Clinically significant drug-drug interaction between tacrolimus and fluconazole in stable renal transplant recipient and literature review.

WHAT IS KNOWN AND OBJECTIVE: Clinical use of fluconazole against fungal infections in renal transplant patients is complicated by the potentially marked and unpredictable drug-drug interactions (DDIs). We report a case of tacrolimus-fluconazole DDI in a stable renal transplant recipient and describe the mechanism, magnitude and duration of this DDI through a literature review. CASE SUMMARY: A 38-year-old woman experienced a 9.1-fold increase in dose-normalized tacrolimus trough level (trough concentration/weight-normalized daily dose) and an 87% decrease in weight-normalized daily dose (daily dose/body weight) in the treatment of documented Candida albicans oesophagitis by fluconazole. After discontinuation of fluconazole for 161 day, a 26% reduction in weight-normalized daily dose was required to maintain therapeutic exposure. WHAT IS NEW AND CONCLUSION: Oral fluconazole has a more significant impact on its drug interactions with tacrolimus than intravenous fluconazole. Gene screening for CYP3A5 6986 A>G and ABCB1 3435 C>T in organ transplant recipients may help in preventing DDI and facilitating tacrolimus dose adjustment.

Exploring Rosa roxburghii Tratt polysaccharides: From extraction to application potential in functional products - An in-depth review.

Rosa roxburghii Tratt (R. roxburghii), a unique ethnic medicine native to southwest China, is classified as both medicinal and culinary, offering a multitude of health benefits. Traditionally, it is used to eliminate diet and relieve diarrhea, nourish Yin and invigorate the spleen, dispel wind and dampness, enhance immunity, and promote the healthy development of the body. Furthermore, it serves as a remedy for ailments such as scurvy, night blindness, cancer, hyperlipidemia, hyperglycemia, and hypertension. R. roxburghii contains many nutritious and active ingredients, including proteins, vitamin C, inorganic salts, essential amino acids, polysaccharides, phenols, triterpenes, organic acids, and superoxide dismutase (SOD). Among them, polysaccharides stand out as pivotal bioactive components, comprising mannose, ribose, rhamnose, glucosamine hydrochloride, glucuronic acid, galacturonic acid, glucose, galactose, arabinose, and fucose, among others. R. roxburghii polysaccharides (RTFPs) present diverse biological activities, including antioxidant, anti-fatigue, hypoglycemic, anti-tumor, immune modulation, relief from ulcerative colitis, protection of neural stem cells from glutamate damage, and improvement of intestinal micro-ecology. Due to its distinctive bioactivity, the research on RTFPs is booming. While numerous extraction and purification techniques have successfully isolated and characterized RTFPs, comprehensive understanding of their chemical structure, mechanisms, structure-activity relationships, safety profiles, and practical applications remains limited. This knowledge gap hampers their optimal utilization and development. In response, this research offers an overview of extraction, purification, structure characteristics, biological activities, structure-activity relationships, and pharmaceutical application of RTFPs. Additionally, this research not only lays a theoretical basis for the comprehensive exploration and exploitation of R. roxburghii and its polysaccharide resources but also offers extensive knowledge and insights into the development and application of RTFPs as a novel functional foods and drugs.

Extraction, purification, structural characterization, and bioactivities of the genus Rhodiola L. polysaccharides: A review.

The genus Rhodiola L., an integral part of traditional Chinese medicine and Tibetan medicine in China, exhibits a broad spectrum of applications. This genus contains key compounds such as ginsenosides, polysaccharides, and flavonoids, which possess anti-inflammatory, antioxidant, hypoglycaemic, immune-enhancing, and anti-hypoxic properties. As a vital raw material, Rhodiola L. contributes to twenty-four kinds of Chinese patent medicines and 481 health food products in China, finding extensive application in the health food sector. Recently, polysaccharides have emerged as a focal point in natural product research, with applications spanning the medicine, food, and materials sectors. Despite this, a comprehensive and systematic review of polysaccharides from the genus Rhodiola L. polysaccharides (TGRPs) is warranted. This study undertakes a systematic review of both domestic and international literature, assessing the research advancements and chemical functional values of polysaccharides derived from Rhodiola rosea. It involves the isolation, purification, and identification of a variety of homogeneous polysaccharides, followed by a detailed analysis of their chemical structures, pharmacological activities, and molecular mechanisms, structure-activity relationship (SAR) of TGRPs. The discussion includes the influence of molecular weight, monosaccharide composition, and glycosidic bonds on their biological activities, such as sulfation and carboxymethylation et al. Such analyses are crucial for deepening the understanding of Rhodiola rosea and for fostering the development and exploitation of TGRPs, offering a reference point for further investigations into TGRPs and their resource utilization.

Site-specific apparent optimum air temperature for vegetation photosynthesis across the globe.

The apparent optimum air temperature for vegetation photosynthesis (Topt) is a key temperature parameter in terrestrial ecosystem models estimating daily photosynthesis or gross primary production (GPP, g C/m2/day). To date, most models use biome-specific Topt (Topt-biome) parameter values. Given vegetation acclimation and adaptation to local climate, site-specific Topt (Topt-site) is needed to reduce uncertainties in estimating daily GPP across the scales from site to region and the globe. Previous studies have demonstrated using the Enhanced Vegetation Index (EVI) derived from Moderate Resolution Imaging Spectroradiometer (MODIS) images and daytime air temperature data to estimate the Topt-site at the eddy covariance tower sites. This study used MODIS-derived EVI and ERA5 climate data to estimate and generate global Topt-site data products from 2000 to 2019. The Topt-site of individual pixels within a biome has large variation, which clearly cannot be represented accurately by the widely used Topt-biome. Therefore, using this global dataset of Topt-site estimates might significantly affect GPP simulation in current ecosystem models.

Isolation, structural features, and bioactivities of polysaccharides from Panax notoginseng: A review.

Panax notoginseng a member of the Araliaceous family, is a traditional Chinese medicinal and functional food with a long history. This herb contains various compounds, including saponins, alkaloids, flavones, and polysaccharides. Polysaccharides are the primary bioactive substances in P. notoginseng and have garnered significant attention from researchers globally. Numerous studies have confirmed that Panax notoginseng polysaccharides (PNPs) exhibit a wide range of remarkable bioactivities. These include anti-renal fibrosis, anti-tumor, anti-oxidation, anti-aging, anti-inflammation, immune regulation, liver protection, hypoglycemia, and anti-cerebral ischemia-reperfusion injury effects. They also promote bone growth, defect repair, and improve hematopoietic function. As a natural polysaccharide, PNPs show potential as a drug and functional material with good safety. This review systematically summarizes recent studies on the extraction and purification methods of PNPs, characterizing their chemical structure, biological activity, and application in various fields, aiming to provide theoretical insights and technical guidance for the development of PNPs as a novel functional food.

Thirty years of 3-D urbanization in the Yangtze River Delta, China.

Accurately capturing the urbanization process is essential for planning sustainable cities and realizing the United Nations Sustainable Development Goal 11. However, until recently, most of the studies on urban expansion in the world have focused on area growth but have little knowledge of height dynamics. This study mapped the spatial distribution of urban built-up areas (UBA) in the Yangtze River Delta (YRD), one of the most urbanized regions in China, to investigate the spatio-temporal evolution in both the horizontal and vertical directions from 1990 to 2020. We coupled and analyzed the horizontal and vertical urban expansion from the 3-D perspective and identified the dominant types. The results showed that 30 cities (73.17 % of the total number of cities) were increasing in the 3-D combined expansion intensity. The decreasing cities were mainly located in Anhui Province. Despite the increasing number of skyscrapers, horizontal growth has dominated urban expansion over the past three decades. The UBA area of the YRD has grown from 4,855.30 km2 to 44,447.15 km2, while the average building height has slowly decreased by 1.26 m. Significant unevenness and differences existed in horizontal and vertical expansions of varying provinces and cities. Our study can accurately grasp the 3-D urban expansion process in the YRD and could promote the efficient development and sustainable utilization of urban land resources in China and beyond.

CFD-based pesticide selection for a nozzle used in a six-rotor UAV in hover mode for tea spraying.

BACKGROUND: A key challenge for unmanned aerial vehicle (UAV) spraying sometimes used in tea plantations is the downwash flow structure there stronger than in crops. In addition, the UAV spray is affected by the relationship between the nozzle design and the pesticide. However, there is little current research on this aspect. As a preliminary step this study focuses on the most appropriate pesticide for a designated nozzle in a six-rotor UAV according to the nozzle-pesticide relationship using a three-dimensional computational fluid dynamics model. This model considers the downwash flow structure effect and nozzle spray performance in hover. Nozzle FVP110-02, widely used in six-rotor UAVs, is used as a representative nozzle and bifenthrin and tea saponin water, commonly used in tea plantations, are used as the pesticides. RESULTS: The downwash flow structure of the six-rotor UAV in hover was conveniently controlled by the flight height and rotational speed, thereby causing the turbulence to be more stable. For nozzle FVP110-02, bifenthrin was more appropriate than tea saponin water at the same concentration, whilst bifenthrin and tea saponin water at a concentration of 1:1000 showed the best performance under identical working conditions. CONCLUSION: The numerical model developed here was shown to be effective for investigating the relationship between nozzle and pesticide. Our findings will help to not only improve UAV spraying for tea cultivation but also provide guidelines for pesticide selection in crops. Further work will address the comparison of the rigorous qualification of the numerical simulations with the measurements by the field test. © 2023 Society of Chemical Industry.

Leaf shape, planting density, and nitrogen application affect soybean yield by changing direct and diffuse light distribution in the canopy.

When attempting to maximize the crop yield from field-grown soybean (Glycine max (L.) Merr.) by means of improving the light conditions for photosynthesis in the canopy, it is crucial to find the optimal planting density and nitrogen application rate. The soybean plants that were the subject of our experiment were cultivated in N-dense mutual pairs, and included two cultivars with different leaf shapes; one cultivar sported ovate leaves (O-type) and the other lanceolate leaves (L-type). We analyzed the results quantitatively to determine the amount of spatial variation in light distribution and photosynthetic efficiency across the canopy, and to gauge the effect of the experimental parameters on the yield as well as the photosynthetic light and nitrogen use efficiency of the crop. Results indicate that the different leaf shapes were responsible for significant disparities between the photosynthetic utilization of direct and diffuse light. As the nitrogen fertilizer rate and the planting density increased, the soybean plants responded by adjusting leaf morphology in order to maximize the canopy apparent photosynthetic light use efficiency, which in turn affected the leaf nitrogen distribution in the canopy. Despite the fact that the light interception rate of the canopy of the L-type cultivar was lower than that of the canopy of the O-type cultivar, we found its canopy apparent photosynthetic nitrogen and light use efficiency were higher. It was interesting to note, however, that the nitrogen and light use efficiency contributions associated with exposure to diffuse light were greater for the latter than for the former.

ALKBH5-mediated m6A demethylation of KCNK15-AS1 inhibits pancreatic cancer progression via regulating KCNK15 and PTEN/AKT signaling.

Long noncoding RNAs (lncRNAs) are regarded as crucial regulators in tumor progression. Potassium two pore domain channel subfamily K member 15 and WISP2 antisense RNA 1 (KCNK15-AS1) has been confirmed to inhibit the migration and invasion of pancreatic cancer (PC) cells. However, its downstream mechanism and effect on other cellular functions in PC remain unknown. This study probed the function and potential mechanism of KCNK15-AS1 in PC cell growth. RT-qPCR and western blot were employed to measure gene expression in PC cells. ISH was applied to analyze KCNK15-AS1 expression in PC tissues. Functional assays were utilized to evaluate PC cell proliferation, apoptosis, migration and EMT. Mechanical experiments were adopted to detect gene interaction in PC cells. The obtained data indicated that KCNK15-AS1 was down-regulated in PC cells and tissues. Overexpressing KCNK15-AS1 hindered cell proliferation, migration and EMT while facilitated cell apoptosis in PC. Mechanically, alkylation repair homolog protein 5 (ALKBH5) was verified to induce m6A demethylation of KCNK15-AS1 to mediate KCNK15-AS1 up-regulation. KCNK15-AS1 combined with KCNK15 5'UTR to inhibit KCNK15 translation. Moreover, KCNK15-AS1 recruited MDM2 proto-oncogene (MDM2) to promote RE1 silencing transcription factor (REST) ubiquitination, thus transcriptionally upregulating phosphatase and tensin homolog (PTEN) to inactivate AKT pathway. In conclusion, our study first confirmed that KCNK15-AS1 hinders PC cell growth by regulating KCNK15 and PTEN, suggesting KCNK15-AS1 as a potential biomarker of PC.

Effects of Initial Water Content on Microstructure and Mechanical Properties of Lean Clay Soil Stabilized by Compound Calcium-Based Stabilizer.

Initial water content significantly affects the efficiency of soil stabilization. In this study, the effects of initial water content on the compressibility, strength, microstructure, and composition of a lean clay soil stabilized by compound calcium-based stabilizer were investigated by static compaction test, unconfined compression test, optical microscope observations, environment scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction. The results indicate that as the initial water content increases in the range studied, both the compaction energy and the maximum compaction force decrease linearly and there are less soil aggregates or agglomerations, and a smaller proportion of large pores in the compacted mixture structure. In addition, for specimens cured with or without external water supply and under different compaction degrees, the variation law of the unconfined compressive strength with initial water content is different and the highest strength value is obtained at various initial water contents. With the increase of initial water content, the percentage of the oxygen element tends to increase in the reaction products of the calcium-based stabilizer, whereas the primary mineral composition of the soil-stabilizer mixture did not change notably.

Mechanical Properties and Carbonation Durability of Engineered Cementitious Composites Reinforced by Polypropylene and Hydrophilic Polyvinyl Alcohol Fibers.

Herein, the mechanical properties and carbonation durability of engineered cementitious composites (ECC) were studied. For the cost-efficient utilization of ECC materials, different types of specimens were cast with polypropylene (PP) and hydrophilic polyvinyl alcohol (HPVA) fibers. The compressive strength, Poisson’s ratio, strength-deflection curves, cracking/post-cracking strength, impact index, and tensile strain-stress curves of two types of ECC materials, with differing fiber contents of 0 vol %, 1 vol %, 1.5 vol %, and 2 vol %, were investigated with the use of compressive tests, four-point bending tests, drop-weight tests, and uniaxial tensile tests. In addition, the matrix microstructure and failure morphology of the fiber in the ECC materials were studied by scanning electron microscopy (SEM) analysis. Furthermore, carbonation tests and characterization of steel corrosion after carbonization were employed to study durability resistance. The results indicated that for both PP fiber- and HPVA fiber-reinforced ECCs, the compressive strength first increases and then decreases as fiber content increases from 0 vol % to 2 vol %, reaching a maximum at 1 vol % fiber content. The bending strength, deformation capacity, and impact resistance show significant improvement with increasing fiber content. The ECC material reinforced with 2 vol % PP fiber shows superior carbonized durability with a maximum carbonation depth of only 0.8 mm.