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Arachidonic acid can be metabolized to prostaglandins and epoxyeicosatrienoic acids (EETs) by cyclooxygenase-2 (COX-2) and cytochrome P450 (CYP), respectively. While protective EETs are degraded by soluble epoxide hydrolase (sEH) very fast. We have reported that dual inhibition of COX-2 and sEH with specific inhibitor PTUPB shows anti-pulmonary fibrosis and renal protection. However, the effect of PTUPB on cecal ligation and puncture (CLP)-induced sepsis remains unclear. The current study aimed to investigate the protective effects of PTUPB against CLP-induced sepsis in mice and the underlying mechanisms. We found that COX-2 expressions were increased, while CYPs expressions were decreased in the liver, lung, and kidney of mice undergone CLP. PTUPB treatment significantly improved the survival rate, reduced the clinical scores and systemic inflammatory response, alleviated liver and kidney dysfunction, and ameliorated the multiple-organ injury of the mice with sepsis. Besides, PTUPB treatment reduced the expression of hypoxia-inducible factor-1α in the liver, lung, and kidney of septic mice. Importantly, we found that PTUPB treatment suppressed the activation of NLRP3 inflammasome in the liver and lung of septic mice. Meanwhile, we found that PTUPB attenuated the oxidative stress, which contributed to the activation of NLRP3 inflammasome. Altogether, our data, for the first time, demonstrate that dual inhibition of COX-2 and sEH with PTUPB ameliorates the multiple organ dysfunction in septic mice.

Rationale: Dysregulation of arachidonic acid (ARA) metabolism results in inflammation; however, its role in acute lung injury (ALI) remains elusive. In this study, we addressed the role of dysregulated ARA metabolism in cytochromes P450 (CYPs) /cyclooxygenase-2 (COX-2) pathways in the pathogenesis of lipopolysaccharide (LPS)-induced ALI in mice. Methods: The metabolism of CYPs/COX-2-derived ARA in the lungs of LPS-induced ALI was investigated in C57BL/6 mice. The COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation in ALI. Primary murine macrophages were used to evaluate the underlying mechanism of PTUPB involved in the activation of NLRP3 inflammasome in vitro. Results: Dysregulation of CYPs/COX-2 metabolism of ARA occurred in the lungs and in primary macrophages under the LPS challenge. Decrease mRNA expression of Cyp2j9, Cyp2j6, and Cyp2j5 was observed, which metabolize ARA into epoxyeicosatrienoic acids (EETs). The expressions of COX-2 and soluble epoxide hydrolase (sEH), on the other hand, was significantly upregulated. Pre-treatment with the dual COX-2 and sEH inhibitor, PTUPB, attenuated the pathological injury of lung tissues and reduced the infiltration of inflammatory cells. Furthermore, PTUPB decreased the pro-inflammatory factors, oxidative stress, and activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in LPS-induced ALI mice. PTUPB pre-treatment remarkably reduced the activation of macrophages and NLRP3 inflammasome in vitro. Significantly, both preventive and therapeutic treatment with PTUPB improved the survival rate of mice receiving a lethal dose of LPS. Conclusion: The dysregulation of CYPs/COX-2 metabolized ARA contributes to the uncontrolled inflammatory response in ALI. The dual COX-2 and sEH inhibitor PTUPB exerts anti-inflammatory effects in treating ALI by inhibiting the NLRP3 inflammasome activation.

With the continuous development and innovation of blockchain technology,a large number of blockchain-based applications have been generated.Today’s blockchain systems are mostly heterogeneous and not interconnected,and there is no direct value circulation between chains.This greatly limits the functional expansion and development of blockchains.Cross-chain technology refers to the exchange of information between different blockchain system instances and the use of the exchanged information to achieve interconnection and value transfer between blockchains.Firstly,this paper introduces the development process of blockchain cross-chain technology,and introduces in detail four current mainstream cross-chain technologies including the notary mechanism,the side chain relay,the hash lock and the distributed private key control.Then,based on the above-mentioned cross-chain technology,it further introduces several current mainstream cross-chain projects and applications.Finally,by comparing the similarities and differences of several cross-chain technologies in trust model,security,atomicity,scalability,etc.,the current development trend of cross-chain technology is summarized and analyzed,and the difficulties and future development direction in the field of cross-chain are discussed.

Deep learning has broad applications in various fields.However,users still need to face problems from two aspects when applying deep learning.First,deep learning has a complex theoretical background,non-professional users lack background knowledge in modeling and tuning.It is difficult for them to build performance-optimized models.Second,modules such as data preprocessing,model training,and prediction often involve more complicated programming implementations,which bring some difficulties in getting started for non-professional users who have no programming skill background.In view of the above two issues of usability,this paper proposes an easy-to-use graphical deep learning model construction system,DragDL.The purpose of DragDL is to reduce the difficulty of data preprocessing,model training,monitoring,online prediction and other tasks for users.The system is based on the PaddlePaddle framework and supports building a deep learning network structure on the canvas by dragging graphical operators,supporting inference and prediction functions,and abstracting the data preprocessing operation process into a dataflow graph,which is convenient for users to understand and debug.The system also provides visualization functions for performance monitoring during the training process.At the same time,DragDL provides a classic model library,which allows users to build new DL network by tuning the existing classic model network.DragDL is deployed based on a centralized server and Web client.The server provides a virtual machine service for submitted tasks and supports large-scale asynchronous task scheduling to have concurrent processing capabilities.

The complete mitochondrial genome (mitogenome) of the Rhus gall aphid Schlechtendalia peitan in China was obtained using the shotgun genome-skimming method on an Illumina platform. The complete mitogenome of S. peitan is 15,494 bp in length with a high A + T content of 84.1%. This mitogenome consists of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a control region. All the protein-coding genes initiate with a typical ATN codon and terminate with TAA codon except for COX1, ND4 and ND5 with a single T. The 22 tRNAs range from 59 to 72 bp in length, and each one is predicted as a clover-leaf secondary structure except for tRNA-Ser (AGN), which loses a dihydrouridine (DHU) arm. The ML phylogenetic tree of Fordini aphids constructed using 13 protein-coding genes and two rRNAs showed that S. peitan was sister to the group clustered by the two species Schlechtendalia chinensis and Nurudea ibofushi. [ABSTRACT FROM AUTHOR]