Investigating the impact of lipid molecules and heat transfer on aroma compound formation and binding in roasted chicken skin: A UHPLC-HRMS and GC-O-MS study.

The UHPLCHRMS and Gas Chromatography-Olfactometry-Mass Spectrometry (GC-O-MS) techniques were applied to investigate effects of lipid molecules and heat transfer on the generation of aroma compounds in roasted chicken skin. Nineteen odorants were identified as most important aroma contributors based on odor activity values (OAVs) exceeding 1. Lipidomic analysis identified 3926 lipids in the samples, in which triglycerides (TG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and ceramide (Cer) had a contribution of 20.63%, 12.46%, 11.95%, and 11.39%, respectively. Furthermore, it was observed that PS(18:3e_22:5) and TG(18:0_18:1_18:1) serve as significant chemical markers for distinguishing chicken skin during the roasting (p < 0.05). TGs, notably TG(16:1_18:1_18:2) and TG(18:1_18:2_18:2), were postulated as key retainers for binding crucial aroma compounds. Meanwhile, PC, PE, and Cer played pivotal roles in aroma compound formation. Additionally, higher thermal conductivity and reduced thermal diffusivity significantly contributed to the formation of key odorants.

Simultaneous determination of advanced glycation end products and heterocyclic amines in roast/grilled meat by UPLC-MS/MS.

Advanced glycation end products (AGEs) and heterocyclic amines (HAs) are main harmful Maillard reaction products of meat products. Simultaneous quantification of both with high sensitivity, selectivity and accuracy remains a major challenge due to inconsistencies in their pre-treatment and instrumental methods and the different polarity of AGEs and HAs. We developed a method for the simultaneous determination of AGEs and HAs in roast/grilled meat by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) using dynamic multiple reaction monitoring (D-MRM). The instrument parameters and pre-treatment method were optimized to achieve reasonably good separation and high response for the 11 target analytes within 8 min. From 10 to 200 ng/mL, the limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.3 to 5.5 µg/L and 0.9 to 6.3 µg/L, respectively, and the correlation coefficient (R2) was >0.99. It was acceptable to recoveries, standard deviations (RSDs), and matrix effects. Six types of roast/grilled meat samples were then tested using the developed method.

Characterization of key aroma compounds in roasted chicken using SPME, SAFE, GC-O, GC-MS, AEDA, OAV, recombination-omission tests, and sensory evaluation.

Aroma compounds in the roasted breasts, thighs and skins of chicken were isolated by solvent-assisted flavor evaporation (SAFE), quantitated by gas chromatography-olfactometry-mass (GC-O-MS), analyzed by aroma extract dilution analysis (AEDA), and determined by recombination-omission tests and sensory evaluation. Forty-seven aroma compounds in total, including aldehydes, ketones, furans, pyrazines, and furanones, were selected by AEDA. Twenty-five compounds were selected as pivotal odorants (Odor Activity Value, OAV ≥ 1). Twenty aroma compounds significantly were identified by recombination and omission experiments. Anethole (fennel odor) was the highest OAV (＞ 1843). Hexanal (grassy) and (E, E)-2,4-decadienal (meaty) were the most abundant aldehydes identified in roasted chicken. 1-octen-3-ol (mushroom), methanethiol (cabbage) and dimethyl trisulfide (areca, sulfur) were considered the key compounds of the breast and thighs of roasted chicken. Notably, furanone and pyrazines, 4-hydroxy-5-methyl-3(2H)-furanone (caramel, sweet and burning odor), 3-ethyl-2,5-dimethylpyrazine (nutty, toasty) and 2,3-dimethyl-5-ethylpyrazine (nutty, toasty) had the most significant effect on roasted chicken odor, especially in the skin.

Glutamine Metabolism Promotes Renal Fibrosis through Regulation of Mitochondrial Energy Generation and Mitochondrial Fission.

Fibroblast activation and proliferation is an essential phase in the progression of renal fibrosis. Despite the recognized significance of glutamine metabolism in cellular growth and proliferation, its precise pathophysiological relevance in renal fibrosis remains uncertain. Therefore, this study aims to investigate the involvement of glutamine metabolism in fibroblast activation and its possible mechanism. Our findings highlight the importance of glutamine metabolism in fibroblast activation and reveal that patients with severe fibrosis exhibit elevated serum glutamine levels and increased expression of kidney glutamine synthetase. Furthermore, the deprivation of glutamine metabolism in vitro and in vivo could inhibit fibroblast activation, thereby ameliorating renal fibrosis. It was also detected that glutamine metabolism is crucial for maintaining mitochondrial function and morphology. These effects may partially depend on the metabolic intermediate α-ketoglutaric acid. Moreover, glutamine deprivation led to upregulated mitochondrial fission in fibroblasts and the activation of the mammalian target of rapamycin / mitochondrial fission process 1 / dynamin-related protein 1 pathway. Thus, these results provide compelling evidence that the modulation of glutamine metabolism initiates the regulation of mitochondrial function, thereby facilitating the progression of renal fibrosis. Consequently, targeting glutamine metabolism emerges as a novel and promising avenue for therapeutic intervention and prevention of renal fibrosis.

Study of the Structural Changes and Internal Activator Transport Behavior after Activation of Aluminum-Based Flameless Ration Heaters: Experimental and Molecular Dynamics Simulations.

Aluminum-based flameless ration heaters (AFRHs) are heating elements in food packaging. Water is used to activate AFRHs. The material properties of each region of AFRHs were determined by X-ray diffraction, scanning electron microscopy, and hydrogen and heat generation. The results show that the internal cross-section shows stratification with hydrogen and heat production capacities of 105.2 ± 9.7 mL/g and 1435.0 ± 30.3 J/g for the outer layer, 27.1 ± 4.4 mL/g and 80.4 ± 3.1 J/g for the inner layer, and 1.1 ± 0.01 mL/g and 1.2 ± 0.05 J/g for the middle layer, respectively. According to the correspondence between aluminum and hydrogen in the aluminum-water reaction relationship, the reaction efficiency of the outer layer and the inner layer is as low as 64 and 80%, which is an indication of low reaction efficiency. To analyze the reasons for low reaction efficiency, a pore channel model of 3.5 nm tricalcium aluminate (C3A) was developed using molecular dynamics (MD) to reveal the adsorption behavior of the activator in the pore channel. The results show that the activator is subject to solid surface adsorption in the pore channel with a low diffusion coefficient. Oxygen atoms on the surface adsorb hydrogen atoms to form hydrogen bonds and sodium ions to form ionic bonds with calcium ions. This increases the retention time of the activator on the surface. The MD results explain the low reaction efficiency of AFRHs at the microscopic scale. Moreover, it provides ideas and a basis for the optimization of AFRHs.

Deep Learning-Based Near-Infrared Hyperspectral Imaging for Food Nutrition Estimation.

The limited nutritional information provided by external food representations has constrained the further development of food nutrition estimation. Near-infrared hyperspectral imaging (NIR-HSI) technology can capture food chemical characteristics directly related to nutrition and is widely used in food science. However, conventional data analysis methods may lack the capability of modeling complex nonlinear relations between spectral information and nutrition content. Therefore, we initiated this study to explore the feasibility of integrating deep learning with NIR-HSI for food nutrition estimation. Inspired by reinforcement learning, we proposed OptmWave, an approach that can perform modeling and wavelength selection simultaneously. It achieved the highest accuracy on our constructed scrambled eggs with tomatoes dataset, with a determination coefficient of 0.9913 and a root mean square error (RMSE) of 0.3548. The interpretability of our selection results was confirmed through spectral analysis, validating the feasibility of deep learning-based NIR-HSI in food nutrition estimation.

Exploring the interaction between myofibrillar proteins and pyrazine compounds: Based on molecular docking, molecular dynamics simulation, and multi-spectroscopy techniques.

Flavor is one of the most important factors that affect consumers' preference for processed meat products. This study aimed to investigate effects of heating on interaction between myofibrillar proteins (MPs) and pyrazine compounds and understand the underlying mechanisms. A combination of multispectral, molecular docking, and molecular dynamics technologies was used to achieve study's aim. Results demonstrated that MPs underwent structural reconstruction and expansion during heating, which significantly altered surface hydrophobicity and SH content. MPs' zeta potential reduced from -7.29 to -10.47 when a short heating time. Additionally, a positive correlation was found between ß-sheet content and ability of MPs to adsorb pyrazine compounds. Molecular docking analysis revealed 13 binding sites for pyrazines and MPs. Furthermore, amino acid residues and pyrazine compounds were found to interact by four different forms of forces, primarily van der Waals forces, carbon­hydrogen bonds, alkyl groups, and π-alkyl groups. Obtained results demonstrated that adequate or optimized heat treatment could expose more binding sites, hence enhancing the binding of MPs to pyrazine compounds. This study may be used to better understand how structural changes in MPs during processing affect MPs' capacity to bind flavor substances, which can help improve flavor of processed meats to encourage their consumption.

Elevated Urinary IL-6 Predicts the Progression of IgA Nephropathy.

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. However, biomarkers for predicting the progression or regression of IgAN remain a clinical challenge. In the present study, we aim to identify promising prognostic markers of IgAN. Methods: Using the cytokine antibody array, we detected serum and urinary levels of 9 common cytokines selected from 23 IgAN-related biomarkers in 32 patients with IgAN and 16 healthy controls. The best biomarkers for distinguishing IgAN patients from healthy controls were identified and confirmed in a multicenter cohort with 222 patients with IgAN and 159 age- and sex-matched healthy controls. Their associations with IgAN progression were further explored in 762 patients with IgAN with a median follow-up of 65 months. Results: Among the 9 candidate markers, urinary interleukin-6 (IL-6) and transforming growth factor-ß1 (TGF-ß1) levels were the best for distinguishing patients with IgAN from healthy controls. In the diagnostic cohort, both urinary IL-6 and TGF-ß1 levels were elevated in patients with IgAN and showed good discriminatory power, with an area under curve (AUC) of 0.9725 (95% confidence interval: 0.9593-0.9858). Elevated urinary IL-6 level was independently and significantly correlated with the high risk of composite renal outcome (hazard ratio per log-transformed IL-6:1.420 [1.139-1.769]), but no statistical significance was observed between urinary TGF-ß1 level and IgAN progression after adjusting for multiple confounders. Conclusions: Elevated urinary IL-6 and TGF-ß1 levels predict the progression of IgAN. Urinary IL-6 is an independent risk factor and a promising noninvasive predictor for IgAN progression.

Exploring the mechanism of Cassiae semen in regulating lipid metabolism through network pharmacology and experimental validation.

BACKGROUND: Multiple studies have assessed the role of Cassiae semen (CS) in regulating lipid metabolism. However, the mechanism of action of CS on non-alcoholic fatty liver disease (NAFLD) has seen rare scrutiny. OBJECTIVE: The objective of this study was to explore the regulatory mechanism of CS on lipid metabolism in NAFLD. METHODS: Components of CS ethanol extract (CSEE) were analyzed and identified using UPLC-Q-Orbirap HRMS. The candidate compounds of CS and its relative targets were extracted from the Traditional Chinese Medicine Systems Pharmacology, Swiss-Target-Prediction, and TargetNet web server. The Therapeutic Target Database, Genecards, Online Mendelian Inheritance in Man, and DisGeNET were searched for NAFLD targets. Binding affinity between potential core components and key targets was established employing molecular docking simulations. After that, free fatty acid (FFA)-induced HepG2 cells were used to further validate part of the network pharmacology results. RESULTS: Six genes, including Caspase 3 (CASP3), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA), epidermal growth factor receptor (EGFR), and amyloid ß (A4) precursor protein (APP) were identified as key targets. The mitogen-activated protein kinase (MAPK) signaling pathway was found to associate closely with CS's effect on NAFLD. Per molecular docking findings, toralactone and quinizarin formed the most stable combinations with hub genes. About 0.1 (vs. FFA, P<0.01) and 0.2 (vs. FFA, P<0.05) mg/ml CSEE decreased lipid accumulation in vitro by reversing the up-regulation of CASP3, EGFR, and APP and the down-regulation of PIK3CA. CONCLUSION: CSEE can significantly reduce intracellular lipid accumulation by modulating the MAPK signaling pathway to decrease CASP3 and EGFR expression.

Fermented Angelica sinensis activates Nrf2 signaling and modulates the gut microbiota composition and metabolism to attenuate D-gal induced liver aging.

Aging is an inevitable physiological process associated with an imbalance in the oxidative defense system. Angelica sinensis, a kind of traditional Chinese medicine (TCM), has anti-oxidant effects and has been considered as a potential supplement in anti-aging treatment. Nevertheless, it has the disadvantages of slow efficacy and long duration of treatment. Fermentation, as an efficient biotechnological approach, is beneficial for improving the nutritional capacity of the material. Fermented TCMs are considered to be more effective. In this study, fermented Angelica sinensis (FAS) and non-fermented Angelica sinensis (NFAS) were used to investigate changes in the chemical constituents. Furthermore, the improvement effect of FAS on D-galactose-induced aging in mice and the potential mechanisms were explored. The results revealed that FAS and NFAS had different constituents under the influence of fermentation, such as 3-phenyllactic acid, L-5-hydroxytryptophan, taxifolin and methyl gallate. These elevated constituents of FAS might help increase the ability of FAS to improve aging. The aging model was established by intraperitoneal injection of D-galactose (2.5 g kg-1 day-1) for 44 days, and FAS (3 g kg-1 day-1) was administered daily by oral gavage after 2 weeks of induction with D-galactose. FAS was observed to significantly ameliorate changes associated with liver aging, such as reduction of MDA, AGEs and 8-OHdG. The contents of pro-inflammatory cytokines containing TNF-α, IL-1ß and IL-6 were significantly suppressed in the FAS group. In addition, FAS activated Nrf2 signaling better than NFAS, improved the expression of Nrf2, HO-1, NQO1, GCLC, GCLM and GSS, and further increased the activities of SOD, CAT and other antioxidant enzymes in the liver. Simultaneously, it had a certain repair effect on the liver tissues of mice. The intestinal microbiota analysis showed that FAS could regulate the microbiota imbalance caused by aging, increase the ratio of Firmicutes/Bacteroidetes by 95% and improve the relative abundance of beneficial bacteria related to Nrf2 signaling, such as Lactobacillus. Besides, fecal metabolite analysis identified uric acid as an evidential metabolite, suggesting that FAS participates in purine metabolism to improve aging. Therefore, the regulation of intestinal microbiota and metabolism may be one of the important mechanisms of FAS in alleviating hepatic oxidative stress via the gut-liver axis. The results of this study could provide information for the future development of postbiotic products that may have beneficial effects on the prevention or treatment of aging.

A Hybrid Evolutionary Algorithm Using Two Solution Representations for Hybrid Flow-Shop Scheduling Problem.

As an extension of the classical flow-shop scheduling problem, the hybrid flow-shop scheduling problem (HFSP) widely exists in large-scale industrial production systems and has been considered to be challenging for its complexity and flexibility. Evolutionary algorithms based on encoding and heuristic decoding approaches are shown effective in solving the HFSP. However, frequently used encoding and decoding strategies can only search a limited area of the solution space, thus leading to unsatisfactory performance during the later period. In this article, a hybrid evolutionary algorithm (HEA) using two solution representations is proposed to solve the HFSP for makespan minimization. First, the proposed HEA searches the solution space by a permutation-based encoding representation and two heuristic decoding methods to find some promising areas. Afterward, a Tabu search (TS) procedure based on a disjunctive graph representation is introduced to expand the searching space for further optimization. Two classical neighborhood structures focusing on critical paths are extended to the problem-specific backward schedules to generate candidate solutions for the TS. The proposed HEA is tested on three public HFSP benchmark sets from the existing literature, including 567 instances in total, and is compared with some state-of-the-art algorithms. Extensive experimental results indicate that the proposed HEA performs much better than the other algorithms. Moreover, the proposed method finds new best solutions for 285 hard instances.

Superheated steam processing: An emerging technology to improve food quality and safety.

Heat processing is one of the most efficient strategies used in food industry to improve quality and prolong shelf life. However, conventional processing methods such as microwave heating, burning charcoal treatment, boiling, and frying are energy-inefficient and often lead to inferior product quality. Superheated steam (SHS) is an innovative technology that offers many potential benefits to industry and is increasingly used in food industry. Compared to conventional processing methods, SHS holds higher heat transfer coefficients, which can reduce microorganisms on surface of foodstuffs efficiently. Additionally, SHS generates a low oxygen environment, which prevents lipid oxidation and harmful compounds generation. Furthermore, SHS can facilitate development of desired product quality, such as protein denaturation with functional characteristics, proper starch gelatinization, and can also reduce nutrient loss, and improve the physicochemical properties of foodstuffs. The current work provides a comprehensive review of the impact of SHS on the nutritional, physicochemical, and safety properties of various foodstuffs including meat, fruits, and vegetables, cereals, etc. Additionally, it also provides food manufacturers and researchers with basic knowledge and practical techniques for SHS processing of foodstuffs, which may improve the current scope of SHS and transfer current food systems to a healthy and sustainable one.

Fermented Astragalus and its metabolites regulate inflammatory status and gut microbiota to repair intestinal barrier damage in dextran sulfate sodium-induced ulcerative colitis.

Fermentation represents an efficient biotechnological approach to increase the nutritional and functional potential of traditional Chinese medicine. In this study, Lactobacillus plantarum was used to ferment traditional Chinese medicine Astragalus, the differential metabolites in the fermented Astragalus (FA) were identified by ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS), and the ameliorating effect of FA on dextran sulfate sodium (DSS)-induced colitis in mice were further explored. The results showed that 11 differential metabolites such as raffinose, progesterone and uridine were identified in FA, which may help improve the ability of FA to alleviate colitis. Prophylactic FA supplementation effectively improved DAI score, colon length and histopathological lesion in DSS-treated mice. The abnormal activation of the intestinal immune barrier in mice was controlled after FA supplementation, the contents of myeloperoxidase (MPO) and IgE were reduced and the contents of IgA were increased. The intestinal pro-inflammatory factors TNF-α, IL-1ß, IL-6, and IL-17 were down-regulated and the anti-inflammatory factors IL-10 and TGF-ß were up-regulated, suggesting that FA can intervene in inflammatory status by regulating the balance of Th1/Th2/Th17/Treg related cytokines. In addition, FA supplementation modified the structure of the intestinal microbiota and enriched the abundance of Akkermansia and Alistipes, which were positively associated with the production of short-chain fatty acids. These microbes and their metabolites induced by FA also be involved in maintaining the intestinal mucosal barrier integrity by affecting mucosal immunity. We observed that intestinal tight junction protein and mucous secreting protein ZO-1, occludin, and MUC2 genes expression were more pronounced in mice supplemented with FA compared to unfermented Astragalus, along with modulation of intestinal epithelial cells (IECs) apoptosis, verifying the intestinal mucosal barrier repaired by FA. This study is the first to suggest that FA as a potential modulator can more effectively regulate the inflammatory status and gut microbiota to repair the intestinal barrier damage caused by colitis.

Overcoming Anxiety Disorder by Probiotic Lactiplantibacillus plantarum LZU-J-TSL6 through Regulating Intestinal Homeostasis.

Lactiplantibacillus plantarum LZU-J-TSL6 with high γ-aminobutyric acid (GABA) production (3.838 g/L) was screened and isolated from the Chinese fermented food snack "Jiangshui". The improvement effect on anxiety disorder was explored using mice as animal models. In vitro results revealed that LZU-J-TSL6 had the potential to colonize the intestine (p < 0.01) and the anxiety-like behavior of the mice after seven days' gavage with LZU-J-TSL6 was significantly improved (p < 0.01) when compared to the model group. LZU-J-TSL6 was able to effectively increase the GABA content in the mice hippocampus (p < 0.0001) and restore some markers related to anxiety such as brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and 5-hydroxytryptamine (5-HT). Simultaneously, it had a certain repair effect on Nissl bodies and colon tissue in mice hippocampus. In addition, LZU-J-TSL6 increased the relative abundance of beneficial bacteria Bacteroides and Muribaculum, thereby regulating the imbalance of intestinal microbiota caused by anxiety disorder. It also affects the nerve pathway and intestinal mucosal barrier by increasing the content of glutamine and γ-aminobutyric acid and other related metabolites, thereby improving anxiety. Therefore, the GABA-producing Lactobacillus plantus LZU-J-TSL6 can be used as a probiotic to exert an indirect or direct anti-anxiety effect by maintaining the balance of the intestinal environment, producing related metabolites that affect nerve pathways and repair the intestinal mucosal barrier. It can be used as an adjuvant treatment to improve anxiety disorders.

Structural and compositional segregation of the gut microbiota in HCV and liver cirrhotic patients: A clinical pilot study.

Gut microbial dysbiosis during the development of Hepatitis C virus and liver-related diseases is not well studied. Nowadays, HCV and liver cirrhosis are the major concerns that cause gut bacterial alteration, which leads to dysbiosis. For this purpose, the present study was aimed at correlating the gut bacterial community of the control group in comparison to HCV and liver cirrhotic patients. A total of 23 stool samples were collected, including control (9), liver cirrhotic (8), and HCV (6). The collected samples were subjected to 16 S rRNA Illumina gene sequencing. In comparison with control, a significant gut bacterial alteration was observed in the progression of HCV and liver cirrhosis. Overall, Firmicutes were significantly abundant in the whole study. No significant difference was observed in the alpha diversity of the control and patient studies. Additionally, the beta diversity based on non-metric multidimensional scaling (NMDS) has a significant difference (p = 0.005) (ANOSIM R2 = 0.14) in all groups. The discriminative results based on the LEfSe tool revealed that the HCV-infected patients had higher Enterobacteriaceae and Enterobacterial, as well as Lactobacillus and Bacilli in comparison than the liver-cirrhotic patients. These taxa were significantly different from the control group (p < 0.05). Regarding prospects, a detailed analysis of the function through metagenomics and transcriptomics is needed.

New Rotor Position Redundancy Decoding Method Based on Resolver Decoder.

In view of the frequent safety problems of electric vehicles, the research on accurately obtaining the rotor position of the motor through the resolver is an important means to improve the functional safety of the system. The commonly used resolver decoding method involves the resolver decoding chip method and software decoding method, but few studies integrate the two decoding methods. A single method of motor rotor position acquisition cannot meet the requirements of system functional safety. To fill this gap, this paper proposes a method to simultaneously integrate hardware decoding and software decoding in the motor control system. The decoding chip and software decoding obtain the angle data at the same time, and they provide redundancy to improve the functional safety of the electronic control system. Finally, the effectiveness of the proposed simultaneous operation of hardware decoding and software decoding is verified by experiments.

Lactobacillus plantarum strains attenuated DSS-induced colitis in mice by modulating the gut microbiota and immune response.

Gut microbiota has become a new therapeutic target in the treatment of inflammatory Bowel Disease (IBD). Probiotics are known for their beneficial effects and have shown good efficacy in the clinical treatment of IBD and animal models of colitis. However, how these probiotics contribute to the amelioration of IBD is largely unknown. In the current study, the DSS-induced mouse colitis model was treated with oral administration of Lactobacillus plantarum strains to investigate their effects on colitis. The results indicated that the L. plantarum strains improved dysbiosis and enhanced the abundance of beneficial bacteria related to short-chain fatty acids (SCFAs) production. Moreover, L. plantarum strains decreased the level of pro-inflammatory cytokines, i.e., IL-17A, IL-17F, IL-6, IL-22, and TNF-α and increased the level of anti-inflammatory cytokines, i.e., TGF-ß, IL-10. Our result suggests that L. plantarum strains possess probiotic effects and can ameliorate DSS colitis in mice by modulating the resident gut microbiota and immune response.

Action Mechanism Underlying Improvement Effect of Fuzi Lizhong Decoction on Nonalcoholic Fatty Liver Disease: A Study Based on Network Pharmacology and Molecular Docking.

OBJECTIVE: This study aimed to decipher the bioactive compounds and potential mechanism of traditional Chinese medicine (TCM) formula Fuzi Lizhong Decoction (FLD) for nonalcoholic fatty liver disease (NAFLD) treatment via an integrative network pharmacology approach. METHODS: The candidate compounds of FLD and its relative targets were obtained from the TCMSP and PharmMapper web server, and the intersection genes for NAFLD were discerned using OMIM, GeneCards, and DisGeNET. Then, the PPI and component-target-pathway networks were constructed. Moreover, GO enrichment and KEGG pathway analysis were performed to investigate the potential signaling pathways associated with FLD's effect on NAFLD. Eventually, molecular docking simulation was carried out to validate the binding affinity between potential core components and key targets. RESULTS: A total of 143 candidate active compounds and 129 relative drug targets were obtained, in which 61 targets were overlapped with NAFLD. The PPI network analysis identified ALB, MAPK1, CASP3, MARK8, and AR as key targets, mainly focusing on cellular response to organic cyclic compound, steroid metabolic process, and response to steroid hormone in the biological processes. The KEGG pathway analysis demonstrated that 16 signaling pathways were closely correlated with FLD's effect on NALFD with cancer pathways, Th17 cell differentiation, and IL-17 signaling pathways as the most significant ones. In addition, the molecular docking analysis revealed that the core active compounds of FLD, such as 3'-methoxyglabridin, chrysanthemaxanthin, and Gancaonin H, had a high binding activity with such key targets as ALB, MAPK1, and CASP3. CONCLUSIONS: This study suggested that FLD exerted its effect on NAFLD via modulating multitargets with multicompounds through multipathways. It also demonstrated that the network pharmacology-based approach might provide insights for understanding the interrelationship between complex diseases and interventions of the TCM formula.

Resetting Weight Vectors in MOEA/D for Multiobjective Optimization Problems With Discontinuous Pareto Front.

When a multiobjective evolutionary algorithm based on decomposition (MOEA/D) is applied to solve problems with discontinuous Pareto front (PF), a set of evenly distributed weight vectors may lead to many solutions assembling in boundaries of the discontinuous PF. To overcome this limitation, this article proposes a mechanism of resetting weight vectors (RWVs) for MOEA/D. When the RWV mechanism is triggered, a classic data clustering algorithm DBSCAN is used to categorize current solutions into several parts. A classic statistical method called principal component analysis (PCA) is used to determine the ideal number of solutions in each part of PF. Thereafter, PCA is used again for each part of PF separately and virtual targeted solutions are generated by linear interpolation methods. Then, the new weight vectors are reset according to the interrelationship between the optimal solutions and the weight vectors under the Tchebycheff decomposition framework. Finally, taking advantage of the current obtained solutions, the new solutions in the decision space are updated via a linear interpolation method. Numerical experiments show that the proposed MOEA/D-RWV can achieve good results for bi-objective and tri-objective optimization problems with discontinuous PF. In addition, the test on a recently proposed MaF benchmark suite demonstrates that MOEA/D-RWV also works for some problems with other complicated characteristics.

Mechanism of the Gut Microbiota Colonization Resistance and Enteric Pathogen Infection.

The mammalian gut microbial community, known as the gut microbiota, comprises trillions of bacteria, which co-evolved with the host and has an important role in a variety of host functions that include nutrient acquisition, metabolism, and immunity development, and more importantly, it plays a critical role in the protection of the host from enteric infections associated with exogenous pathogens or indigenous pathobiont outgrowth that may result from healthy gut microbial community disruption. Microbiota evolves complex mechanisms to restrain pathogen growth, which included nutrient competition, competitive metabolic interactions, niche exclusion, and induction of host immune response, which are collectively termed colonization resistance. On the other hand, pathogens have also developed counterstrategies to expand their population and enhance their virulence to cope with the gut microbiota colonization resistance and cause infection. This review summarizes the available literature on the complex relationship occurring between the intestinal microbiota and enteric pathogens, describing how the gut microbiota can mediate colonization resistance against bacterial enteric infections and how bacterial enteropathogens can overcome this resistance as well as how the understanding of this complex interaction can inform future therapies against infectious diseases.