Interfacial Preparation of Polyoxometalate-Based Hybrid Supramolecular Polymers by Orthogonal Self-Assembly.

The construction of organic-inorganic hybrid supramolecular polymers using polyoxometalate (POM) as building block is expected to bring new opportunities to the functionalization of supramolecular polymers and the development of novel POM-based soft materials. Here, by using the orthogonal self-assembly based on host-guest interactions and metal-ligand interactions, we report the in situ construction of a novel POM-based hybrid supramolecular polymer (POM-SP) at the oil-water interface, while the redox and competitive responsiveness can be triggered independently. Moreover, the binding energy of POM-SP at the interface is sufficiently strong so that the assembly of POM-SP jams, allowing the stabilization of liquids in nonequilibrium shapes, offering the possibility of fabricating all-liquid constructs with reconfigurability.

Cadmium exposure promotes ferroptosis by upregulating Heat Shock Protein 70 in vascular endothelial damage of zebrafish.

Cadmium (Cd) exposure is a risk factor for endothelial dysfunction and cardiovascular disease. Ferroptosis is a type of cell death that relies on lipid peroxidation. Whether ferroptosis acts in Cd-induced vascular endothelial damage and the underlying mechanisms remain unclear. Herein, we found that Cd resulted in ferroptosis of vascular endothelial cells (ECs) in vivo and in vitro. In the visualized zebrafish embryos, Cd accumulated in vascular ECs, ROS and lipid peroxidation levels were increased, and the oxidoreductase system was disturbed after exposure. Moreover, Cd decreased Gpx4 in ECs and caused smaller mitochondria with increased membrane density. Accompanied by ferroptosis, the number of ECs and the area of the caudal venous plexus in zebrafish embryos were reduced, and the survival rate of HUVECs decreased. These effects were partially reversed by ferrostatin-1 and aggravated by erastin. Mechanistically, an excessive increase in Heat Shock Protein 70 (Hsp70) was identified by transcriptomics after Cd exposure. Inhibition of Hsp70 by VER-155008 or siRNA ameliorated Cd-induced ferroptosis, thereby alleviating endothelial injury. Furthermore, Hsp70 regulated Cd-induced ferroptosis by targeting multiple targets, including Gpx4, Fth1, Nrf2 and Acsl4. Our findings provide a new approach to investigating the endothelial damage of Cd and indicate that regulation of Hsp70 is an important target for alleviating this process.

Polyoxometalate-Surfactant Assemblies: Responsiveness to Orthogonal Stimuli.

Integrating different types of supramolecular interactions opens the possibility to generate nanoparticle surfactants (NPSs) at the liquid-liquid interface that are responsive to multiple stimuli. Here we develop a covalently modified polyoxometalate/ß-cyclodextrin (POM/ß-CD) organic-inorganic hybrid, consisting of a negatively charged POM cluster with ß-CD host groups. The POM/ß-CD hybrid can be dispersed in water and interacts at a water/oil interface with ligands dissolved in an oil phase through electrostatic or host-guest interactions, thereby generating POM-surfactants (POMSs) having pH, redox, and guest-competitive responsiveness, respectively. By taking advantage of the jamming of POMSs at the interface, a reconfigurable all-liquid system could be produced that is responsive to orthogonal changes in the external environment.

Self-Assembly of Polyoxometalate-Based Nanoparticle Surfactants in Solutions.

Nanoparticle surfactants (NPSs) are an emergent class of amphiphiles attractive for their controllable assembly at the liquid-liquid interface. In this work, intriguing self-assembly behavior and stimuli-responsiveness of NPSs in homogeneous solutions are presented. With ß-cyclodextrin-grafted polyoxometalates (POMs) and ferrocene (or azobenzene)-terminated polystyrene in water/tetrahydrofuran, POM-based NPSs are formed via host-guest interactions and self-organize to vesicles driven by solvent-phobic effects. The tunable supramolecular interactions allow these assemblies to be responsive to redox or light stimulus, respectively, affording an on-demand assembly/disassembly capacity that shows promise in delivery and release applications.

Association of multiple blood metals and systemic atherosclerosis: A cross-sectional study in the CAD population.

BACKGROUND: Coronary atherosclerotic disease (CAD) is often accompanied by peripheral atherosclerosis, resulting in a higher risk of ischemia and cardiovascular death. Exposure to metals is associated with atherosclerotic plaques at specific sites. However, less is known about the effects of mixed metals on systemic atherosclerotic burden in CAD patients. OBJECTIVES: To investigate the association of metal mixtures with systemic atherosclerotic burden in a CAD population. METHODS: A cross-sectional study including 1562 CAD patients from Southwest China was conducted. The levels of 10 blood metals were measured via inductively coupled plasma spectrometry. More than one vessel with a stenosis ≥50% vessel diameter was defined as CAD. Carotid and lower limb atherosclerosis was assessed by using ultrasound, and coronary atherosclerosis was quantified via arterial angiography. Systemic atherosclerosis was scored according to the presence or absence of lesions at the three sites and the total number of lesions. To investigate the combined impacts and interaction effects of metals, Bayesian kernel machine regression was used. Weighted quantile regression was used to identify the contributions of the metals. RESULTS: Significant overall associations of mixed metals with systemic atherosclerotic burden were found. These positive overall associations were mainly driven by Cd, Cu and Pb in systemic atherosclerosis. The main contributing factors were As and Cu for coronary atherosclerosis as well as Cd, Cu and Pb for carotid and lower limb atherosclerosis. Cd and Pb or Cr can interact, and Pb interacts with age, sex and alcohol. CONCLUSIONS: In CAD patients, exposure to combinations of metals was highly positively associated with systemic atherosclerotic burden. These significant trends were more pronounced in the peripheral arteries and carotid arteries. Controlling environmental metal exposure can contribute to reducing systemic atherosclerosis in CAD patients.

Upregulation of mitochondrial calcium uniporter contributes to paraquat-induced neuropathology linked to Parkinson's disease via imbalanced OPA1 processing.

Paraquat (PQ) is the most widely used herbicide in agriculture worldwide and has been considered a high-risk environmental factor for Parkinson's disease (PD). Chronic PQ exposure selectively induces dopaminergic neuron loss, the hallmark pathologic feature of PD, resulting in Parkinson-like movement disorders. However, the underlying mechanisms remain unclear. Here, we demonstrated that repetitive PQ exposure caused dopaminergic neuron loss, dopamine deficiency and motor deficits dose-dependently in mice. Accordingly, mitochondrial calcium uniporter (MCU) was highly expressed in PQ-exposed mice and neuronal cells. Importantly, MCU knockout (KO) effectively rescued PQ-induced dopaminergic neuron loss and motor deficits in mice. Genetic and pharmacological inhibition of MCU alleviated PQ-induced mitochondrial dysfunction and neuronal death in vitro. Mechanistically, PQ exposure triggered mitochondrial fragmentation via imbalance of the optic atrophy 1 (OPA1) processing manifested by cleavage of L-OPA1 to S-OPA1, which was reversed by inhibition of MCU. Notably, the upregulation of MCU was mediated by miR-129-1-3p posttranscriptionally, and overexpression of miR-129-1-3p could rebalance OPA1 processing and attenuate mitochondrial dysfunction and neuronal death induced by PQ exposure. Consequently, our work uncovers an essential role of MCU and a novel molecular mechanism, miR-MCU-OPA1, in PQ-induced pathogenesis of PD, providing a potential target and strategy for environmental neurotoxins-induced PD treatment.