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The tracking and analysis of geophysical network data has been fully carried out at stations and central stations. In the past five years, the effectiveness of the work has gradually become apparent. The event records generated by the tracking and analysis of earthquake precursor data demonstrate the dynamic changes in the observation data of the precursor network，which is beneficial for the persons to analyze and summarize various events, so that similar problems can be quickly solved in the next encounter. However, in the actual process of data tracking and analysis，some station personnel may have some defects in the production of maps. This article analyzes and explores common problems in selecting mapping time periods, text annotations, missing event recording maps, multi-component measurement item recording maps, earthquake event recording maps, and other common problems in the maps produced by data tracking and analysis, proposes specific methods to solve the problems, and assigns them to practice. It provides useful assistance for station personnel to complete data tracking and analysis research results, and also provides certain reference and reference for encountering other difficulties in work.

This study aimed to compare the efficacy of Single-Port plus One Port Laparoscopy (SILS + 1) with Conventional Multi-Port Laparoscopic Surgery (CLS) and investigate risk factors associated with postoperative complications in patients with sigmoid colon cancer undergoing laparoscopy. Male patients with sigmoid colon cancer treated at our hospital were selected and evenly distributed into the CLS and SILS + 1 groups and further categorized into complication and non-complication groups based on their complications status within 30 days post-surgery. Compared to the CLS group, the SILS + 1 group had significantly shorter incision length, greater distance to the lower edge of the tumor and shorter time to first postoperative ambulation (p < 0.05). A total of 20 cases (16.67%) developed complications within 30 days post-surgery, and among them, 8 (13.33%) were in the SILS + 1 group and 12 (20.00%) in the CLS group (p = 0.327). Logistic multivariable regression analysis showed that age (p = 0.028; Odds Ratio (OR) = 1.028; 95% confidence interval (CI): 1.003–1.054), body mass index (BMI) (p = 0.002; OR = 1.950; 95% CI: 1.248–2.961) and operation time (p < 0.001; OR = 1.067; 95% CI: 1.030–1.106) were independent risk factors for complication occurrence within 30 days post-surgery, and at 2-year follow-up, there was no significant difference in overall survival between both groups (p > 0.05). In conclusion, age, BMI and duration of surgery were identified as independent risk factors for postoperative complications in male sigmoid colon cancer patients, among whom SILS + 1 was found to reduce postoperative discomfort and accelerate recovery compared to CLS while maintaining surgical efficacy.

Abstract Background The efficacy of reduced-port laparoscopic surgery (RLS) for total gastrectomy remains unclear. This study focused on evaluating the short-term outcomes of RLS compared with conventional laparoscopic surgery (CLS) for total gastrectomy. Methods One hundred and ten patients who underwent completed laparoscopic total gastrectomy for gastric cancer between September 2018 and June 2022 were retrospectively collected and classified into two groups (65 CLS and 45 RLS) according to different operation approach. Twenty-four RLS cases underwent single-incision plus two ports laparoscopic surgery (SILS + 2) and twenty-one underwent single-incision plus one port laparoscopic surgery (SILS + 1). Surgical outcomes, pain intensity, cosmetic and postoperative morbidity, and mortality were compared between groups. Results The overall incidence of postoperative complications was similar between the CLS group and the RLS group (16.9% vs. 8.9%, P = 0.270). It was also comparable in the Clavien-Dindo classification (P = 0.774). However, compared with the CLS group, the RLS group had a significantly shorter total length of incision (5.6 ± 1.0 cm vs. 7.1 ± 0.7 cm, P = 0.000); shorter time to first ambulation (24.9 ± 5.9 h vs. 27.6 ± 5.0 h, P = 0.009), flatus (3.0 ± 0.8 d vs. 3.5 ± 1.0 d, P = 0.022) and oral intake (4.0 ± 1.6 d vs. 6.1 ± 5.1 d, P = 0.011); lower white blood cell count on the third day after the operation (9.8 ± 4.0*109/L vs. 11.6 ± 4.7*109/L, P = 0.037); and lower visual analogue scale score on postoperative days 1 and 3(3.0 ± 0.7 vs. 3.3 ± 0.7, P = 0.044 and 0.6 ± 0.7 vs. 1.6 ± 0.6, P = 0.000 respectively). On the other hand, it didn’t find any difference in short-term outcomes between the SILS + 2 group and the SILS + 1 group (P > 0.05). But the proximal resection margin was longer in the SILS + 2 group than in the SILS + 1 group (2.6 ± 0.7 cm vs. 1.5 ± 0.9 cm, P = 0.046) in patients with adenocarcinoma of the esophagogastric junction (AEG). Conclusions RLS for total gastrectomy is a feasible and safe technique when performed by an experienced laparoscopic surgeon. Moreover, compared with SILS + 1, SILS + 2 might have some advantages in AEG patients.

Incense burning is a significant source of indoor air pollution in many Asian regions. There is emerging evidence that maternal prenatal exposure to incense-burning smoke may be a risk factor for childhood obesity. We aimed to extend this new line of research by investigating the independent and joint effect of incense-burning smoke exposure, and children’s outdoor activity in early life, on preschoolers’ obesity. A total of 69,637 mother–child dyads were recruited from all kindergartens in the Longhua District of Shenzhen, China. Information on sociodemographic characteristics, maternal exposure to incense-burning smoke (IBS) during pregnancy, and frequency and duration of outdoor activity at the age of 1–3 years was collected by a self-administered questionnaire. In addition, the heights and weights of the children were measured by the research team. Logistic regression models and cross-over analyses were conducted to investigate the independent and combined effects of maternal exposure to incense-burning smoke during pregnancy and children’s early outdoor activity on obesity in preschoolers. We found that prenatal exposure to incense-burning smoke increased the risk of the presence of obesity in preschoolers’ (AOR = 1.13, 95% CI = 1.03–1.23). Additionally, lower frequencies (

Grasshopper disasters threaten grassland animal husbandry, and overgrazing is widely recognized as one of the main causes of locust infestation in grassland regions. However, the impact of overgrazing on grasshopper disasters remains unclear. To address this knowledge gap, this study interviewed 541 households living in locust-prone areas in Inner Mongolia, China. The generalized Poisson model and OLS regression examined the relationship between herders’ production behavior and locust disasters. The results showed that 42% of the herders had suffered from locusts more than three times over the past 15 years, with an average of 49 ha of grassland damaged per household. In addition, with the increase in grazing rates, the scale of locust disasters decreased before it increased. The results also showed that operating grassland areas and feeding forage reduced locust disasters significantly, while renting grassland areas and grazing rates worked oppositely. These results suggest that grazing intensity can make a significant difference in the occurrence of locust disasters.

Abstract Background In rectal cancer surgery, recent studies have found associations between clinical factors, especially pelvic parameters, and surgical difficulty; however, their findings are inconsistent because the studies use different criteria. This study aimed to evaluate common clinical factors that influence the operative time for the laparoscopic anterior resection of low and middle rectal cancer. Methods Patients who underwent laparoscopic radical resection of low and middle rectal cancer from January 2018 to December 2020 were retrospectively analyzed and classified according to the operative time. Preoperative clinical and magnetic resonance imaging (MRI)-related parameters were collected. Logistic regression analysis was used to identify factors for predicting the operative time. Results In total, 214 patients with a mean age of 60.3 ± 8.9 years were divided into two groups: the long operative time group (n = 105) and the short operative time group (n = 109). Univariate analysis revealed that the male sex, a higher body mass index (BMI, ≥ 24.0 kg/m2), preoperative treatment, a smaller pelvic inlet (

Taking the computer of seismic station as the object of discussion, the causes of “system crash” “automatic shutdown” “blue screen” and other faults that frequently occur in the computer at the precursor site area are analyzed and studied. Reasonable and effective solutions are proposed to eliminate the fault in time and effectively ensure the normal operation of the station computers. It has certain guiding significance for the computer maintenance and management person of the seismic station.

Abstract Background When dizziness/vertigo patients presented with balance disorder, it will bring severe morbidity. There is currently lack of research to explore risk factor related balance disorder in dizziness patients, especially in those who walk independently. Aim To investigate risk factors related balance disorder in dizziness/vertigo patients who walk independently. Methods Medical data of 1002 dizziness/vertigo patients registered in vertigo/balance disorder registration database were reviewed. The demographic data, medical history, and risk factors for atherosclerosis (AS) were collected. Enrolled dizziness/vertigo patients could walk independently, completed Romberg test, videonystagmography (VNG), and limits of stability (LOS). The subjective imbalance was patient complained of postural symptom when performing Romberg test. Multivariable logistic regression analyzed risk factors related balance disorder. The receiver operating characteristic (ROC) curve evaluated the utility of regression model. Results Five hundred fifty-three dizziness/vertigo patients who walk independently were included in the final analysis. According to LOS, patients were divided into 334 (60%) normal balance and 219 (40%) balance disorder. Compared with normal balance, patients with balance disorder were older (P = 0.045) and had more risk factors for AS (P

Based on the analysis of all kinds of interference changes and rules in the water temperature observation data of Yong’an well，it is concluded that the significant influences on the data are the atmospheric precipitation and the surface lateral supply，air pressure，instrument failure，human interference，and seismic response caused by the precipitation，etc. Finally，some discussions and suggestions are put forward.

In the process of digital observation，efficient observation means，reliable observation information and accurate calibration method are the important guarantees for observation quality. The ground water observation station of Yongan seismic station is unattended. Calibrate the water level gauge quarterly，according to relevant regulations. Observers check the water level every quarter. The calibration value is the basis for judging whether the water level gauge is working normally. In order to ensure the accuracy and efficiency of water level calibration，the author has developed a set of water level calibration device. It consists of two parts: a water level measurement module and a digital display module. It basically realizes the transformation from analog calibration to digital calibration. The device has been applied to the quarterly water level inspection of Yongan well. Compared with the measuring bell method used by Yongan station in the past，this device can reduce the error of water level calibration data to some extent，save working time and greatly improve the efficiency of calibration work.

Metabolic syndrome (MetS) is a complex syndrome cluster of metabolic disorders, which greatly increases the risks of diabetic and cardiovascular diseases. Although it has become a significantly worldwide public health burden, its pathogenesis largely remains unknown. In this study, we first performed an integrated analysis of proteomic and metabonomic data of liver tissues of rats between MetS and control groups to reveal possible mechanisms of MetS. A total of 16 significantly perturbed pathways were identified, of which three pathways were shared by patients with MetS and diabetes identified by analysis of serum samples, including alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, and glycine, serine and threonine metabolism. Additionally, it was found that 18 differential metabolites were closely related with 36 differential proteins, which were considered as significantly discriminant metabolites and proteins between two groups and were mainly involved in metabolic processes of gamma-aminobutyric acid and acetyl-CoA, biosynthetic processes of cholesterol and amino acids. The results of PPI network analysis and topological parameter calculation of four methods revealed that 16 proteins can serve as hub proteins of MetS. Followed by searching the PubMed database and molecular docking of Cyp7a1 and Got1, we concluded that atorvastatin and resveratrol may be potential drugs for MetS.

Objective: The effect of active ingredients of Chaishaoliujun Decoction (CD) on chronic atrophic gastritis (CAG) was screened by network pharmacological method and verified by preliminary experiment. Methods: Firstly, the active ingredients and drug targets of CD were retrieved in TCMSP database; CAG-related targets from PharmGkb, OMIM, GeneCards and DrugBank databases were collected as well. Secondly, the drug targets and disease targets were mapped to obtain the intersection targets. PPI network and active ingredient-common target network were constructed for the intersection targets obtained and KEGG enrichment analysis was also carried out. Finally, the core active ingredient (kaempferol), effective targets (IL-1β、IL-6) and hedgehog signaling pathway were verified by animal experiments. Results: There were 137 active ingredients, 243 potential target so and 48 intersection targets with CAG in CD. 147 KEGG enrichment pathways were obtained, mainly involving JAK/STAT signaling pathway, PI3K/Akt signaling pathway, hedgehog signaling pathway, etc. The results of animal experiments showed: The content of IL-1β and IL-6 in model group was significantly increased compared with the normal group, while the mRNA and protein expressions of Shh, Ptch1 and Gli1 were also significantly decreased (P

Tires are often in service under dynamic conditions. Realizing the high-precision prediction of the mechanical response of rubber materials under cyclic loading can provide guidance for the design of high-performance tires. In this work, the tensile recovery stress-strain responses of rubber materials in nine different components of a truck and bus radial (TBR) tire were obtained through experiments. Before fitting, an experimental data processing method was proposed to facilitate the parameter identification for a hyper-pseudo-viscoelastic model, that is, the raw experimental data were changed to the adjusted test data. The HyperFit software was used to fit the adjusted test data based on the Yeoh hyperelastic model and the Ogden-Roxburgh pseudoelastic model to obtain the initial material parameters for the two models. In order to describe the permanent set, the Prony series viscoelastic model was introduced. The Isight software was adopted to optimize the parameters. The results showed that the hyper-pseudo-viscoelastic model (i.e., the combination of Yeoh, Ogden-Roxburgh and Prony series models) can describe the tensile recovery mechanical responses (loading curve, unloading curve and permanent set) of nine different rubber components in TBRs. The fitting results are in good agreement with the adjusted data, and all the coefficients of determination (R2) exceed 0.975. Finally, the cyclic deformation simulation of a dumbbell rubber specimen was carried out based on the above constitutive model and fitted parameters. R2 was used to describe the simulation accuracy and its value reached 0.968.

Background: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo, especially in the elderly. Several studies have revealed a possible seasonality to BPPV. However, whether the seasonality of BPPV also exists in China is unclear. The characteristics of cardio-cerebrovascular risk factors for BPPV in the cold season have not yet been investigated.Objectives: (1) To investigate the seasonality of BPPV; (2) To explore the relationship between cardio-cerebrovascular risk factors and seasonality of BPPV.Methods: A retrospective observational study was performed in Beijing Tiantan Hospital from Jan 2016 to Dec 2018. The study included 1,409 new-onset BPPV patients aged 18–88 years. The demographic data, onset time, and medical history of BPPV were collected. The meteorological data, including temperature, atmospheric pressure, rainfall, and insolation, was obtained from Beijing Meteorological service. The x2 goodness of fit test was used to evaluate whether BPPV patients' numbers were significantly different among different months of the year. The Spearman correlation was used to detect the correlation between numbers of BPPV patients diagnosed monthly with each climatic parameter. The chi-square test for linear-by-linear association were used to investigate the relationship between cardio-cerebrovascular risk factor and seasonality of BPPV.Results: November to next March is the top 5 months with higher BPPV patient numbers (P < 0.001). The numbers of BPPV diagnosed monthly were conversely correlated with temperature and rainfall (r = −0.736, P = 0.010; r = −0.650, P = 0.022, respectively), positively correlated with atmospheric pressure (r = 0.708, P = 0.010), but no significant correlated with insolation. BPPV in the cold season (including January, February, March, November, and December) had a higher proportion, accounting for 54.2% of all BPPV patients. Among BPPV patients with ≥2, 1, and none cardio-cerebrovascular risk factors, the cold season accounted for 57.0, 56.0, 49.8%, respectively. As the number of cardio-cerebrovascular risk factors increased, the proportion of patients in the cold season of BPPV increased (P = 0.025).Conclusions: BPPV patients are seen more in the months with low temperature, low rainfall, and high atmospheric pressure. Compared with the non-cold season, BPPV patients have more risk factors for cardio-cerebrovascular diseases in the cold season.

This study aimed to discover concurrences of adverse drug reactions (ADRs) and derive models of the most frequent items of ADRs based on the SIDER database, which included 1430 marketed drugs and 5868 ADRs. First, common ADRs of organic drugs were manually reclassified according to side effects in the human system and followed by an association rule analysis, which found ADRs of digestive and nervous systems often occurred at the same time with a good association rule. Then, three algorithms, linear discriminant analysis (LDA), support vector machine (SVM) and deep learning, were used to derive models of ADRs of digestive and nervous systems based on 497 organic monomer drugs and to identify key structural features in defining these ADRs. The statistical results indicated that these kinds of QSAR models were good tools for screening ADRs of digestive and nervous systems, which gave the ROC AUC values of 81.5%, 98.9%, 91.5%, 69.5%, 78.4% and 78.8%, respectively. Then, these models were applied to investigate ADRs of 1536 organic compounds with four phase and zero rule-of-five (RO5) violations from the ChEMBL database. Based on the consensus ADRs’ predictions of models, 58.1% and 42.6% of compounds were predicted to cause these two ADRs, respectively, indicating the significance of initial assessment of ADRs in early drug discovery.

Agricultural transformation is a transition process of agriculture from the low development stage to the high development stage. Identifying the agricultural transformation stage and analyzing the evolution of agricultural development types based on Total Factor Productivity (TFP) are of great significance for the rational formulation of agricultural development policies. Based on the total factor productivity analysis framework, the DEA-Malmquist index model was used to measure the agricultural TFP of the 87 counties in Gansu Province from 1988 to 2017. The cumulative anomaly method was used to help identify agricultural transformation stages. Agricultural development types of counties in different stages and their evolution process were analyzed. Results show that (1) the agricultural transformation of Gansu Province can be divided into three stages: Traditional agriculture in 1988–1998; low-capacity technology agriculture in 1999–2011; and high-capacity technology agriculture in 2012–2017. (2) From 1988 to 2017, the agricultural TFP showed periodic U-shaped fluctuations, and the areas with high TFP value expanded from the central region to the western region and then to the entire region of the province. (3) Gansu Province presented a significant spatiotemporal variation of agricultural development types. From 1988 to 1998, type-I (low technological efficiency and slow technological progress) and type-VI (high technological efficiency and fast technological progress) agricultural development was mainly observed, and these two kinds of counties accounted for 55.17% of all evaluation units. From 1999 to 2011, the number of counties with type-I agricultural development increased significantly, reaching 35, followed by the number of counties with type IV (low technological efficiency) agricultural development, reaching 18. They together accounted for 60.92% of all evaluation units. From 2012 to 2017, the number of counties with type-IV and type-VI agricultural development was the largest, reaching 29 and 25, respectively. They together accounted for 62.07% of all evaluation units. (4) Types of agricultural development frequently change—from 1988 to 2017, the influencing factors of agricultural development had undergone a transition from both technological efficiency and technological improvement to technological efficiency or technological improvement alone.

Gastric cancer (GC) is one of the common reasons of cancer-related death with few biomarkers for diagnosis and prognosis. Solute carrier family 2 (facilitated glucose transporter) member 1 protein SLC2A1, also known as glucose transporter type 1 (GLUT1), has been associated with tumor progression, metastasis, and poor prognosis in many human solid tumors. However, little is reported about its clinical significance and biological functions in GC. Here we observed a strong up-regulation of SLC2A1 in patients with GC and found that SLC2A1 was significantly correlated with depth of invasion and clinical stage. Additionally, over-expression of SLC2A1 in GC cells promotes cellular proliferation and metastasis in vitro and enhances tumor growth in vivo as well as enhancement of glucose utilization. Meanwhile, elevated SLC2A1 also contributes to tumor metastasis in vitro. Our results indicate SLC2A1 exhibits a pivotal role in tumor growth, metastasis and glucose metabolism, and also suggest SLC2A1 as a promising target for gastric cancer therapy.

Licorice is a popular sweetener and a thirst quencher in many food products particularly in Europe and the Middle East and also one of the oldest and most frequently used herbs in traditional Chinese medicine. As a wide application of food additive, it is necessary to clarify bioactive chemical ingredients and the mechanism of action of licorice. In this study, a network pharmacology approach that integrated drug-likeness evaluation, structural similarity analysis, target identification, network analysis, and KEGG pathway analysis was established to elucidate the potential molecular mechanism of licorice. First, we collected and evaluated structural information of 282 compounds in licorice and found 181 compounds that met oral drug rules. Then, structural similarity analysis with known ligands of targets in the ChEMBL database (similarity threshold = 0.8) was applied to the initial target identification, which found 63 compounds in licorice had 86 multi-targets. Further, molecular docking was performed to study their binding modes and interactions, which screened out 49 targets. Finally, 17 enriched KEGG pathways (p < 0.01) of licorice were obtained, exhibiting a variety of biological activities. Overall, this study provided a feasible and accurate approach to explore the safe and effective application of licorice as a food additive and herb medicine.

Activating Liver X receptors (LXRs) represents a promising therapeutic option for dyslipidemia. However, activating LXRα may cause undesired lipogenic effects. Discovery of highly LXRβ-selective agonists without LXRα activation were indispensable for dyslipidemia. In this study, in silico approaches were applied to develop highly potent LXRβ-selective agonists based on a series of newly reported 3-(4-(2-propylphenoxy)butyl)imidazolidine-2,4-dione-based LXRα/β dual agonists. Initially, Kohonen and stepwise multiple linear regression SW-MLR were performed to construct models for LXRβ agonists and LXRα agonists based on the structural characteristics of LXRα/β dual agonists, respectively. The obtained LXRβ agonist model gave a good predictive ability (R2train = 0.837, R2test = 0.843, Q2LOO = 0.715), and the LXRα agonist model produced even better predictive ability (R2train = 0.968, R2test = 0.914, Q2LOO = 0.895). Also, the two QSAR models were independent and can well distinguish LXRβ and LXRα activity. Then, compounds in the ZINC database met the lower limit of structural similarity of 0.7, compared to the 3-(4-(2-propylphenoxy)butyl)imidazolidine-2,4-dione scaffold subjected to our QSAR models, which resulted in the discovery of ZINC55084484 with an LXRβ prediction value of pEC50 equal to 7.343 and LXRα prediction value of pEC50 equal to −1.901. Consequently, nine newly designed compounds were proposed as highly LXRβ-selective agonists based on ZINC55084484 and molecular docking, of which LXRβ prediction values almost exceeded 8 and LXRα prediction values were below 0.

Metabolic syndrome (MS) is becoming a worldwide health problem. Wendan decoction (WDD)—a famous traditional Chinese medicine formula—has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators.

In this paper, a three level in silico approach was applied to investigate some important structural and physicochemical aspects of a series of anthranilic acid derivatives (AAD) newly identified as potent partial farnesoid X receptor (FXR) agonists. Initially, both two and three-dimensional quantitative structure activity relationship (2D- and 3D-QSAR) studies were performed based on such AAD by a stepwise technology combined with multiple linear regression and comparative molecular field analysis. The obtained 2D-QSAR model gave a high predictive ability (R2train = 0.935, R2test = 0.902, Q2LOO = 0.899). It also uncovered that number of rotatable single bonds (b_rotN), relative negative partial charges (RPC−), oprea's lead-like (opr_leadlike), subdivided van der Waal’s surface area (SlogP_VSA2) and accessible surface area (ASA) were important features in defining activity. Additionally, the derived3D-QSAR model presented a higher predictive ability (R2train = 0.944, R2test = 0.892, Q2LOO = 0.802). Meanwhile, the derived contour maps from the 3D-QSAR model revealed the significant structural features (steric and electronic effects) required for improving FXR agonist activity. Finally, nine newly designed AAD with higher predicted EC50 values than the known template compound were docked into the FXR active site. The excellent molecular binding patterns of these molecules also suggested that they can be robust and potent partial FXR agonists in agreement with the QSAR results. Overall, these derived models may help to identify and design novel AAD with better FXR agonist activity.

The title compound, C35H31NO3, was obtained by the reaction of (S)-benzyl 2-amino-3-(4-hydroxyphenyl)propanoate and (chloromethanetriyl)tribenzene. The enantiomer has been assigned by reference to an unchanging chiral centre in the synthetic procedure. In the crystal, molecules are linked into chains running along the a axis by intermolecular O—H...O hydrogen bonds.