Summary The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live-imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. As Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2−/− mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity.

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Excessive poly(ADP-ribose) polymerase-1 (PARP-1) activation plays a significant role in ischemic brain damage. Increasing evidence has supported the hypothesis that PARP-1 induces cell death by depleting intracellular NAD+. Based on our in vitro finding that NAD+ treatment can abolish PARP-1-mediated cell death, we hypothesized that NAD+ administration may decrease ischemic brain injury. In this study, we used a rat model of transient focal ischemia to test this hypothesis. We observed that intranasal NAD+ delivery significantly increased NAD+ contents in the brains. Intranasal delivery with 10 mg/kg NAD+ at 2 hours after ischemic onset profoundly decreased infarct formation when assessed either at 24 or 72 hours after ischemia. The NAD+ administration also significantly attenuated ischemia-induced neurological deficits. In contrast, intranasal administration with 10 mg/kg nicotinamide did not decrease ischemic brain damage. These results provide the first in vivo evidence that NAD+ metabolism is a new target for treating brain ischemia, and that NAD+ administration may be a novel strategy for decreasing brain damage in cerebral ischemia and possibly other PARP-1-associated neurological diseases.

Visual Abstract

Green H2 production from renewable energy sources by water splitting is desired to reduce the use of fossil fuels and CO2 emissions. The past decade has witnessed the fast development of electrolytic water splitting for H2 generation, with most of the studies focusing on the development of superior electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Equally important is the innovation of water splitting system design to tackle the critical issues confronted by conventional water electrolysis. Some interesting developments have recently emerged with additional redox-mediated process to separate the HER and OER in time and space. In this Review, the various strategies for decoupled H2 production are critically reviewed. Based on the additional process, which is introduced in conjunction with the electrochemical process for decoupled electrochemical or chemical H2 production, the distinct operating principle is highlighted for each strategy, and the underlying connections to other strategies are delineated. Lastly, the implications of the decoupled operations in addressing the formidable issues of conventional water electrolysis, their inherent constraints for practical implementation, and potential solutions are broadly discussed.