Evaluation of pharmacological and pharmacokinetic herb-drug interaction between irinotecan hydrochloride injection and Kangai injection in colorectal tumor-bearing mice and healthy rats

Introduction: Kangai (KA) injection, a Chinese herbal injection, is often used in combination with irinotecan (CPT-11) to enhance the effectiveness of anti-colorectal cancer treatment and alleviate side effects. However, the combined administration of this herb-drug pair remains controversial due to limited pre-clinical evidence and safety concerns. This study aimed to determine the pre-clinical herb-drug interactions between CPT-11 and KA injection to provide a reference for their clinical co-administration.Methods: In the pharmacological study, BALB/c mice with CT26 colorectal tumors were divided into four groups and treated with vehicle alone (0.9% saline), CPT-11 injection (100 mg/kg), KA injection (10 mL/kg), or a combination of CPT-11 and KA injection, respectively. The tumor volume of mice was monitored daily to evaluate the therapeutic effect. Daily body weight, survival rate, hematopoietic toxicity, immune organ indices, and gut toxicity were analyzed to study the adverse effects. Healthy Sprague-Dawley rats in the pharmacokinetic study were administered KA injection only (4 mL/kg), or a combination of CPT-11 injection (20 mg/kg) and KA injection, respectively. Six key components of KA injection (oxymatrine, matrine, ginsenoside Rb1, Rg1, Re, and astragaloside IV) in rat plasma samples collected within 24 h after administration were determined by LC-MS/MS.Results: The pharmacological study indicated that KA injection has the potential to enhance the anti-colorectal cancer efficacy of CPT-11 injection and alleviate the severe weight loss induced by CPT-11 injection in tumor-bearing mice. The pharmacokinetic study revealed that co-administration resulted in inhibition of oxymatrine metabolism in rats, evidenced by the significantly reduced Cmax and AUC0-t of its metabolite, matrine (p < 0.05), from 2.23 ± 0.24 to 1.38 ± 0.12 μg/mL and 8.29 ± 1.34 to 5.30 ± 0.79 μg h/mL, respectively. However, due to the similar efficacy of oxymatrine and matrine, this may not compromise the anti-cancer effect of this herb-drug pair.Discussion: This study clarified the pre-clinical pharmacology and pharmacokinetic benefits and risks of the CPT-11-KA combination and provided a reference for their clinical co-administration

Aroma precursors of cigars from different tobacco parts and origins, and their correlations with sensory characteristics

Cigars are developing rapidly around the world, but the content characteristics of aroma precursors and their contribution to sensory perception have not been fully elucidated. In this study, 69 aroma precursors from 61 tobaccos of different parts and origins were systematically determined, and the sensory characteristics of middle leaves from different origins and their correlation with aroma precursors were evaluated. The results showed that tobacco parts mainly affected amino acid content, and contents of nicotine, oxalic acid, malic acid, isovaleric acid, cystine, glutarnine, glycine, isoleucine, glutamicacid, asparticacid, and fructose-proline were significantly changed. Tobacco origins mainly influenced the contents of amino acids, polyacids and high fatty acids, and sugar alcohols, and significantly affected the contents of myosmine, anabasine, nonanoic acid, propanetriol, mannitol, mannose, glucose, alanine, arginine, glutarnine, glutamicacid, histidine, serine, threonine, tryptophan, fructose-alanine, and fructose-asparagine. The flavor characteristics were prominent by wood aroma, and the style and quality characteristics varied greatly among different origins of middle leaves. There were 34, 21, and 22 aroma precursors with high correlations with flavor, style, and quality characteristics. This study provides support for regulating the content and coordination of aroma precursors in different tobacco parts and origins to improve sensory characteristics

Downregulation of Hlx

T-bet plays an important role in immunoregulation; it induces the differentiation of Th1 together with the homeobox transcription factor gene Hlx. Recent studies show that T-bet and Th1-associated factors are critical in regulating tumor development. However, the contributions of Hlx in the occurrence and development of cancer remain unknown. In this study, the Hlx, T-bet, Runx3, and IFN-γ were measured in PBMC from patients with gastric cancer and the correlation between Hlx and T-bet or IFN-γ was assessed. The expression levels of Hlx, T-bet, and IFN-γwere significantly decreased, and there was a positive correlation between Hlx and T-bet or IFN-γ. In addition, the Runx3 expression was also downregulated with the lower T-bet mRNA level. These results suggested that the decreased Hlx expression was closely associated with T-bet and Runx3 downregulations and may contribute to the development of gastric cancer

Soil functions and ecosystem services research in the Chinese karst Critical Zone

Covering extensive parts of China, karst is a critically important landscape that has experienced rapid and intensive land use change and associated ecosystem degradation within only the last 50 years. In the natural state, key ecosystem services delivered by these landscapes include regulation of the hydrological cycle, nutrient cycling and supply, carbon storage in soils and biomass, biodiversity and food production. Intensification of agriculture since the late-20th century has led to a rapid deterioration in Critical Zone (CZ) state, evidenced by reduced crop production and rapid loss of soil. In many areas, an ecological ‘tipping point’ appears to have been passed as basement rock is exposed and ‘rocky desertification’ dominates. This paper reviews contemporary research of soil processes and ecosystems service delivery in Chinese karst ecosystems, with an emphasis on soil degradation and the potential for ecosystem recovery through sustainable management. It is clear that currently there is limited understanding of the geological, hydrological and ecological processes that control soil functions in these landscapes, which is critical for developing management strategies to optimise ecosystem service delivery. This knowledge gap presents a classic CZ scientific challenge because an integrated multi-disciplinary approach is essential to quantify the responses of soils in the Chinese karst CZ to extreme anthropogenic perturbation, to develop a mechanistic understanding of their resilience to environmental stressors, and thereby to inform strategies to recover and maintain sustainable soil function. © 2019 Elsevier B.V

Compliance optimization of a continuum with bimodulus material under multiple load cases

Topology optimization of a continuum with bimodulus material under multiple load cases (MLC) is investigated by using material replacement method. Using traditional methods to solve such a problem will encounter two difficulties for the sake of the stress-dependent behavior of bimodulus material. One is the nonlinear behavior of bimodulus material. The other is the definition of local material property under MLC. The present method can overcome the difficulties easily. It contains three major aspects. Firstly, the bimodulus material is replaced with two isotropic materials in optimization. Secondly, the local stiffness is modified according to the stress states because of material replacement. Meanwhile, which one of the isotropic materials to be adopted for each element in the next structural analysis in optimization is determined by the replacement criterion under MLC, i.e., comparing the local CSED (strain energy density (SED) caused by compression stresses) and the TSED (SED caused by tension stresses), the isotropic material which modulus equal to the compression modulus of bimodulus material is used as the material properties of the element if the CSED is greater than the TSED, or vice versa. Finally, the relative densities of elements as the design variables are updated using a gradient-based method. As the reanalysis with respect to material properties for obtaining the accurate deformation is merged into the global iterations of optimization, the efficiency of optimization is highly improved. Numerical examples are given to express the validity and high efficiency of the present method. Results also show that the difference between tension modulus and compression modulus influences the optimal topology of a structure with bimodulus material under MLC, obviously

Effect of Adjuvants on the Wetting Behaviors of Bifenthrin Droplets on Tea Leaves

The hydrophobic epicuticle wax on fresh leaves of tea tree (Camellia sinensis (L.) 0. Kuntze) leads to the loss of pesticide droplets, reducing efficacy. In this study, four adjuvants were selected to improve the diffusion and adhesion of bifenthrin droplets on the surface of tea leaves at different growth stages. The coupling effect of bifenthrin and adjuvants on the time-dependent and concentration-dependent wettability of droplets was investigated, and the difference in the wettability between bud and leaf was explained by observing the surface morphology. It was found that adjuvants effectively reduced the contact angle of droplets and accelerated the diffusion speed, and the above phenomenon became obvious with the increase in the adjuvant concentration. The wetting promotion of young leaves was more significant due to the reduced epicuticle wax and the greater roughness compared with fresh buds. The surface tension of the pesticide mixture was negatively correlated with the cosine of contact angle after adding the four adjuvants regardless of the growth stage of tea leaves. The contact angle of 0.2% Silwet L-77 decreased to 0° within 10 s, but the extreme wettability led to the decrease in adhesion with the increase in concentration. However, the wettability and adhesion on the surface of tea leaves were simultaneously suitable with more than 0.1% nonionic surfactant. The minimum concentration of the optimal adjuvant proposed in this study can provide an experimental basis and guide more efficient plant protection in tea gardens

Effect of Adjuvants on the Wetting Behaviors of Bifenthrin Droplets on Tea Leaves

The hydrophobic epicuticle wax on fresh leaves of tea tree (Camellia sinensis (L.) 0. Kuntze) leads to the loss of pesticide droplets, reducing efficacy. In this study, four adjuvants were selected to improve the diffusion and adhesion of bifenthrin droplets on the surface of tea leaves at different growth stages. The coupling effect of bifenthrin and adjuvants on the time-dependent and concentration-dependent wettability of droplets was investigated, and the difference in the wettability between bud and leaf was explained by observing the surface morphology. It was found that adjuvants effectively reduced the contact angle of droplets and accelerated the diffusion speed, and the above phenomenon became obvious with the increase in the adjuvant concentration. The wetting promotion of young leaves was more significant due to the reduced epicuticle wax and the greater roughness compared with fresh buds. The surface tension of the pesticide mixture was negatively correlated with the cosine of contact angle after adding the four adjuvants regardless of the growth stage of tea leaves. The contact angle of 0.2% Silwet L-77 decreased to 0° within 10 s, but the extreme wettability led to the decrease in adhesion with the increase in concentration. However, the wettability and adhesion on the surface of tea leaves were simultaneously suitable with more than 0.1% nonionic surfactant. The minimum concentration of the optimal adjuvant proposed in this study can provide an experimental basis and guide more efficient plant protection in tea gardens

A Comparison of Electrical Breakdown Models for Polyethylene Nanocomposites

The development of direct current high-voltage power cables requires insulating materials having excellent electrically insulation properties. Experiments show that appropriate nanodoping can improve the breakdown strength of polyethylene (PE) nanocomposites. Research indicates that traps, free volumes, and molecular displacement are key factors affecting the breakdown strength. This study comprehensively considered the space charge transport, electron energy gain, and molecular chain long-distance movement during the electrical breakdown process. In addition, we established three simulation models focusing on the electric field distortion due to space charges captured by traps, the energy gain of mobile electrons in free volumes, the free volume expansion caused by long-distance movement of molecular chains under the Coulomb force, and the energy gained by the electrons moving in the enlarged free volumes. The three simulation models considered the electrical breakdown modulated by space charges, with a maximum electric field criterion and a maximum electron energy criterion, and the electrical breakdown modulated by the molecular displacement (EBMD), with a maximum electron energy criterion. These three models were utilized to simulate the breakdown strength dependent on the nanofiller content of PE nanocomposites. The simulation results of the EBMD model coincided best with the experimental results. It was revealed that the breakdown electric field of PE nanodielectrics is improved synergistically by both the strong trapping effect of traps and the strong binding effect of molecular chains in the interfacial regions

Spatiotemporal Patterns and Key Driving Factors of Soil Salinity in Dry and Wet Years in an Arid Agricultural Area with Shallow Groundwater Table

Soil salinization is a major eco-environmental problem in irrigated agro-ecosystems. Understanding regional soil salinity spatial patterns and seasonal dynamics and their driving factors under changing environments is beneficial to managing soil salinity to maintain agricultural production in arid agricultural areas. To better investigate this topic, soil salinity was measured, ranging from topsoil to the depth of 1.8 m in an irrigation district with 68 sampling sites before and after the crop growing seasons of the dry year of 2017 and wet year of 2018. Soil texture, groundwater table depth, groundwater salinity, and crop type were monitored. The results indicated that an increase in soil salinity in the root zone (0–0.6 m) was accompanied by a decrease in soil salinity in the deep soil (0.6–1.8 m) through the crop growing season due to water movement from the deep layer to shallow layer, whereas the opposite trend was observed during the fallow seasons. During the dry year, the area with soil desalted was measured to be 19.89%, 14.42%, and 2.78% lower at depths of 0–0.6 m, 0.6–1.2 m, and 1.2–1.8 m than that during the wet year. The groundwater table depth in the crop growing season had the least impact on the change in root zone soil salinity (p > 0.05). Interactions between crop types and groundwater table depth had a significant effect on the change of soil salinity in the root zone during the growing season of the dry year, but were insignificant during the wet year. Crop types, groundwater table depth, and climate conditions determined the contribution of shallow groundwater to crop water consumption and, to a greater extent, soil salinity. Regression tree analysis showed that groundwater salinity and soil texture had a greater influence on soil salinity than groundwater table depth and land elevation. The effect of groundwater on soil salinity is strongly related to soil texture, and the salinity of fine-textured soil was 36–54% greater than that of coarse-textured soil due to large capillary action. Therefore, we suggest strengthening groundwater management in areas with fine-textured soil to relieve soil salinization, particularly during dry years