Controlling traumatic bleeding from damaged internal organs while effectively sealing the wound is critical for saving the lives of patients. Existing bioadhesives suffer from blood incompatibility, insufficient adhesion to wet surfaces, weak mechanical properties, and complex application procedures. Here, we engineered a ready-to-use hemostatic bioadhesive with ultra-strengthened mechanical properties and fatigue resistance, robust adhesion to wet tissues within a few seconds of gentle pressing, deformability to accommodate physiological function and action, and the ability to stop bleeding efficiently. The engineered hydrogel, which demonstrated high elasticity (>900%) and toughness (>4600 kJ/m³), was formed by fine-tuning a series of molecular interactions and crosslinking mechanisms involving N-hydroxysuccinimide (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe³⁺ ions. Dual adhesive moieties including mussel-inspired pyrogallol/catechol and NHS synergistically enhanced wet tissue adhesion (>400 kPa in a wound closure test). In conjunction with physical sealing, the high affinity of TA/Fe³⁺ for blood could further augment hemostasis. The engineered bioadhesive demonstrated excellent in vitro and in vivo biocompatibility as well as improved hemostatic efficacy as compared to commercial Surgicel®. Overall, the hydrogel design strategy described herein holds great promise for overcoming existing obstacles impeding clinical translation of engineered hemostatic bioadhesives.

SUMMARY: Robotic interventional neuroradiology is an emerging field with the potential to enhance patient safety, reduce occupational hazards, and expand systems of care. Endovascular robots allow the operator to precisely control guidewires and catheters from a lead-shielded cockpit located several feet (or potentially hundreds of miles) from the patient. This has opened up the possibility of expanding telestroke networks to patients without access to life-saving procedures such as stroke thrombectomy and cerebral aneurysm occlusion by highly-experienced physicians. The prototype machines, first developed in the early 2000s, have evolved into machines capable of a broad range of techniques, while incorporating newly automated maneuvers and safety algorithms. In recent years, preliminary clinical research has been published demonstrating the safety and feasibility of the technology in cerebral angiography and intracranial intervention. The next step is to conduct larger, multisite, prospective studies to assess generalizability and, ultimately, improve patient outcomes in neurovascular disease.

Introduction Tortuous vascular anatomy is one of the greatest challenges in mechanical thrombectomy. This study examines the impact of vascular tortuosity on the performance of stent retrievers and evaluates the efficacy of the newer generation stent retrievers with segmented design. Materials and methods Models with mild, moderate, and severe tortuosity with an internal carotid artery (ICA) and a middle cerebral artery (MCA) were created. An elastic and cohesive clot was placed in the MCA lying from distal M1 and proximal M2. We assessed the revascularization rates of two commonly used stent retrievers (Trevo XP and Solitaire FR) and two newer stent retrievers with segmented design (Embotrap and Versi) in each vascular model. Results Both the type of stent retriever and the severity of vessel tortuosity significantly affected the successful recanalization rate. Post-hoc tests showed that the rate of revascularization was significantly less in severe tortuosity than in mild or moderate tortuosity (P<0.001). The Versi resulted in higher success rates than the Solitaire (P<0.01) and the Trevo (P<0.05). The success rates of the Embotrap were higher than the Solitaire and Trevo stent retrievers, although the difference was not statistically significant. Conclusions Severe tortuosity reduces the performance of mechanical thrombectomy. The segmented design in stent retrievers could improve the efficacy of mechanical thrombectomy in tortuous vessels. Trial registration ESCAPE NCT01778335;SWIFT PRIME > NCT01657461; REVASCAT > NCT01692379; All post-results.

Sjögren’s syndrome is a chronic autoimmune disorder whose pathogenesis is poorly understood and that lacks effective therapies. Detailed quantitative and spatial analyses of tissues affected by Sjögren’s syndrome were undertaken, including the quantitation of the frequency of selected cell–cell interactions in the disease milieu. Quantitative analyses of CD4⁺T cell subsets and of CD8⁺T cells in the labial salivary glands from untreated patients with primary Sjögren’s syndrome revealed that activated CD8⁺cytotoxic T cells (CD8⁺CTLs) were the most prominent T cells in these infiltrates. An accumulation of apoptotic glandular epithelial cells, mainly ductal and acinar cells, was observed, consistent with the impaired salivary secretion often observed in patients with this disease. FasL expressing activated CD8⁺T cells were seen to accumulate around Fas expressing apoptotic epithelial cells. Quantitative analyses of apoptotic cell types and of conjugates between cytotoxic T cells and epithelial cells undergoing apoptosis suggest that Sjögren’s syndrome is primarily driven by CD8⁺CTL mediated execution of epithelial cells mainly represented by ductal and acinar cells.

We previously showed that ΔNp63β, a splicing variant of ΔNp63, mediated EMT and affected cell motility. DNA microarray was thus performed to elucidate the mechanism that ΔNp63β affects cell motility. As the results, Wnt5a was significantly down-regulated by ΔNp63β overexpression in tongue SCC cell line (SQUU-B) with EMT phenotype. Seven OSCC cell lines were used. Expression of ΔNp63, Wnt5a, its receptor Ror2, and matrix metalloproteinases (MMPs) were analyzed by RT-PCR, real-time PCR, and western blotting, and gelatin zymography. Furthermore, we examined the effects of siRNA for Wnt5a or Ror2 and recombinant human Wnt5a (rhWnt5a) on motility of tongue SCC cells. Biopsy specimens from tongue SCC patients were used for immunohistochemical staining of Wnt5a and Ror2. Wnt5a and Ror2 were expressed only in SQUU-B cells without ΔNp63 expression, and negatively associated with ΔNp63 expression in other cells. ΔNp63β overexpression in SQUU-B cells decreased Wnt5a and Ror2 expression. By Wnt5a or Ror2 knockdown, cell motility was remarkably inhibited, but EMT markers expression was unaffected. MMP-2 expression and the activities inversely correlated with ΔNp63 expression, and were inhibited by Wnt5a or Ror2 knockdown. Cell motility and MMP-2 activities were recovered by adding rhWnt5a in the cells with Wnt5a knockdown, but not in those with Ror2 knockdown. Moreover, immunohistochemical analyses in tongue SCC specimens found that high expression of Wnt5a or Ror2 was associated with poorer prognosis. Wnt5a-Ror2 signaling enhanced tongue SCC cell aggressiveness and promoted production of MMP-2 following ΔNp63β-mediated EMT.