S-scheme heterojunction Cu-porphyrin/TiO2 nanosheets with highly efficient photocatalytic reduction of CO2 in ambient air.

Directly capturing CO2 in ambient air and converting it into value-added fuels using photocatalysis is a potentially valuable technology. In this study, Cu-porphyrin (tetrakis-carboxyphenyl porphyrin copper, CuTCPP) was innovatively anchored on the surface of TiO2 (titanium dioxide) nanosheets to form an S-scheme heterojunction. Based on this, a photocatalytic reaction system for stably converting CO2 in ambient air into value-added fuels at the gas-solid interface was constructed without addition of sacrificial agents and alkaline liquids. Under the illumination of visible light and sunlight, the evolution rate of CO is 56 µmol·g-1·h-1 and 73 µmol·g-1·h-1, respectively, with a potential CO2 conversion rate of 35.8 % and 50.4 %. The enhanced of photocatalytic performance is attributed to the introduction of CuTCPP, which provides additional active sites, significantly improves capture capacity of CO2 and the utilization of electrons. Additionally, the formation of S-scheme heterojunction expands the redox range and improves the separation efficiency of photo-generated charges.

Identification of an immune-related gene signature for predicting prognosis and immunotherapy efficacy in liver cancer via cell-cell communication.

BACKGROUND: Liver cancer is one of the deadliest malignant tumors worldwide. Immunotherapy has provided hope to patients with advanced liver cancer, but only a small fraction of patients benefit from this treatment due to individual differences. Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies, thereby improving patient survival rates. Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer, the impact of cell-cell interactions in the tumor microenvironment has not been adequately considered. AIM: To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy. METHODS: Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways. Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells. The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features, and a least absolute shrinkage and selection operator (LASSO) regression model was constructed to screen for diagnostic-related features. Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model. Finally, 3 genes (stathmin 1, cofilin 1, and C-C chemokine ligand 5) significantly associated with survival were identified and used to construct an immune-related gene signature. RESULTS: The immune-related gene signature composed of stathmin 1, cofilin 1, and C-C chemokine ligand 5 was identified through cell-cell communication. The effectiveness of the identified gene signature was validated based on experimental results of predictive immunotherapy response, tumor mutation burden analysis, immune cell infiltration analysis, survival analysis, and expression analysis. CONCLUSION: The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment, providing insights for personalized treatment strategies.

Active Dendrite Suppression by Ferroelectric Membrane Separators in Rechargeable Batteries.

Anodic dendrite formation is a critical issue in rechargeable batteries and often leads to poor cycling stability and quick capacity loss. Prevailing strategies for dendrite suppression aim at slowing down the growth rate kinetically but still leaving possibilities for dendrite evolution over time. Herein, we report a complete dendrite elimination strategy using a mesoporous ferroelectric polymer membrane as the battery separator. The dendrite suppression is realized by spontaneously reversing the surface energetics for metal ion reduction at the protrusion front, where a positive piezoelectric polarization is generated and superimposed as the protrusion compresses the separator. This effect is demonstrated first in a Zn electroplating process, and further in Zn-Zn symmetric cells and Zn-NaV3O8·1.5H2O full cells, where the dendritic Zn anode surfaces are completely turned into featureless flat surfaces. Consequently, a substantially longer charging/discharging cycle is achieved. This study provides a promising pathway toward high-performance dendrite-free rechargeable batteries.

Layer-by-layer assembly of homopolypeptide polyelectrolytes on asymmetric nanochannels for the detection of nickel ions.

Nickel stands out as one of the prevalent heavy metal ionic pollutants found in water. It is urgent to devise a simple, efficient, budget-friendly, highly-selective and proficient method for detecting Ni(II). This work reports an approach to design a nanofluidic diode for the ultrasensitive and label-free detection of nickel ions based on layer-by-layer assembly of polyarginine (PA) and polyglutamic acid (γ-PGA) on the inner surface of asymmetric nanochannels. We can tune the adsorption/desorption characteristics of the asymmetric nanochannels for Ni2+ by adjusting the pH changes, i.e., the PA-γ-PGA modified nanochannels adsorb Ni2+ at pH 6 and desorb at pH 3 in aqueous solution. This pivotal adjustment facilitates the reusable and specific detection of nickel ions with a detection limit of 1 × 10-8 M. Moreover, the system demonstrates commendable stability and recyclability, enhancing its practical applicability. This innovative system holds promise for recognizing and detecting nickel ions in diverse environments such as water, blood, and cells. The robust performance and adaptability of our proposed system instill confidence in its potential for future applications.

Plasma Membrane (PM) H+-ATPase Mediates Rhizosphere Acidification and Regulates Herbicide Imazethapyr Toxicity in Wheat.

The plasma membrane (PM) H+-ATPase is crucial for a plant defense system. However, there is currently no consensus on whether the PM H+-ATPase plays a role in alleviating the toxic effects of herbicides on nontarget plants. We found that under the herbicide imazethapyr (IM) exposure, PM H+-ATPase activity in wheat roots increased by approximately 69.53%, leading to rhizosphere acidification. When PM H+-ATPase activity is inhibited, the toxicity of IM significantly increases: When exposed to IM alone, the total Fe content of wheat roots decreased by 29.07%, the relative Fe2+ content increased by 27.75%, and the ROS content increased by 27.74%. When the PM H+-ATPase activity was inhibited, the corresponding data under IM exposure were 37.36%, 215%, and 57.68%, respectively. This work delves into the role of PM H+-ATPase in mediating the detoxification mechanism in plants exposed to herbicides, offering new insights into enhancing crop resistance against herbicides.

Design of Pentanary Mixed-Chalcogenides Ag2In2SiS6-xSex (x = 1, 2) Based on the Bucket Effect: Local Structural Difference and High-Performance Nonlinear-Optical Properties Realized by Partial Congener Substitution.

Noncentrosymmetric chalcogenides are promising candidates for infrared nonlinear-optical (NLO) crystals, and exploring high-performance ones is a hot topic and challengeable. Herein, the combination of AgQ4, InQ4, and SiQ4 (Q = S, Se) units with different S/Se ratios resulted in the discovery of the tetrahedral chalcogenides Ag2In2SiS4Se2 (1) and Ag2In2SiS5Se (2). They both crystallize in the monoclinic Cc space group with different local structures. Co-occupied S/Se sites only exist in 2, and the arrangement of [In2SiQ3] six-membered rings builds different helical chains and 3D [(In2SiQ6)2-]n polyanionic frameworks in 1 and 2. They show balanced NLO performances, including phase-matchable moderate NLO responses (0.7 and 0.5 × AGS) and enhanced laser-induced damage thresholds (4.5 and 5.1 × AGS). Theoretical calculations reveal that their NLO responses are predominantly contributed by the AgQ4 and InQ4 units.

DFT investigation of the DDQ-catalytic mechanism for constructing C-O bonds.

In this study, we investigated the photo-catalytic mechanisms for the construction of C-O bonds from arenes (benzene, 2',6'-dimethyl-[1,1'-biphenyl]-2-carboxylic acid, or 2,4-dichloro-1-fluorobenzene), catalyzed by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). All the structures for the Gibbs free surfaces were calculated at the M06-2X-D3/ma-def2-SVP level in the SMD solvent model. Also, TDDFT calculations of DDQ were performed at the PBE1PBE-D3/ma-def2-SVP level in the SMD solvent model. The computational results indicated that DDQ, serving as a photo-catalyst, would be excited under visible light of 450 nm, aligning well with experimental observations as reflected in the UV-vis spectrum. Gibbs free energy surface analyses of the three reactions suggested that the path involving 3DDQ* activating the reactant (-COOH, H2O, or CH3OH) is favorable. Additionally, the role of O2 was investigated, revealing that it could facilitate the recycling of DDQ by lowering the energy barrier for the conversion of the DDQH˙ radical (not DDQH2) into DDQ. The use of ρhole and ρele can reveal the photo-catalytic reaction and charge transfer processes, while localized orbital locator isosurfaces and electron spin density isosurface graphs were employed to analyze structures and elucidate the single electron distribution. These computational results offer valuable insights into the studied interactions and related processes, shedding light on the mechanisms governing C-O bond formation from arenes catalyzed by DDQ.

Hybridizing carbonate and ether at molecular scales for high-energy and high-safety lithium metal batteries.

Commonly-used ether and carbonate electrolytes show distinct advantages in active lithium-metal anode and high-voltage cathode, respectively. While these complementary characteristics hold promise for energy-dense lithium metal batteries, such synergy cannot be realized solely through physical blending. Herein, a linear functionalized solvent, bis(2-methoxyethyl) carbonate (BMC), is conceived by intramolecularly hybridizing ethers and carbonates. The integration of the electron-donating ether group with the electron-withdrawing carbonate group can rationalizes the charge distribution, imparting BMC with notable oxidative/reductive stability and relatively weak solvation ability. Furthermore, BMC also offers advantages including the ability to slightly dissolve LiNO3, excellent thermostability and nonflammability. Consequently, the optimized BMC-based electrolyte, even with typical concentrations in the single solvent, demonstrates high-voltage tolerance (4.4 V) and impressive Li plating/stripping Coulombic efficiency (99.4%). Moreover, it fulfills practical lithium metal batteries with satisfactory cycling performance and exceptional tolerance towards thermal/mechanical abuse, showcasing its suitability for safe high-energy lithium metal batteries.

Early growth response 1 regulates dual­specificity protein phosphatase 1 and inhibits cell migration and invasion of tongue squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC.

Effects of fermentation with different probiotics on the quality, isoflavone content, and flavor of okara beverages.

The present study aimed to prepare and evaluate a new probiotic functional beverage, using single-probiotic and compound probiotic fermentation on okara. Four different forms of fermentation microorganisms used were Lacticaseibacillus rhamnosus S24 (Lr), Lacticaseibacillus paracasei 6244 (Lp), Lactobacillus acidophilus 11,073 (La), and mixed fermentation (Lr + Lp + La). The physicochemical properties, antioxidant activity, flavor change, and storage period of fermented okara beverages with probiotics were investigated. The results showed that different fermentation schemes could significantly improve the physicochemical properties, antioxidant activity, and sensory quality of the okara beverages. The number of viable bacteria in the Lp group (3.53 × 108 CFU/mL), isoflavone content (0.514 µg/mL) were the highest; total phenol and flavonoid content were 3.32 and 5.68 times higher than in the CK group, respectively. DPPH and ABTS+ free radical scavenging rates were increased by 11.32% and 20%, respectively (p < .05). Through SPME/GC-MS analysis, 44 volatile compounds were identified in the Lr + Lp + La groups, mainly as a result of changes in alcohols and aldehydes produced by fermentation metabolism. It enhances the floral and fruity aroma of the okara beverage. All probiotic-fermented okara beverages can be stored at 4°C for 15 days, with probiotic activity greater than 107 CFU/mL. This study can obtain a probiotic okara beverage rich in soybean isoflavones and with good flavor. Overall, okara can be used to develop functional beverages containing probiotics and contribute to a zero-waste approach in the food industry.

Investigation of autophagy­related genes and immune infiltration in calcific aortic valve disease: A bioinformatics analysis and experimental validation.

The present study aimed to elucidate the role of autophagy-related genes (ARGs) in calcific aortic valve disease (CAVD) and their potential interactions with immune infiltration via experimental verification and bioinformatics analysis. A total of three microarray datasets (GSE12644, GSE51472 and GSE77287) were obtained from the Gene Expression Omnibus database, and gene set enrichment analysis was performed to identify the relationship between autophagy and CAVD. After differentially expressed genes and differentially expressed ARGs (DEARGs) were identified using CAVD samples and normal aortic valve samples, a functional analysis was performed, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, protein-protein interaction network construction, hub gene identification and validation, immune infiltration and drug prediction. The results of the present study indicated a significant relationship between autophagy and CAVD. A total of 46 DEARGs were identified. GO and pathway enrichment analyses revealed the complex roles of DEARGs in regulating CAVD, including multiple gene functions and pathways. A total of 10 hub genes were identified, with three (SPP1, CXCL12 and CXCR4) consistently upregulated in CAVD samples compared with normal aortic valve samples in multiple datasets and experimental validation. Immune infiltration analyses demonstrated significant differences in immune cell proportions between CAVD samples and normal aortic valve samples, thus showing the crucial role of immune infiltration in CAVD development. Furthermore, therapeutic drugs were predicted that could target the identified hub genes, including bisphenol A, resveratrol, progesterone and estradiol. In summary, the present study illuminated the crucial role of autophagy in CAVD development and identified key ARGs as potential therapeutic targets. In addition, the observed immune cell infiltration and predicted autophagy-related drugs suggest promising avenues for future research and novel CAVD treatments.

A Framework for Single-Panicle Litchi Flower Counting by Regression with Multitask Learning.

The number of flowers is essential for evaluating the growth status of litchi trees and enables researchers to estimate flowering rates and conduct various phenotypic studies, particularly focusing on the information of individual panicles. However, manual counting remains the primary method for quantifying flowers, and there has been insufficient emphasis on the advancement of reliable deep learning methods for estimation and their integration into research. Furthermore, the current density map-based methods are susceptible to background interference. To tackle the challenges of accurately quantifying small and dense male litchi flowers, a framework counting the flowers in panicles is proposed. Firstly, an existing effective algorithm YOLACT++ is utilized to segment individual panicles from images. Secondly, a novel algorithm FlowerNet based on density map regression is proposed to accurately count flowers in each panicle. By employing a multitask learning approach, FlowerNet effectively captures both foreground and background information, thereby overcoming interference from non-target areas during pixel-level regression tasks. It achieves a mean absolute error of 47.71 and a root mean squared error of 61.78 on the flower dataset constructed. Additionally, a regression equation is established using a dataset of inflorescences to examine the application of the algorithm for flower counting. It captures the relationship between the predicted number of flowers by FlowerNet and the manually counted number, resulting in a determination coefficient (R2) of 0.81. The proposed algorithm shows promise for automated estimation of litchi flowering quantity and can serve as a valuable reference for litchi orchard management during flowering period.

Charge-Reversed Exosomes for Targeted Gene Delivery to Cartilage for Osteoarthritis Treatment.

Gene therapy has the potential to facilitate targeted expression of therapeutic proteins to promote cartilage regeneration in osteoarthritis (OA). The dense, avascular, aggrecan-glycosaminoglycan (GAG) rich negatively charged cartilage, however, hinders their transport to reach chondrocytes in effective doses. While viral vector mediated gene delivery has shown promise, concerns over immunogenicity and tumorigenic side-effects persist. To address these issues, this study develops surface-modified cartilage-targeting exosomes as non-viral carriers for gene therapy. Charge-reversed cationic exosomes are engineered for mRNA delivery by anchoring cartilage targeting optimally charged arginine-rich cationic motifs into the anionic exosome bilayer by using buffer pH as a charge-reversal switch. Cationic exosomes penetrated through the full-thickness of early-stage arthritic human cartilage owing to weak-reversible ionic binding with GAGs and efficiently delivered the encapsulated eGFP mRNA to chondrocytes residing in tissue deep layers, while unmodified anionic exosomes do not. When intra-articularly injected into destabilized medial meniscus mice knees with early-stage OA, mRNA loaded charge-reversed exosomes overcame joint clearance and rapidly penetrated into cartilage, creating an intra-tissue depot and efficiently expressing eGFP; native exosomes remained unsuccessful. Cationic exosomes thus hold strong translational potential as a platform technology for cartilage-targeted non-viral delivery of any relevant mRNA targets for OA treatment.

A two-step method of cyclolinopeptide (linusorb) preparation from flaxseed cake via dry-screening.

Linusorbs (LO), cyclolinopeptides, are a group of cyclic hydrophobic peptides and considered a valuable by-product of flaxseed oil due to numerous health benefits. Currently applied acetone or methanol extraction could contaminate the feedstocks for further food-grade application. Using flaxseed cake as feedstock, this study established a practical method for preparing LO from pressed cake. Firstly, LO composition of 15 flaxseed cultivars was analyzed. Next, cold-pressed cake was milled and screened mechanically. The kernel and hull fractions were separated based on the disparity of their mechanical strength. Monitored by hyperspectral fluorescence, the LO-enriched kernel fraction separated from cold-pressed flaxseed cake was further used as feedstock for LO production. After ethanol extraction, partition, and precipitation, LOs were extracted from cold-pressed flaxseed cake with a purity of 91.4%. The proposed method could serve as feasible flaxseed cake valorization strategy and enable the preparation of other polar compounds such as flax lignan and mucilage.

Bruceantinol works as a CDK2/4/6 inhibitor to inhibit the growth of breast cancer cells.

Bruceantinol (BOL), isolated from the dried fruit of the Brucea javanica (L.) Merr., exhibits cytotoxic effects on breast cancer cells. However, the underlying mechanism remains to be fully addressed. In this paper, the MCF-7 and MDA-MB-231 human breast cancer cell lines were used as experimental models to uncover how BOL inhibits breast cancer cell growth. The effects of BOL on cell growth, proliferation, the cell cycle, and apoptosis were investigated using the MTT assays, EdU incorporation assays, and flow cytometry, respectively. Bioinformatics techniques were applied to predict the key targets of BOL in breast cancer. Subsequent validation of these targets and the anti-breast cancer mechanism of BOL was conducted through Western blotting, RT-PCR, siRNA transfection, and molecular docking analysis. The results demonstrated that BOL dose- and time-dependently reduced the growth of both cell lines, impeded cell proliferation, disrupted the cell cycle, and induced necrosis in MCF-7 cells and apoptosis in MDA-MB-231 cells. Furthermore, CDK2/4/6 were identified as BOL targets, and their knockdown reduced cell sensitivity to BOL. BOL was found to potentially bind with CDK2/4/6 to facilitate protein degradation through the proteasome pathway. Additionally, BOL activated ERK in MDA-MB-231 cells, and this activation was required for BOL's functions in these cells. Collectively, BOL may act as an inhibitor of CDK2/4/6 to exert anti-breast cancer effects. Its effects on cell growth and CDK2/4/6 expression may also depend on ERK activation in HRs-HER2- breast cancer cells. These results suggest the potential of using BOL for treating breast cancer.

Integration of transcriptome, gut microbiota, and physiology reveals toxic responses of the red claw crayfish (Cherax quadricarinatus) to imidacloprid.

Imidacloprid enters the water environment through rainfall and causes harm to aquatic crustaceans. However, the potential chronic toxicity mechanism of imidacloprid in crayfish has not been comprehensively studied. In this study, red claw crayfish (Cherax quadricarinatus) were exposed to 11.76, 35.27, or 88.17 µg/L imidacloprid for 30 days, and changes in the physiology and biochemistry, gut microbiota, and transcriptome of C. quadricarinatus and the interaction between imidacloprid, gut microbiota, and genes were studied. Imidacloprid induced oxidative stress and decreased growth performance in crayfish. Imidacloprid exposure caused hepatopancreas damage and decreased serum immune enzyme activity. Hepatopancreatic and plasma acetylcholine decreased significantly in the 88.17 µg/L group. Imidacloprid reduced the diversity of the intestinal flora, increased the abundance of harmful flora, and disrupted the microbiota function. Transcriptomic analysis showed that the number of up-and-down-regulated differentially expressed genes (DEGs) increased significantly with increasing concentrations of imidacloprid. DEG enrichment analyses indicated that imidacloprid inhibits neurotransmitter transduction and immune responses and disrupts energy metabolic processes. Crayfish could alleviate imidacloprid stress by regulating antioxidant and detoxification-related genes. A high correlation was revealed between GST, HSPA1s, and HSP90 and the composition of gut microorganisms in crayfish under imidacloprid stress. This study highlights the negative effects and provides detailed sequencing data from transcriptome and gut microbiota to enhance our understanding of the molecular toxicity of imidacloprid in crustaceans.

Carbonaceous particulate matter promotes the horizontal transfer of antibiotic resistance genes.

There is growing concern about the transfer of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in airborne particulate matter. In this study, we investigated the effects of various types of carbonaceous particulate matter (CPM) on the transfer of ARGs in vitro. The results showed that CPM promoted the transfer of ARGs, which was related to the concentration and particle size. Compared with the control group, the transfer frequency was 95.5, 74.7, 65.4, 14.7, and 3.8 times higher in G (graphene), CB (carbon black), NGP (nanographite powder), GP1.6 (graphite powder 1.6 micron), and GP45 (graphite powder 45 micron) groups, respectively. Moreover, the transfer frequency gradually increased with the increase in CPM concentration, while there was a negative relationship between the CPM particle size and conjugative transfer frequency. In addition, the results showed that CPM could promote the transfer of ARGs by increasing ROS, as well as activating the SOS response and expression of conjugative transfer-related genes (trbBp, trfAp, korA, kroB, and trbA). These findings are indicative of the potential risk of CPM for the transfer of ARGs in the environment, enriching our understanding of environmental pollution and further raising awareness of environmental protection.

miR-1268a Regulates Fatty Acid Metabolism by Targeting CD36 in Angiotensin II-induced Heart Failure.

Multiple RNAs have been involved in the progress of heart failure. However, the role of miR-1268a in heart failure is still unclear. The differentially expressed miRNAs in heart failure was analyzed based on GEO dataset GSE104150. AC16 cells were treated with Angiotensin II (Ang II) to explore the role of miR-1268a in heart failure. The web tool miRWalk was used to analyze the targets of miR-1268a. miR-1268a was up-regulated in Ang II-treated AC16 cells. Ang II treatment markedly inhibited cell proliferation, ATP production, fatty acid (FA) uptake and enhanced levels of HF markers BNP and ST2, and oxidative stress of AC16 cells. Notably, inhibition of miR-1268a eliminated the inhibiting effect of Ang II on cell proliferation, ATP production, FA uptake and decreased levels of BNP an ST2, and oxidative stress on AC16 cells. Furthermore, CD36 was a target of miR-1268a and the CD36 level was decreased by miR-1268a mimics but increased by miR-1268a inhibitor in AC16 cells. miR-1268a regulates FA metabolism and oxidative stress in myocardial cells by targeting CD36 in heart failure.

Characterization of the metabolic contributions of cytochrome P450 isoforms to bicyclol using the relative activity factor method.

Bicyclol is a hepatoprotective agent widely used for treating chronic hepatitis and drug-induced liver injuries in clinics. The purpose of the study was to elucidate the contribution of CYP450 enzymes to the metabolism of bicyclol using the relative activity factor approach. After incubation with human liver microsomes and recombinant human liver CYP450 enzymes, the calculated contribution of CYP3A4 and 2C19 to the metabolism of bicyclol was 85.6-90.3% and 9.2-9.7%, respectively. The metabolism was interrupted in the presence of CYP3A4 and 2C19 selective inhibitors. These findings help to predict or avoid metabolic drug-drug interactions or toxicity in clinical applications of bicyclol.