The identification and lead optimization of a series of pyrazolo [3,4-d]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound 8. Compound 8 exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound 8 demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.
With the development of Agriculture 4.0, the requirements for sustainable agriculture and precision agriculture continue to grow. As one of the three major staple foods globally, the quality and safety of rice affect human health as well as social development. To ensure the quality and safety of rice and reduce the flow of problematic rice, a multi-layer blockchain-based rice supply chain refinement supervision model MBRRSM (Multi-blockchain Rice Refined Supervision Model) is proposed from the information level. First, the characteristics of information flow in the rice supply chain are analyzed, and a classification table of key information is constructed. Second, the MBRRSM framework is designed. Based on a multi-party hybrid encryption algorithm, secure multi-party computing algorithm, multi-mode storage mechanism, and SPOP (Supervision Proof of Peers) consensus algorithm, a set of mechanisms is designed for the transmission, use, storage, and consensus of rice data in MBRRSM. Subsequently, the security and performance capabilities of MBRRSM are analyzed. Meanwhile, the SPOP consensus algorithm is analyzed. Finally, a prototype system is built based on MBRRSM and verified through exemplary scenarios in different usage situations. The results show that research on the refined supervision of the rice supply chain based on multi-blockchain can finely supervise all types of data in the rice supply chain, and provide a guarantee for enterprise users to safely transmit and use data with different privacy levels. This study presents a unique research paradigm that introduces the theories and methods of the new information field generation into the field of agricultural research, and thus assists in the strategy implementation of “holding grain in the land and storing grain in technology”.
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