Blockade of VEGFR1 and 2 Suppresses Pathological Angiogenesis and Vascular Leakage in the Eye

VEGFR1 and 2 signaling have both been increasingly shown to mediate complications of ischemic retinopathies, including retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and diabetic retinopathy (DR). This study evaluates the effects of blocking VEGFR1 and 2 on pathological angiogenesis and vascular leakage in ischemic retinopathy in a model of ROP and in choroidal neovascularization (CNV) in a model of AMD.H]-mannitol leakage from blood vessels into the retina. Gene expression was measured by real-time quantitative (Q)PCR.VEGFR1 and VEGFR2 expressions were up-regulated during CNV pathogenesis. Both MF1 and DC101 significantly suppressed CNV at 50 mg/kg: DC101 suppressed CNV by 73±5% (p<0.0001) and MF1 by 64±6% (p = 0.0002) in a dosage-dependent manner. The combination of MF1 and DC101 enhanced the inhibitory efficacy and resulted in an accumulation of retinal microglia at the CNV lesion. Similarly, both MF1 and DC101 significantly suppressed retinal NV in OIR at 50 mg/kg: DC101 suppressed retinal NV by 54±8% (p = 0.013) and MF1 by 50±7% (p<0.0002). MF1 was even more effective at inhibiting ischemia-induced BRB breakdown than DC101: the retina/lung leakage ratio for MF1 was reduced by 73±24%, p = 0.001 and for DC101 by 12±4%, p = 0.003. The retina/renal leakage ratio for MF1 was reduced by 52±28%, p = 0.009 and for DC101 by 13±4%, p = 0.001.Our study provides further evidence that both VEGFR1 and 2 mediate pathological angiogenesis and vascular leakage in these models of ocular disease and suggests that antagonist antibodies to these receptor tyrosine kinases (RTKs) are potential therapeutic agents

Wildfire Smoke Impacts on Indoor Air Quality Assessed Using Crowdsourced Data in California

Wildfires have become the dominant source of particulate matter (PM2.5, < 2.5 µm diameter) leading to unhealthy air quality index occurrences in the western United States. Since people mainly shelter indoors during wildfire smoke events, the infiltration of wildfire PM2.5 into indoor environments is a key determinant of human exposure, and is potentially controllable with appropriate awareness, infrastructure investment, and public education. Using time-resolved observations outside and inside over 1400 buildings from the crowdsourced PurpleAir sensor network in California, we found that infiltration ratios (indoor PM­2.5 of outdoor origin/outdoor PM2.5) were reduced on average from 0.4 during non-fire days to 0.2 during wildfire days. Even with reduced infiltration, mean indoor concentration of PM2.5 nearly tripled during wildfire events, with lower infiltration in newer buildings and those utilizing air conditioning or filtration. </p

Wildfire smoke impacts on indoor air quality assessed using crowdsourced data in California

Wildfires have become an important source of particulate matter (PM2.5 &lt; 2.5-µm diameter), leading to unhealthy air quality index occurrences in the western United States. Since people mainly shelter indoors during wildfire smoke events, the infiltration of wildfire PM2.5 into indoor environments is a key determinant of human exposure and is potentially controllable with appropriate awareness, infrastructure investment, and public education. Using time-resolved observations outside and inside more than 1,400 buildings from the crowdsourced PurpleAir sensor network in California, we found that the geometric mean infiltration ratios (indoor PM2.5 of outdoor origin/outdoor PM2.5) were reduced from 0.4 during non-fire days to 0.2 during wildfire days. Even with reduced infiltration, the mean indoor concentration of PM2.5 nearly tripled during wildfire events, with a lower infiltration in newer buildings and those utilizing air conditioning or filtration

Air quality, health, and equity impacts of vehicle electrification in India

Ambient air pollution in India accounts for 870 000 deaths per year, including 43 000 from road transportation. Vehicle electrification could posit a sustainable solution. However, 3/4th of India’s electric grid is powered by coal, emitting large amounts of PM _2.5 , SO _2 , and NO _x . This leads to uncertainty regarding the health benefits and distributional consequences from vehicle electrification. Our results show that if electric vehicles made up 30% of vehicle kilometers traveled, there would be 1000–2000 additional deaths each year under present day conditions. Higher increases in pollution exposure are seen in scheduled castes/tribes, poor, and rural populations particularly in high coal production states. Switching to net zero-emitting electricity generation for charging would reduce air pollution attributable deaths by 6000–7000 annually and PM _2.5 exposure across all groups of population