Graphene Quantum Dots Reduce Hypertrophic Scar by Inducing Myofibroblasts To Be a Quiescent State.

Contrary to the initial belief that myofibroblasts are terminally differentiated cells, myofibroblasts have now been widely recognized as an activation state that is reversible. Therefore, strategies targeting myofibroblast to be a quiescent state may be an effective way for antihypertrophic scar therapy. Graphene quantum dots (GQDs), a novel zero-dimensional and carbon-based nanomaterial, have recently garnered significant interest in nanobiomedicine, owing to their excellent biocompatibility, tunable photoluminescence, and superior physiological stability. Although multiple nanoparticles have been used to alleviate hypertrophic scars, a GQD-based therapy has not been reported. Our in vivo studies showed that GQDs exhibited significant antiscar efficacy, with scar appearance improvement, collagen reduction and rearrangement, and inhibition of myofibroblast overproliferation. Further in vitro experiments revealed that GQDs inhibited α-SMA expression, collagen synthesis, and cell proliferation and migration, inducing myofibroblasts to become quiescent fibroblasts. Mechanistic studies have demonstrated that the effect of GQDs on myofibroblast proliferation blocked cell cycle progression by disrupting the cyclin-CDK-E2F axis. This study suggests that GQDs, which promote myofibroblast-to-fibroblast transition, could be a novel antiscar nanomedicine for the treatment of hypertrophic scars and other types of pathological fibrosis.

JAM-A Overexpression in Human Umbilical Cord-Derived Mesenchymal Stem Cells Accelerated the Angiogenesis of Diabetic Wound By Enhancing Both Paracrine Function and Survival of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) is promising in promoting wound healing mainly due to their paracrine function. Nonetheless, the transplanted MSCs presented poor survival with cell dysfunction and paracrine problem in diabetic environment, thus limiting their therapeutic efficacy and clinical application. JAM-A, an adhesion molecule, has been reported to play multi-functional roles in diverse cells. We therefore investigated the potential effect of JAM-A on MSCs under diabetic environment and explored the underlying mechanism. Indeed, high-glucose condition inhibited MSCs viability and JAM-A expression. However, JAM-A abnormality was rescued by lentivirus transfection and JAM-A overexpression promoted MSCs proliferation, migration and adhesion under hyperglycemia. Moreover, JAM-A overexpression attenuated high-glucose-induced ROS production and MSCs apoptosis. The bio-effects of JAM-A on MSCs under hyperglycemia were confirmed by RNA-seq with enrichment analyses. Moreover, Luminex chip results showed JAM-A overexpression dramatically upregulated PDGF-BB and VEGF in the supernatant of MSCs, which was verified by RT-qPCR and western blotting. The supernatant was further found to facilitate HUVECs proliferation, migration and angiogenesis under hyperglycemia. In vivo experiments revealed JAM-A overexpression significantly enhanced MSCs survival, promoted wound angiogenesis, and thus accelerated diabetic wound closure, partially by enhancing PDGF-BB and VEGF expression. This study firstly demonstrated that JAM-A expression of MSCs was inhibited upon high-glucose stimulation. JAM-A overexpression alleviated high-glucose-induced MSCs dysfunction, enhanced their anti-oxidative capability, protected MSCs from hyperglycemia-induced apoptosis and improved their survival, thus strengthening MSCs paracrine function to promote angiogenesis and significantly accelerating diabetic wound healing, which offers a promising strategy to maximize MSCs-based therapy in diabetic wound.

Metabolic Reprogramming and Its Regulatory Mechanism in Sepsis-Mediated Inflammation.

Sepsis is a systemic inflammatory disease caused by an infection that can lead to multiple organ failure. Sepsis alters energy metabolism, leading to metabolic reprogramming of immune cells, which consequently disrupts innate and adaptive immune responses, triggering hyperinflammation and immunosuppression. This review summarizes metabolic reprogramming and its regulatory mechanism in sepsis-induced hyperinflammation and immunosuppression, highlights the significance and intricacies of immune cell metabolic reprogramming, and emphasizes the pivotal role of mitochondria in metabolic regulation and treatment of sepsis. This review provides an up-to-date overview of the relevant literature to inform future research directions in understanding the regulation of sepsis immunometabolism. Metabolic reprogramming has great promise as a new target for sepsis treatment in the future.

Cooperative USV-UAV marine search and rescue with visual navigation and reinforcement learning-based control.

This paper investigates visual navigation and control of a cooperative unmanned surface vehicle (USV)-unmanned aerial vehicle (UAV) system for marine search and rescue. First, a deep learning-based visual detection architecture is developed to extract positional information from the images taken by the UAV. With specially designed convolutional layers and spatial softmax layers, the visual positioning accuracy and computational efficiency are improved. Next, a reinforcement learning-based USV control strategy is proposed, which could learn a motion control policy with an enhanced ability to reject wave disturbances. The simulation experiment results show that the proposed visual navigation architecture can provide stable and accurate position and heading angle estimation in different weather and lighting conditions. The trained control policy also demonstrates satisfactory USV control ability under wave disturbances.

Reinforcement Learning With Task Decomposition for Cooperative Multiagent Systems.

In this article, we study cooperative multiagent systems (MASs) with multiple tasks by using reinforcement learning (RL)-based algorithms. The target for a single-agent RL system is represented by its scalar reward signals. However, for an MAS with multiple cooperative tasks, the holistic reward signal consists of multiple parts to represent the tasks, which makes the problem complicated. Existing multiagent RL algorithms search distributed policies with holistic reward signals directly, making it difficult to obtain an optimal policy for each task. This article provides efficient learning-based algorithms such that each agent can learn a joint optimal policy to accomplish these multiple tasks cooperatively with other agents. The main idea of the algorithms is to decompose the holistic reward signal for each agent into multiple parts according to the subtasks, and then the proposed algorithms learn multiple value functions with the decomposed reward signals and update the policy with the sum of distributed value functions. In addition, this article presents a theoretical analysis of the proposed approach. Finally, the simulation results for both discrete decision-making and continuous control problems have demonstrated the effectiveness of the proposed algorithms.

[Clinical application of abductor digiti minimi muscle flap].

OBJECTIVE: To discuss the surgery procedure and the clinical effectiveness of repairing skin and soft tissue defects in the lateral foot and the heel with the abductor digiti minimi muscle flap. METHODS: Between July 2002 and October 2010, 8 patients with skin and soft tissue defects in the lateral foot and the heel were treated. There were 6 males and 2 females with an average age of 42 years (range, 28-65 years). The locations were the left foot in 5 cases and the right foot in 3 cases. Defects were caused by ulcer of the heel in 2 cases, by poor healing of incision after calcaneus fracture surgery in 1 case, and by crushing in 5 cases. The defect size ranged from 1.5 cmx 1.0 cm x 8.0 cm x 2.6 cm. The disease duration was 30 minutes to 26 months. The result of bacterial culture was positive in 2 cases. After 9 to 15 days of debridement and dressing change, defects were repaired with the abductor digiti minimi muscle flap of 5.6 cm x 1.5 cm to 7.6 cm x 1.8 cm at size. The donor site were sutured directly. RESULTS: Partial necrosis of muscle flap occurred in 1 case at 4 days after operation, which was cured by symptomatic treatment, and the other muscle flaps survived. All incisions of the donor sites healed by first intention. The muscle flaps survived and the granulation grew well at 9-21 days after operation, and the muscle flap wounds were repaired by free leg edge thickness skin grafting. Wounds were repaired by one-stage free skin grafting in 1 case and by two-stage free skin grafting in 7 cases; all skin flaps survived and wounds healed by first intention. Seven patients were followed up 9-18 months (mean, 11 months). The appearance, texture, and sensation were satisfactory. The two-point discrimination was 16-23 mm (mean, 19.5 mm). Epidermal abrasion occurred in 1 case of heel ulcer after weigt-bearing walking. Hallux valgus and muscle weakness occurred in 1 case of necrosis of the peroneus length tendons; and the satisfactory results were achieved in the other patients. CONCLUSION: It has satisfactory effectiveness to use the abductor digiti minimi muscle flap for repairing skin and soft tissue defects in the lateral foot and the heel, which has the advantages of easy-to-operate, safe, less injury at donor site, good appearance and texture, and good recovery of sensation.