The poor patency rate following small-diameter vascular grafting remains a major hurdle for the widespread clinical application of artificial blood vessels to date. Our previous studies found that electrospun poly(L-lactide-co-epsilon-caprolactone) (P[LLA-CL]) nanofibers facilitated the attachment and growth of endothelial cells (EC), and heparin incorporated into P(LLA-CL) nanofibers was able to release in a controlled manner. Hence, we hypothesized that heparin-bonded P(LLA-CL) vascular scaffolds with autologous EC pre-endothelialization could significantly promote the graft patency rate. To construct a small-diameter vascular scaffold, the inner layer was fabricated by heparin-bonded P(LLA-CL) nanofibers through coaxial electrospinning, while the outer layer was woven by pure P(LLA-CL) nanofibers. Except dynamic compliance (5.4 ± 1.7 versus 12.8 ± 2.4 × 10-4/mmHg, P < 0.05), maximal tensile strength, burst pressure, and suture retention of the composite, scaffolds were comparable to those of canine femoral arteries. In vitro studies indicated that the scaffolds can continuously release heparin for at least 12 weeks and obtain desirable endothelialization through dynamic incubation, which was confirmed by EC viability and proliferation assay and scanning electronic microscopy. Furthermore, in vivo studies demonstrated that pre-endothelialization by autologous ECs provided a better effect on graft patency rate in comparison with heparin loading, and the united application of pre-endothelialization and heparin loading markedly promoted the 24 weeks patency rate of P(LLA-CL) scaffolds (88.9% versus 12.5% in the control group, P < 0.05) in the canine femoral artery replacement model. These results suggest that heparin-bonded P(LLA-CL) scaffolds have similar biomechanical properties to those of native arteries and possess a multiporous and biocompatible surface to achieve satisfactory endothelialization in vitro. Heparin-bonded P(LLA-CL) scaffolds with autologous EC pre-endothelialization have the potential to be substitutes for natural small-diameter vessels in planned vascular bypass surgery.
1 November 2017 in Journal of Cellular Biochemistry
True sea snakes (Hydrophiini) are among the last and most successful clades of vertebrates that show secondary marine adaptation, exhibiting diverse phenotypic traits and lethal venom systems. To better understand their evolution, we generated the first chromosome-level genomes of two representative Hydrophiini snakes, Hydrophis cyanocinctus and H. curtus. Through comparative genomics we identified a great expansion of the underwater olfaction-related V2R gene family, consisting of more than 1,000 copies in both snakes. A series of chromosome rearrangements and genomic structural variations were recognized, including large inversions longer than 30 megabase (Mb) on sex chromosomes which potentially affect key functional genes associated with differentiated phenotypes between the two species. By integrating multiomics we found a significant loss of the major weapon for elapid predation, three-finger toxin genes, which displayed a dosage effect in H. curtus. These genetic changes may imply mechanisms that drove the divergent evolution of adaptive traits including prey preferences between the two closely related snakes. Our reference-quality sea snake genomes also enrich the repositories for addressing important issues on the evolution of marine tetrapods, and provide a resource for discovering marine-derived biological products.
Poly(L-lactide-co-caprolactone)–collagen–chitosan (P(LLA-CL)–COL–CS) composite grafts were electrospun in this study. Based on the test results for mechanical properties, biodegradability and in vitro cellular compatibility, the optimal weight ratio of P(LLA-CL) to COL/CS was set as 3 : 1. In vivo study was further performed in a canine femoral artery model. The results showed that the 3 : 1 grafts possessed excellent structural integrity, higher patency rate, better endothelial cell (EC) and smooth muscle cells (SMC) growth, as well as higher levels of gene and protein expression of angiogenesis-related cues than those of grafts based on P(LLA-CL). The findings confirmed that the addition of natural materials, such as collagen and chitosan, could effectively improve endothelialization, SMC incursion into the tunica media, and vascular remodeling for tissue engineering.
Introduction: Malnutrition is a frequent problem associated with detrimental clinical outcomes in critically ill patients. To avoid malnutrition, most studies focus on the prevention of inadequate nutrition delivery, whereas little attention is paid to the potential role of exocrine pancreatic insufficiency (EPI). In this trial, we aim to evaluate the prevalence of EPI and identify its potential risk factors in critically ill adult patients without preexisting pancreatic diseases. Methods: In this prospective cross-sectional study, we recruited 563 adult patients with critical illnesses. All details of the patients were documented, stool samples were collected three to five days following the initiation of enteral nutrition, and faecal elastase 1 (FE-1) concentrations were assayed using an enzyme-linked immunosorbent assay kit. Blood samples were also taken to determine serum amylase and lipase activity. Results: The percentages of recruited patients with EPI (FE-1 concentration <200 μg/g) and severe EPI (FE-1 concentration <100 μg/g) were 52.2% and 18.3%, respectively. The incidences of steatorrhea were significantly different (P < 0.05) among the patients without EPI, with moderate EPI (FE-1 concentration = 100 to 200 μg/g) and severe EPI (FE-1 concentration < 100 μg/g). Both multivariate logistic regression analysis and z-tests indicated that the occurrence of EPI was closely associated with shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis. Conclusions: More than 50% of critically ill adult patients without primary pancreatic diseases had EPI, and nearly one-fifth of them had severe EPI. The risk factors for EPI included shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis. Trial registration: NCT01753024