Current elastography techniques are limited in application to accurately assess spatially resolved corneal elasticity in vivo for human eyes. The air‐puff optical coherence elastography (OCE) with an eye motion artifacts correction algorithm is developed to distinguish the in vivo cornea vibration from the eye motion and visualize the Lamb wave propagation clearly in healthy subjects. Based on the Lamb wave model, the phase velocity dispersion curve in the high‐frequency is calculated to obtain spatially resolved corneal elasticity accurately with high repeatability. It is found that the corneal elasticity has regional variations and is correlated with intraocular pressure, which suggests that the method has the potential to provide noninvasive measurement of spatially resolved corneal elasticity in clinical practice.

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Near-infrared (NIR) in vivo fluorescence imaging has exhibited the distinct advantage of high optical resolution at deeper penetration into biological tissues. Ag2Te quantum dots (QDs), with a relatively narrow band gap, show great promise for fluorescence emission at long wavelengths in the second near-infrared (NIR-II) window for bioimaging. However, existing Ag2Te QDs have severely hindered the application of in vivo bioimaging due to their poor fluorescence brightness and stability, so it is important to prepare Ag2Te QDs with high quantum yield and stability as well as high biocompatibility in the NIR-II window. Herein, we designed an integrated method for the preparation of water-soluble Ag2Te QDs by mutual adaptation of QD synthesis and surface modification. We first synthesized high-quality Ag2Te QDs with different NIR-II emission wavelengths and the photoluminescence quantum yields (PLQYs) up to 6.51% by rapidly injecting the TBP-Te precursor into a hot solvent to form a highly fluorescent Ag2Te core. Then water-dispersible Ag2Te QDs were obtained by direct exchange of the hydrophobic Ag2Te QD surface ligands with thiol ligands. The PLQY of the water-soluble Ag2Te QDs obtained by this method can still be maintained at 4.94%. With these highly bright and stable Ag2Te QDs, the abdominal vessels, hindlimb arterial vessels, venous vessels, sacral lymph nodes, and tumor vessels were visualized non-invasively in vivo in the NIR-II window in mice. The results demonstrate that the integrated strategy of QD synthesis and modification provides valuable technical support for further in-depth applications of Ag2Te QDs.

Aberrant α-synuclein (α-Syn) accumulation resulting from proteasome dysfunction is considered as a prominent factor to initiate and aggravate the neurodegeneration in Parkinson's disease (PD). Although the involvement of 26S proteasome in proteostasis imbalance has been widely accepted, our knowledge about the regulation of immunoproteasome function and its potential role in α-Syn pathology remains limited. Immunoproteasome abundance and proteolytic activities depend on the finely tuned assembly process, especially β-ring formation mediated by the only well-known chaperone proteasome maturation protein (POMP). Here, we identified that α-Syn overexpression was associated with a reduction in immunoproteasome function, which in turn limited the degradation of polo-like kinase 2 (PLK2), exacerbated α-Syn Ser129 phosphorylation and aggregation, ultimately leading to the neurodegeneration. These effects could be dramatically attenuated by β5i overexpression. Mechanistically, α-Syn suppressed the transcriptional regulation of POMP by nuclear factor erythroid 2-related factor 2 (NRF2), thereby preventing the assembly of immunoproteasome β subunits. Dopaminergic neurons-specific overexpression of NRF2-POMP axis effectively rescued the aggregation of α-Syn and PD-like phenotypes. These findings characterized abnormal immunoproteasome assembly as a key contributor governing α-Syn accumulation and neurodegeneration, which might open up a new perspective for the implication of immunoproteasome in PD and provide approaches of manipulating immunoproteasome assembly for therapeutic purposes.

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