Idiopathic pulmonary fibrosis(IPF)is a progressive and fatal interstitial lung disease characterized by excessive fibrotic remodeling,for which effective therapeutic options remain severely limited.Among the pathogeni...Idiopathic pulmonary fibrosis(IPF)is a progressive and fatal interstitial lung disease characterized by excessive fibrotic remodeling,for which effective therapeutic options remain severely limited.Among the pathogenic mechanisms implicated in IPF,epithelial-to-mesenchymal transition(EMT)is recognized as a pivotal driver of fibroblast activation and extracellular matrix deposition.In this study,we aimed to develop low-molecular-weight dextran sulfate sodium(LMW-DSS)derivatives and assess their capacity to interfere with EMT,thereby offering novel therapeutic avenues for IPF management.Starting with dextran(2 kDa)as a precursor,we successfully synthesized two sulfated derivatives,DSS-LS and DSS-HS,via distinct sulfonation processes.Using a TGF-β1-stimulated A549 alveolar epithelial cell model,we demonstrated that LMW-DSS compounds exhibited no cytotoxicity,as validated by CCK-8 viability assays.Importantly,Transwell migration assays revealed that LMW-DSS markedly attenuated TGF-β1-induced A549 cell migration,indicating a potent anti-fibrotic effect.Moreover,qPCR and Western blotting analyses confirmed that LMW-DSS significantly suppressed the expression and secretion of key pro-fibrotic mediators,including TGF-β1 and VEGF-A,and downregulated critical EMT-associated markers such as Snail and vimentin.Notably,reducedα-SMA expression following LMW-DSS treatment further substantiated its role in hindering EMT progression.Collectively,these findings highlighted the capacity of LMW-DSS to effectively impede EMT and fibrotic processes,thereby delaying the progression of pulmonary fibrosis.This work not only underscored the therapeutic potential of LMW-DSS in IPF but also provided compelling experimental evidence to support its development as a promising anti-fibrotic agent for clinical application.展开更多
Adding a reputation incentive system to peer-to-peer(P2P)energy transactions can encourage prosumers to regulate their trading behavior,which is important for ensuring the efficiency and reliability of P2P transaction...Adding a reputation incentive system to peer-to-peer(P2P)energy transactions can encourage prosumers to regulate their trading behavior,which is important for ensuring the efficiency and reliability of P2P transactions.This study proposed a P2P transaction mechanism and game optimization model for prosumers involved in distributed energy sources considering reputation-value incentives.First,the deviation of P2P transactions and the non-consumption rate of distributed renewable energy in P2P transactions were established as indicators to quantify the influencing factors of the reputation value,and a reputation incentive model of P2P transactions for prosumers was constructed.Then,the penalty coefficient was applied to the cost function of the prosumers,and a non-cooperative game model of P2P transactions based on the complete information of multi-prosumers was established.Furthermore,the Nash equilibrium problem was transformed into a nonlinear optimization problem by constructing the modified optimal reaction function,and the Nash equilibrium solution of the game was obtained via a relaxation algorithm.Finally,the modified IEEE 33-node test system based on electricity market P2P and an IEEE 123-node test system were used to analyze and verify the cost and P2P participation of prosumers considering the reputation value.The results show that the addition of the reputation incentive system can encourage prosumers to standardize their interactive transaction behavior and actively participate in P2P transactions.It can also improve the operation efficiency of the power grid and promote the perfection of the P2P transaction mechanism.展开更多
Capsular polysaccharides(CPS)of Colwellia psychrerythraea 34H consist of linear tetrasaccharides repeating units in a glycosaminoglycan-like fashion.Their biological function is likely involved in the cold adaptation ...Capsular polysaccharides(CPS)of Colwellia psychrerythraea 34H consist of linear tetrasaccharides repeating units in a glycosaminoglycan-like fashion.Their biological function is likely involved in the cold adaptation of microbial organisms.The low availability of these glycosaminoglycan structures greatly limits the study of their functions and biological activities.Here,an efficient semisynthetic strategy for CPS tetrasaccharide derivatives is achieved by using disaccharide units degraded from hyaluronic acids.This new synthetic process is suitable for largescale preparation,and several rare tetrasaccharide derivatives containing GalA-GalNAc were readily obtained in high yields.Biological evaluation of their anti-inflammatory effects demonstrated that these CPS tetrasaccharides effectively attenuated the lipopolysaccharide-induced sepsis and acute lung injury by decreasing macrophage infiltration and secretion of microphage-related cytokines in mice.All these results suggest that this new type of CPS tetrasaccharide can be developed as an anti-inflammation agent.展开更多
基金the National Natural Science Foundation of China(Grant Nos.92478133,81930097,and 82151223)by the State Key Laboratory of Natural and Biomimetic Drugs(Grant No.K202430).
文摘Idiopathic pulmonary fibrosis(IPF)is a progressive and fatal interstitial lung disease characterized by excessive fibrotic remodeling,for which effective therapeutic options remain severely limited.Among the pathogenic mechanisms implicated in IPF,epithelial-to-mesenchymal transition(EMT)is recognized as a pivotal driver of fibroblast activation and extracellular matrix deposition.In this study,we aimed to develop low-molecular-weight dextran sulfate sodium(LMW-DSS)derivatives and assess their capacity to interfere with EMT,thereby offering novel therapeutic avenues for IPF management.Starting with dextran(2 kDa)as a precursor,we successfully synthesized two sulfated derivatives,DSS-LS and DSS-HS,via distinct sulfonation processes.Using a TGF-β1-stimulated A549 alveolar epithelial cell model,we demonstrated that LMW-DSS compounds exhibited no cytotoxicity,as validated by CCK-8 viability assays.Importantly,Transwell migration assays revealed that LMW-DSS markedly attenuated TGF-β1-induced A549 cell migration,indicating a potent anti-fibrotic effect.Moreover,qPCR and Western blotting analyses confirmed that LMW-DSS significantly suppressed the expression and secretion of key pro-fibrotic mediators,including TGF-β1 and VEGF-A,and downregulated critical EMT-associated markers such as Snail and vimentin.Notably,reducedα-SMA expression following LMW-DSS treatment further substantiated its role in hindering EMT progression.Collectively,these findings highlighted the capacity of LMW-DSS to effectively impede EMT and fibrotic processes,thereby delaying the progression of pulmonary fibrosis.This work not only underscored the therapeutic potential of LMW-DSS in IPF but also provided compelling experimental evidence to support its development as a promising anti-fibrotic agent for clinical application.
基金supported by the National Natural Science Foundation of China(U2066211,52177124,52107134)the Institute of Electrical Engineering,CAS(E155610101)+1 种基金the DNL Cooperation Fund,CAS(DNL202023)the Youth Innovation Promotion Association of CAS(2019143).
文摘Adding a reputation incentive system to peer-to-peer(P2P)energy transactions can encourage prosumers to regulate their trading behavior,which is important for ensuring the efficiency and reliability of P2P transactions.This study proposed a P2P transaction mechanism and game optimization model for prosumers involved in distributed energy sources considering reputation-value incentives.First,the deviation of P2P transactions and the non-consumption rate of distributed renewable energy in P2P transactions were established as indicators to quantify the influencing factors of the reputation value,and a reputation incentive model of P2P transactions for prosumers was constructed.Then,the penalty coefficient was applied to the cost function of the prosumers,and a non-cooperative game model of P2P transactions based on the complete information of multi-prosumers was established.Furthermore,the Nash equilibrium problem was transformed into a nonlinear optimization problem by constructing the modified optimal reaction function,and the Nash equilibrium solution of the game was obtained via a relaxation algorithm.Finally,the modified IEEE 33-node test system based on electricity market P2P and an IEEE 123-node test system were used to analyze and verify the cost and P2P participation of prosumers considering the reputation value.The results show that the addition of the reputation incentive system can encourage prosumers to standardize their interactive transaction behavior and actively participate in P2P transactions.It can also improve the operation efficiency of the power grid and promote the perfection of the P2P transaction mechanism.
基金financially supported by the National Natural Science Foundation of China (grant nos.82151223,81930097,and 21977005)the National Key R&D Program of China (grant nos.2022YFF1203005 and 2022YFC2303700).
文摘Capsular polysaccharides(CPS)of Colwellia psychrerythraea 34H consist of linear tetrasaccharides repeating units in a glycosaminoglycan-like fashion.Their biological function is likely involved in the cold adaptation of microbial organisms.The low availability of these glycosaminoglycan structures greatly limits the study of their functions and biological activities.Here,an efficient semisynthetic strategy for CPS tetrasaccharide derivatives is achieved by using disaccharide units degraded from hyaluronic acids.This new synthetic process is suitable for largescale preparation,and several rare tetrasaccharide derivatives containing GalA-GalNAc were readily obtained in high yields.Biological evaluation of their anti-inflammatory effects demonstrated that these CPS tetrasaccharides effectively attenuated the lipopolysaccharide-induced sepsis and acute lung injury by decreasing macrophage infiltration and secretion of microphage-related cytokines in mice.All these results suggest that this new type of CPS tetrasaccharide can be developed as an anti-inflammation agent.
