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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by complex pathogenesis mechanisms. Among these, β‐amyloid plaques and hyperphosphorylated Tau protein tangles have been identified as significant contributors to neuronal damage. This study investigates thonningianin A (TA) from Penthorum chinense Pursh (PCP) as a potential inhibitor targeting these pivotal proteins in AD progression. The inhibitory potential of PCP and TA on Aβ fibrillization was initially investigated. Subsequently, ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight tandem mass spectrometry and biolayer interferometry were employed to determine TA's affinity for both Aβ and Tau. The inhibitory effects of TA on the levels and cytotoxicity of AD‐related proteins were then assessed. In 3xTg‐AD mice, the therapeutic potential of TA was evaluated. Additionally, the molecular interactions between TA and either Aβ or Tau were explored using molecular docking. We found that PCP‐total ethanol extract and TA significantly inhibited Aβ fibrillization. Additionally, TA demonstrated strong affinity to Aβ and Tau, reduced levels of amyloid precursor protein and Tau, and alleviated mitochondrial distress in PC‐12 cells. In 3xTg‐AD mice, TA improved cognition, reduced Aβ and Tau pathology, and strengthened neurons. Moreover, molecular analyses revealed efficient binding of TA to Aβ and Tau. In conclusion, TA, derived from PCP, shows significant neuroprotection against AD proteins, highlighting its potential as an anti‐AD drug candidate. [ABSTRACT FROM AUTHOR]

Auxetic materials with multifunctional properties are highly sought after for application in modern nano-devices. However, the majority of reported inorganic auxetic materials exhibit low negative Poisson's ratios (NPR), poor flexibility, and limited functionality. In this study, we employ density-functional-theory (DFT) first-principles simulations to design a series of two-dimensional (2D) metal-organic frameworks (MOFs) M 2 C 4 X 4 (M = Cu, Ag, Au; X = O, S, NCN) that display intriguing auxetic behavior, superior flexibility and appropriate photocatalytic water-splitting properties. These M 2 C 4 X 4 MOFs are assembled from carbon tetragon motifs and exist in both cis - and trans -isomer forms, with the NPR ranging from -0.17 to -0.90. Notably, trans -Cu 2 C 4 (NCN) 4 exhibits a high NPR of -0.90, while cis -Cu 2 C 4 (NCN) 4 achieves an NPR of -0.67. Both isomers demonstrate excellent flexibility, characterized by ultra-low Young's modulus and high fracture strengths. Furthermore, their direct band gaps, strong light-harvesting capabilities, and long excited-state lifetimes make them promising candidates for the photocatalytic oxygen evolution reaction in water. These results provide a viable strategy for the design and synthesis of novel optoelectronic multifunctional materials.

Two-dimensional (2D) materials with negative Poisson's ratios (NPRs) hold tremendous potential in diverse electronic devices. However, most 2D auxetic materials exhibit small out-of-plane NPRs and materials with bi-directional NPRs are rare. In this work, the SiS 2 monolayer and its derivatives MX 2 (M = Si, Ge, Sn and X = S, Se, Te) are systematically studied via first-principles simulation. We demonstrate that a SiS 2 monolayer possesses a remarkable out-of-plane NPR with a value of -1.09 and an in-plane NPR (-0.13). Furthermore, a higher out-of-plane NPR (-1.79) can be achieved in a SnS 2 monolayer by element substitution. Remarkably, SiS 2 and its derivative MX 2 monolayers exhibit excellent light harvesting over the ultraviolet and visible range, and the corresponding electronic properties show robustness against strains. Our results confirm that MX 2 monolayers provide an ideal platform to explore auxeticity in two-dimensional limits.

Morphine-induced microglia activation and neuroinflammation have been considered as the contributors of morphine tolerance. Corilagin (Cori) has been reported to exhibit strong anti-inflammatory property. The present study aims to investigate whether and how Cori alleviates morphine-induced neuroinflammation and microglia activation. Mouse BV-2 cells were exposed to different concentrations of Cori (0.1, 1 and 10 μM) prior to morphine stimulation (200 μM). Minocycline (10 μM) acted as the positive control. Cell viability was determined by CCK-8 assay and trypan blue assay. The levels of inflammatory cytokines were determined using ELISA. IBA-1 level was examined via immunofluorescence. TLR2 expression level was examined by quantitative real-time PCR and western blot. The expression levels of corresponding proteins were measured by western blot. It was found that Cori was non-toxic to BV-2 cells but greatly inhibited morphine-induced IBA-1 expression, overproduction of pro-inflammatory cytokines, activation of NLRP3 inflammasome and endoplasmic reticulum stress (ERS), and upregulation of COX-2 and iNOS. TLR2 was negatively regulated by Cori, and could promote the activation of ERS. A high affinity between Cori and TLR2 protein was confirmed via Molecular docking investigation. Moreover, TLR2 overexpression or tunicamycin (TM), an agonist of ERS, partly abolished the inhibitory effects of Cori on morphine-induced alternations on neuroinflammation and microglial activation in BV-2 cells as above. In summary, our study suggested that Cori effectively alleviated morphine-induced neuroinflammation and microglia activation through inhibiting TLR2-mediated ERS in BV-2 cells, providing a novel potential drug to overcome morphine tolerance.