1. A pharmacokinetic study of valnemulin was conducted in healthy Muscovy ducks after intravenous (IV), intramuscular (IM) and oral administrations at a dose rate of 15 mg/kg body weight. 2. Drug concentrations in plasma were determined by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetics parameters of valnemulin were analysed by compartmental analysis using the WinNonlin program. 3. After IV administration, valnemulin was widely distributed with a volume of distribution based on a terminal phase (V(z)) of 8·19 ± 3·07 l/kg, a mean elimination half-life (t(1/2Ke)) of 2·63 h, and a clearance (Cl) value of 5·56 ± 1·53 l/kg/h. Following intramuscular and oral administration, valnemulin was rapidly absorbed; the C(max) was 0·44 ± 0·13 and 0·12 ± 0·02 µg/ml (achieved at 0·28 and 1·80 h), the t(1/2Ke) was 3·17 ± 3·83 and 4·83 ± 1·81 h, and the absolute bioavailability (F) was 72% and 37%, respectively. 4. The plasma profile of valnemulin exhibited favourable pharmacokinetic characteristics in Muscovy ducks, such as wide distribution, and rapid absorption and elimination, though oral bioavailability was low.
Nitrogen (N) and phosphorus (P) are two primary components of fertilizers for crop production. Coordinated acquisition and utilization of N and P are crucial for plants to achieve nutrient balance and optimal growth in a changing rhizospheric nutrient environment. However, little is known about how N and P signaling pathways are integrated. We performed transcriptomic analyses and physiological experiments to explore gene expression profiles and physiological homeostasis in the response of rice (Oryza sativa) to N and P deficiency. We revealed that N and P shortage inhibit rice growth and uptake of other nutrients. Gene Ontology (GO) analysis of differentially expressed genes (DEGs) suggested that N and Pi deficiency stimulate specific different physiological reactions and also some same physiological processes in rice. We established the transcriptional regulatory network between N and P signaling pathways based on all DEGs. We determined that the transcript levels of 763 core genes changed under both N or P starvation conditions. Among these core genes, we focused on the transcription factor gene NITRATE-INDUCIBLE, GARP-TYPE TRANSCRIPTIONAL REPRESSOR 1 (NIGT1) and show that its encoded protein is a positive regulator of P homeostasis and a negative regulator of N acquisition in rice. NIGT1 promoted Pi uptake but inhibited N absorption, induced the expression of Pi responsive genes PT2 and SPX1 and repressed the N responsive genes NLP1 and NRT2.1. These results provide new clues about the mechanisms underlying the interaction between plant N and P starvation responses.
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