Climate and soil properties regulate the vertical heterogeneity of minor and trace elements in the alpine topsoil of the Hengduan Mountains.

Soil minor and trace elements are vital regulators of ecological processes that sustain alpine ecosystem functions. In this study, the vertical pattern and driving factors of element concentrations in alpine soils of the Tibetan Plateau were investigated. Three snow mountains (Meili, Baima, and Haba) part of the Hengduan Mountain range, were selected as the study area to determine the vertical distribution of 12 typical elements (Cr, Ni, Cu, Fe, Mn, Zn, Cd, Pb, Ca, Sr, As, and Se) in topsoil with increasing and decreasing elevation, as well as the dominant driving factors of their spatial heterogeneity. Results showed that all elements, except Se, showed strong vertical heterogeneity, among which Cr, Ni, Cu, and Fe showed peak concentrations at 2700-3000 m; the highest concentrations of Mn and Zn were at 3200 m and 2700 m, with Cd and Pb at 2500 m. Ca and Sr levels gradually decreased with increasing elevation. According to the structural equation model and random forest analysis, the vertical heterogeneity of soil elements is directly regulated by the variability of climate and soil properties due to changes in elevation. A three-way PERMANOVA further quantized the contributions of climate and soil properties on vertical heterogeneity of all soil elements, which were 35.2 % and 50.5 %, respectively. This study used various statistical tools to reveal the dominant factors affecting the vertical heterogeneity of soil elements. These findings provided a scientific overview of element distribution on the Tibetan Plateau and significant references for the vertical distribution of elements in the topsoil of other snow mountains worldwide.

[Coupling Relationship Between Soil Functions and Environmental Factors Along an Altitudinal Gradient: A Case Study of the Meili Mountain].

Soil respiration and extracellular enzyme activity are important components of the material cycle of mountain ecosystems and play key roles in maintaining ecosystem functions. To explore the coupling relationship between soil functions and environmental factors, the soil functional indicators, environmental factors, and effects of altitude on the soil function of 36 soil samples from 12 altitudes of the Meili Mountain were analyzed. The results showed that there were significant differences in soil respirations and enzyme activities among altitudes of Meili Mountain, and high-altitude areas had higher soil functions. Soil functions increased with altitudinal difference. PCA analysis showed that the first three axes explained 56.7%, 17.4%, and 8.7% of the variance in soil functional elevation change, respectively, indicating that the functional changes related to carbon and phosphorus were higher than those related to nitrogen. There were significant correlations between environmental factors and soil functional indicators; soil function indicators had stronger correlations with soil physicochemical properties than with climatic factors. Altitude mainly affected soil function indirectly by affecting soil physicochemical properties and climatic factors. These results have great scientific significance for improving the understanding of the material cycle and ecological function of the Meili Mountain ecosystem and provide an important reference for in-depth study of the altitude distribution pattern and evolution characteristics of the soil function of the mountain ecosystem.

Niclosamide attenuates inflammatory cytokines via the autophagy pathway leading to improved outcomes in renal ischemia/reperfusion injury.

Renal ischemia/reperfusion (I/R) injury is a debilitating condition that leads to loss renal function and damage to kidney tissue in the majority of patients with acute kidney disease. Previous studies have indicated that autophagy serves a protective function in renal I/R injury. In the present study, the effect of the anthelmintic niclosamide in the regulation of inflammatory responses in kidney I/R was investigated. A total of 40 Sprague-Dawley rats were randomly divided into the following 5 groups (n=8 in each group): Sham group; renal I/R injury; renal I/R injury plus 3­methyladenine (3­MA) treatment (15 mg/kg); renal I/R injury plus niclosamide (25 mg/kg); and renal I/R injury plus rapamycin (10 mg/kg). The expression levels of autophagy­associated proteins in kidney samples obtained from rats with I/R injury were examined using reverse transcription­quantitative polymerase chain reaction and western blotting techniques. In addition, histopathological alterations, the expression of cytokines and renal function were evaluated. Treatment with niclosamide was associated with induction of autophagy and an overall improvement in renal function. There was an increased expression of autophagosome­associated proteins, suggesting a strong correlation between autophagy and improvement of renal function. The increased levels of anti­inflammatory cytokines and decreased levels of pro­inflammatory cytokines provided additional evidence that niclosamide may be effective for the treatment of renal I/R injury. Clinical studies are required to further validate the results of the present study.

Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation.

To identify a new drug candidate for treating endometriosis which has fewer side effects, a new polymeric nanoparticle gene delivery system consisting of polyethylenimine-grafted chitosan oligosaccharide (CSO-PEI) with hyaluronic acid (HA) and small interfering RNA (siRNA) was designed. There was no obvious difference in sizes observed between (CSO-PEI/siRNA)HA and CSO-PEI/siRNA, but the fluorescence accumulation in the endometriotic lesion was more significant for (CSO-PEI/siRNA)HA compared with CSO-PEI/siRNA due to the specific binding of HA to CD44. In addition, the (CSO-PEI/siRNA)HA nanoparticle gene therapy significantly decreased the endometriotic lesion sizes with atrophy and degeneration of the ectopic endometrium. The epithelial cells of ectopic endometrium from rat models of endometriosis showed a significantly lower CD44 expression than control after treatment with (CSO-PEI/siRNA)HA. Furthermore, observation under an electron microscope showed no obvious toxic effect on the reproductive organs. Therefore, (CSO-PEI/siRNA)HA gene delivery system can be used as an effective method for the treatment of endometriosis.

[Expression and regulation of drug transporters in placenta].

Placenta, an important organ, mediates the exchange of nutrients and metabolites between mother and fetus. The transporters, including ATP-binding cassette (ABC) transporters and solute carrier (SLC), expressed in the syncytiotrophoblast play a vital role in substance exchange. Some transporters, such as organic cation transporters (OCTs) and organic anion transporters (OATs), mediate the uptake of endogenous substances and drugs. Some transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins(MRPs), can excrete their substrates from the syncytiotrophoblast to the maternal circulation. However, the expression and activity of these transporters are not uniform throughout the gestation period, since they can be affected by physiological and pathological changes during pregnancy or drugs. Thus, an understanding of the role of placental transporters and the variation in their expression and activity in response to physiological and pathological changes is essential for efficient and safe therapy during pregnancy, and it also has important value in the development of drug treatment in pregnancy.

Stereoselective metabolism of tetrahydropalmatine enantiomers in rat liver microsomes.

Tetrahydropalmatine (THP), with one chiral center, is an active alkaloid ingredient in Rhizoma Corydalis. The aim of the present paper is to study whether THP enantiomers are metabolized stereoselectively in rat, mouse, dog, and monkey liver microsomes, and then, to elucidate which Cytochrome P450 (CYP) isoforms are predominately responsible for the stereoselective metabolism of THP enantiomers in rat liver microsomes (RLM). The results demonstrated that (+)-THP was preferentially metabolized by liver microsomes from rats, mice, dogs, and monkeys, and the intrinsic clearance (Cl(int)) ratios of (+)-THP to (-)-THP were 2.66, 2.85, 4.24, and 1.67, respectively. Compared with the metabolism in untreated RLM, the metabolism of (-)-THP and (+)-THP was significantly increased in dexamethasone (Dex)-induced and ß-naphthoflavone (ß-NF)-induced RLM; meanwhile, the Cl(int) ratios of (+)-THP to (-)-THP in Dex-induced and ß-NF-induced RLM were 5.74 and 0.81, respectively. Ketoconazole had stronger inhibitory effect on (+)-THP than (-)-THP, whereas fluvoxamine had stronger effect on (-)-THP in untreated and Dex-induced or ß-NF-induced RLM. The results suggested that THP enantiomers were predominately metabolized by CYP3A1/2 and CYP1A2 in RLM, and CYP3A1/2 preferred to metabolize (+)-THP, whereas CYP1A2 preferred (-)-THP.

Relative contribution of small and large intestine to deglycosylation and absorption of flavonoids from Chrysanthemun morifolium extract.

The flower of Chrysanthemum morifolium Ramat (CM) is an established part of traditional Chinese medicine (TCM). Luteolin and apigenin flavonoids are the effective components of the CM extract (CME); however, they exist in the orally consumed CME as glycosides. The present study was carried out to determine the relative contribution of the small and large intestine to the deglycosylation and absorption of flavonoids from CME using a rat model system. The distribution of luteolin and apigenin in rat gastrointestinal (GI) luminal contents, tissues, and plasmas was assessed after the oral administration of CME. The hydrolysis and absorption of CME flavonoids in different rat GI segments were further evaluated by using in situ ligated models and cell-free extracts prepared from rat GI segments. The results demonstrated that after the oral administration of CME, the magnitude of deglycosylation in rats was surprisingly high (about 30%) in the stomach and upper intestine within the first 5 min after ingestion, and early absorption in the plasma was detected. The results from site-limited administration revealed that the stomach was the initial hydrolysis site, while the duodenum was the first effective absorption site for CME flavonoids. Diminishing microbial flora in the jejunum had no significant effect on the hydrolysis of the flavonoids from CME, but the cell-free extracts prepared from rat GI segments demonstrated a strong ability to hydrolyze. Taken together, our findings suggest that enteric disposition contributes to the pharmacokinetics of luteolin and apigenin after oral administration of CME. Moreover, the upper digestive tract plays a key role in the hydrolysis and absorption of flavonoids in CME.

Crystalline characteristics of alpha precipitates in Ti-15V-3Sn-3Al-3Cr alloy.

The experiment was designed to analyse the orientation relationship between alpha precipitates and beta matrix and to determine the habit plane of alpha phase in Ti-15-3 alloy using transmission electron microscopy. The orientation relationship was turned out to be 110(alpha)||111(beta) and (001)(alpha)||{110}(beta) obtained from diffraction patterns, which corresponded to Burgers orientation relationship. Based on the patterns and the crystal structure, it was determined that there were 12 possible orientation relationships between alpha precipitates with beta matrix and alpha precipitates had 12 variants. Meanwhile, the transformation matrixes of 12 orientation relationships were established. Diffraction patterns of 001(beta), 110(beta) and 311(beta) zone axes were also calibrated by these matrixes, which verified the correctness of proposed orientation relationship. Diffraction spots of lamelliform alpha precipitates spread along the [111](beta) and [1 1 1 ](beta) directions in diffraction patterns of [1 1 0](beta) zone axis, but they do not spread in diffraction patterns of [111](beta) zone axis, which indicates that the habit plane of variant 1, 2 and 3 is (111)(beta). Moreover, the habit planes of variant 4-6, variant 7-9 and variant 10-12 are (1 1 1)(beta), (1 1 1)(beta) and (1 1 1 )(beta) respectively. To sum up, the habit plane of alpha precipitates is {111}(beta).

Stereoselective protein binding of tetrahydropalmatine enantiomers in human plasma, HSA, and AGP, but not in rat plasma.

Tetrahydropalmatine (THP) is one of the active alkaloid ingredients of Rhizoma Corydalis. THP has a chiral center, and the stereoselective pharmacokinetics and tissue distribution have been reported. The aim of the present article is to study the stereoselective protein binding of THP using equilibrium dialysis followed by HPLC-UV analysis. The results showed that THP stereoselectively binds to human serum albumin (HSA), alpha(1)-acid glycoprotein (AGP), and proteins in human plasma. The fraction binding of (+)-THP was significantly higher than that of (-)-THP, whereas such stereoselectivity was not found in rat plasma. The affinity of HSA and AGP to (+)-THP, expressed as nK(A), were 9.0 x 10(3) M(-1) and 2.34 x 10(5) M(-1), respectively, which were notablely higher than to (-)-THP, with the nK(A) of 3.4 x 10(3) M(-1) and 1.44 x 10(5) M(-1), respectively. The binding site of HSA for (-)-THP was Site I, whereas for (+)-THP was both Site I and Site II. The F1/S variants of AGP were proved to be the key variants (-)- and (+)-THP binding to both. Finally, the AGP binding drugs, such as mifepristone, were demonstrated to reduce the fraction binding of (-)- and (+)-THP with pure AGP (1 mg/ml) but did not affect the fraction binding of both (-)- and (+)-THP with proteins in human plasma. It can be concluded that protein binding of THP is species dependent and stereoselective, both HSA and AGP contribute to the stereoselective binding to THP enatiomers, and AGP binding drugs may not cause the drug-drug interaction on THP in healthy human plasma.

[Determination of bis (p-fluorobenzyl) trisulfide and bis (p-fluoro-benzyl) disulfide in lungs of rat by HPLC].

OBJECTIVE: To establish an HPLC method for analysis of bis(p-fluorobenzyl) trisulfide(BFTS) and bis(p-fluorobenzyl)disulfide(BFDS) in the lungs of rat. METHODS: 5.0 ml extract solvent (n-hexane: isopropyl alcohol=95:5, v/v) and 20 microl of 11.50 microg/ml dibenzyl disulfide (internal standard) were added to 0.2 g lung sample followed by homogenization. After centrifugation, 4.0 ml of supernatant was separated and vaporized to dryness, and the residue was reconstituted in mobile phase for HPLC analysis. The HPLC analysis was performed on an SB C18 column using acetonitrile and water (65:35, v/v) as mobile phase with a flow rate of 1.0 ml/min with UV detection at 220 nm. RESULT: The calibration curves for BFTS and BFDS in sample were linear over the concentration ranges of 0.04712-14.78 microg/g(r=0.999) and 0.04831-23.96 microg/g(r=0.999), respectively. The limits of quantification were 0.04712 microg/g and 0.04831 microg/g for BFTS and BFDS, respectively. The assay recoveries for BFTS and BFDS ranged from 95.71%-107.2% and 90.00%-110.5%, respectively. The precisions were obtained with RSD of <10%. The developed method was successfully applied to study the content of BFTS and BFDS in the lungs of rats after intravenous injection of 12.5 mg/kg BFTS. CONCLUSION: The method developed is simple, selective, repeatable and accurate, which can be applied to study the tissue distribution of BFTS and BFDS.