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1.
Sci Total Environ ; : 152991, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35026259

RESUMO

Increasing environmental stress strongly affects soil microbial communities, but the responses of the microbial assembly and the functional potential of the dominant microbial community in the presence of environmental stress in drylands are still poorly understood. Here, we undertook a broad appraisal of the abundance, diversity, similarity, community assembly, network properties and functions of soil microbiomes in 82 dryland grasslands along environmental gradients. We found that the bacterial and fungal diversity and community similarity showed different sensitivities to environmental stress (decreased mean annual precipitation (MAP) and soil nutrient levels and increased soil pH), and MAP was the most important factor influencing microbial community patterns. In addition, the dominant subcommunity of both bacteria and fungi was more sensitive to environmental stress than the nondominant subcommunity. Although increasing environmental stress decreased microbial phylogenetic clustering, it had no effects on the stochastic and deterministic assembly process balance. Moreover, we identified 101 bacterial and 34 fungal environmental stress-discriminatory taxa that were sensitive to environmental stress, and these bacterial markers showed a high correlation with the abundance of carbon (C) and nitrogen (N) cycling-related genes, whereas the taxa classified as connectors in the network were mainly correlated with carbon degradation genes. Our study shows that the different responses of bacteria and fungi to environmental stress bring challenges to predicting microbial function, but a relatively small number of taxa play an important role in driving C and N cycling-related functional genes, indicating that identifying an organism's phenotypic characteristics or traits of key taxa may improve our knowledge of the microbial response to ongoing global changes.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35014796

RESUMO

The rapid development of electrochemical power systems has prompted high demand for nonprecious trifunctional electrocatalysts with superior performance, prolonged stability, and low cost for oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER). Here, a valence engineering strategy is devised to construct a morphology with polyvalent cobalt encapsulated in nitrogen-doped carbon nanofibers (Co/N-CNFs). The diverse cobalt valence states of the Co/N-CNF catalysts contribute to their excellent catalytic effect and high durability in multiple electrochemical processes. The optimal Co/N-CNF catalyst fabricated exhibits a high half-wave potential of ORR (0.86 V) and low overpotentials of OER (380 mV) and HER (241 mV) at 10 mA cm-2. The Co/N-CNF-based Zn-air battery possesses a high charge-discharge efficiency as well as a good cycle stability (50 h at 10 mA cm-2 and 120 h at 20 mA cm-2), much superior to the Pt/C-based batteries. Furthermore, the Co/N-CNF catalyst could perform efficient overall water splitting.

3.
Chin J Integr Med ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35015223

RESUMO

In conclusion, this case should remind clinicians of the potential dangers of glycyrrhizin (high blood pressure, low blood potassium and abnormal changes in ECG, among other effects). The timely detection and effective treatment of glycyrrhizin-induced PsHA can prevent the occurrence of serious complications. The importance of taking a detailed medical history is also emphasized.

4.
Soft comput ; : 1-9, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35002501

RESUMO

For usual uncertain heat equations, it is challenging to acquire their analytic solutions. A forward difference Euler method has been used to compute the uncertain heat equations' numerical solutions. Nevertheless, the Euler scheme is instability in some cases. This paper proposes an implicit task to overcome this disadvantage, namely the Crank-Nicolson method, which is unconditional stability. An example shows that the Crank-Nicolson scheme is more stable than the previous scheme (Euler scheme). Moreover, the Crank-Nicolson method is also applied to compute two characteristics of uncertain heat equation's solution-expected value and extreme value. Some examples of uncertain heat equations are designed to show the availability of the Crank-Nicolson method.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34993756

RESUMO

The benefits and risks of inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) remain a subject of debate. In this study, we investigated the effect of ferulic acid (FA) on the proliferation and migration of VSMCs induced by platelet-derived growth factor (PDGF) and the associated mechanism and used ApoE-/- mice to study whether the effect of FA on VSMC proliferation and migration is beneficial in alleviating AS plaques. It was found that FA not only reduced blood lipid levels but also promoted the production of nitric oxide (NO) by MOVAS cells through the endothelial nitric oxide synthase (eNOS) pathway, inhibited the migration and proliferation of VSMCs induced by PDGF, promoted the expression of p21 in VSMCs, and exerted a therapeutic effect against AS.

6.
Mol Ecol Resour ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35007382

RESUMO

The cottids (Cottidae) are a taxonomically diverse and ecologically important component of many marine and freshwater ecosystems. Despite recent breakthroughs in long-read sequencing, high quality genomic resources are still limited for studies of ecological and evolutionary processes in cottids. Here we generated a high-quality, chromosome-scale genome assembly (521.26 Mb) of the catadromous roughskin sculpin (Trachidermus fasciatus Heckel) with a contig N50 of 2.93 Mb and a scaffold N50 of 24.06 Mb. Approximately 21.97% of the genome was composed of repetitive elements. A total of 21,872 protein-coding genes were predicted, of which 19,900 genes (90.98%) were functionally annotated. Phylogenetic analysis supported the validity of Scorpaenoidei and Cottioidei as two suborders of the Perciformes. Chromosome-scale collinearity analyses identified four chromosome fusions leading to the reduction of chromosome number in T. fasciatus. Gene families related to cell apoptosis and cell death were expanded and those related to immune system were contracted, suggesting that these gene families might be relevant to a host of phenotypic differences between T. fasciatus and other teleosts. Gene families associated with osmoregulation were also expanded, which might be associated with its catadromous life history. A total of 50 aging-associated genes were found to be under positive selection, which might be associated with the short lifespan of T. fasciatus. The high-quality genome assembly and annotation will promote researches into the evolution of catadromous life history and short lifespan for T. fasciatus and facilitate comparative genomic studies of cottids in the near future.

7.
IEEE Trans Med Imaging ; PP2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020590

RESUMO

The accurate prediction of isocitrate dehydrogenase (IDH) mutation and glioma segmentation are important tasks for computer-aided diagnosis using preoperative multimodal magnetic resonance imaging (MRI). The two tasks are ongoing challenges due to the significant inter-tumor and intra-tumor heterogeneity. The existing methods to address them are mostly based on single-task approaches without considering the correlation between the two tasks. In addition, the acquisition of IDH genetic labels is expensive and costly, resulting in a limited number of IDH mutation data for modeling. To comprehensively address these problems, we propose a fully automated multimodal MRI-based multi-task learning framework for simultaneous glioma segmentation and IDH genotyping. Specifically, the task correlation and heterogeneity are tackled with a hybrid CNN-Transformer encoder that consists of a convolutional neural network and a transformer to extract the shared spatial and global information learned from a decoder for glioma segmentation and a multi-scale classifier for IDH genotyping. Then, a multi-task learning loss is designed to balance the two tasks by combining the segmentation and classification loss functions with uncertain weights. Finally, an uncertainty-aware pseudo-label selection is proposed to generate IDH pseudo-labels from larger unlabeled data for improving the accuracy of IDH genotyping by using semi-supervised learning. We evaluate our method on a multi-institutional public dataset. Experimental results show that our proposed multi-task network achieves promising performance and outperforms the single-task learning counterparts and other existing state-of-the-art methods. With the introduction of unlabeled data, the semi-supervised multi-task learning framework further improves the performance of glioma segmentation and IDH genotyping. The source codes of our framework are publicly available at https://github.com/miacsu/MTTU-Net.git.

8.
Adv Mater ; : e2109399, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35023217

RESUMO

Organic semiconducting emitters integrated with butterfly-mimetic photonic crystals (PhCs) are fascinating for dramatic advantages over light outcoupling efficiency and multifunctional strain sensors, as well as the key step toward electrically pumped lasers. Herein, we report an unprecedentedly direct mesoscale self-assembly into one-dimensional PhCs, through a covalently gridization-driven approach of wide-bandgap conjugated polymers. A simple solvent-casting procedure allows for in-situ self-assembly of the state-of-the-art conjugated nanopolymer, poly{[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]grid}-co-{[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]grid} (PODPFG), into well-defined multilayer architectures with an excellent toughness (30∼40 J m-3 ). This ordered meso-architecture shows a typical Bragg-Snell diffraction behavior to testify the PhC nature, along with a high effective refractive index (1.80∼1.88) and optical transmittance (85∼87%). The PhC films also exhibit an angle-dependent blue/green photoluminescence switching, an electroluminescence efficiency enhancement by 150%∼250%, and an amplified spontaneous emission enhancement with ultralow waveguide loss coefficient (2.60 cm-1 ). Gridization of organic semiconductors offers promising opportunities for cross-scale morphology-directed molecular design in multifunctional organic mechatronics and intelligences. This article is protected by copyright. All rights reserved.

9.
Bioinformatics ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34999771

RESUMO

MOTIVATION: Recently, with the development of high-throughput experimental technology, reconstruction of gene regulatory network (GRN) has ushered in new opportunities and challenges. Some previous methods mainly extract gene expression information based on RNA-seq data, but the associated information is very limited. With the establishment of gene expression image database, it is possible to infer GRN from image data with rich spatial information. RESULTS: Firstly, we propose a new convolutional neural network (called SDINet), which can extract gene expression information from images and identify the interaction between genes. SDINet can obtain the detailed information and high-level semantic information from the images well. And it can achieve satisfying performance on image data(Acc: 0.7196, F1: 0.7374). Secondly, we apply the idea of our SDINet to build an RNA-model, which also achieves good results on RNA-seq data(Acc: 0.8962, F1: 0.8950). Finally, we combine image data and RNA-seq data, and design a new fusion network to explore the potential relationship between them. Experiments show that our proposed network fusing two modalities can obtain satisfying performance(Acc: 0.9116, F1: 0.9118) than any single data. CONCLUSION: We propose a new network that can better extract gene expression information from image data. Besides, we combine image data and RNA-seq data to infer GRN and design a new fusion network to learn the joint features of these two data types for the first time. AVAILABILITY: Data and code are available from https://github.com/guofei-tju/Combine-Gene-Expression-images-and-RNA-seq-data-For-infering-GRN.

10.
Zhongguo Zhen Jiu ; 42(1): 75-8, 2022 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-35025161

RESUMO

To summarize SUN Shen-tian's treatment ideas and clinical features. SUN applies meridian syndrome differentiation to the diagnosis and treatment of diseases; advocates that prevention and treatment of diseases should be regulated mind firstly; applies transcranial repetitive acupuncture combined modern cerebral cortex function positioning; emphasizes the application of multiple acupuncture methods and manipulation, and includes the meridian penetrating needling method, the flat needling and penetrating needling method, and the stagnant needle lifting method, pays attention to the importance of achieving qi and manipulation for the effect.

11.
Nano Lett ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35025517

RESUMO

Integration of entangled photon sources in a quantum photonic chip has enabled the most envisioned quantum photonic technologies to be performed in a compact platform with enhanced complexity and stability as compared to bulk optics. However, the technology to generate entangled photon states in a quantum photonic chip that are neither probabilistic nor restricted to low efficiency is still missing. Here, we introduce a hybrid quantum photonic chip where waveguide-coupled self-assembled quantum dots (QDs) are heterogeneously integrated onto a piezoelectric actuator. By exerting an anisotropic stress, we experimentally show that the fine structure splitting of waveguide-coupled quantum dots can be effectively eliminated. This allows for the demonstration of chip-integrated self-assembled QDs for generating and routing polarization-entangled photon pairs. Our results presented here would open up an avenue for implementing on-demand quantum information processing in a quantum photonic chip by employing all-solid-state self-assembled quantum dot emitters.

12.
Curr Res Food Sci ; 5: 34-40, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35028592

RESUMO

Highly manufacturing process of chestnut paste leaves a considerable space for Economically Motivated Adulteration (EMA) with cheaper ingredients such as mung bean. In this paper a novel quantitative detection of mung bean in chestnut paste using duplex digital PCR was reported. Two sets of primers and probes were designed according to mung bean and chestnut specific genomic genes suitable for duplex droplet digital PCR (ddPCR) and duplex chip digital PCR (cdPCR) to set up a mass ratio quantitative detection method for mung bean, a common alternative plant-derived ingredient in chestnut paste products. The manufacturing process of chestnut paste products was considered to establish the linear relationship formula between mass ratio and gene copy number (CN) ratio of the two ingredients. The limits of quantification for gene CN concentrations (LOQcopy) of mung bean and chestnut were both 6 copies/µL, at the same time a mass ratio of mung bean in chestnut paste range from 5% to 80% was able to be quantified accurately to provide technical support for the identification of fraudulent substitution or adventitious contamination.

13.
Cardiol Young ; : 1-6, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34986917

RESUMO

OBJECTIVE: To evaluate the association of systolic blood pressure percentile, race, and body mass index with left ventricular hypertrophy on electrocardiogram and echocardiogram to define populations at risk. STUDY DESIGN: This is a retrospective cross-sectional study design utilising a data analytics tool (Tableau) combining electrocardiogram and echocardiogram databases from 2003 to 2020. Customized queries identified patients aged 2-18 years who had an outpatient electrocardiogram and echocardiogram on the same date with available systolic blood pressure and body measurements. Cases with CHD, cardiomyopathy, or arrhythmia diagnoses were excluded. Echocardiograms with left ventricle mass (indexed to height2.7) were included. The main outcome was left ventricular hypertrophy on echocardiogram defined as Left ventricle mass index greater than the 95th percentile for age. RESULTS: In a cohort of 13,539 patients, 6.7% of studies had left ventricular hypertrophy on echocardiogram. Systolic blood pressure percentile >90% has a sensitivity of 35% and specificity of 82% for left ventricular hypertrophy on echocardiogram. Left ventricular hypertrophy on electrocardiogram was a poor predictor of left ventricular hypertrophy on echocardiogram (9% sensitivity and 92% specificity). African American race (OR 1.31, 95% CI = 1.10, 1.56, p = 0.002), systolic blood pressure percentile >95% (OR = 1.60, 95% CI = 1.34, 1.93, p < 0.001), and higher body mass index (OR = 7.22, 95% CI = 6.23, 8.36, p < 0.001) were independently associated with left ventricular hypertrophy on echocardiogram. CONCLUSIONS: African American race, obesity, and hypertension on outpatient blood pressure measurements are independent risk factors for left ventricular hypertrophy in children. Electrocardiogram has little utility in the screening for left ventricular hypertrophy.

14.
Clin Exp Nephrol ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34988726

RESUMO

BACKGROUND: The association of transient acute kidney injury (AKI) with mortality was controversial. Our study aims to investigate the prevalence and impact of transient AKI on mortality in patients following coronary angiography (CAG). METHODS: Our study retrospectively enrolled 3970 patients with pre-operative serum creatinine (Scr) and twice measurements within 48 h after procedure. Transient AKI defined as the diagnosis of AKI (Scr > 0.3 mg/dL or > 50% from the baseline level) on day 1 when Scr failed to meet the criteria for AKI on the day 2. Maintained AKI was defined as AKI not meeting the definition for transient AKI. The primary outcome was 1-year all-cause mortality. Multivariable logistic regression was used to assess the association between transient AKI and 1-year mortality. RESULTS: Among 3,970 participants, 861 (21.7%) occurred AKI, of whom 128 (14.9%) was transient AKI and 733 (85.1%) was maintained AKI. 312 (7.9%) patients died within 1-year after admission. After multivariable analysis, transient AKI was not associated with higher 1-year mortality [adjusted odds ratio (aOR), 1.37; CI 0.68-2.51] compared without AKI. Among AKI patients, transient AKI was associated with a 52% lower 1-year mortality compared with maintained AKI. Additionally, maintained AKI was significantly associated with higher 1-year mortality (aOR, 2.67; CI 2.05-3.47). CONCLUSIONS: Our data suggested that transient AKI within 48 h was a common subtype of AKI following CAG, without increasing mortality. More attention needs to be paid to the patients suffering from maintained AKI following CAG.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34994317

RESUMO

Mesenchymal stem cells (MSCs) are remarkable and noteworthy. Identification of markers for MSCs enables the study of their niche in vivo. It has been identified that glioma-associated oncogene 1 positive (Gli1+) cells are mesenchymal stem cells supporting homeostasis and injury repair, especially in the skeletal system and teeth. This review outlines the role of Gli1+ cells as an MSC subpopulation in both bones and teeth, suggesting the prospects of Gli1+ cells in stem cell-based tissue engineering.

16.
J Inorg Biochem ; 226: 111656, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34798307

RESUMO

A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.

17.
J Hazard Mater ; 423(Pt B): 127056, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34547692

RESUMO

Reducing the cost of pellet additives as a substitute for reducing bentonite binder is an important research direction of new pellet additives. There are some industrial solid wastes that have the similar physical and chemical properties to bentonite, and SiO2 content of them may be much lower than bentonite, but also contains a lot of Fe2O3, Al2O3, MgO, B2O3 and other components beneficial to the quality of pellets, which have been paid more attention by many pellet workers. In this review, the effect mechanism of Fe2O3, Na2O/K2O, Al2O3, SiO2, CaO, MgO and B2O3 in the industrial solid wastes on the fired strength and reduction expansion of pellets were systematically summarized. At the same time, the influences of five representative large scale modified industrial solid waste additives including iron tailings, bauxite tailings, fly ash, red mud and boron sludge on the properties of green pellets and finished pellets were described in detail. It can be seen that the applications of industrial solid waste in pellet additives can partially or completely replace bentonite binder, especially fly ash, red mud and boron sludge, which can not only improve the quality of pellets, but also decrease the cost, save energy and reduce pollution, with significant economic benefits.

18.
Pest Manag Sci ; 78(1): 63-72, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34418274

RESUMO

BACKGROUND: It is a common phenomenon that insecticides affect insect reproduction and insect hormones. After cyantraniliprole treatment, the egg production and remating behavior of female Bactrocera dorsalis were affected, a phenomenon of 'hormesis' appeared, but the change at the molecular level was unknown. Therefore, we investigated the fertility, insect hormone titers and transcription levels and used RNAi to prove the function of genes, to explore the molecular mechanism of cyantraniliprole causing reproductive changes in female B. dorsalis. RESULTS: LC20 treatment promoted egg production, while LC50 treatment inhibited it. Both high and low concentrations inhibited female ovaries' development and reduced the length of the ovarian tubes. Among insect hormones, only the titer of 20-hydroxyecdysone (20E) changed significantly. According to the KEGG pathway enrichment analysis of RNA-seq, there are significant differences in insect hormone synthesis and MAPK signal pathways between treatments. Furthermore, 20E biosynthetic genes, BdVgs and BdVgR were all down-regulated, and multiple MAPK signaling pathway genes were up-regulated. Based on qRT-PCR, the expression of BdCyp307A1, BdCyp302A1, BdMEKK4 and BdMAP2K6 within 1-11 days after treatment were consistent with the change of 20E titer. The BdVg1 and BdVg2 in LC50 were still suppressed, while the LC20 returned to normal in 9-11 days. RNAi indicated that BdMEKK4 and BdMAP2K6 participated in the transcriptional regulation of BdCyp307A1 and BdCyp302A1, then affected the levels of BdVgs. CONCLUSION: Cyantraniliprole affected 20E through MAPK signal pathway, causing many genes to be down-regulated during the early period but up-regulated during the late period, ultimately affecting the reproduction of B. dorsalis. © 2021 Society of Chemical Industry.


Assuntos
Tephritidae , Animais , Feminino , Pirazóis , Reprodução , Transdução de Sinais , Tephritidae/genética , ortoaminobenzoatos
19.
Neural Regen Res ; 17(3): 618-624, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34380902

RESUMO

Patients with type 2 diabetes mellitus (T2DM) often have cognitive impairment and structural brain abnormalities. The magnetic resonance imaging (MRI)-based brain atrophy and lesion index can be used to evaluate common brain changes and their correlation with cognitive function, and can therefore also be used to reflect whole-brain structural changes related to T2DM. A total of 136 participants (64 men and 72 women, aged 55-86 years) were recruited for our study between January 2014 and December 2016. All participants underwent MRI and Mini-Mental State Examination assessment (including 42 healthy control, 38 T2DM without cognitive impairment, 26 with cognitive impairment but without T2DM, and 30 T2DM with cognitive impairment participants). The total and sub-category brain atrophy and lesion index scores in patients with T2DM with cognitive impairment were higher than those in healthy controls. Differences in the brain atrophy and lesion index of gray matter lesions and subcortical dilated perivascular spaces were found between non-T2DM patients with cognitive impairment and patients with T2DM and cognitive impairment. After adjusting for age, the brain atrophy and lesion index retained its capacity to identify patients with T2DM with cognitive impairment. These findings suggest that the brain atrophy and lesion index, based on T1-weighted and T2-weighted imaging, is of clinical value for identifying patients with T2DM and cognitive impairment. Gray matter lesions and subcortical dilated perivascular spaces may be potential diagnostic markers of T2DM that is complicated by cognitive impairment. This study was approved by the Medical Ethics Committee of University of South China (approval No. USC20131109003) on November 9, 2013, and was retrospectively registered with the Chinese Clinical Trial Registry (registration No. ChiCTR1900024150) on June 27, 2019.

20.
J Ethnopharmacol ; 282: 114643, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34534597

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: With the features of multiple-components and targets as well as multifunction, traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of various diseases for a long time. During the application of TCM, the researches about bioavailability enhancement of the bioactive constituents in formula are flourishing. Bushen-Yizhi formula (BSYZ), a TCM prescription with osthole (OST) as one of the main bioactive ingredients, have been widely used to treat kidney deficiency, mental retardation and Alzheimer's disease. However, the underlying biological mechanism and compound-enzyme interaction mediated bioavailability enhancement of OST are still not clearly illuminated. AIM OF THE STUDY: The aim of this study is to explore the material basis and molecular mechanism from BSYZ in the bioavailability enhancement of OST. Screening the potential CYP3A4 inhibitors using theoretical prediction and then verifying them in vitro, and pharmacokinetics study of OST in rat plasma under co-administrated of screened CYP3A4 inhibitors and BSYZ were also scarcely reported. MATERIALS AND METHODS: Screening of CYP3A4 inhibitors from BSYZ was performed with molecular docking simulation from systems pharmacology database. The screened compounds were verified by using P450-Glo Screening Systems. A multiple reaction monitoring (MRM) mass spectrometry method was established for OST quantification. Male Sprague-Dawley rats divided into four groups and six rats in each group were employed in the pharmacokinetics study of OST. The administrated conditions were group I, OST (20 mg/kg); group II, BSYZ (containing OST 1 mg/mL, at the dose of 20 mg/kg OST in BSYZ); group III, co-administration of ketoconazole (Ket, 75 mg/kg) and OST (20 mg/kg); group IV, co-administration of CYP3A4 inhibitor (10 mg/kg) and OST (20 mg/kg). They were determined by using HPLC-MS/MS (MRM) and statistical analysis was performed using student's t-test with p < 0.05 as the level of significance. RESULTS: 21 potential CYP3A4 inhibitors were screened from BSYZ compounds library. From the results of verification in vitro, we found 4 compounds with better CYP3A4 inhibition efficiency including Oleic acid, 1,2,3,4,6-O-Pentagalloylglucose, Rutin, and Schisantherin B. Under further verification, Schisantherin B exhibited the best inhibitory effect on CYP3A4 (IC50 = 0.339 µM), and even better than the clinically used drug (Ket) at the concentration of 5 µM. In the study of pharmacokinetics, the area under the curve (AUC, ng/L*h) of OST after oral administration of BSYZ, Ket and Schisantherin B (2196.23 ± 581.33, 462.90 ± 92.30 and 1053.03 ± 263.62, respectively) were significantly higher than that of pure OST treatment (227.89 ± 107.90, p < 0.01). CONCLUSIONS: Schisantherin B, a profoundly effective CYP3A4 inhibitor screened from BSYZ antagonized the metabolism of CYP3A4 on OST via activity inhibition, therefore significantly enhanced the bioavailability of OST in rat plasma. The results of this study will be helpful to explain the rationality of the compatibility in TCM formula, and also to develop new TCM formula with more reasonable drug compatibility.

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