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Graphical abstract, The use of herbs to treat various human diseases has been recorded for thousands of years. In Asia's current medical system, numerous herbal formulas have been repeatedly verified to confirm their effectiveness in different periods, which is a great resource for drug innovation and discovery. Through the mining of these clinical effective formulas by network pharmacology and bioinformatics analysis, important biologically active ingredients derived from these natural products might be discovered. As modern medicine requires a combination of multiple drugs for the treatment of complex diseases, previously clinical formulas are also combinations of various herbs according to the main causes and accompanying symptoms. However, the herbs that play a major role in the treatment of diseases are always unclear. Therefore, how to rank each herb's relative importance and determine the core herbs, is the first step to assisting herb selection for active ingredients discovery. To solve this problem, we built the platform FangNet, which ranks all herbs on their relative topological importance using the PageRank algorithm, based on the constructed symptom-herb network from a collection of clinical empirical prescriptions. Three types of herb hidden knowledge, including herb importance rank, herb-herb co-occurrence, and associations to symptoms, were provided in an interactive visualization. Moreover, FangNet has designed role-based permission for teams to store, analyze, and jointly interpret their clinical formulas, in an easy and secure collaboration environment, aiming at creating a central hub for massive symptom-herb connections. FangNet can be accessed at http://fangnet.org or http://fangnet.herb.ac.cn.

Objective To search for specific metabolites in the lungs of pneumonia rats fed with a high-calorie diet, as well as explore the changes in the lung metabolites of young rats treated with Yinlai Decoction (YD) and its effects on inflammation-related metabolic pathways. Methods Lipopolysaccharides (LPS) and a special high-calorie diet were used to induce Sprague Dawley (SD) rats to simulate the intestinal state of infant pneumonia. Liquid chromatography-mass spectrometry technology (LC-MS/MS) was used to detect metabolites in each group. Supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model values were used for the detection results to find the differential metabolites. The metabolic pathways that are involved with the differential metabolites were clarified through enrichment analysis and topological analysis. Finally, the T cell receptor signaling pathway (TCR) signal conversion was analyzed by the network pharmacology method. Results In the high-calorie diet combined with pneumonia group (M3), a total of 55 metabolites were determined to be different from the normal group (N). A total of 36 metabolites were determined to be different from those in the lung metabolites of the YD treatment group (T1). YD had a regulatory effect on glutathione metabolism, arginine and proline metabolism, ascorbic acid and aldehyde metabolism and phenylalanine metabolism. And the small molecule metabolites could act on the FYN and lymphocyte-specific protein tyrosine kinase (LCK) target proteins in the TCR signaling pathway, thereby affecting the immune function of the lungs. Conclusion A high-calorie diet can cause abnormal sphingolipid metabolism in the lungs of young rats, thereby creating chronic lung inflammation in young rats. YD has a beneficial effect when used to treat young rats with LPS-induced pneumonia fed on high-calorie diets. Its mechanisms of action may affect the body’s immune pathways by regulating the oxidative stress pathway affected by glutathione metabolism.

The intestinal flora plays an important role in the inflammatory response to the systemic or local infections in the host. A high-calorie diet has been shown to aggravate pneumonia and delay recovery, especially in children. However, the underlying mechanisms remain unclear. Our previous studies demonstrated that a high-calorie diet and LPS atomization synergistically promoted lung inflammation injury in juvenile rats. In this study, specific pathogen-free juvenile rats were placed in a routine environment, and subjected to a high-calorie diet or LPS atomization in isolation as well as combination. Our data revealed that LPS nebulization combined with a high-calorie diet resulted in significant changes in rats, such as slow weight gain, increased lung index, and aggravated lung inflammatory damage. Meanwhile, we found that the aggravation of LPS-induced pneumonia by a high-calorie diet disturbs the balance of Th17/Treg cells. Furthermore, high-throughput sequencing of intestinal contents revealed that a high-calorie diet changed the gut microbiome composition, decreased microbial diversity, and particularly reduced the abundance of the intestinal microbiota associated with the production of short-chain fatty acids (SCFAs) in rats. Consequently, the levels of SCFAs, especially acetate, propionate, and butyrate, were significantly decreased following the intervention of a high-calorie diet. More critically, the effects of a high-calorie diet were shown to be transmissible among pneumonia rats through cohousing microbiota transplantation. Taken together, we provide evidence to support that a high-calorie diet can potentially reset the gut microbiome and metabolites, disrupt Th17/Treg cell balance and immune homeostasis, and aggravate LPS-induced lung inflammatory damage, which may provide a new perspective on the pathogenesis of lung inflammation injury, and suggest a novel microbiota-targeting therapy for inflammatory lung diseases.

Objective: To investigate the association between gastrointestinal heat retention syndrome (GHRS) and adult chronic eczema. Methods: This case–control study compared GHRS/GHRS accompanied by damp-heat syndrome (GHRS-DHS) and other patient characteristics between subjects with (cases) and without chronic eczema (controls) to identify potential factors associated with this condition. Semi-structured questionnaires were used to collect data via face-to-face interviews. Participants were recruited from Dongzhimen Hospital affiliated with Beijing University of Chinese Medicine. A logistic regression analysis was performed on the collected data, and odds ratios (ORs) were calculated. Results: A total of 168 cases and 172 controls were recruited. Among the cases of adult chronic eczema, there were 79 subjects with GHRS and 68 with GHRS-DHS. Sex (P = .02, OR = 0.54, 95% confidence interval [CI]: 0.32–0.91), GHRS (P = .04, OR = 1.90, 95% CI: 1.02–3.51), GHRS-DHS (P

Objective: Bushen Chengyun granule (BCG) is an empirical treatment for female infertility (FI) caused by low endometrial receptivity (LER) involving a poorly understood mechanism. In this study, network pharmacology was used to explore the potential therapeutic mechanism of BCG on FI caused by LER. Methods: The corresponding herb targets were obtained by conducting a search in the Traditional Chinese Medicine Systems Pharmacology Database and PubMed-reported literature. Disease targets were obtained from the following databases: Comparative Toxicogenomics Database, Human Phenotype Ontology, and Therapeutic Target Database. Treatments for LER using BCG have used target matching (BCG – LER target). Then, the predicted targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins database for gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Furthermore, triptorelin acetate for injection + menotrophin + chorionic gonadotropin for injection were used to establish a mouse model of blastocyst implantation disorder and to evaluate the in vivo effect of BCG on blastocyst implantation. Results: Overall, 156 bioactive chemical components and 1092 targets of BCG were identified. The results indicated that 482 biological processes (FDR

Intestinal flora plays an important role in inflammatory response to systemic or local organs of its host. High calorie diet has been shown to aggravate the condition of pneumonia and delay recovery, especially in children. However, the underlying mechanisms remain unclear. This study placed SPF rats in a conventional environment, high calorie diet or LPS atomization was performed respectively or combined. Analysis of high-throughput sequencing of intestinal content combined with animal weight, organ index, serum inflammatory factors indicators and bioinformatics found that after pulmonary infection combined with a high-calorie diet, rats showed significant changes such as weight loss and increased lung weight index, and their lung and intestinal tissues showed more obvious inflammatory changes. And its gut flora structure suggests, the abundance of Leuconostocaceae in significantly reduced; abundance of Staphylococcus, Planococcaceae, Staphylococcus, Staphylococcaceae, Bacillales, Gemellales and Aerococcus significant increased. The study showed that high calorie diet and LPS atomization synergistically promoted pneumonia process in rat pups, which is related to changes in structure of intestinal flora. It is worth noting that pneumonia rats fed by convention diet also causing intestinal flora imbalance.

Background Communication between colorectal cancer and stromal cells alters the tumor microenvironment to regulate locoregional disease and cancer progression. However, colon cancer–stromal cell interactions are difficult to study in vivo. Limitations of existing animal models include the use of immunocompromised mice, the inability to genetically modify a cell population in a single organ system, or a lack of anatomic context. Our goal was to develop a novel mouse model of colorectal cancer that is capable of studying tumor-stromal cell interactions in the native colon of immune-competent mice. Methods Primary mouse myofibroblasts were isolated from the colon of C57BL/6 mice and were grown in cell culture. Genetically defined (ApcΔ/Δ; Kras G12D/+; Trp53Δ/Δ) primary mouse colon cancer cells were suspended in serum-free media (20 μL) at varying concentrations (5 × 103 to 4 × 104 cells) either alone or in combination with syngeneic myofibroblasts (2 × 105 cells). After isoflurane anesthesia, a colonoscopy was performed on immune-competent 8- to 10-week-old C57BL/6 mice with endoscopic microinjection of the cell suspension into the submucosal space of the colon wall utilizing a small animal colonoscope. Surveillance endoscopy was used to assess for tumor growth, along with histologic analysis. Tumor size is presented on a grading system based on tumor diameter relative to colon circumference. Results A total of 33 mice were injected with a survival rate of 88% (29/33). Endoscopic microinjection of colorectal cancer cells resulted in dose-dependent tumor growth in the distal mouse colon that could be assessed endoscopically without animal sacrifice. Growth curves varied depending on the concentration of injected colorectal cancer cells, with no growth at the lowest concentration of injected cells (5 × 103 cells), progressive growth over 4 wk using 1-2 × 104 cells, while the highest colorectal cancer cell concentration (4 × 104 cells) led to larger tumors at week 1 followed by a steady decline in tumor growth over the 4-wk time period. Combined microinjection of 2 × 104 colorectal cancer cells with 2 × 105 myofibroblasts resulted in much larger tumors that persisted over the 4-wk time period and which were composed primarily of colorectal cancer cells. Immunofluorescence microscopy after coinjection of colorectal cancer cells with green fluorescent protein positive myofibroblasts confirmed that the injected myofibroblasts are present and remain viable over the 4-wk time period. Conclusions Endoscopic submucosal microinjection of primary mouse colorectal cancer cells is feasible and leads to reliable and reproducible short-term growth of colon tumors in immune-competent mice. Coinjection of primary mouse colorectal cancer cells with syngeneic myofibroblasts leads to enhanced tumor growth. Coimplantation of colorectal cancer cells with syngeneic myofibroblasts provides a novel platform to study tumor-stromal interactions in the native colon of immune-competent mice.

We intended to explore the mechanism ofThirty Sprague-Dawley rats were randomly assigned to the blank control group (N), the pneumonia group (P), and theLung tissue inflammation was prevented by

Background Increasing attention has been paid to the potential relationship between gut and lung. The bacterial dysbiosis in respiratory tract and intestinal tract is related to inflammatory response and the progress of lung diseases, and the pulmonary diseases could be improved by regulating the intestinal microbiome. This study aims to generate the knowledge map to identify major the research hotspots and frontier areas in the field of gut–lung axis. Materials and methods Publications related to the gut–lung axis from 2011 to 2021 were identified from the Web of Science Core Collection. CiteSpace 5.7.R2 software was used to analyze the publication years, journals, countries, institutions, and authors. Reference co-citation network has been plotted, and the keywords were used to analyze the research hotspots and trends. Results A total of 3315 publications were retrieved and the number of publications per year increased over time. Our results showed that Plos One (91 articles) was the most active journal and The United States (1035 articles) published the most articles. We also observed the leading institution was the University of Michigan (48 articles) and Huffnagle Gary B, Dickson Robert P and Hansbro Philip M, who have made outstanding contributions in this field. Conclusion The Inflammation, Infection and Disease were the hotspots, and the regulation of intestinal flora to improve the efficacy of immunotherapy in lung cancer was the research frontier. The research has implications for researchers engaged in gut–lung axis and its associated fields.

In this work, we show that the modified ghost fluid method might suffer overheating and leads to inaccurate numerical results when directly applied to a moving rigid boundary with acceleration. We discover the insightful reasons and then develop a new technique to take into account the effect of boundary acceleration on the definition of ghost fluid states based on a generalized Piston–Riemann problem. Theoretical analysis and numerical results show that the modified ghost fluid method with acceleration correction can overcome such difficulty effectively.

In this paper, a third-order reconstructed DG( p 1 p 2 ) method based on the variational reconstruction (VR) (Wang et al., 2017 [24] ) is developed for simulating the two dimensional steady-state compressible flows on unstructured and hybrid grids. The proposed method combines the advantages of the DG discretization with the flexibility of the variational reconstruction, which exhibits its superior potential in enhancing the level of accuracy compared to the underlying DG method. In this variational rDG( p 1 p 2 ) method, the low order degrees of freedom are evolved through the underlying DG( p 1 ) method, while the high order degrees of freedom are reconstructed through the variational reconstruction, in which the constitutive relations are built by minimizing the so-called ‘cost function’. The cost function is defined by the total interfacial jump integration in the computational domain using the variational method. The large sparse linear system resulted by the variational reconstruction is solved in an efficient way coupled with the temporal discretization for the steady-state simulations. A number of test cases are presented to assess the performance of the new high order variational rDG( p 1 p 2 ) method.

In this work, an adjoint-based airfoil shape optimization algorithm is developed based on the adaptive isogeometric discontinuous Galerkin method for compressible Euler equations to investigate the significance of each design variable of airfoil B-spline parameterization. We first parameterize the airfoil by B-spline curve approximation with some control points viewed as design variables, and build the B-spline representation of the flow field with the curve to apply the goal-oriented h -adaptive isogeometric DG method for flow solution. Then we compute and employ the discrete adjoint solutions for both multi-target error estimation in adaptive mesh refinement. With the isogeometric nature, not only all the geometrical cells but also the numerical basis functions can be analytically expressed by the design variables, indicating that the numerical solutions and objective could be differentiable with respect to those variables. Consequently, the gradient is totally computed in an accurate approach, and the sensitivity analysis is thus improved, by reducing the spatial discretization error and introducing the analytical expression of derivative, to reveal the key parameters for optimization in an intuitive and efficient manner. Although the SQP optimization algorithm is adopted in the paper, the given accurate gradient can be applied to any gradient-based optimization algorithm. The proposed algorithm is demonstrated on RAE2822 airfoil with inviscid transonic flow, where the shape is optimized to minimize the drag coefficient at a constrained lift and airfoil area. The numerical results show that the drag is much more sensitive to the design variables near the tailing edge at the beginning but sensitivity is reduced when optimal.

Objective: Pediatric pneumonia is a common respiratory disease and Yinlai Decoction (YLD) is a commonly used treatment in China. We explored the anti-inflammatory mechanism of action of this traditional Chinese medicine for pneumonia. Methods: We studied, by experimentation, the mechanism of action of YLD in treating pneumonia according to network pharmacology. By comparing YLD with dexamethasone (DXMS), we investigated the efficacy of YLD in treating pneumonia induced by lipopolysaccharide (LPS) in juvenile rats. Results: In an aqueous extract of YLD, 22 chemical compounds were identified, among which 10 were related to inflammation, involving 78 target genes and 16 signaling pathways. Among them, 45 core target proteins were related to biologic processes and functions, such as response to stimuli, biologic regulation, cell communication and protein binding. Animal experiments showed that YLD relieved pulmonary inflammation and demonstrated no significant damage to the liver, spleen or kidneys of rats. YLD could regulate expression of inflammatory cytokines in serum and inflammation-related proteins in lung tissues to some extent, but its effect is less significant than that of DXMS. Conclusions: YLD protected juvenile rats against LPS-induced pneumonia, and showed fewer side effects in comparison with DXMS. YLD could be efficacious treatment for pediatric respiratory infections and even pneumonia. Keywords: Pediatric pneumonia, Yinlai decoction, Traditional Chinese medicine, Network pharmacology, Immunity

In this work, a solution remapping technique is developed to accelerate the flow convergence for the intermediate shapes when a high-order discontinuous Galerkin (DG) method is employed as a compressible Euler flow solver in the airfoil design problems. Once the shape is updated, the proposed technique is applied to initialize the flow simulation for the new shape via a solution remapping formula and a maximum-and-minimum-preserving limiter. First, the solution remapping formula is used to remap the solution of the current shape into a piecewise polynomial on the mesh of the new shape. Then the piecewise polynomial is constrained with the maximum-and-minimum-preserving limiter. The modified piecewise polynomial is used as the initial value for the new shape. Numerical experiments show that the proposed technique can attractively accelerate flow convergence and significantly reduce up to 80% of the computational time in the airfoil design problems with a high-order DG solver.

Level set (LS) method is a widely used interface capturing method. In the simulations of incompressible two-phase flows, in order to avoid discontinuities at interfaces, the LS function is usually taken as a smeared-out Heaviside function bounded on [0, 1] and advected by a given velocity field $$\mathbf {u}$$ obtained from the solution of the incompressible Navier-Stokes equations. In the incompressible limit $$\nabla \cdot \mathbf {u}=0$$ , the advection equation for the LS function can be written and discretized in conservative form. However, due to numerical errors, the resulting velocity field is in general not divergence free which leads to the solution of the advection equation in conservative form does not satisfy the maximum principle. To overcome this issue, in this work, we develop a high-order discontinuous Galerkin (DG) method to directly solve the advection equation for the LS function in non-conservative form. Moreover, we prove that by applying a linear scaling limiter, the proposed method together with a strong stability preserving (SSP) time discretization scheme can satisfy the strict maximum principle under a suitable CFL condition. Numerical simulations of several well-known benchmark problems, including the application to incompressible two-phase flows, are presented to demonstrate the high-order accuracy and maximum-principle-satisfying property of the proposed method.

Background: Honeysuckle is a traditional Chinese herbal medicine. It is widely used in the treatment of respiratory infectious diseases in Asia and even worldwide reported in the literature. However, its mechanism remains unclear. Pneumonia is one of the most common clinical manifestations of respiratory infections. This study is aim to find out the molecular mechanism of honeysuckle in the treatment of pneumonia.Methods: LPS-induced pneumonia rats were administered with honeysuckle decoction and compared its efficacy with dexamethasone. The components in honeysuckle decoction were analyzed by liquid-phase mass spectrometry. The target proteins for those components were obtained by database search, target fishing and text mining methods, and then were matched with the genes of pneumonia in the CTD database. Analyzed interactions of target protein by using String database, enrichment analysis by David database, molecular docking was performed by AUTODOCK and PyRx. Its related network diagrams drew by Cytoscape.Results: Our results indicate that honeysuckle can alleviate the inflammation of rat lung tissue to a certain extent, and has similar therapeutic effects as dexamethasone. There are 31 compounds in honeysuckle, and 366 genes associated with these compounds and pneumonia. Among them, 18 of the top 5%, including GAPDH, TNF, FOS, VEGFA, BDNF, etc., were enriched in pathway closely related to pneumonia: Glycine, serine and threonine metabolism, Nitrogen metabolism, and Neuroactive ligand-receptor interaction, etc. The results of molecular docking confirmed that Inosito binds to the PTEN protein of the Phosphatidylinositol signaling system pathway.Conclusions: This study suggests that honeysuckle can play a role in the treatment of pneumonia by affecting multiple targets and pathways, of which Inosito-PTEN-Phosphatidylinositol signaling system may be the most important mechanism. This reflects the multi-target multi-pathway of traditional Chinese medicine, and has a certain specific therapeutic effect on the disease. By interfering with the signaling pathways of the body cells, honeysuckle can be used as a drug candidate for clinical pneumonia treatment.

In this work, we develop a quasi-conservative discontinuous Galerkin method for the simulation of compressible gas-gas and gas-water two-medium flows by solving the five-equation transport model. This spatial discretization is a direct extension of the quasi-conservative finite volume discretization to the discontinuous Galerkin framework, thus, preserves uniform velocity and pressure fields at an isolated material interface. Furthermore, for discontinuities with a large pressure ratio, low density, and a dramatic change of material property where nonphysical values may occur, a strategy for imposing the bound-preserving limiting for volume fraction and a positivity-preserving limiting for density of each fluid and internal energy is developed and analyzed based on the quasi-conservative DG( $$p_1$$ ) discretization. Typical test cases for both one- and two-dimensional problems are provided to demonstrate the performance of the proposed method.

Background Pneumonia is a common respiratory disorder, which brings an enormous financial burden to the medical system. However, the current treatment options for pneumonia are limited because of drug resistance and side effects. Our previous study preliminarily confirmed that Yinlai Decoction (YD), a common prescription for pneumonia in clinical practice, can regulate the expression of inflammatory factors, but the mechanisms are unknown yet. Methods In our work, a method named network pharmacology was applied, which investigated the underlying mechanisms of herbs based on a variety of databases. We obtained bioactive ingredients of YD on TCMSP database and collected potential targets of these ingredients by target fishing. Then the pneumonia-related targets database was built by TTD, Drugbank, HPO, OMIM, and CTD. Based on the matching targets between YD and pneumonia, the PPI network was built by STRING to analyze the interactions among these targets and then input into Cytoscape for further topological analysis. DAVID and KEGG were utilized for GO and pathway enrichment analysis. Then rat model based on LPS stimulated pneumonia was used to verify the possible mechanism of YD in treating pneumonia. Results Sixty-eight active ingredients, 103 potential targets and 8 related pathways, which likely exert a number of effects, were identified. Three networks were constructed using Cytoscape, which were herb-component-network, YD-pneumonia target network, and herb-component-YD target-pneumonia network. YD was verified to treat LPS-induced pneumonia by regulating the inflammatory factor IL-6, which was a predicted target. Conclusion Network analysis indicated that YD could alleviate the symptoms and signs of pneumonia through regulating host immune inflammatory response, angiogenesis and vascular permeability, the barrier function of the airway epithelial cells, hormone releasing and cell growth, proliferation, and apoptosis.

In this work, we use exact solutions of one-dimensional Burgers equation to train an artificial neuron as a shock wave detector. The expression of the artificial neuron detector is then modified into a practical form to reflect admissible jump of eigenvalues. We show the working mechanism of the practical form is consistent with compressing or intersecting of characteristic curves. In addition, we prove there is indeed a discontinuity inside the cell detected by the practical form, and smooth extrema and large gradient regions are never marked. As a result, we apply the practical form to numerical schemes as a shock wave indicator with its easy extension to multi-dimensional conservation laws. Numerical results are present to demonstrate the robustness of the present indicator under Runge–Kutta Discontinuous Galerkin framework, its performance is generally compared to TVB-based indicators more efficiently and accurately. To treat the initial inadmissible jumps, including linear contact discontinuities and those evolving into rarefaction waves, a preliminary strategy of combining a traditional indicator in the beginning with the present indicator is suggested. We believe the present indicator can be applied to unstructured mesh in the future.

In general, it needs to take about nearly 10 grid points inside a wall boundary layer for low accuracy order methods to get satisfactory wall-normal gradient related results, such as friction coefficient and wall heat flux. If there exist extreme points inside the boundary layer, this situation becomes even worse. In this work, with the help of the analytic solution of the one-dimensional steady compressible Navier-Stokes equations under some restrictions, we show that the flow variables actually vary in the form of an exponential function instead of a polynomial one inside the boundary layer. Then, we propose an exponential space for approximating the solutions inside the boundary layer and numerically implementing it in the frame of direct discontinuous Galerkin (DDG) method. We show that the DDG methods based on the exponential boundary-layer space give much better numerical results for both conservative variables and wall-normal gradients than those with the standard polynomial space. Generally only 1–2 grid points inside the boundary layer are demanded to resolve the wall boundary layer to obtain satisfactory wall-normal gradients under the exponential space. Preliminary extension to two-dimensional laminar boundary-layer flow shows a similar performance of the proposed exponential boundary-layer space, exhibiting its potential applications in high dimensions.

Introduction The myofibroblast is a gastrointestinal stromal cell that is a target of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine strongly implicated in colitis-associated cancer. Crosstalk between TNF-α and other pro-inflammatory mediators amplify inflammatory signaling but the mechanism is unknown. Angiogenin (ANG) is a 14-kDa angiogenesis protein that is regulated in patients with inflammatory bowel disease. However, the role of ANG on inflammatory mediator crosstalk in the myofibroblast is unknown. Methods The human colonic myofibroblast cell line 18Co, as well as primary mouse and human colonic myofibroblasts, were exposed to TNF-α (10 ng/ml) and bradykinin (BK, 100 nM). ANG was quantified by ELISA. The expression of cyclo-oxygenase-2 (COX-2) and phosphorylation of PKD was assessed by Western Blot. Results Primary mouse and human colonic myofibroblasts exposed to TNF-α/BK led to enhanced PKD phosphorylation and synergistic COX-2 expression. 18Co cells secrete high levels of ANG (24h, 265 ± 5 pg/ml). The monoclonal antibody 26-2F, which neutralizes ANG, inhibited TNF-α/BK-mediated PKD phosphorylation and synergistic COX-2 expression in primary human myofibroblasts. Likewise, in primary mouse myofibroblasts that do not express ANG (ANG-KO), TNF-α/BK failed to enhance PKD phosphorylation and COX-2 expression. Conclusions TNF-α/BK enhance PKD phosphorylation and COX-2 expression in primary mouse and human colonic myofibroblasts. Angiogenin is produced by the myofibroblast, and inhibition of ANG signaling, either by its absence (ANG-KO) or by pharmacologic inhibition, blocks enhanced PKD phosphorylation and synergistic COX-2 expression induced by TNF-α/BK. ANG mediates crosstalk signaling between TNF-α/BK in the regulation of stroma-derived COX-2 and may be a novel therapeutic target for the management of colitis-associated cancer.

Traditional Chinese medicine (TCM) was widely used in the treatment of recurrent respiratory tract infections (RRTIs) in East Asia, but its mechanism was not clear because of its complex prescription rules. This research prospectively collected 100 prescriptions of RRTI children treated with TCM. The characteristics of TCM in prescriptions were described and analyzed, and the rules of prescriptions were analyzed by hierarchical clustering and association rules. The results showed that the principle of RRTI was to pay equal attention to cold and mild, and six new meaningful prescriptions were obtained. Among them, the new prescription composed of Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu), Saposhnikoviae Radix (Fangfeng), Angelicae Sinensis Radix (Danggui), and Paeoniae Radix Rubra (Chishao) was an important method to treat RRTI. In order to explore the mechanism of the new prescription, the research obtained the action target of each herb of the core prescription on Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine, TCMIP v2.0. The target genes were enriched by Metascape, and 93 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. According to the classification and statistics of KEGG type, it was found that the new prescription mainly intervened in the metabolic pathway dominated by amino acid metabolism. In addition, there were also many interventions in the nervous system-, endocrine system-, and digestive system-related pathways. This study summarized the prescription rule of TCM in the treatment of RRTI, analyzed the mechanism of supplementing deficiency, and provided a new idea for the treatment of RRTI.

Additional file 1:Table S1. Active ingredients and ADME parameters of YD. Table S2. Target information of related active ingredients. Table S3. The relationship between active ingredients and potential targets.

Usually, the temperature dependence of specific heats is neglected or the specific heats are frozen in interface computations for compressible two-material flows. In this paper, we present a practical interface treatment to faithfully capture the effect of high temperature on interface evolutions. A general technique for solving the Riemann problem equipped with a wide variety of equations of state (EOS) is established. In a unified framework for computing the interfacial states, it provides a convenient way to deal with the thermally perfect gas (PG) that considers the effect of temperature on specific heats. The algorithm of the complete and exact solution to Riemann problem with thermally PG is also designed in detail. Based on this technique, the modified ghost fluid method with an approximate Riemann solver is further extended to handle the interface of two-material flows involving thermally PG with chemical reactions. Several typical problems are selected to validate and test the present algorithm for the interaction between the thermally PG and other gases or liquids. The results indicate that the present algorithm enables an effective implementation for simulating various two-material multi-species flows with different types of EOS. As temperature increases, the behavior of the interfacial flows under the assumption of thermally PG EOS gradually differs from that under the assumption of calorically PG EOS.

In this work, an integral exact solution is proposed for one-dimensional elastic-perfectly plastic solid Riemann problem. Owing to the possible existence of elastic to plastic “phase” transition within the solid, the exact solution of its Riemann problem is much more complicated than that for the medium equipped with a uniform equation of state (EOS) or constitutive model. By constructing a five-equation hyperbolic governing system fully describing the nonlinear behavior of the solid in the Eulerian reference frame and scrutinizing every possible wave pattern of its Riemann problem, we acquire a complete list of exact solutions that contains as many as sixty-four different solution types neglecting the generation of vacuum. Each type of exact solutions is presented, and numerical simulations agree well with the obtained theoretical results.

In this paper, a class of new high order reconstructed DG (rDG) methods based on the compact least-squares (CLS) reconstruction [23] , [24] is developed for simulating the two dimensional steady-state compressible flows on hybrid grids. The proposed method combines the advantages of the DG discretization with the flexibility of the compact least-squares reconstruction, which exhibits its superior potential in enhancing the level of accuracy and reducing the computational cost compared to the underlying DG methods with respect to the same number of degrees of freedom. To be specific, a third-order compact least-squares rDG( p 1 p 2 ) method and a fourth-order compact least-squares rDG( p 2 p 3 ) method are developed and investigated in this work. In this compact least-squares rDG method, the low order degrees of freedom are evolved through the underlying DG( p 1 ) method and DG( p 2 ) method, respectively, while the high order degrees of freedom are reconstructed through the compact least-squares reconstruction, in which the constitutive relations are built by requiring the reconstructed polynomial and its spatial derivatives on the target cell to conserve the cell averages and the corresponding spatial derivatives on the face-neighboring cells. The large sparse linear system resulted by the compact least-squares reconstruction can be solved relatively efficient when it is coupled with the temporal discretization in the steady-state simulations. A number of test cases are presented to assess the performance of the high order compact least-squares rDG methods, which demonstrates their potential to be an alternative approach for the high order numerical simulations of steady-state compressible flows.

In this paper, an adjoint-based high-order h-adaptive direct discontinuous Galerkin method is developed and analyzed for the two dimensional steady state compressible Navier–Stokes equations. Particular emphasis is devoted to the analysis of the adjoint consistency for three different direct discontinuous Galerkin discretizations: including the original direct discontinuous Galerkin method (DDG), the direct discontinuous Galerkin method with interface correction (DDG(IC)) and the symmetric direct discontinuous Galerkin method (SDDG). Theoretical analysis shows the extra interface correction term adopted in the DDG(IC) method and the SDDG method plays a key role in preserving the adjoint consistency. To be specific, for the model problem considered in this work, we prove that the original DDG method is not adjoint consistent, while the DDG(IC) method and the SDDG method can be adjoint consistent with appropriate treatment of boundary conditions and correct modifications towards the underlying output functionals. The performance of those three DDG methods is carefully investigated and evaluated through typical test cases. Based on the theoretical analysis, an adjoint-based h-adaptive DDG(IC) method is further developed and evaluated, numerical experiment shows its potential in the applications of adjoint-based adaptation for simulating compressible flows.

To date, there are very few studies on the transition beyond second Hopf bifurcation in a lid–driven square cavity, due to the difficulties in theoretical analysis and numerical simulations. In this paper, we study the characteristics of the third Hopf bifurcation in a driven square cavity by applying a consistent fourth-order compact finite difference scheme rectently developed by us. We numerically identify the critical Reynolds number of the third Hopf bifurcation located in the interval of (13944.7021,13946.5333) by the method of bisection. Through Fourier analysis, it is discovered that the flow becomes chaotic with a characteristic of period-doubling bifurcation when the Reynolds number is beyond the third bifurcation critical interval. Nonlinear time series analysis further ascertains the flow chaotic behaviors via the phase diagram, Kolmogorov entropy and maximal Lyapunov exponent. The phase diagram changes interestingly from a closed curve with self-intersection to an unclosed curve and the attractor eventually becomes strange when the flow becomes chaotic.

In a recent work Feng, Liu and Wang (2020) [10] , we imbedded characteristic compressing into an artificial neuron (AN) to propose a shock wave indicator on uniform mesh. In this work, the indicator is developed to unstructured grid. To achieve that, we retrain an AN on 1D randomly perturbed mesh, two prior information, (a) eigenvalue variable and (b) side-weighted average, is used in data pre-processing for reducing the influence of mesh size and keeping AN structure simple. The output of AN is then modified into a generalized and explicable form, which is used as the present shock wave indicator. We show that the troubled-cells detected by the present indicator include discontinuities caused by compressing of characteristic curves. The present indicator is then extended to multi-dimensional unstructured grid through constructing side-weighted average of eigenvalue on each spatial dimension. Numerical results are presented to demonstrate the performance of the present indicator combined with slope limiter and artificial viscosity, respectively, on various unstructured grids, the results show that the present indicator can detect shock and contact waves with low noise, and improves the indicating efficiency as well, the present indicator provides an attractive alternative in detecting shock waves on arbitrary grids and can be combined with various discontinuity-processing techniques.

In this paper, a residual-based h-adaptive high-order reconstructed DG (rDG) method based on the hybrid reconstruction strategy is developed for solving the compressible Euler equations on unstructured grids. The proposed method combines the advantages of high-order rDG discretization with appropriate residual-based error estimation techniques and h-adaptive refinement strategies, which exhibits its superior potential compared to the underlying DG methods. To be specific, a third-order hybrid rDG(p1p2) method has been carefully designed and evaluated on incompatible quadrilateral grids with hanging nodes in order to preserve 2-exactness property during the implementation of mesh refinement and coarsening. A residual-based error estimator is used as local error indicator during the h-adaptive procedures. A number of test cases are presented to assess the performance of the high-order h-adaptive rDG method. The hybrid reconstruction strategy combined with h-adaptive techniques presented in this work demonstrates promise for improving the level of accuracy and reducing the computational cost for numerical simulations of compressible inviscid flows.

Riemann-problem-solver-based ghost fluid method (GFM) provides us an effective manner to simulate compressible gas-liquid flows. Interfacial parameters are indispensable to define interface conditions and usually solved by an implicit approximate Riemann problem solver (ARPS). In this work, we design explicit pressure-based/velocity-based ARPS with a stiffened equation of state. Moreover, the ranges of application of these implicit and explicit ARPSs are discussed in detail. Equipped with these explicit ARPSs, it is more convenient to utilize the idea of modified GFM (MGFM) or practical GFM (PGFM) to define ghost fluid states in numerical applications. Results from the proposed explicit method compare well with that from the implicit method. Especially the PGFM with the present explicit velocity-based ARPS is more widely used and more efficient for large scale scientific computation.

Objective To examine the effects of accumulated heat in GI tract (AHGIT) on lung tissue protein expression in pneumonic mice. Methods Nebulized lipopolysaccharides (LPS) were administered to induce a pneumonic mouse model (M1), and a high-calorie/protein diet combined with nebulized LPS was used to induce AHGIT pneumonia (M2). Isobaric tag for relative and absolute quantitation (iTRAQ) proteomics was applied to study lung protein expression, followed by bioinformatics analysis. Results M1 mice developed alveolar damage with prominent septum thickening, vascular dilation, hyperaemia and infiltration of large amounts of inflammatory cells. M2 mice developed more severe pathological responses. A total of 2626 proteins were reliably identified in the lung tissue. Compared with normal mice, the M1 mice had 344 differentially expressed proteins in their lungs, which are involved in the following biological processes: response to organic substance, response to cytokine, response to external stimulus, defense response and immune system process. They are also involved in the following Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways: ECM-receptor interaction, leukocyte transendothelial migration, Fc gamma R-mediated phagocytosis, complement and coagulation cascades, and antigen processing and presentation. Compared with the M1 group, the M2 mice had 164 differentially expressed proteins in their lungs, including 14 upregulated and 150 downregulated proteins. These proteins are involved in the following biological processes: small molecule metabolism, ribose phosphate metabolic process, cell adhesion and biological adhesion. The relevant KEGG pathways included oxidative phosphorylation, Citrate cycle (TCA cycle), complement and coagulation cascades, and vascular smooth muscle contraction. Conclusions AHGIT aggravated the lung inflammatory damage in the mice with LPS-induced pneumonia. It may affect the mouse substance/energy metabolism, and therefore the immune function, to aggravate the LPS-induced inflammatory damage.

A parallel, high-order direct Discontinuous Galerkin (DDG) method has been developed for solving the three dimensional compressible Navier-Stokes equations on 3D hybrid grids. The most distinguishing and attractive feature of DDG method lies in its simplicity in formulation and efficiency in computational cost. The formulation of the DDG discretization for 3D Navier-Stokes equations is detailed studied and the definition of characteristic length is also carefully examined and evaluated based on 3D hybrid grids. Accuracy studies are performed to numerically verify the order of accuracy using flow problems with analytical solutions. The capability in handling curved boundary geometry is also demonstrated. Furthermore, an SPMD (single program, multiple data) programming paradigm based on MPI is proposed to achieve parallelism. The numerical results obtained indicate that the DDG method can achieve the designed order of accuracy and is able to deliver comparable results as the widely used BR2 scheme, clearly demonstrating that the DDG method provides an attractive alternative for solving the 3D compressible Navier-Stokes equations.

The equation of state (EOS) plays a crucial role in hyperbolic conservation laws for the compressible fluid. Whereas, the solid constitutive model with elastic-plastic phase transition makes the analysis of the solid Riemann problem more difficult. In this paper, one-dimensional elastic-perfectly plastic solid Riemann problem is investigated and its exact Riemann solver is proposed. Different from previous works treating the elastic and plastic phases integrally, we resolve the elastic wave and plastic wave separately to understand the complicate nonlinear waves within the solid and then assemble them together to construct the exact Riemann solver for the elastic-perfectly plastic solid. After that, the exact solid Riemann solver is associated with the fluid Riemann solver to decouple the fluid-solid multi-material interaction. Numerical tests, including gas-solid, water-solid high-speed impact problems are simulated by utilizing the modified ghost fluid method (MGFM).

An isogeometric discontinuous Galerkin method for Euler equations is proposed. It integrates the idea of isogeometric analysis with the discontinuous Galerkin framework by constructing each element through the knots insertion and degree elevation techniques in non-uniform rational B-splines. This leads to the solution inherently shares the same function space as the non-uniform rational B-splines representation, and results in that the curved boundaries as well as the interfaces between neighboring elements are naturally and exactly resolved. Additionally, the computational cost is reduced in contrast to that of structured grid generation. Numerical tests demonstrate that the presented method can be high order of accuracy and flexible in handling curved geometry. Copyright © 2016 John Wiley & Sons, Ltd.

A Direct Discontinuous Galerkin (DDG) method is developed for solving the compressible NavierStokes equations on arbitrary grids in the framework of DG methods. The DDG method, originally introduced for scalar diffusion problems on structured grids, is extended to discretize viscous and heat fluxes in the NavierStokes equations. Two approaches of implementing the DDG method to compute numerical diffusive fluxes for the NavierStokes equations are presented: one is based on the conservative variables, and the other is based on the primitive variables. The importance of the characteristic cell size used in the DDG formulation on unstructured grids is examined. The numerical fluxes on the boundary by the DDG method are discussed. A number of test cases are presented to assess the performance of the DDG method for solving the compressible NavierStokes equations. Based on our numerical results, we observe that DDG method can achieve the designed order of accuracy and is able to deliver the same accuracy as the widely used BR2 method at a significantly reduced cost, clearly demonstrating that the DDG method provides an attractive alternative for solving the compressible NavierStokes equations on arbitrary grids owning to its simplicity in implementation and its efficiency in computational cost.

Background: Low endometrial receptivity is associated with infertility in women through multiple and complex mechanisms. Existing treatments are not always effective. Symptomatic drugs such as estradiol valerate and/or aspirin do not completely solve the problem. Traditional Chinese herbs have been widely used in infertility and uterine disease including low endometrial receptivity. However, their effectiveness and safety are still obscure and deserve further investigation. Objective: To assess the effect and safety of traditional Chinese herbs in treating low endometrial receptivity. Methods: We will summarize and meta-analyze randomized controlled trials (RCTs) of traditional Chinese herbs for the treatment of low endometrial receptivity. RCTs comparing traditional Chinese herbs with blank control, placebo, or conventional therapies will be included. RCTs comparing traditional Chinese herbs plus conventional therapies with conventional therapies alone will also be included. The following electronic databases will be searched: PubMed, Cochrane Library, EMBASE, CNKI, CBM, VIP, and WANFANG DATA. The methodological quality of RCTs will be assessed using the Cochrane risk assessment tool. All trials included will be analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software will be used for publication bias analysis. GRADE pro GDT web solution will be used for evidence evaluation. Results: This review will evaluate the effects of traditional Chinese herbs on estradiol, progesterone, thickness, volume, and perfusion index(PI) of the endometrium, pregnancy rate, and symptoms. Conclusions: This review will provide clear evidence to assess the effectiveness and safety of traditional Chinese herbs for low endometrial receptivity. OSF registration number: DOI 10.17605/OSF.IO/M85VT.

Free Wanderer Powder (FWP) is a classic formula for depression with digestive dysfunctions, i.e., liver-depression and spleen-deficiency syndrome (LDSDS) in Chinese Medicine. But its protective mechanism has not been fully clarified. Here a chronic restraint stress (CRS) induced rat model showed depression with LDSDS in food intake, metabolism, and behaviour tests. Then 75 rats were randomly divided, and received CRS and different treatment with behaviour tests. Expressions of c-Fos and AMPA-type glutamate receptor subunits GluR1-3 in hippocampus CA1, CA3, DG and amygdala BLA were detected by immunohistochemistry, western blot and RT-PCR, respectively. In CRS rats, FWP alleviated depressive behaviour and c-Fos expression. FWP suppressed the increasement of GluR1 in CA1 and DG, p-GluR1 in CA1, and p-GluR2 and GluR3 in BLA. FWP also blocked the decrease of GluR1 and Glur2/3 in CA3, p-GluR1 in CA3, and p-GluR2 in CA1 and CA3. Furthermore, constituents of FWP and their potential targets were explored using UHPLC-MS and systematic bioinformatics analysis. There were 23 constituents identified in FWP, 9 of which regulated glutamatergic synapse. Together, these results suggest that FWP contains effective constituents and alleviates depression with LDSDS by regulating AMPA-type glutamate receptor homeostasis in amygdala and hippocampus.