[Optimization of mulched drip irrigation amount for peanut based on AHC model in northwestern Liaoning, China]. / 基于AHC模型的辽西北花生膜下滴灌灌水量优化.

To evaluate the applicability of AHC (agro-hydrological chemical and crop systems simulator) model and explore the suitable irrigation amount for peanut (Arachis hypogaea) under mulched drip irrigation in the semi-arid areas of northwestern Liaoning Province, based on the two-year field experimental data of peanut in 2016 and 2017, the model parameters were firstly chosen for global sensitivity analysis. Then, module parameters of soil moisture and crop growth were calibrated and validated. Finally, AHC model was used to analyze the responses of peanut yield and water use efficiency (WUE) to different irrigation amounts. The results showed that the two extremely sensitive parameters of the model were saturated hydraulic conductivity in the first and second layers of soil. Root mean square error (RMSE) and mean relative error (MRE) between simulated and measured values of soil water content ranged from 0.02 to 0.03 cm3·cm-3 and 1.5% to 2.3%, respectively. The RMSE and MRE of leaf area index and plant height were 0.3-0.6, 4.2-4.5 cm, and 5.0%-8.9%, 5.2%-6.8%, respectively. The MRE of peanut yield and water consumption were both within 5%, indicating that the model was suitable for simulating soil moisture and peanut growth in the northwest Liaoning Province. With the increases of irrigation amounts, peanut yield increased and water use efficiency decreased. Considering both peanut yield and WUE, we recommend that the optimal mulched drip irrigation amounts for peanut in the semi-arid areas of Northwestern Liaoning in test year (normal year) was 80-97 mm.

Intensive fibrosarcoma-binding capability of the reconstituted analog and its antitumor activity.

Fibrosarcomas are highly aggressive malignant tumors. It is urgently needed to explore targeted drugs and modalities for more effective therapy. Matrix metalloproteinases (MMPs) play important roles in tumor progression and metastasis, while several MMPs are highly expressed in fibrosarcomas. In addition, tissue inhibitor of metalloproteinase 2 (TIMP2) displays specific interaction with MMPs. Therefore, TIMP2 may play an active role in the development of fibrosarcoma-targeting agents. In the current study, a TIMP2-based recombinant protein LT and its enediyne-integrated analog LTE were prepared; furthermore, the fibrosarcoma-binding intensity and antitumor activity were investigated. As shown, intense and selective binding capability of the protein LT to human fibrosarcoma specimens was confirmed by tissue microarray. Moreover, LTE, the enediyne-integrated analog of LT, exerted highly potent cytotoxicity to fibrosarcoma HT1080 cells, induced apoptosis, and caused G2/M arrest. LTE at 0.1 nM markedly suppressed the migration and invasion of HT1080 cells. LTE at tolerated dose of 0.6 mg/kg inhibited the tumor growth of fibrosarcoma xenograft in athymic mice. The study provides evidence that the TIMP2-based reconstituted analog LTE may be useful as a targeted drug for fibrosarcome therapy.

Effect of a poloxamer 407-based thermosensitive gel on minimization of thermal injury to diaphragm during microwave ablation of the liver.

AIM: To assess the insulating effect of a poloxamer 407 (P407)-based gel during microwave ablation of liver adjacent to the diaphragm. METHODS: We prepared serial dilutions of P407, and 22.5% (w/w) concentration was identified as suitable for ablation procedures. Subsequently, microwave ablations were performed on the livers of 24 rabbits (gel, saline, control groups, n = 8 in each). The P407 solution and 0.9% normal saline were injected into the potential space between the diaphragm and liver in experimental groups. No barriers were applied to the controls. After microwave ablations, the frequency, size and degree of thermal injury were compared histologically among the three groups. Subsequently, another 8 rabbits were injected with the P407 solution and microwave ablation was performed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cr) in serum were tested at 1 d before microwave ablation and 3 and 7 d after operation. RESULTS: In vivo ablation thermal injury to the adjacent diaphragm was evaluated in the control, saline and 22.5% P407 gel groups (P = 0.001-0.040). However, there was no significant difference in the volume of ablation zone among the three groups (P > 0.05). Moreover, there were no statistical differences among the preoperative and postoperative gel groups according to the levels of ALT, AST, BUN and Cr in serum (all P > 0.05). CONCLUSION: Twenty-two point five percent P407 gel could be a more effective choice during microwave ablation of hepatic tumors adjacent to the diaphragm. Further studies for clinical translation are warranted.

Inhibition of murine breast cancer growth and metastasis by survivin-targeted siRNA using disulfide cross-linked linear PEI.

Biodegradable disulfide-containing polyethyleneimine (PEI) derivatives showed great potential as siRNA vectors for the treatment of cancer due to the reduction-sensitive property. In this study, we developed and characterized a hyperbranched disulfide cross-linked PEI (lPEI-SS) based on linear PEI (lPEI) by ring-opening reaction of propylene sulfide. We evaluated the efficiency of lPEI-SS as a siRNA vector in vitro with luciferase reporter gene system, and investigated the anti-tumor efficacy of survivin-targeted siRNA (siRNA(sur)) on 4T1 murine breast cancer model using lPEI-SS synthesized here. Results from cytotoxicity and hemolysis assay proved that lPEI-SS showed favorable cell and blood compatibility. lPEI-SS/siRNA polyplexes prepared under the optimized condition were compact spherical particles with the average size of 229.0nm and zeta potential of 42.67mV. Cellular uptake of lPEI-SS/siRNA polyplexes was significantly improved due to the higher branching degree of lPEI-SS over the parent lPEI. lPEI-SS/siRNA(sur) exhibited great anti-proliferation effect on 4T1 cell line, which was found to be caused by the induction of apoptosis. Most importantly, results of tumor volume, tumor weight and histological observation demonstrated that lPEI-SS/siRNA(sur) polyplexes effectively inhibited the tumor growth and metastasis of 4T1 murine breast cancer model.

[Transpiration of Hedysarum scoparium in arid desert region of Shiyang River basin, Gansu Province].

By using heat pulse technique, an investigation on the transpiration of Hedysarum scoparium was conducted in the arid desert region of Shiyang River basin, Gansu Province. The results indicated that with increasing inserted depth of probe, the sap flow velocity in H. scoparium xylem had a trend from high to low. In the taproot with smaller diameter, the average sap flow velocity at different positions was faster, and the change range was bigger. Among the taproots with different diameters, there existed a larger difference in the magnitude of sap flux, but the change trend was similar, i. e., smaller at nighttime and larger at daytime, and showing a multi-peak curve. A linear correlation was observed between the diurnal sap flux and the reference crop evapotranspiration, and the transpiration mainly occurred during the period from June to September, occupying 79.04% of the total annual transpiration. The diurnal sap flux of H. scoparium at its later growth period had significant correlation with the moisture content in 0-50 cm sand layer, but no correlations with that in other sand layers. The effects of main meteorological factors on the sap flux of H. scoparium were in the sequence of air temperature > vapor pressure difference > wind speed.

[Relative bioavailability of cyclosporine A-loaded hydroxypropyl methylcellulose phthalate nanoparticles for oral administration in rats].

AIM: To study the preparation of hydroxypropyl methylcellulose phthalate (HPMCP) nanoparticles and compare its pharmacokinetic characteristics with Neoral. METHODS: HPMCP nanoparticles loaded cyclosporine A were prepared by solvent-nonsolvent method. CyA-HP50 nanoparticles, CyA-HP55 nanoparticles and Neoral were orally administered at the dosage of 15 mg x kg(-1) to rats. The CyA concentration in blood were determined by HPLC. Pharmacokinetic parameters were calculated by 3P97 program. RESULTS: The concentration-time data of the three preparations were best fit by two compartment model. The relative bioavailability of CyA-HP50 and CyA-HP55 nanoparticles calculated by the AUC0-72 were 82.3% and 119.6%, bioequivalent to the reference of Neoral. The relative bioavailability of CyA-HP55 nanoparticles was 145.3% of CyA-HP50 nanoparticles. CONCLUSION: CyA HPMCP nanoparticles could be prepared easily and reproducibly. It was found that the oral absorption of CyA can be increased by using the HPMCP nanoparticles.

[Influence of suspending agents on relative bioavailability of cyclosporine A-loaded HPMCP nanoparticles for oral administration to rats].

OBJECTIVE: To study the influence of suspending agents on the relative bioavailability of Cyclosporine A-loaded HPMCP(HP55) nanoparticles for oral administration. METHODS: Suspending agents such as Vanzan, HPMC, Carbopol were added into cyclosporine A-loaded HP55 nanoparticles. The suspended nanoparticle formulations and Neoral were administered orally in a dosage of 15 mg/kg to rats. The CyA concentrations in the blood sample were determined by HPLC. Pharmacokinetic parameters were calculated by 3P97. RESULTS: The concentration-time data of these preparations were best fit by two compartment model with a weight of 1/C(2). Compared with the reference Neoral microemulsion, the relative bioavailability of 2 g/L Carbopol, 5 g/L Vanzan, 8, 5, 3 g/L HPMC suspended nanoparticles were 70.2%, 84.3%, 90.0%, 94.5% and 97.7%, respectively. Their viscosity values were 550, 362, 105, 30 and 15 mPaxs, respectively. CONCLUSION: With the increase in viscosity, the relative bioavailability of nanoparticle formulations decreased. So, it is important to select the appropriate viscosity of suspending agents in the formulation design.

Bioavailability and pharmacokinetics of cyclosporine A-loaded pH-sensitive nanoparticles for oral administration.

The pH-sensitive cyclosporine A (CyA) nanoparticles were prepared by the solvent displacement method with enteric dissolved polymer of hydroxypropyl methylcellulose phthalate (HPMCP; including HP50 and HP55). The CyA nanoparticles were analyzed by HPLC for yield and encapsulation efficiency, dynamic light scattering for particle size and transmission electron microscopy (TEM) for morphology. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids were evaluated in rats, compared with the current available CyA microemulsion (Neoral). The bioavailability of CyA-HP55 nanoparticle colloids with various suspending agents was also investigated. The results obtained demonstrated that the pH-sensitive CyA nanoparticles with a particle size of 50-60 nm and encapsulation efficiency over 95% could be reproducibly prepared. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids calculated by the AUC(0-72) were 82.3% and 119.6%, similar to the reference of Neoral, while the bioavailability of CyA-HP55 nanoparticle colloids was found to be higher than that of CyA-HP50 nanoparticle colloids. The increase of mean residence time (MRT) and the decrease of elimination constant of the central compartment (K10) for both CyA-HP50 and CyA-HP55 nanoparticle colloids compared with the reference indicated significant sustained release of CyA from the nanoparticles. The effects of the suspending agents on the bioavailability of CyA-HP55 nanoparticles were observed, and the bioavailability decreased as the concentration of suspending agents or the viscosity of the nanoparticle colloids increased.