Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammatory disease in the lower gastrointestinal tract. Mounting evidence suggests that the ...predominance of the classically activated (M1) macrophages versus the alternatively activated (M2) macrophages plays a role in the progression of IBD. Thus, agents able to shift pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages may be beneficial to IBD. The pentacyclic triterpene Lup-20(29)-en-3β-ol (Lupeol), a potent anti-inflammatory natural product, has been shown to inhibit pro-inflammatory cytokine production, suggesting it is potentially able to modulate macrophage polarization, thereby beneficial to IBD.
CD4+ monocytes were differentiated to M1 or M2 macrophages, which were cocultured with epithelial cell lines, T84 and Caco-2, in the absence or presence of Lupeol (10μM). Experimental colitis was induced with dextran sodium sulfate (DSS), with or without oral administration of Lupeol (50mg/kg, q.d.). Cytokines were measured with Luminex kits. M1/M2 genes were measured with real-time polymerase chain reaction. Macrophage phenotypes were defined by measuring M1 and M2 markers with confocal microscopy. Proteins were measured with Western blotting, while cell surface markers were measured with confocal microscopy or flow cytometry. Histology was evaluated with H&E staining.
Treatment of M1 macrophages with Lupeol resulted in a marked decrease in the production of pro-inflammatory cytokines, including IL-12, IL6, IL-1β and TNFα, and a marked increase in the production of IL-10, an anti-inflammatory cytokine. This was associated with a down-regulation of CD86, a typical marker of M1 macrophages, and an up-regulation of CD206, a typical M2 macrophage marker. IRF5, a transcription factor that is critically involved in M1 polarization, was down-regulated in M1 macrophages after being incubated with Lupeol, associated with a marked decrease in the phosphorylation of p38 mitogen activated protein kinase. Coculture of epithelial cells with M1 macrophages resulted in down-regulation of the tight junction protein ZO-1 and disruption of epithelial integrity, which were blocked by Lupeol treatment of the M1 macrophages. Moreover, oral administration of Lupeol to dextran sulfate sodium (DSS)-induced colitis mice resulted in mitigated intestinal inflammation and increased survival from lethal colitis, associated with decreased expression of M1-related genes and increased expression of M2-related genes.
Lupeol ameliorates experimental inflammatory bowel disease through, at least in part, inhibiting M1 and promoting M2 macrophages.
•The pentacyclic triterpene Lup-20(29)-en-3β-ol (Lupeol), a potent anti-inflammatory natural product, was able to switch macrophages from M1 to M2 phenotype.•Moreover, oral administration of Lupeol to dextran sulfate sodium (DSS)-induced colitis mice resulted in mitigated intestinal inflammation and increased survival from lethal colitis, associated with decreased expression of M1-related genes and increased expression of M2-related genes in the lesion.•Our data suggest Lupeol ameliorates experimental IBD through, at least in part, inhibiting M1 and promoting M2 macrophages.•Considering the very low toxicity of Lupeol, we believe that these findings are significant.
In order to solve the problem that high-dimensional mixed reality interface brings low task performance and heavy cognitive load to users in cross-layer operation, we study the information fusion ...interface of human-computer interaction and propose two kinds of fusion interfaces. The experimental results show that the deep fusion interface performs better than the combined interface in cognitive difficulty, cognitive load, operational efficiency and subjective evaluation. The research conclusion can guide the design of human-computer interaction interface in mixed reality.
•The morphology of the droplet is divided into three regions based on Weber number.•A prediction equation for the maximum spread diameter is proposed.•In a certain range of D*, the groove structure ...is beneficial to reduce the contact time.
The dynamic behavior of droplets impacting a grooved cylindrical superhydrophobic surface (a circular cylindrical shape with groove) was studied via experiments performed over D* (defined as the ratio of cylinder diameter D to initial droplet diameter D0) ranging from 4 to 9 and We ranging from 3 to 210. Parameters including the spreading, receding, splashing, and contact time were investigated. Five possible behaviors of the droplets, including complete rebound, partial rebound, no rebound, stretched breakup rebound and stretched breakup, were observed on the grooved cylindrical superhydrophobic surface. Based on the Weber number, the sites of these phenomena into three regions, namely complete rebound region (complete rebound), transition region (partial rebound, non-rebound), and splash region (stretched breakup rebound and stretched breakup) were divided. The results revealed that the diameter ratio D*, We, and grooved structure have a significant effect on the droplet morphology. The grooved structure hindered the droplet spreading and splashing in the perpendicular direction of the droplet and promoted the droplet spreading and splashing in the parallel direction. In addition, an equation for predicting the maximum axial and azimuthal spread diameter was proposed. Compared with the cylindrical surface, the grooved cylindrical surface could reduce the contact time of droplets within a certain range of We.
Optically active (S)-2-aryl-4 (or 5)-phenyl-1,3-oxazolines and (S)-2-fluoroalkyl-4-phenyl-1,3-oxazolines were synthesized from a tandem one-pot reaction of (S)-2-amino-2-phenylethanol with a ...corresponding carboxylic acid in toluene at 90 °C in the presence of PPh3/CBr4 and excess Et3N. The use of aromatic carboxylic acids were determined to proceed through N-(2-bromo-1-phenyl-ethyl)-arylamides 5 and N-aroyl aziridine intermediates 6, which resulted in the formation of (S)-2-aryl-4-phenyl-1,3-oxazolines and (S)-2-aryl-5-phenyl-1,3-oxazolines, respectively. Concurrently, the reaction with fluorinated aliphatic carboxylic acid substrates proceeded via N-(2-hydroxy-1-phenyl-ethyl)-fluoroalkyl amide intermediates 8, which were converted into N-(2-bromo-1-phenyl-ethyl)-fluoroalkyl amide intermediates 9, and then into (S)-2-fluoroalkyl-4-phenyl-1,3-oxazolines as final products. Reaction mechanisms that mainly passed through the formation of aziridine intermediates 6 in the reaction with aromatic carboxylic acids and the formation of fluoroalkyl amide intermediates 8 and 9 in the reaction with fluorinated aliphatic carboxylic acid were proposed. The acidities of the carboxylic acids that were employed were found to play a key role in the selective formation of various intermediates during this reaction.
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Nucleophile-dependent regioselectivities in the nucleophilic reaction of (S)-4-benzyl-2-fluoroalkyl-1,3-oxazoline to different types of fluorinated compounds were investigated experimentally and ...theoretically. The ring opening of (S)-4-benzyl-2-bromodifluoromethyl-1,3-oxazoline by arenethiolates exclusively occurred at the C5 position of the 1,3-oxazoline ring, whereas completely different regioselectivity was observed for a unimolecular radical nucleophilic substitution (SRN1) at the terminal bromine atom of the CF2Br group when arenolates were employed as the nucleophiles. The reaction of (S)-4-benzyl-2-trifluoromethyl-1,3-oxazoline with nucleophiles such as arenethiols, arenols, and TMSCl underwent nucleophilic ring opening in a regiospecific way, while the use of TMSCF3 was determined to proceed through nucleophilic addition to the CN bond.
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► A facile one-pot preparation of 2-bromodifluoromethyl benzo-1,3-diazoles was disclosed. ► CF
2Br-containing heterocyclic building blocks were rarely reported in the past. ► The ...reaction mechanism involves the formation imidoyl bromide and intramolecular ring-closure reaction. ► The 2-bromodifluoromethyl benzo-1,3-thiazole building block was successfully utilized. ►
gem-Difluoromethylene linked benzothiazole-containing aryl ethers were synthesized.
A facile preparation of 2-bromodifluoromethyl benzo-1,3-diazoles as novel CF
2Br-containing heterocyclic building blocks has been developed through a one-pot process of reaction of 2-OH, 2-SH, or 2-NH
2 substituted aniline with bromodifluoroacetic acid in the presence of 3 molar equivalents of CBr
4 and Ph
3P in refluxing toluene. 2-Bromodifluoromethyl benzo-1,3-thiazole (
2b) was successfully utilized in the preparation of
gem-difluoromethylene linked aryl ether compounds through the reaction with phenolates or thiophenolate in DMF in good yields.
Access control, as a security mechanism governing system resources access, integrates with blockchain to reinforce decentralization, enhance data security, and ensure that only authorized users can ...access and execute specific operations. To optimize access control in the context of blockchain, enhance response speed, and address the requirements of the medical emergency application, this paper proposed a Hierarchical Filtering Access Control (HFAC) model based on blockchain. This model integrates blockchain, smart contract, access control list, attribute-based access control, and token. The experimental result showed that HFAC exhibits outstanding performance in average response time, making it particularly suitable for emergency vehicle dispatch platforms. This paper provided a feasible solution for the efficient operation of emergency vehicle dispatch systems in the medical emergency application.
An Emergency Rescue System Architecture Based on Metaverse Wu, Yeshan; Zhu, Yishui; Wang, Luyang ...
2022 IEEE Intl Conf on Dependable, Autonomic and Secure Computing, Intl Conf on Pervasive Intelligence and Computing, Intl Conf on Cloud and Big Data Computing, Intl Conf on Cyber Science and Technology Congress (DASC/PiCom/CBDCom/CyberSciTech),
2022-Sept.-12
Conference Proceeding
The imperfect staffing in pre-hospital first aid and the unreasonable dispatching of ambulances pose a threat to the life and health of the public. In order to solve the above problems, this paper ...proposes an emergency rescue system based on metaverse, which adds the function of personal doctor on the basis of the shared vehicle scheduling system based on blockchain. Metaverse is the fusion and interaction between the virtual and the real world, with blockchain, smart contracts, and other main technologies. Through the combination of metaverse and intelligent doctor assistant, the function and use process of personal doctor are designed. This paper also proposes an insurance-like payment mechanism, which is based on the premise of controlling the packing order of transactions in the blockchain by controlling the level of Gas Price and solving the problem of who pays and how to pay the transaction fee of the system. It not only ensures the normal operation of emergency rescue activities but also protects the interests of each node in the blockchain.
