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The dinoflagellate Karenia mikimotoi is a toxic bloom-forming species that threatens aquaculture and public health worldwide. Previous studies showed that K. mikimotoi induces neurotoxicity; however, the underlying mechanism is poorly understood. In this study, three neural cell lines were used to investigate the potential neurotoxicity of K. mikimotoi. The tested cells were exposed to a ruptured cell solution (RCS) of K. mikimotoi at different concentrations (0.5 × 105, 1.0 × 105, 2.0 × 105, 4.0 × 105, and 6 × 105 cells mL−1) for 24 h, and the RCS decreased cell viabilities and promoted Neuro-2a (N2A) cell apoptosis in a dose-dependent manner. The underlying mechanism was further investigated in N2A cells. At the biochemical level, the RCS stimulated reactive oxygen species (ROS) and malondialdehyde (MDA) formation, decreased SOD activity, and reduced mitochondrial membrane potential (MMP). At the gene level, the moderate RCS treatment (2.0 × 105 cells mL−1) upregulated antioxidant response genes (e.g., nrf -2, HO -1, NQO -1, and cat) to alleviate RCS-induced oxidative stress, while the high RCS treatment (4.0 × 105 cells mL−1) downregulated these genes, thereby aggravating oxidative stress. Meanwhile, apoptosis-related genes (e.g., p53 , caspase 3 , and bax2) were significantly upregulated and the anti-apoptotic gene bcl2 was suppressed after RCS treatment. Western blotting results for Caspase 3, Bax2 and Bcl2 were consistent with the mRNA trends. These results revealed that K. mikimotoi RCS can induce neural cell apoptosis via the oxidative stress-mediated mitochondrial pathway, providing novel insights into the neurotoxicity of K. mikimotoi. [Display omitted] • K. mikimotoi RCS shows toxicity to neural cells. • K. mikimotoi RCS induces oxidative stress and mitochondrial dysfunction in Neuro-2a cells. • K. mikimotoi RCS promotes apoptosis in Neuro-2a cells via a mitochondrial-dependent pathway. [ABSTRACT FROM AUTHOR]

Bixafen, a pyrazole-carboxamide fungicide, is a potent toxicant that may elicit multiple adverse effects in non-target organisms. However, knowledge of the mechanisms involved in developmental defects caused by bixafen in aquatic organisms remains limited. In this study, the effects of bixafen on retinal development were evaluated in embryo-larval zebrafish. We exposed zebrafish embryos to 0, 0.1, and 0.3 μM bixafen. Exposure of zebrafish embryos to bixafen caused severe retinal defects, including extreme microphthalmia and a significantly increased cell density of the ganglion cell layer (GCL). Compared with the controls, the expression levels of rod and cone photoreceptor marker genes (rho , opn1sw2 , opn1mw1 , opn1lw1 , and opn1sw1) in the outer nuclear layer (ONL) were significantly downregulated after bixafen exposure. Furthermore, bixafen caused significantly increased expression levels in the GCL marker ath5 and decreased expression levels in the inner nuclear layer (INL) markers prox1a , vsx1 , and sox2. Accordingly, we observed a significantly increased rate of cell apoptosis in the retina after bixafen exposure. Taken together, our data demonstrate that bixafen exhibits retinal developmental toxicity to zebrafish embryos/larvae, and thus, it may pose a significant environmental threat to aquatic organisms. • Bixafen caused developmental eye disorders in zebrafish embryos. • Bixafen disrupted transcription of retinal layer marker genes. • Bixafen induced microphthalmia by increasing retinal apoptosis in zebrafish. [ABSTRACT FROM AUTHOR]

• Glycolysis-related proteins and lactate production was related with increased expression of PRMT6 in the ipsilateral spinal cord dorsal horn of CCI mice. • PRMT6 deficiency or prophylactic and therapeutic intrathecal administration of PRMT6 inhibitor (EPZ020411) ameliorated CCI-induced NP, inflammation and glycolysis. • PRMT6 could interact with and methylate HIF-1α, which increased HIF-1α protein stability. • Inhibiting PRMT6 might be a new treatment strategy for NP. Microglia induced chronic inflammation is the critical pathology of Neuropathic pain (NP). Metabolic reprogramming of macrophage has been intensively reported in various chronic inflammation diseases. However, the metabolic reprogramming of microglia in chronic pain remains to be elusive. Here, we reported that immuno-metabolic markers (HIF-1α, PKM2, GLUT1 and lactate) were related with increased expression of PRMT6 in the ipsilateral spinal cord dorsal horn of the chronic construction injury (CCI) mice. PRMT6 deficiency or prophylactic and therapeutic intrathecal administration of PRMT6 inhibitor (EPZ020411) ameliorated CCI-induced NP, inflammation and glycolysis in the ipsilateral spinal cord dorsal horn. PRMT6 knockout or knockdown inhibited LPS-induced inflammation, proliferation and glycolysis in microglia cells. While PRMT6 overexpression exacerbated LPS-induced inflammation, proliferation and glycolysis in BV2 cells. Recent research revealed that PRMT6 could interact with and methylate HIF-1α, which increased HIF-1α protein stability. In sum, increased expression of PRMT6 exacerbates NP progress by increasing glycolysis and neuroinflammation through interacting with and stabilizing HIF-1α in a methyltransferase manner, which outlines novel pathological mechanism and drug target for NP. [ABSTRACT FROM AUTHOR]