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Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons is well understood, which can alleviate inflammation. Nevertheless, potential effects of Nr4a2 on neuroinflammation associated with depression still remains unclear. Chronic lipopolysaccharides (LPS) stress induced depressive-behaviors were confirmed via behavioral tests. Differentially expressed genes were detected by using RNA-sequencing. The anterior cingulate cortex (ACC) tissues were collected for biochemical experiments. The Golgi-Cox staining and virus labeling were used to evaluate the dendritic spines. We applied fluoxetine (FLX) and amodiaquine dihydrochloride (AQ, a highly selective agonist of Nr4a2) in mice. Overexpression experiments were performed by injecting with AAV-Nr4a2-EGFP into ACC. Chemogenetic activation of CamkII neurons via injecting the hM3Dq virus. Mice treated with LPS displayed depressive- and anxiety-like behaviors. The reduction of Nr4a2 and FosB induced by LPS were rescued by pretreatment with FLX or AQ. More importantly, LPS-induced behavior deficits in mice were also alleviated via fluoxetine treatment and pharmacological activation the expression of Nr4a2. Meanwhile, enhancing the level of Nr4a2 could improve dendritic spines loss of neuron and morphological changes in microglia. Overexpression of Nr4a2 in ACC reversed the depressive- and anxiety-like behaviors caused by LPS administration. Activation of CamkII neurons in ACC could robustly increase the expression of Nr4a2 and improve LPS-induced behavior deficits. Our findings demonstrate that the Nr4a2 may regulate depressive-like behaviors via alleviating the impairment of morphology and function on microglia and CamkII neurons induced by chronic neuroinflammation., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Oxidative stress caused by the overexpression of reactive oxygen species (ROS) plays an important role in the pathogenesis of traumatic brain injury (TBI). Accumulation of ROS can lead to cell death, neurodegeneration, and neurological deficit. Therefore, the design and application of functional materials with ROS scavenging ability is of great significance for neural repair. Herein, an injectable and antioxidant hydrogel was developed for TBI treatment based on the Schiff base reaction of gallic acid-conjugated gelatin (GGA) and oxidized dextran (Odex). The resulting GGA/Odex hydrogel could effectively scavenge DPPH and ABTS radicals, as well as protect cells from the oxidative damage in vitro. Moreover, GGA/Odex hydrogel possessed well biocompatible features. In a moderate TBI mouse model, in situ implantation of GGA 6 Odex hydrogel efficiently facilitated neurogenesis and promoted the motor, learning and memory abilities. Also, this composite hydrogel suppressed oxidative stress and inflammation via the activation of Nrf2/HO-1 pathway and the regulating of inflammatory factors secretion and macrophage/microglia polarization. Therefore, this injectable and ROS-scavenging GGA 6 Odex hydrogel is a promising biomaterial for tissue regenerative medicine, including TBI and other tissue repair relevant to raised ROS circumstance., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Infected wound healing has always been a challenge in clinic. Effective and economic wound dressings with combined antibacterial activity and pro-healing function are highly desirable, especially in the context of infected wounds. An obvious advantage of antibacterial wound dressing is to avoid the overuse of antibiotics and the occurrence of drug resistance. Herein, an injectable hyaluronic acid hydrogel with antioxidative and photothermal antibacterial activity as a functional dressing was prepared, characterized and evaluated in an experimental infected wound model. This hydrogel was developed by loading graphene oxide (GO) in a natural polymer network consisting of hyaluronic acid grafted with tyramine (HT) and gelatin grafted with gallic acid (GGA). The HT/GGA/GO hydrogels have a porous cross-linked network structure and demonstrate a good stability, biocompatibility, antioxidant, hemostatic and photothermal antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, in vivo studies have shown that HT 1 /GGA 2 /GO 0.1 hydrogel dressing combined with photothermal therapy can effectively prevent early infection and accelerate wound healing. These results indicated this functionalized injectable hydrogel HT 1 /GGA 2 /GO 0.1 has a great potential in wound dressing application., (Copyright © 2022 Elsevier B.V. All rights reserved.)