Single-cell RNA-sequencing analysis reveals α-syn induced astrocyte-neuron crosstalk-mediated neurotoxicity.

Accumulation of alpha-synuclein (α-syn) is a key pathological hallmark of synucleinopathies and has been shown to negatively impact neuronal function and activity. α-syn is an important factor contributing to astrocyte overactivation, though the effect of astrocyte overactivation on neurons remains unclear. Single-cell RNA sequencing data of mouse brain frontal cortex and midbrain from Hua-Syn (A53T) and wild type mice were utilized from the GEO database. Enrichment analysis, protein-protein interaction networks, and cell-cell interaction networks all indicated enhanced communication between astrocytes and neurons, along with the involvement of TNF and inflammation-related signaling pathways. In vitro experiments were performed to further explore the mechanism of neurotoxicity in astrocyte-neuron crosstalk. Astrocytes were treated by α-syn, neuronal TNFR1 receptors were antagonized by R-7050, and the cells were co-cultured after 24 h treatment. ELISA results revealed that cytokines such as TNF-α and IL-6 were significantly upregulated in astrocytes following the endocytosis of α-syn. Immunofluorescence (IF) showed neuronal dendritic reduction, axon elongation and increased co-localisation of TNFR1 receptor expression. Western blot showed up-regulation of PKR, P-eIF2α and ATF4 protein expression. Conversely, after antagonizing neuronal TNFR1 receptors with the R-7050 chemical inhibitor, neuronal synaptic structure was significantly restored and the expression of PKR, P-eIF2α and ATF4 was down-regulated. In summary, TNF-α acts as a signaling molecule mediating the up-regulated astrocyte-neuron crosstalk, providing new insights into the pathogenesis of α-syn-related neurological disorders.

Anode-Free Aqueous Aluminum Ion Batteries.

Aqueous aluminum ion batteries (AAIBs) possess the advantages of high safety, cost-effectiveness, eco-friendliness and high theoretical capacity. However, the Al2O3 film on the Al anode surface, a natural physical barrier to the plating of hydrated aluminum ions, is a key factor in the decomposition of the aqueous electrolyte and the severe hydrogen precipitation reaction. To circumvent the obnoxious Al anode, a proof-of-concept of an anode-free AAIB is first proposed, in which Al2TiO5, as a cathode pre-aluminum additive (Al source), can replenish Al loss by over cycling. The Al-Cu alloy layer, formed by plating Al on the Cu foil surface during the charge process, possesses a reversible electrochemical property and is paired with a polyaniline (cathode) to stimulate the battery to exhibit high initial discharge capacity (175 mAh g-1), high power density (≈410 Wh L-1) and ultra-long cycle life (4000 cycles) with the capacity retention of ≈60% after 1000 cycles. This work will act as a primer to ignite the enormous prospective researches on the anode-free aqueous Al ion batteries.