Complex Knowledge Base Question Answering for Intelligent Bridge Management Based on Multi-Task Learning and Cross-Task Constraints.

In the process of bridge management, large amounts of domain information are accumulated, such as basic attributes, structural defects, technical conditions, etc. However, the valuable information is not fully utilized, resulting in insufficient knowledge service in the field of bridge management. To tackle these problems, this paper proposes a complex knowledge base question answering (C-KBQA) framework for intelligent bridge management based on multi-task learning (MTL) and cross-task constraints (CTC). First, with C-KBQA as the main task, part-of-speech (POS) tagging, topic entity extraction (TEE), and question classification (QC) as auxiliary tasks, an MTL framework is built by sharing encoders and parameters, thereby effectively avoiding the error propagation problem of the pipeline model. Second, cross-task semantic constraints are provided for different subtasks via POS embeddings, entity embeddings, and question-type embeddings. Finally, using template matching, relevant query statements are generated and interaction with the knowledge base is established. The experimental results show that the proposed model outperforms compared mainstream models in terms of TEE and QC on bridge management datasets, and its performance in C-KBQA is outstanding.

Characterisation of hederacoside C metabolites using ultrahigh-performance liquid chromatography quadrupole Orbitrap mass spectrometry based on automatic fragment ion search.

INTRODUCTION: Hederacoside C (HDC) is a bioactive natural triterpenoid saponins constituent originating from traditional Chinese medicines, playing an important role in the treatment of acute respiratory infections and chronic inflammatory bronchitis. Meanwhile, it is recognised by Korea as a botanical drug. OBJECTIVES: In order to develop an integrated template approach to analysing screening and identification of the metabolites of traditional Chinese medicines. This study will provide available information for further pharmaceutical studies of HDC and other triterpene saponins. METHODOLOGY: An analysis strategy based on ultrahigh-performance liquid chromatography quadrupole Orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS) technique combined with automatic fragment ion search (FISh) was firstly exploited for the characterisation metabolites of HDC in vivo and in vitro. Accurate full mass scan combined with an on-line FISh annotations approach was developed to rapidly identify all the potential metabolites of HDC. Furthermore, FISh accurately located the structure of the target compound in a large number of mass spectral data. RESULTS: A total of 34 metabolites were detected and tentatively identified by analysing comprehensive biological samples. The results clearly demonstrated that HDC underwent general metabolic reactions including dealkylation, reduction, oxidation, desaturation, dehydration, cysteine conjugation, GSH conjugation, taurine conjugation, and glycine conjugation to produce 26 phase I and eight phase II metabolites. CONCLUSION: In the present study, UHPLC-Q-Exactive Orbitrap MS technique combined with FISh provided a rapid and efficient platform to characterise metabolites of HDC in vivo and in vitro. The proposed method could develop an integrated template approach to screen and identify the constituents and metabolites of traditional Chinese medicines.

Safety assessment and antioxidant evaluation of betulin by LC-MS combined with free radical assays.

Betulin, as a new type of natural food preservative, is widely used in various kinds of meat products. However, its detailed mechanism of action and metabolism have not been clarified. In this study, for further gain insight of the mechanism of betulin as a preservative, an efficient method has been applied for measuring the antioxidant capacity of betulin, based on the absorbance of the DPPH• and ABTS• radical cation. When the concentration of betulin was more than 2.0 mg/mL, the scavenging rate of ABTS and DPPH radical reached over 90%, which was equivalent to the antioxidant capacity of Trolox. It is indicated that betulin has significant DPPH and ABTS free radical scavenging ability. This should be one of the important mechanisms for betulin as a preservative. A sensitive method using UHPLC-Q-TOF-MS/MS was established to determine the metabolite profile in vivo and in vitro of betulin. 32 phase I and 2 phase II metabolites were structurally characterized. This study will provide theoretical support for the safety and effectiveness of betulin in the field of preservatives and provide theoretical basis for the further study of betulin and the other natural preservatives. This research also contributes to the development of the food industry.

A high-throughput metabolomics approach for the comprehensive differentiation of four Pulsatilla Adans herbs combined with a nontargeted bidirectional screen for rapid identification of triterpenoid saponins.

Pulsatilla Adans (PSA) herbs (Ranunculaceae) have been widely used in traditional medicine in China and other countries. However, the authentication and quality control of PSA herbs have always been a challenging task due to their similar morphological characteristics and the diversity of the multiple components that exist in the complicated matrix. Herein, a novel integrated strategy combining UHPLC/Q-Orbitrap-MS techniques with chemometrics analysis is proposed for the discrimination of PSA materials. We developed a comprehensive method integrating a nontargeted bidirectionally screened (NTBDS) MS data set and a targeted extraction peak area analysis for the characterization of triterpenoid saponins of PSA from different species. After that, partial least-squares discriminant analysis (PLS-DA) was performed on the obtained MS data set and the parameter variable importance for the projection (VIP) value and P value were employed to screen the valuable MS features to discriminate PSA from different species. In addition, the receiver operating characteristic (ROC) curve is used to verify the reliability of MS features. Finally, heatmap visualization was employed to clarify the distribution of the identified triterpenoid saponins, and four medicinal species of PSA were successfully differentiated. Additionally, 34 constituents were reported in PSAs for the first time, 81 triterpenoid saponins were identified as differential components, and 12 chemical ingredients were characterized as potential chemical markers to differentiate the four officinal PSA herbs. This is the first time that the differences in different PSA herbs have been observed systematically at the chemical level. The results suggested that using the identified characteristic components as chemical markers to identify different PSA herbs was effective and viable. This method provides promising perspectives in the analysis and identification of the ingredients of Chinese herbal medicines, and the identification of similar herbs from the same species.

Study on the metabolites of betulinic acid in vivo and in vitro by ultra high performance liquid chromatography with time-of-flight mass spectrometry.

Betulinic acid is a triterpenoid organic acid with remarkable antitumor properties and is naturally present in many fruits, condiments and traditional Chinese medicines. Currently, a strategy was developed for the identification of metabolites following the in vivo and in vitro biotransformation of Betulinic acid with rat intestinal bacteria utilizing ultra high performance liquid chromatography with time-of-flight mass spectrometry with polymeric solid-phase extraction. As a result, 46 metabolites were structurally characterized. The results demonstrated that Betulinic acid is universally metabolized in vivo and in vitro, and Betulinic acid could undergo general metabolic reactions, including oxidation, methylation, desaturation, loss of O and loss of CH2 . Additionally, the main metabolic pathways in vivo and in vitro were determined by calculating the relative content of each metabolite. This is the first study of Betulinic acid metabolism in vivo, whose results provide novel and useful data for better understanding of the safety and efficacy of Betulinic acid.

Miniaturized solid-phase extraction using a mesoporous molecular sieve SBA-15 as sorbent for the determination of triterpenoid saponins from Pulsatilla chinensis by ultrahigh-performance liquid chromatography-charged aerosol detection.

A simple, sensitive and efficient solid-phase extraction method, combined with ultrahigh-performance liquid chromatography-charged aerosol detection, was applied to the pre-concentration and determination of four triterpenoid saponins from Pulsatilla chinensis (P. chinensis) ultrasound extract samples. Mesoporous molecular sieve Santa Barbara Amorphous 15 (SBA-15) displayed higher selectivity compared to Mobil Composition of Matter 41 (MCM-41), NH2-SBA-15 and mesoporous carbon when it comes to being used in pretreatment methods. It was applied as an effective sorbent in the SPE for the enrichment of the target analytes. Additionally, several key experimental parameters including the kinds of sorbents, the amount of SBA-15, the elute pH and types of elution solvent were investigated in detail. Under the optimized conditions, the satisfactory linearity (r2 ≥ 0.9940) was acquired and the limits of detection reached 0.461-0.976 µg/mL for the target analytes. The recoveries ranged from 95.1%-103.2%. The experimental results showed that SBA-15 was a candidate material for the purification and concentration of target triterpenoid saponins from complex P. chinensis samples. The study provided theoretical support for the application of mesoporous materials in the field of drug separation and provided references for the extraction and determination of trace compounds in the complex systems of traditional Chinese medicine.

Integrated strategy for accurately screening biomarkers based on metabolomics coupled with network pharmacology.

Screening diagnostic biomarkers can be challenging due to the complexity of traditional Chinese medicine (TCM) and ambiguous pharmacological mechanisms. In this study, we reported an integrated strategy for accurately screening diagnostic biomarkers based on metabolomics coupled with network pharmacology. First, a feasible pharmacological model was established through systems pharmacology and based on metabolomics-based techniques to explore diagnostic biomarkers. While the components satisfying the q-value < 0.05, fold change (FC) ≥ 1.2 or FC ≤ 0.8, coefficient of variance (CV) ≤ 30%(QC) and the variable importance in the project (VIP) value > 1 are considered to be diagnostic biomarkers. Second, the ingredients were retained only when oral bioavailability (OB), Caco-2 permeability, drug half-life, TPSA and drug likeness (DL) satisfied the criteria (OB ≥ 40%; Caco-2 ≥ -0.4; HL ≥ 4 h; TPSA˂140; DL ≥ 0.18) suggested by the TCMSP database. Moreover, ingredients that exhibit extensive biological activity in TCM are also retained. Third, the effect targets of TCM were screened using the TCMSP database, Swiss Target Prediction and STICH online software. Disease targets were gathered from the therapeutic target database (TTD), PharmGkb and TCMSP database. Hub genes were screened by potential protein-protein interaction (PPI) network pharmacology analysis. Finally, a metabolic network pathway is established between the diagnostic biomarker and the hub gene. In the network analysis of metabolic pathways, most of the genes involved in this pathway are the second-step-obtained hub genes, which can explain the accuracy of the identified biomarkers. The proposed integrated strategy was successfully applied to explore the mechanism of action of Pulsatilla decoction (PD) in the treatment of acute ulcerative colitis (UC). Based on this integrated strategy, 23 potential biomarkers of acute UC treated with PD were identified. In conclusion, the integrated strategy provides novel insights into network pharmacology and metabolomics as effective tools to illuminate the mechanism of action of TCM.