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.

A molecular atlas reveals the tri-sectional spinning mechanism of spider dragline silk.

The process of natural silk production in the spider major ampullate (Ma) gland endows dragline silk with extraordinary mechanical properties and the potential for biomimetic applications. However, the precise genetic roles of the Ma gland during this process remain unknown. Here, we performed a systematic molecular atlas of dragline silk production through a high-quality genome assembly for the golden orb-weaving spider Trichonephila clavata and a multiomics approach to defining the Ma gland tri-sectional architecture: Tail, Sac, and Duct. We uncovered a hierarchical biosynthesis of spidroins, organic acids, lipids, and chitin in the sectionalized Ma gland dedicated to fine silk constitution. The ordered secretion of spidroins was achieved by the synergetic regulation of epigenetic and ceRNA signatures for genomic group-distributed spidroin genes. Single-cellular and spatial RNA profiling identified ten cell types with partitioned functional division determining the tri-sectional organization of the Ma gland. Convergence analysis and genetic manipulation further validated that this tri-sectional architecture of the silk gland was analogous across Arthropoda and inextricably linked with silk formation. Collectively, our study provides multidimensional data that significantly expand the knowledge of spider dragline silk generation and ultimately benefit innovation in spider-inspired fibers.

Corrigendum: Alterations of cerebral perfusion and functional connectivity in children with idiopathic generalized epilepsy.

[This corrects the article DOI: 10.3389/fnins.2022.918513.].

The medication for pneumocystis pneumonia with glucose-6-phosphate dehydrogenase deficiency patients.

Pneumocystis pneumonia (PCP) is an opportunity acquired infection, which is usually easy to occur in patients with AIDS, organ transplantation, and immunosuppressive drugs. The prevention and treatment must be necessary for PCP patients with immunocompromise. And the oxidants are currently a typical regimen, including sulfanilamide, dapsone, primaquine, etc. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked gene-disease that affects about 400 million people worldwide. The lack of G6PD in this population results in a decrease in intracellular glutathione synthesis and a weakening of the detoxification ability of the oxidants. As a result, oxidants can directly damage haemoglobin in red blood cells, inducing methemoglobin and hemolysis. When patients with G6PD deficiency have low immunity, they are prone to PCP infection, so choosing drugs that do not induce hemolysis is essential. There are no clear guidelines to recommend the drug choice of this kind of population at home and abroad. This paper aims to demonstrate the drug choice for PCP patients with G6PD deficiency through theoretical research combined with clinical cases.

Alterations of Cerebral Perfusion and Functional Connectivity in Children With Idiopathic Generalized Epilepsy.

Background: Studies have demonstrated that adults with idiopathic generalized epilepsy (IGE) have functional abnormalities; however, the neuropathological pathogenesis differs between adults and children. This study aimed to explore alterations in the cerebral blood flow (CBF) and functional connectivity (FC) to comprehensively elucidate the neuropathological mechanisms of IGE in children. Methods: We obtained arterial spin labeling (ASL) and resting state functional magnetic resonance imaging data of 28 children with IGE and 35 matched controls. We used ASL to determine differential CBF regions in children with IGE. A seed-based whole-brain FC analysis was performed for regions with significant CBF changes. The mean CBF and FC of brain areas with significant group differences was extracted, then its correlation with clinical variables in IGE group was analyzed by using Pearson correlation analysis. Results: Compared to controls, children with IGE had CBF abnormalities that were mainly observed in the right middle temporal gyrus, right middle occipital gyrus (MOG), right superior frontal gyrus (SFG), left inferior frontal gyrus (IFG), and triangular part of the left IFG (IFGtriang). We observed that the FC between the left IFGtriang and calcarine fissure (CAL) and that between the right MOG and bilateral CAL were decreased in children with IGE. The CBF in the right SFG was correlated with the age at IGE onset. FC in the left IFGtriang and left CAL was correlated with the IGE duration. Conclusion: This study found that CBF and FC were altered simultaneously in the left IFGtriang and right MOG of children with IGE. The combination of CBF and FC may provide additional information and insight regarding the pathophysiology of IGE from neuronal and vascular integration perspectives.

RetroScan: An Easy-to-Use Pipeline for Retrocopy Annotation and Visualization.

Retrocopies, which are considered "junk genes," are occasionally formed via the insertion of reverse-transcribed mRNAs at new positions in the genome. However, an increasing number of recent studies have shown that some retrocopies exhibit new biological functions and may contribute to genome evolution. Hence, the identification of retrocopies has become very meaningful for studying gene duplication and new gene generation. Current pipelines identify retrocopies through complex operations using alignment programs and filter scripts in a step-by-step manner. Therefore, there is an urgent need for a simple and convenient retrocopy annotation tool. Here, we report the development of RetroScan, a publicly available and easy-to-use tool for scanning, annotating and displaying retrocopies, consisting of two components: an analysis pipeline and a visual interface. The pipeline integrates a series of bioinformatics software programs and scripts for identifying retrocopies in just one line of command. Compared with previous methods, RetroScan increases accuracy and reduces false-positive results. We also provide a Shiny app for visualization. It displays information on retrocopies and their parental genes that can be used for the study of retrocopy structure and evolution. RetroScan is available at https://github.com/Vicky123wzy/RetroScan.