inhibitor (MK-571) and EDTA-Na 2 (tight junction modulator) on the absorption of puerarin were observed. Then the influence of extract of Radix Angelicae Dahuricae on the transport of puerarin was studied. Drug concentration was measured by HPLC and the apparent permeability coefficients ( Papp ) and apparent permeability ratio ( PDR ) were calculated. Results and conclusions The results showed that the transport ( Papp ) of puerarin in Caco-2 cell monolayer model had time and concentration dependence, and the transport showed saturation characteristics with the time and concentration of puerarin to a certain degree. The Papp of puerarin transported on Caco-2 cell monolayer model was significantly changed when the specified inhibitors of P-gp were added to the model and the PDR decreased from 1.74 to 0.43. The absorption of puerarin was improved when combined with Radix Angelicae Dahuricae . The intestinal absorption of puerarin is by passive diffusion as the dominating process and active transportation was mediated by P-gp and MRP transporter in Caco-2 cell monolayer model, and Radix Angelicae Dahuricae could enhance the intestinal absorption of puerarin.

The aqueous solutions of lower alcohols such as methanol, ethanol, 1-propanol and 2-propanol, were studied by fluorescence spectroscopy of pyrene, defining the Py scale for polarity. Sigmoidal curves were used to fit the Py values of aqueous alcohol solutions as a function of the logarithm of water–alcohol mole ratio, i.e., log(WAR). The results from curve fittings were discussed in terms of the structural transitions of aqueous alcohol solutions, as well as the dissociation constants for alcohol– and water–pyrene complexes. The microscopic alcohol and water phases were considered to be saturated with each other, and the structures of dilute aqueous alcohol solutions were found to be more complicated than those of concentrated ones.

Biocompatible three-dimensional scaffolds for cell culturing may facilitate methods for the repair of damaged human tissues. A novel hybrid porous scaffold of poly(lactic-co-glycolic acid), hydroxyapatite and collagen was prepared using a supercritical CO2 saturation technique. Expansion factors of scaffolds with different compositions were studied after supercritical CO2 treatment to choose the optimal composition for three-dimensional culture. The supercritical CO2 process conditions, such as saturation temperature, saturation time and saturation pressure were varied to evaluate their influence on pore structure. The results showed that the pore size and porosity of the scaffold could be controlled by manipulating these process conditions. The porous samples were characterized by environmental scanning electron microscopy, energy-dispersive X-ray spectroscope, Fourier transform infrared spectroscopy and X-ray diffractometry. Finally, MG-63 cells were successfully cultured on the porous scaffold as assessed by electron and confocal microscopy, confirming the biocompatibility of this new hybrid porous scaffold.

Decolorization of Acid Red GR by a newly isolated biphenyl-degrading bacterium, Dyella ginsengisoli LA-4 was presented in this paper. The optimal decolorization conditions were determined by response surface methodology (RSM) based on the rotatable central composite design. The results indicated that strain LA-4 possessed the highest decolorizing activity under anaerobic conditions with inoculation amount 6.49%, pH 7.06 and temperature 29 degrees C. Some ions such as Cu(2+), Zn(2+) could inhibit the decolorization, whereas 1 mmol/L of Mg(2+), Ca(2+), Co(2+), Fe(3+), Ni(2+) and Mn(2+) had no effects on the process. It was demonstrated that anthraquinone as a redox mediator could significantly accelerate the reduction process of azo dyes.

The hygroscopic properties of supersaturated aerosols as a function of relative humidity (RH) can be determined on the molecular level by the solutes with varied structures, as well as the solvent in the state of solvated water or free water. Although the former has been investigated by FTIR and Raman spectroscopy, the latter has gone mostly unnoticed. In this work, the state of water in supersaturated Mg(NO(3))(2) and NaNO(3) aerosols were investigated through the application of the Raman difference spectra with respect to pure water. This technique could be developed from the observation that the Raman scattering and infrared absorbance cross sections of the molecular vibrations of interest remain practically unchanged from diluted solutions to supersaturated aerosols at low RHs. The results were expressed in terms of the percentage of free water (W(free)) as a function of RH, as well as the solvated water-to-solute ratio (W(solvated)SR) and the free water-to-solute ratio (W(free)SR) as a function of the total water-to-solute ratio (WSR). Solvated water observed in the Raman difference spectra was primarily related to the first hydration layers. In Mg(NO(3))(2) aerosols, three phases were identified with distinct mechanisms for the transition of the state of water. One unique structure with W(solvated)SR = 4 was proposed to occur in supersaturated Mg(NO(3))(2) aerosols at low RHs. In NaNO(3) aerosols, it was found that the equality of solvated and free water could not provide a necessary condition for efflorescence, in contrast to the recent investigations by fluorescence spectroscopy. According to this investigation, solvated water could be more abundant than free water not only prior to the efflorescence of supersaturated NaNO(3) aerosols, but also in relatively diluted droplets.

FTIR/ATR (attenuated total reflection) spectroscopy has been used to investigate supersaturated MgSO 4 and NaClO 4 aerosols. The experimental ATR spectra of MgSO 4 and NaClO 4 aerosols were found to show little disturbance from water vapor, and thus were always of high quality independent of relative humidity (RH). Some relatively weak absorbing bands, such as the v 1 and v 3 bands of SO 4 2− in supersaturated MgSO 4 aerosols and the v 1 band of ClO 4 − and the residual bands of the water O–H stretching envelope in supersaturated NaClO 4 aerosols, could be identified by their peak positions comparable with those obtained by other experimental methods. In contrast, the relatively strong absorbing v 3 band of ClO 4 − in supersaturated NaClO 4 aerosols could be distorted very seriously, so that quantitative analysis with regard to band shape and peak position should be avoided. The above observations for MgSO 4 and NaClO 4 aerosols by FTIR/ATR spectroscopy could be understood, primarily in terms of the effects on weak and strong absorbing bands of anomalous dispersion and penetration depth ( d p ) dependence on wavelength ( λ ) inherent in FTIR/ATR technique. Though rather limited in straightforward spectral analysis, the experimental high quality ATR spectra obtained under given conditions may be used to derive the optical constants of supersaturated aerosols.

Arylidene-3-oxobutanenitrile derivatives (III) prepared by Knoevenagel condensation of aldehydes with 3-oxobutanenitrile, react with cyclohexanedione in ethylene glycol to give benzopyran derivatives (V).

Arsenic is a multi-system toxicant. However, the mechanism of arsenic toxicity is not fully clarified and few effective protein biomarkers could be used for arsenic poisoning. This study was to investigate the differentially expressed proteins in the serum of rats subchronically exposed to arsenic. Sixty male rats were randomly divided into four groups, and the dose of sodium arsenite in drinking water for each group was 0, 2, 10, and 50 mg L−1, respectively. The exposure lasted for 12 weeks. An Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach was used to identify the differentially expressed proteins in serum between control and 50 mg L−1 groups. A total of 201 serum proteins were identified by iTRAQ, of which 12 were significantly changed by arsenic exposure with two up-regulated and ten down-regulated proteins. One down-regulated protein 14-3-3 ζ, an abundant protein expressed in the brain, was verified by ELISA using serum samples and by immunohistochemical, real time PCR, and western blot methods using brain tissues in four groups. Our work provided valuable insight into the serum protein changes in rats exposed to arsenic, and indicated that 14-3-3 ζ may serve as a useful biomarker for nervous damage caused by arsenic poisoning.

Target compounds (VI) were prepared by condensation of 3-methoxyphenol (I) with β-dicyanostyrenes (II) followed by reaction with cyclic β-dicarbonyl compounds (IV) and cyclization of the intermediate enamines (V).

Ethnopharmacological relevance Angelicae Dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav combined with Radix Scutellariae baicalensis Georgi has been widely used in traditional Chinese medicine (TCM) as an antipyretic analgesic and anti-inflammatory drug. Modern pharmacological studies have demonstrated that the compatible application of these two drugs is an effective treatment for hepatitis. A previous study indicated that a Radix Angelicae Dahuricae extract enhanced the intestinal absorption of the baicalin found in Radix Scutellariae ; however, the underlying compatibility mechanism of these two herbs remains unknown. In this study, we further examined the effect of a Radix Angelicae Dahuricae extract on the absorption and transport properties of baicalin in a Caco-2 cell model to determine the compatibility mechanism of these two herbs. Aim of the study The aim of this work was to study the transport properties of baicalin in Radix Scutellariae across cell membranes and the effects of a Radix Angelicae Dahuricae extract on baicalin absorption using the well-characterized, human-based intestinal Caco-2 cell model. Materials and methods We assessed the absorption, bidirectional transport and toxicity of baicalin using a range of parameters, including drug concentration, pH, a P-glycoprotein (P-gp) inhibitor (Verapamil), an MRP inhibitor (MK-571) and EDTA-Na 2 (tight junction modulator). Next, we studied the influence of a Radix Angelicae Dahuricae extract on the transport of baicalin under the same conditions. Drug concentration was measured by HPLC, and the apparent permeability coefficient (Papp) and apparent permeability ratio (PDR) were subsequently calculated. Results The results showed that baicalin is non-toxic within a concentration range of 800 µg/mL to 4800 µg/mL. The transport of baicalin showed time and concentration dependence. The absorption of baicalin was optimal at pH 7.4 in 37 °C; however, the absorption decreased at 4 °C. The Papp of baicalin transport through the Caco-2 cell monolayer model was altered when specific inhibitors of P-gp or MRP were added to the cells. However, there was no significant difference in the PDR value. The Papp of baicalin improved when it was combined with the Radix Angelicae Dahuricae extract. The influence of EDTA-Na 2 on the transport of baicalin showed that the permeability of baicalin significantly increased. The result further indicated that the mechanism of baicalin intestinal absorption in the Caco-2 cell monolayer involves passive transcellular diffusion. Conclusions Passive diffusion is the main mode of intestinal absorption of bacalin and it involved in the efflux of proteins. The enhanced intestinal absorption of baicalin by Radix Angelicae Dahuricae can be due to opening of the tight junctions between cells and inhibition of MRP efflux protein expression or function.

OBJECTIVE To study the effect of extractive Angelica dahutica on intestinal absorption of puerarin, the mechanism of the absorption enhancement of A. dahutica was investigated, providing a new thread of combinations of the Chinese herbal drugs. METHOD Everted intestinal sac and in situ single pass perfusion were used to study the effect of gut absorption of puerarin solution containing the extractive A. dahurica as well as the influence of P-gp on the absorption of puerarin, and explore weather the extractive A. dahutica can enhance the absorption of puerarin and the mechanism of absorption of puerarin. RESULT The puerarin could be absorbed at all of four intestinal segments with increaing absorption amount perunit as follows: ileum > colon > jejunum > duodenum. The absorption of puerarin in jejunum was significantly increased with the extractive A. dahutica in situ single pass perfusion of jejunum. The apparent permeability coefficient (Papp) and absorption rate constant (Ka) of puerarin in the jejunum were descreased gradually with higher concentrations, and the Papp with the Ka of jejunum solution containing the P-gp inhibitor of verapamil were increasing respectively 2.49, 2.60 (P < 0.001) than only the jejunum solution in absorption. The absorption of jejunum in pH 5.0, 6.8 were better than it in pH 7.4. CONCLUSION The mechanism of absorption of jejunum was active absorption and was effected by P-gp. The extrative A. dahurica can enhance the absorption of the jejunum.

Ethnopharmacological relevance Angelicae Dahurica(Hoffm.)Benth.&Hook.f.ex Franch.&Sav combined with Scutellaria baicalensis Georgi. has been widely used as herb-pairs in traditional Chinese medicine (TCM) to treat migraine headache and cataract, but the underlying compatibility mechanism of the two herbs remains unknown. Aim of study In the present work, we investigated the additive or synergistic effects of absorption behavior of Radix Angelicae dahuricae extracts on baicalin, and the absorption-enhancing mechanism of Radix Angelicae dahuricae extracts on baicalin. Materials and methods Total coumarins (Cou) and volatile oil (VO), as the two main components of Radix Angelicae dahuricae , were extracted by supercritical fluid extraction (SFE) further treated with liquid–liquid separation method. The absorption behavior was investigated by applying the everted gut sac technique and in situ single-pass intestinal perfusion method. Results and conclusions The results showed that both the Cou and the VO could improve the intestinal absorption of baicalin in vivo, and had synergistic action the enhanced absorption of baicalin. Since verapamil did not affect the P app and K a of baicalin significantly, we concluded that the absorption of Baicalin could not be an active transportation in dependent of P-glycoprotein-Mediated efflux systems. Based on intestinal absorption of drug studying was one of the efficacious methods to clarify the compatibility of principles of herb-pairs. The everted gut sac technique and in situ single-pass intestinal perfusion technique model were the effective methods to study the absorption of drug, the application of the animal model to investigating the absorption of herb–drug interactions or other relevant research purposes is envisioned.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitously distributed endocrine-disrupting chemical and reproductive toxicant. In order to elucidate low-dose TCDD-mediated effects on reproductive or endocrine functions, female Sprague-Dawley rats were orally administered various concentrations (20, 50, or 125 ng/kg once weekly) TCDD for 29 wk. A proteomic analysis of the ovaries by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry showed distinct changes in the levels of several proteins that are relevant markers of TCDD toxicity. Serum estradiol (E2) levels of TCDD-treated animals were markedly lower than control. There were no significant differences in bone mineral density (BMD) of femurs. The body weight of the 125-ng/kg TCDD group was significantly decreased relative to control and there was also a significant reduction in absolute and relative ovarian weights. Expressions of selenium binding protein 2, glutathione S-transferase mu type 3, Lrpap1 protein, NADPH, and peptidylprolyl isomerase D were upregulated, while prohibitin and N-ethylmaleimide-sensitive factor expression levels were downregulated. Data provide further insight into the mechanisms by which TCDD disrupts ovarian function by indicating which differential protein expressions following low-dose TCDD exposure.

The NaNO(3) droplets with sizes of 1-5 microm generated from a nebulizer were deposited on a ZnSe substrate in a Fourier transform infrared attenuated total reflection (FTIR-ATR) chamber. After solidification of the droplets with dry N(2) gas passing through the chamber, the solid NaNO(3) particles were monitored by in situ FTIR-ATR spectra in cycles of deliquescence and efflorescence processes with varying relative humidities (RHs). With an increase in the RH, a dominant peak at approximately 3539 cm(-1), together with three relatively weak peaks at approximately 3400, approximately 3272, and approximately 3167 cm(-1), in the O-H stretching band of water was resolved by the high signal-to-noise ratio FTIR-ATR spectra. The dominant peak and the three relatively weak peaks were contributed by the water monomers and the aggregated water molecules adsorbed on the surfaces of solid NaNO(3) particles, respectively. When the RH approached approximately 72%, slightly lower than the deliquescence RH (74.5%), the band component at approximately 3400 cm(-1) became the main peak, indicating that the water monomers and the aggregated water molecules aggregated to form a thin water layer on the surfaces of solid NaNO(3) particles. A splitting of the nu(3)-NO(3)(-) band at 1363 and 1390 cm(-1) at the RH of approximately 72%, instead of the single nu(3)-NO(3)(-) band at 1357 cm(-1) for the initial solid NaNO(3), was observed. We suggested that this reflected a phase transition from the initial solid to a metastable solid phase of NaNO(3). The metastable solid phase deliquesced completely in the region from approximately 87% to approximately 96% RH according to the fact that the nu(3)-NO(3)(-) band showed two overlapping peaks at 1348 and 1405 cm(-1) similar to those of bulk NaNO(3) solutions. In the efflorescence process of the NaNO(3) droplets, the nu(1)-NO(3)(-) band presented a continuous blueshift from 1049 cm(-1) at approximately 77% RH to 1055 cm(-1) at approximately 36% RH, indicating the formation of contact ion pairs between Na(+) and NO(3)(-). Moreover, in the RH range from approximately 53% down to approximately 26%, two peaks at 836 and 829 cm(-1) were observed in the nu(2)-NO(3)(-) band region, demonstrating the coexistence of NaNO(3) solid particles and droplets.

The ATR-FTIR spectra of aqueous LiClO4, NaClO4, and Mg(ClO4)2 solutions with ClO4− concentrations ranging from 0 to 3.00 mol dm−3 were obtained. After subtracting the spectra of pure water, positive peaks on the high wavenumber side and negative peaks on the low wavenumber side of the O–H stretching bands are observed in the difference spectra. The positive peaks appear constantly at about 3580 cm−1 independent of cation, which are assigned to the water molecules weakly hydrogen-bonded with ClO4−. However, the negative peaks appear at 3203, 3196, and 3254 cm−1 for LiClO4, NaClO4, and Mg(ClO4)2 solutions, respectively, and the peak areas show significant difference with increasing the concentration of perchlorate anions and are dependent on cations. The negative peaks are attributed to the “structure breaking” effect of perchlorate ions on the hydrogen bond network of water, which is in agreement with Raman spectroscopic studies. Besides the “structure breaking” effect of ClO4− on destroying the strong hydrogen bonds of the water molecules with fully hydrogen-bonded five-molecule tetrahedral nearest neighbor structure, the difference of the negative peaks are the results of the different “structure making” effect of the three cations, which is consistent with the ability of the polarization and hydration, in the order of Na+

Background The NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3) is an intracellular protein complex that plays an important role in innate immune sensing. Its activation leads to the maturation of caspase-1 and regulates the cleavage of interleukin (IL)-1β and IL-18. Various studies have shown that activation of the immune system plays a pivotal role in the development of fatigue. However, the mechanisms underlying the association between immune activation and fatigue remained elusive, and few reports have described the involvement of NLRP3 inflammasome activation in fatigue. Methods We established a mouse fatigue model with lipopolysaccharide (LPS, 3 mg/kg) challenge combined with swim stress. Both behavioural and biochemical parameters were measured to illustrate the characteristics of this model. We also assessed NLRP3 inflammasome activation in the mouse diencephalon, which is the brain region that has been suggested to be responsible for fatigue sensation. To further identify the role of NLRP3 inflammasome activation in the pathogenesis of chronic fatigue syndrome (CFS), NLRP3 KO mice were also subjected to LPS treatment and swim stress, and the same parameters were evaluated. Results Mice challenged with LPS and subjected to the swim stress test showed decreased locomotor activity, decreased fall-off time in a rota-rod test and increased serum levels of IL-1β and IL-6 compared with untreated mice. Serum levels of lactic acid and malondialdehyde (MDA) were not significantly altered in the treated mice. We demonstrated increased NLRP3 expression, IL-1β production and caspase-1 activation in the diencephalons of the treated mice. In NLRP3 KO mice, we found remarkably increased locomotor activity with longer fall-off times and decreased serum IL-1β levels compared with those of wild-type (WT) mice after LPS challenge and the swim stress test. IL-1β levels in the diencephalon were also significantly decreased in the NLRP3 KO mice. By contrast, IL-6 levels were not significantly altered. Conclusions These findings suggest that LPS-induced fatigue is an IL-1β-dependent process and that the NLRP3/caspase-1 pathway is involved in the mechanisms of LPS-induced fatigue behaviours. NLRP3/caspase-1 inhibition may be a promising therapy for fatigue treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0539-1) contains supplementary material, which is available to authorized users.