Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole

Simultaneous quantification of 6,7-di-hydroxyligustilide and gastrodin in rat plasma by LC-MS: application to pharmacokinetic study of tianshu capsule

A LC-MS method was developed and validated for simultaneous determination of 6, 7-di-hydroxyligustilide and gastrodin in rat plasma, and which was subsequently applied in the pharmacokinetic analysis of an administration of a Chinese herbal extract containing Chuanxiong Rhizoma and Gastrodia Elata Rhizome, i.e. TianShu capsule against migraine. The analytes were separated on a Kromasil C18 column with a gradient elution program and detected without interference in the selected ion monitoring mode with positive electrospray ionization. The linear range was 0.010-10.0 μg/mL for 6,7-di-hydroxyligustilide and 0.025-25.0 μg/mL for gastrodin with the limit of quantitation of 0.01 and 0.025 μg/mL, respectively. The intra-day and inter-day precisions for the entire validation were less than14.7 % of RSD. The pharmacokinetic parameters indicated that 6, 7-di-hydroxyligustilide and gastrodin are absorbed rapidly and reached a maximum concentration within one hour, which was consistent with the clinical requirements for the rapid relieving the symptoms of migraine.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Effects of a ‘one film for 2 years’ system on the grain yield, water use efficiency and cost-benefit balance in dryland spring maize (Zea mays L.) on the Loess Plateau, China

‘One film for 2 years’ (PM2) has been proposed as a practice to control the residual film pollution; however, its effects on grain-yield, water-use-efficiency and cost-benefit balance in dryland spring maize production have still not been systematically explored. In this study, we compared the performance of PM2 with the annual film replacement treatment (PM1) and no mulch treatment (CK) on the Loess Plateau in 2015-2016. Our results indicated the following: (1) PM2 was effective at improving the topsoil moisture (0-20 cm) at sowing time and at seedling stage, but there was no significant influence on soil water storage, seasonal average soil moisture or evapotranspiration; (2) PM2 induced significantly higher cumulative soil temperatures compared to CK, and there was no significant difference between PM2 and PM1; (3) no significant differences were identified in grain-yield and water-use-efficiency between PM1 and PM2, and compared to CK, they improved by 16.3% and 15.5%, respectively; (4) because of lower cost of plastic film, tillage, film laying and remove in PM2, economic profits improved by 21% and 70% compared to PM1 and CK. This research suggested that PM2 was effective at alleviating the spring drought and was beneficial in reducing poverty traps in dryland

Effects of Biodegradable Plastic Film on Carbon Footprint of Crop Production

Polyethylene film mulch (PM) is a kind of widely used technology to improve crop yields worldwide; however, because of a problem related with plastic residual pollution, it has gradually been replaced by biodegradable plastic film mulch (BDP). Although BDP has helped to solve the plastic residual pollution, its consequences in terms of greenhouse gas (GHG) emissions have rarely been revealed. Related knowledge is important for forming low-carbon development strategies for the plastic industry and agriculture. The objective of this study is to evaluate the influence of BDP on GHG emissions at different stages of its life cycle, and determine whether replacing polyethylene (PE) film with BDP film is a helpful way to reduce national GHG emissions. The results of this study suggest that the application of BDP improved the GHG emissions associated with agricultural inputs, but induced lower GHG emissions at the growing stage and the waste disposal stage, and resulted in lower total area-scale GHG emissions. Compared to the no mulch (NM) cultivation system, the yield-scale carbon footprint was reduced in both the PM and BDP cultivation systems, which meant that both PM and BDP produced lower GHG emissions than NM for the production of the same amount of grain. It was concluded that BDP is not only a measure to control the problem of plastic residue pollution in agriculture, but it can also mitigate the GHG emissions

Modelling soil water dynamic in rain-fed spring maize field with plastic mulching

Numerical solution of the Richards equation with Hydrus-2D model is a low cost and fast way to get information on spatio-temporal soil water dynamics. Previous researches with Hydrus-2D have developed two different approaches to represent the rainfall infiltration in irrigated field with plastic mulching: ‘BP’ – an approach comprised by bare strip boundary and plastic strip boundary without consideration of film side infiltration;‘BP + ’- an approach comprised by bare strip and plastic strip with integrating the process of film side infiltration by increasing the rainfall infiltration amount in bare strip. Nevertheless, the performance of these approaches has not yet been evaluated in rain-fed fields. Considering much more dominant role of rainfall infiltration in rain-fed agriculture, we tested an additional approach which comprised a bare strip, plastic strip and planting hole (BPH) to take into account the effect of the rainfall canopy redistribution and film side infiltration, and we compared its performance to the two existing approaches. Results suggested BP completely failed to reproduce the soil water content (SWC) in all soil layers of plastic strip and in the deep soil layers of bare strip. BP+ overestimated the SWC in 0–20 cm of the bare strip, while the performance of BPH was acceptable in different positions. After that, we compared the soil water distribution between no-mulched field (NM) and plastic mulched field (PM) with approach BPH. Our simulation showed that the highest SWC in PM occurred near the planting hole, SWC in the center zone of plastic strip was lower, while SWC in the bare strip was lowest. PM improves the soil water availability not only in the plastic strip but also in the bare strip as compared to NM

Soil nitrogen and its fractions between long-term conventional and no-tillage systems with straw retention in dryland farming in northern China

Knowledge about the changes in soil nitrogen pools under different tillage managements is necessary to assess the feasibility of adoption of conservation practices for sustaining productivity and protecting the environment in dryland farming in northern China. We investigated the long-term effects (22 years) of no-till with residue retention (NTR) on total soil N and its fractions in a dry-land winter wheat (Triticum aestivum L.) cropping system in northern China. Compared with conventional tillage without residue retention (CT), significantly higher soil total N (STN) concentrations were observed in the surface soil layer (0–10 cm) under NTR. Meanwhile, more soil N accumulated for the whole soil profile (0 to 60 cm) in the NTR (3.38 Mg ha− 1) treatment relative to the CT (3.17 Mg ha− 1) treatment. The particulate organic matter N (PON), microbial biomass N (MBN), and water extractable organic N (WEON) levels in the NTR treatments were 52.3%, 116%, and 69.4% greater at a depth of 0–5 cm and 41.6%, 108%, and 44.9% greater at a depth of 5–10 cm, respectively, compared with the CT treatment. However, no differences were observed below the 10 cm layer. At a depth of 0–60 cm, the soil NH4-N content under CT was higher than that under NTR. However, the soil NO3-N contents in the NTR treatments were significantly greater at a depth of 0–10 cm and were not significantly different at a depth of 10–60 cm, relative to the CT treatment. Significantly positive correlations were observed between the STN and the labile organic N fractions. Overall, the results show that no-till coupled with residue retention is an effective management method for improving soil N stocks and increasing soil fertility. Nonetheless, other benefits associated with NT and residue retention present greater challenges regarding their popularization and application in the dryland farming areas in northern China

A Bibliometric and Visualized Overview of Hydrogen Embrittlement from 1997 to 2022

The mechanical properties of materials deteriorate when hydrogen embrittlement (HE) occurs, seriously threatening the reliability and durability of the hydrogen system. Therefore, it is important to summarize the status and development trends of research on HE. This study reviewed 6676 publications concerned with HE from 1997 to 2022 based on the Web of Science Core Collection. VOSviewer was used to conduct the bibliometric analysis and produce visualizations of the publications. The results showed that the number of publications on HE increased after 2007, especially between 2017 and 2019. Japan was the country with the highest numbers of productive authors and citations of publications, and the total number of citations of Japanese publications was 24,589. Kyushu University was the most influential university, and the total number of citations of Kyushu University publications was 7999. Akiyama was the most prolific and influential author, publishing 88 publications with a total of 2565 citations. The USA, South Korea and some European countries are also leading in HE research; these countries have published more than 200 publications. It was also found that the HE publications generally covered five topics: “Hydrogen embrittlement in different materials”, “Effect of hydrogen on mechanical properties of materials”, “Effect of alloying elements or microstructure on hydrogen embrittlement”, “Hydrogen transport”, and “Characteristics and mechanisms of hydrogen related failures”. Research hotspots included “Fracture failure behavior and analysis”, “Microstructure”, “Hydrogen diffusion and transport”, “Mechanical properties”, “Hydrogen resistance”, and so on. These covered the basic methods and purposes of HE research. Finally, the distribution of the main subject categories of the publications was determined, and these categories covered various topics and disciplines. This study establishes valuable reference information for the application and development of HE research and provides a convenient resource to help researchers and scholars understand the development trends and research directions in this field

Dynamic Evolution of the Ecological Carrying Capacity of Poverty-Stricken Karst Counties Based on Ecological Footprints: A Case Study in Northwestern Guangxi, China

The karst area in northwestern Guangxi is poor, underdeveloped, and ecologically fragile. It is experiencing rocky desertification, which creates challenges that are more severe than those of other regional ecological environments. In this paper, the ecological footprint (EF) model is used to analyze the ecological carrying capacity (EC) in northwestern Guangxi from 1995 to 2015, and the differences in karst counties with different poverty levels are discussed. The results show that (1) since 1995, the EC of northwestern Guangxi has continued to decrease, the EF has continued to increase, the ecological deficit (ED) has been expanding, and the status of the region has been unsustainable for a long time. (2) The evolutionary patterns, EF and EC of karst counties with different poverty levels are different. The county with the lowest poverty rate has the fastest growth rate of the per capita EF. The county with the largest proportion of karst area has the lowest EC. (3) It is recommended that different types of counties take different measures, including strengthening ecological environment protection, carrying out rocky desertification control and ecological resettlement projects, and reducing energy consumption. This study can provide information for the sustainable development of the karst region and provide decision support for regional poverty alleviation