Detection and structural characterization of the metabolites of dihydroresveratrol in rats by liquid chromatography coupled to high-resolution tandem mass spectrometry.

RATIONALE: Dihydroresveratrol has been demonstrated to possess a wide spectrum of bioactivities, such as anti-oxidant and anti-inflammatory effects. The aim of the present study was to investigate the metabolic profiles of dihydroresveratrol in rats. METHODS: The in vitro metabolism was elucidated by incubating dihydroresveratrol with rat hepatocytes for 2 h at 37°C. For in vivo metabolism, dihydroresveratrol was orally administered to rats at a single dose of 50 mg/kg and the resulting biliary and urinary samples were collected. All the samples were analyzed by liquid chromatography combined with electrospray ionization high-resolution mass spectrometry. The structures of the metabolites were proposed based on their accurate masses and their MS/MS product ions. RESULTS: A total of 16 metabolites including three phase I metabolites and 13 phase II metabolites were detected and structurally proposed. Among these metabolites, M6 and M14 were unambiguously identified as 3'-hydroxylresveratrol and resveratrol, respectively, using reference standards. Dihydroresveratrol was mainly metabolized into resveratrol (M14) and a glucuronide conjugate (M12), which were excreted into urine and bile as the major metabolites. CONCLUSIONS: The metabolic pathways of dihydroresveratrol involved hydroxylation, dehydrogenation, glucuronidation, glutathione (GSH) conjugation and methylation. The present study provided useful information with regard to the metabolic profiles of dihydroresveratrol in rats.

MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via down-regulation of GADD45α.

BACKGROUND: MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms. METHODS: We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting. RESULTS: miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45α down-regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45α expression in a xenograft model. Consistently, the knockdown of GADD45α expression partially neutralized the effects of miR-362-5p inhibition. Furthermore study suggested that GADD45α mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways. CONCLUSION: miR-362-5p acts as an oncomiR that down-regulates GADD45α, which consequently activates the JNK1/2 and P38 signalling. This finding provides novel insights into CML leukaemogenesis and may help identify new diagnostic and therapeutic targets.

Effect of Sancaijiangtang on plasma nitric oxide and endothelin-1 levels in patients with type 2 diabetes mellitus and vascular dementia: a single-blind randomized controlled trial.

OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine in type 2 diabetes mellitus and vascular dementia, and to explicate the material basis for treating the different diseases with the same method in Traditional Chinese Medicine. METHODS: In total, 168 patients with type 2 diabetes mellitus and vascular dementia were enrolled in the study, and randomly divided into two groups by simple randomization. Patients in the treatment group received oral Sancaijiangtang powders with pioglitazone hydrochloride three times daily, while patients in the control group received pioglitazone hydrochloride alone. The treatment course was for 12 weeks. Mini-mental state examinations (Chinese version) and Montreal Cognitive Assessments (Beijing version) were performed, and fasting plasma glucose, fasting insulin, hemoglobin A1c, homeostasis model assessment of insulin resistance, plasma nitric oxide and endothelin-1 levels were measured before and after the treatment. RESULTS: The post-treatment levels for all measurements in both groups were better than pre-treat- ment levels (P < 0.05). The post-treatment levels for all measurements in the treatment group were better than the levels measured in the control group (P < 0.05). CONCLUSION: Type 2 diabetes mellitus and vascular dementia have common pathological mechanisms for insulin resistance and endothelium dysfunction. Sancaijiangtang powders could improve the release of nitric oxide and inhibit the secretion of endothelin-1. Therefore, the material basis exists for treating the different diseases with the same method in Traditional Chinese Medicine.

[Risk factors and short-term prognosis of acute kidney injury in elderly patients].

OBJECTIVE: To explore the risk factors and short-term outcomes of acute kidney injury (AKI) in elderly patients. METHODS: A total of 232 elderly AKI patients at Chinese PLA General Hospital from June 2008 to December 2009 were enrolled. They were divided into two groups according to their outcomes at 28 days and at 29 days to 3 months after AKI respectively. Their clinical data were analyzed to explore the risk factors and their effects on the outcomes of AKI. RESULTS: There were 215 males and 17 females with an average age of (86.7 ± 5.3) years. Thirty-eight cases (16.4%) died within 28 days after AKI and 57 (24.6%) died within 3 months. Infection (43.1%) was the major cause of AKI. The other causes included hypovolemia (19.0%), use of nephrotoxic drugs (16.8%) and cardiovascular events (15.1%) respectively. Logistic regression analysis revealed that low body mass index (BMI), oliguria, mechanical ventilation, hypoalbuminemia and peak serum level of creatinine (Scr >246.5 µmol/L) were the prognostic factors of AKI in those patients dying within 28 days after AKI (P < 0.05). Low BMI, hypoalbuminemia and high blood level of urea nitrogen (BUN) were the prognostic factors of AKI in those patients dying within 29 days to 3 months after AKI (P < 0.05). CONCLUSION: Infection, hypovolemia, use of nephrotoxic drugs and cardiovascular events are common causes of AKI in elderly patients.Low BMI, oliguria, mechanical ventilation, hypoalbuminemia, high level of BUN and peak level of Scr ( > 246.5 µmol/L) are the prognostic factors of AKI in elderly patients.

Morphologic studies of high fall injuries.

OBJECTIVE: By studying the mode and morphologic character of high fall injuries on the scene, and exploring the injury situation of different heights, different fall ways and postures, to provide a reference for the forensic identification of high fall injury. METHODS: All the high fall cases were statistically analysed according to their gender, age, ground-touching posture, fall height, site and type of the injury. RESULTS: Among 134 high fall cases, 98 were male and 36 were female with the age ranging from 2-71 years (37.6+/-16.9 on average), in which, 10-60 years old group consisted of 110 cases (82%). Most cases fell from windows or roofs (73%) and the touching objects were cement ground or shaft bottom of elevators. Among these cases, head injury was generally serious, followed by chest and abdominal injuries. The morphologic changes depend upon the height, nature, as well as the posture at the point while the body touches the ground. CONCLUSION: Morphologic study of high fall injury assists medicolegal physicians to make correct identifications of the cause and nature of high fall injuries.

Further sesquiterpenoids from Pittosporum qinlingense and their anti-inflammatory activity.

Four new sesquiterpenoid glycoside esters, Pitqinlingoside N-Q (1-4), together with eleven known metabolites (5-15), were isolated from 95% EtOH extract of the twigs, fruits and leaves of P. qinlingense. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses, including IR, UV, HRMS, NMR and electronic circular dichroism spectra. Unusal glycoside esters are characterized by the presence of polyacylated ß-D-fucopyranosyl and ß-d-glucopyranosyl units. Pitqinlingoside N (1), O (2), P (3), boscialin (5) and arvoside C (6) showed significant nitric oxide production inhibition in lipopolysaccharide (LPS)-induced BV-2 microglial cells with IC50 values ranging from 1.58 to 28.74 µM. Structure-activity relationships of the isolated compounds are discussed.

Design, synthesis, and biological evaluation of dinuclear bismuth(III) complexes with Isoniazid-derived Schiff bases.

Four dinuclear bismuth(III) Schiff-base complexes bearing Schiff-base ligands have been synthesized and structurally characterized by single-crystal X-ray diffraction, elemental analysis, and spectral techniques (FT-IR, NMR and MS). The analytical data reveal the bismuth(III) complexes possess 1:1 metal-ligand ratios. In vitro biological studies have revealed that bismuth(III) complexes displayed much higher antibacterial and antitumor activities than their parent ligands, which involves two gram-negative (S. aureus, B. subtili) and two gram-positive (E. coli, P. aeruginosa) bacteria, and human gastric cancer SNU-16 cells. The power-time curves of S. pombe exposed to tested compounds were detected by bio-microcalorimetry. Some thermokinetic parameters (k, Pmax,tG and Qtotal) were derived based on the metabolic power-time curves, and their quantitative relationships with the concentrations (c) were further discussed.

Caloric restriction inhibits renal artery ageing by reducing endothelin-1 expression.

BACKGROUND: The renal artery plays a central role in renal perfusion and is critical for proper renal function. Ageing is an independent risk factor for both impaired renal function and vascular disorders, and associated with an increase in the expression of the vasoconstrictor endothelin-1 (ET-1), and caloric restriction (CR) without malnutrition has been shown to be an effective inhibitor of renal dysfunction induced by ageing. The objective of this study was to determine whether CR-mediated alleviation of renal dysfunction is mediated by ET-1 expression. METHODS: The young (2 months, 2 M) and old (12 months, 12 M) Sprague-Dawley male rats were used and fed ad libitum. The 12-month-old rats were further divided into 12 M and 12 M-caloric restriction (CR) (30% calorie restriction). After 8 weeks, the renal tissues were showed by PAS staining, and age-related metabolic parameters and renal functions were detected in each group of rats. The inflammatory cytokines of interleukin (IL)-6, IL-1ß, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-ß1) were analyzed using ELISA. The mRNA and protein expression in the renal artery were analysis by qRT-PCR and Immunoblot analysis. RESULTS: Ageing was associated with significant increases in 24 h urine protein content and serum triglyceride and cholesterol in 12 M rats, both of which were significantly inhibited in 12 M-CR. The mRNA expression and the secretion of IL-6, IL-1ß, TNF-α, and TGF-ß1 in the renal artery was significantly increased with ageing and inhibited by CR. CR also inhibited ageing-induced Edn1 (encoding ET-1) mRNA and protein expression in the renal artery. In addition, CR could regulate ET-1 expression by inhibiting the activation of NF-κB signaling and activation and induction in the expression of NF-E2-related factor 2 (Nrf2) and histone deacetylase and gene repressor sirtuin 1 (SIRT1), both of which play a central role in mitigating oxidative stress in young rats. CONCLUSIONS: Moderate CR can reverse the ageing related kidney dysfunction by reducing the ET-1 expression. CR might be used as an alternative to prevent the ageing induced renal artery dysfunction.

[Erosion process of loess slope and influencing factors in the loess hilly-gully region, China]. / é»„åœŸä¸˜é™µæ²Ÿå£‘åŒºé»„åœŸå¡é¢ä¾µèš€è¿‡ç¨‹åŠå ¶å½±å“å› ç´ .

Rainfall intensity, slope length, and slope gradient are the important factors affecting runoff and sediment yield. In order to quantitatively analyze the effects of rainfall intensity, slope length, and slope gradient on the erosion process of Ansai loess slope in loess hilly and gully region, we analyzed the variation of runoff and sediment yield on Ansai loess with two slope lengths (5, 10 m), three slopes (5°, 10°, 15°) and two rainfall intensities (60, 90 mm·h-1) in an indoor simulated rainfall experiment. The results showed that the initial runoff generation time decreased with the increases of slope length, though the overall change was not significant. The initial runoff generation time decreased with the increases of rainfall intensity. Compared with the intensity of 60 mm·h-1, the initial runoff generation time decreased by 5.7-18 min under the intensity of 90 mm·h-1. Among them, the runoff initiation time on the slope of 10° was the fastest. With the duration of rainfall, runoff yield rate increased rapidly at first, and then gradually fluctuated around a certain value. The sediment yield rate increased rapidly in a short period of time at the initial stage of runoff generation, and then decreased after reaching the maximum, and being gradua-lly stable. The rates of runoff and sediment yield increased with the increases of slope length and rainfall intensity, but the law of change with slope was not obvious. With the increases of rainfall intensity, slope length and gradient, the total sediment yield increased accordingly. Under the rainfall intensity of 90 mm·h-1, the slope surface with the length of 10 m and slope of 15° generated rill, leading to the highest total erosion amount (11885.66 g). Under the rainfall intensity of 60 mm·h-1, the erosion amount per unit area decreased with the increases of slope length, and there was a critical erosion slope length in 5-10 m slope section. Slope length, slope and rainfall intensity all played a promoting role in runoff process. Rainfall intensity, slope length, and their interaction contributed more to runoff yield rate and total erosion amount. Rainfall intensity contributed the most to runoff yield rate, with a contribution rate of 49.8%. The contribution rate of slope length to the total erosion was the largest, which reached 37.8%.

A Novel 3D Reconstruction Algorithm of Motion-Blurred CT Image.

The majority of medical workers are eager to obtain realistic and real-time CT 3D reconstruction results. However, autonomous or involuntary motion of patients can cause blurring of CT images. For the 3D reconstruction scene of motion-blurred CT image, this paper consists of two parts: firstly, a GAN image translation network deblurring algorithm is proposed to remove blurred results. This algorithm adopts the clear image to supervise the training process of the blurred image, which creates solutions that are close to the clear image. Secondly, this paper proposes a Marching Cubes (MC) algorithm based on the fusion of golden section and isosurface direction smooth (GI-MC) for 3D reconstruction of CT images. The golden section algorithm is used to calculate the equivalent points and normal vectors, which reduces the calculation numbers from four to one. The isosurface direction smooth algorithm computes the mean value of the normal vector, so as to smooth the direction of all triangular patches in spatial arrangement. The experimental results show that for different blurred angle and blurred amplitude, comparing the results of the Shannon entropy ratio and peak signal-to-noise ratio, our GAN image translation network deblurring algorithm has better restoration than other algorithms. Furthermore, for different types of liver patients, the reconstruction accuracy of our GI-MC algorithm is 9.9%, 7.7%, and 3.9% higher than that of the traditional MC algorithm, Li's algorithm, and Pratomo's algorithm, respectively.

Strong and Tough Glass with Self-Dispersed Nanoparticles via Solidification.

Glassy materials can be broadly defined as any amorphous solid, which are important in nature and have significant societal value for their applications in daily life and industry. Although many methods have been applied, the fracture toughness of traditional glasses is still very low due to intrinsic brittleness, significantly limiting their use for structural applications. While nanoelements may be added into glasses and ceramics to form nanocomposites with enhanced properties, it is extremely difficult to distribute and disperse them inside the liquid glass/ceramic matrix with traditional processing methods. It is shown that a strong and tough glass can be fabricated through a direct-solidification process using a nanoparticle self-dispersion mechanism in a glass melt (2MgO·2Al2 O3 ·5SiO2 ) with the assistance of B2 O3 , delivering a 6.1% strain limit and strength up to E/14 (E is elastic modulus), which is close to the theoretical limit of E/10 and one of the highest among all materials reported so far. The fracture toughness of the glass with 30 vol% SiC nanoparticles is significantly higher than any other inorganic glass tested under similar conditions. This new method opens up remarkable opportunities for glass and ceramic research, manufacturing, and applications.

A simple method for AFM tip characterization by polystyrene spheres.

An AFM image would not be the true topography of a surface because of the limitation of a finite size of the tip. The true topography of the surface can be deduced if we can know the tip shape. In this paper a simple method has been established to determine the profile of an AFM tip. A geometrical model for the tip and a spherical object has been proposed to show the procedure for deducing the tip shape from AFM images. Isolated spheres and closely packed spheres with different diameters have been observed to confirm the tip shape by this method. It is a non-destructive method to determine the tip shape and the results can be used for future reconstruction of an AFM image.

Microcalorimetric study of the effect of Ce(III) on metabolic activity of mitochondria isolated from indice rice 9311.

Rare earth elements (REEs) have beneficial influence on plant growth and are widely used in agriculture practice, but little is known about behavior of the REEs on mitochondria in plant cells. Thermogenic metabolic curves were determined by the ampoule method at 303 K using a TAM air isothermal microcalorimeter in mitochondria isolated from indice rice 9311 (Oryza sativa L.), and the effect of Ce(III) on mitochondrial metabolism was investigated. By analyzing the obtained heat flux curves, the crucial parameters such as activity recovery rate constant (k) and maximum heat power (P(m)) were investigated. Application of Ce3+ in concentrations ranging from 0 to 120 microg/ml significantly increased k and P(m) values, with the maximum reaching 261 and 180% of the control, respectively. Concentrations from 140 to 150 microg/ml had the opposite effect. These results were consistent with previous reports on the effects of REEs on plant growth. It was concluded that the Ce(III)-induced change of mitochondrial metabolic activity is a possible mechanism by which Ce(III) influenced indice rice 9311 growth.

Characterization of humic and fulvic acids extracted from landfill by elemental composition, 13C CP/MAS NMR and TMAH-Py-GC/MS.

Humic acid (HA) and fulvic acid (FA) extracted from landfills at different landfill ages were characterized by elemental composition, (13)C CP/MAS NMR, and TMAH-Py-GC/MS. The elemental composition analysis revealed high O/C and low H/C ratios in the FA, indicating a high proportion of O-alkyl and carboxylic acids in the FA. The analytical results of (13)C CP/MAS NMR suggested that there were more oxygenated aliphatic carbons and fewer aromatic carbons in FA than in HA. The Py-GC/MS products showed that the HA and FA extracted from the refuse in the landfill were mainly composed of various lignin-derived compounds. Oxidized aromatic acid derivatives originated from the oxidation of side-chains of lignin-like compounds, and this process played a significant role in the process of HA and FA formation in the landfill. All of the results demonstrated that the degree of humification increased with landfill age.

Characteristics and mobility of heavy metals in an MSW landfill: implications in risk assessment and reclamation.

To assess the reclamation feasibility of a landfill, the characteristics, distribution, and mobility of heavy metals in the landfill were investigated. The refuse was characterized as containing high concentrations of heavy metals, a relatively high pH, and a high ratio of NH(4)-N to total nitrogen (TN). The results of heavy metal distribution showed that relatively high levels of heavy metals were accumulated in the landfill. Sequential extraction revealed that the relative amounts of heavy metals were different in the samples. Zn demonstrated the greatest mobility compared to other heavy metals, whereas Cd was well retained in the landfill. Leaching experiments indicated that the mobility of heavy metals in the landfill was generally low under normal neutral conditions. However, release of heavy metals can be increased greatly when medium conditions become more acidic and aerobic.

Bioenergetic investigation of action of lithium to Tetrahymena thermophila bF5 by microcalorimetry.

Microcalorimetry was employed to investigate the action of Li(I) to aquatic ecosystem from the point view of bioenergetics. Tetrahymena thermophila BF5 was chosen as the model organism. The power-time curves of T. thermophila BF5 growth metabolism in the absence and presence of Li(I) were obtained. The corresponding thermokinetic parameters were derived. The generation time was calculated as 592.3 min, which was consistent with the biomass values. Low concentration of Li(I) (1-20 mmol l-1) stimulated the growth of T. thermophila BF5, whereas the inhibition effect was observed in high concentration (30-100 mmol l-1). The value of IC50 was 52.8 mmol l-1. In the concentration range of 30-100 mmol l-1, the growth rate constants (k) and the maximum heat out power (P max) decrease with the concentration of Li(I), whereas the heat output (Q) increases slightly compared to the control. Other than the classic mechanism of inositol-phosphate cycle, the involvement of mitochondria mechanism was discussed and suggested.

Scorpion venom activates natural killer cells in hepatocellular carcinoma via the NKG2D-MICA pathway.

Previous studies have demonstrated that polypeptides extracted from scorpion venom (PESV) inhibited cell proliferation in several tumors, however, the effect on dysfunctional and exhausted natural killer cells which contribute to tumor escape from immune surveillance remain to be elucidated. In this study, we determined the effect of PESV on NK infiltration into H22 cells orthotopic transplantation tumors and on the expression of MHC class I chain-related proteins A (MICA) in HepG2 cells. We found that tumor growth in mice was significantly inhibited by PESV and the survival time of tumor-bearing mice treated with PESV was significantly prolonged. Moreover, levels of tumor-infiltrating NK cells, NKG2D protein, perforin and granzyme B mRNA were significantly increased in the group treated with PESV compared with the tumor-bearing control group. In addition, In addition, up-regulation of MICA by PESV enhances the susceptibility of HepG2 cells to NK lysis in vitro. These results indicate that the inhibitory effects of PESV on hepatic carcinoma are likely mediated by up-regulation of NK cell activity via the MICA-NKG2D pathway.

Synthesis, crystal structure and spectroscopic studies of bismuth(III) complex with 2-substituted benzimidazole ligands.

Reaction of BiCl3 with 2-(2-hydroxy-3-methoxyphenyl)benzimidazole (HL) in tetrahydrofuran (THF) under reflux gave mononuclear complex of formula [Bi(HL)2Cl3·H2O]. The binding interaction of the complex with bovine serum albumin (BSA) was investigated using the fluorescence quenching method. The experimental results showed that the complex could bind to BSA in the proportion of about 1:1. The binding reaction was spontaneous and hydrophobic force played major role in the reaction. The binding of the complex to BSA could change the microenvironment and conformation of BSA.

[Studies on the optimized extraction technology of Paeonia suffruticosa].

OBJECTIVE: To obtain the optimized extraction technology of Paeonia suffruticosa by comparing several extraction method. METHOD: Extract P. suffruticosa by ethanol circumfluence, distillation-decoction, CO2-SFE and traditional decoction, and analyse the results according to the total extraction rate, extraction rate of paeono, extraction of other ingredients and production feasibility. RESULT: Total extraction rates of which are 12.66%, 13.51%, 7.28%, 7.56% respectively; extraction rates of paeonol are 2.45%, 2.26%, 0.31%, 1.15% in turn; Phenolic glycosides can be extracted by ethanol circumfluence, distillation-decoction, traditional decoction, but not by CO2-SFE. CONCLUSION: Distillation-decoction is the most proper extraction technology of P. suffuticosa at present.