Mitochondrion-targeted carboxymethyl chitosan hybrid nanoparticles loaded with Coenzyme Q10 protect cardiac grafts against cold ischaemia‒reperfusion injury in heart transplantation

Abstract Background Heart transplantation (HT) has been approved as an optimal therapeutic regimen for patients with terminal-stage cardiac failure. However, cold ischaemia‒reperfusion (I/R) injury remains an unavoidable and outstanding challenge, which is a major factor in early graft dysfunction and an obstacle to long-term survival in HT. Cold I/R injury induces cardiac graft injury by promoting mitochondrial dysfunction and augmenting free radical production and inflammatory responses. We therefore designed a mitochondrion-targeted nanocarrier loaded with Coenzyme Q10 (CoQ10) (CoQ10@TNPs) for treatment of cold I/R injury after cardiac graft in a murine heterotopic cardiac transplantation model. Methods Hybrid nanoparticles composed of CaCO3/CaP/biotinylated-carboxymethylchitosan (CaCO3/CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used for characterisation. In vitro, the hypoxia-reoxygenation model of H9c2 cells was employed to replicate in vivo cold I/R injury and treated with CoQ10@TNPs. The impact of CoQ10@TNPs on H9c2 cell injury was assessed by analysis of oxidative damage and apoptosis. In vivo, donor hearts (DHs) were perfused with preservation solution containing CoQ10@TNPs and stored in vitro at 4 °C for 12 h. The DHs were heterotopically transplanted and analysed for graft function, oxidative damage, apoptosis, and inflammatory markers 1 day post-transplantation. Results CoQ10@TNPs were successfully synthesized and delivered CoQ10 to the mitochondria of the cold ischaemic myocardium. In vitro experiments demonstrated that CoQ10@TNPs was taken up by H9c2 cells at 4 °C and localized within the mitochondria, thus ameliorating oxidative stress damage and mitochondrial injury in cold I/R injury. In vivo experiments showed that CoQ10@TNPs accumulated in DH tissue at 4 °C, localized within the mitochondria during cold storage and improved cardiac graft function by attenuating mitochondrial oxidative injury and inflammation. Conclusions CoQ10@TNPs can precisely deliver CoQ10 to the mitochondria of cold I/R-injured cardiomyocytes to effectively eliminate mitochondrial reactive oxygen species (mtROS), thus reducing oxidative injury and inflammatory reactions in cold I/R-injured graft tissues and finally improving heart graft function. Thus, CoQ10@TNPs offer an effective approach for safeguarding cardiac grafts against extended periods of cold ischaemia, emphasizing the therapeutic potential in mitigating cold I/R injury during HT. These findings present an opportunity to enhance existing results following HT and broaden the range of viable grafts for transplantation

Medical resources and coronavirus disease (COVID-19) mortality rate: Evidence and implications from Hubei province in China.

In light of the ongoing coronavirus disease (COVID-19) pandemic, this study aims to examine the relationship between the availability of public health resources and the mortality rate of this disease. We conducted empirical analyses using linear regression, a time-varying effect model, and a regression discontinuity design to investigate the association of medical resources with the mortality rate of the COVID-19 patients in Hubei, China. The results showed that the numbers of hospital beds, healthcare system beds, and medical staff per confirmed cases all had significant negative effects on the coronavirus disease mortality rate. Furthermore, in the context of the severe pandemic currently being experienced worldwide, the present study summarized the experience and implications in pandemic prevention and control in Hubei province from the perspective of medical resource integration as follows: First, hospitals' internal medical resources were integrated, breaking interdepartmental barriers. Second, joint pandemic control was realized by integrating regional healthcare system resources. Finally, an external medical resource allocation system was developed

Changjiang Delta in the Anthropocene: Multi-scale hydro-morphodynamics and management challenges

The Changjiang Delta (CD) is one of well-studied large deltas of critical socio-economical and ecological importance regionally and global representativeness. Cumulated field data and numerical modeling has facilitated scientific understanding of its hydro-morphodynamics at multiple spatial and time scales, but the changing boundary forcing conditions and increasing anthropogenic influences pose management challenges requiring integrated knowledge. Here we provide a comprehensive synthesis of the multi-scale deltaic hydro-morphodynamics, discuss their relevance and management perspectives in a global context, and identify knowledge gaps for future study. The CD is classified as a river-tide mixed-energy, muddy and highly turbid, fluvio-deltaic composite system involving large-scale land-ocean interacted processes. Its hydro-morphodynamic evolution exhibits profound temporal variations at the fortnightly, seasonal, and inter-annual time scales, and strong spatial variability between tidal river and tidal estuary, and between different distributary channels. As the river-borne sediment has declined >70%, the deltaic morphodynamic adaptation lags behind sediment decline because sediment redistribution within the delta emerges to play a role in sustaining tidal flat accretion. However, the deltaic channels have become narrower, deepened and growingly constrained under cumulated human activities, e.g., extensive embankment and construction of jetties and groins, possibly initiating a decrease in morphodynamic activities and sediment trapping efficiency. Overall, the CD undergoes transitions from net sedimentation and naturally slow morphodynamic adaptation to erosion and human-driven radical adjustment. A shift in management priority from delta development to ecosystem conservation provides an opportunity for restoring the resilience to flooding and erosion hazards. The lessons and identified knowledge gaps inform study and management of worldwide estuaries and deltas undergoing intensified human interferences.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Coastal Engineerin

Mismatching integration-enabled strains and defects engineering in LDH microstructure for high-rate and long-life charge storage.

Layered double hydroxides (LDH) have been extensively investigated for charge storage, however, their development is hampered by the sluggish reaction dynamics. Herein, triggered by mismatching integration of Mn sites, we configured wrinkled Mn/NiCo-LDH with strains and defects, where promoted mass & charge transport behaviors were realized. The well-tailored Mn/NiCo-LDH displays a capacity up to 518 C g-1 (1 A g-1), a remarkable rate performance (78%@100 A g-1) and a long cycle life (without capacity decay after 10,000 cycles). We clarified that the moderate electron transfer between the released Mn species and Co2+ serves as the pre-step, while the compressive strain induces structural deformation with promoted reaction dynamics. Theoretical and operando investigations further demonstrate that the Mn sites boost ion adsorption/transport and electron transfer, and the Mn-induced effect remains active after multiple charge/discharge processes. This contribution provides some insights for controllable structure design and modulation toward high-efficient energy storage