[Discrete element simulation study of mixing process of Guizhi Fuling Capsules: parameter calibration].

The mixing process is a critical link in the formation of oral solid preparations of traditional Chinese medicine. This paper took the extract powder of Guizhi Fuling Capsules and Paeonol powder as research objects. The angle of repose, loose packing density, and particle size of the two powders were measured to calibrate discrete element simulation parameters for the mixing process. The discrete element method was used to calibrate the simulated solid density of Paeonol powder and extract powder of Guizhi Fuling Capsules based on the Hertz-Mindlin with JKR V2 contact model and particle scaling. The Plackett-Burman experimental design was used to screen out the critical contact parameters that had a significant effect on the simulation of the angle of repose. The regression model between the critical contact parameters and the simulated angle of repose was established by the Box-Behnken experimental design, and the critical contact parameters of each powder were optimized based on the regression model. The best combination of critical contact parameters of the extract powder of Guizhi Fuling Capsules was found to be 0.51 for particle-particle static friction coefficient, 0.31 for particle-particle rolling friction coefficient, and 0.64 for particle-stainless steel static friction coefficient. For Paeonol powder, the best combination of critical contact parameters was 0.4 for particle-particle static friction coefficient and 0.19 for particle-particle rolling friction coefficient. The best combination of contact parameters between Paeonol powder and extract powder of Guizhi Fuling Capsules was 0.27 for collision recovery coefficient, 0.49 for static friction coefficient, and 0.38 for rolling friction coefficient. The verification results show that the relative error between the simulated value and the measured value of the angle of repose of the two single powders is less than 1%, while the relative error between the simulated value and the measured value of the angle of repose of the mixed powder with a mass ratio of 1∶1 is less than 4%. These research results provide reliable physical property simulation data for the mixed simulation experiment of extract powder of Guizhi Fuling Capsules and Paeonol powder.

Global research trends of artificial intelligence applied in esophageal carcinoma: A bibliometric analysis (2000-2022) via CiteSpace and VOSviewer.

Objective: Using visual bibliometric analysis, the application and development of artificial intelligence in clinical esophageal cancer are summarized, and the research progress, hotspots, and emerging trends of artificial intelligence are elucidated. Methods: On April 7th, 2022, articles and reviews regarding the application of AI in esophageal cancer, published between 2000 and 2022 were chosen from the Web of Science Core Collection. To conduct co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references, and keywords in this field, VOSviewer (version 1.6.18), CiteSpace (version 5.8.R3), Microsoft Excel 2019, R 4.2, an online bibliometric platform (http://bibliometric.com/) and an online browser plugin (https://www.altmetric.com/) were used. Results: A total of 918 papers were included, with 23,490 citations. 5,979 authors, 39,962 co-cited authors, and 42,992 co-cited papers were identified in the study. Most publications were from China (317). In terms of the H-index (45) and citations (9925), the United States topped the list. The journal "New England Journal of Medicine" of Medicine, General & Internal (IF = 91.25) published the most studies on this topic. The University of Amsterdam had the largest number of publications among all institutions. The past 22 years of research can be broadly divided into two periods. The 2000 to 2016 research period focused on the classification, identification and comparison of esophageal cancer. Recently (2017-2022), the application of artificial intelligence lies in endoscopy, diagnosis, and precision therapy, which have become the frontiers of this field. It is expected that closely esophageal cancer clinical measures based on big data analysis and related to precision will become the research hotspot in the future. Conclusions: An increasing number of scholars are devoted to artificial intelligence-related esophageal cancer research. The research field of artificial intelligence in esophageal cancer has entered a new stage. In the future, there is a need to continue to strengthen cooperation between countries and institutions. Improving the diagnostic accuracy of esophageal imaging, big data-based treatment and prognosis prediction through deep learning technology will be the continuing focus of research. The application of AI in esophageal cancer still has many challenges to overcome before it can be utilized.

Glucose-Potentiated Amikacin Killing of Cefoperazone/Sulbactam Resistant Pseudomonas aeruginosa.

Multidrug-resistant Pseudomonas aeruginosa has become one of global threat pathogens for human health due to insensitivity to antibiotics. Recently developed reprogramming metabolomics can identify biomarkers, and then, the biomarkers were used to revert the insensitivity and elevate antibiotic-mediated killing. Here, the methodology was used to study cefoperazone/sulbactam (SCF)-resistant P. aeruginosa (PA-RSCF) and identified reduced glycolysis and pyruvate cycle, a recent clarified cycle providing respiratory energy in bacteria, as the most key enriched pathways and the depressed glucose as one of the most crucial biomarkers. Further experiments showed that the depression of glucose was attributed to reduction of glucose transport. However, exogenous glucose reverted the reduction to elevate intracellular glucose via activating glucose transport. The elevated glucose fluxed to the glycolysis, pyruvate cycle, and electron transport chain to promote downstream proton motive force (PMF). Consistently, exogenous glucose did not promote SCF-mediated elimination but potentiated aminoglycosides-mediated killing since aminoglycosides uptake is PMF-dependent, where amikacin was the best one. The glucose-potentiated amikacin-mediated killing was effective to both lab-evolved PA-RSCF and clinical multidrug-resistant P. aeruginosa. These results reveal the depressed glucose uptake causes the reduced intracellular glucose and expand the application of metabolome-reprogramming on selecting conventional antibiotics to achieve the best killing efficacy.

NFATc1 is a Necessary Transcription Factor in Polarisation of T Helper Type 2 Lymphocytes Induced by Thymic Stromal Lymphopoietin.

Thymic stromal lymphopoietin (TSLP) activates lung dendritic cells (DCs) to promote a T helper type 2 lymphocyte (Th2) response in animal models. However, the mechanism behind this process remains unclear. In this study, we investigate the role of a nuclear factor for activated T-cells 1 (NFATc1) in the TSLP-induced polarisation towards a Th2 response. A cluster of differentiated (CD)14+ peripheral blood mononuclear cells (PBMCs) and naïve T cells were isolated from blood collected from healthy human volunteers, and TSLP was used to induce DC maturation. The effects of TSLP-DCs and treatments with FK506, an NFATc1 inhibitor, on naïve T cell differentiation were monitored by measuring the interleukin (IL)-4, IL-13, and interferon-γ (IFN-γ) expression levels. In addition, the mRNA levels of T-box expression in T cells (T-bet), GATA binding protein 3 (GATA-3), TSLP, and NFATc1 were measured for the same purpose. IL-4, IL-13, and mRNA levels of GATA-3 and NFATc1 significantly increased with TSLP-DC induction (P<0.01), indicating polarization towards the Th2 response. These changes were reversed by treatment with FK506 (P<0.01). Our findings suggest that NFATc1 plays a key role in the TSLP-induced differentiation of T cells to Th2, and NFATc1 is a potential therapeutic target for treating allergic diseases.

Thymic stromal lymphopoietin induced early stage of epithelial-mesenchymal transition in human bronchial epithelial cells through upregulation of transforming growth factor beta 1.

Purpose: Epithelial-mesenchymal transition (EMT) involved in asthmatic airway remodeling. Thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine, was a key component in airway immunological response in asthma. But the role of TSLP in the EMT process was unknown. We aimed to access whether TSLP could induce EMT in airway epithelia and its potential mechanism. Materials and Methods: Human bronchial epithelial (HBE) cells were incubated with TSLP or transforming growth factor beta 1 (TGF-ß1) or both. SB431542 was used to block TGF-ß1 signal while TSLP siRNA was used to performed TSLP knockdown. Changes in E-cadherin, vimentin, collagen I and fibronectin level were measured by real-time PCR, western blot and immunofluorescence staining. Expressions of TGF-ß after TSLP administration were measured by real-time PCR, western blot and ELISA. Results: TSLP induced changes of EMT relevant markers alone and promoted TGF-ß1-induced EMT in HBEs. Intracellular and extracellular expression of TGF-ß1 were upregulated by TSLP. SB431542 blocked changes of EMT relevant markers induced by TSLP. Knockdown of TSLP not only reduced TSLP and TGF-ß1 expression but also inhibited changes of EMT relevant markers induced by TGF-ß1 in HBEs. Conclusions: TSLP could induce early stage of EMT in airway epithelial cells through upregulation of TGF-ß1. This effect may act as a targeting point for suppression of asthma.

Syntheses, crystal structures, luminescent and magnetic properties of two molecular solids containing naphthylmethylene triphenylphosphinium cations and tetra(isothiocyanate)cobalt(II) dianion.

The reaction of CoCl2 with the naphthalene methylated triphenylphosphinium bromide [n-NAPMeTPP]Br (n=1, 2) and KSCN, in a methanolic medium at ambient temperature, leads to the self-assembly formation of hybrid 2:1 organic-inorganic molecular solids, [1-NAPMeTPP]2[Co(NCS)4](1) and [2-NAPMeTPP]2[Co(NCS)4](2) ([NAPMeTPP](+)=(naphthylmethylene)(triphenyl)phosphinium), which have been characterized by elemental analyses, IR spectroscopy, UV-Vis spectra, ESI-MS, molar conductivity and single-crystal X-ray diffraction structural analyses. Compound 1 crystallizes in the orthorhombic space group Pna21, while 2 does in the monoclinic space group C2/c. The cations form a dimer through the weak intermolecular C-H⋯π interactions in 1 and π⋯π interaction in 2, while the anion and cation are linked by the C-H⋯S hydrogen bond in 1. Two molecular solids show dual functionalities: (1) the broad fluorescence emission around 400nm in the solid state at room temperature; (2) the weak antiferromagnetic coupling behavior.