Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis

Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant‐bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 ± 37 μg/mL at 15 min. The systemic clearance was 347 ± 117 mL/h/kg, and the steady‐state volume of distribution was 223 ± 67 mL/kg. Dialysis clearance was 71.1 ± 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 ± 0.150. The half‐life (T_1/2) in dogs with IHD decreased compared with those without IHD, and the reduction in T_1/2 was greater in renal failure patients than in normal patients. Sixty‐nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.     

Generation of Salmonella ghost cells expressing fimbrial antigens of enterotoxigenic Escherichia coli and evaluation of their antigenicity in a murine model

Salmonella Typhimurium ghost cells expressing K88ab, K88ac, K99, and FasA fimbriae of enterotoxigenic Escherichia coli (ETEC) in their envelopes were constructed. The genes encoding the fimbriae were individually cloned into an expression plasmid, pMMP81, carrying the asd gene, which was subsequently electroporated into the Δasd S. Typhimurium mutant. Plasmid pJHLP99, carrying the phiX174 lysis gene E, was also subsequently electroporated into the Salmonella mutant. The presence of the individual fimbriae on the ghost cells was examined by Western blot analysis. Forty BALB/c mice were equally divided into 2 groups of 20 mice each. Group A mice were intramuscularly vaccinated with a mixture of the 4 ghost cells expressing the individual fimbriae. The group B mice were inoculated with sterile phosphate-buffered saline as a control. The antigen-specific serum IgG concentrations were significantly higher in group A than in group B from week 2 until week 6 after inoculation. In addition, the antigen-specific IgA concentrations in fecal samples were significantly higher in group A than in group B at week 2 after inoculation. A large difference between the groups in the number of antigen-specific IgA-secreting cells in the small intestine was observed by immunohistochemical study. Also, the splenic lymphocyte proliferative responses were significantly greater in group A than in the control mice. These results suggest that vaccination with our Salmonella ghost cells can induce both humoral and cell-mediated immune responses and that the increased number of antigen-specific IgA-secreting cells in the small intestine may be correlated with the elevated fecal IgA immune response.     

Tumour necrosis factor stimulated gene 6 intrinsically regulates PD-L1 expressions in breast cancer cells,leading to modulation of tumour microenvironment

Recent studies have shown that tumour cells express tumour necrosis factor-inducible gene 6 (TSG-6) and its protein, which is known to play a key role in regulating excessive immune responses and proliferation and growth of mesenchymal stem cells (MSCs). It has not been confirmed whether the inhibition of TSG-6 for tumour cells can suppress tumour cell growth and regulate the activation of immune cells in the tumour microenvironment (TME). TSG-6-specific small interfering RNA was transfected into canine and human breast cancer cells (CIPp, CIPm and BT-20). TSG-6-down-regulated (siTSG-6) cells showed decreased cell proliferation, migration, and invasion abilities. Decreased mRNA expressions of NF-κB, STAT3 and Sox2, confirming that TSG-6 is an upper factor governing tumour growth and metastasis. Notably, siTSG-6 cells showed significantly decreased expression levels of CD44 and PD-L1. Direct and indirect co-culture of canine peripheral blood mononuclear cells (cPBMCs) and the siTSG-6 cells showed significant activation in M1 type macrophages and cytotoxic T cells. They also showed a tendency to decrease in the expression of CTLA-4 and increase in the expression of PD-1. In conclusion, this study suggests that the down-regulation of TSG-6 in breast cancer cells could not only suppress tumour growth and metastasis, and but also regulate TME. Since modulation of immune checkpoint proteins occurs in both tumour cells and immune cells, inhibiting TSG-6 and its protein within the TME could be novel therapeutic target for anticancer treatment.     

Effects of AMF inoculation on growth of Panax ginseng C.A. Meyer seedlings and on soil structures in mycorrhizosphere

We aimed to investigate the effects of inoculating Panax ginseng C.A. Meyer seedlings with arbuscular mycorrhizal fungi (AMF) by examining the root colonization, plant nutrition uptake, growth characteristics, and soil aggregation of P. ginseng seedlings inoculated at the time of transplantation. At 16 weeks, the AMF spore density per 30 g of fresh mycorrhizosphere in seedlings inoculated with AMF (AMF+ seedlings) was 256.8 and that in seedlings not inoculated with AMF (AMF− seedlings) was 186.3, respectively. The colonization rate of AMF in the lateral roots of AMF+ seedlings was approximately 19% higher than that in the lateral roots of AMF− seedlings. The patterns of AMF colonization in ginseng roots were similar to those of the Paris-type mycorrhizal association. Plant growth characteristics, such as plant height, root length, leaf area, number of lateral roots, fresh weight of shoots and roots, and chlorophyll content, were significantly enhanced in AMF+ seedlings compared to AMF− seedlings. The macronutrient content (P, K, and Ca) and micronutrient content (Cu, Fe, and Zn) of both shoots and roots were also significantly higher in AMF+ seedlings compared to AMF− seedlings. Furthermore, glomalin content and soil aggregation were significantly enhanced in AMF inoculated areas. Our results indicate that AMF inoculation may enhance the growth of ginseng seedlings by improving the uptake of mineral nutrients and the soil structure in mycorrhizosphere.     

Hydroxycinnamoylmalic acids and their methyl esters from pear (Pyrus pyrifolia Nakai) fruit peel

Two novel caffeoylmalic acid methyl esters, 2-O-(trans-caffeoyl)malic acid 1-methyl ester (6) and 2-O-(trans-caffeoyl)malic acid 4-methyl ester (7), were isolated from pear (Pyrus pyrifolia Nakai cv. Chuhwangbae) fruit peels. In addition, 5 known hydroxycinnamoylmalic acids and their methyl esters were identified: 2-O-(trans-coumaroyl)malic acid (1), 2-O-(cis-coumaroyl)malic acid (2), 2-O-(cis-coumaroyl)malic acid 1-methyl ester (3), 2-O-(trans-coumaroyl)malic acid 1-methyl ester (4), and 2-O-(trans-caffeoyl)malic acid (phaselic acid, 5). The chemical structures of these compounds were determined by spectroscopic data from ESI MS and NMR. Of all the isolated compounds, five hydroxycinnamoylmalic acids and their methyl esters (2-4, 6, 7) were identified in the pear for the first time.     

Root‐associated microbes in sustainable agriculture: models,metabolites and mechanisms

Since the discovery of penicillin in 1928 and throughout the ‘age of antibiotics’ from the 1940s until the 1980s, the detection of novel antibiotics was restricted by lack of knowledge about the distribution and ecology of antibiotic producers in nature. The discovery that a phenazine compound produced by Pseudomonas bacteria could suppress soilborne plant pathogens, and its recovery from rhizosphere soil in 1990, provided the first incontrovertible evidence that natural metabolites could control plant pathogens in the environment and opened a new era in biological control by root‐associated rhizobacteria. More recently, the advent of genomics, the availability of highly sensitive bioanalytical instrumentation, and the discovery of protective endophytes have accelerated progress toward overcoming many of the impediments that until now have limited the exploitation of beneficial plant‐associated microbes to enhance agricultural sustainability. Here, we present key developments that have established the importance of these microbes in the control of pathogens, discuss concepts resulting from the exploration of classical model systems, and highlight advances emerging from ongoing investigations. © 2019 Society of Chemical Industry     

The grafting of recycled polyol from waste polyurethane foam onto new polyurethane and its impact on shape recovery and water vapor permeation

Recycled polyols from waste polyurethane (PU) foams were grafted onto PU to improve the properties such as tensile strength, shape recovery, low-temperature flexibility, and water compatibility. The recycled polyol was either purified by column chromatography before grafting or was used directly for grafting. The soft segment melting temperature of PU did not notably increase with the addition of polyol, whereas the glass transition temperature increased with increased polyol content. The tensile strength sharply increased at low polyol content and decreased at high polyol content, while the strain at break did not significantly change with an increase in polyol content. The shape recovery at 10 oC notably improved compared with unmodified PU and remained high after four cyclic tests. Polyol-grafted PU demonstrated better lowtemperature flexibility and reduced the water vapor permeability of PU membranes. Overall, grafting recycled polyol onto PU significantly improved the tensile stress, shape recovery, and low-temperature flexibility of PU.     

贵州省城乡人口变化与建设用地扩张的脱钩关系

[目的]研究贵州省人口与建设用地变化的关系,以促进土地资源优化配置。[方法]利用贵州省2000—2017年城乡人口及建设用地数据,采用脱钩模型和GIS空间分析方法,研究城乡人地关系演化过程。[结果]贵州省城镇人口持续增加,乡村人口逐年减少;城乡建设用地面积不断扩大,城镇和乡村建设用地同向增长。2000—2008年,贵州省城乡人口变化与建设用地扩张关系为强负脱勾类型,乡村人口与乡村建设用地变化为强负脱钩类型,城镇人口与城镇建设用地变化为扩张负脱钩类型。农村人口减少伴随着建设用地增加,农村人地关系处于较不合理状态;城镇人口和建设用地二者均增长,但建设用地增幅快于人口增幅。[结论]贵州省应积极推动农村宅基地流转,提高城乡建设用地集约利用水平,促进城乡融合。     

Glutamic acid supplementation recovers the reduced performance of weanling pigs fed reduced crude protein diets

This study was conducted to evaluate the supplementation of glutamic acid(Glu)to reduced protein diets on the performance of weanling pigs.One hundred and eighty crossbred weanling pigs([Yorkshire
Landrace]
Duroc,21 d old)having similar body weight(BW)of 6.45 kg were randomly allotted to 1 of 6 dietary treatments(5 pigs per pen[2 barrows and 3 gilts];6 pens per treatment)based on BW and sex during a 6-week trial.Dietary treatments consisted of positive control(PC)diet formulated to have 226.9,205.6,and 188.8 g crude protein(CP)during phases 1,2,and 3,respectively,and negative control(NC)diets with 20 g CP reduction from PC diets and addition of Glu with increasing levels,resulting in the calculated Lys-to-Glu ratios of 1:2.25,1:2.30.1:2.35,1:2.40,and 1:2.45,designated as NC,NC1,NC2,NC3,and NC4,respectively.The BW of pigs receiving PC diet was higher(P<0.05)than those receiving NC diet at d 7,21 and 42.A higher(P<0.05)average daily gain(ADG)from d 1 to 7,8 to 21,22 to 42 and during the overall experiment period was observed in pigs fed PC than NC diet.Pigs fed NC diets including the graded level of Glu linearly increased(P<0.05)BW at d 42,ADG and gain-to-feed ratio(G:F)during the overall experimental period.In addition,trends in linear increase in BW(P=0.056)at d 7 and ADG from d 1 to 7 and d 22 to 42(linear effect,P=0.081,P=0.058 respectively)were observed.A tendency in the linear increment of NH3(P=0.082)at d 21 and linear reduction in methyl mercaptans(P=0.054)emission at d 42 was observed in pigs fed NC diets supplemented with graded level of Glu.In conclusion,supplementing the reduced protein diet with Glu enhanced the growth performance in weanling pigs suggesting that supplementation of Glu can compensate the reduction of 2%CP in the basal diets.     

Identification and quantification of cyclolinopeptides in five flaxseed cultivars

Cyclolinopeptides are a group of naturally occurring hydrophobic cyclic peptides found in flaxseed and flax oil that have immunosuppressive activity. This study describes the measurement of flaxseed cyclolinopeptide concentrations using an internal standard HPLC method. In addition, the concentration of cyclolinopeptides in the seed of Canadian flax cultivars grown at two locations over two years is reported. The data are consistent with the formation of flaxseed cyclolinopeptides from two ribosome-derived precursors. Each precursor protein includes the sequences corresponding to three cyclolinopeptides from which those cyclolinopeptides are presumably derived by precursor processing. The concentrations of cyclolinopeptides C and E, which are encoded by the same gene sequence, are highly correlated, and the concentrations of cyclolinopeptides D, F, and G, which are encoded by a second gene sequence, are also highly correlated. The strong correlation between the cyclolinopeptides arising from the same gene may prove to be important in understanding how peptide concentration is controlled. Additional research may lead to approaches to improve flax either as a platform for peptide production or as a source of oil with improved drying properties and flavor.