Transcriptomic analysis and oxidative stress induced by sodium dichloroisocyanurate in the intestine of Phascolosoma esculenta.

Sodium dichloroisocyanurate (NaDCC, C3Cl2N3NaO3) is a solid chlorine-containing product that is widely used as a disinfectant in living environments, which has potential toxic effects on human and rats. Phascolosoma esculenta is a species native to the southeast coast of China and can be used as an indicator organism. In the present study, 150 P. esculenta were used to determine the LC50 of NaDCC for P. esculenta, then 100 P. esculenta were used to analysis the change of histopathology, oxidative stress and transcriptome after NaDCC exposure. The results showed that the LC50 of NaDCC for 48 h was 50 mg/L. NaDCC stress induced pathological events in P. esculenta, including blisters, intestinal structural damage and epithelial cell ruptured or even loss. The highest and lowest intestinal activity of superoxide dismutase in individual survivors was detected at 12 h and 72 h, respectively. Malondialdehyde levels in the intestine declined gradually from 3 h and increased at 9 h, and peaked at 12 h. Total antioxidant capacity declined at 3 h and dropped below the levels of control group after 9 h. Transcriptome sequencing analysis yielded a total of 48.65 Gb of clean data. A total of 34,759 new genes were found including 957 differentially expressed genes (DEGs). The DEGs were significantly enriched in ferroptosis, response to chemicals, response to stress, immune system, ion transport, cell death, oxidation-reduction, cellular homeostasis, protein ubiquitination, and protein neddylation. Additionally, the levels of detoxification enzymes, such as glutathione-S-transferase, cytochrome P450, ABC, UDP-glycosyltransferase and SLC transporters of endogenous and exogenous solutes were significantly changed. Overall, the results provide reference for reasonable use of disinfectants during farming, and also provide insight into the mechanisms related to NaDCC toxicity in P. esculenta.

Marginative Delivery-Mediated Extracellular Leakiness and T Cell Infiltration in Lung Metastasis by a Biomimetic Nanoraspberry.

T lymphocytes infiltrate the most devastating metastatic tumors for immunotherapy, allowing the potential for tumor metastasis suppression. However, tumor heterogeneity often restricts the infiltration of immune cells and possesses immune privilege that leads to protection from the immune attack, especially for invading metastatic clusters. Here, an exosome-camouflaged nanoraspberry (RB@Exo) doubling as a metastases-targeting agent and T cell-infiltration inducer that delivers an anticancer drug and energy is reported. The RB@Exo integrated an exosome-derived margination effect, and density-mediated nanoparticle-induced extracellular leakiness (nanoEL) exhibited more than a 70% colocalization of the RB@Exo to metastatic tumors in the lung in vivo. The release of cancer cell-cell interactions at the metastasis via nanoEL also elicited the 10-fold infiltration of T lymphocytes. The synergy of the T cell infiltration and photolytic effects transported by the RB@Exo deep into the metastatic tumors effectively inhibited the tumor in 60 days when treated with a single alternating magnetic field (AMF).