Research review on methods of grassland health assessment.

Grassland health refers to the degree to which the integrity of soil and ecological processes is maintained, which primarily reflects the health status and productivity of grasslands. Evaluating the degree of grassland health is vital for the sustainable develop of grasslands. There are many methods for evaluating grassland health, with advantages and disadvantages for each one. However, there is still a lack of systematic literature offering an overview of methods of grassland health assessment and their applicability. We summarized 10 methods of grassland health assessment, including vigor-organization-resilience (VOR) index evaluation model, condition-vigor-organization-resilience (CVOR) index evaluation model, principal component analysis method, analytic hierarchy process, cluster analysis method, grey relational analysis, pressure-state-response evaluation model, fuzzy comprehensive evaluation method, comprehensive evaluation model of grassland health, and evaluation model using remote sensing technology. The advantages, disadvantages, and applicability of these methods were discussed, aiming to provide scientific basis for selecting more suitable methods of grassland health assessment for different scenarios in the future.

Effector Avr4 in Phytophthora infestans Escapes Host Immunity Mainly Through Early Termination.

Effector genes play critical roles in the antagonistic interactions between plants and pathogens. However, knowledge of mutation mechanisms and evolutionary processes in effector genes and the contribution of climatic factors to the evolution of effector genes are fragmented but important in sustainable management of plant diseases and securing food supply under changing climates. Here, we used a population genetic approach to explore the evolution of the Avr4 gene in Phytophthora infestans, the causal agent of potato blight. We found that the Avr4 gene exhibited a high genetic diversity generated by point mutation and sequence deletion. Frameshifts caused by a single base-pair deletion at the 194th nucleotide position generate two stop codons, truncating almost the entire C-terminal, which is important for effector function and R4 recognition in all sequences. The effector is under natural selection for adaptation supported by comparative analyses of population differentiation (FST ) and isolation-by-distance between Avr4 sequences and simple sequence repeat marker loci. Furthermore, we found that local air temperature was positively associated with pairwise FST in the Avr4 sequences. These results suggest that the evolution of the effector gene is influenced by local air temperature, and the C-terminal truncation is one of the main mutation mechanisms in the P. infestans effector gene to circumvent the immune response of potato plants. The implication of these results to agricultural and natural sustainability in future climate conditions is discussed.

Evidence for a synergistic effect of post-translational modifications and genomic composition of eEF-1α on the adaptation of Phytophthora infestans.

Genetic variation plays a fundamental role in pathogen's adaptation to environmental stresses. Pathogens with low genetic variation tend to survive and proliferate more poorly due to their lack of genotypic/phenotypic polymorphisms in responding to fluctuating environments. Evolutionary theory hypothesizes that the adaptive disadvantage of genes with low genomic variation can be compensated for structural diversity of proteins through post-translation modification (PTM) but this theory is rarely tested experimentally and its implication to sustainable disease management is hardly discussed. In this study, we analyzed nucleotide characteristics of eukaryotic translation elongation factor-1α (eEF-lα) gene from 165 Phytophthora infestans isolates and the physical and chemical properties of its derived proteins. We found a low sequence variation of eEF-lα protein, possibly attributable to purifying selection and a lack of intra-genic recombination rather than reduced mutation. In the only two isoforms detected by the study, the major one accounted for >95% of the pathogen collection and displayed a significantly higher fitness than the minor one. High lysine representation enhances the opportunity of the eEF-1α protein to be methylated and the absence of disulfide bonds is consistent with the structural prediction showing that many disordered regions are existed in the protein. Methylation, structural disordering, and possibly other PTMs ensure the ability of the protein to modify its functions during biological, cellular and biochemical processes, and compensate for its adaptive disadvantage caused by sequence conservation. Our results indicate that PTMs may function synergistically with nucleotide codes to regulate the adaptive landscape of eEF-1α, possibly as well as other housekeeping genes, in P. infestans. Compensatory evolution between pre- and post-translational phase in eEF-1α could enable pathogens quickly adapting to disease management strategies while efficiently maintaining critical roles of the protein playing in biological, cellular, and biochemical activities. Implications of these results to sustainable plant disease management are discussed.

Altitudinal Heterogeneity of UV Adaptation in Phytophthorainfestans Is Associated with the Spatial Distribution of a DNA Repair Gene.

Climate change is considered a major threat to society and nature. UV irradiation is the most important environmental genotoxic agent. Thus, how elevated UV irradiation may influence human health and ecosystems has generated wide concern in the scientific community, as well as with policy makers and the public in general. In this study, we investigated patterns and mechanisms of UV adaptation in natural ecosystems by studying a gene-specific variation in the potato late blight pathogen, Phytophthora infestans. We compared the sequence characteristics of radiation sensitive 23 (RAD23), a gene involved in the nucleotide excision repair (NER) pathway and UV tolerance, in P. infestans isolates sampled from various altitudes. We found that lower genetic variation in the RAD23 gene was caused by natural selection. The hypothesis that UV irradiation drives this selection was supported by strong correlations between the genomic characteristics and altitudinal origin (historic UV irradiation) of the RAD23 sequences with UV tolerance of the P. infestans isolates. These results indicate that the RAD23 gene plays an important role in the adaptation of P. infestans to UV stress. We also found that different climatic factors could work synergistically to determine the evolutionary adaptation of species, making the influence of climate change on ecological functions and resilience more difficult to predict. Future attention should aim at understanding the collective impact generated by simultaneous change in several climate factors on species adaptation and ecological sustainability, using state of the art technologies such as experimental evolution, genome-wide scanning, and proteomics.

The effectiveness of phenobarbital in patients with refractory status epilepticus undergoing therapeutic plasma exchange.

This study aimed to elucidate the therapeutic concentration range of phenobarbital (PB) for adults, as well as the influence of therapeutic plasma exchange (TPE) on plasma concentration of PB. We retrospectively reviewed consecutive patients diagnosed with refractory status epileptic (RSE) and treated with a bolus injection of PB as well as TPE, admitted to our neurocritical care unit from November 2015 to October 2016. Continuous electroencephalographic monitoring was performed routinely for these patients. TPE was performed using a continuous-flow cell separator. PB concentrations in the plasma and cerebrospinal fluid were measured by gas chromatography-mass spectrometer analysis before and after TPE. A total of seven patients were included; among these, one patient had RSE related to anti-N-methyl-D-aspartate receptor encephalitis, another patient had Hashimoto encephalopathy, and five patients had undetermined etiology. For patients with clinical and electrographic control (n=6), the plasma concentration of PB ranged from 138 to 243.7 µg/ml. In addition, of six paired plasma samples (before and after TPE) obtained from three patients, no significant differences between the concentrations of PB were detected (P=0.6), suggesting that TPE may not significantly affect the plasma concentration of PB. This study confirmed that PB more than 100 µg/ml was effective for adults with RSE. Moreover, TPE may not have an influence on the plasma concentration of PB.Video abstract: http://links.lww.com/WNR/A489.

Mechanism and kinetics of halogenated compound removal by metallic iron: Transport in solution, diffusion and reduction within corrosion films.

A detailed kinetic model comprised of mass transport (ktra), pore diffusion (kdif), adsorption and reduction reaction (krea), was developed to quantitatively evaluate the effect of corrosion films on the removal rate (kobs) of halogenated compounds by metallic iron. Different corrosion conditions were controlled by adjusting the iron aging time (0 or 1 yr) and dissolved oxygen concentration (0-7.09 mg/L DO). The kobs values for bromate, mono-, di- and tri-chloroacetic acids (BrO3-, MCAA, DCAA and TCAA) were 0.41-7.06, 0-0.16, 0.01-0.53, 0.10-0.73 h-1, with ktra values at 13.32, 12.12, 11.04 and 10.20 h-1, kdif values at 0.42-5.82, 0.36-5.04, 0.30-4.50, 0.30-3.90 h-1, and krea values at 14.94-421.18, 0-0.19, 0.01-1.30, 0.10-3.98 h-1, respectively. The variation of kobs value with reaction conditions depended on the reactant species, while those of ktra, kdif and krea values were irrelevant to the species. The effects of corrosion films on kdif and krea values were responsible for the variation of kobs value for halogenated compounds. For a mass-transfer-limited halogenated compound such as BrO3-, an often-neglected kdif value primarily determined its kobs value when pore diffusion was the rate-limiting step of its removal. In addition, the value of kdif might influence product composition during a consecutive dechlorination, such as for TCAA and DCAA. For a reaction-controlled compound such as MCAA, an increased krea value was achieved under low oxic conditions, which was favorable to improve its kobs value. The proposed model has a potential in predicting the removal rate of halogenated compounds by metallic iron under various conditions.

Effects of metal ions on disinfection byproduct formation during chlorination of natural organic matter and surrogates.

The effects of calcium, cupric, ferrous and ferric ions on the formation of trihalomethanes (THMs) and haloacetic acids (HAAs) were investigated using natural organic matter (NOM), small molecular weight NOM surrogates and natural water samples. The results showed that the effects were greatly dependent on the disinfection byproduct (DBP) precursor structure and molecular weight, and metal ions species. While using NOM as precursors, addition of 4.00 mM calcium ions increased the formation of THMs, dihaloacetic acids (DHAAs) and trihaloacetic acids (THAAs) by 24-47%, 51-61% and 15-25%, respectively. Addition of cupric ions at 0.02 mM increased the formation of THMs and DHAAs by 74-83% and 90-100%, respectively, but decreased the formation of THAAs by 26-27%. Similar effect was not observed when 0.04 mM ferrous or ferric ions were added. The effects of calcium and cupric ions on DBP formation were generally more evident for the NOM surrogates than that for NOM. The primary catalytic effect of calcium ions was due to complexation and less sensitive to molecular structure or weight, while that of cupric ions was attributed to redox reactions and greatly dependent on molecular structure. Both ferric and ferrous iron had substantial effects on the DBP formation of surrogates (citric acid and catechol in particular), which implied that the catalytic effects of ferric and ferrous iron mainly depended on molecular weight. The catalytic effect of cupric ions was also observed on natural water samples, while the effects of calcium, ferrous and ferric ions on natural water samples were not evident.

Afatinib reverses multidrug resistance in ovarian cancer via dually inhibiting ATP binding cassette subfamily B member 1.

ABCB1-mediated multidrug resistance (MDR) remains a major obstacle to successful chemotherapy in ovarian cancer. Herein, afatinib at nontoxic concentrations significantly reversed ABCB1-mediated MDR in ovarian cancer cells in vitro (p < 0.05). Combining paclitaxel and afatinib caused tumor regressions and tumor necrosis in A2780T xenografts in vivo. More interestingly, unlike reversible TKIs, afatinib had a distinctive dual-mode action. Afatinib not only inhibited the efflux function of ABCB1, but also attenuated its expression transcriptionally via down-regulation of PI3K/AKT and MAPK/p38-dependent activation of NF-κB. Furthermore, apart from a substrate binding domain, afatinib could also bind to an ATP binding domain of ABCB1 through forming hydrogen bonds with Gly533, Gly534, Lys536 and Ala560 sites. Importantly, mutations in these four binding sites of ABCB1 and the tyrosine kinase domain of EGFR were not correlated with the reversal activity of afatinib on MDR. Given that afatinib is a clinically approved drug, our results suggest combining afatinib with chemotherapeutic drugs in ovarian cancer. This study can facilitate the rediscovery of superior MDR reversal agents from molecular targeted drugs to provide a more effective and safer way of resensitizing MDR.

[Pharmacokinetics of amphotericin B in the cerebrospinal fluid during continuous intrathecal administration for treatment of cryptococcal neoformans meningitis].

OBJECTIVE: To explore the pharmacokinetics of amphotericin B (AMB) in the cerebrospinal fluid (CSF) during continuous intrathecal administration of AMB for treatment of cryptococcal neoformans meningitis (CNM). METHODS: The concentration of AMB in the CSF was measured using reversed phase high performance liquid chromatography (RP-HPLC) in 3 patients receiving continuous intrathecal infusion of AMB for CNM. RESULTS: AMB concentrations in the CSF of the 3 patients exceeded the minimal inhibitory concentration (MIC) of AMB against Cryptococcus neoformans. The concentration-time curve showed that AMB concentration in the CSF underwent obvious variations on the first day of intrathecal infusion and after additional AMB doses, but maintained a stable level (0.61-1.21 µg/ml) on the next day. CONCLUSION: [corrected] Continuous intrathecal administration of AMB can enhance the drug concentration in the CSF and maintain a stable and effective drug level for treatment of CNM.

[Pharmacokinetics, tissue distribution and magnetic resonance's response characterstics of folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles in mice and rats].

Folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles (FA-OCMCS-USPIO-NPs) are a novel molecular targeting MR contrast agent. This paper reperts the pharmacokinetics and magnetic resonance response characteristics of FA-OCMCS-USPIO-NPs in normal rats and mice, and discussed its distributing regularity in animals, providing basis for tumor targeting imaging. O-phenanthroline method was used to determine iron content in rats' plasma and mice's organs following high and low doses of nanoparticles injected through tail vein, and the blood concentration-time curve was drawn, the calculated t1/2 of two groups were greater than 7 h. The results of tissue distribution showed that only a small part of nanoparticles were swallowed by the liver and spleen, while none in the heart, lung and kidney. At the same times, the phagocytosis of nanoparticles did not change with the dose. The results of MRI showed that renal excretion occurred 4 hours after injection, and signal to noise ratio (SNR) of liver and kidney returned to normal levels 24 hours after injection. There were no nanoparticles in the lungs. So a part of nanoparticles escaped from phagocytosis of liver and spleen, and it owned lower toxicity and longer half-life. indicated its use for tumor-targeting imaging. All of these indicated its use for tumor-targeting imaging.

[Preparation and characterization of superparamagnetic iron oxide nanoparticles].

OBJECTIVE: To determine the physical and magnetic properties of superparamagnetic iron oxide (SPIO) nanoparticle prepared in our laboratory and evaluate its possibility for use as contrast agents in magnetic resonance imaging (MRI). METHODS: The SPIO nanoparticle was obtained by means of classical coprecipitation in dextran solution and its size determined by electron microscopy and photon-correlation spectroscopy. The iron content was determined by phenanthroline photometry, and T(2) values as well as relaxivity evaluated with a clinical MR system at 1.5T. RESULTS: Dextran-coated magnetite particles with a hydrodynamic diameter of 85.9 nm were prepared. The iron core size was 15 nm and the formation of Fe(3)O(4) crystal in SPIO nanoparticles was confirmed by X-ray diffraction (XRD) analysis. These particles possessed some characteristics of superparamagnetic and show a smaller spin-spin relaxation, with relaxivity and saturation magnetization of 0.1567 mmol(-1)/ms(-1) and 80 emu/g Fe, respectively. CONCLUSIONS: A stable SPIO nanoparticle with a dextran coating have been developed, and in vitro evaluation of its physical and magnetic properties suggests its potential for use as the contrast agent in MRI.

[Sampling of exhaled gas after intravenous administration of octafluoropropane-containing human albumin micropheres in dogs].

OBJECTIVE: To develop a method for quantitative collection of exhaled gas in anesthetized dogs at given time following intravenous administration of octafluoropropane (OFP)-containing human albumin micropheres for assessing the gas kinetics of OFP. METHODS: OFP-containing albumin micropheres were administered intravenously at 0.4, 0.8 and 1.2 ml/kg, respectively, in anesthetized and ventilated dogs. The exhaled air samples were analyzed by gas chromatography-tandem mass spectrometry (GC-MS-MS). RESULTS: The correlation curve between the area under curve (AUC) and administered dose was roughly linear (Y=1162.5X-417.38, r square=0.949 9). The total recovery rate was (119.49-/+27.62)% which was not significantly different from the rate of 100% (P>0.05). GC-MS-MS was accurate, sensitive, precise and applicable for OFP determination. CONCLUSION: The sampling method is useful for characterizing OFP pharmacokinetics in dogs, and also applicable for studying the pharmacokinetics of other gas-containing drugs.

Effect of Changtong oral liquid on serum cytokine concentrations in rats with postoperative intestinal adhesion.

OBJECTIVE: To observe the effects of Changtong oral liquid (CTOL) on the serum levels of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta(1), interleukin (IL)-1beta, IL-4, IL-6 and IL-10 in rats with postoperative intestinal adhesions. METHODS: Fifty-four male Sprague-Dawley rats were randomized into 6 equal groups, namely the normal control, model, Simo decoction (SMD) groups and three CTOL groups of low, moderate, and high doses, respectively. Intestinal adhesion was induced in the rats of the groups other than the normal control group. The rats in the normal control and model groups received intragastric administration of distilled water (10 ml/kg), and those in the 4 treatment groups had SMD (10 ml/kg) and CTOL (at 4.3, 8.6 and 17.2 g/kg for low, moderate, and high dose groups, respectively). On day 7 after surgery, blood samples were obtained from the rats for measurement of serum cytokine levels with enzyme-linked immunosorbent assay followed by adhesion grading according to a 5-grade scale. RESULTS: CTOL evidently reduced the severity of postoperative adhesions and decreased the serum levels of the proinflammatory cytokines such as TNF-alpha, IL-1beta, TGF-beta(1) and IL-6. However, it had no significant impact on serum levels of the anti-inflammatory cytokines IL-4 and IL-10 in rats with postoperative adhesion. CONCLUSION: Significant indices for postoperative adhesion assessment are established, which provides the experimental basis for evaluating clinical therapeutic effects of postoperative adhesions as well as for developing new therapeutic drugs.

[High-performance liquid chromatography combined with mass spectrum analysis for chromatographic fingerprinting of compound dandelion enema].

OBJECTIVE: To identify the active components of compound dandelion enema, a preparation from 7 traditional Chinese herbal drugs for treatment of gynecological diseases. METHODS: Three-dimensional high-performance liquid chromatography (3D-HPLC) was employed to separate the ethyl acetate extract of compound dandelion Enema, and HPLC combined with mass spectrum (MS) analysis used for chromatographic fingerprinting. RESULT: By comparing the ionic fragments of MS and retention time of each peak, the main active components in compound dandelion enema were determined, including caffeic acid, ferulic acid and protocatechualdehyde. CONCLUSION: HPLC coupled with mass spectroscopy can be used for qualitative analysis of compound dandelion enema.