Toxicity of hexagonal boron nitride nanosheets to freshwater algae: Phospholipid membrane damage and carbon assimilation inhibition.

Hexagonal boron nitride (h-BN) nanomaterials have attracted numerous attentions for application in various fields, including environmental governance. Understanding the environmental implications of h-BN is a prerequisite for its safe and sustainable use; nevertheless, information on the negative effect of h-BN on aquatic organisms and the underlying toxicity mechanisms is scarce. The present study found that low exposure doses (0.1-1 µg/mL) of micron-sized h-BN lamella apparently suppressed (maximally 45.3%) the growth of Chlorella vulgaris (a freshwater alga) via membrane damages and metabolic reprogramming. Experimental and simulation results verified that h-BN can penetrate into and then extract phospholipids from the cell membrane of algae due to the strong hydrophobic interactions between h-BN nanosheets and lipids, resulting in membrane permeabilization and integrity reduction. Oxidative stress-triggered lipid peroxidation also contributes to membrane destruction of algae. Metabolomics assay demonstrated that h-BN down-regulated the CO2-fixation associated Calvin cycle and glycolysis/gluconeogenesis pathways in algae, thereby inhibiting energy synthesis and antioxidation process. Despite releasing soluble B inside cells, the B species exhibited negligible toxicity. These findings highlight the phenomena and mechanisms of h-BN toxicity in photosynthetic algae, which have great implications for guiding their safe use under the scenarios of global carbon neutrality.

A novel endomorphin-2/salmon calcitonin hybrid peptide with enhancing anti-allodynic and anti-anxiety effects.

Pain, a worldwide problem with a high incidence and complex pathogenesis, has attracted the attention of pharmaceutical enterprises for the development of safer and more effective drugs. Extensive experimental and clinical evidence has demonstrated the analgesic effects of two endogenous peptides: endomorphin-2 (EM-2) and salmon calcitonin (sCT). However, EM-2 has limitations, such as poor ability to cross the blood-brain barrier (BBB) and little therapeutic effect in chronic pain due to rapid in vivo proteolysis. Herein, we propose the design of a novel hybrid peptide TEM2CT by combining EM-2, sCT16-21, and the cell-penetrating peptide HIV-1 trans-activator protein (TAT) with the aim of enhancing their analgesic effects. TEM2CT treatment attenuated nociceptive behavior in both acute and chronic pain mouse models, exhibiting increased anti-allodynic and anti-anxiety effects compared to sCT treatment. Furthermore, TEM2CT also regulated the excitability of pyramidal neurons in the anterior cingulate cortex (ACC) in spared nerve injury (SNI) model mice. The improved efficacy of this hybrid peptide provides a promising strategy for developing analgesic drugs.