Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.
Robust superhydrophobic foam is fabricated by combining an ordered graphdiyne-based hierarchical structure with a low-surface-energy coating. This foam shows not only superhydrophobicity both in air (≈160.1°) and in oil (≈171.0°), but also high resistance toward abrasion cycles. Owing to its 3D porous structures and numerous superhydrophobic surfaces, it can easily separate oil from water with high efficiency and good recyclability.
A general and simple route to fabricate graphdiyne nanowalls on arbitrary substrates is developed by using a copper envelope catalysis strategy. The GDY/BiVO system is but one example of combing the unique properites of GDY with those target substrates where GDY improves the photoelectrochemical performance dramatically.
Graphdiyne analogs, linked carbon monolayers with acetylenic scaffoldings, are fabricated by adopting low-temperature chemical vapor deposition which provides a route for the synthesis of two-dimensional carbon materials via molecular building blocks. The electrical conductivity of the as-grown films can reach up to 6.72 S cm . Moreover, the films show potential as promising substrates for fluorescence suppressing and Raman advancement.
Accumulation evidence shows that β-amyloid (Aβ) is a neurotoxic and accumulation of Aβ is responsible for the pathology of Alzheimer's disease (AD). However, it is currently not fully understood what makes Aβ toxic and accumulated. Previous studies demonstrate that Aβ is a suitable substrate for glycation, producing one form of the advanced glycation endproducts (AGEs). We speculated that Aβ-AGE formation may exacerbate the neurotoxicity. To explore whether the Aβ-AGE is more toxic than the authentic Aβ and to understand the molecular mechanisms, we synthesized glycated Aβ by incubating Aβ with methylglyoxal (MG) in vitro and identified the formation of glycated Aβ by fluorescence spectrophotometer. Then, we treated the primary hippocampal neurons cultured 8 days in vitro with Aβ-AGE or Aβ for 24 h. We observed that glycation exacerbated neurotoxicity of Aβ with upregulation of receptor for AGE (RAGE) and activation of glycogen synthase kinase-3 (GSK-3), whereas simultaneous application of RAGE antibody or GSK-3 inhibitor reversed the neuronal damages aggravated by glycated Aβ. Thereafter, we found that Aβ is also glycated with an age-dependent elevation of AGEs in Tg2576 mice, whereas inhibition of Aβ-AGE formation by subcutaneously infusion of aminoguanidine for 3 months significantly rescued the early cognitive deficit in mice. Our data reveal for the first time that the glycated Aβ is more toxic. We propose that the glycated Aβ with the altered secondary structure may be a more suitable ligand than Aβ for RAGE and subsequent activation of GSK-3 that can lead to cascade pathologies of AD, therefore glycated Aβ may be a new therapeutic target for AD.
The ability of cells to perceive and translate versatile cues into differential chromatin and transcriptional states is critical for many biological processes. In plants, timely transition to a flowering state is crucial for successful reproduction. EARLY BOLTING IN SHORT DAY (EBS) is a negative transcriptional regulator that prevents premature flowering in Arabidopsis thaliana. We found that EBS contains bivalent bromo-adjacent homology (BAH)-plant homeodomain (PHD) reader modules that bind H3K27me3 and H3K4me3, respectively. We observed co-enrichment of a subset of EBS-associated genes with H3K4me3, H3K27me3, and Polycomb repressor complex 2 (PRC2). Notably, EBS adopted an autoinhibition mode to mediate its switch in binding preference between H3K27me3 and H3K4me3. This binding balance was critical because disruption of either EBS-H3K27me3 or EBS-H3K4me3 interaction induced early floral transition. Our results identify a bivalent chromatin reader capable of recognizing two antagonistic histone marks, and we propose a distinct mechanism of interaction between active and repressive chromatin states.
Two-dimensional (2D) materials composed of sp and sp(2) carbon atoms (e.g., graphyne and graphdiyne) show many interesting properties. These materials can be constructed through alkyne homocoupling; however, the occurrence of various side reactions increases the difficulty of their synthesis and structural characterization. Here, we investigate the thermodynamic properties and vibrational spectra of several aryl-alkynes. Both homocoupling and side reactions are found to occur spontaneously at room temperature in terms of thermodynamics. The calculated Raman spectra of the homocoupling products show regular changes with increasing polymerization degree. By rationalizing the vibrational modes of various oligomers, the Raman spectrum of a 2D sp-sp(2) carbon sheet is predicted; it exhibits three sharp peaks at 2241, 1560, and 1444 cm(-1). Although the target and byproducts display similar vibrational modes, a combination of Raman and infrared spectroscopies can be used to differentiate them. The theoretical results are then used to analyze the structure of a synthesized sample and provide useful information.
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