The impact of gene polymorphism and hepatic insufficiency on voriconazole dose adjustment in invasive fungal infection individuals

Voriconazole (VRZ) is a broad-spectrum antifungal medication widely used to treat invasive fungal infections (IFI). The administration dosage and blood concentration of VRZ are influenced by various factors, posing challenges for standardization and individualization of dose adjustments. On the one hand, VRZ is primarily metabolized by the liver, predominantly mediated by the cytochrome P450 (CYP) 2C19 enzyme. The genetic polymorphism of CYP2C19 significantly impacts the blood concentration of VRZ, particularly the trough concentration (Ctrough), thereby influencing the drug’s efficacy and potentially causing adverse drug reactions (ADRs). Recent research has demonstrated that pharmacogenomics-based VRZ dose adjustments offer more accurate and individualized treatment strategies for individuals with hepatic insufficiency, with the possibility to enhance therapeutic outcomes and reduce ADRs. On the other hand, the security, pharmacokinetics, and dosing of VRZ in individuals with hepatic insufficiency remain unclear, making it challenging to attain optimal Ctrough in individuals with both hepatic insufficiency and IFI, resulting in suboptimal drug efficacy and severe ADRs. Therefore, when using VRZ to treat IFI, drug dosage adjustment based on individuals’ genotypes and hepatic function is necessary. This review summarizes the research progress on the impact of genetic polymorphisms and hepatic insufficiency on VRZ dosage in IFI individuals, compares current international guidelines, elucidates the current application status of VRZ in individuals with hepatic insufficiency, and discusses the influence of CYP2C19, CYP3A4, CYP2C9, and ABCB1 genetic polymorphisms on VRZ dose adjustments and Ctrough at the pharmacogenomic level. Additionally, a comprehensive summary and analysis of existing studies’ recommendations on VRZ dose adjustments based on CYP2C19 genetic polymorphisms and hepatic insufficiency are provided, offering a more comprehensive reference for dose selection and adjustments of VRZ in this patient population

Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis

ObjectiveThe aim of this study was to investigate whether the nuclear receptor farnesoid X receptor (FXR) could regulate FNDC5/Irisin expression and the role of Irisin in hyperlipidemia and atherosclerosis in ApoE-/- mice.Methods and ResultsWe treated primary human hepatocytes, HepG2 cells, and Rhesus macaques with FXR agonist (CDCA, GW4064, and ivermectin). FNDC5 expression was highly induced by CDCA and GW4064 in hepatocytes, HepG2 cells, and the circulating level of Irisin increased in Rhesus macaques. Luciferase reporter and CHIP assays were used to determine whether FXR could regulate FNDC5 promoter activity. Irisin-ApoE-/- and ApoE-/- mice were used to study the metabolic function of Irisin in dyslipidemia and atherosclerosis. Irisin-ApoE-/- mice showed improved hyperlipidemia and alleviated atherosclerosis as compared with ApoE-/- mice. Irisin upregulated the expression of Abcg5/Abcg8 in liver and intestine, which increased the transport of biliary cholesterol and fecal cholesterol output.ConclusionActivation of FXR induces FNDC5 mRNA expression in human and increased the circulating level of Irisin in Rhesus macaques. FNDC5/Irisin is a direct transcriptional target of FXR. Irisin may be a novel therapeutic strategy for dyslipidemia and atherosclerosis

Chinese steamed bread and novel wheat products

Wheat is one of the most important agricultural crops globally, and the third-largest food crop after rice and maize in China; in particular, wheat is one of the primary provisions in human diets in Northern China. Research on the quality of wheat flour is important for wheat food production. Steam bread was one of staple foods in the northern part of China due to the combination of unique cultures and dietary habits. The Chinese steamed bread-making process is a complex system. There is significant value in research on the aroma characteristics of wheat flour, fermented dough, and steamed bread. The solid phase micro-extraction (SPME) GC-MS was used to investigate the compounds of volatile aroma in gelatinized-flour. Volatile compounds of steamed bread vary depending on the content of gluten in wheat flour. In the three physical stages of making Chinese steamed bread, the quantity of hydrocarbons and aldehydes first decreased and then increased. Chinese steamed bread made from wheat flour with added 3% of stachyose, has the greatest elasticity and extensibility, and has the highest scores when conducted for sensory evaluation, thus making nutrient fortified steamed bread. Along with the developing and applying of the modern food process technology, wheat also can be made for novel wheat products with different flavors, such as wheat bran, wheat germ flour, wheat germ oil and “popwheat”, and further caramel treats. In addition, volatile compounds of wheat bran and germ differ between high gluten, middle gluten and low gluten flour. Therefore, the research on the processing quality of wheat dough has been a hot topic.</p

Dynamic Force Identification Problem Based on a Novel Improved Tikhonov Regularization Method

The main purpose of this paper is to identify the dynamic forces between the conical pick and the coal-seam. According to the theory of time domain method, the dynamic force identification problem of the system is established. The direct problem is described by Green kernel function method. The dynamic force is expressed by a series of functions superposed by impulses, and the dynamic response of the structure is expressed as a convolution integral form between the input dynamic force and the response of Green kernel function. Because of the ill-conditioned characteristics of the structure matrix and the influence of measurement noise in the process of dynamic force identification, it is difficult to deal with this problem by the usual numerical method. In present content, a novel improved Tikhonov regularization method is proposed to solve ill-posed problems. An engineering example shows that the proposed method is effective and can obtain stable approximate solutions to meet the engineering requirements

Reliability Calculation Method of Shipborne Vehicles’ Sortie Mission for Dynamic Network Structure

To provide decision support to the commander, it is necessary to calculate shipborne vehicles’ sortie mission reliability during the formulation of the layout plan. Therefore, this paper presents the sortie mission network model and reliability calculation method for shipborne vehicles. Firstly, the shipborne vehicle layout and sortie task characteristics are used to establish the sortie mission network model. The shipborne vehicles' sortie mission reliability problem is transformed into a two-terminal network reliability problem. Secondly, the minimal path set method is used to calculate the two-terminal network reliability. An improved tabu search algorithm based on a strategy of breaking up the whole into parts is proposed to search for the minimal path set that matches the length. Finally, the sum of disjoint products is used to process the minimal path set to obtain the shipborne vehicles’ sortie mission reliability calculation formula. A numerical analysis of two simplified shipborne vehicles’ layouts is given to illustrate the calculation process of the method. This study provides a new evaluation index and an effective quantitative basis for the evaluation system of shipborne vehicles’ layout. It also provides theoretical support for the development of decision-making related to the sortie mission of shipborne vehicles

The effect and mechanism of highland barley β-glucan in improving liver regeneration after partial hepatectomy

Studies have shown the beneficial effect of highland barley β-glucan (HBBG) on multiple acute and chronic liver diseases, however, whether it can improve liver regeneration following 2/3 partial hepatectomy (PH) is yet unknown. This study investigated the positive effect of β-glucan on liver regeneration in acute liver injury after PH. Before PH or CCl4 administration, mice were fed either a chow diet or that containing 5 or 10% HBBG for two weeks. The experimental mice were weighed on days 0, 1, and 2 after PH or CCl4 treatment, and the serum and liver tissue were collected. qRT-PCR, Western blotting, TUNEL staining, and immunostaining analysis were performed to measure the associated indices of proliferation and apoptosis of hepatocytes. We found that 5% HBBG promoted hepatocyte proliferation and liver regeneration and increased the liver/body weight ratio at 1 and 2 days after PH in mice. Mechanistically, HBBG activated the STAT3-CyclinD1 signaling pathway to increase hepatocyte proliferation, accelerating their transition from the G0 to S phase. Additionally, the HBBG intervention decreased hepatocyte apoptosis in the CCl4-induced liver injury model of mice. Concisely, HBBG can promote hepatocyte proliferation and liver regeneration via the STAT3-CyclinD1 signaling pathway in acute liver injury or PH

Effects of Fertilizer Application Patterns on Foxtail Millet Root Morphological Construction and Yield Formation during the Reproductive Stage in the Loess Plateau of China

With crop yields continually increasing, chemical fertilizer consumption in China is increasing in parallel. The excessive use of synthetic fertilizer can lead to soil compaction, acidification, and degeneration, which can all be mitigated through additional organic manure application. The combined application of organic manure and inorganic fertilizer plays crucial roles in the root morphology and yield formation of dryland crops. In this study, foxtail millet (Chang Sheng 07) was used as the experimental material and sown in a dry farming area with five different fertilizing patterns, which were composed of chemical N, P, organic manure, and microbial manure. These patterns included a single application of 45 kg·ha−1 of nitrogen fertilizer as the control (N45), the combined application of 60 kg·ha−1 of nitrogen fertilizer with 30 kg·ha−1 of phosphorus fertilizer (N60P30), the combined application of 90 kg·ha−1 of nitrogen fertilizer with 45 kg·ha−1 of phosphorus fertilizer (N90P45), 60 kg·ha−1 of nitrogen fertilizer and 40 kg·ha−1 of phosphorus fertilizer with 2000 kg·ha−1 of organic manure (N60P40-O), and 60 kg·ha−1 of nitrogen fertilizer and 40 kg·ha−1 of phosphorus fertilizer with 5 kg·ha−1 of microbial manure (N60P40-M). Each treatment was performed with four repeats. The results show that (1) the different fertilization patterns had significant effects on the morphological construction of foxtail millet roots, and the root length (RL) with N60P40–O underwent a significant increase of 88.23% and 61.59% in the two stages, respectively, (2) as confirmed by the correlation analysis, the root surface area (RSA) was positively correlated with the RL and root volume (RV), (3) the yields with N90P45 and N60P30 exhibited a significant increase of 54.43% and 59.86%, and those with N60P40–O and N60P40–M stably increased by 13.12–24.11% compared to those with N45, and (4) the water use efficiency (WUE) of foxtail millet under the N60P30 and N90P45 patterns significantly increased by 33.40–62.39%, while that under the N60P40–O and N60P40–M patterns increased by 12.89–29.20%. In summary, the application of additional organic matter and microbial manure promoted the morphological construction of foxtail millet roots, led to better stability in grain production, and is an ecofriendly option in terms of sustainable land use

A Full-Color Holographic System Based on Taylor Rayleigh–Sommerfeld Diffraction Point Cloud Grid Algorithm

Real objects-based full-color holographic display systems usually collect data with a depth camera and then modulate the input light source to reconstruct the color three-dimensional scene of the real object. However, at present, the main problems of the real-time high quality full-color 3D display are slow speed, low reconstruction quality, and high consumption of hardware resources caused by excessive computing. Based on the hybrid Taylor Rayleigh–Sommerfeld diffraction algorithm and previous studies on full-color holographic systems, our paper proposes Taylor Rayleigh–Sommerfeld diffraction point cloud grid algorithm (TR-PCG), which is to perform Taylor expansion on the radial value of Rayleigh–Sommerfeld diffraction in the hologram generation stage and modify the data type to effectively accelerate the calculation speed and ensure the reconstruction quality. Compared with the wave-front recording plane, traditional point cloud gridding (PCG), C-PCG, and Rayleigh–Sommerfeld PCG without Taylor expansion, the computational complexity is significantly reduced. We demonstrate the feasibility of the proposed method through experiments