Geospatial analysis in the United States reveals the changing roles of temperature on COVID-19 transmission.

Environmental factors are known to affect outbreak patterns of infectious disease, but their impacts on the spread of COVID-19 along with the evolution of this relationship over time intervals and in different regions are unclear. This study utilized 3 years of data on COVID-19 cases in the continental United States from 2020 to 2022 and the corresponding weather data. We used regression analysis to investigate weather impacts on COVID-19 spread in the mainland United States and estimate the changes of these impacts over space and time. Temperature exhibited a significant and moderately strong negative correlation for most of the US while relative humidity and precipitation experienced mixed relationships. By regressing temperature factors with the spreading rate of waves, we found temperature change can explain over 20% of the spatial-temporal variation in the COVID-19 spreading, with a significant and negative response between temperature change and spreading rate. The pandemic in the continental United States during 2020-2022 was characterized by seven waves, with different transmission rates and wave peaks concentrated in seven time periods. When repeating the analysis for waves in the seven periods and nine climate zones, we found temperature impacts evolve over time and space, possibly due to virus mutation, changes in population susceptibility, social behavior, and control measures. Temperature impacts became weaker in 6 of 9 climate zones from the beginning of the epidemic to the end of 2022, suggesting that COVID-19 has increasingly adapted to wider weather conditions.

Effect of axitinib regulating the pathological blood-brain barrier functional recovery for glioblastoma therapeutics.

AIMS: Dysfunction of the blood-brain barrier (BBB) is a prominent pathological feature of glioblastoma (GBM). Vascular endothelial growth factor (VEGF) is confirmed to be abnormally elevated in the pathogenesis of GBM, causing BBB pathological disruption, which further allows the leakage of neurotoxic blood-derived molecules into the central nervous system (CNS), interfering brain homeostasis and leading to poor patient outcome. Since BBB is an integral and pivotal part of the brain microenvironment, which strongly supports the occurrence and the pathological progression of GBM, here we have selected the VEGFR antagonist axitinib as a BBB functional regulator and hypothesized to regulate pathological BBB restoration for GBM effective treatment. METHODS: The pathological BBB cell model was constructed to investigate the timeliness and dose effect of axitinib regulating pathological BBB restoration. In order to investigate the efficacy and safety of axitinib regulating pathological BBB restoration for anti-GBM treatment, the orthotropic GBM-bearing mice model was established for in vivo study, and bioluminescent imaging was used to real-time and noninvasively monitor tumor growth response in vivo, and survival time was also recorded. RESULTS: Axitinib under non-cytotoxic dosage regulated pathological BBB restoration in a time-dependent mode, and multiple intervention of axitinib could realize a visible restoration of pathological BBB in vitro. Moreover, axitinib treatment restored pathological BBB in orthotropic GBM-bearing mice. We further confirmed that functional restoration of pathological BBB with axitinib had certain curative effect in prolonging median survival of orthotropic GBM-bearing mice at non-cytotoxic dosages in vivo. CONCLUSION: The mechanism of axitinib involved in BBB functional regulation in the treatment of GBM is first illuminated in this report; moreover, this is the first report first referring to regulating pathological BBB functional recovery for GBM effective therapeutics. Overall, the view of regulating pathological BBB functional recovery may offer a novel sight for other CNS diseases relating to BBB permeability effective therapeutics.