Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells.

BACKGROUND: A main obstacle in current valvular heart disease research is the lack of high-quality homogeneous functional heart valve cells. Human induced pluripotent stem cells (hiPSCs)-derived heart valve cells may help with this dilemma. However, there are no well-established protocols to induce hiPSCs to differentiate into functional heart valve cells, and the networks that mediate the differentiation have not been fully elucidated. METHODS: To generate heart valve cells from hiPSCs, we sequentially activated the Wnt, BMP4, VEGF (vascular endothelial growth factor), and NFATc1 signaling pathways using CHIR-99021, BMP4, VEGF-165, and forskolin, respectively. The transcriptional and functional similarity of hiPSC-derived heart valve cells compared with primary heart valve cells were characterized. Longitudinal single-cell RNA sequencing was used to uncover the trajectory, switch genes, pathways, and transcription factors of the differentiation. RESULTS: An efficient protocol was developed to induce hiPSCs to differentiate into functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells. After 6-day differentiation and CD144 magnetic bead sorting, ≈70% CD144+ cells and 30% CD144- cells were obtained. On the basis of single-cell RNA sequencing data, the CD144+ cells and CD144- cells were found to be highly similar to primary heart valve endothelial cells and primary heart valve interstitial cells in gene expression profile. Furthermore, CD144+ cells had the typical function of primary heart valve endothelial cells, including tube formation, uptake of low-density lipoprotein, generation of endothelial nitric oxide synthase, and response to shear stress. Meanwhile, CD144- cells could secret collagen and matrix metalloproteinases, and differentiate into osteogenic or adipogenic lineages like primary heart valve interstitial cells. Therefore, we identified CD144+ cells and CD144- cells as hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells, respectively. Using single-cell RNA sequencing analysis, we demonstrated that the trajectory of heart valve cell differentiation was consistent with embryonic valve development. We identified the main switch genes (NOTCH1, HEY1, and MEF2C), signaling pathways (TGF-ß, Wnt, and NOTCH), and transcription factors (MSX1, SP5, and MECOM) that mediated the differentiation. Finally, we found that hiPSC-derived valve interstitial-like cells might derive from hiPSC-derived valve endothelial-like cells undergoing endocardial-mesenchymal transition. CONCLUSIONS: In summary, this is the first study to report an efficient strategy to generate functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells from hiPSCs, as well as to elucidate the differentiation trajectory and transcriptional dynamics of hiPSCs differentiated into heart valve cells.

CProtMEDIAS: clustering of amino acid sequences encoded by gene families by MErging and DIgitizing Aligned Sequences.

Protein phylogenetic analysis focuses on the evolutionary relationships among related protein sequences and can help researchers infer protein functions and developmental trajectories. With the advent of the big data era, the existing protein phylogenetic methods, including distance matrix and character-based methods, are facing challenges in both running time and application scope. Here, we developed an R package that we call CProtMEDIAS that is useful for protein phylogenetic analysis. In contrast to existing phylogenetic analysis methods, CProtMEDIAS utilizes dimensionality reduction algorithms to digitize multiple sequence alignments and quickly conduct phylogenetic analysis with a large number of amino acid sequences from similarly distant protein families and species. We used CProtMEDIAS to perform a dimensionality reduction, clustering, pseudotime, specific residue and evolutionary trajectory analysis of the plant homeobox superfamily. We found that CProtMEDIAS delivers consistent clustering, fast running and elegant presentation and thus provides powerful new tools and methods for protein clustering and evolutionary analysis.

NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, and aging-associated interstitial lung disease with a poor prognosis and limited treatment options, while the pathogenesis remains elusive. In this study, we found that the expression of nuclear receptor subfamily 2 group F member 2 (NR2F2), a member of the steroid thyroid hormone superfamily of nuclear receptors, was reduced in both IPF and bleomycin-induced fibrotic lungs, markedly in bleomycin-induced senescent epithelial cells. Inhibition of NR2F2 expression increased the expression of senescence markers such as p21 and p16 in lung epithelial cells, and activated fibroblasts through epithelial-mesenchymal crosstalk, inversely overexpression of NR2F2 alleviated bleomycin-induced epithelial cell senescence and inhibited fibroblast activation. Subsequent mechanistic studies revealed that overexpression of NR2F2 alleviated DNA damage in lung epithelial cells and inhibited cell senescence. Adenovirus-mediated Nr2f2 overexpression attenuated bleomycin-induced lung fibrosis and cell senescence in mice. In summary, these data demonstrate that NR2F2 is involved in lung epithelial cell senescence, and targeting NR2F2 may be a promising therapeutic approach against lung cell senescence and fibrosis.

Selective Cleavage of the Strong or Weak C-C Bonds in Biphenylene Enabled by Rare-Earth Metals.

Selective cleavage of C-C bonds within arene rings is of great interest but remains elusive, especially for the molecules possessing the active and inert C-C bonds. Here, we report that the active and inert C-C bonds of biphenylene could be controllably cleaved by the reaction of biphenylene, potassium graphite, and rare-earth complexes with different metal centers. For scandium, the bond activation occurs at the Caryl-Caryl single bond, yielding 9-scandafluorene. For Lu, the reaction goes through ring contraction of the aromatic ring in biphenylene to provide benzopentalene dianionic lutetium. The origin of the selectivity and the reaction mechanism were illustrated by the isolation of intermediates and DFT calculations.

Intrinsic properties and extrinsic factors of food matrix system affecting the effectiveness of essential oils in foods: a comprehensive review.

Essential oils (EOs) have been proved as natural food preservatives because of their effective and wide-spectrum antimicrobial activity. They have been extensively explored for potential applications in food industry, and substantial progresses have been achieved. However well EOs perform in antibacterial tests in vitro, it has generally been found that a higher level of EOs is needed to achieve the same effect in foods. Nevertheless, this unsimilar effect has not been clearly quantified and elaborated, as well as the underlying mechanisms. This review highlights the influence of intrinsic properties (e.g., oils and fats, carbohydrates, proteins, pH, physical structure, water, and salt) and extrinsic factors (e.g., temperature, bacteria characteristics, and packaging in vacuum/gas/air) of food matrix systems on EOs action. Controversy findings and possible mechanism hypotheses are also systematically discussed. Furthermore, the organoleptic aspects of EOs in foods and promising strategies to address this hurdle are reviewed. Finally, some considerations about the EOs safety are presented, as well as the future trends and research prospects of EOs applications in foods. The present review aims to fill the evidenced gap, providing a comprehensive overview about the influence of the intrinsic and extrinsic factors of food matrix systems to efficiently orientate EOs applications.

Both intrinsic properties and extrinsic factors of food matrix affect the EOs action.EOs influence on the food organoleptic aspects were reviewed.Promising strategies for overcoming the organoleptic aspects of EOs were listed.Future research prospects are outlined to accelerate EOs application in foods.

Cellular Senescence: A Troy Horse in Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by myofibroblast abnormal activation and extracellular matrix deposition. However, the pathogenesis of PF remains unclear, and treatment options are limited. Epidemiological studies have shown that the average age of PF patients is estimated to be over 65 years, and the incidence of the disease increases with age. Therefore, PF is considered an age-related disease. A preliminary study on PF patients demonstrated that the combination therapy of the anti-senescence drugs dasatinib and quercetin improved physical functional indicators. Given the global aging population and the role of cellular senescence in tissue and organ aging, understanding the impact of cellular senescence on PF is of growing interest. This article systematically summarizes the causes and signaling pathways of cellular senescence in PF. It also objectively analyzes the impact of senescence in AECs and fibroblasts on PF development. Furthermore, potential intervention methods targeting cellular senescence in PF treatment are discussed. This review not only provides a strong theoretical foundation for understanding and manipulating cellular senescence, developing new therapies to improve age-related diseases, and extending a healthy lifespan but also offers hope for reversing the toxicity caused by the massive accumulation of senescence cells in humans.

Activity and Characterization of Tocopherol Oxidase in Corn Germs and Its Relationship with Oil Color Reversion.

Color reversion has long been a major problem for the vegetable oil industry, and the enzymatic oxidation of γ-tocopherol is thought to trigger this phenomenon. In this study, first, the extraction, purification, and detailed characterization of tocopherol oxidase from fresh corn germs were performed. Then, the relationship between the enzyme reaction of γ-tocopherol and oil color reversion was verified. The results showed that the membrane-free extracts of raw corn germ performed specific catalysis of tocopherol in the presence of lecithin. In terms of the oxidation product, tocored (the precursor of color reversion) was detected in the mixture after the catalytic reactions, indicating that this anticipated enzyme reaction was probably correlated with the color reversion. Furthermore, the optimal pH and temperature for the tocopherol oxidase enzyme were 4.6 and 20 °C, respectively. In addition, ascorbic acid at 1.0 mM completely inhibited the enzymatic reaction.

Blow-Spun Nanofibrous Membrane for Simultaneous Treatment of Emulsified Oil/Water Mixtures, Dyes, and Bacteria.

Membrane separation is of great significance due to its unique performance in treating wastewater. However, the simultaneous treatment of oily emulsions and other complex pollutants in water remains challenging. Herein, we have proposed a simple strategy to prepare a multifunctional titanium dioxide/silver nanoparticles/polyacrylonitrile (TiO2/AgNPs/PAN) nanofibrous membrane. The experimental results showed that the combination of the hierarchical structure composed of PAN nanofibers and Ag/TiO2 nanoprotrusions contributed to the superhydrophilicity and superoleophobicity (UOCA = 153.3 ± 2.0°). Further, the nanofibrous membrane exhibited a rapid gravity-driven permeate flux (>1829.37 ± 83.51 L m-2 h-1) and an ultrahigh separation efficiency (>99.9%) for the surfactant-stabilized oil/water emulsions. Moreover, due to the synergistic effect between the PAN fibers and TiO2/Ag heterojunction, Rhodamine B dye in water can be removed quickly and efficiently (up to 97.67% in 90 min). More importantly, the obtained nanofibrous membrane exhibited ultrahigh stability in different harsh environments. The design of superoleophobic nanofiber membrane with a high separation efficiency and high photocatalytic activity has great potential for practical applications in the purification of oily wastewater.

Multicompartmental Microcapsules for Enzymatic Cascade Reactions Prepared through Gas Shearing and Surface Gelation.

Inspired by the structure of eukaryotic cells, multicompartmental microcapsules have gained increasing attention. However, challenges remain in the fabrication of "all-aqueous" (i.e., oil-free) microcapsules composed of accurately adjustable hierarchical compartments. This study reports on multicompartmental microcapsules with an innovative architecture. While multicompartmental cores of the microcapsules were fabricated through gas shearing, a shell was applied on the cores through surface gelation of alginate. Different from traditional multicompartmental microcapsules, thus obtained microcapsules have well-segregated compartments while the universal nature of the surface-gelation method allows us to finely tune the shell thicknesses of the microcapsules. The microcapsules are highly stable and cytocompatible and allow repeated enzymatic cascade reactions, which might make them of interest for complex biocatalysis or for mimicking physiological processes.

Polarized light compass decoding.

The brains of some insects can encode and decode polarization information and obtain heading angle information. Referring to the encoding ability of insects, exponential function encoding is designed to improve the stability of the polarized light compass artificial neural network. However, in the decoding process, only neurons with the largest activation degree are used for decoding (maximum value decoding), so the heading information contained in other neurons is not used. Therefore, average value decoding (AVD) and weighted AVD are proposed to use the heading information contained in multiple neurons to determine the heading. In addition, concerning the phenomenon of threshold activation of insect neurons, threshold value decoding (TVD) and weighted TVD are proposed, which can effectively eliminate the interference of neurons with low activation. Moreover, this paper proposes to improve the heading determination accuracy of the artificial neural network through pre-training. The simulation and experimental results show that the new, to the best of our knowledge, decoding methods and pre-training can effectively improve the heading determination accuracy of the artificial neural network.

Case Report: Multiple Ocular Manifestations Assisted in the Diagnosis of Systemic Sarcoidosis.

SIGNIFICANCE: Sarcoidosis is a variable, multisystem granulomatous disease, which can affect many organs including the lungs, lymph nodes, and eyes. It is difficult to differentiate sarcoidosis and tuberculosis because of their similar clinical and pathological features. PURPOSE: This study aimed to describe a sarcoidosis case with typical ocular and systemic manifestations combined with suspected tuberculosis infection. CASE REPORT: A 30-year-old Chinese man, initially diagnosed with tuberculosis, presented with typical ocular sarcoidosis during antituberculosis therapy. The ocular surface, anterior chamber, anterior chamber angle, ciliary body, vitreous, optic disc, and lacrimal gland of the patient all exhibited manifestations of sarcoidosis, although optic disc involvement has rarely been reported. Typical ocular sarcoidosis manifestations and positive responses to corticosteroid therapy of the patient helped us reach the diagnosis of systemic sarcoidosis. The patient was followed up for 48 months and showed significant improvement of miliary nodules and lymph nodes in both lungs. However, the appearance of uveitis in the right eye persisted because of nonadherence to steroid treatment. CONCLUSIONS: This case shows the importance of ophthalmic evaluation in the diagnosis and management of sarcoidosis and supports a possible role of Mycobacterium tuberculosis in the pathogenesis of sarcoidosis.

Retardation of Myopia by Multifocal Soft Contact Lens and Orthokeratology: A 1-Year Randomized Clinical Trial.

OBJECTIVES: This randomized, single-blind, clinical trial compared the effectiveness of multifocal soft contact lenses (MFSCLs), orthokeratology contact lenses (Ortho-kCLs), and single vision spectacles (SVSs) for myopia control. METHODS: Sixty-six eligible Chinese subjects, aged 7 to 15 years old with cycloplegic refraction measurements between -1.00 and -8.00 diopters (D), astigmatism not more than 1.00 D, and no history of myopia control treatment, were randomly assigned to wear MFSCLs, Ortho-kCLs, or SVSs for 1 year. For all three groups, baseline measurements of cycloplegic refraction, axial length (AL), and corneal endothelial cell density (CECD) were made. At the 6- and 12-month follow-up visits, changes in cycloplegic refraction, AL, and CECD were measured in the MFSCL and SVS groups. For the Ortho-kCL group, only changes in the AL were measured at 6 and 12 months, and CECD was measured at the 12-month follow-up visit. RESULTS: After 1 year of lens wear, myopia progression of the SVS group, -0.938±0.117 D, was greater than that of the MFSCLs group, -0.591±0.106 D (P=0.032). Thus, MFSCLs reduced the rate of myopia progression by 37.0% compared with the SVSs. The AL elongations after 1 year were 0.30±0.03 mm for MFSCLs (P=0.027 vs SVSs), 0.31±0.04 mm for Ortho-kCLs (P=0.049 vs SVSs), and 0.41±0.04 mm for SVSs. Compared with the SVS group, the reduction in AL elongation was 26.8% and 24.4% in the MFSCL and Ortho-kCL groups, respectively. There were no significant differences in CECD among the three groups (P>0.05). CONCLUSIONS: Compared with SVSs, wearing MFSCLs and Ortho-kCLs significantly delayed myopia progression. MFSCLs and Ortho-kCLs are safe and promising methods of myopia control (chictr.org number, ChiCTR2100048452).

Self-Healing Fibrous Membranes.

Inspired by the self-healing function of living organisms, self-healing materials have been developed in recent decades to very high standards. As a new direction, self-healing fibrous membranes (SFMs) exhibit both the configuration of a porous structure and self-healing capability within one material. Different from nonporous self-healing materials, it is more challenging to introduce self-healing properties to porous fibrous membrane materials owing to the more complex healing mechanism and microstructure of SFMs. This Minireview focuses on the self-healing mechanisms, design principles, and preparation strategies of SFMs. The characteristics of SFM self-healing performance are introduced in detail, and insights and perspectives of SFM preparation and healing mechanisms are put forward. Furthermore, remaining challenges and future developments of SFMs are presented, where the ultimate goal is the design of highly efficient self-healing and superstable fibrous membranes.

Superstable and Intrinsically Self-Healing Fibrous Membrane with Bionic Confined Protective Structure for Breathable Electronic Skin.

Considerable effort has been devoted to the fabrication of electronic skin that can imitate the self-healing and sensing function of biological skin. Almost all self-healing electronic skins are composed of airtight elastomers or hydrogels, which will cause skin inflammation. Fibrous membranes are ideal materials for preparing highly sensitive breathable electronic skins. However, the development of intrinsically self-healing fibrous membranes with high stability is still a challenge. Here, a novel interface protective strategy is reported to develop intrinsically self-healing fibrous membranes with a bionic confined structure for the first time, which were further assembled into an all-fiber structured electronic skin through interfacial hydrogen bonding. The electronic skin is multifunctional with self-powering, self-healing, breathability, stretchability, and thermochromism functionalities, which is highly promising for application in intelligent wearable sensing systems.

A survey of 3D object detection algorithms for intelligent vehicles development.

With the rapid development of Artificial Intelligent algorithms on Computer Vision, 2D object detection has greatly succeeded and been applied in various industrial products. In the past several years, the accuracy of 2D object detection has been dramatically improved, even beyond the human eyes detection ability. However, there is still a limitation of 2D object detection for the applications of Intelligent Driving. A safe and reliable self-driving car needs to detect a 3D model of the around objects so that an intelligent driving car has a perception ability to real driving situations. This paper systematically surveys the development of 3D object detection methods applied to intelligent driving technology. This paper also analyzes the shortcomings of the existing 3D detection algorithms and the future development directions of 3D detection algorithms on intelligent driving.

Selective Coupling of Lanthanide Metallacyclopropenes and Nitriles via Azametallacyclopentadiene and η2-Pyrimidine Metallacycle.

Exploring new lanthanide metallacycles and finding their unique chemistry different from the analogues of transition metals are of great interest and importance. In this work, we reported the synthesis, characterization, and reactivity toward nitriles of two lanthanide metallacyclopropenes: lutetacyclopropene 2a and dysprosacyclopropene 2b. The selective coupling of 2a and three molecules of PhCN was found for the first time to provide the unexpected fused lutetacycle 3a with one 1,6-dihydropyrimidine ring. Mechanistic studies by DFT calculations reveal that the triple insertion of PhCN into 2a proceeds through four key steps: the insertion of the first PhCN into 2a giving azalutetacyclopentadiene IM1, the insertion of the second PhCN into the Lu-N bond of IM1, the intramolecular electrocyclization providing a highly strained η2-pyrimidine metallacycle, and the insertion of the third PhCN into the Lu-Csp3 bond. Isolation and characterization of two active intermediates, azalutetacyclopentadiene IM1 and η2-pyrimidine dysprosacycle, provide critical evidence for the formation of 3a. Furthermore, IM1 was also reported to react with TMSCN, isocyanides, or W(CO)6 to furnish the fused [4,5] lutetacycles. The chemistry of two lanthanide metallacyclopropenes with nitriles is significantly different from these metallacyclopropenes of scandium and other metals. Most notably, the azalutetacyclopentadienes, η2-pyrimidine complex, and other metallacycles all represent the first examples in rare-earth organometallic chemistry; the formation of these new lutetacycles provides concrete evidence for understanding the mechanism of transition metal promoted or catalyzed [2+2+2] cycloaddition between alkynes and nitriles.

Insertion Chemistry of Lutetacyclopropene toward Unsaturated C-O/C-N Bonds.

Although the reaction chemistry of transition metallacyclopropenes has been well-established in the last decades, the reactivity of rare-earth metallacyclopropenes remains elusive. Herein, we report the reaction of lutetacyclopropene 1 toward a series of unsaturated molecules. The reaction of 1 with one equiv. of PhCOMe, Ar1 CHO (Ar1 =2,6-Me2 C6 H3 ), W(CO)6 , and PhCH=NPh provided oxalutetacyclopentenes, metallacyclic lutetoxycarbene, and azalutetacyclopentene via 1,2-insertion of C=O, C≡O, or C=N bonds into Lu-Csp2 bond, respectively. However, the reaction between 1 and Ar2 N=C=NAr2 (Ar2 =4-MeC6 H4 ) gave an acyclic lutetium complex with a diamidinate ligand by the coupling of one molecule of 1 with two carbodiimides, irrespective of the amount of carbodiimide employed. More interestingly, when 1 was treated with two equiv. of Ar1 CHO, the reductive coupling of two C=O bonds was discovered to give a lutetium pinacolate complex along with the release of tolan. Remarkably, the reactivity of 1 is significantly different from that of scandacyclopropenes; these metallacycles derived from 1 all represent the first cases in rare-earth organometallic chemistry.

Correlation of GSTP1 rs1695 and CAT rs769217 with elevated AST induced by valproate sodium in Chinese children with epilepsy.

Valproate (VPA)-induced hepatotoxicity is a fatal adverse drug reaction，and children is a high-risk population. Our study aimed to explore whether key genetic polymorphisms of antioxidant pathway is associated with VPA-mediated AST elevation. We included 194 newly diagnosed epilepsy children (aged from 1 to 16 years old) and treated with VPA. These patients were divided into two groups: one group for AST is normal and another group is AST elevated. AST elevation occurred in 25.8% of patient treated with VPA. During VPA monotherapy, the maximum AST in patients of GSTP1 rs1695 with AA genotype was significantly higher than carrying G alleles (36.50 ±14.89 vs 32.88±10.69, P=0.003). Patients with AG+GG genotype of GSTP1 rs1695 had a reduced risk of elevated AST (adjusted OR=0.37, 95% CI: 0.16-0.84, P=0.017). There is a significant difference in the maximum AST value of CAT rs769217 genotype (P=0.011, P= 0.045, respectively). Children with CAT rs769217 CT genotype or CT+TT genotype have a lower risk of elevated AST (adjusted OR=0.30, 95% CI: 0.13-0.68, P=0.004 and adjusted OR=0.41, 95% CI:0.20-0.82,P=0.012, respectively). Children who with GSTP1 rs1695 G allele have a reduced risk of AST abnormalities. We conducted CAT rs769217 CC genotype is a risk factor for AST elevation in children.

Variability of voriconazole concentrations in patients with hematopoietic stem cell transplantation and hematological malignancies: influence of loading dose, procalcitonin, and pregnane X receptor polymorphisms.

AIMS: Voriconazole (VCZ) displays highly variable pharmacokinetics affecting treatment efficacy and safety. We aimed to identify the factors affecting VCZ steady-state trough concentration (Cssmin) to provide evidence for optimizing VCZ treatment regimens. METHODS: A total of 510 Cssmin of 172 patients with hematopoietic stem cell transplantation and hematologic malignancies and their clinical characteristics and genotypes of FMO, POR, and PXR were included in this study. RESULTS: In univariate analysis, the standard loading dose of VCZ significantly increased the Cssmin of VCZ (P < 0.001). The Cssmin of VCZ was significantly correlated with patients' total bilirubin (TB) (P < 0.001) and procalcitonin (PCT) (P < 0.001). FMO3 rs2266780 (P = 0.025), POR rs10954732 (P = 0.015), PXR rs2461817 (P = 0.010), PXR rs7643645 (P = 0.003), PXR rs3732359 (P = 0.014), PXR rs3814057 (P = 0.005), and PXR rs6785049 (P = 0.013) have a significant effect on Cssmin of VCZ. Loading dose, TB, PCT level, and PXRrs3814057 polymorphism were independent influencing factors of VCZ Cssmin in the analysis of multivariate linear regression. And loading dose, PCT, and PXR rs3814057 had significant effects on the probability of the therapeutic window of VCZ. CONCLUSION: The high variability of VCZ Cssmin may be partially explained by loading dose, liver function, inflammation, and PXR polymorphisms. This study suggests the VCZ standard loading dose regimen significantly increased Cssmin and probability of the therapeutic window providing treatment benefits. Patients in the high PCT group may be more likely to exceed 5.5 µg/mL, thus suffering from VCZ toxicity.

Effect of cyclosporine a and polymorphisms in CYP2C19 and ABCC2 on the concentration of voriconazole in patients undergoing allogeneic hematopoietic stem cell transplantation.

1. Voriconazole is known to display highly variable pharmacokinetics affecting treatment efficacy and safety. This study aimed to identify the factors causing the variation of voriconazole concentration in patients with allogeneic hematopoietic stem cell transplantation.2. The data of patients was collected, including clinical characteristics and voriconazole concentrations. A total of 5 single nucleotide polymorphisms of 3 candidate genes (CYP2C19, ABCC2, ABCG2) related to voriconazole metabolism were genotyped by MassArray method. The correlation between polymorphisms and voriconazole concentration was analyzed.3. A total of 244 voriconazole concentrations of 43 patients were included in this study. The voriconazole concentration was significantly correlated with patients' total bile acid (p = 0.001) and cyclosporin A (p < 0.001). The median concentration of the CYP2C19 normal metabolizers was remarkably lower than poor metabolizers (0.86 vs 2.27 µg/mL). The median concentration of ABCC2 rs2273697 GG genotype carriers was significantly higher than that of GA genotype carriers (p = 0.026).4. The variability of voriconazole concentration is partially explained by total bile acid, metabolic types of CYP2C19. The voriconazole concentration of CYP2C19 normal metabolizers is likely to be lower than 1.0 µg/mL and thus at risk of infection due to inadequate treatment.