Abstract Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment. SNHL (SNHL health however disease Recently therapies (MSCs products namely immunogenicity concerns accessibility Nevertheless MSCderived MSC unclear neomycininduced neomycin induced vitro addition effect Mechanistically formation survival ototoxicity summary exosomemediated exosome mediated endocytosisdependent endocytosis dependent manner treatment

ABSTRACT Expressways in China are developing rapidly, as is traffic pollution, which is one of the major sources of urban pollution. In this study, we chose the greenbelt in the idle zone near the Lin’an toll station along the Hang Rui expressway as our sampling area. Five points in the sampling area along Qianjin road were marked vertically at distances of 0, 15, 30, 45 and 60 m to monitor concentrations of PM2.5 and learn the varying patterns of these concentrations and influencing factors. The results showed that in spring (March, April and May), the average PM2.5 concentrations in the greenbelt were 32.56 ± 22.51, 77.71 ± 32.11 and 64.15 ± 29.00 μg m-3, respectively. The ranking of concentrations at different monitoring points in the same period was 0 > 15 > 60 > 30 > 45 m. The average concentrations in winter (November and December 2017, and February 2018) were 33.56 ± 9.34, 60.78 ± 17.67 and 124.71 ± 43.19 μg m-3, respectively. However, the ranking of concentrations at different monitoring points in the same period revealed some differences. Except at 0 m, the concentrations of PM2.5 in the other four positions were higher in winter than in spring. The reduction rate at 45 m reached its maximum in both spring and winter. PM2.5 concentrations were significantly correlated with meteorological factors, the structure of the plant community and traffic flow. PM2.5 concentrations were negatively correlated with temperature, positively correlated with relative humidity and was not significantly correlated with wind speed. The correlations of PM2.5 concentrations with the canopy density and degree of porosity differed greatly due to different seasons, and concentrations were significantly correlated with the amount of traffic flow, especially when there were large trucks.

RESUMEN Las vías rápidas se están desarrollando con gran celeridad en China y junto con ellas la contaminación por tráfico, que es una de las mayores fuentes de contaminación urbana. En este estudio se eligió como área de muestreo el cinturón verde ubicado en la zona de amortiguamiento cercana a la estación de peaje Lin’an en la autopista Hang Rui. Se seleccionaron cinco puntos verticales a lo largo de la carretera Qianjin a distancias de 0, 15, 30, 45 y 60 m para monitorear las concentraciones de PM2.5 y conocer tanto sus patrones de variaciones como los factores que influyen en ellos. Los resultados mostraron que durante la primavera (marzo, abril y mayo) las concentraciones promedio de PM2.5 en el cinturón verde fueron de 32.56 ± 22.51, 77.71 ± 32.11 y 64.15 ± 29.00 μg m-3, respectivamente. La categorización de las concentraciones en diferentes puntos de monitoreo en el mismo periodo fue de 0 > 15 > 60 > 30 > 45 m. Las concentraciones promedio en invierno (noviembre y diciembre de 2017, y febrero de 2018) fueron de 33.56 ± 9.34, 60.78 ± 17.67 y 124.71 ± 43.19 μg m-3, respectivamente. Sin embargo, la categorización de las concentraciones en diferentes puntos de monitoreo mostró algunas diferencias. Con excepción del punto de muestreo ubicado a 0 m, las concentraciones de PM2.5 en los otros cuatro puntos fueron superiores en invierno que en primavera. La tasa de reducción a una distancia de 45 m alcanzó su máximo tanto en primavera como en invierno. Las concentraciones de PM2.5 tuvieron una correlación significativa con factores meteorológicos, la estructura de la comunidad vegetal y el flujo de tráfico; asimismo, tuvieron una correlación negativa con la temperatura, correlación positiva con la humedad relativa, y correlación no significativa con la velocidad del viento. Las correlaciones de PM2.5 con la densidad y el grado de porosidad de la cubierta vegetal difirieron de manera considerable como resultado de la estacionalidad, y las concentraciones se correlacionaron significativamente con la densidad del flujo de tráfico, especialmente en presencia de camiones pesados.

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, still causes higher mortality than any other bacterial pathogen until now. With the emergence and spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR-TB) strains, it becomes more important to search for alternative targets to develop new antimycobacterial drugs. Lupulone is a compound extracted from Hops (Hurnulus lupulus), which exhibits a good antimicrobial activity against M. tuberculosis with minimal inhibitory concentration (MIC) value of 10 µg/mL, but the response mechanisms of lupulone against M. tuberculosis are still poorly understood. In this study, we used a commercial oligonucleotide microarray to determine the overall transcriptional response of M. tuberculosis H37Rv triggered by exposure to MIC of lupulone. A total of 540 genes were found to be differentially regulated by lupulone. Of these, 254 genes were upregulated, and 286 genes were downregulated. A number of important genes were significantly regulated which are involved in various pathways, such as surface-exposed lipids, cytochrome P450 enzymes, PE/PPE multigene families, ABC transporters, and protein synthesis. Real-time quantitative RT-PCR was performed for choosed genes to verified the microarray results. To our knowledge, this genome-wide transcriptomics approach has produced the first insights into the response of M. tuberculosis to a lupulone challenge.