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Acrylamide (ACR) is an irritant that can cause damage to the eyes, skin, and nervous and reproductive systems. This study aims to illustrate a case of central nervous system and optic nerve damage from exposure to ACR. In this case, a 49-year-old male material handler was accidentally splashed with ACR solution on both of his upper limbs. Consequently, he was admitted to the hospital with toxic encephalopathy, characterized by cerebellar ataxia and slurred speech. Magnetic resonance imaging scan, a brain computed tomography scan blood sample analyses, optic coherence tomography, electroneuromyogram, and visual evoked potentials examination were performed. After 20 days of receiving symptomatic support treatment, the patient continued to experience disturbances in consciousness. Then, he developed vision loss, memory disorders, and symptoms of peripheral neuropathy such as skin peeling, extremity weakness, and absent tendon reflexes. This case report underscores the severe consequences of acute dermal exposure to high concentrations of ACR, resulting in toxic encephalopathy, visual impairment, and memory disorders, which will contribute to a broader understanding of ACR toxicity. [ABSTRACT FROM AUTHOR]

Stimulator of interferon genes (STING) agonism presents a powerful weapon for cancer immunotherapy. This study reports a novel dimerized STING agonist diBSP01, which exhibited promising STING binding and activation properties in vitro , based on the benzo[ b ]selenophene scaffold. Meanwhile, shielding the pharmacophores of diBSP01 with photoremovable protecting groups (PPGs) resulted in the generation of the first photoactivatable STING agonist, caged-diBSP01, that exerted no biological potency in the absence of light stimulation while regaining its STING agonistic activity after 400 nm irradiation. Optically controlled in vivo anticancer activity was also proven with caged-diBSP01 in a zebrafish xenograft model. Our study provides insights into developing novel STING agonists for cancer treatment and a solution for precise STING activation to avoid the on-target systemic inflammatory response responsible for normal cell damage caused by systemic STING agonism., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To investigate the cellular target selectivity of small molecules targeting thioredoxin reductase 1, we reported the construction and functional research of a stable TrxR1 gene (encode thioredoxin reductase 1) knockout HCT-116 cell line. We designed and selected TrxR1 knockout sites according to the TrxR1 gene sequence and CRISPR/Cas9 target designing principles. SgRNA oligos based on the selected TrxR1 knockout sites were obtained. Next, we constructed knockout plasmid by cloning the sgRNA into the pCasCMV-Puro-U6 vector. After transfection of the plasmid into HCT-116 cells, TrxR1 knockout HCT-116 cells were selected using puromycin resistance. The TrxR1 knockout efficiency was identified and verified by DNA sequencing, immunoblotting, TRFS-green fluorescent probe, and cellular TrxR1 enzyme activity detection. Finally, the correlation between TrxR1 expression and cellular effects of drugs specifically targeting TrxR1 was investigated by CCK-8 assay. The results demonstrated that the knockout plasmid expressing the sgRNA effectively knocked-out TrxR1 gene within HCT-116 cells, and no expression of TrxR1 protein could be observed in stable TrxR1 knockout HCT-116 (HCT116- TrxR1 -KO) cells. The TrxR1-targeting inhibitor auranofin did not show any inhibitory activity against either cellular TrxR1 enzyme activity or cell proliferation. Based on these results, we conclude that a stable TrxR1 gene knockout HCT-116 cell line was obtained through CRISPR/Cas9 techniques, which may facilitate investigating the role of TrxR1 in various diseases.

An efficient protocol for synthesizing furo[3,2- c ]coumarin derivatives is described. The novel reaction could afford the desired furocoumarins with good to excellent yields in a mild and rapid manner. Large substrate scope screening and scale-up preparation have also been accomplished, and selected compounds were evaluated for their photophysical properties.