Mitochondrial flashes (mitoflashes) are recently discovered excitable mitochondrial events in many cell types. Here we investigate their occurrence in the context of structural long-term potentiation (sLTP) at hippocampal synapses. At dendritic spines stimulated by electric pulses, glycine, or targeted glutamate uncaging, induction of sLTP is associated with a phasic occurrence of local, quantized mitochondrial activity in the form of one or a few mitoflashes, over a 30-min window. Low-dose nigericin or photoactivation that elicits mitoflashes stabilizes otherwise short-term spine enlargement into sLTP. Meanwhile, scavengers of reactive oxygen species suppress mitoflashes while blocking sLTP. With targeted photoactivation of mitoflashes, we further show that the stabilization of sLTP is effective within the critical 30-min time-window and a spatial extent of ~2 μm, similar to that of local diffusive reactive oxygen species. These findings indicate a potential signaling role of dendritic mitochondria in synaptic plasticity, and provide new insights into the cellular function of mitoflashes.

Proteinuria and decline of renal function are associated with progression of kidney disease. The Renin Angiotensin Aldosterone System (RAAS) plays an important role in blood pressure regulation, fluid volume, and sodium balance. Overactivity of RAAS contributes to the pathogenesis of a variety of clinical conditions including progress of chronic kidney disease (CKD). This review summarizes the use of RAAS inhibitors as dual therapy or monotherapy in different stages of kidney disease. Experimental and clinical studies have demonstrated RAAS inhibitors prevent proteinuria, kidney fibrosis and slow decline of renal function and thus play a protective role in both early and end stages of kidney disease. While combination use of RAAS inhibitors showed higher efficiency compared with monotherapy, it is also associated with higher incidence of adverse events. Besides ACEI/ARBs, more mechanism research of mineralocorticoid receptor antagonists in kidney disease should be performed.

In patients with spinal chordoma, young age, location in sacral spine, dedifferentiated pathology, and chemotherapy were negative predictors of PFS, while young and old age, bladder or bowel dysfunction at presentation, dedifferentiated pathology, recurrence or progression, and metastases portended a worse OS.