Ceftiofur (CEF), a broad-spectrum third-generation cephalosporin, exhibits a good activity against a broad range of gram-negative and gram-positive bacteria, including many that produce β-lactamase. To design a rational dosage regimen for the drug in lactating Holstein dairy cows, the pharmacokinetic properties of ceftiofur hydrochloride injection were investigated in six cows after intravenous, intramuscular, and subcutaneous administration of single dose of 2.2 mg/kg BW (body weight). Plasma concentration-time curves and relevant parameters were best described by noncompartmental analysis through WinNonlin 6.3 software. After subcutaneous administration, the absolute bioavailability was 61.12% and the T (elimination half-life) was 8.67 ± 0.72 hr. The C (maximum plasma concentration) was 0.88 ± 0.21 μg/ml and T (the time after initial injection to when C occurs) was 1.50 ± 0.55 hr. The MRT (mean residence time) was 11.00 ± 0.30 hr. Following intramuscular administration, the C (1.09 ± 0.21 μg/ml) was achieved at T (1.20 ± 0.26 hr) with an absolute availability of 70.52%. In this study, the detailed pharmacokinetic profiles of free and total CEF showed that this drug is widely distributed and rapidly eliminated and may contribute to a better understanding of the usage of ceftiofur hydrochloride injection in Holstein dairy cows.

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The objective of this study was to investigate the pharmacokinetic profile of tildipirosin (TD) in 24 beagle dogs following intravenous (i.v.) and intramuscular (i.m.) administration, respectively, at 2, 4, and 6 mg/kg. Plasma samples at certain time points (0-14 days) were collected, and the concentrations of drug were quantified by UPLC-MS/MS. Plasma concentration-time data and relevant parameters were described by noncompartmental through WinNonlin 6.4 software. After single i.m. injection at 2, 4, and 6 mg/kg body weight, mean maximum concentration (C max ) was 412.73 ± 76.01, 1,051 ± 323, and 1,061 ± 352 ng/ml, respectively. Mean time to reach C max was 0.36 ± 0.2, 0.08 ± 0.00, and 0.13 ± 0.07 hr after i.m. injection at 2, 4, and 6 mg/kg, respectively. The mean value of T 1/2λz for i.m. administration at doses of 2, 4, and 6 mg/kg was 71.39 ± 28.42, 91 .33 ± 50.02, and 96.43 ± 45.02 hr, respectively. The mean residence times were 63.81 ± 10.96, 35.83 ± 15.13, and 38.18 ± 16.77 hr for doses of 2, 4, and 6 mg/kg, respectively. These pharmacokinetic characteristics after i.m. administration indicated that TD could be rapidly distributed into tissues on account of the high lipid solubility and then released into plasma. In addition, the absolute bioavailability of 2 mg/kg after i.m. injection was 112%. No adverse effects were observed after i.v. and i.m. administration. Tildipirosin (20,

SUMMARYCultivar selection is a dominant factor in crop production to obtain high yield. While previous studies have evaluated a range of impacts and adaptation of climate change (CC) on crop yield, few studies have focused on evaluating the effectiveness of changing cultivars with different vernalization requirements as an adaptation. In the present study, mean and inter-annual variability of yield were quantified for three winter wheat cultivar types at three ecological sites (Shangzhuang in Beijing, Quzhou in Hebei and Huangfanqu in Henan) in the North China Plain, by linking a crop model and the outputs of Providing Regional Climates for Impacts Studies (PRECIS) for both the baseline (1961–90) and future SRES scenarios A2 and B2 (2070–2100). The results showed that a warming trend prolonged the length of the vegetative growth period of local cultivars through reduced vernalization, generally leading to a negative impact on yield. However, the introduction of cultivars with relatively lower vernalization demands from warmer southern to cooler northern regions could be an effective adaptation strategy to offset the negative impact of climatic change. Adjustment in cultivars increased yield at Shangzhuang and maintained it at Quzhou and Huangfanqu. Elevated CO2 would significantly increase yield in the future with or without considering the sensitivities of the selected cultivars. The inter-annual variability of yield generally increased in the A2 scenario, but decreased in the B2 scenario. Overall, winter wheat with semi-winter types or weak-winter types would grow preferentially, while cultivars with winter types would probably be reduced in future.

Aims This study evaluated the effects of Bacillus amyloliquefaciens TL106, isolated from Tibetan pigs’ faeces, on the growth performance, immune response, intestinal barrier function, morphology of jejunum, caecum and colon, and gut microbiota in the mice with enterohaemorrhagic Escherichia coli (EHEC)‐induced intestinal diseases. Methods and Results In all, 40 female C57BL/6J mice were randomly divided into four groups: mice fed a normal diet (Control), mice oral administration of TL106 daily (Ba), mice challenged with EHEC O157:H7 on day 15 (O157) and mice oral administration of TL106 daily and challenged with EHEC O157:H7 on day 15 (Ba+O157). The TL106 was administrated to mice for 14 days, and mice were infected with O157:H7 at day 15. We found that TL106 could prevent the weight loss caused by O157:H7 infection and alleviated the associated increase in pro‐inflammatory factors (TNF‐α, IL‐1β, IL‐6 and IL‐8) and decrease in anti‐inflammatory factor (IL‐10) in serum and intestinal tissues of mice caused by O157:H7 infection (P < 0·05). Additionally, TL106 could prevent disruption of gut morphology caused by O157:H7 infection, and alleviate the associated decrease in expression of tight junction proteins (ZO‐1, occludin and claudin‐1) in jejunum and colon (P < 0·05). In caecum and colon, the alpha diversity for bacterial community analysis of Chao and ACE index in Ba+O157 group were higher than O157 group. The TL106 stabilized gut microbiota disturbed by O157:H7, including increasing Lachnospiraceae, Prevotellaceae, Muribaculaceae and Akkermansiaceae, and reducing Lactobacillaceae. Conclusions We indicated the B. amyloliquefaciens TL106 can effectively protect mice against EHEC O157:H7 infection by relieving inflammation, improving intestinal barrier function, mitigating permeability disruption and stabilizing the gut microbiota. Significance and Impact of the Study Bacillus amyloliquefaciens TL106 can prevent and treat intestinal disease induced by EHEC O157:H7 in mice, which may be a promising probiotic for disease prevention in animals.