Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds.Control of inflammation and immune cell functions thus represents a promising approach ...Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds.Control of inflammation and immune cell functions thus represents a promising approach in the development of advanced therapeutic strategies.Here we describe immunomodulatory hyaluronan/collagen(HA-AC/coll)-based hydrogels containing high-sulfated hyaluronan(sHA)as immunoregulatory component for the modulation of inflammatory macrophage activities in disturbed wound healing.Solute sHA downregulates inflammatory activities of bone marrow-derived and tissue-resident macrophages in vitro.This further affects macrophage-mediated pro-inflammatory activation of skin cells as shown in skin ex-vivo cultures.In a mouse model of acute skin inflammation,intradermal injection of sHA downregulates the inflammatory processes in the skin.This is associated with the promotion of an anti-inflammatory gene signature in skin macrophages indicating a shift of their activation profile.For in vivo translation,we designed HA-AC/coll hydrogels allowing delivery of sHA into wounds over a period of at least one week.Their immunoregulatory capacity was analyzed in a translational experimental approach in skin wounds of diabetic db/db mice,an established model for disturbed wound healing.The sHA-releasing hydrogels improved defective tissue repair with reduced inflammation,augmented pro-regenerative macrophage activation,increased vascularization,and accelerated new tissue formation and wound closure.展开更多
Most close double helium white dwarfs will merge within a Hubble time due to orbital decay by gravitational wave radiation.However,a significant fraction with low mass ratios will survive for a long time as a conseque...Most close double helium white dwarfs will merge within a Hubble time due to orbital decay by gravitational wave radiation.However,a significant fraction with low mass ratios will survive for a long time as a consequence of stable mass transfer.Such stable mass transfer between two helium white dwarfs（He WDs） provides one channel for the production of AM CVn binary stars.In previous calculations of double He WD progenitors,the accreting He WD was treated as a point mass.We have computed the evolution of 16 double He WD models in order to investigate the consequences of treating the evolution of both components in detail.We find that the boundary between binaries having stable and unstable mass transfer is slightly modified by this approach.By comparing with observed periods and mass ratios,we redetermine masses of eight known AM CVn stars by our double He WDs channel,i.e.HM Cnc,AM CVn,V406 Hya,J0926,J1240,GP Com,Gaia14 aae and V396 Hya.We propose that central spikes in the triple-peaked emission spectra of J1240,GP Com and V396 Hya and the surface abundance ratios of N/C/O in GP Com can be explained by the stable double He WD channel.The mass estimates derived from our calculations are used to discuss the predicted gravitational wave signal in the context of the Laser Interferometer Space Antenna（LISA） project.展开更多
基金This work was funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)project number 59307082-TRR67 subprojects A3,B3,Z3project FR2671/4-1 to SFproject 420160411 to SR.
文摘Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds.Control of inflammation and immune cell functions thus represents a promising approach in the development of advanced therapeutic strategies.Here we describe immunomodulatory hyaluronan/collagen(HA-AC/coll)-based hydrogels containing high-sulfated hyaluronan(sHA)as immunoregulatory component for the modulation of inflammatory macrophage activities in disturbed wound healing.Solute sHA downregulates inflammatory activities of bone marrow-derived and tissue-resident macrophages in vitro.This further affects macrophage-mediated pro-inflammatory activation of skin cells as shown in skin ex-vivo cultures.In a mouse model of acute skin inflammation,intradermal injection of sHA downregulates the inflammatory processes in the skin.This is associated with the promotion of an anti-inflammatory gene signature in skin macrophages indicating a shift of their activation profile.For in vivo translation,we designed HA-AC/coll hydrogels allowing delivery of sHA into wounds over a period of at least one week.Their immunoregulatory capacity was analyzed in a translational experimental approach in skin wounds of diabetic db/db mice,an established model for disturbed wound healing.The sHA-releasing hydrogels improved defective tissue repair with reduced inflammation,augmented pro-regenerative macrophage activation,increased vascularization,and accelerated new tissue formation and wound closure.
基金supported by the CAS ‘Light of West China’ program(2015-XBQNA-02)the National Natural Science Foundation of China(NSFC,Grant Nos.10933002,11703001 and 11273007)+5 种基金the Joint Research Fund in Astronomy(U1631236) under cooperative agreement between the NSFC and the Chinese Academy of Sciences(CAS)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB2304100)the China Postdoctoral Science Foundationthe Fundamental Research Funds for the Central UniversitiesThe Armagh Observatory and Planetarium are supported by a grant from the Northern Ireland Department for Communitiessupport from the UK Science and Technology Facilities Council(STFC)(Grant No.ST/M000834/1)
文摘Most close double helium white dwarfs will merge within a Hubble time due to orbital decay by gravitational wave radiation.However,a significant fraction with low mass ratios will survive for a long time as a consequence of stable mass transfer.Such stable mass transfer between two helium white dwarfs（He WDs） provides one channel for the production of AM CVn binary stars.In previous calculations of double He WD progenitors,the accreting He WD was treated as a point mass.We have computed the evolution of 16 double He WD models in order to investigate the consequences of treating the evolution of both components in detail.We find that the boundary between binaries having stable and unstable mass transfer is slightly modified by this approach.By comparing with observed periods and mass ratios,we redetermine masses of eight known AM CVn stars by our double He WDs channel,i.e.HM Cnc,AM CVn,V406 Hya,J0926,J1240,GP Com,Gaia14 aae and V396 Hya.We propose that central spikes in the triple-peaked emission spectra of J1240,GP Com and V396 Hya and the surface abundance ratios of N/C/O in GP Com can be explained by the stable double He WD channel.The mass estimates derived from our calculations are used to discuss the predicted gravitational wave signal in the context of the Laser Interferometer Space Antenna（LISA） project.
