Design Principles of Quinone Redox Systems for Advanced Sulfide Solid-State Organic Lithium Metal Batteries.

The emergence of solid-state battery technology presents a potential solution to the dissolution challenges of high-capacity small molecule quinone redox systems. Nonetheless, the successful integration of argyrodite-type Li6PS5Cl, the most promising solid-state electrolyte system, and quinone redox systems remains elusive due to their inherent reactivity. Here, a library of quinone derivatives is selected as model electrode materials to ascertain the critical descriptors governing the (electro)chemical compatibility and subsequently the performances of Li6PS5Cl-based solid-state organic lithium metal batteries (LMBs). Compatibility is attained if the lowest unoccupied molecular orbital level of the quinone derivative is sufficiently higher than the highest occupied molecular orbital level of Li6PS5Cl. The energy difference is demonstrated to be critical in ensuring chemical compatibility during composite electrode preparation and enable high-efficiency operation of solid-state organic LMBs. Considering these findings, a general principle is proposed for the selection of quinone derivatives to be integrated with Li6PS5Cl, and two solid-state organic LMBs, based on 2,5-diamino-1,4-benzoquinone and 2,3,5,6-tetraamino-1,4-benzoquinone, are successfully developed and tested for the first time. Validating critical factors for the design of organic battery electrode materials is expected to pave the way for advancing the development of high-efficiency and long cycle life solid-state organic batteries based on sulfides electrolytes.

Exploring the association between social isolation and utilization of primary health services by older adults: evidence from China.

Objective: This study aims to investigate the impact of social isolation on the utilization of primary health services among older adults in China. Methods: Data from the China Longitudinal Aging Social Survey (CLASS) conducted in 2018 were utilized. A binary logistic regression model was established, and propensity score matching (PSM) was employed for analysis. Results: The results of the binary logistic regression showed that family isolation within social isolation had a significant negative impact on the utilization of primary health services for older adults. In contrast, there was no significant association between friend isolation, community isolation, and the utilization of primary health services. Furthermore, the PSM results, using three matching methods (nearest neighbor matching, radius matching, and kernel matching), confirmed that family isolation significantly reduced older adults' utilization of primary health services, consistent with the baseline regression findings. Conclusion: Reducing the occurrence of family isolation among older adults may be a cost-effective intervention measure. Efforts should be directed toward improving family support for older adults, promoting the utilization of primary health services, and strengthening disease prevention.

Preliminary study of improving immune tolerance in vivo of bioprosthetic heart valves through a novel antigenic removal method.

The durability of bioprosthetic heart valves is always compromised by the inherent antigenicity of biomaterials. Decellularization has been a promising approach to reducing the immunogenicity of biological valves. However, current methods are insufficient in eliminating all immunogenicity from the biomaterials, necessitating the exploration of novel techniques. In this study, we investigated using a novel detergent, fatty alcohol polyoxyethylene ether sodium sulfate (AES), to remove antigens from bovine pericardium. Our results demonstrated that AES treatment achieved a higher pericardial antigen removal rate than traditional detergent treatments while preserving the mechanical properties and biocompatibility of the biomaterials. Moreover, we observed excellent immune tolerance in the in vivo rat model. Overall, our findings suggest that AES treatment is a promising method for preparing biological valves with ideal clinical application prospects.

A proteomics analysis of neointima formation on decellularized vascular grafts reveals regenerative alterations in protein signature running head: Proteomics analysis of neointima formation.

Background: Neointima formation contributes to vascular grafts stenosis and thrombosis. It is a complex reaction that plays a significant role in the performance of vascular grafts. Despite its critical implications, little is known about the mechanisms underlying neointima formation. This study compares neointima proteome in different stages and plasma samples. Methods: Heterogenous acellular native arteries were implanted as abdominal aortic interposition grafts in a rabbit model. Grafts were harvested at 0.5, 1, 4, 6, 7, 14, 21, and 28 days post-surgery for histological and proteomic analysis of the neointima. Results: Histological examination showed a transformed morphological pattern and components, including serum proteins, inflammatory cells, and regenerative cells. Proteomics analysis of the neointima showed distinct characteristics after 14 days of implantation compared to early implantation. Early changes in the neointima samples were proteins involved in acute inflammation and thrombosis, followed by the accumulation of extracellular matrix (ECM) proteins. A total of 110 proteins were found to be differentially expressed in later samples of neointima compared to early controls. The enriched pathways were mainly protein digestion and adsorption, focal adhesion, PI3K-Akt signaling pathway, and ECM-receptor interaction in the late stage. All distributions of proteins in the neointima are different compared to plasma. Conclusion: The biological processes of neointima formation at different stages identified with proteome found developmental characteristics of vascular structure on a decellularized small vascular graft, and significant differences were identified by proteomics in the neointima of early-stage and late-stage after implantation. In the acute unstable phase, the loose and uniform neointima was mainly composed of plasma proteins and inflammatory cells. However, in the relatively stable later stage, the most notable results were an up-regulation of ECM components. The present study demonstrates an interaction between biological matter and vascular graft, provides insights into biological process changes of neointima and facilitates the construction of a functional bioengineered small vascular graft for future clinical applications.

A Novel Crosslinking Method for Improving the Anti-Calcification Ability and Extracellular Matrix Stability in Transcatheter Heart Valves.

More than 200,000 patients with aortic diseases worldwide undergo surgical valve replacement each year, and transcatheter heart valves (THV) have been more widely used than ever before. However, THV made by the glutaraldehyde (Glut) crosslinking method has the disadvantage of being prone to calcification, which significantly reduces the durability of biomaterials. In this study, we applied a novel crosslinking method using ribose in THV for the first time, which can decrease calcification and increase the stability of the extracellular matrix (ECM). We incubated the bovine pericardium (BP) in ribose solution at 37°C by shaking for 12 days and confirmed that the structure of the BP was more compact than that of the Glut group. Moreover, the ribose method remarkably enhanced the biomechanical properties and provided reliable resistance to enzymatic degradation and satisfactory cellular compatibility in THV. When the BP was implanted subcutaneously in vivo, we demonstrated that ECM components were preserved more completely, especially in elastin, and the immune-inflammatory response was more moderate than that in the Glut treatment group. Finally, the ribose-cross-linked materials showed better anti-calcification potential and improved durability of THV than Glut-cross-linked materials.

Improved Cytocompatibility and Reduced Calcification of Glutaraldehyde-Crosslinked Bovine Pericardium by Modification With Glutathione.

Bioprosthetic heart valves (BHVs) used in clinics are fabricated via glutaraldehyde (GLUT) crosslinking, which results in cytotoxicity and causes eventual valve calcification after implantation into the human body; therefore, the average lifetime and application of BHVs are limited. To address these issues, the most commonly used method is modification with amino acids, such as glycine (GLY), which is proven to effectively reduce toxicity and calcification. In this study, we used the l-glutathione (GSH) in a new modification treatment based on GLUT-crosslinked bovine pericardium (BP) as the GLUT + GSH group, BPs crosslinked with GLUT as GLUT-BP (control group), and GLY modification based on GLUT-BP as the GLUT + GLY group. We evaluated the characteristics of BPs in different treatment groups in terms of biomechanical properties, cell compatibility, aldehyde group content detection, and the calcification content. Aldehyde group detection tests showed that the GSH can completely neutralize the residual aldehyde group of GLUT-BP. Compared with that of GLUT-BP, the endothelial cell proliferation rate of the GLUT + GSH group increased, while its hemolysis rate and the inflammatory response after implantation into the SD rat were reduced. The results show that GSH can effectively improve the cytocompatibility of the GLUT-BP tissue. In addition, the results of the uniaxial tensile test, thermal shrinkage temperature, histological and SEM evaluation, and enzyme digestion experiments proved that GSH did not affect the ECM stability and biomechanics of the GLUT-BP. The calcification level of GLUT-BP modified using GSH technology decreased by 80%, indicating that GSH can improve the anti-calcification performance of GLUT-BP. Compared with GLUT-GLY, GLUT + GSH yielded a higher cell proliferation rate and lower inflammatory response and calcification level. GSH can be used as a new type of anti-calcification agent in GLUT crosslinking biomaterials and is expected to expand the application domain for BHVs in the future.

Photooxidation and Pentagalloyl Glucose Cross-Linking Improves the Performance of Decellularized Small-Diameter Vascular Xenograft In Vivo.

Small-diameter vascular grafts have a significant need in peripheral vascular surgery and procedures of coronary artery bypass graft (CABG); however, autografts are not always available, synthetic grafts perform poorly, and allografts and xenografts dilate, calcify, and induce inflammation after implantation. We hypothesized that cross-linking of decellularized xenogeneic vascular grafts would improve the mechanical properties and biocompatibility and reduce inflammation, degradation, and calcification in vivo. To test this hypothesis, the bovine internal mammary artery (BIMA) was decellularized by detergents and ribozymes with sonication and perfusion. Photooxidation and pentagalloyl glucose (PGG) were used to cross-link the collagen and elastin fibers of decellularized xenografts. Modified grafts' characteristics and biocompatibility were studied in vitro and in vivo; the grafts were implanted as transposition grafts in the subcutaneous of rats and the abdominal aorta of rabbits. The decellularized grafts were cross-linked by photooxidation and PGG, which improved the grafts' biomechanical properties and biocompatibility, prevented elastic fibers from early degradation, and reduced inflammation and calcification in vivo. Short-term aortic implants in the rabbits showed collagen regeneration and differentiation of host smooth muscle cells. No occlusion and stenosis occurred due to remodeling and stabilization of the neointima. A good patency rate (100%) was maintained. Notably, implantation of non-treated grafts exhibited marked thrombosis, an inflammatory response, calcification, and elastin degeneration. Thus, photooxidation and PGG cross-linking are potential tools for improving grafts' biological performance within decellularized small-diameter vascular xenografts.

Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response.

Small-diameter vascular grafts (diameter <6 mm) are in high demand in clinical practice. Neointimal hyperplasia, a common complication after implantation of small-diameter vascular grafts, is one of the common causes of graft failure. Modulation of local inflammatory responses is a promising strategy to attenuates neointimal hyperplasia. Vascular endothelial growth factor (VEGF) is an angiogenesis stimulator that also induces macrophage polarization and modulates inflammatory responses. In the present study, we evaluated the effect of VEGF on the neointima hyperplasia and local inflammatory responses of decellularized vascular grafts. In the presence of rhVEGF-165 in RAW264.6 macrophage culture, rhVEGF-165 induces RAW264.6 macrophage polarization to M2 phenotype. Decellularized bovine internal mammary arteries were implanted into the subcutaneous and infrarenal abdominal aorta of New Zealand rabbits, with rhVEGF-165 applied locally to the adventitial of the grafts. The vascular grafts were removed en-bloc and submitted to histological and immunofluorescence analyses on days 7 and 28 following implantation. The thickness of the fibrous capsule and neointima was thinner in the VEGF group than that in the control group. In the immunofluorescence analysis, the number of M2 macrophages and the ratio of M2/M1 macrophages in vascular grafts in the VEGF group were higher than those in the control group, and the proinflammatory factor IL-1 was expressed less than in the control group, but the anti-inflammatory factor IL-10 was expressed more. In conclusion, local VEGF administration attenuates neointimal hyperplasia in decellularized small-diameter vascular grafts by inducing macrophage M2 polarization and modulating the inflammatory response.

Yak Pericardium as an Alternative Biomaterial for Transcatheter Heart Valves.

Transcatheter aortic valve implantation (TAVI) has received much attention and development in the past decade due to its lower risk of complication and infections compared to a traditional open thoracotomy. However, the current commercial transcatheter heart valve does not fully meet clinical needs; therefore, new biological materials must be found in order to meet these requirements. We have discovered a new type of biological material, the yak pericardium. This current research studied its extracellular matrix structure, composition, mechanical properties, and amino acid content. Folding experiment was carried out to analyze the structure and mechanics after folding. We also conducted a subcutaneous embedding experiment to analyze the inflammatory response and calcification after implantation. Australian bovine pericardium, local bovine pericardium, and porcine pericardium were used as controls. The overall structure of the yak pericardium is flat, the collagen runs regularly, it has superior mechanical properties, and the average thickness is significantly lower than that of the Australian bovine and the local bovine pericardium control groups. The yak pericardium has a higher content of elastic fibers, showing that it has a better compression resistance effect during the folding experiment as well as having less expression of transplantation-related antigens. We conducted in vivo experiments and found that the yak pericardium has less inflammation and a lower degree of calcification. In summary, the yak pericardium, which is thin and strong, has lower immunogenicity and outstanding anti-calcification effects may be an excellent candidate valve leaflet material for TAVI.