In the Tibetan Plateau, the black carbon (BC) concentration in surface snow and snow pits has received much attention, whereas the seasonal behavior of aerosol-in-snow concentration, vertical profile, melt-scavenging, and enrichment have received relatively little attention. Here we investigate these processes and their impacts on radiative forcing on the Muji glacier in the westernmost Tibetan Plateau during the 2012 snowmelt season. Increasing impurity concentrations were mostly due to post-deposition effects rather than new deposition. On 5 July, BC concentrations in the surface snow were higher than those of fresh snow, implying enrichment via sublimation and/or melting of previous snow. Fresh snow contained 25ngg-1 BC on 27 July; afterward, BC gradually increased, reaching 730.6ngg-1 in September. BC, organic carbon (OC), and dust concentrations co-varied but differed in magnitude. Melt-scavenging efficiencies were estimated at 0.19±0.05 and 0.04±0.01 for OC and BC, respectively, and the BC in surface snow increased by 20-25 times depending on melt intensity. BC-in-snow radiative forcing (RF) was approximately 2.2Wm-2 for fresh snow and 18.1-20.4Wm-2 for aged snow, and was sometimes reduced by the presence of dust.

Iron is a mineral essential for blood production and a variety of critical cellular functions. Altered iron metabolism has been increasingly observed in many diseases and disorders, but a comprehensive and mechanistic understanding of the cellular impact of impaired iron metabolism is still lacking. We examined the effects of iron overload or iron deficiency on cellular stress responses and autophagy which collectively regulate cell homeostasis and survival. Acute iron loading led to increased mitochondrial ROS (mtROS) production and damage, lipid peroxidation, impaired autophagic flux, and ferroptosis. Iron-induced mtROS overproduction is the mechanism of increased lipid peroxidation, impaired autophagy, and the induction of ferroptosis. Iron excess-induced ferroptosis was cell-type dependent and regulated by activating transcription factor 4 (ATF4). Upregulation of ATF4 mitigated iron-induced autophagic dysfunction and ferroptosis, whereas silencing of ATF4 expression impaired autophagy and resulted in increased mtROS production and ferroptosis. Employing autophagy-deficient hepatocytes and different autophagy inhibitors, we further showed that autophagic impairment sensitized cells to iron-induced ferroptosis. In contrast, iron deficiency activated the endoplasmic reticulum (ER) stress response, decreased autophagy, and induced apoptosis. Decreased autophagy associated with iron deficiency was due to ER stress, as reduction of ER stress by 4-phenylbutyric acid (4-PBA) improved autophagic flux. The mechanism of decreased autophagy in iron deficiency is a disruption in lysosomal biogenesis due to impaired posttranslational maturation of lysosomal membrane proteins. In conclusion, iron excess and iron deficiency cause different forms of cell stress and death in part through the common mechanism of impaired autophagic function.

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO₃), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration.