Genetically Engineered Macrophages Co-Loaded with CD47 Inhibitors Synergistically Reconstruct Efferocytosis and Improve Cardiac Remodeling Post Myocardial Ischemia Reperfusion Injury.

Efferocytosis, mediated by the macrophage receptor MerTK (myeloid-epithelial-reproductive tyrosine kinase), is a significant contributor to cardiac repair after myocardial ischemia-reperfusion (MI/R) injury. However, the death of resident cardiac macrophages (main effector cells), inactivation of MerTK （main effector receptor), and overexpression of "do not eat me" signals (brake signals, such as CD47), collectively lead to the impediment of efferocytosis in the post-MI/R heart. To date, therapeutic strategies targeting individual above obstacles are relatively lacking, let alone their effectiveness being limited due to constraints from the other concurrent two. Herein, inspired by the application research of chimeric antigen receptor macrophages (CAR-Ms) in solid tumors, a genetically modified macrophage-based synergistic drug delivery strategy that effectively challenging the three major barriers in an integrated manner is developed. This strategy involves the overexpression of exogenous macrophages with CCR2 (C-C chemokine receptor type 2) and cleavage-resistant MerTK, as well as surface clicking with liposomal PEP-20 (a CD47 antagonist). In MI/R mice model, this synergistic strategy can effectively restore cardiac efferocytosis after intravenous injection, thereby alleviating the inflammatory response, ultimately preserving cardiac function. This therapy focuses on inhibiting the initiation and promoting active resolution of inflammation, providing new insights for immune-regulatory therapy.

High resolution mapping of nighttime light and air pollutants during the COVID-19 lockdown in Wuhan.

The novel coronavirus (COVID-19) has induced unprecedented improvements of air quality due to drastic shrinking of human activities during the pandemic lockdown in 2020. While declines of most air pollutants have been globally evidenced in most cities worldwide, there is few detailed spatial knowledge at local scale. Therefore, we present here a high resolution mapping of the 2018-2020 evolution of human activities and air pollutants in Wuhan. Human activities were assessed by nighttime light radiance. We measured the air quality index (AQI) as the maximum value among air quality sub-indices of SO2, NO2, CO, O3 and particulate matter. We also compared mean monthly pollutant concentration during January-April in 2018, 2019 and 2020. Mapping results show that variations of nighttime light radiance were heterogenous at local scale, showing both rises and declines in the same district. The radiance decreased in eight districts located mostly in the city center, as a result of lower human activity, but the radiance increased in the five surrounding districts, as a consequence of people staying at home. AQI was low during lockdown, averaging at 57, but showed strong daily variations with a slight pollution around February 5 with AQI rising to 126. During this pollution event, particulate matter, SO2, NO2 and CO levels were positively correlated, suggesting common sources, but were not correlated with ozone; and particulate matter, SO2, NO2 and CO decreased with relative humidity, suggesting removal by precipitation. Comparison of 2020 data with previous years shows that particulate matter and NO2 were highly reduced, CO was less reduced due to ongoing power industries, SO2 first declined then increased to exceed 2018-19 values due to coal combustion, and ozone levels was more abundant due both to less NOx pollution and the weekend effect. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10311-021-01222-x.