High-entropy solvent design enabling a universal electrolyte with a low freezing point for low-temperature aqueous batteries.

Amide additives acting as hydrogen-bonding ligands effectively break the cross-linking structures between water molecules and increase the entropy of mixed solvents, thus enabling a mixed solvent with an ultralow freezing point of -98 °C. Zinc-ion batteries using this hybrid solvent exhibit good cycling stability over a wide temperature range from -60 °C to 50 °C.

Acellular Vascular Scaffolds Preloaded With Heparin and Hepatocyte Growth Factor for Small-Diameter Vascular Grafts Might Inhibit Intimal Hyperplasia.

To develop small-diameter (<6 mm) scaffolds capable of accelerating rapid endothelialization and improving long-term patency rate, we created acellular vascular scaffolds preloaded with heparin and hepatocyte growth factor (HGF). Heparin was conjugated to suppress thrombogenic responses, and HGF was immobilized to induce endothelial cells (ECs) proliferation and migration. The scaffolds immobilized with heparin exhibited highly effective localization and sustained release of HGF for 30 days in vitro. We implanted this modified scaffold into the carotid artery of a rabbit model to investigate the efficacy in vivo. The acellular vascular scaffold with heparin only was used as control. After transplantation, the patency of this modified scaffold was 91.67% at 1, 3, 6, and 12 months, while the patency rate in the group with grafted heparin only was 83.33% at 1, 3, 6, and 12 months. This modified scaffold significantly stimulated ECs proliferation and the endothelium aligned in the direction of flow after 12 months. In addition, intimal hyperplasia was significantly reduced in the grafts coated with HGF compared with the control grafts. The small-diameter vascular grafts with an inner diameter of 2.5 mm preloaded with heparin and HGF may be a substitute for autologous blood vessels in clinic.

Isotropic Amorphous Protective Layer with Uniform Interfacial Zincophobicity for Stable Zinc Anode.

Aqueous zinc-ion batteries (AZIBs) have drawn the attention of numerous researchers owing to their high safety and cost-effectiveness. However, the dendrite growth and side reactions of the zinc (Zn) anodes limit their further practical applications. Herein, a porous amorphous silicon nitride protective layer with high zincophobicity is constructed on the Zn anode surface, which can guide the uniform stripping/plating of Zn2+ underneath the protective layer through its isotropic Zn affinity to alleviate the growth of dendrites and by-products. As a result, the amorphous silicon nitride-protected Zn anode can maintain a stable Coulombic efficiency (CE) of 98.8% and low voltage hysteresis for 710 cycles in the half cell. The full cell with the as-prepared Zn anode can deliver excellent electrochemical performances (89.0% capacity retention and 144.4 mAh g-1 discharge capacity after 1000 cycles at 4 A g-1 ). This work reveals the key role of uniform metal affinity induced by the amorphous materials in the interface modification of metal anodes, which is instructive for the design of stable metal anodes.

The crescendo pulse frequency of shear stress stimulates the endothelialization of bone marrow mesenchymal stem cells on the luminal surface of decellularized scaffold in the bioreactor.

A completely confluent endothelial cell (EC) monolayer is required to maintain proper vascular function in small diameter tissue-engineered vascular graft (TEVG). However, the most effective method for EC attachment to the luminal surface and formation of an entire endothelium layer that works in vitro remains a complicated challenge that requires urgent resolution. Although pulsatile flow has been shown to be better suited for the generation of functional endothelium, the optimal frequency setting is unknown. Several pulsatile flow frequencies were used to implant rat bone mesenchymal stem cells (MSC) into the lumen of decellularized porcine carotid arteries. The endothelium's integrity and cell activity were investigated in order to determine the best pulse frequency settings. The results showed that MSC were maximally preserved and exhibited maximal morphological changes with improved endothelialization performance in response to increased pulse stimulation frequency. Increased pulse frequency stimulation stimulates the expression of mechanoreceptor markers, cytoskeleton reorganization in the direction of blood flow, denser skeletal proteins fibronectin, and stronger intercellular connections when compared to constant pulse frequency stimulation. MSC eventually develops an intact endothelial layer with anti-thrombotic properties on the inner wall of the decellularized tubular lumen. Conclusion: The decellularized vessels retain the three-dimensional structure of the vasculature, have a surface topography suitable for MSC growth, and have good mechanical properties. By increasing the frequency of pulsed stimulation, MSC endothelialize the lumen of the decellularized vasculature. It is expected to have anti-thrombotic and anti-neointimal hyperplasia properties after implantation, ultimately improving the patency of TEVG.

A Next-Generation Sequencing of Plasma Exosome-Derived microRNAs and Target Gene Analysis with a Microarray Database of Thermally Injured Skins: Identification of Blood-to-Tissue Interactions at Early Burn Stage.

BACKGROUND: Plasma exosome-derived microRNA (miRNA) profiles following thermal injury and their relationship with gene expression derangements in burned skin remain unexplored. This study focused on the identification of key miRNA-mRNA axes in potential blood-to-tissue interactions at early burn stage. METHODS: Plasma exosomes were obtained from 6 severe burn patients 4-7 days post injury and 6 healthy volunteers. Next-generation sequencing (NGS) of exosomal small RNAs presented the differentially expressed miRNAs (DEMs). Target genes of the DEMs were predicted in the mirDIP database. Dataset GSE8056 was enrolled to acquire differentially expressed genes (DEGs) in burned skin compared to normal skin. Overlap between the DEGs and target genes of the DEMs were focus genes. The protein-protein interaction (PPI) network and enrichment analyses of the focus genes demonstrated hub genes and suggested underlying mechanisms and pathways. The hub genes and upstream DEMs were selected to construct key miRNA-mRNA axes. RESULTS: The NGS of plasma exosome-derived small RNAs identified 85 DEMs (14 downregulated miRNAs and 71 upregulated miRNAs) with 12,901 predicted target genes. Dataset GSE8056 exhibited 1861 DEGs in partial-thickness burned skins 4-7 days postburn. The overlap between DEGs and target genes of DEMs displayed 1058 focus genes. The top 9 hub genes (CDK1, CCNB1, CCNA2, BUB1B, PLK1, KIF11, AURKA, NUSAP1 and CDCA8) in the PPI network of the focus genes pointed to 16 upstream miRNAs in DEMs, including 4 downregulated miRNAs (hsa-miR-6848-3p, has-miR-4684-3p, has-miR-4786-5p and has-miR-365a-5p) and 12 upregulated miRNAs (hsa-miR-6751-3p, hsa-miR-718, hsa-miR-4754, hsa-miR-6754-3p, hsa-miR-4739, hsa-miR-6739-5p, hsa-miR-6884-3p, hsa-miR-1224-3p, hsa-miR-6878-3p, hsa-miR-6795-3p, hsa-miR-550a-3p, and hsa-miR-550b-3p). A key miRNA-mRNA network in potential blood-to-tissue interactions at early burn stage was therefore constructed. CONCLUSION: An NGS and bioinformatic analysis in the study identified key miRNA-mRNA axes in potential blood-to-tissue interactions at early burn stage, suggesting plasma exosome-derived miRNAs may impact on the alteration patterns of gene expressions in a burn wound.

Decellularization of porcine carotid arteries using low-concentration sodium dodecyl sulfate.

BACKGROUND: The decellularized scaffold is a promising material for producing tissue-engineered vascular grafts (TEVGs) because of its complex, native-like three-dimensional structure and mechanical properties. Sodium dodecyl sulfate (SDS), one of the most commonly used decellularization reagents, appears to be more effective than other detergents for removing cells from dense tissues. The concentrations of SDS used in previous studies and their effects on decellularization are not consistent. METHODS: In this study, porcine carotid arteries were decellularized using detergent-based protocols using Triton X-100 followed by SDS at different concentrations and exposing time. Cell removal efficiency and composition were evaluated by histological analysis, and DNA and collagen quantification. Ultrastructure, mechanical properties, pore size distribution, and in vivo biocompatibility of decellularized arteries were also evaluated. RESULTS: The DNA content of decellularized scaffolds treated with 0.3% SDS for 72 h or 0.5% SDS for 48 h was significantly less than that treated with 1% SDS for 30 h. There was a significant loss of soluble collagen after treatment with 1% SDS relative to native arteries. The extensive loss of elastin and glycosaminoglycans was observed in decellularized arteries treated with 0.5% SDS or 1% SDS. The basement membrane and biomechanics were also damaged by these two protocols. Moreover, decellularized scaffolds became more porous with many large pores after treatment with 0.3% SDS. CONCLUSION: Low-concentration SDS could be a suitable choice for artery decellularization. Decellularized porcine carotid arteries, prepared using Triton X-100 followed by 0.3% SDS, may be a promising biological scaffold for TEVGs.

Porcine carotid arteries decellularized with a suitable concentration combination of Triton X-100 and sodium dodecyl sulfate for tissue engineering vascular grafts.

Tissue engineering vascular grafts (TEVGs) constructed by decellularized arteries have the potential to replace autologous blood vessels in bypass surgery for patients with cardiovascular disease. There are various methods of decellularization without a standard protocol. Detergents approaches are simple, and easy control of experimental conditions. Non-ionic detergent Triton X-100 and ionic detergent sodium dodecyl sulfate (SDS) are the most commonly used detergents. In this study, we used Triton X-100 and SDS with different concentrations to decellularize porcine carotid arteries. After that, we investigated the acellular effect and mechanical properties of decellularized arteries to find a promising concentration combination for decellularization. Results showed that any detergents' combination would damage the inherent structure of extracellular matrix, and the destruction increased with the increase of detergents' concentration. We concluded that the decellularization approach of 0.5% Triton X-100 for 24 h combined with 0.25% SDS for 72 h could help to obtain decellularized arteries with minimum destruction. This protocol may be able to prepare a clinically suitable vascular scaffold for TEVGs.

Analysis of 17 years of surgical treatment for chronic limb ischemia in a Chinese National Clinical Center for Geriatric Disorders (2002 to 2018).

OBJECTIVE: The purpose of this study was to determine the trends in patient numbers, procedures numbers, amputation rate, length of stay (LOS) and hospitalization expenses in a National Clinical Research Center for Geriatric Disorders over 17 years (2002-2018). METHODS: The data of inpatients with chronic lower extremity ischemia caused by atherosclerosis in Xuanwu Hospital from 2002 to 2018 was reviewed. RESULTS: 5137 patients were reviewed, of whom 58% (2976/5137) were diabetic. The numbers of annual inpatients, endovascular treatment cases, and mean hospitalization expenses increased over time, and the mean LOS progressively decreased. The amputation rate decreased from 8.12% in 2002 to 2007 to 0.87% in 2008 to 2018 (P < .0001). The mean LOS decreased from 28.20 days in 2002 to 2007 to 11.12 days in 2008 to 2018 (P < .0001). The mean hospitalization expenses rose from 54,466.94 yuan in 2002 to 2007 to 76,469.40 yuan in 2008-2018 (p = .0013). There were no significant differences in mean LOS and mean hospitalization expenses between the diabetic and the non-diabetic groups. In the diabetic subgroup, the amputation rate decreased from 8.83% in 2002 to 2007 into 0.99% in 2008 to 2018 (P < .0001). CONCLUSION: From 2002 to 2018, the number of inpatients with atherosclerotic chronic lower limb ischemia increased gradually, and the number of endovascular treatments increased significantly; concomitantly, the amputation rate and mean LOS decreased, and the mean hospitalization expenses increased. The decreased amputation rate may be related to increased implementation of endovascular treatment or angiogenesis therapy.

Characterization of a heparinized decellularized scaffold and its effects on mechanical and structural properties.

Decellularization is a promising approach in tissue engineering to generate small-diameter blood vessels. However, some challenges still exist. We performed two decellularization phases to develop an optimal decellularized scaffold and analyze the relationship between the extracellular matrix (ECM) composition and mechanical properties. In decellularization phase I, we tested sodium dodecylsulfate (SDS), Triton X-100 (TX100) and trypsin at different concentrations and exposure times. In decellularization phase II, we systematically compared five combined decellularization protocols based on the results of phase I to identify the optimal method. These protocols tested cell removal, ECM preservation, mechanical properties, and residual cytotoxicity. We further immobilized heparin to optimal decellularized scaffolds and determined its anticoagulant activity and mechanical properties. The combined decellularization protocol comprising treatment with 0.5% SDS followed by 1% TX100 could completely remove the cellular contents and preserve the mechanical properties and ECM architecture better. In addition, the heparinized decellularized scaffolds not only had sustained anticoagulant activity, but also similar mechanical properties to native vessels. In conclusion, heparinized decellularized scaffolds represent a promising direction for small-diameter vascular grafts, although further in vivo studies are needed.

Midterm Outcome of Directional Atherectomy Combined with Drug-Coated Balloon Angioplasty Versus Drug-Coated Balloon Angioplasty Alone for Femoropopliteal Arteriosclerosis Obliterans.

BACKGROUND: The "leave nothing behind" strategies have been becoming a popular treatment for femoropopliteal arteriosclerosis obliterans. Atherectomy before drug-coated balloon (DCB) angioplasty may have an advantage in improving the efficiency of drug delivery into the blood vessel wall. This study aimed to compare the therapeutic effects of directional atherectomy combined with DCB angioplasty with DCB angioplasty alone in the treatment of femoropopliteal arteriosclerosis obliterans. METHODS: Patients with femoropopliteal arteriosclerosis obliterans who received endovascular therapy from June 2016 to June 2018 in our hospital and presented with life-limiting claudication or severe chronic limb ischemia comprised the study cohort. The patients were randomized to receive directional atherectomy combined with DCB angioplasty (n = 45) or DCB alone (n = 49). Ninety-four patients were enrolled in our study with 72 males, and the mean age was 67 ± 10 years. The mean lesion length was 112 ± 64 mm. RESULTS: There were no significant differences in the baseline characteristics of patients and lesions between the 2 randomized groups (P > 0.05). Flow-limiting dissections occurred more frequently in the DCB group (n = 12; 24.5%) than in the DA-DCB group (n = 2; 4.4%; P = 0.006). The technical success rate in the DA-DCB group was superior to that in the DCB group (95.6% vs. 75.5%, P = 0.006). The mean follow-up duration was 16.7 ± 6.1 months in the DCB group and 15.3 ± 5.8 months in the DA-DCB group. No amputations were performed. The overall mortality in the DCB group was 4.1% (2/49), while all patients survived in the DA-DCB group. The 12-month and 24-month primary patencies in the DA-DCB group were greater than those in the DCB group (80.5% vs. 75.7% and 67.1% vs. 55.1%, respectively); however, using all available patency data, no significant differences over time were observed (P = 0.377). CONCLUSIONS: In this study, directional atherectomy combined with DCB angioplasty can decrease the flow-limiting dissection rate in the treatment of femoropopliteal arteriosclerosis obliterans compared with DCB angioplasty alone. There was no significant difference between the 2 groups in terms of primary patency rate which was needed to be further clarified.

Decellularization, cross-linking and heparin immobilization of porcine carotid arteries for tissue engineering vascular grafts.

Tissue engineering vascular grafts (TEVGs) have the potential to replace small-diameter grafts in bypass surgery which is good news for patients with cardiovascular disease. Decellularized arteries can be ideal TEVGs because their natural three-dimensional structures support the migration of host cells and vascular remodeling. There are many methods for decellularization without a standard protocol. In this study, a combination of Triton X-100 and sodium dodecyl sulfate (SDS) were used to prepare decellularized arteries. However, decellularization may damage the biochemical and mechanical properties to some degree. We used the cross-linking agents N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to improve mechanical properties and immobilize heparin to inhibit thrombogenesis. Histological analysis, scanning electron microscopy, biomechanical properties test, determination of immobilized heparin, active partial thrombin time assay, and subcutaneous embedding experiment were used to evaluate the efficiency of decellularization and the efficacy of heparinized cross-linked vascular scaffold. Results showed 1% Triton X-100 combined with 0.3% SDS can decellularize successfully. EDC and NHS cross-linking can improve the mechanical properties, reduce the inflammatory reaction and slow the degradation time. Heparin immobilized on the scaffolds can inhibit thrombogenesis effectively. This study indicated the heparinized cross-linked vascular scaffolds may be ideal scaffolds for TEVGs.

Wavelength-scanning surface plasmon resonance microscopy: A novel tool for real time sensing of cell-substrate interactions.

This paper, for the first time, presents a wavelength-scanning surface plasmon resonance microscope (WS-SPRM) as a label-free biosensor capable of measuring cell-substrate interaction. The approach utilized a liquid crystal tunable filter (LCTF) as a fast and flexible wavelength-scanning device that can implement a wavelength-scanning and SPR imaging cycle within 1 s. The system was verified by monitoring the dynamics of cellular processes including cell detachment and electroporation of individual cells. It was found that the WS-SPRM presented better performance than the intensity-based SPRM (I-SPRM) in the imaging of cell adhesion. The results also indicated that the WS-SPRM exhibited a larger dynamic range in monitoring cell electroporation than that of I-SPRM. In summary, the developed WS-SPRM in this study provides a promising technique for real-time monitoring of cell-substrate interaction.