A core/shell stretchable conductive composite of a few-walled carbon nanotube network coated on a poly(m-phenylene isophthalamide) fiber (FWNT/PMIA) was fabricated by a dip-coating method and an annealing process that greatly enhanced interactions between the FWNT network and PMIA core as well as within the FWNT network. The first strain-conductivity test of the as-prepared FWNT/PMIA fiber showed a stretching-induced alignment of nanotubes in the shell during the deformation process and a good conductivity stability with a slight conductivity drop from 109.63 S/cm to 98.74 S/cm (Δσ/σ0 = 10%) at a strain of ∼150% (2.5 times the original length). More importantly, after the first stretching process, the fiber can be recovered with a slight increase in length but a greatly improved conductivity of 167.41 S/cm through an additional annealing treatment. The recovered fiber displays a similarly superb conductivity stability against stretching, with a decrease of only ∼13 S/cm to 154.49 S/cm (Δσ/σ0 = 8%) at a strain of ∼150%. We believe that this conductivity stability came from the formation and maintaining of aligned nanotube structures during the stretching process, which ensures the good tube-tube contacts and the elongation of the FWNT network without losing its conductivity. Such stable conductivity in stretchable fibers will be important for applications in stretchable electronics.

This study shows that taurine and ginsenoside Rf act synergistically to increase the expression of brain-derived neurotrophic factor (BDNF) in SH-SY5Y human neuroblastoma cells in a dose- and time-dependent manner. The increase of BDNF mRNA by taurine and ginsenoside Rf was markedly attenuated by inhibitors of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. In addition, taurine and ginsenoside Rf protected cells from corticosterone-induced BDNF suppression and reduced cell viability and lactate dehydrogenase release. The results from this study showed that combined treatment with both taurine and ginsenoside Rf enhanced BDNF expression and protected cells against corticosterone-induced damage.

With the high efficacy of protein-based therapeutics and plenty of intracellular drug targets, cytosolic protein delivery in a cell-specific manner has attracted considerable attention in the field of precision medicine. Herein, we present an intracellular protein delivery system based on a target-specific repebody and the translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform was constructed by genetically fusing an EGFR-specific repebody as a targeting moiety to the translocation domain, while a protein cargo was fused to the C-terminal end of the delivery platform. The delivery platform was revealed to efficiently translocate a protein cargo to the cytosol in a target-specific manner. We demonstrate the utility and potential of the delivery platform by showing a remarkable tumor regression with negligible toxicity in a xenograft mice model when gelonin was used as the cytotoxic protein cargo. The present platform can find wide applications to the cell-selective cytosolic delivery of diverse proteins in many areas.

Neuronal expression of beta-secretase 1 (BACE1) has been implicated in the progression of Alzheimer's disease. However, the mechanisms that regulate BACE1 expression are unclear. Here, we show that peroxisome proliferator-activated receptor delta (PPARd) decreases BACE1 expression by upregulating suppressor of cytokine signaling 1 (SOCS1) in SH-SY5Y neuroblastoma cells. The activation of PPARd by GW501516, a specific PPARd agonist, inhibited expression of BACE1. This effect was abrogated by shRNA-mediated knockdown of PPARd and by treatment with the PPARd antagonist GSK0660, indicating that PPARd is involved in GW501516-mediated suppression of BACE1 expression. On the other hand, GW501516-activated PPARd induced expression of SOCS1, which is a negative regulator of cytokine signal transduction, at the transcriptional level by binding to a PPAR response element in its promoter. This GW501516-mediated induction of SOCS1 expression led to down-regulation of BACE1 expression via inactivation of signal transducer and activator of transcription 1. GW501516-activated PPARd suppressed the generation of neurotoxic amyloid beta (Ab) in accordance with the decrease in BACE1 expression. Taken together, these results indicate that PPARd attenuates BACE1 expression via SOCS1-mediated inhibition of signal transducer and activator of transcription 1 signaling, thereby suppressing BACE1-associated generation of neurotoxic Ab.

Intracellular iron accumulation in dopaminergic neurons contributes to neuronal cell death in progressive neurodegenerative disorders such as Parkinson’s disease. However, the mechanisms of iron homeostasis in this context remain incompletely understood. In the present study, we assessed the role of the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) in cellular iron homeostasis. We identified that PPARδ inhibited 6-hydroxydopamine (6-OHDA)-triggered neurotoxicity in SH-SY5Y neuroblastoma cells. PPARδ activation with GW501516, a specific PPARδ agonist, mitigated 6-OHDA-induced neuronal damage. Further, PPARδ activation also suppressed iron accumulation, which contributes to 6-OHDA-induced neuronal damage. PPARδ activation attenuated 6-OHDA-induced neuronal damage in a similar manner to that of the iron chelator deferoxamine. We further elucidated that PPARδ modulated cellular iron homeostasis by regulating expression of divalent metal transporter 1, ferroportin 1, and ferritin, but not transferrin receptor 1, through iron regulatory protein 1 in 6-OHDA-treated cells. Interestingly, PPARδ activation suppressed 6-OHDA-triggered generation of reactive oxygen species and lipid peroxides. The effects of GW501516 were abrogated by shRNA knockdown of PPARδ, indicating that the effects of GW501516 were PPARδ-dependent. Taken together, these findings suggest that PPARδ attenuates 6-OHDA-induced neurotoxicity by preventing intracellular iron accumulation, thereby suppressing iron overload-associated generation of reactive oxygen species and lipid peroxides, key mediators of ferroptotic cell death.