Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. However, attaining consistently high performance of these functions in vivo in one single nano-construct remains extremely challenging. Here we demonstrate the use of one single polymer to develop a smart “all-in-one” nanoporphyrin platform that conveniently integrates a broad range of clinically relevant functions. Nanoporphyrins can be used as amplifiable multimodality nanoprobes for near-infrared fluorescence imaging (NIRFI), magnetic resonance imaging (MRI), positron emission tomography (PET) and dual modal PET-MRI. Nanoporphyrins greatly increase the imaging sensitivity for tumor detection through background suppression in blood, as well as preferential accumulation and signal amplification in tumors. Nanoporphyrins also function as multiphase nanotransducers that can efficiently convert light to heat inside tumors for photothermal-therapy (PTT), and light to singlet oxygen for photodynamic-therapy (PDT). Furthermore, nanoporphyrins act as programmable releasing nanocarriers for targeted delivery of drugs into tumors.

Autophagy requires diverse membrane sources and involves membrane trafficking of mATG9, the only membrane protein in the ATG family. However, the molecular regulation of mATG9 trafficking for autophagy initiation remains unclear. Here we identified two conserved classic adaptor protein sorting signals within the cytosolic N-terminus of mATG9, which mediate trafficking of mATG9 from the plasma membrane and trans-Golgi network (TGN) via interaction with the AP1/2 complex. Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation. Our findings uncover novel mechanisms of mATG9 trafficking and suggest a coordination of basal and stress-induced autophagy.

Although zinc oxide nanoparticles (ZnO NPs) have been widely used, their potential hazards on mammalian and human remain largely unknown. In this study, the biochemical compositions of urine and kidney from the rats treated with ZnO NPs (100, 300 and 1000 mg/kg, respectively) were investigated using (1)H nuclear magnetic resonance (NMR) technique with the pattern recognition of partial least squares-discriminant analysis. Hematology, clinical biochemistry and kidney histopathological examinations were also performed. Metabolic profiles from rats treated with ZnO NP(S) exhibited increases in the levels of taurine, lactate, acetate, creatine, phosphocholine, trimethylamine-N-oxide, α-glucose, and 3-D-hydroxybutyrate, as well as decreases in lipid, succinate, citrate, α-ketoglutarate, hippurate and 4-hydroxyphenylacetic acid in urine after ZnO NPs treatment for 14 days. A similar alteration pattern was also identified in kidney. Urine choline and phosphocholine increased significantly shortly after ZnO NPs treatment, moreover, some amino acids and glucose also increased during the experimental period. However, succinate, citrate and α-ketoglutarate in urine exhibited a different alteration trend, which showed increases on the first day after ZnO NPs treatment, but decreases gradually until the termination of the study. A similar alteration pattern of urinary (1)H NMR spectra was also detected in kidney. Moreover, ZnO NPs (1000 mg/kg) resulted in significant increases in serum creatine and blood urea nitrogen, decreases in hemoglobin, haematocrit and mean corpuscular hemoglobin concentration, and overt tubular epithelial cell necrosis. These findings show that ZnO NPs can disturb the energy metabolism and cause mitochondria and cell membrane impairment in rat kidney, which may contribute to ZnO NPs-induced nephrotoxicity.

Interleukin 17(A) (IL-17) is a potent pro-inflammatory cytokine that acts as a central regulator of inflammatory response within the brain, but its physiological roles under non-inflammatory conditions remain elusive. Here we report that endogenous IL-17 ablates neurogenesis in the adult dentate gyrus (DG) of hippocampus. Genetic deletion of IL-17 increased the number of adult-born neurons in the DG. Further, we found that IL-17 deletion altered cytokine network, facilitated basal excitatory synaptic transmission, enhanced intrinsic neuronal excitability, and increased expression of proneuronal genes in neuronal progenitor cells (NPCs). Our findings suggest a profound role of IL-17 in the negative regulation of adult hippocampal neurogenesis under physiology conditions.