Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury.

ABSTRACT: The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro. Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Greenway Cyclists' Visual Perception and Landscape Imagery Assessment.

Greenway is a kind of corridors in the city that takes natural elements as the main constituent foundation and connects open spaces with functions such as leisure and recreation. The assessment of the built greenway is a review of the past construction experiences, and it is also a supplement and improvement to the future greenway planning concept system, which has important academic and application value. This study will explore how greenway design factors influenced the local cyclists' perception of the landscape using on-site questionnaire and photo rating method. The results indicated that greenways with continuous cycling paths, high security awareness, open landscapes, and rich human activities evoke positive perceptions. Among the visual elements, natural elements such as plants and sky are more favorable than artificial elements. The research results show that the formation of greenway cyclists' landscape imagery is affected by visual perception elements, which suggests that special consideration should be given to the laws of cyclists' mental perception when designing greenways.

Associations Between Built Environment Characteristics and Walking in Older Adults in a High-Density City: A Study From a Chinese Megacity.

The built environment is an important factor affecting physical activity, especially walkability. Walkability is used to characterize the user friendliness of outdoor physical activity. However, studies on walkability and physical activity are mainly concentrated on low-density Western cities. Study on the walkability of high-density cities in Asia, especially with the elderly, is seriously lacking. And walkability is often used as a composite indicator. This study mainly re-examines the relationship between the common indicators of walkability (population density, street connectivity, land-use mix, and retail density), transport-related walking, and leisure-time walking with older adults in China's megacities. Twelve housing estates in Wuhan were selected for study areas. We explored the association between the walking activities of 1,161 elderly people (≥60 years old) and the indicators of walkability in their neighborhoods. Socio-demographic characteristics were controlled in the multilevel logistic regression models of the built environment walking associations. We found that there was no significant correlation between the four indicators of walkability and transport-related walking. Street connectivity is significantly positively correlated with the participants' leisure-time walking (OR = 1.499, 95% CI = 1.068~2.103), and there was no significant correlation between the other indicator of walkability and leisure-time walking. The results show that there was no statistical correlation between walkability and transport-related walking in the elderly, and only one indicator was related to leisure-time walking. It is extremely important to re-examine the characteristics of built environments and elderly walking activities in high-density cities. Only by implementing effective intervention strategies in different urban backgrounds can cities move toward a more active and healthier path.