TGF-ß1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson's disease models and patients.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Optimization and mechanism of the novel eco-friendly additives for solidification and stabilization of dredged sediment.

Solidification/stabilization technology is commonly used in the rehabilitation of dredged sediment due to its cost-effectiveness. However, traditional solidification/stabilization technology relies on cement, which increases the risk of soil alkalization and leads to increased CO2 emissions during cement production. To address this issue, this study proposed an innovative approach by incorporating bentonite and citrus peel powder as additives in the solidifying agent, with the aim of reducing cement usage in the dredged sediment solidification process. The research results showed that there is a significant interaction among cement, bentonite, and citrus peel powder. After response surface methodology (RSM) optimization, the optimal ratio of the cementitious mixture was determined to be 14.86 g/kg for cement, 5.85 g/kg for bentonite, and 9.31 g/kg for citrus peel powder. The unconfined compressive strength (UCS) of the solidified sediments reached 3144.84 kPa. The reaction products of the solidification materials, when mixed with sediment, facilitated adsorption, gelation, and network structure connection. Simultaneously, the leaching concentration of heavy metals was significantly decreased with five heavy metals (Zn, As, Cd, Hg, and Pb) leaching concentrations decreasing by more than 50%, which met the prescribed thresholds for green planting. This study demonstrated the ecological benefits of employing bentonite and citrus peel powder in the solidification process of dredged sediment, providing an effective solution for sediment solidification.

Accessing the Inaccessible: Analyzing the Oxygen Reduction Reaction in the Diffusion Limit.

The oxygen reduction reaction (ORR) is one of the key processes in electrocatalysis. In this communication, the ORR is studied using a rotating disk electrode (RDE). In conventional work, this method limits the potential region where kinetic (mass transport free) reaction rates can be determined to a narrow range. Here, we applied a new approach, which allows us to analyze the ORR rates in the diffusion-limited potential region of high mass transport. Thus, for the first time, the effect of anion adsorption on the ORR can be studied at such potentials.

Pt-group bimetallic nanocrystals with high-index facets as high performance electrocatalysts.

Bimetallic nanocrystals bound by high-index facets are promising catalysts, as they have both electronic effects from alloying and surface structure effects from high-index facets. Herein, we mainly focused on electrochemical preparation of two new Pt-Rh nanocrystals with high-index facets: {830}-bound tetrahexahedron and {311}-bound trapezohedron, and their excellent electrocatalytic properties for ethanol oxidation, especially the ability to break C-C bonds. Combining previous results about surface-modified tetrahexahedral Pt nanocrystals, we discuss the correlation of alloy and surface effects of the bimetallic system.