Measurement plane of the cross-sectional area of the masseter muscle in patients with skeletal Class III malocclusion: An artificial intelligence model.

INTRODUCTION: This study aimed to determine a measurement plane that could represent the maximum cross-sectional area (MCSA) of masseter muscle using an artificial intelligence model for patients with skeletal Class III malocclusion. METHODS: The study included 197 patients, divided into subgroups according to sex, mandibular symmetry, and mandibular plane angle. The volume, MCSA, and the cross-sectional area (CSA) at different levels were calculated automatically. The vertical distance between MCSA and mandibular foramen, along with the ratio of the masseter CSA at different levels to the MCSA (R), were also calculated. RESULTS: The MCSA and volume showed a strong correlation in the total sample and each subgroup (P <0.001). The correlation between the CSA at each level and MCSA was statistically significant (P <0.001). The peak of the r and the correlation coefficient between the CSA at different levels and MCSA were mostly present 5-10 mm above the mandibular foramen for the total sample and the subgroups. The mean of RA5 to RA10 was >0.93, whereas the corresponding correlation coefficient was >0.96, both for the entire sample and for the subgroups. CONCLUSIONS: MCSA could be used as an indicator for masseter muscle size. For patients with skeletal Class III malocclusion, the CSA 5-10 mm above the mandibular foramen, parallel to the Frankfort plane, could be used to estimate the masseter muscle MCSA.

Changes in masseter muscle morphology after surgical-orthodontic treatment in patients with skeletal Class III malocclusion with mandibular asymmetry: The automatic masseter muscle segmentation model.

INTRODUCTION: This study evaluated the masseter muscle changes after surgical-orthodontic treatment in patients with a skeletal Class III malocclusion using automatic segmentation. METHODS: Images of 120 patient with skeletal Class III malocclusion were obtained and reconstructed at T0 (pretreatment), T1 (presurgery), and T2 (6-12-month postsurgery). The patients were divided into symmetrical and asymmetrical groups. The volume, major axis length, maximum cross-sectional area, horizontal cross-sectional area 5 mm above the mandibular foramen (CSAF), and orientation were calculated automatically. RESULTS: In the asymmetrical group, the volume and major axis length on the deviated side were lower than on the nondeviated side at T0, T1, and T2 (P <0.05). There were no significant differences in maximum cross-sectional area and CSAF bilaterally. The orientation was coronally more vertical and sagittally more forward on the deviated side (both P <0.001). In the symmetrical group, there were no significant bilateral differences at T0, T1, and T2. The volume, major axis length, and CSAF decreased, and the coronal orientation was more vertical on the nondeviated side at T2 than at T0 in both groups (P <0.05). The coronal plane orientation was more inclined on the deviated side at T2 than at T0 in the asymmetrical group (P <0.05). CONCLUSIONS: The smaller volume on the deviated side at T2 indicates the need for myofunctional training after surgery. The masseter muscle volume and the cross-sectional area did not recover to the preorthodontic levels. Studies with longer follow-up durations are needed to confirm these findings.

Early and 1-year postsurgical stability and its factors in patients with complicated skeletal Class â ¢ malocclusion treated by conventional and surgery-first approach: A prospective cohort study.

INTRODUCTION: This study aimed to compare postsurgical stability between conventional (CSA) and surgery-first (SFA) approaches and investigate its prognostic factors in patients with a skeletal Class Ⅲ extraction. METHODS: Twenty and 19 patients treated with LeFort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) with premolar extraction were enrolled in SFA and CSA groups, respectively. Serial cone-beam computed tomography images obtained before surgery, immediately after surgery (T1), 3 months after surgery, and 12 months after surgery were used for 3-dimensional quantitative analysis. The condyle was segmented for analyzing volumetric changes. Repeated measures analysis of variance, independent t test, and chi-square test were used to compare time-course and intergroup differences. Pearson and Kendall correlation and multivariate linear regression analyses were used to explore prognostic factors affecting skeletal stability. RESULTS: In both CSA and SFA, postsurgical relapse mainly occurred in the mandible sagittal and vertical dimensions and during the first 3 months after surgery. Stability in SFA was significantly less than that in CSA. Intraoperatively, inferolateral condylar displacement with proximal segment inwards, clockwise rotation, and return movements after surgery were observed regardless of the treatment approach. The condylar volume remained stable over time. Multivariate regression analysis showed that posterior vertical dimension (VD) at T1 (-1.63 mm), surgical amount of mandibular setback (-10.33 mm), surgical condylar downwards displacement (-1.28 mm), and anterior overjet at T1 (6.43 mm) were the most important predictors of early mandibular relapse (r2 = 0.593). CONCLUSIONS: The risk of early relapse could be reduced by controlling the anterior, middle, and posterior constraints provided by the prediction model.

Translating Research Evidence Into Marketplace Application: Cohort Study of Internet-Based Intervention Platforms for Perinatal Depression.

BACKGROUND: Internet-based intervention platforms may improve access to mental health care for women with perinatal depression (PND). Though the majority of platforms in the market lack an evidence base, a small number of them are supported by research evidence. OBJECTIVE: This study aims to assess the current status of internet-based PND intervention platforms supported by published evidence, understand the reasons behind the disappearance of any of these previously accessible platforms, examine adjustments made by those active platforms between research trials and market implementation, and evaluate their current quality. METHODS: A cohort of internet-based PND intervention platforms was first identified by systematic searches in multiple academic databases from database inception until March 26, 2021. We searched on the World Wide Web and the iOS and Android app stores to assess which of these were available in the marketplace between April and May 2021. The basic characteristics of all platforms were collected. For inaccessible platforms, inquiries were made via email to the authors of publications to determine the reasons for their unavailability. We compared the intervention-related information of accessible platforms in the marketplace with that reported in original publications and conducted quality assessments using the App Evaluation Model of the American Psychiatric Association. Fisher exact tests were used to compare the functional characteristics in publications of available and unavailable platforms and to investigate potential associations between functional adjustments or quality indices and platform survival time. RESULTS: Out of 35 platforms supported by research evidence, only 19 (54%) were still accessible in the marketplace. The main reason for platforms disappearing was the termination of research projects. No statistically significant differences were found in functional characteristics between available and unavailable platforms. A total of 18 (95%) platforms adapted their core functions from what was reported in related publications. The adjustments included changes to intervention methods (11/19, 58%), target population (10/19, 53%), human resources for intervention support (9/19, 47%), mood assessment and monitoring (8/19, 42%), communication modality (4/19, 21%), and platform type (2/19, 11%). Quality issues across platforms included low frequency of update, lack of crisis management mechanism, poor user interactivity, and weak evidence base or absence of citation of supporting evidence. Platforms that survived longer than 10 years had a higher tendency to use external resources from third parties compared to those that survived less than 10 years (P=.04). No significant differences were found for functional adjustments or other quality indices. CONCLUSIONS: Internet-based platforms supported by evidence were not effectively translated into real-world practice. It is unclear if adjustments to accessible platforms made during actual operation may undermine the proven validity of the original research. Future research to explore the reasons behind the success of the implementation of evidence-based platforms in the marketplace is warranted.

Trichloroethylene induces immune renal tubular injury through SIRT 1/HSP 70/TLR 4 pathway in BALBc mice.

Trichloroethylene (TCE) is a volatile chlorinated solvent widely used for cleaning and degreasing industrial metal parts. Due to the widespread use and improper disposal of TCE, exposure to TCE causes a variety of adverse effects on human and animal health. However, the underlying mechanism of the damage remains unclear. The purpose of this study is to investigate the role of Sirtuin-1 (SIRT 1) in TCE-induced immune renal tubular injury. 6-8-week-old female BALB/c mice were used to construct a TCE sensitized mouse model. SIRT 1 activator, SRT 1720 (0.1 ml, 5 mg/kg) and toll like receptor 4 (TLR 4) inhibitor, TAK-242 (0.1 ml, 3 mg/kg) were used for treatment. Results show that SIRT 1 and heat shock protein 70 (HSP 70) levels are significantly down-regulated in renal tubules, serum and urine HSP 70 levels are significantly increased, and inflammatory cytokines levels are significantly increased in renal tubules in TCE-sensitized positive mice. After SRT 1720 treatment, intracellular HSP 70 level is significantly increased and extracellular HSP 70 level is decreased, and inflammatory cytokines levels get alleviated. In addition, HSP 70 and Toll-like Receptor 4 (TLR 4) proteins exist an interaction that can be significantly attenuated by SIRT 1. Subsequently, inflammation of the renal tubules mediated by SIRT 1 downregulation is attenuated after TAK-242 treatment. In conclusion, SIRT 1 alleviates renal tubular epithelial cells immune injury by inhibiting the release of HSP 70 and thereby weakening interaction with HSP 70 and TLR 4.

Effects of Exercise on Patients with Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

With exercise being more frequently utilized in treatment for obstructive sleep apnea (OSA), a systematic review of the intervention efficacy of exercise on OSA is necessary. PubMed, EBSCO, Web of Science, VIP, and CNKI databases were searched to collect randomized controlled trials (RCTs) of exercise applied to OSA from January 2000 to January 2022. The literature screening, data extraction, and risk of bias assessment of included studies were conducted independently by two reviewers. Meta-analysis was then performed using Rev Man 5.4 software. A total of 9 RCTs were included, including 444 patients. Compared with the control group, exercise made an improvement in apnea-hypopnea index (AHI) [MD = -6.65, 95% CI (-7.77, -5.53), p < 0.00001], minimum oxygen saturation (SaO2min%) [MD = 1.67, 95% CI (0.82, 2.52), p = 0.0001], peak oxygen uptake (VO2peak) [SMD = 0.54, 95% CI (0.31, 0.78), p < 0.00001], Pittsburgh sleep quality index (PSQI) [MD = -2.08, 95% CI (-3.95, -0.21), p = 0.03], and Epworth Sleepiness Scale (ESS) values [MD = -1.64, 95% CI, (-3.07, -0.22), p = 0.02]. However, there were no significant changes in body mass index (BMI). As for the results of subgroup analysis, aerobic exercise combined with resistance exercise [MD = -7.36, 95% CI (-8.64, -6.08), p < 0.00001] had a better effect on AHI reduction than aerobic exercise alone [MD = -4.36, 95% CI (-6.67, -2.06), p = 0.0002]. This systematic review demonstrates that exercise reduces the severity of OSA with no changes in BMI, and the effect of aerobic exercise combined with resistance training is better than aerobic exercise alone in AHI reduction. Exercise also improves cardiopulmonary fitness, sleep quality, and excessive daytime sleepiness.

Effects of mitochondrial reactive oxygen species-induced NLRP3 inflammasome activation on trichloroethylene-mediated kidney immune injury.

This study aimed to investigate the activating mechanism of the NLRP3 inflammasome in trichloroethylene-sensitized mice. In total, 88 BALB/c female mice were used to establish the trichloroethylene (TCE)-sensitized mouse model. Some of the mice received MitoTEMPO, MCC 950 or soluble recombinant CD59-Cys to inhibit mitochondrial reactive oxygen species (mtROS) production, NLRP3 assembly, or C5b-9 formation. Mouse tubular epithelial cell expression levels of NLRP3, ASC, Caspase 1, IL-1ß, IL-18 and mitochondrial antiviral signaling protein (MAVS) were detected by western blot. Mitochondrial numbers, membrane potential (ΔΨm) and mtROS were detected by using MitoScene Green II, JC-1 dye and MitoSOX Red indicator, respectively. Tubular epithelial cell calcium levels were detected by a Fluo-8 no wash calcium assay kit. Human kidney-2 (HK-2) cells were cultured and stimulated by C5b6 and normal human serum (NHS) to verify the role of C5b-9-induced mitochondrial ROS in activating NLRP3 inflammasome. Urine α1-MG, ß2-MG, and mtROS production and calcium levels were increased, while mitochondrial numbers were decreased in TCE-sensitized positive mice. After treatment with MitoTEMPO, renal tubular injury was alleviated, JC-1 fluorescence and mitochondrial numbers were significantly increased, and mitochondrial ROS were inhibited. The NLRP3 inflammasome was activated in TCE-sensitized positive mice, while Mito TEMPO inhibited MAVS expression and NLRP3 inflammasome activation. The in vitro studies proved that C5b-9 can induce mtROS release and activate the assembly of NLRP3 inflammasome in HK-2 cells. In conclusion, in TCE-sensitized positive mouse renal tubular epithelial cells, C5b-9 caused calcium influx and thus induced mitochondrial injury and mtROS overexpression, finally inducing MAVS expression and NLRP3 inflammasome activation and kidney injury.

Endothelin-1 down-regulated vascular endothelial growth factor A is involved in trichloroethene-induced kidney injury.

The mechanism of kidney injury in occupational medicamentosa-like dermatitis due to trichloroethylene exposure is not well understood. This study aimed to investigate the role of endothelin-1 (ET-1)/vascular endothelial-derived growth factor-A (VEGF-A) in trichloroethylene (TCE)-induced renal injury. Forty BALB/c female mice were used in this study to build the TCE-sensitization mouse model. Transmission electron microscopic observation, histological examination, periodic acid-Schiff staining, serum urea nitrogen, creatinine, and urinary total protein levels were used to reflect renal injury. Glypican1, syndecan1, ET-1 and VEGF-A protein levels were measured by western blot. Serum ET-1 level was also measured. Tumor necrosis factor alpha (TNF-α) and vascular cell adhesion molecule-1 (VCAM-1) were detected by immunohistochemistry. The results showed that TCE-sensitized mouse kidneys were damaged and accompanied by increased serum ET-1. After treatment with CGS 35066, the inhibitor of endothelin converting enzyme-1 (ECE-1), kidney ET-1, TNF-α and VCAM-1 levels decreased, and renal function improved in TCE+CGS 35066-sensitized positive mice. In addition, kidney VEGF-A, glomerular endothelial cell glypican1 and syndecan1 levels increased, and endothelial cell damage was alleviated after treatment with CGS 35066. The results suggest that inhibiting ECE-1 could alleviate glomerular endothelial cell injury by inhibiting ET-1 expression, thus promoting endothelial cell repair by upregulating VEGF-A.

Automatic Masseter Muscle Accurate Segmentation from CBCT Using Deep Learning-Based Model.

Segmentation of the masseter muscle (MM) on cone-beam computed tomography (CBCT) is challenging due to the lack of sufficient soft-tissue contrast. Moreover, manual segmentation is laborious and time-consuming. The purpose of this study was to propose a deep learning-based automatic approach to accurately segment the MM from CBCT under the refinement of high-quality paired computed tomography (CT). Fifty independent CBCT and 42 clinically hard-to-obtain paired CBCT and CT were manually annotated by two observers. A 3D U-shape network was carefully designed to segment the MM effectively. Manual annotations on CT were set as the ground truth. Additionally, an extra five CT and five CBCT auto-segmentation results were revised by one oral and maxillofacial anatomy expert to evaluate their clinical suitability. CBCT auto-segmentation results were comparable to the CT counterparts and significantly improved the similarity with the ground truth compared with manual annotations on CBCT. The automatic approach was more than 332 times shorter than that of a human operation. Only 0.52% of the manual revision fraction was required. This automatic model could simultaneously and accurately segment the MM structures on CBCT and CT, which can improve clinical efficiency and efficacy, and provide critical information for personalized treatment and long-term follow-up.

Endothelin-1/Endothelin Receptor Type A-Angiopoietins/Tie-2 Pathway in Regulating the Cross Talk Between Glomerular Endothelial Cells and Podocytes in Trichloroethylene-Induced Renal Immune Injury.

INTRODUCTION: This study aimed to investigate the mechanism in regulating the cross talk between glomerular endothelial cells and podocytes in "occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT)" patients. METHODS: Totally 6 OMLDT patients, 18 controls, and 102 BALB/c female mice were involved in this study. Patient's serum endothelin-1 (ET-1), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), blood urea nitrogen (BUN), and podocalyxin (PCX) were detected. All the mice were used to establish the trichloroethylene (TCE) sensitized mouse model. Transmission electron microscope results were used to reflect renal glomerulus injury. Protein levels were detected by Western blot. Ang-1/Ang-2 gene level was reflected by RT-PCR. Cell apoptosis level was detected by using TUNEL assay kit. RESULTS: We found that in OMLDT patients, ET-1, Ang-2, BUN, and PCX were highly expressed but Ang-1 was inhibited. In TCE sensitized positive mouse, the downregulation of Ang-1, pTie-2 and the upregulation of Ang-2 were mediated by ET-1/ETAR but not ET-1/ETBR. The promotor of apoptosis proteins was downregulated and the inhibitor of apoptosis proteins was upregulated by treating with BQ123. DISCUSSION: ET-1/ETAR-Angs/Tie-2 pathway mediated the cross talk between glomerular endothelial cells and podocytes. BQ123 can alleviate glomerulus immune injury.

Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments.

Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62 nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors.

Identification of potential AMPK activator by pharmacophore modeling, molecular docking and QSAR study.

AMP-activated protein kinase (AMPK) plays a major role in maintaining cellular energy homeostasis by sensing and responding to AMP/ADP concentrations relative to ATP. AMPK has attracted widespread attention as a potential therapeutic target for metabolic diseases such as cancer and cardiovascular diseases. The structure-based 3D pharmacophore model was developed based on the training set. The best pharmacophore model Hypo5 was proposed and validated using a decoy set, an external test set. Hypo5, with the correlation coefficient value of 0.936, cost difference value of 112.08 and low RMS value of 1.63, includes a ionizable positive, a hydrogen bond donor, a hydrogen bond acceptor and two hydrophobic features, which showed a high goodness of fit and enrichment factor. Thus it was used as a 3D query to find potential activator from the SPECS Database. Then the ADMET descriptors were used to filter all of 158 screening molecules. The 41 filtering compounds were subsequently subjected to molecular docking and Quantitative structure-activity relationship (QSAR) analysis. Finally, the compound H2 was picked out from those filtering compounds based on the receptor-ligand interaction analysis and the prediction of the QSAR models. And then it was submitted for molecular dynamics (MD) simulations to explore the stability of complex. The result indicates that the candidate could be considered a potential AMPK activator.

Discovery of novel indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors by virtual screening.

In this study, a combination of virtual screening methods were utilized to identify novel potential indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. A series of IDO1 potential inhibitors were identified by a combination of following steps: Lipinski's Rule of Five, Veber rules filter, molecular docking, HipHop pharmacophores, 3D-Quantitative structure activity relationship (3D-QSAR) studies and Pan-assay Interference Compounds (PAINS) filter. Three known categories of IDO1 inhibitors were used to constructed pharmacophores and 3D-QSAR models. Four point pharmacophores (RHDA) of IDO1 inhibitors were generated from the training set. The 3D-QSAR models were obtained using partial least squares (PLS) analyze based on the docking conformation alignment from the training set. The leave-one-out correlation (q2) and non-cross-validated correlation coefficient (r2pred) of the best CoMFA model were 0.601 and 0.546, and the ones from the best CoMSIA model were 0.506 and 0.541, respectively. Six hits from Specs database were identified and analyzed to confirm their binding modes and key interactions to the amino acid residues in the protein. This work may provide novel backbones for new generation of inhibitors of IDO1.

Pharmacophore modeling, molecular docking and molecular dynamics simulations toward identifying lead compounds for Chk1.

Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase, plays an important role in G2/M checkpoint, which is a key regulator in response to DNA damage. In this study, the structure-based drug design approach and molecular dynamics (MD) simulations were used to explore potent Chk1 inhibitors. A series of the best fitting candidates were picked out from the Specs database. Out of these, five candidates were submitted for MD simulations to explore the stability of complex. The result indicates that these five candidates could be considered potential Chk1 inhibitors and represents a promising starting point for developing potent inhibitors of Chk1 for the treatment of tumor.

Discovery of FIXa inhibitors by combination of pharmacophore modeling, molecular docking, and 3D-QSAR modeling.

Human Coagulation Factor IXa (FIXa), specifically inhibited at the initiation stage of the blood coagulation cascade, is an excellent target for developing selective and safe anticoagulants. To explore this inhibitory mechanism, 86 FIXa inhibitors were selected to generate pharmacophore models and subsequently SAR models. Both best pharmacophore model and ROC curve were built through the Receptor-Ligand Pharmacophore Generation module. CoMFA model based on molecular docking and PLS factor analysis methods were developed. Model propagations values are q2 = 0.709, r2 = 0.949, and r2pred = 0.905. The satisfactory q2 value of 0.609, r2 value of 0.962, and r2pred value of 0.819 for CoMSIA indicated that the CoMFA and CoMSIA models are both available to predict the inhibitory activity on FIXa. On the basis of pharmacophore modeling, molecular docking, and 3D-QSAR modeling screening, six molecules are screened as potential FIXa inhibitors.

Pharmacophore modeling, molecular docking and molecular dynamics studies on natural products database to discover novel skeleton as non-purine xanthine oxidase inhibitors.

Gout is a common inflammatory arthritis caused by the deposition of urate crystals within joints. It is increasingly in prevalence during the past few decades as shown by the epidemiological survey results. Xanthine oxidase (XO) is a key enzyme to transfer hypoxanthine and xanthine to uric acid, whose overproduction leads to gout. Therefore, inhibiting the activity of xanthine oxidase is an important way to reduce the production of urate. In the study, in order to identify the potential natural products targeting XO, pharmacophore modeling was employed to filter databases. Here, two methods, pharmacophore based on ligand and pharmacophore based on receptor-ligand, were constructed by Discovery Studio. Then GOLD was used to refine the potential compounds with higher fitness scores. Finally, molecular docking and dynamics simulations were employed to analyze the interactions between compounds and protein. The best hypothesis was set as a 3D query to screen database, returning 785 and 297 compounds respectively. A merged set of the above 1082 molecules was subjected to molecular docking, which returned 144 hits with high-fitness scores. These molecules were clustered in four main kinds depending on different backbones. What is more, molecular docking showed that the representative compounds established key interactions with the amino acid residues in the protein, and the RMSD and RMSF of molecular dynamics results showed that these compounds can stabilize the protein. The information represented in the study confirmed previous reports. And it may assist to discover and design new backbones as potential XO inhibitors based on natural products.

Structure-Activity Relationship of Xanthones as Inhibitors of Xanthine Oxidase.

Polygala plants contain a large number of xanthones with good physiological activities. In our previous work, 18 xanthones were isolated from Polygala crotalarioides. Extented study of the chemical composition of the other species Polygala sibirica led to the separation of two new xanthones-3-hydroxy-1,2,6,7,8-pentamethoxy xanthone (A) and 6-O-ß-d-glucopyranosyl-1,7-dimethoxy xanthone (C)-together with 14 known xanthones. Among them, some xanthones have a certain xanthine oxidase (XO) inhibitory activity. Furthemore, 14 xanthones as XO inhibitors were selected to develop three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. The CoMFA model predicted a q² value of 0.613 and an r² value of 0.997. The best CoMSIA model predicted a q² value of 0.608 and an r² value of 0.997 based on a combination of steric, electrostatic, and hydrophobic effects. The analysis of the contour maps from each model provided insight into the structural requirements for the development of more active XO inhibitors.

In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking.

Coagulation Factor Xa (FXa) is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways. The inhibition of FXa is an effective approach against thrombotic diseases. In the present study, a specific strategy is reported to discover 10 novel FXa inhibitors based on ligand-based (pharmacophore) virtual screening and molecular docking analysis from a dataset of specs(containing 220000 molecules). The binding modes analysis provide insights into the contribution of particular structural moieties of the compounds towards their activity against FXa, and 10 novel structural compounds were discovered as potent candidate molecules. This work could be helpful in further design and development of FXa inhibitors.