Chlorogenic acid regulates the expression of NPC1L1 and HMGCR through PXR and SREBP2 signaling pathways and their interactions with HSP90 to maintain cholesterol homeostasis.

BACKGROUND: Hypercholesterolemia is widely implicated in the etiology of coronary heart disease, stroke, and dementia. Evidence suggests that chlorogenic acid (CA) reduces the risk of cardiovascular disease. PURPOSE: The current study aims to explore the underlying molecular mechanism of CA in lowering cholesterol based on pregnane X receptor (PXR) and sterol regulatory element-binding protein 2 (SREBP2) regulatory pathways and their interactions with heat shock protein 90 (HSP90). METHODS: A hypercholesterolemic mouse model, HepG2 and Caco2 cell models, metabolomics analysis, and co-immunoprecipitation (COIP) were used to study the mechanism of CA lowering cholesterol. RESULTS: Treatment of the hypercholesterolemic mice with CA for 12 weeks significantly reduced body weight, blood lipid, hepatic lipid accumulation, and increased lipid excretion. The nuclear aggregation of PXR and SREBP2 was inhibited simultaneously. In addition, the expression of downstream target genes, including Niemann-pick C1-like 1 (NPC1L1) and 3­hydroxy-3-methylglutaryl-CoA reductase (HMGCR), was downregulated after CA administration. Furthermore, in HepG2 and Caco2 cell models, CA reduced intracellular cholesterol levels by inhibiting the nuclear translocation of PXR and SREBP2 and the expression of NPC1L1 and HMGCR. SREBP2 interacts with PXR through HSP90, and CA reduces the binding stability of SREBP2 and HSP90 and enhances the binding of PXR and HSP90, thus reducing the nuclear accumulation of SREBP2 and PXR simultaneously. Moreover, CA promoted the phosphorylation of AMP-activated protein kinase (AMPK) and its binding to SREBP2. This was not conducive to the binding of HSP90 and SREBP2 but enhanced the binding of HSP90 and PXR, thereby inhibiting the nuclear translocation of SREBP2 and PXR and reducing intracellular cholesterol levels. However, no noticeable direct binding between AMPK and PXR was observed. CONCLUSION: CA downregulates NPC1L1 and HMGCR expression by acting on the AMPK/SREBP2 direct pathway and the AMPK/SREBP2/HSP90/PXR indirect pathway, thus retaining cholesterol homeostasis.

Butterfly Wing Hears Sound: Acoustic Detection Using Biophotonic Nanostructure.

The biophotonic nanostructures of Morpho butterfly wing display iridescent colors through the combined effect of light diffraction and interference. These nanostructures have attracted wide attention due to their high optical sensitivity and deformable material properties and have been applied to various infrared (IR), volatile organic compound (VOC), and pH sensors. This work explores the application of such biophotonic nanostructures of butterfly wing for acoustic detection and voice recognition. The pressure variation of the acoustic waves induces the vibration of butterfly wing diaphragm, resulting in the periodic change of reflectance. The integrated butterfly wing-based acoustic sensor shows high fidelity in replicating the original acoustic signals. The sensor also demonstrates promise in distinguishing human voices, which provides an alternative approach for voice recognition.

Clinical Features and Peripheral Blood T Lymphocyte Subsets in Hand, Foot, and Mouth Disease According to Different Pathogens.

OBJECTIVE: To investigate the changes in lymphocyte subsets that are caused by infection with different pathogens in children with hand, foot, and mouth disease. METHODS: T lymphocyte subsets were measured in the patients' peripheral blood, and serum, throat swab, and fecal samples were tested for enterovirus. RESULTS: Fecal and throat swab samples exhibited similar positive detection rates, and were significantly more likely to be positive, compared to serum samples (P < 0.01). The EV71-positive group exhibited significantly lower CD4 + TM cell counts (QR: 1.058), compared to the CD4 + TM cell counts in the CoxA16-positive group (QR: 1.391; P < 0.05). CONCLUSIONS: Throat swab and fecal samples exhibited significantly higher positive detection rates, compared to serum samples. In addition, EV71-infected children exhibited significantly lower CD4+ T-cell counts, compared to CoxA16-infected children, which suggests that EV71 infection may be associated with a poorer prognosis.

Subtractive Structural Modification of Morpho Butterfly Wings.

Different from studies of butterfly wings through additive modification, this work for the first time studies the property change of butterfly wings through subtractive modification using oxygen plasma etching. The controlled modification of butterfly wings through such subtractive process results in gradual change of the optical properties, and helps the further understanding of structural optimization through natural evolution. The brilliant color of Morpho butterfly wings is originated from the hierarchical nanostructure on the wing scales. Such nanoarchitecture has attracted a lot of research effort, including the study of its optical properties, its potential use in sensing and infrared imaging, and also the use of such structure as template for the fabrication of high-performance photocatalytic materials. The controlled subtractive processes provide a new path to modify such nanoarchitecture and its optical property. Distinct from previous studies on the optical property of the Morpho wing structure, this study provides additional experimental evidence for the origination of the optical property of the natural butterfly wing scales. The study also offers a facile approach to generate new 3D nanostructures using butterfly wings as the templates and may lead to simpler structure models for large-scale man-made structures than those offered by original butterfly wings.