Science Bulletin最新文献

Transcranial electrical stimulation (tES) is a non-invasive technique widely used in modulating brain activity and behavior, but its effects differ across individuals and are influenced by head anatomy. In this study, we investigated how the electric field (EF) generated by high-definition tES varies across the lifespan among different demographic groups and its relationship with neural responses measured by functional magnetic resonance imaging (fMRI). We employed an MRI-guided finite element method to simulate the EF for the two most common tES montages (i.e., targeting the dorsolateral prefrontal cortex and motor cortex, respectively) in two large cohorts of white and Asian participants aged 12 to 100 years. We found that the EF intensity decreased with age, particularly in individuals under 25 years of age, and was influenced by gender and ethnicity. We identified skull thickness, scalp thickness, and epidural cerebrospinal fluid thickness, as the primary anatomical factors accounting for the inter-individual EF variability. Using a concurrent tES-fMRI approach, we observed a spatial consistency between the simulated EF and the brain activity changes induced by tES in the target region. Finally, we developed an open-source toolbox incorporating age-stratified head models to facilitate efficient EF calculations. These findings characterize and quantify the individual differences in tES-induced EF, offering a reference for implementing personalized neuromodulation strategies.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life. Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression. The microbiota-gut-brain axis (MGBA) is closely associated with the occurrence and development of PD and is an effective therapeutic target. Tetrahedral framework nucleic acids (tFNAs) can modulate the microbiome and immune regulation. However, such nucleic acid nanostructures are very sensitive to acids which hinder this promising approach. Therefore, we prepared exosome-like nanovesicles (Exo@tac) from ginger that are acid resistant and equipped with tFNAs modified by antimicrobial peptides (AMP). We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally. Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD. Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.

Neurotransmitters are increasingly recognized to play important roles in limiting anti-tumor immunity. N-acetyl-aspartyl-glutamate (NAAG) has been extensively studied in neurological disorders; however, its potential role in restricting anti-tumor immunity has not been investigated. Here, we demonstrated that NAAG or its synthetase RimK-like family member B (RIMKLB) significantly disrupted anti-tumor immunity by rewiring the myeloid progenitor differentiation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which in turn promoted breast cancer growth and metastasis. Mechanistically, NAAG sustained the tumor immunosuppressive microenvironment by activating an NR2B-containing NMDA receptor (NR2B-NMDAR)-dependent p38-NOTCH1 axis, and subsequently stimulating tumor cell migration and invasion, as well as inducing PMN-MDSC differentiation and expansion. In mouse models, RIMKLB ablation or NMDAR inhibition enhanced the efficacy of anti-PD-1 therapy and suppressed tumor progression. An analysis of clinical samples revealed that high levels of NAAG and NR2B-NMDAR predicted a poor prognosis in TNBC patients. Collectively, our findings have uncovered a signaling role for tumor-derived NAAG beyond its classic function as a neurotransmitter that can be targeted pharmacologically to enhance immunotherapy against breast cancer.