Mei Zhang

Diabetic retinopathy (DR) is a common diabetes condition that contributes significantly to vision impairment and blindness in working-age people. The classical theory contends that DR is solely a retinal microvascular disorder. Nevertheless, a growing body of research has demonstrated that the pathological variations of DR consist of retinal microangiopathy and retinal neurodegeneration triggered by hyperglycemia. When these two pathological alterations arise, they are commonly accompanied by programmed cell death (PCD) in the retina. With the intensification of research on retinal pathology, PCD has emerged as a matter of concern in the study of DR. Programmed cell death includes apoptosis, pyroptosis, autophagy and ferroptosis. These four approaches can deal with DR by mediating the death of blood vessels and nerve cells to preserve the homeostasis of the internal environment within the retina. Notably, numerous natural products have been demonstrated to influence PCD, resulting in vascular and neuroprotective effects. This study offers a thorough analysis of the molecular processes that underlie different types of PCDs and clarifies how they affect the development of neurodegeneration and retinal microangiopathy. Additionally, this review systematically outlines the regulatory effects of natural products on PCD, highlighting their potential mechanisms and clinical applications in two pathological stages of treatment. This targeted approach not only enhances the relevance of this paper in the study of diabetic retinal microangiopathy and neurodegeneration but also provides new insights into the development of drug treatments for different stages of DR.

The fine control of the nanogap and morphology of metal nanoparticles (NPs) has always been an obstacle, hindering the development and application of surface-enhanced Raman scattering (SERS) quantitative detection. Here, Au/4-mercaptobenzoic acid@Ag@Au-Ag bimetal core-shell nanocubes (NCs) with a "crescent arc" facet (C-Au/4MBA@Ag NCs) as a highly reliable and sensitive surface-enhanced Raman scattering SERS substrate is proposed for the first time. The bifunctional internal standard (IS) molecules (4MBA) govern the morphology of metal shells to maintain cubic configuration and provide calibration for SERS signals' flotation. In parallel, the controllable curvature of the C-Au/4MBA@Ag NCs is directly modulated by adjusting the relative rates of the galvanic replacement and co-reduction reaction, which generates a controllable interparticle nanogap to offer large depositing spaces for analytes and improve authoritative SERS signals' enhancement. The proposed C-Au/4MBA@Ag NCs exhibit an enhancement factor of up to 4.8 × 10¹⁰ and contribute to the ultralow RSD (7.9%). These C-Au/4MBA@Ag NCs also enable the detection of hazardous pesticide residues such as methamidophos and thiram in herbal plants with a complex matrix, with an average detection accuracy of up to 96%. In summary, this study achieves a fine control strategy of the "crescent arc" surface for improving SERS performance and explores the practical application potential for accurate and sensitive Raman detection of hazardous substances.