Silicone-layered waterproof electrohydraulic soft actuators for bio-inspired underwater robots.

Electrohydraulic soft actuators are a promising soft actuation technology for constructing bio-inspired underwater robots owing to the features of this technology such as large deformations and forces, fast responses, and high electromechanical efficiencies. However, this actuation technology requires high voltages, thereby limiting the use of these actuators in water and hindering the development of underwater robots. This paper describes a method for creating bio-inspired underwater robots using silicone-layered electrohydraulic soft actuators. The silicone layer functions as an insulator, enabling the application of high voltages underwater. Moreover, bending and linear actuation can be achieved by applying the silicone layers on one or both sides of the actuator. As a proof of concept, bending and linear actuators with planar dimensions of 20 mm × 40 mm (length × width) are fabricated and characterized. Underwater actuation is observed in both types of actuators. The bending actuators exhibit a bending angle and blocked force of 39.0° and 9.6 mN, respectively, at an applied voltage of 10 kV. Further, the linear actuators show a contraction strain and blocked force of 6.6% and 956.1 mN, respectively, at an applied voltage of 10 kV. These actuators are tested at a depth near the surface of water. This ensured that they can operate at least at that depth. The actuators are subsequently used to implement various soft robotic devices such as a ray robot, a fish robot, a water-surface sliding robot, and a gripper. All of the robots exhibit movements as expected; up to 31.2 mm/s (0.91 body length/s) of locomotion speed is achieved by the swimming robots and a retrieve and place task is performed by the gripper. The results obtained in this study indicate the successful implementation of the actuator concept and its high potential for constructing bio-inspired underwater robots and soft robotics applications.

Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation.

Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin DNA and contents of granules, such as myeloperoxidase (MPO) and neutrophil elastase (NE). NETs are usually released from neutrophils undergoing NETosis, a neutrophil-specific cell death mode characterized by the collapse and disappearance of cell membranes and nuclear envelopes. It is well known that production of reactive oxygen species (ROS) triggers NETosis and NET formation. However, details of intracellular signaling downstream of ROS production during NETosis and NET formation remains uncertain. Here, we demonstrated that the peroxidation of phospholipids plays a critical role in NETosis and NET formation induced by phorbol 12-myristate13-acetate (PMA) or immune complex in vitro and by lipopolysaccharide (LPS) in vivo. This phospholipid peroxidation is mediated by the enzymatic activity of MPO. On the other hand, NE, which was previously reported to be released from granules to cytosol by MPO during NET formation, is not required for either the peroxidation of phospholipids or the execution of NETosis, but contributes to chromatin decondensation and nuclear swelling independently of MPO-mediated oxidized phospholipids. Analysis of isolated nuclei clearly demonstrated that oxidized phospholipids and NE differently yet synergistically execute chromatin decondensation and nuclear swelling, and the subsequent release of nuclear contents. These findings indicate the dual roles of MPO in NETosis and NET formation, and provide new insight into the molecular mechanism of these phenomena.

Immunoregulatory Monocyte Subset Promotes Metastasis Associated With Therapeutic Intervention for Primary Tumor.

Systemic and local inflammation associated with therapeutic intervention of primary tumor occasionally promotes metastatic recurrence in mouse and human. However, it remains unclear what types of immune cells are involved in this process. Here, we found that the tissue-repair-promoting Ym1+Ly6Chi monocyte subset expanded as a result of systemic and local inflammation induced by intravenous injection of lipopolysaccharide or resection of primary tumor and promoted lung metastasis originating from circulating tumor cells (CTCs). Deletion of this subset suppressed metastasis induced by the inflammation. Furthermore, transfer of Ym1+Ly6Chi monocytes into naïve mice promoted lung metastasis in the mice. Ym1+Ly6Chi monocytes highly expressed matrix metalloproteinase-9 (MMP-9) and CXCR4. MMP-9 inhibitor and CXCR4 antagonist decreased Ym1+Ly6Chi-monocyte-promoted lung metastasis. These findings indicate that Ym1+Ly6Chi monocytes are therapeutic target cells for metastasis originating from CTCs associated with systemic and local inflammation. In addition, these findings provide a novel predictive cellular biomarker for metastatic recurrence after intervention for primary tumor.

Corrigendum to: "CD204-positive monocytes and macrophages ameliorate septic shock by suppressing proinflammatory cytokine production in mice".

[This corrects the article DOI: 10.1016/j.bbrep.2020.100791.].

CD204-positive monocytes and macrophages ameliorate septic shock by suppressing proinflammatory cytokine production in mice.

Sepsis is defined as a life-threatening multiorgan dysfunction caused by dysregulated inflammatory response to infection. It remains the primary cause of death from infection if not diagnosed and treated promptly. Therefore, a better understanding of the mechanism for resolving inflammation is needed. Monocytes and macrophages play a pivotal role not only in the induction but also in the suppression of inflammation. However, a tissue-resident macrophage subset that regulates a hyperinflammatory state during sepsis has not been explored. Here we show that CD204+ monocytes and/or macrophages rescued mice from endotoxin-induced septic shock. Serum and tissue proinflammatory cytokine levels were significantly upregulated in the absence of these cells. This study provided evidence that CD204+ monocytes and/or macrophages ameliorate septic shock by suppressing proinflammatory cytokine production.

Emergence of immunoregulatory Ym1+Ly6Chi monocytes during recovery phase of tissue injury.

Ly6Chi monocytes migrate to injured sites and induce inflammation in the acute phase of tissue injury. However, once the causes of tissue injury are eliminated, monocyte-derived macrophages contribute to the resolution of inflammation and tissue repair. It remains unclear whether the emergence of these immunoregulatory macrophages is attributed to the phenotypic conversion of inflammatory monocytes in situ or to the recruitment of bone marrow-derived regulatory cells de novo. Here, we identified a subpopulation of Ly6Chi monocytes that contribute to the resolution of inflammation and tissue repair. Ym1+Ly6Chi monocytes greatly expanded in bone marrow during the recovery phase of systemic inflammation or tissue injury. Ym1+Ly6Chi monocytes infiltrating into an injured site exhibited immunoregulatory and tissue-reparative phenotypes. Deletion of Ym1+Ly6Chi monocytes resulted in delayed recovery from colitis. These results demonstrate that a distinct monocyte subpopulation destined to act in immunoregulation is generated in bone marrow and participates in resolution of inflammation and tissue repair.

The effects of moderate exercise on secretory IgA production in mice depends on dietary carbohydrate intake.

Secretory immunoglobulin A (sIgA) is produced from intestinal mucosa and is essential in preventing infection. We analyzed the influence of moderate exercise on intestinal sIgA production and antioxidative function under different carbohydrate nutritional conditions. Thirty-six mice were fed an experimental diet for 10 weeks-a high-carbohydrate (HC) diet, a low-carbohydrate (LC) diet, or a control (C) diet. After 1 week on the experimental diets, mice were divided into sedentary and exercise groups (n = 6/group), where the exercise consisted of treadmill running for 30 min/day at 11 m/min for 6 days/week in 9 consecutive weeks. Intestinal sIgA levels in the exercise groups fed C or LC diets were significantly lower compared with the parallel sedentary groups, or exercise-group mice fed HC diet. Expression of the polymeric immunoglobulin receptor (pIgR) in the small intestine was significantly higher in the exercise group fed a HC diet. Superoxide dismutase activity in the small intestine was higher in the exercise group than in the sedentary group, with no effects resulting from intake carbohydrate levels. Our results indicated that moderate exercise reduced the levels of intestinal sIgA depending on decreasing of carbohydrate intake, which is connected with the expression of pIgR.

Isolation and characterization of vasohibin-2 as a homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin.

OBJECTIVE: We recently isolated vasohibin, a novel vascular endothelial growth factor (VEGF)-inducible endothelium-derived angiogenesis inhibitor. Our aim is to find DNA sequences homologous to vasohibin and determine their expression profile. METHODS AND RESULTS: By the search of DNA sequences in the database, we found one homologous gene and designated it vasohibin-2. Overall amino acid sequence homology between the prototype vasohibin (vasohibin-1) and vasohibin-2 was >50%. Vasohibin-2 exhibited antiangiogenic activity. Vasohibin-2 expression in cultured endothelial cells was low and not inducible by the stimulation that induced vasohibin-1. However, the immunohistochemical analysis revealed that vasohibin-1 and -2 were diffusely expressed in endothelial cells in embryonic organs during mid-gestation. After that time point, vasohibin-1 and -2 became faint, but persisted to a certain extent in arterial endothelial cells from late gestation to neonate. Expression of vasohibin-1 and -2 could be augmented in vivo by local transfection with the VEGF gene in the embryonic brain or by cutaneous wounding in adult mice. CONCLUSIONS: These results suggest that vasohibin-2, in combination with vasohibin-1, forms a novel family of angiogenesis inhibitors.