Affiliated Eye Hospital of Wenzhou Medical College

Chronic wounds, such as diabetic foot ulcers, often exhibit lower temperatures due to impaired local circulation, leading to reduced cellular metabolism and delayed healing. This study explores a new strategy to accelerate wound healing by enhancing the cell metabolism of essential amino acids through a "hot spring" mimetic photothermal effect. We engineered an extracellular matrix mimetic nanofiber aerogel co-delivering an eight essential-amino-acid cocktail and photothermally active SrCuSi4O10 bioceramic particles to support chronic wound repair. In vitro, fibroblasts cultured at 25°C versus 37°C showed that physiological temperature preserved the pro-healing bioactivity of the amino-acid treatment with minimal cytotoxicity and was associated with enhanced glutathione redox metabolism. In vivo, the amino acid-loaded aerogel combined with SrCuSi4O10-mediated photothermal therapy accelerated wound closure and improved regenerative outcomes, including increased cellular proliferation, collagen deposition, and neovascularization. Immunohistochemical analysis showed a reduction in neutrophil infiltration, M1 macrophage polarization, and pro-inflammatory cytokines, while increasing M2 macrophage polarization and anti-inflammatory cytokine production, thus shifting the local inflammatory response from pro-inflammatory to regenerative. This approach demonstrates potential as an effective therapeutic option for enhancing the healing of chronic wounds.

Visual deficits are prominent features of autism spectrum disorder (ASD), yet the underlying neural mechanisms remain unclear. Mutations in FOXP1, which is a major risk factor for ASD, are often associated with visual issues. This study aims to investigate how the loss of cortical Foxp1 may contribute to the visual problems. A mouse model of ASD was generated by specific knockout of Foxp1 in cortical progenitors and their descendant excitatory neurons (Foxp1-cKO). We assessed visual depth perception using the visual cliff test. Visual signal conduction was evaluated through flash visual evoked potentials (FVEPs) and light-induced c-Fos neuronal activation in the primary visual cortex (V1). Geniculocortical afferents and connectivity were evaluated by immunolabeling of pre- and post-synaptic markers in V1. Dendrites and spines of layer IV neurons were analyzed using Golgi staining, and mitochondria were examined by Western blots and in neuronal cultures from V1. Foxp1-cKO mice showed deficits in binocular depth perception. The knockout mice exhibited reduced FVEP amplitudes and diminished c-Fos activation in V1 neurons. Knocking out Foxp1 reduced geniculocortical connectivity and decreased dendrites and spines of layer IV neurons of V1. Deletion of Foxp1 impaired the mitochondria in the V1 cortex. Foxp1-cKO mice have deficits in visual signal transmission and depth perception, indicating binocular vision abnormalities. This study highlights the importance of geniculocortical connectivity for binocular vision and offers new insights into the mechanisms underlying ASD-related visual impairments, suggesting future studies to explore therapies aimed at restoring mitochondrial function.

Abstract Background Thyroid-associated orbitopathy (TAO) is an autoimmune disorder characterized by inflammation, fibrosis, and adipogenesis in the orbital tissues, driven primarily by activated orbital fibroblasts (OFs).This study aims to investigated the link between fatty acid metabolism, Pax6 expression, and EMT/fibrosis in TAO; determine the functional role of Pax6 in regulating OF activation, proliferation, migration, and fibrogenesis both in vivo and in vitro ; and explore Pax6 as a potential therapeutic target. Methods Our study employs single-cell RNA sequencing (scRNA-seq) to characterize cellular heterogeneity and identify pathogenic subpopulations and their metabolic profiles, aiming to elucidate the relationship between fatty acid metabolism, Pax6 expression, and EMT in the context of TAO. Results Using scRNA-seq on TAO and normal mouse orbital tissues, we identified distinct cellular populations, including a pathogenic epithelial-like cell subcluster (EPC1) marked by enhanced fatty acid metabolism and EMT markers. Pax6 expression increased along the EMT trajectory, especially in mesenchymal cells. In vivo experiments using a TAO mouse model demonstrated that Pax6 knockdown reduced orbital fibrosis, decreased pro-fibrotic markers (α-SMA, COL1A1, FN1), and inhibited OF activation and migration. Additionally, primary OF cultures showed that Pax6 regulates cellular proliferation and fibrogenesis in vitro . Conclusion Our findings suggest that dysregulated fatty acid metabolism in TAO enhances Pax6 expression. This, in turn, promotes EMT and contributes to orbital fibrosis. Targeting the Pax6–fatty acid metabolism axis represents a novel therapeutic strategy to mitigate the TAO-related orbital fibrosis. This study establishes Pax6 as a key driver of EMT and fibrosis in TAO and highlights its potential as a future therapeutic target.

To characterise the temporal dynamics of choroidal changes relative to myopia onset and determine their associations with myopia onset in school children. The 3-year prospective cohort study consisted of 180 emmetropic school-children. Cycloplegic auto-refractions were performed annually. Choroidal images acquired via swept-source optical coherence tomography until myopia onset were analysed. Choroidal architecture was characterised based on submacular choroidal thickness (ChT), choroidal vascularity index (CVI), luminal area (LA), stromal area (SA) and total choroidal area (TCA) measurements. Time to myopia onset was defined as the first annual follow-up visit with spherical equivalent ≤-0.50 dioptres. A total of 165 participants (330 eyes, 91.7%) who completed at least one annual follow-up were included. During 36 months, 168 eyes of 100 participants developed myopia. Refractive shift and axial elongation showed significant non-linear trends in which they accelerated dramatically approximately 2 years prior to myopia onset. Notably, ChT, as well as CVI, LA, SA and TCA, exhibited significant linear declines throughout the 3 years when these eyes progressed to myopia, whereas they remained unchanged in persistent non-myopic eyes. Multivariable accelerated failure time models showed that a greater decline rate of these choroidal parameters (per SD) shortened the time to myopia onset, with time ratios ranging from 1.26 to 1.76. The area under receiver-operating characteristic curves for annual choroidal changes effectively distinguished incident myopia (0.83-0.89). Alterations in choroidal architecture are an early indicator for the disruption of normal emmetropisation and the onset of myopia.

Colloidal Gelation In their Research Article (10.1002/adfm.202521726), Yonghang Tai, Feng Wen, Tao Li, and co-workers show that, when utilizing rough colloids to produce Pickering droplets, a low surface coverage is generally enough for stabilizing the entire system. The “saving” in surface area, therefore, offers vast space for these colloids to arrangement and assembly at the liquid-liquid interface. Here, they are mischievously mimicking “The Mask”.