Exploring Bitter and Sweet: The Application of Large Language Models in Molecular Taste Prediction.

The perception of bitter and sweet tastes is a crucial aspect of human sensory experience. Concerns over the long-term use of aspartame, a widely used sweetener suspected of carcinogenic risks, highlight the importance of developing new taste modifiers. This study utilizes Large Language Models (LLMs) such as GPT-3.5 and GPT-4 for predicting molecular taste characteristics, with a focus on the bitter-sweet dichotomy. Employing random and scaffold data splitting strategies, GPT-4 demonstrated superior performance, achieving an impressive 86% accuracy under scaffold partitioning. Additionally, ChatGPT was employed to extract specific molecular features associated with bitter and sweet tastes. Utilizing these insights, novel molecular compounds with distinct taste profiles were successfully generated. These compounds were validated for their bitter and sweet properties through molecular docking and molecular dynamics simulation, and their practicality was further confirmed by ADMET toxicity testing and DeepSA synthesis feasibility. This research highlights the potential of LLMs in predicting molecular properties and their implications in health and chemical science.

Correlation Between Blood Cadmium Levels and Platelet Characteristics, As Well As Their Impact on Susceptibility to Coronary Heart Disease: Findings from NHANES 2005-2018 Data.

Investigating the correlation between blood cadmium levels, platelet characteristics, and susceptibility to coronary heart disease (CHD). Utilized NHANES 2005-2018 data with covariates such as age, sex, race, marital status, and socio-economic status. Blood cadmium served as the independent variable, while platelet count (PC) and mean platelet volume (MPV) were dependent variables. The average age of the participants was 68.77 ± 11.03 years, and 67.4% of them were male. The mean values for WBC, MPV, PC, and blood cadmium were 7.53 ± 3.36 × 103 cells/µL, 11.33 ± 0.27fL, 57.61 ± 5.34 × 103 cells/µL, and 2.58 ± 0.61 µg/L, respectively. Adjusting for other variables revealed increased MPV and PC with rising blood cadmium levels in cardiac patients, indicating a higher risk of CHD in those with elevated blood cadmium. The average age of the participants was 68.77 ± 11.03 years, and 67.4% of them were male. The mean values for WBC, MPV, PC, and blood cadmium were 7.53 ± 3.36 × 103 cells/µL, 11.33 ± 0.27fL, 57.61 ± 5.34 × 103 cells/µL, and 2.58 ± 0.61 µg/L, respectively. Adjusting for other variables revealed increased MPV and PC with rising blood cadmium levels in cardiac patients, indicating a higher risk of CHD in those with elevated blood cadmium. This study enhances understanding of how cadmium impacts platelet characteristics, contributing to increased CHD risk, providing insights for primary prevention strategies.

Effects of dietary supplementation of fish oil plus vitamin D3 on gut microbiota and fecal metabolites, and their correlation with nonalcoholic fatty liver disease risk factors: a randomized controlled trial.

We previously reported that fish oil plus vitamin D3 (FO + D) could ameliorate nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether the beneficial effects of FO + D on NAFLD are associated with gut microbiota and fecal metabolites. In this study, we investigated the effects of dietary supplementation of FO + D on gut microbiota and fecal metabolites and their correlation with NAFLD risk factors. Methods: A total of 61 subjects were randomly divided into three groups: FO + D group (2.34 g day-1 of eicosatetraenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3), FO group (2.34 g day-1 of EPA + DHA), and corn oil (CO) group (1.70 g d-1 linoleic acid). Blood and fecal samples were collected at the baseline and day 90. Gut microbiota were analyzed through 16S rRNA PCR analysis, and fecal co-metabolites were determined via untargeted ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results: The relative abundance of Eubacterium (p = 0.03) and Lactobacillus (p = 0.05) increased, whereas that of Streptococcus (p = 0.02) and Dialister (p = 0.04) decreased in the FO + D group compared with the CO group. Besides, changes in tetracosahexaenoic acid (THA, C24:6 n-3) (p = 0.03) levels were significantly enhanced, whereas 8,9-DiHETrE levels (p < 0.05) were reduced in the FO + D group compared with the CO group. The changes in 1,25-dihydroxyvitamin D3 levels in the fecal samples were inversely associated with insulin resistance, which was determined using the homeostatic model assessment model (HOMA-IR, r = -0.29, p = 0.02), and changes in 8,9-DiHETrE levels were positively associated with adiponectin levels (r = -0.43, p < 0.05). Conclusion: The present results indicate that the beneficial effects of FO + D on NAFLD may be partially attributed to the impact on gut microbiota and fecal metabolites.

Sigmoido-rectal intussusception anastomosis in the Altemeier procedure for complete rectal prolapse: preliminary results of a new technique.

Purpose: Our research introduces an innovative surgical approach, combining the Altemeier Procedure with Sigmoido-rectal Intussusception Anastomosis, effectively reducing recurrence, minimizing complications, and improving postoperative anal function in rectal prolapse patients. Materials and methods: This retrospective study, conducted at tertiary referral hospitals including Shandong University of Traditional Chinese Medicine's Affiliated Hospital, Linyi People's Hospital, and Pingyi People's Hospital, examined data from patients undergoing conventional Altemeier surgery or Altemeier combined with Sigmoido-rectal Intussusception Anastomosis. Analyzing hospitalization and follow-up data from January 2009 to December 2022, the study focused on prolapse recurrence, complications, and anal function as primary outcome indicators across these three study centers. Results: In the study, both groups had an average follow-up of (12.5 ± 2.41) months, and only two traditional group patients experienced mortality. Recurrence rates significantly differed, with 26.47% in the traditional group and 1.54% in the modified group (P < 0.001). The modified group showed no perioperative anastomotic dehiscence, contrasting with a 13.24% occurrence in the conventional group (P = 0.003). Primary complications in the modified group included anastomotic hemorrhage, with rates of 17.65% and 6.15% in the traditional and modified groups, respectively (P = 0.077). At 12 months postoperatively, both groups improved in anal manometry parameters and the Wexner anal incontinence score. Resting pressure was significantly lower in the traditional group (32.50 ± 1.76 mmHg) than the modified group (33.24 ± 2.06 mmHg) (P = 0.027), while the extrusion pressure was higher in the modified group (64.78 ± 1.55 mmHg) than the traditional group (62.85 ± 2.30 mmHg) (P < 0.001). The Wexner anal incontinence score was significantly lower in the modified group (2.69 ± 1.65) than the traditional group (3.69 ± 1.58, P = 0.001). Conclusion: This retrospective study affirms that adding Sigmoido-rectal Intussusception Anastomosis to the Altemeier procedure reduces recurrence and complications. While both approaches enhance postoperative anal function in complete rectal prolapse patients, the combined method, particularly with Sigmoido-rectal Intussusception Anastomosis, proves more effective.

Using deep learning and molecular dynamics simulations to unravel the regulation mechanism of peptides as noncompetitive inhibitor of xanthine oxidase.

Xanthine oxidase (XO) is a crucial enzyme in the development of hyperuricemia and gout. This study focuses on LWM and ALPM, two food-derived inhibitors of XO. We used molecular docking to obtain three systems and then conducted 200 ns molecular dynamics simulations for the Apo, LWM, and ALPM systems. The results reveal a stronger binding affinity of the LWM peptide to XO, potentially due to increased hydrogen bond formation. Notable changes were observed in the XO tunnel upon inhibitor binding, particularly with LWM, which showed a thinner, longer, and more twisted configuration compared to ALPM. The study highlights the importance of residue F914 in the allosteric pathway. Methodologically, we utilized the perturbed response scan (PRS) based on Python, enhancing tools for MD analysis. These findings deepen our understanding of food-derived anti-XO inhibitors and could inform the development of food-based therapeutics for reducing uric acid levels with minimal side effects.

Fluorescence color change of supramolecular polymer networks controlled by crown ether-cation recognition.

We report a fluorescent supramolecular polymer networks (SPNs) system based on crown ether-cation recognition. The polymer side chains bear ammonium cations, which can be recognized by host molecules with a B15C5 unit and a quinoline group at each end. The quinoline group makes the host molecule exhibit blue fluorescence. After the formation of SPNs, the recognition of the crown ether-cation transforms the blue fluorescence into yellow fluorescence. The accompanying fluorescence color change during the formation of SPNs makes it with potential applications in the fields of display, printing, information storage, and bioimaging.

Network Pharmacology Combined with Machine Learning to Reveal the Action Mechanism of Licochalcone Intervention in Liver Cancer.

There are reports indicating that licochalcones can inhibit the proliferation, migration, and invasion of cancer cells by promoting the expression of autophagy-related proteins, inhibiting the expression of cell cycle proteins and angiogenic factors, and regulating autophagy and apoptosis. This study aims to reveal the potential mechanisms of licochalcone A (LCA), licochalcone B (LCB), licochalcone C (LCC), licochalcone D (LCD), licochalcone E (LCE), licochalcone F (LCF), and licochalcone G (LCG) inhibition in liver cancer through computer-aided screening strategies. By using machine learning clustering analysis to search for other structurally similar components in licorice, quantitative calculations were conducted to collect the structural commonalities of these components related to liver cancer and to identify key residues involved in the interactions between small molecules and key target proteins. Our research results show that the seven licochalcones molecules interfere with the cancer signaling pathway via the NF-κB signaling pathway, PDL1 expression and PD1 checkpoint pathway in cancer, and others. Glypallichalcone, Echinatin, and 3,4,3',4'-Tetrahydroxy-2-methoxychalcone in licorice also have similar structures to the seven licochalcones, which may indicate their similar effects. We also identified the key residues (including ASN364, GLY365, TRP366, and TYR485) involved in the interactions between ten flavonoids and the key target protein (nitric oxide synthase 2). In summary, we provide valuable insights into the molecular mechanisms of the anticancer effects of licorice flavonoids, providing new ideas for the design of small molecules for liver cancer drugs.

Probing the mechanisms of hydrazide-based HDAC inhibitors binding to HDAC3 using Gaussian accelerated molecular dynamics (GaMD) simulations.

Histone deacetylases (HDACs) have emerged as promising targets for anticancer drug development. They regulate gene expression by removing acetyl groups from lysine residues on histone tails, leading to chromatin condensation. A hydrazide-based HDAC inhibitor, N-(4-(2-Propylhydrazine-1-carbonyl)benzyl)-1H-indole-2-carboxamide (11h), has been reported to exhibit significant in vivo antitumor activity. In comparison to the lead compound N-(4-(2-Propylhydrazine-1-carbonyl)benzyl)cinnamamide (17), compound 11h demonstrates 2- to 5-fold higher HDAC inhibition and cell-based antitumor activity. However, the inhibitory mechanism of 11h remains insufficiently explored. In this study, we conducted 500 ns Gaussian Accelerated Molecular Dynamics (GaMD) simulations on Histone deacetylase 3 (HDAC3) and two complex systems (HDAC3-17 and HDAC3-11h). Our findings revealed that upon inhibitor binding, the active pocket volume of HDAC3 undergone alterations, and the movement of the L6-loop toward the active site impeded substrate entry. Moreover, we observed a destabilization of the α-helix in the aa75-89 region of HDAC3 compared to the two complex systems, indicating partial unwinding. Notably, 11h exhibited a closer proximity of its carbonyl oxygen to the active pocket's Zn2+ metal compared to 17, increasing the likelihood of coordination with the Zn2+ metal. The analysis of protein-ligand interactions highlighted a greater number of hydrogen bonds and other interactions between 11h and the receptor protein when compared to 17, underscoring the stronger binding of 11h to HDAC3. In conclusion, our study provided theoretical insights into the inhibitory mechanism of hydrazide-based HDAC inhibitors on HDAC3, thereby contributing to the development of improved drug targets for cancer therapy.Communicated by Ramaswamy H. Sarma.

Computer-Aided Screening and Revealing Action Mechanism of Green Tea Polyphenols Intervention in Alzheimer's Disease.

The accumulation of cross-ß-sheet amyloid fibrils is a hallmark of the neurodegenerative process of Alzheimer's disease (AD). Although it has been reported that green tea substances such as epicatechin (EC), epicatechin-3-gallate (ECG), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) could alleviate the symptoms of AD and other neurodegenerative diseases, the pharmacological mechanism remains largely unexplored. This study aimed to reveal the underlying mechanism of EC, ECG, EGC and EGCG in AD using a computer-aided screening strategy. Our results showed that the four tea polyphenols interfered with the signaling pathways of AD via calcium signaling channels, neurodegeneration-multiple disease signal pathways and others. We also identified the key residues of the interaction between VEGFA and the four active components, which included Glu64 and Phe36. Overall, we have provided valuable insights into the molecular mechanism of tea polyphenols, which could be used as a reference to improve therapeutic strategies against AD.

Green Surfactant Made from Cashew Phenol for Enhanced Oil Recovery.

Surfactants play an important role in enhancing oil recovery (EOR). With the development of tertiary oil recovery technology and the continuous improvement of environmental protection requirements, green environmentally friendly surfactants play an important role in replacing conventional surfactants. In this paper, cardanol polyoxyethylene ether (CPE) was synthesized from natural biomass cardanol. Its structure was characterized, and its surface/interface properties, salt and temperature resistance, wettability, emulsification, and oil displacement effect were studied experimentally. The results showed that CPE had good interfacial activity and temperature and salt tolerance, which can reduce the oil-water interfacial tension to 10-1 mN/m. The emulsion formed by CPE had good stability. With the increase in CPE dosage, the droplet size of the emulsion decreases. The emulsion stabilized by CPE can effectively enhance oil recovery by 11.8%. Therefore, CPE not only is environmentally friendly but also has great application potential in the field of EOR.

High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma.

Background: Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC. Methods: Kaplan-Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC. Results: DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC. Conclusion: This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.

Correlation between systemic inflammatory response index and thyroid function: 2009-2012 NHANES results.

Aims: This study investigates the relationship between the Systemic Inflammatory Response Index (SIRI) and thyroid function. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2009-2012, we excluded participants lacking SIRI or thyroid function data, those under 20 years, and pregnant individuals. SIRI was determined using blood samples. We conducted weighted multivariate regression and subgroup analyses to discern the independent relationship between SIRI and thyroid function. Results: The study included 1,641 subjects, with an average age of 47.26±16.77 years, including 48.65% males and 51.35% females. The population was divided into three SIRI-based groups (Q1-Q3). Q3, compared to Q1, exhibited higher age-at-onset, greater male prevalence, and increased levels of FT3, FT4, TT4, leukocytes, and triglycerides. This group also showed a higher incidence of diabetes, hypertension, and smoking. Notably, Q1 had lower LDL and HDL levels. SIRI maintained a positive association with FT4 (ß = 0.01, 95% CI = 0.00-0.03, P for trend = 0.0071), TT4 (ß = 0.20, 95% CI = 0.10, 0.31, P for trend=0.0001), and TPOAb (ß = 8.0, 95% CI = 1.77-14.30, P for trend = 0.0120), indicating that each quartile increase in SIRI corresponded to a 0.01 ng/dL increase in FT4, a 0.2 g/dL increase in TT4, and an 8.03 IU/mL rise in TPOAb. The subgroup analysis suggested the SIRI-thyroid function correlation was influenced by hypertension. Conclusion: Inflammation may impact the development and progression of thyroid function disorders. Proactive anti-inflammatory treatment might mitigate thyroid abnormalities.

In Silico Discovery of Anticancer Peptides from Sanghuang.

Anticancer peptide (ACP) is a short peptide with less than 50 amino acids that has been discovered in a variety of foods. It has been demonstrated that traditional Chinese medicine or food can help treat cancer in some cases, which suggests that ACP may be one of the therapeutic ingredients. Studies on the anti-cancer properties of Sanghuangporus sanghuang have concentrated on polysaccharides, flavonoids, triterpenoids, etc. The function of peptides has not received much attention. The purpose of this study is to use computer mining techniques to search for potential anticancer peptides from 62 proteins of Sanghuang. We used mACPpred to perform sequence scans after theoretical trypsin hydrolysis and discovered nine fragments with an anticancer probability of over 0.60. The study used AlphaFold 2 to perform structural modeling of the first three ACPs discovered, which had blast results from the Cancer PPD database. Using reverse docking technology, we found the target proteins and interacting residues of two ACPs with an unknown mechanism. Reverse docking results predicted the binding modes of the ACPs and their target protein. In addition, we determined the active part of ACPs by quantum chemical calculation. Our study provides a framework for the future discovery of functional peptides from foods. The ACPs discovered have the potential to be used as drugs in oncology clinical treatment after further research.

Theoretical Analysis and Experimental Verification of the Stress and Strain of Axially Compressed Steel-Reinforced Concrete Columns under Long-Term Loads.

The objective of this study is to provide a theoretical method to accurately calculate the stress and strain of steel-reinforced concrete (SRC) columns under long-term axial compression. First, considering the cross-sectional stress redistribution and the influence of each stress increment in the process, the theoretical formula of stress and strain under long-term loading was deduced. Then, the stress and strain calculation program of SRC columns under long-term axial compression was programmed by using object-oriented Visual C++ language. Finally, an experimental study on the long-term deformation performance of SRC axial compression columns was performed to validate the accuracy of the proposed theoretical method. By comparing the calculated results with the experimental results, the influence of steel bars on the long-term stress and strain of SRC columns under axial compression was analyzed and the corresponding long-term stress-strain variation law was studied. Results show that the changing trend of the long-term strain of plain concrete (PC) and SRC with loading time is basically the same, increasing rapidly in the first 270 days and gradually tending to be stable beyond 270 days. After 750 days, the maximum difference in the total strain between the PC columns and SRC columns reaches 26.60%, and the steel bars have a strong influence on the long-term strain of the concrete columns. The errors between the measured values of the two SRC columns, and the calculated results are 2.96% and 5.78%, respectively. Therefore, the derived stress-strain calculation formula and calculation program of SRC columns under long-term loads are accurate and reliable. When the loading time is 750 days, the tensile stress increment of 1.92 MPa and a compressive stress increment of 168.26 MPa are produced in concrete and steel bars. The long-term stress of concrete columns is markedly influenced by steel bars. In the first three years, the stress and strain of the concrete and steel bars develop rapidly and then gradually slow down.

Recent Advances in the Heterogeneous Photocatalytic Hydroxylation of Benzene to Phenol.

Phenol is an important chemical material that is widely used in industry. Currently, phenol is dominantly produced by the well-known three-step cumene process, which suffers from severe drawbacks. Therefore, developing a green, sustainable, and economical strategy for the production of phenol directly from benzene is urgently needed. In recent years, the photocatalytic hydroxylation of benzene to phenol, which is economically feasible and could be performed under mild conditions, has attracted more attention, and development of highly efficient photocatalyst would be a key issue in this field. In this review, we systematically introduce the recent achievements of photocatalytic hydroxylation of benzene to phenol from 2015 to mid-2022, and various heterogeneous photocatalysts are comprehensively reviewed, including semiconductors, polyoxometalates (POMs), graphitic carbon nitride (g-C3N4), metal-organic frameworks (MOFs), carbon materials, and some other types of photocatalysts. Much effort is focused on the physical and chemical approaches for modification of these photocatalysts. The challenges and future promising directions for further enhancing the catalytic performances in photocatalytic hydroxylation of benzene are discussed in the end.

Alisol A attenuates malignant phenotypes of colorectal cancer cells by inactivating PI3K/Akt signaling.

Despite the advancement in the diagnosis and therapeutic strategies for colorectal cancer, the outcomes of patients with colorectal cancer remain unsatisfactory. Alisol A is a natural constituent of Alismatis rhizoma (zexie) and has demonstrated anti-cancer properties; however, the function of Alisol A in colorectal cancer is still unknown. In the present study, the effect of Alisol A on colorectal cancer progression was investigated. MTT and colony formation assays showed that treatment with Alisol A repressed colorectal cancer cell proliferation in a dose-dependent manner. Similarly, western blot analysis demonstrated that Alisol A upregulated E-cadherin protein expression levels, but downregulated N-cadherin and Vimentin protein expression levels in colorectal cancer cells. In addition, the number of cells in G0/G1 phase was enhanced, while that of S phase was reduced in Alisol A-treated colorectal cancer cells. Apoptosis and pyroptosis of colorectal cancer cells were stimulated following treatment with Alisol A. Alisol A suppressed the migration ability of colorectal cancer cells in a dose-dependent manner. Moreover, Alisol A increased the chemotherapeutic sensitivity of colorectal cancer cells to cisplatin. Mechanically, western blot analysis confirmed that Alisol A repressed the phosphorylation levels of PI3K, Akt and mTOR in colorectal cancer cells. The Akt activator, SC79 reversed the effect of Alisol A on colorectal cancer cell proliferation and apoptosis. In conclusion, Alisol A induced an inhibitory effect on colorectal cancer progression by inactivating PI3K/Akt signaling.

ISLR affects colon cancer progression by regulating the epithelial-mesenchymal transition signaling pathway.

This study aims to determine the mechanism of ISLR on the progression of colon cancer. TCGA database was used to analyze ISLR expression in colon cancer tumor tissues. QRT-PCR and western blotting were used to detect ISLR expression in colon cancer cells. CCK-8, colony formation, EDU, wound healing and transwell assays were used to measure cell viability, proliferation, migration and invasion of colon cancer cells, respectively. The signaling pathway enrichment analysis of ISLR was analyzed on the basis of the KEGG database. The protein expression of genes related to signaling pathway was measured by western blotting. Results of TCGA analysis, qRT-PC and western blotting showed that ISLR was upregulated in colon cancer tumor tissues and cells. High level of ISLR was related to low overall survival of patients with colon cancer. ISLR silence significantly inhibited cell viability, proliferation, migration and invasion of colon cancer cells. ISLR overexpression markedly enhanced the cell viability, proliferation, migration and invasion of colon cancer cells. KEGG database analyzed showed that ISLR can activate the EMT signaling pathway. Inhibition of the EMT signaling pathway can suppress the growth, migration, and invasion of colon cancer cells and eliminate the promoted effect of ISLR overexpression on colon cancer progression. ISLR promotes the progression of colon cancer by activating the EMT signaling pathway.

In silico study to predict potential precursors of human dipeptidyl peptidase-IV inhibitors from hazelnut.

Chinese hazelnut was chosen to become a probable precursor of biological active peptides via computer simulations in this article. There were a large number of bioactive peptides in Chinese hazelnut sequences according to analytical results from the BIOPEP database. The most prominent of these was the inhibitory peptide for dipeptidyl peptidase-IV (DPP-IV; EC 3.4.14.5), which can be used to treat type 2 diabetes, so the theoretical method to obtain DPP-IV inhibitory peptides by hydrolysis with a single or combination of enzymes was studied. Cytotoxicity analysis performed by ToxinPred showed that all of the DPP-IV inhibitory peptides generated from protein hydrolysis were not cytotoxic. Structural interaction fingerprint analysis revealed that Asp663 and Phe357 may be important residues for ligand binding. In order to further understand the inhibitory mechanism of peptide, VR with lowest half maximum inhibitory concentration (IC50) and IPI (inhibitors have been reported) were selected as ligand of DPP-IV to perform steered molecular dynamics simulations and PMF calculations. The results showed that P1 is the preferred (un)binding tunnel for the inhibitors obtained. Our findings help in the development of new DPP-IV inhibitors which were derived from common food.Communicated by Ramaswamy H. Sarma.

Chemical Compounds, Antioxidant Activities, and Inhibitory Activities Against Xanthine Oxidase of the Essential Oils From the Three Varieties of Sunflower (Helianthus annuus L.) Receptacles.

Background/Aim: Essential oils of sunflower receptacles (SEOs) have antibacterial and antioxidant potential. However, the differences of biological activities from the different varieties of sunflowers have not been studied till now. The purpose of this study was to compare the differences of chemical compounds, antioxidant activities, and inhibitory activities against xanthine oxidase (XO) of SEOs from the three varieties of sunflowers including LD5009, SH363, and S606. Methods: SEOs were extracted by using the optimal extraction conditions selected by response surface methodology (RSM). Chemical compounds of SEOs were identified from the three varieties of sunflowers by gas chromatography-mass spectrometry (GC-MS). Antioxidant activities of SEOs were detected by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and iron ion reduction ability. Inhibitory activities of SEOs against XO were measured by using UV spectrophotometer. XO inhibitors were selected from the main chemical compounds of SEOs by the high-throughput selections and molecular simulation docking. Results: The extraction yields of SEOs from LD5009, SH363, and S606 were 0.176, 0.319, and 0.580%, respectively. A total of 101 chemical compounds of SEOs were identified from the three varieties of sunflowers. In addition, the results of inhibitory activities against XO showed that SEOs can reduce uric acid significantly. Eupatoriochromene may be the most important chemical compounds of SEOs for reducing uric acid. The results of antioxidant activities and inhibitory activities against XO showed that SEOs of LD5009 had the strongest antioxidant and XO inhibitory activities. The Pearson correlation coefficient (r > 0.95) showed that γ-terpinene, (E)-citral, and L-Bornyl acetate were highly correlated with the antioxidant activities and XO inhibitory ability. Conclusion: SEOs had antioxidant activities and XO inhibitory ability. It would provide more scientific information for utilization and selection of varieties of sunflowers, which would increase the food quality of sunflowers and incomes of farmers.